Publications by authors named "Jie Wu"

2,519 Publications

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Efficacy of Coxsackievirus A2 vaccine candidates correlating to humoral immunity in mice challenged with a mouse-adapted strain.

Vaccine 2022 Jun 24. Epub 2022 Jun 24.

Wuhan Institute of Biological Products Co. Ltd., No.1 Huangjin Industrial Park Road, Jiangxia District, Wuhan 430207, China. Electronic address:

Background: In recent years, Coxsackievirus A2 (CV-A2) has become one of the main serotypes of enterovirus species A associated with hand, foot and mouth disease (HFMD) in China. It has also caused HFMD epidemics in many countries all over the world. Currently, there are no effective, preventive vaccines against it.

Methods: A CV-A2 strain was isolated in RD cells and then adapted to grow in Vero cells. This is in compliance with guidelines for cell substrates allowed for human vaccines by the Chinese regulatory authority. Groups of newborn Kunming mice were inoculated on day 3 and day 9 using two formulations of candidate vaccines, empty particles and full particles. They were then challenged on day 14 at a lethal dose with a mouse-adapted strain.

Results: The mice in the control group all died within 14 days post-challenge whereas most of the mice in the candidate vaccine groups survived. It was found that the titers of neutralizing antibodies was dose-dependent in sera of immunized mice. The results also showed that the vaccine candidates stimulated a strong humoral immune response and protected the mice from disease and death. The virus loads in tissues or organs were significantly reduced and pathological changes were either weak or not observed in the immunized groups compared with those in Al(OH) control group. Preliminary mapping of the nucleotide and amino acid residues potentially related to cell tropism of the vaccine strain and virulence of the challenge strain was performed.

Conclusion: The results showed that the RD cell-isolated and Vero cell-adapted CV-A2 strain is a promising vaccine candidate. This active immunization-challenge mouse model mimics the vaccination and then exposure to wildtype viruses, compared with passive immunization-challenge model, and is invaluable for efficacy evaluation in studies on multivalent vaccines containing CV-A2 against HFMD.
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http://dx.doi.org/10.1016/j.vaccine.2022.06.021DOI Listing
June 2022

The Pyruvate Dehydrogenase Complex Mitigates LPS-Induced Endothelial Barrier Dysfunction by Metabolic Regulation.

Shock 2022 Jun;57(6):308-317

Department of Pathophysiology, Guangdong Provincial Key Lab of Shock and Microcirculation, Southern Medical University, Guangzhou, Guangdong, China.

Abstract: Sepsis is a fatal health issue induced by an aberrant host response to infection, and it correlates with organ damage and a high mortality rate. Endothelial barrier dysfunction and subsequent capillary leakage play major roles in sepsis-induced multiorgan dysfunction. Anaerobic glycolysis is the primary metabolic mode in sepsis and the pyruvate dehydrogenase complex (PDHC) serves as a critical hub in energy regulation. Therefore, it is important to understand the role of PDHC in metabolic regulation during the development of sepsis-induced endothelial barrier dysfunction.In present study, human umbilical vein endothelial cells (HUVECs) and C57 BL/6 mice were treated with lipopolysaccharide (LPS) as models of endotoxemia. LPS increased basal glycolysis, compensatory glycolysis, and lactate secretion, indicating increased glycolysis level in endothelial cells (ECs). Activation of PDHC with dichloroacetate (DCA) reversed LPS-induced glycolysis, allowing PDHC to remain in the active dephosphorylated state, thereby preventing lactic acid production and HUVECs monolayers barrier dysfunction, as assessed by transendothelial electrical resistance and Fluorescein Isothiocyanate-labeled dextran. The in vivo study also showed that the lactate level and vascular permeability were increased in LPS-treated mice, but pretreatment with DCA attenuated these increases. The LPS-treated HUVEC model showed that DCA reversed LPS-induced phosphorylation of pyruvate dehydrogenase E1α Ser293 and Ser300 to restore PDHC activity. Immunoprecipitation results showed that LPS treatment increased the acetylation level of PDH E1α in HUVECs.Our study suggested that activation of PDHC may represent a therapeutic target for treatment of LPS-induced endothelial barrier dysfunction.
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http://dx.doi.org/10.1097/SHK.0000000000001931DOI Listing
June 2022

Association of methylenetetrahydrofolate reductase () gene polymorphisms (C677T and A1298C) with thyroid dysfunction: A meta-analysis and trial sequential analysis.

Arch Endocrinol Metab 2022 Jun 23. Epub 2022 Jun 23.

State Key Laboratory of Reproductive Medicine, Department of Obstetrics and Gynecology, The First Affiliated Hospital of Nanjing Medical University, Jiangsu Province Hospital, Jiangsu Women and Children Health Hospital, Nanjing, China,

Recent studies have shown that two common methylenetetrahydrofolate reductase () gene polymorphisms (C677T and A1298C) might correlate with thyroid dysfunction, but the results remain inconsistent. We carried out a meta-analysis aiming to assess the relationship of both polymorphisms with thyroid dysfunction. The PubMed, EMBASE, CNKI (China National Knowledge Infrastructure), CBMdisc (China Biology Medicine disc), WeiPu and Wanfang databases were searched up to September 2021. Case-control and cohort studies on polymorphism and thyroid dysfunction were identified. Eight studies from six publications were finally included in our meta-analysis, including 817 patients and 566 controls. After pooled analysis, we found that the C677T polymorphism was associated with an increased risk of hypothyroidism (TT CC+CT/recessive model: OR = 2.07, 95% CI: 1.02-4.20, P = 0.04; TT CC/homozygote model: OR = 2.35, 95% CI: 1.13-4.86, P = 0.02), while trial sequential analysis (TSA) revealed that it could be a false positive result. The A1298C polymorphism was related to a decreased risk of hypothyroidism (C A/allele model: OR = 0.63, 95% CI: 0.44-0.92, P = 0.02; CC AC+AA/recessive model: OR = 0.42, 95% CI: 0.22-0.79, P = 0.007; CC AA/homozygote model: OR = 0.43, 95% CI: 0.25-0.85, P = 0.02), which was conclusive according to TSA. The results of this meta-analysis suggest that A1298C seems to be a protective factor for hypothyroidism, while the C677T polymorphism may be a risk factor. However, more well-designed studies with larger sample sizes are needed to obtain more reliable results of the association between the C677T polymorphism and hypothyroidism.
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http://dx.doi.org/10.20945/2359-3997000000471DOI Listing
June 2022

A Preliminary Study on the Effects of Black Cohosh Preparations on Bone Metabolism of Rat Models With GnRH-a-Induced Peri-Menopausal Symptoms.

Front Endocrinol (Lausanne) 2022 9;13:854345. Epub 2022 Jun 9.

Department of Obstetrics and Gynecology, The Affiliated Changzhou No.2 People's Hospital of Nanjing Medical University, Changzhou, China.

Background: Endometriosis (EMS) is a relapsing and estrogen-dependent disease. For endometriosis such as deep endometriosis and ovarian endometrioid cysts, surgery is the most effective treatment. Long-term follow-up showed that the recurrence rate of endometriosis after surgical treatment was high, so postoperative drugs were needed to reduce recurrence, and Gonadotropin-releasing hormone agonists (GnRH-a) were the most commonly used drug for postoperative management.GnRH-a may reduce the post-treatment endometriosis relapses by lowering the hormone levels in the body. However, the use of GnRH-a can give rise to perimenopausal symptoms, especially osteoporosis, bone loss, and bone pain, for which reason GnRH-a use is often limited. The add-back therapy is often used to alleviate the untoward effects caused by GnRH-a. However, long-term use of hormone drugs may lead to EMS recurrence, thrombosis, and breast cancer. Therefore, a safer and more effective drug is urgently needed to alleviate the untoward effects caused by GnRH-a. In recent years, scholars at home and abroad have found that isopropanolic Cimicifuga racemosa extract (ICR), as a plant extract, can better relieve the symptoms of perimenopausal women. At the same time, some studies have initially confirmed that black cohosh preparations can relieve the perimenopausal symptoms caused by GnRH-a treatment in EMS patients.

Objective: To investigate the effect of black cohosh preparations on the bone metabolism of rat models with GnRH-a-induced perimenopausal symptoms.

Methods: The rat models of perimenopausal symptoms were established by GnRH-a injection. and normal saline (NS injection) was used as the control. According to the modeling method and drug intervention, the rats were randomly divided into four groups: GnRH-a injection + saline intervention group (GnRH-a + NS), saline injection control + saline intervention group (NS + NS), GnRH-a injection + estradiol intervention group (GnRH-a + E2), and GnRH-a injection + black cohosh preparation intervention group (GnRH-a + ICR). The rat models were identified with the vaginal smear method, and then the corresponding drug intervention was administrated for 28 days. After the intervention, the rats were sacrificed. The rats' bone mineral density (BMD) of the distal femur was detected by a dual-energy X-ray bone density scanner. Rat tibia bone tissues were decalcified and made into slices. The pathological and morphological changes of rat tibial bones in each group were observed through HE staining. Histomorphometry parameters of rat tibial bones in each group, such as trabecular bone volume (TBV), trabecular thickness (TbTh), trabecular number (TbN), and trabecular spacing (TbSp), were detected and analyzed by using an automatic image analysis system.

Results: (1) The BMD level of the distal femur in the GnRH-a + NS group was significantly lower than the NS + NS, GnRH-a + E2, and GnRH-a + ICR groups (<0.01), the BMD levels in GnRH-a + E2 and GnRH-a + ICR groups were slightly lower than the NS + NS group, but there was no significant difference among the three groups (>0.05). (2) The pathological changes of the tibia bones under the microscope in different groups were as follows: The tibia bone trabecular structure was normal in the NS + NS group, without trabecular thinning or fracture, and the arch structure was normal. In the GnRH-a + NS group, some trabecular structures tapered, the arch structure disappeared, but no obvious bone fracture was observed in the trabecula. In the GnRH-a + E2 and GnRH-a + ICR groups, the trabecular structures were normal, without trabecular bone thinning or fracture, and the arch structures were normal. (3) The TBV level of the GnRH-a + INS group was significantly lower than that of the NS + NS, GnRH-a + E2 and GnRH-a + ICR groups (<0.01, <0.05, <0.01), while there was no significant difference among NS + NS, GnRH-a + E2 and GnRH-a + ICR groups (>0.05). (4) The TbTh levels in the four groups had no significant difference (>0.05). Compared with the NS + NS group, the TbTh levels in the GnRH-a + NS, GnRH-a + E2, and GnRH-a + ICR groups showed a descending tendency, while the TbTh levels in the GnRH-a + E2 and GnRH-a + ICR groups were slightly higher than that of the GnRH-a + NS group. However, such differences were not significant statistically (P>0.05). (5) Compared with the NS + NS group, the TbN levels in the GnRH-a + NS, GnRH-a + E2, and GnRH-a + ICR groups decreased remarkably (<0.05). Compared with the GnRH-a + NS group, the TbN levels in the GnRH-a + E2 and GnRH-a + ICR groups showed a mild descending tendency, but such differences were not significant statistically (>0.05). (6) The TbSp level of the GnRH-a + NS group was significantly higher than that of the NS + NS, GnRH-a + E2, and GnRH-a + ICR groups (<0.01), while there was no significant difference among NS + NS, GnRH-a + E2 and GnRH-a + ICR groups (>0.05).

Conclusion: The GnRH-a injection could achieve the desired effect. GnRH-a injection may lead to the loss of bone mass in rats. Black cohosh preparations, like estrogen, may have a protective effect on bone mass loss caused by GnRH-a injection.
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http://dx.doi.org/10.3389/fendo.2022.854345DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9224413PMC
June 2022

Adenosine-A Receptor Signaling Plays a Crucial Role in Sudden Unexpected Death in Epilepsy.

Front Pharmacol 2022 9;13:910535. Epub 2022 Jun 9.

Department of Pediatric Neurology, Randall Children's Hospital, Legacy Emanuel Medical Center, Portland, OR, United States.

Adenosinergic activities are suggested to participate in SUDEP pathophysiology; this study aimed to evaluate the adenosine hypothesis of SUDEP and specifically the role of adenosine A receptor (AR) in the development of a SUDEP mouse model with relevant clinical features. Using a combined paradigm of intrahippocampal and intraperitoneal administration of kainic acid (KA), we developed a boosted-KA model of SUDEP in genetically modified adenosine kinase (ADK) knockdown (Adk) mice, which has reduced ADK in the brain. Seizure activity was monitored using video-EEG methods, and recording of local field potential (LFP) was used to evaluate neuronal activity within the nucleus tractus solitarius (NTS). Our boosted-KA model of SUDEP was characterized by a delayed, postictal sudden death in epileptic mice. We demonstrated a higher incidence of SUDEP in Adk mice (34.8%) vs. WTs (8.0%), and the ADK inhibitor, 5-Iodotubercidin, further increased SUDEP in Adk mice (46.7%). We revealed that the NTS level of ADK was significantly increased in epileptic WTs, but not in epileptic Adk mutants, while the AR level in NTS was increased in epileptic (WT and Adk) mice vs. non-epileptic controls. The AR antagonist, SCH58261, significantly reduced SUDEP events in Adk mice. LFP data showed that SCH58261 partially restored KA injection-induced suppression of gamma oscillation in the NTS of epileptic WT mice, whereas SCH58261 increased theta and beta oscillations in Adk mutants after KA injection, albeit with no change in gamma oscillations. These LFP findings suggest that SCH58261 and KA induced changes in local neuronal activities in the NTS of epileptic mice. We revealed a crucial role for NTS AR in SUDEP pathophysiology suggesting AR as a potential therapeutic target for SUDEP risk prevention.
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http://dx.doi.org/10.3389/fphar.2022.910535DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9218562PMC
June 2022

Clinical value of the expression levels of protein tyrosine phosphatase non-receptor type 22.6 mRNA in peripheral blood mononuclear cells in Crohn's disease.

Clin Exp Immunol 2022 Jun 25. Epub 2022 Jun 25.

Department of Gastroenterology, The Central Hospital of Wuhan, Tongji Medical College, Huazhong University of Science and Technology; Key Laboratory for Molecular Diagnosis of Hubei Province, Wuhan 430014, China.

Objective: To explore the relationship between the expression levels of protein tyrosine phosphatase non-receptor type (PTPN) 22.6 mRNA in peripheral blood mononuclear cells (PBMCs) and the disease activity as well as clinical characteristics in Crohn's disease (CD) patients.

Methods: A total of 480 subjects were enrolled. Data were collected including baseline information, expression levels of PTPN22.6 mRNA in PBMCs for all subjects, C-reactive protein (CRP) levels in serum, clinical characteristics, and disease activity for all patients. Expression levels of PTPN22.6 mRNA in PBMCs, CRP levels in serum, clinical characteristics according to Montreal Classification 8, and Crohn's disease activity Index (CDAI) was the primary observation outcomes.

Results: The expression levels of PTPN22.6 mRNA (P = 0.032) in PBMCs and serum CRP levels (P < 0.001) were significantly higher in active CD patients than that in inactive CD patients (P = 0.032). Correlation analysis showed that there was a positive correlation between expression levels of PTPN22.6 mRNA and CDAI value (r = 0.512, P = 0.003), as well as expression levels of PTPN22.6 mRNA and CRP levels in CD group (r = 0.456, P = 0.006). There were significantly higher expression levels of PTPN22.6 mRNA in PBMCs in patients with stricturing behavior than that in patients with non-stricturing and non-penetrating (NSNP) behaviors (P = 0.018) and penetrating behaviors (P = 0.024).

Conclusions: The expression levels of PTPN22.6 mRNA can be used as an indicator to help predict CD diagnosis, disease activity, serum CRP level and behavior type of CD disease.
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http://dx.doi.org/10.1093/cei/uxac061DOI Listing
June 2022

Letter: gut-brain axis dysfunction underlies symptom generation in irritable bowel syndrome-a plea for rational interpretation of irrational doses of FODMAPs. Authors' reply.

Aliment Pharmacol Ther 2022 Jul;56(2):368-369

Laboratory for Brain-Gut Axis Studies (LaBGAS), Translational Research Centre for Gastrointestinal Disorders (TARGID), Department of Chronic Diseases & Metabolism (CHROMETA), KU Leuven, Leuven, Belgium.

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http://dx.doi.org/10.1111/apt.17074DOI Listing
July 2022

Maternal One-Carbon Supplement Reduced the Risk of Non-Alcoholic Fatty Liver Disease in Male Offspring.

Nutrients 2022 Jun 19;14(12). Epub 2022 Jun 19.

Department of Nutrition, Texas A&M University, College Station, TX 77840, USA.

Recent studies have suggested that prevention of obesity and non-alcoholic fatty liver disease (NAFLD) should start with maternal dietary management. We previously reported disrupted methionine cycle, associated with NAFLD, in male offspring liver due to maternal high-fat (HF) diet, thus we hypothesize that maternal one-carbon supplement may reduce the risk of NAFLD in offspring via the normalizing methionine cycle. To test it, female mice (F0) were exposed to either a maternal normal-fat diet (NF group) a maternal HF diet (HF group), or a maternal methyl donor supplement (H1S or H2S group) during gestation and lactation. The offspring male mice (F1) were exposed to a postweaning HF diet to promote NAFLD. While the HF offspring displayed obesity, glucose intolerance and hepatic steatosis, the H1S and H2S offspring avoided hepatic steatosis. This phenotype was associated with the normalization of the methionine cycle and the restoration of L-carnitine and AMPK activity. Furthermore, maternal HF diet induced epigenetic regulation of important genes involved in fatty acid oxidation and oxidative phosphorylation via DNA methylation modifications, which were recovered by maternal one-carbon supplementation. Our study provides evidence that maternal one-carbon supplement can reverse/block the adverse effects of maternal HF diet on promoting offspring NAFLD, suggesting a potential nutritional strategy that is administered to mothers to prevent NAFLD in the offspring.
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http://dx.doi.org/10.3390/nu14122545DOI Listing
June 2022

A simple and green method to prepare non-typical yolk/shell nanoreactor with dual-shells and multiple-cores: Enhanced catalytic activity and stability in Fenton-like reaction.

J Hazard Mater 2022 08 26;436:129234. Epub 2022 May 26.

Key Laboratory of Functional Inorganic Material Chemistry, Ministry of Education, School of Chemistry and Materials Science, Heilongjiang University, Harbin 150080, China. Electronic address:

Nowadays, non-typical yolk/shell structure has drawn much attentions due to the better catalytic performance than traditional counterparts (one yolk/one shell). In this study, ZIF-67 @CoSiO/SiO yolk/shell structure was prepared in one-step at room temperature, in which ZIF-67 was served as the hard-template, HO was served as etchant and tetraethyl orthosilicat was served as the raw material for CoSiO/SiO. After calcination, the non-typical CoO @CoSiO/SiO yolk/shell nanoreactor with CoSiO/SiO dual-shells and CoO multiple-cores was obtained. On the one hand, more active sites were exposed on multiple-cores surface and better protection were provided by dual-shells. On the other hand, the sheet-like CoSiO inner shell not only extended the travel path and retention time of pollutants trapped in cavity, but also separated the multiple-cores from aggregation. Therefore, the nanoreactor displayed the outstanding catalytic activity and recyclability in Fenton-like reaction. Metronidazole (20 mg/L) was completely degraded after 30 min, rhodamine B (50 mg/L) and methyl orange (20 mg/L) were removed even within 5.0 min. Catalytic mechanism indicated that O greatly contributed to the pollutant degradation. This paper presented a simple, versatile, green and energy-saving method for non-typical yolk/shell nanoreactor, and it could inspire to prepare other catalysts with high activity and stability for environmental remediation.
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http://dx.doi.org/10.1016/j.jhazmat.2022.129234DOI Listing
August 2022

Composition Engineering of Amorphous Nickel Boride Nanoarchitectures Enabling Highly Efficient Electrosynthesis of Hydrogen Peroxide.

Adv Mater 2022 Jun 23:e2202995. Epub 2022 Jun 23.

Institute of Functional Nano and Soft Materials (FUNSOM), Jiangsu Key Laboratory for Carbon-Based Functional Materials and Devices, Soochow University, Suzhou, 215123, P. R. China.

Developing advanced electrocatalysts with exceptional two electron (2e ) selectivity, activity and stability are crucial for driving oxygen reduction reaction (ORR) to produce hydrogen peroxide (H O ). Herein, a composition engineering strategy has been adapted to flexibly regulate the intrinsic activity of amorphous nickel boride nanoarchitectures for efficient 2e ORR by oriented reduction of Ni with different amounts of BH . Among borides, the amorphous NiB delivers the 2e selectivity close to 99% at 0.4 V and over 93% in a wide potential range, together with a negligible activity decay under prolonged time. Notably, an ultrahigh H O production rate of 4.753 mol g h has been achieved upon assembling NiB in the practical gas diffusion electrode. The combination of X-ray absorption and in situ Raman spectroscopy, as well as transient photovoltage measurements with density functional theory unequivocally reveal that the atomic ratio between Ni and B induces the local electronic structure diversity, allowing optimization of the adsorption energy of Ni towards *OOH and reducing the interfacial charge transfer kinetics to inhibit the formation of O-O. This article is protected by copyright. All rights reserved.
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http://dx.doi.org/10.1002/adma.202202995DOI Listing
June 2022

STING signaling sensing of DRP1-dependent mtDNA release in kupffer cells contributes to lipopolysaccharide-induced liver injury in mice.

Redox Biol 2022 Jun 15;54:102367. Epub 2022 Jun 15.

Guangdong Provincial Key Laboratory of Shock and Microcirculation, Department of Pathophysiology, School of Basic Medical Sciences, Southern Medical University, Guangzhou, 510515, China; Department of Critical Care Medicine, Nanfang Hospital, Southern Medical University, Guangzhou, 510515, China. Electronic address:

Aberrant pro-inflammatory activation of Kupffer cells (KCs) is strongly involved in the pathogenesis of septic liver injury. Recent evidence indicates the crucial roles of excessive stimulator of interferon genes (STING) signaling activation during sepsis. However, the role of STING signaling in septic liver injury remains unclear. In this study, we demonstrated that STING signaling was markedly activated in KCs isolated from wild type mice after lipopolysaccharide (LPS) treatment. STING deficiency effectively protected liver function, attenuated systemic inflammatory response and decreased mortality in LPS-treated mice, which were aggravated by STING agonist (DMXAA). Importantly, STING signaling activation in KCs contributed to LPS-induced liver injury through promoting hepatocyte death. Mechanistically, STING signaling could be activated by release of mitochondrial DNA (mtDNA) through dynamin-related protein 1 (DRP1)-dependent mitochondrial fission in LPS-treated KCs. Additionally, LPS stimulation enhanced DRP1-dependent mitochondrial ROS production, which promoted the leak of mtDNA into the cytosol and subsequent STING signaling activation in KCs. The in vivo experiments showed that pharmacological inhibition of DRP1 with Mdivi-1 partially prevented the activation of STING signaling in KCs isolated from LPS-challenged mice, as well as alleviated liver injury and inhibited systemic inflammatory response. In summary, our study comprehensively confirmed that STING signaling senses the DRP1-dependent release of mtDNA in KCs and its activation might play a key role in LPS-induced liver injury, which offers new sights and therapeutic targets for management of septic liver injury.
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http://dx.doi.org/10.1016/j.redox.2022.102367DOI Listing
June 2022

The High-Effective Catalytic Degradation of Benzo[a]pyrene by Mn-Corrolazine Regulated by Oriented External Electric Field: Insight From DFT Study.

Front Chem 2022 2;10:884105. Epub 2022 Jun 2.

School of Chemistry and Chemical Engineering, Guizhou University, Guiyang, China.

The degradation of BaP into hydroxybenzo[a]pyrene by Mn-corrolazine and its regulation by an oriented external electronic field (OEEF) were systematically studied using first-principle calculations. Extensive density function calculations showed that the degradation of BaP into hydroxybenzo[a]pyrene by Mn-corrolazine occurs a three-step process in the absence of OEEF, in which a more toxic and stable epoxide intermediate is generated. However, upon application of OEEF along the intrinsic Mn-O reaction axis, the degradation of BaP into hydroxybenzo[a]pyrene is greatly simplified. The negative charge on the terminal O atom of Mn-OO corrolazine increases with an increase in the OEEF intensity. As the intensity of the OEEF increases over 0.004 a.u., the negatively charged terminal O atom has the ability to directly abstract the positively charged H atom of BaP and the degradation of BaP into hydroxybenzo[a]pyrene can be completed a one-step process, avoiding the production of more toxic epoxide intermediates.
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http://dx.doi.org/10.3389/fchem.2022.884105DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9201028PMC
June 2022

Targeting PCSK9 Ameliorates Graft Vascular Disease in Mice by Inhibiting NLRP3 Inflammasome Activation in Vascular Smooth Muscle Cells.

Front Immunol 2022 26;13:894789. Epub 2022 May 26.

Department of Cardiovascular Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.

Background: Graft vascular disease (GVD), which limits the long-term survival of patients after solid-organ transplantation, is associated with both immune responses and nonimmune factors, including dyslipidemia. Recent studies have shown that inhibition of proprotein convertase subtilisin/kexin type 9 (PCSK9), a U.S. Federal Drug Administration-approved treatment for hyperlipidemia, reduces cardiovascular events, regulates inflammatory responses, and enhances the efficacy of immune checkpoint therapy in cancer treatment through a cholesterol-independent mechanism. However, whether targeting PCSK9 is a potential therapeutic strategy for GVD remains unknown.

Methods: Serum samples and grafts were harvested from male mice undergoing abdominal aortic transplantation. The pathological alterations in the aortic grafts were detected by hematoxylin and eosin staining, Verhoeff's Van Gieson staining, and Masson staining. Inflammatory cell infiltration and proinflammatory cytokine expression in the aortic grafts were detected by immunohistochemistry and quantitative real-time polymerase chain reaction (qRT-PCR), respectively. The regulatory effects of PCSK9 on vascular smooth muscle cell (VSMC) migration and proliferation were examined by transwell, EdU, and western blot assays. The effect of Evolocumab, a PCSK9 inhibitor, on GVD in humanized PCSK9 mice was also evaluated.

Results: PCSK9 was upregulated in the serum, grafts, and liver of mice in the allograft group subjected to abdominal aortic transplantation. knockout significantly reduced vascular stenosis, the intimal hyperplasia area and collagen deposition. depletion also inhibited macrophage recruitment and the mRNA expression of proinflammatory cytokines in aortic grafts. Furthermore, knockout suppressed the migration and proliferation of VSMCs, which was related to the inhibition of NLRP3 inflammasome activation. Meanwhile, Evolocumab significantly ameliorated GVD in humanized PCSK9 mice.

Conclusion: PCSK9 is upregulated in a mouse model of GVD, and knockout reduces vascular occlusion, suggesting that PCSK9 may be a promising target for the treatment of GVD.
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http://dx.doi.org/10.3389/fimmu.2022.894789DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9204514PMC
June 2022

Decreased Macular Retinal Thickness in Patients With Pterygium.

Front Neurol 2022 1;13:881190. Epub 2022 Jun 1.

Department of Ophthalmology, First Affiliated Hospital of Nanchang University, Nanchang, China.

Purpose: To explore alterations in macular retinal thickness (RT) and analyze correlation between macular RT and pterygium area, length in pterygium patients.

Methods: Totally 13 patients with pterygium (left eye) and 13 healthy controls (left eye) were recruited. OCTA was applied to scan each eye to generate three-dimensional images. Based on the Early Treatment Diabetic Retinopathy Study (ETDRS) method, each image was divided into nine subregions for the ETDRS: central (C); inner superior (IS); outer superior (OS); inner nasal (IN); outer nasal (ON); inner inferior (II); outer inferior (OI); inner temporal (IT); and outer temporal (OT). The macular RT in each subregion was measured. Furthermore, the correlation between RT and the area, length of pterygium was analyzed.

Results: The visual acuity of pterygium patient was different from that of the control ( < 0.05). Besides, decreased intraretinal thickness of the IN and ON, increased intraretinal thickness of OT, decreased extraretinal thickness of OT, IN, ON, OS, and decreased retinal full layer thickness of medial superior, OS, IN, ON, and II subregions in pterygium group were observed. There was a negative correlation between RT of the IN and ON subregions and the length of pterygium (r = -0.5803 and r = -0.6013, = 0.0376 and = 0.0297). The RT of IN subregion was negatively correlated with pterygium area (r = -0.5844, = 0.0359). According to the receiver operating characteristic analysis, in the ON subregion, the areas under the curve of the inner retinal thickness, outer retinal thickness and the whole retinal thickness were 1.0 (95% CI: 1.0), 0.882 (95% CI: 0.715 and 0.963), and 1.0 (95% CI: 1.0). The smallest area under the curve of retinal thickness in OT subregion was 0.018 (95% CI: 0-0.059).

Conclusion: RT of pterygium patients was significantly decreased, and the main alterations occurred in the temporal side suggesting there might exist retinal structural alterations in pterygium.
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http://dx.doi.org/10.3389/fneur.2022.881190DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9201995PMC
June 2022

Endoscopic Endonasal Supraoptic and Infraoptic Approaches for Complex "Parasuprasellar" Lesions: Surgical Anatomy, Technique Nuances, and Case Series.

Front Oncol 2022 26;12:847250. Epub 2022 May 26.

Department of Neurosurgery, The First Affiliated Hospital of Nanchang University, Nanchang, China.

Objective: The surgical management of lesions involving the lateral area of the suprasellar region, including the lateral aspect of the planum sphenoidale and the tight junction region of the optic canal (OC), anterior clinoid process (ACP), and internal carotid artery (ICA) and its dural rings, is extremely challenging. Here, these regions, namely, the "parasuprasellar" area, are described from the endonasal perspective. Moreover, the authors introduce two novels endoscopic endonasal supraoptic (EESO) and endoscopic endonasal infraoptic (EEIO) approaches to access the parasuprasellar area.

Methods: Surgical simulation of the EESO and EEIO approaches to the parasuprasellar area was conducted in 5 silicon-injected specimens. The same techniques were applied in 12 patients with lesions involving the parasuprasellar area.

Results: The EESO approach provided excellent surgical access to the lateral region of the planum sphenoidale, which corresponds to the orbital gyrus of the frontal lobe. With stepwise bone (OC, optic strut and ACP) removal, dissociation of the ophthalmic artery (OA) and optic nerve (ON), the EEIO approach enables access to the lateral region of the supraclinoidal ICA. These approaches can be used independently or in combination, but are more often employed as a complement to the endoscopic endonasal midline and transcavernous approaches. In clinical application, the EESO and EEIO approaches were successfully performed in 12 patients harboring tumors as well as multiple aneurysms involving the parasuprasellar area. Gross total and subtotal tumor resection were achieved in 9 patients and 1 patient, respectively. For two patients with multiple aneurysms, the lesions were clipped selectively according to location and size. Visual acuity improved in 7 patients, remained stable in 4, and deteriorated in only 1. No postoperative intracranial infection or ICA injury occurred in this series.

Conclusions: The EESO and EEIO approaches offer original treatment options for well-selected lesions involving the parasuprasellar area. They can be combined with the endoscopic endonasal midline and transcavernous approaches to remove extensive pathologies involving the intrasellar, suprasellar, sphenoid, and cavernous sinuses and even the bifurcation of the ICA. This work for the first time pushes the boundary of the endoscopic endonasal approach lateral to the supraclinoidal ICA and ON.
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http://dx.doi.org/10.3389/fonc.2022.847250DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9204328PMC
May 2022

Circulating Abnormal Extracellular Vesicles: Their Mechanism for Crossing Blood-Brain Barrier, Effects on Central Nervous System and Detection Methods.

J Biomed Nanotechnol 2022 Mar;18(3):640-659

Nanjing Drum Tower Hospital Clinical College of Jiangsu University, Nanjing, 210008, China.

Central nervous system (CNS) diseases are difficult to treat and harmful. Many CNS diseases are secondary to peripheral diseases, such as tumor brain metastases (BMS), viral infections and inflammation of the brain, and their pathogenic factors travel through the circulatory system to the brain, eventually leading to lesions. Extracellular vesicles (EVs) play an important role in this process. Recent studies have shown that, extracellular EVs can effectively cross the blood- brain barrier (BBB) through endocytosis and they transmit molecular signals in cell-to-cell communication. Abnormal EVs produced in the lesion portion transport pathogenic factors, including miRNAs, proteins, and virions into the CNS. These pathogenic factors participate in cellular pathways to interfere with homeostasis or are themselves pathogens that directly damage CNS. In addition, different or specific pathological molecules in EVs are potential disease markers. We herein reviewed pathways through which the abnormal EVs cross BBB and adverse effects of abnormal exosomes. We also and summarized their existing detection techniques, so as to provide basis for prevention and early diagnosis of secondary diseases.
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http://dx.doi.org/10.1166/jbn.2022.3293DOI Listing
March 2022

Perioperative Outcomes of Video-Assisted Thoracoscopic Surgery Versus Open Thoracotomy After Neoadjuvant Chemoimmunotherapy in Resectable NSCLC.

Front Oncol 2022 31;12:858189. Epub 2022 May 31.

The Second Department of Thoracic Surgery, Hunan Clinical Medical Research Center of Accurate Diagnosis and Treatment for Esophageal Carcinoma, Hunan Cancer Hospital and The Affiliated Cancer Hospital of Xiangya School of Medicine, Central South University, Changsha, China.

Background: Neoadjuvant chemoimmunotherapy becomes more widespread in the treatment of NSCLC, but few studies have reported the details of surgical techniques and perioperative challenges following neoadjuvant chemoimmunotherapy until now. The primary aim of our study was to address the feasibility and safety of pulmonary resection after neoadjuvant chemoimmunotherapy different surgical approaches, video-assisted thoracoscopic surgery (VATS) and open thoracotomy.

Methods: Patients with an initial diagnosis of clinical stage IB-IIIB(T3-4N2) NSCLC, who received neoadjuvant chemoimmunotherapy and surgery between January 2019 and August 2021 were included. Patients were retrospectively divided into two groups (VATS, and thoracotomy), and differences in perioperative, oncological, and survival outcomes were compared.

Results: In total, there were 131 NSCLC patients included. Surgery was delayed beyond 42 days in 21 patients (16.0%), and radical resection (R0) was achieved in 125 cases (95.4%). Lobectomy was the principal method of pulmonary resection (102 cases, 77.9%) and pneumonectomy was performed in 11 cases (8.4%). Postoperative complications within 30 days occurred in 28 patients (21.4%), and no 90-day mortality was recorded. There were 53 patients (38.5%) treated with VATS, and 78 (59.5%) with open thoracotomy. VATS could achieve similar definitive resection rates, postoperative recovery courses, comparable morbidities, and equivalent RFS rates(p>0.05), with the advantages of reduced operative time (160.1 ± 40.4 177.7 ± 57.7 min, p=0.042), less intraoperative blood loss (149.8 ± 57.9 321.2 ± 72.3 ml, p=0.021), and fewer intensive care unit(ICU) stays after surgery (3.8% 20.5%, p=0.006) compared with open thoracotomy. However, the mean number of total lymph nodes resected was lower in the VATS group (19.5 ± 7.9 23.0 ± 8.1, p=0.013). More patients in the thoracotomy group received bronchial sleeve resection/bronchoplasty (53.8% 32.1%, p=0.014) and vascular sleeve resection/angioplasty (23.1% 3.8%, p=0.003). After propensity score matching (PSM) analysis, VATS still had the advantage of fewer ICU stays after surgery (2.3% . 20.5%, p=0.007).

Conclusions: Our results have confirmed that pulmonary resection following neoadjuvant PD-1 inhibitors plus chemotherapy is safe and feasible. VATS could achieve similar safety, definitive surgical resection, postoperative recovery, and equivalent oncological efficacy as open thoracotomy, with the advantage of fewer ICU stays after surgery.
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http://dx.doi.org/10.3389/fonc.2022.858189DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9194512PMC
May 2022

Identification of an Endoplasmic Reticulum Stress-Related Gene Signature to Evaluate the Immune Status and Predict the Prognosis of Hepatocellular Carcinoma.

Front Genet 2022 27;13:850200. Epub 2022 May 27.

Department of Thoracic Surgery, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, China.

Liver cancer is the sixth most frequently diagnosed primary malignancy and ranks as the third leading cause of cancer-related death worldwide in 2020. ER stress also plays a vital role in the pathogenesis of malignancies. In the current study, we aimed to construct an endoplasmic reticulum stress-related genes (ERGs) signature to predict the overall survival (OS) of patients with HCC. Differentially expressed ERGs (DE-ERGs) were analyzed using The Cancer Genome Atlas (TCGA-LIHC cohort) and International Cancer Genome Consortium (ICGC-LIRI-JP cohort) databases. The prognostic gene signature was identified by the univariate Cox regression and Least Absolute Shrinkage and Selection Operator (LASSO)-penalized Cox proportional hazards regression analysis. The predictive ability of the model was evaluated by utilizing Kaplan-Meier curves and time-dependent receiver operating characteristic (ROC) curves. Gene set variant analysis (GSVA) was performed to explore the underlying biological processes and signaling pathways. CIBERPORT and single-sample Gene Set Enrichment Analysis (ssGSEA) were implemented to estimate the immune status between the different risk groups. A total of 113 DE-ERGs were identified between 50 normal samples and 365 HCC samples in the TCGA-LIHC cohort, and 48 DE-ERGs were associated with OS through the univariate Cox regression. A six DE-ERGs (, , , , , ) signature was constructed and classified patients into high-risk and low-risk groups. The risk score was an independent prognostic indicator for OS (HR > 1, < 0.001). The function enrichment analysis indicated that cell cycle, RNA degradation, protein localization, and cell division were the main biological processes. The high-risk group had higher immune cell infiltration levels than those of the low-risk group. We predicted the response to targeted therapy in high- and low-risk patients with HCC and found that the high-risk patients were more sensitive to pazopanib. At last, we verified the expression of the six gene patterns in HCC tissues by qRT-PCR and immunohistochemistry. This signature may be a potential tool to provide a choice for prognosis prediction and personal management of patients with HCC.
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http://dx.doi.org/10.3389/fgene.2022.850200DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9197218PMC
May 2022

Postoperative hypothalamic damage predicts postoperative weight gain in patients with adult-onset craniopharyngioma.

Obesity (Silver Spring) 2022 Jun 16. Epub 2022 Jun 16.

Department of Neurosurgery, The First Affiliated Hospital of Nanchang University, Nanchang, China.

Objective: This study aimed to recapitulate the change trajectory of postoperative weight and investigate the association between postoperative hypothalamic damage and weight gain and hypothalamic obesity (HO) in patients with adult-onset craniopharyngioma.

Methods: The data of 96 patients with surgically treated primary adult-onset craniopharyngioma were retrospectively analyzed. The association between postoperative hypothalamic damage based on magnetic resonance images or endoscopic observation and postoperative weight gain and HO was determined by multivariable logistic regression.

Results: Forty-seven (49.0%) patients and 18 (18.8%) patients experienced clinically meaningful weight gain (≥5%) and HO at last follow-up, respectively. Postoperative weight significantly increased during the first 6 months following surgery, followed by stabilization. Both grade 2 postoperative hypothalamus damage, as evaluated by the magnetic resonance imaging classification system of Müller et al., and higher scores based on the Roth et al. hypothalamic lesion score were significantly associated with postoperative weight gain of ≥5% (p = 0.005 and p = 0.002) and with HO (p = 0.001 and p = 0.008). Additionally, bilateral hypothalamic injury as evaluated by the Hong et al. hypothalamic injury pattern based on endoscopic observation (p = 0.008) could predict postoperative weight gain ≥5%.

Conclusions: Significant postoperative weight gain is common in patients with adult-onset craniopharyngioma. Postoperative hypothalamic damage can predict clinically meaningful weight gain and HO.
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http://dx.doi.org/10.1002/oby.23447DOI Listing
June 2022

International trends in esophageal cancer incidence rates by histological subtype (1990-2012) and prediction of the rates to 2030.

Esophagus 2022 Jun 11. Epub 2022 Jun 11.

State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, National Clinical Research Center for Infectious Diseases, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, 310003, China.

Background: We provide an up-to-date overview of recent international trends (1990-2012) and predicted trends (2013-2030) in the incidence rates of esophageal cancer.

Methods: We used data from the Cancer Incidence in Five Continents (CI5plus) database that contains annual incidence data by cancer site, age, and sex as well as corresponding populations. The age-standardized esophageal cancer incidence rates of each country were calculated and plotted from 1990 through 2012 and were predicted to 2030 using a Bayesian age-period-cohort model.

Results: Globally, esophageal squamous cell carcinoma (ESCC) and esophageal adenocarcinoma (EAC) showed opposing trends between 1990 and 2012; ESCC showed a decreasing trend, with an AAPC of - 1.5 (95% CI - 2.4, - 0.7), yet EAC showed an increasing trend, with an AAPC of 5.2 (95% CI 4.2, 6.2). The increasing trend in EAC was commonly observed in high-income countries. The predicted trend to 2030 indicated that most countries will continue to experience a decreasing trend or a stable trend in esophageal cancer incidence, except Denmark, the Netherlands, and the UK, where the overall esophageal cancer incidence rates, mainly driven by EAC, are predicted to increase.

Conclusions: Decreasing trends in ESCC have been observed worldwide in both low- and middle-income countries and high-income countries, which may have been offset by increasing trends in EAC in high-income countries. The changing patterns of these two main subtypes of esophageal cancer may call for interventions, especially innovative interventions, to address obesity, GERD, and Barrett's esophagus.
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http://dx.doi.org/10.1007/s10388-022-00927-4DOI Listing
June 2022

Long-term Effects of Riboflavin Ultraviolet-A-Induced CXL With Different Irradiances on the Biomechanics of In Vivo Rabbit Corneas.

J Refract Surg 2022 Jun 1;38(6):389-397. Epub 2022 Jun 1.

Purpose: To evaluate the long-term effects of ultraviolet-A corneal cross-linking (CXL) with different irrandiances on the biomechanical properties of rabbit corneas and the corresponding changes in stromal microstructure.

Methods: The study involved the left eyes of 85 healthy white Japanese rabbits, randomly divided into five groups (n = 16 to 18 each). After removing the epithelium, the first four groups were exposed to riboflavin (0.22% concentration by volume) and ultraviolet-A (370 nm) at different CXL irradiations but with the same total dose (5.4 J/cm). The four groups were defined as standard CXL (SCXL; 3 mW/cm for 30 minutes, n = 17), accelerated CXL1 (ACXL1; 9 mW/cm for 10 minutes, n = 16), accelerated CXL2 (ACXL2; 18 mW/cm for 5 minutes, n = 17), and accelerated CXL3 (ACXL3; 30 mW/cm for 3 minutes, n = 17). The control group (n = 18) was treated with riboflavin without ultraviolet-A exposure. Nine months after CXL, 10 corneas from each group were tested ex vivo under inflation, and the tangent modulus (Et) was estimated using an inverse analysis process. The remaining six to eight specimens in each group were examined by electron microscopy to determine the mean fibril diameter and interfibrillar spacing.

Results: The SCXL and ACXL1 groups showed statistically significant differences in Et at all stresses (0.005, 0.010, and 0.015 MPa) analyzed compared to the control group (all < .01), but the differences were non-significant in the ACXL3 group ( = 1.000, .785, and .679, respectively). For the ACXL2 group, there was no statistical difference in Et under the low stress of 0.005 MPa ( = .155), but the differences became significant at 0.010 and 0.015 MPa when compared with the control group (all < .05).

Conclusions: CXL had a significant effect on corneal biomechanics in both standard and accelerated procedures. However, standard CXL was the most effective, and this effectiveness decreased gradually with increasing ultraviolet-A power intensity. .
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http://dx.doi.org/10.3928/1081597X-20220425-01DOI Listing
June 2022

A Prediction Model for Acute Kidney Injury in Adult Patients With Minimal Change Disease.

Front Med (Lausanne) 2022 24;9:862160. Epub 2022 May 24.

Department of Nephrology, First Medical Center of Chinese PLA General Hospital, Nephrology Institute of the Chinese PLA, State Key Laboratory of Kidney Diseases, National Clinical Research Center for Kidney Diseases, Beijing Key Laboratory of Kidney Disease Research, Beijing, China.

Background: Early prediction of acute kidney injury (AKI) can allow for timely interventions, but there are still few methods that are easy and convenient to apply in predicting AKI, specially targeted at patients with minimal change disease (MCD). Motivated by this, we aimed to develop a predicting model for AKI in patients with MCD within the KDIGO criteria.

Methods: Data on 401 hospitalized adult patients, whose biopsy was diagnosed as MCD from 12/31/2010 to 15/7/2021, were retrospectively collected. Among these data, patients underwent biopsy earlier formed the training set ( = 283), while the remaining patients formed the validation set ( = 118). Independent risk factors associated with AKI were analyzed. From this, the prediction model was developed and nomogram was plotted.

Results: AKI was found in 55 of 283 patients (19%) and 15 of 118 patients (13%) in the training and validation cohorts, respectively. According to the results from lasso regression and logistic regression, it was found that four factors, including mean arterial pressure, serum albumin, uric acid, and lymphocyte counts, were independent of the onset of AKI. Incorporating these factors, the nomogram achieved a reasonably good concordance index of 0.84 (95%CI 0.77-0.90) and 0.75 (95%CI 0.62-0.87) in predicting AKI in the training and validation cohorts, respectively. Decision curve analysis suggested clinical benefit of the prediction models.

Conclusions: Our predictive nomogram provides a feasible approach to identify high risk MCD patients who might develop AKI, which might facilitate the timely treatment.
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http://dx.doi.org/10.3389/fmed.2022.862160DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9170996PMC
May 2022

Assessment of the Benefits of Targeted Interventions for Pandemic Control in China Based on Machine Learning Method and Web Service for COVID-19 Policy Simulation.

Biomed Environ Sci 2022 May;35(5):412-418

Center for Global Public Health, Chinese Center for Disease Control and Prevention, Beijing 102206, China.

Taking the Chinese city of Xiamen as an example, simulation and quantitative analysis were performed on the transmissions of the Coronavirus Disease 2019 (COVID-19) and the influence of intervention combinations to assist policymakers in the preparation of targeted response measures. A machine learning model was built to estimate the effectiveness of interventions and simulate transmission in different scenarios. The comparison was conducted between simulated and real cases in Xiamen. A web interface with adjustable parameters, including choice of intervention measures, intervention weights, vaccination, and viral variants, was designed for users to run the simulation. The total case number was set as the outcome. The cumulative number was 4,614,641 without restrictions and 78 under the strictest intervention set. Simulation with the parameters closest to the real situation of the Xiamen outbreak was performed to verify the accuracy and reliability of the model. The simulation model generated a duration of 52 days before the daily cases dropped to zero and the final cumulative case number of 200, which were 25 more days and 36 fewer cases than the real situation, respectively. Targeted interventions could benefit the prevention and control of COVID-19 outbreak while safeguarding public health and mitigating impacts on people's livelihood.
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http://dx.doi.org/10.3967/bes2022.057DOI Listing
May 2022

Evaluation of an intelligent artificial climate chamber for high-throughput crop phenotyping in wheat.

Plant Methods 2022 Jun 7;18(1):77. Epub 2022 Jun 7.

College of Engineering, Nanjing Agricultural University, Nanjing, 210031, China.

Background: The superposition of COVID-19 and climate change has brought great challenges to global food security. As a major economic crop in the world, studying its phenotype to cultivate high-quality wheat varieties is an important way to increase grain yield. However, most of the existing phenotyping platforms have the disadvantages of high construction and maintenance costs, immobile and limited in use by climatic factors, while the traditional climate chambers lack phenotypic data acquisition, which makes crop phenotyping research and development difficult. Crop breeding progress is slow. At present, there is an urgent need to develop a low-cost, easy-to-promote, climate- and site-independent facility that combines the functions of crop cultivation and phenotype acquisition. We propose a movable cabin-type intelligent artificial climate chamber, and build an environmental control system, a crop phenotype monitoring system, and a crop phenotype acquisition system.

Result: We selected two wheat varieties with different early vigor to carry out the cultivation experiments and phenotype acquisition of wheat under different nitrogen fertilizer application rates in an intelligent artificial climate chamber. With the help of the crop phenotype acquisition system, images of wheat at the trefoil stage, pre-tillering stage, late tillering stage and jointing stage were collected, and then the phenotypic information including wheat leaf area, plant height, and canopy temperature were extracted by the crop type acquisition system. We compared systematic and manual measurements of crop phenotypes for wheat phenotypes. The results of the analysis showed that the systematic measurements of leaf area, plant height and canopy temperature of wheat in four growth periods were highly correlated with the artificial measurements. The correlation coefficient (r) is positive, and the determination coefficient (R) is greater than 0.7156. The root mean square error (RSME) is less than 2.42. Among them, the crop phenotype-based collection system has the smallest measurement error for the phenotypic characteristics of wheat trefoil stage. The canopy temperature RSME is only 0.261. The systematic measurement values of wheat phenotypic characteristics were significantly positively correlated with the artificial measurement values, the fitting degree was good, and the errors were all within the acceptable range. The experiment showed that the phenotypic data obtained with the intelligent artificial climate chamber has high accuracy. We verified the feasibility of wheat cultivation and phenotype acquisition based on intelligent artificial climate chamber.

Conclusion: It is feasible to study wheat cultivation and canopy phenotype with the help of intelligent artificial climate chamber. Based on a variety of environmental monitoring sensors and environmental regulation equipment, the growth environment factors of crops can be adjusted. Based on high-precision mechanical transmission and multi-dimensional imaging sensors, crop images can be collected to extract crop phenotype information. Its use is not limited by environmental and climatic factors. Therefore, the intelligent artificial climate chamber is expected to be a powerful tool for breeders to develop excellent germplasm varieties.
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http://dx.doi.org/10.1186/s13007-022-00916-9DOI Listing
June 2022

Refillable Fuel-Loading Microshell Motors for Persistent Motion in a Fuel-Free Environment.

ACS Appl Mater Interfaces 2022 Jun 6. Epub 2022 Jun 6.

State Key Laboratory of Analytical Chemistry for Life Science, School of Chemistry and Chemical Engineering, Nanjing University, Nanjing 210023, P. R. China.

Artificial micro-/nanomotors that harvest environmental energy to move require energy surroundings; thus, their motion generally occurs in fuel solutions or under the real-time stimuli of external energy sources. Herein, inspired by vehicles, a refillable fuel-loading micromotor is proposed based on a 2 μm hemispherical multimetallic shell using catalase or platinum on its concave surface as the engine and the bowl structure as the fuel tank. HO fuel is drawn into the microbowl by capillary action and restricted inside the bowl space through a self-generated O bubble cap on the microshell mouth. The periodic growth and burst of the O cap cause the enhanced diffusion motion of micromotors. This motion behavior can last for at least 30 min in a fuel-free environment with one HO fueling. Additionally, the micromotor can be refilled repeatedly to achieve permanent motion. This demonstration of a refillable fuel-loading micromotor provides a model design of an energy built-in micromotor.
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http://dx.doi.org/10.1021/acsami.2c05442DOI Listing
June 2022

Melatonin and Its Analogs for Prevention of Post-cardiac Surgery Delirium: A Systematic Review and Meta-Analysis.

Front Cardiovasc Med 2022 18;9:888211. Epub 2022 May 18.

Department of Anaesthesiology, Nanfang Hospital, Southern Medical University, Guangzhou, China.

Background: The effectiveness of melatonin and its analogs in preventing postoperative delirium (POD) following cardiac surgery is controversial. The purpose of this systematic review and meta-analysis was to confirm the benefits of melatonin and its analogs on delirium prevention in adults who underwent cardiac surgery.

Methods: We systematically searched the PubMed, Cochrane Library, Web of Science, Embase, and EBSCOhost databases, the last search was performed in October 2021 and repeated before publication. The controlled studies were included if investigated the impact of melatonin and its analogs on POD in adults who underwent cardiac surgery. The primary outcome was the incidence of delirium. The Stata statistical software 17.0 was used to perform this study.

Results: This meta-analysis included eight randomized controlled trials (RCTs) and two cohort studies with a total of 1,714 patients. The results showed that melatonin and ramelteon administration were associated with a significantly lower incidence of POD in adults who underwent cardiac surgery (odds ratio [OR], 0.46; 95% confidence interval [CI], 0.29-0.74; = 0.001). The subgroup analyses confirmed that melatonin 3 mg (OR, 0.37; 95% CI, 0.18-0.76; = 0.007) and 5 mg (OR, 0.34; 95% CI, 0.21-0.56; < 0.001) significantly reduced the incidence of POD.

Conclusion: Melatonin at dosages of 5 and 3 mg considerably decreased the risk of delirium in adults who underwent cardiac surgery, according to our results. Cautious interpretation of our results is important owing to the modest number of studies included in this meta-analysis and the heterogeneity among them.

Systematic Review Registration: PROSPERO registration number: CRD42021246984.
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http://dx.doi.org/10.3389/fcvm.2022.888211DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9157569PMC
May 2022

The SES-CD Could Be a Predictor of Short- and Long-Term Mucosal Healing After Exclusive Enteral Nutrition in Pediatric Crohn's Disease Patients.

Front Pediatr 2022 18;10:874425. Epub 2022 May 18.

Department of Gastroenterology, Pediatric Inflammatory Bowel Disease Research Center, National Children's Medical Center, Children's Hospital of Fudan University, Shanghai, China.

Aims: To explore the predictors of mucosal healing (MH) for short- and long-term after exclusive enteral nutrition (EEN) in pediatric Crohn's disease (CD) patients.

Methods: A retrospective analysis was performed for newly diagnosed active CD patients admitted to our center from January 2017 to 30 December 2020, who were treated with EEN for induction therapy with a minimum of 12 months of follow-up post-EEN. According to the simple endoscopic score for CD (SES-CD), at 1-year post-EEN, 17 patients with an SES-CD < 3 were classified into the sustained MH group (sMH), and 33 patients with an SES-CD ≥ 3 were classified into the sustained non-MH group (sNMH). Statistical methods were used to compare the differences between the two groups and explore the predictors of MH at the end of EEN and 1-year post-EEN.

Results: The SES-CD in the sMH group was lower than that in the sNMH group both at baseline and the end of EEN [sMH vs. sNMH: 8.7 ± 1.2 vs. 16.2 ± 1.0, respectively, < 0.001 at baseline; 1.0 (3.5) vs. 4.0 (2.0), respectively, < 0.01 at the end of EEN]. The weighted Pediatric Crohn's Disease Activity Index and erythrocyte sedimentation rate in the sMH group were lower than those in the sNMH group at baseline (both < 0.05), but showed no difference at the end of EEN. From baseline to 1-year post-EEN, compared with patients in the sNMH group, there were more patients classified with L1 in the sMH group at each time point (all < 0.001) and fewer patients classified with L3 in the sMH group at baseline and 1-year post-EEN. After EEN, fewer patients received infliximab and had a longer exposure time to infliximab in the sMH group than in the sNMH group. Only the SES-CD at baseline was negatively associated with MH at the end of EEN (OR = 1.40 95% CI = 1.12-1.67, = 0.00) and 1-year post-EEN (OR = 1.33, 95% CI = 1.12-1.58, = 0.001), and the cut off value was 11.5.

Conclusion: The SES-CD could predict both short- and long-term MH for EEN. Patients with an SES-CD < 11.5 had a high probability of reaching MH by EEN-inducing therapy and maintaining sustained MH at 1-year post-EEN. Patients with an SES-CD greater than 11.5 at baseline should be treated more aggressively with biologics.
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http://dx.doi.org/10.3389/fped.2022.874425DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9157786PMC
May 2022

Nomograms to Predict Endocrinological Deficiency in Patients With Surgically Treated Craniopharyngioma.

Front Oncol 2022 19;12:840572. Epub 2022 May 19.

Department of Neurosurgery, The First Affiliated Hospital of Nanchang University, Nanchang, China.

Objective: Postoperative hypopituitarism associated with increased risks of premature mobility and mortality is often encountered in craniopharyngioma patients. The aim of our study is to construct nomograms related to injury types of the hypothalamus-pituitary axis (HPA) to predict hypopituitarism 1 year after surgery.

Methods: Craniopharyngioma patients undergoing initial endoscopic endonasal surgery between December 2012 and March 2021 in our center were retrospectively reviewed, and injury types of the HPA were categorized according to intraoperative endoscopic observation. Included patients were randomly divided into a training group and a validation group. Nomograms were established based on the results of multivariate logistic analysis. The predictive performance of the nomograms was evaluated in the training and validation groups.

Results: A total of 183 patients with craniopharyngioma were enrolled, and seven injury types of the HPA were summarized. Relative to intact HPA, exclusive hypothalamus injury significantly increased the risk of anterior (OR, 194.174; 95% CI, 21.311-1769.253; p < 0.001) and posterior pituitary dysfunction (OR, 31.393; 95% CI, 6.319-155.964; p < 0.001) 1 year after surgery, while exclusively sacrificing stalk infiltrated by tumors did not significantly increase the risk of anterior (OR, 5.633; 95% CI, 0.753-42.133; p = 0.092) and posterior pituitary dysfunction (OR, 1.580; 95% CI, 0.257-9.707; p = 0.621) 1 year after surgery. In the training group, the AUCs of nomograms predicting anterior and posterior pituitary dysfunction 1 year after surgery were 0.921 and 0.885, respectively, compared with 0.921 and 0.880 in the validation group.

Conclusions: Intact hypothalamus structure is critical in maintaining pituitary function. Moreover, our preliminary study suggests that the pituitary stalk infiltrated by craniopharyngioma could be sacrificed to achieve radical resection, without substantially rendering significantly worse endocrinological efficiency 1 year after surgery. The user-friendly nomograms can be used to predict hypopituitarism 1 year after surgery.
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http://dx.doi.org/10.3389/fonc.2022.840572DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9161152PMC
May 2022

INSC Is Down-Regulated in Colon Cancer and Correlated to Immune Infiltration.

Front Genet 2022 19;13:821826. Epub 2022 May 19.

Department of Neurosurgery, Renmin Hospital of Wuhan University, Wuhan, China.

Previous studies have verified that Inscuteable Spindle Orientation Adaptor Protein (INSC) can regulate cell proliferation and differentiation in the developing nervous system. It also plays an important role in spindle orientation during mitosis and asymmetric division of fibroblasts and participates in the process of stratification of the squamous epithelium. The role and potential mechanism of INSC in the development of colonic adenocarcinoma (COAD) have not been fully understood. This study aimed at exploring the prognostic value of INSC in COAD and the correlation of its expression with immune infiltration. The Cancer Genome Atlas (TCGA), Genotype-Tissue Expression (GTEx) project, Gene Expression Profiling Interactive Analysis (GEPIA), and Gene Expression Omnibus (GEO) database were used to analyze the expression of INSC in COAD. The INSC protein expression level was analyzed by immunohistochemistry staining and the Human Protein Atlas (HPA) database. The diagnostic and prognostic values of INSC in COAD patients were analyzed using receiver operating characteristic (ROC) and Kaplan-Meier (KM) survival curves. In order to understand whether INSC is an independent prognostic factor, we used univariable and multivariate Cox analyses to analyze INSC expression and several clinical characteristics with survival. We use STRING analysis to find INSC-related proteins and related biological events analyzed by Gene Ontology (GO) annotation and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis. At last, GEPIA and the Tumor Immune Estimation Resource (TIMER) were employed to explore the relationship between INSC and immune infiltrates and its marker gene set. INSC was lower expressed in COAD tissues than in normal colon tissues, which was correlated with tumor stage. Patients with lower expression of INSC had shorter overall survival (OS). Moreover, univariable Cox analysis demonstrated that high expression of INSC was an independent prognostic factor for COAD. ROC analysis showed INSC was an accurate marker for identifying tumors from normal colon tissue, and the AUC of the curve was 0.923. Significant GO term analysis by GSEA showed that genes correlated with INSC were found to be enriched in several immune-related pathways. Specifically, INSC expression showed significant negative correlations with infiltration levels of B cells, CD4 T cells, macrophages, DCs, and their marker sets in COAD. INSC was provided with prognostic value in COAD and related to immune invasion.
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http://dx.doi.org/10.3389/fgene.2022.821826DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9161087PMC
May 2022

Underwater endoscopic mucosal resection for rectal neuroendocrine tumors (with videos): a single center retrospective study.

BMC Gastroenterol 2022 Jun 2;22(1):276. Epub 2022 Jun 2.

Department of Gastroenterology, The Second Affiliated Hospital of Xi'an Jiaotong University, 157 Xiwu Street, Xi'an, 710004, Shaanxi, China.

Background: Underwater endoscopic mucosal resection (UMER) is a new method of endoscopic resection to completely remove the lesion without submucosal injection. But few attempts have been carried out for rectal neuroendocrine tumors (rectal NETs).

Methods: We retrospectively investigated data on the tumor characteristics and outcomes of patients with ≤ 10 mm rectal NETs who underwent UEMR or endoscopic submucosal dissection (ESD) from January 2019 to June 2021 in our institute.

Results: The endoscopic resection rate was 100% in both UEMR and ESD groups. The histological complete resection rate of the UEMR group (95.5%) was lower than that of the ESD group (96.4%) with no significant difference. The average operation time, hospitalization time and operation cost of UEMR group were less than those of ESD group (P < 0.05). The incidence of postoperative abdominal pain and abdominal distention in the UEMR group was lower than that in the ESD group (P < 0.05). There was no significant difference in the incidence of delayed bleeding and perforation between the two groups. There was no local recurrence or distant metastasis in the two groups during the follow-up period.

Conclusions: Both the UEMR and ESD can effectively treat ≤ 10 mm rectal NETs with invasion depth confined to the mucosa and submucosa. UEMR is superior to ESD in operation time, hospitalization time, operation cost, postoperative abdominal pain and abdominal distention.
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http://dx.doi.org/10.1186/s12876-022-02350-6DOI Listing
June 2022
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