Publications by authors named "Lei Zhou"

2,118 Publications

  • Page 1 of 1

Dietary supplementation with perillartine ameliorates lipid metabolism disorder induced by a high-fat diet in broiler chickens.

Biochem Biophys Res Commun 2022 Aug 2;625:66-74. Epub 2022 Aug 2.

State Key Laboratory for Conservation and Utilization of Subtropical Agro-bioresources, College of Animal Science and Technology, Guangxi University, Nanning, Guangxi Zhuang Autonomous Region, 530004, PR China. Electronic address:

Lipid metabolism disorders affect the growth and jeopardize the health of poultry, thus, decreasing economic benefits. Perillartine, a sweetener derived from Perilla frutescens, has excellent potential in regulating lipid metabolism. In this study, we explored the effects of perillartine on lipid metabolism in broiler chickens by establishing a nonalcoholic fatty liver model induced by a high-fat diet. By using network pharmacology and molecular docking, we analyzed the potential molecular targets and pathways through which perillartine regulates lipid metabolism and alleviates fatty liver. Perillartine was found to regulate the expression of genes associated with lipogenesis, lipolysis, and lipid transport, including FASN, PPARα, CPT-1, ACCα, APOB, and APOA1 in the liver, and to decrease lipid accumulation in the liver and blood in broilers without affecting growth performance. In addition, we discovered 24 candidate targets of perillartine, including SRD5A2 and XDH, through network pharmacology analysis and successfully constructed a compound-target-pathway-disease network. Our results suggested that perillartine may be a promising, long-lasting therapeutic molecule for modulating lipid metabolism disorders in broilers.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.bbrc.2022.07.116DOI Listing
August 2022

IL-1β induced by PRRSV co-infection inhibited CSFV C-strain proliferation via the TLR4/NF-κB/MAPK pathways and the NLRP3 inflammasome.

Vet Microbiol 2022 Jul 15;273:109513. Epub 2022 Jul 15.

Key Laboratory of Animal Epidemiology of the Ministry of Agriculture, College of Veterinary Medicine, China Agricultural University, Beijing 100193, People's Republic of China.

PRRSV and CSFV are both the main pathogens of pigs and pose great threats to the pig industry. Previous studies have shown that PRRSV infection or attenuated virus vaccination can reduce the antibody level of attenuated CSFV vaccine and even cause immune failure. The higher pro-inflammatory cytokines induced by PRRSV might play a significant role in inhibiting the proliferation of CSFV-C. However, the molecular mechanism has not been elucidated yet. Here, the effect of IL-1β, a central mediator of immune-regulating inflammatory responses, on CSFV-C proliferation was investigated, as well as the mechanisms responsible for the production of IL-1β in the PRRSV and CSFV-C co-infection systems. The results showed that co-infection could significantly increase IL-1β production both at mRNA and protein levels with the infection progressing, and the IL-1β upregulation was mainly triggered by PRRSV infection. Additional experiments indicated that IL-1β inhibited the proliferation of CSFV-C in a cell-type independent manner at the replication and release stages. Furthermore, the IL-1β production induced via the TLR4/MyD88 pathway and the downstream signaling pathways NF-κB, ERK1/2, P38, and JNK were involved by treatment with specific inhibitors or siRNA knockdown assays. Finally, we clarified that the NLRP3 inflammasome played a meaningful role in the maturation and release of IL-1β. Together, the accumulated results provided a deeper understanding of the vaccination failure of CSFV caused by PRRSV co-infection as well as targets for the development of novel approaches for the vaccination and control of CSF.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.vetmic.2022.109513DOI Listing
July 2022

Nav1.8 in keratinocytes contributes to ROS-mediated inflammation in inflammatory skin diseases.

Redox Biol 2022 Aug 5;55:102427. Epub 2022 Aug 5.

Department of Dermatology, Xiangya Hospital, Central South University, Changsha, China; Hunan Key Laboratory of Aging Biology, Xiangya Hospital, Central South University, Changsha, China; National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Changsha, Hunan, 410008, China. Electronic address:

Reactive oxygen species (ROS)-activated proinflammatory signals in keratinocytes play a crucial role in the immunoregulation of inflammatory skin diseases, including rosacea and psoriasis. Nav1.8 is a voltage-gated sodium ion channel, and its abnormal expression in the epidermal layer contributes to pain hypersensitivity in the skin. However, whether and how epidermal Nav1.8 is involved in skin immunoregulation remains unclear. This study was performed to identify the therapeutic role of Nav1.8 in inflammatory skin disorders. We found that Nav1.8 expression was significantly upregulated in the epidermis of rosacea and psoriasis skin lesions. Nav1.8 knockdown ameliorated skin inflammation in LL37-and imiquimod-induced inflammation mouse models. Transcriptome sequencing results indicated that Nav1.8 regulated the expression of pro-inflammatory mediators (IL1β and IL6) in keratinocytes, thereby contributing to immune infiltration in inflammatory skin disorders. In vitro, tumor necrosis factor alpha (TNFα), a cytokine that drives the development of various inflammatory skin disorders, increased Nav1.8 expression in keratinocytes. Knockdown of Nav1.8 eliminated excess ROS production, thereby attenuating the TNFα-induced production of inflammatory mediators; however, a Nav1.8 blocker did not have the same effect. Mechanistically, Nav1.8 reduced superoxide dismutase 2 (SOD2) activity by directly binding to SOD2 to prevent its deacetylation and mitochondrial localization, subsequently inducing ROS accumulation. Collectively, our study describes a central role for Nav1.8 in regulating pro-inflammatory responses in the skin and indicates a novel therapeutic strategy for rosacea and psoriasis.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.redox.2022.102427DOI Listing
August 2022

Cold plasma effects on the nutrients and microbiological quality of sprouts.

Food Res Int 2022 Sep 9;159:111655. Epub 2022 Jul 9.

Department of Food Science and Nutrition, College of Culture and Tourism, University of Jinan, Jinan 250002, China. Electronic address:

Sprouts have been more and more popular among people all over the world due to their health benefits and good taste. Cold plasma (CP) is a promising and efficient nonthermal technology that has been applied to various aspects, including seed germination, plant growth, the synthesis of secondary metabolites. This review aims to represent the current knowledge status and future insights of CP on germination, nutritional quality and microbial inactivation of sprouts, and influencing mechanism was also discussed. CP under favorable conditions can promote the growth of sprouts, thus increase the yield of sprouts and microgreens. Numerous studies suggest that CP can promote the accumulation of bioactive compounds in sprouts, and subsequently enhance biological activities and so on the antioxidant capacity and antiproliferative effect. CP is an effective method for the inactivation of microorganisms on seeds and sprouts by reactive species. Therefore, CP is a promising technology for the sustainable development of sprouts industry.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.foodres.2022.111655DOI Listing
September 2022

Low-Density Lipoprotein Cholesterol and Mortality in Peritoneal Dialysis.

Front Nutr 2022 21;9:910348. Epub 2022 Jul 21.

Department of Nephrology, Zhejiang University Medical College Affiliated Sir Run Run Shaw Hospital, Hangzhou, China.

Background: In dialysis patients, lowering low-density lipoprotein cholesterol (LDL-C) did not provide benefits, which seemed implausible in clinical practice. We hypothesized a U-shaped association between LDL-C and mortality in dialysis patients.

Methods: In this multi-center retrospective real-world cohort study, 3,565 incident Chinese peritoneal dialysis (PD) patients between January 1, 2005, and May 31, 2020, were included. The associations between baseline LDL-C and mortality were examined using cause-specific hazard models.

Results: Of 3,565 patients, 820 died, including 415 cardiovascular deaths. As compared with the reference range (2.26-2.60 mmol/L), both higher levels of LDL-C (> 2.60 mmol/L) and lower levels of LDL-C (< 2.26 mmol/L) were associated with increased risks of all-cause mortality (hazard ratio [HR],1.35, 95% confidence index [CI], 1.09-1.66; HR 1.36, 95%CI, 1.13-1.64) and cardiovascular mortality (HR, 1.31, 95% CI, 1.10-1.72; HR, 1.64; 95% CI, 1.22-2.19). Malnutrition (albumin < 36.0 g/L) modified the association between LDL-C and cardiovascular mortality (P for interaction = 0.01). A significantly increased risk of cardiovascular mortality was observed among patients with malnutrition and lower levels of LDL-C (HR 2.96, 95%CI 1.43-6.12) or higher levels of LDL-C (HR 2.81, 95%CI 1.38-5.72).

Conclusion: Low and high levels of LDL-C at the start of PD procedure were associated with increased all-cause and cardiovascular mortality risks. Malnutrition may modify the association of LDL-C with cardiovascular mortality.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3389/fnut.2022.910348DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9351358PMC
July 2022

Soil properties, rhizosphere bacterial community, and plant performance respond differently to fumigation and bioagent treatment in continuous cropping fields.

Front Microbiol 2022 22;13:923405. Epub 2022 Jul 22.

School of Minerals Processing and Bioengineering, Central South University, Changsha, China.

Continuous cropping barriers lead to huge agriculture production losses, and fumigation and biological agents are developed to alleviate the barriers. However, there is a lack of literature on the differences between strong chemical fumigant treatment and moderate biological agent treatment. In this study, we investigated those differences and attempted to establish the links between soil properties, rhizosphere microbial community, and plant performance in both fumigation- and bioagent-treated fields. The results showed that the fumigation had a stronger effect on both soil functional microbes, i.e., ammonia oxidizers and soil-borne bacterial pathogens, and therefore, led to a significant change in soil properties, higher fertilizer efficiency, lower disease infections, and improved plant growth, compared with untreated control fields. Biological treatment caused less changes to soil properties, rhizosphere bacterial community, and plant physiology. Correlation and modeling analyses revealed that the bioagent effect was mainly direct, whereas fumigation resulted in indirect effects on alleviating cropping barriers. A possible explanation would be the reconstruction of the soil microbial community by the fumigation process, which would subsequently lead to changes in soil characteristics and plant performance, resulting in the effective alleviation of continuous cropping barriers.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3389/fmicb.2022.923405DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9354655PMC
July 2022

Abdominal Computed Tomography Enhanced Image Features under an Automatic Segmentation Algorithm in Identification of Gastric Cancer and Gastric Lymphoma.

Comput Math Methods Med 2022 26;2022:2259373. Epub 2022 Jul 26.

Department of Radiology, Wuhan Fourth Hospital, Wuhan, 430034 Hubei, China.

To analyze the application value of CT-enhanced scanning based on artificial intelligence algorithm in the diagnosis of gastric cancer and gastric lymphoma, the CT images of 80 patients with Borrmann type IV gastric cancer or primary gastric lymphoma diagnosed by endoscopic pathology were retrospectively collected. Meanwhile, a lymph node recognition algorithm based on OTSU threshold segmentation was proposed for CT image processing. The results showed that the missed diagnosis rate of suspected lymph nodes and the missed lymph node detection rate of this algorithm were substantially lower than those of other algorithms ( < 0.05). The probability of gastric wall motility disappearance, perigastric fat infiltration, and type A enhancement pattern in the Borrmann type IV gastric cancer group was higher than that in the gastric lymphoma group, with remarkable differences ( < 0.05). There was no remarkable difference between the Borrmann type IV gastric cancer group and the gastric lymphoma group in the probability of swollen lymph nodes under the renal hilum ( > 0.05). In addition, 5the sensitivity (83.17%), specificity (95.52%), and accuracy (93.08%) of the combined detection of the three CT signs (stomach wall motility, perigastric fat infiltration, and enhancement mode) were substantially improved compared with those of a single sign ( < 0.05). To sum up, the lymph node recognition algorithm based on OTSU threshold segmentation had better performance in detecting gastric lymph nodes than traditional algorithms. The CT image characteristics of gastric wall motility, perigastric fat infiltration, and enhancement pattern based on artificial intelligence algorithms were effective indicators for distinguishing gastric cancer and gastric lymphoma.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1155/2022/2259373DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9345719PMC
August 2022

Biotransformation, Pharmacokinetics, and Pharmacological Activities of Ginsenoside Rd Against Multiple Diseases.

Front Pharmacol 2022 19;13:909363. Epub 2022 Jul 19.

Jilin Ginseng Academy, Key Laboratory of Active Substances and Biological Mechanisms of Ginseng Efficacy, Ministry of Education, Jilin Provincial Key Laboratory of Bio-Macromolecules of Chinese Medicine, Changchun University of Chinese Medicine, Changchun, China.

C.A. Mey. has a history of more than 4000 years and is widely used in Asian countries. Modern pharmacological studies have proved that ginsenosides and their compounds have a variety of significant biological activities on specific diseases, including neurodegenerative diseases, certain types of cancer, gastrointestinal disease, and metabolic diseases, in which most of the interest has focused on ginsenoside Rd. The evidentiary basis showed that ginsenoside Rd ameliorates ischemic stroke, nerve injury, cancer, and other diseases involved in apoptosis, inflammation, oxidative stress, mitochondrial damage, and autophagy. In this review, we summarized available reports on the molecular biological mechanisms of ginsenoside Rd in neurological diseases, cancer, metabolic diseases, and other diseases. We also discussed the main biotransformation pathways of ginsenoside Rd obtained by fermentation.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3389/fphar.2022.909363DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9343777PMC
July 2022

Photocatalytic Defluorinative Three-Component Reaction of α-Trifluoromethyl Alkenes, Alkenes, and Sodium Sulfinates: Synthesis of Monofluorocyclopentenes.

Org Lett 2022 Aug 4. Epub 2022 Aug 4.

School of Chemistry, Sun Yat-Sen University, Guangzhou 510006, China.

A photocatalytic three-component reaction of α-trifluoromethyl alkenes, electron-rich alkenes, and sodium sulfinates for the synthesis of -difluoroalkenes in a radical/polar crossover manner was developed. Due to the strong electron-withdrawing nature of the sulfonyl group, the resultant -difluoroalkenes can be converted into various monofluorocyclopentenes via intramolecular base-mediated SV reactions in one pot.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1021/acs.orglett.2c02202DOI Listing
August 2022

Analysis of Pregnancy-Related Attacks in Neuromyelitis Optica Spectrum Disorder: A Systematic Review and Meta-Analysis.

JAMA Netw Open 2022 Aug 1;5(8):e2225438. Epub 2022 Aug 1.

Department of Neurology and Rare Disease Center, Huashan Hospital, Shanghai Medical College, Fudan University, Shanghai, China.

Importance: Risk of relapse may be increased in the postpartum period of neuromyelitis optica spectrum disorder (NMOSD). Information regarding factors associated with pregnancy-related attacks is still lacking.

Objectives: To identify factors associated with pregnancy-related NMOSD attacks, investigate the integrated annualized relapse rate (ARR) and Expanded Disability Status Scale (EDSS) score in each phase of pregnancy, and summarize pregnancy outcomes and complications in patients with NMOSD.

Data Sources: An electronic search was performed in the MEDLINE, PubMed in-process and non-MEDLINE, EMBASE, Web of Science, and Cochrane databases using the OvidSP search platform, updated through December 30, 2021.

Study Selection: All published and unpublished studies in English were considered, covering all patients with NMOSD with an informative pregnancy.

Data Extraction And Synthesis: Two independent reviewers extracted the published data with a standardized procedure following MOOSE and PRISMA guidelines. The end points were calculated with the DerSimonian and Laird inverse variance (for random effects) method.

Main Outcomes And Measures: The primary outcome was the rate of pregnancies with pregnancy-related NMOSD attacks, measured by risk ratios (RRs). The mean differences (MDs) in ARR and EDSS scores between each phase of pregnancy, pregnancy outcomes, and complications were defined as the secondary outcomes.

Results: A total of 15 studies were analyzed, including 443 patients with NMOSD with 639 informative pregnancies. Patients receiving immunosuppressive treatment during pregnancy (RR, 0.43; 95% CI, 0.32-0.57; P < .001) and with older age at conception (RR, 0.67; 95% CI, 0.47-0.95; P = .02) had lower rates of pregnancy with pregnancy-related attacks. The increase in the ARR was highest in the first trimester after delivery compared with before pregnancy (MD, 1.28; 95% CI, 0.94-1.62; P < .001). The EDSS scores increased significantly both during pregnancy (MD, 0.44; 95% CI, 0.20-0.69; P < .001) and in the postpartum period (MD, 0.88; 95% CI, 0.51-1.26; P < .001) compared with before pregnancy.

Conclusions And Relevance: This systematic review and meta-analysis found that receiving immunosuppressive treatment during pregnancy and older age at conception were associated with reduced risk of pregnancy-related NMOSD attacks, which mostly occurred in the first trimester of the postpartum period, although more high-quality prospective studies are needed.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1001/jamanetworkopen.2022.25438DOI Listing
August 2022

Study on Psychological Stress Response and Intervention Countermeasures of Exposed Population under Sudden Public Health Crisis.

Biomed Res Int 2022 25;2022:3411960. Epub 2022 Jul 25.

Wei Fang Medical University, Weifang City, Shandong 261053, China.

Background: After the occurrence of public health emergencies, people will have a series of physiological reactions, which will develop into psychological stress disorder in serious cases. Based on this, the purpose of this study is to analyze the psychological stress response and intervention countermeasures of exposed people under sudden public health crisis.

Objective: To explore the psychological stress response and intervention countermeasures of exposed population under sudden public health crisis.

Methods: A total of 400 people under the sudden public health crisis that bring about serious damage to public health, mass diseases of unknown causes, major food and occupational poisoning, and other events that seriously affect public health from December 2020 to December 2021 were selected as the subjects of the study. It was randomly and equally divided into two groups to take different intervention measures, the control group was given routine public health crisis intervention measures, and the research group was given comprehensive intervention. The metabolism, social function defects, health symptoms, psychological status, quality of life, sleep quality, and stress reaction were compared between the two groups.

Results: The rate of good metabolism in the research group was significantly higher than that in the control group ( < 0.05). After intervention, the scores of Social Disability Screening Schedule (SDSS) and Symptom Checklist 90 (SCL-90) decreased in both groups, and the scores of SDSS and SCL-90 in the research group were lower than those in the control group. After intervention, the scores of self-rating depression scale and self-rating anxiety scale in the two groups decreased, and the scores of self-rating depression scale and self-rating anxiety scale in the research group were lower than those in the control group ( < 0.05). The sleep quality of the research group was better than that of the control group ( < 0.05). The stress response indexes such as cortisol, blood glucose, and C-reactive protein in the two groups were decreased after intervention. The stress response indexes such as cortisol, blood glucose, and C-reactive protein in the research group were lower than those in the control group ( < 0.05).

Conclusion: Giving that comprehensive intervention measures to people exposed to sudden public health crisis can effectively relax their stress response, reinvigorate their quality of life and sleep, reduce depression and anxiety, and improve their metabolism, therefore, in the case of the outbreak of public health crisis in the future, it is worth applying for reference and popularizing.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1155/2022/3411960DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9343183PMC
August 2022

Bovine Bone Gelatin-Derived Peptides: Food Processing Characteristics and Evaluation of Antihypertensive and Antihyperlipidemic Activities.

J Agric Food Chem 2022 Aug 2. Epub 2022 Aug 2.

Key Lab of Meat Processing and Quality Control, MOE; Key Laboratory of Meat Products Processing, MOA; Jiangsu Collaborative Innovation Center of Meat Production and Processing, Quality and Safety Control; MOE Joint International Research Laboratory of Animal Health and Food Safety, Nanjing Agricultural University, Nanjing 210095, P. R. China.

This study aimed to evaluate the food processing properties of bovine bone gelatin-derived peptides (BGPs) and their effects and mechanisms on hypertension and hypertension complications in spontaneously hypertensive rats (SHRs). BGPs had good acid, high temperature, and NaCl resistance abilities . Additionally, Maillard reaction of BGPs with low-dose reducing sugar (≤15%) exhibited a free radical scavenging effect. BGPs significantly reduced the blood pressure, triglyceride levels, and the low-density lipoprotein cholesterol/high-density lipoprotein cholesterol ratio in SHRs through downregulated angiotensin converting enzyme (ACE), angiotensin II (Ang II), and Ang II type 1 receptor (AT1R) levels and the upregulated Ang II type 2 receptor (AT2R) level. In brief, BGP could alleviate hypertension and dyslipidemia in SHRs by inhibiting ACE/Ang II/AT1R and activating the Ang II/AT2R signaling pathway. Our study suggests that BGP has good food processing properties and could be a potential nutraceutical for antihypertensive and antihyperlipidemic issues.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1021/acs.jafc.2c02982DOI Listing
August 2022

Genome-wide identification of long non-coding (lncRNA) in 's adaptability to resistant rice.

PeerJ 2022 25;10:e13587. Epub 2022 Jul 25.

Hubei Key Laboratory of Food Crop Germplasm and Genetic Improvement, Food Crops Institute, Hubei Academy of Agricultural Sciences, Wuhan, China.

Background: The brown planthopper (BPH), (Stål), is a very destructive pest that poses a major threat to rice plants worldwide. BPH and rice have developed complex feeding and defense strategies in the long-term co-evolution.

Methods: To explore the molecular mechanism of BPH's adaptation to resistant rice varieties, the lncRNA expression profiles of two virulent BPH populations were analyzed. The RNA-seq method was used to obtain the lncRNA expression data in TN1 and YHY15.

Results: In total, 3,112 highly reliable lncRNAs in TN1 and YHY15 were identified. Compared to the expression profiles between TN1 and YHY15, 157 differentially expressed lncRNAs, and 675 differentially expressed mRNAs were identified. Further analysis of the possible regulation relationships between differentially expressed lncRNAs and differentially expressed mRNAs, identified three pair antisense targets, nine pair -regulation targets, and 3,972 pair co-expressed targets. Function enriched found arginine and proline metabolism, glutathione metabolism, and carbon metabolism categories may significantly affect the adaptability in BPH when it is exposed to susceptible and resistant rice varieties. Altogether, it provided scientific data for the study of lncRNA regulation of brown planthopper resistance to rice. These results are helpful in the development of new control strategies for host defense against BPH and breeding rice for high yield.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.7717/peerj.13587DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9332332PMC
July 2022

Precisely Targeted Nano-Controller of PD-L1 Level for Non-Small Cell Lung Cancer Spinal Metastasis Immunotherapy.

Adv Healthc Mater 2022 Jul 29:e2200938. Epub 2022 Jul 29.

Department of Orthopaedic Surgery, Zhongshan Hospital, Fudan University, Shanghai, 200032, P. R. China.

Although immune checkpoint inhibitors (ICIs) have been widely applied to treat non-small cell lung cancer (NSCLC), a significant proportion of patients, especially those with spinal metastasis (NSCLC-SM), are insensitive to anti-programmed death 1 (PD-1)/programmed death ligand 1 (PD-L1) ICIs. A drug delivery nano-controller of PD-L1 that targets NSCLC-SM can solve this problem, however, none have been developed to date. In this study, it is shown that integrin β3 (β3-int) is strongly upregulated in NSCLC-SM. Its inhibitor RGDyK promotes PD-L1 ubiquitination, indicating the potential application of RGDyK as a new PD-L1 inhibitor in nano-controller and a targeting peptide for NSCLC-SM treatment. According to the synergistic effect of photodynamic therapy and ICIs on T-cell activation through the release of tumor antigens, RGDyK-modified and zinc protoporphyrin (ZnPP)-loaded mesoporous silicon nanoparticles ([email protected]) are fabricated. The [email protected] nanoparticles precisely target β3-int to inhibit PD-L1, exhibiting high photodynamic therapy efficiency, and excellent immunotherapeutic effects in an NSCLC-SM mouse model. Collectively, the findings indicate that [email protected] is a promising immunotherapeutic agent for treating NSCLC-SM.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/adhm.202200938DOI Listing
July 2022

Interfacing Perforated Eardrums with Graphene-based Membranes for Broadband Hearing Recovery.

Adv Healthc Mater 2022 Jul 28:e2201471. Epub 2022 Jul 28.

Department of Otorhinolaryngology, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, Shanghai, China.

Eardrum perforation and associated hearing loss is a global health problem. Grafting perforated eardrum with autologous tissues in clinic can restore low-frequency hearing but often leaves poor recovery of high-frequency hearing. In this study, we examine the potential of incorporating a thin multilayered graphene membrane (MGM) into the eardrum for broadband hearing recovery in rats. The MGM shows good biocompatibility and biostability to promote the growth of eardrum cells in a regulated manner with little sign of tissue rejection and inflammatory response. After three weeks of implantation, the MGM is found to be encapsulated by a thin layer of newly grown tissue on both sides without a significant folded overgrowth that is often seen in natural healing. The perforation is well sealed, and broadband hearing recovery (1∼32 kHz) is enabled and maintained for at least 2 months. Mechanical simulations show that the high elastic modulus of MGM and thin thickness of the reconstructed eardrum play a critical role in the recovery of high-frequency hearing. This work demonstrates the promise of the use of MGM as a functional graft for perforated eardrum to recover hearing in the broadband frequency region and suggests a new acoustics-related medical application for graphene-related 2D materials. This article is protected by copyright. All rights reserved.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/adhm.202201471DOI Listing
July 2022

Effect of Malondialdehyde on the Digestibility of Beef Myofibrillar Protein: Potential Mechanisms from Structure to Modification Site.

Foods 2022 Jul 22;11(15). Epub 2022 Jul 22.

Key Laboratory of Meat Processing and Quality Control, Ministry of Education China, College of Food Science and Technology, Nanjing Agricultural University, Nanjing 210095, China.

Lipid oxidation and protein oxidation occur side by side in meat. Here, the effect of malondialdehyde (MDA), the major product of lipid oxidation, on the digestibility of beef myofibrillar proteins (MP) was studied. MP samples were incubated with 0, 0.1, 0.3, 0.5, and 0.7 mM MDA at 4 °C for 12 h and then subjected to in vitro gastrointestinal digestion. The result showed that MDA remarkably reduced the digestibility of MP ( < 0.05). MDA treatments significantly increased carbonyl and Schiff base contents in MP ( < 0.05). The microstructure observed by atomic force microscopy showed that MDA treatments resulted in the aggregation of MP. Non-reducing and reducing electrophoresis suggested the aggregation was mainly caused by covalent bonds including disulfide bond and carbonyl-amine bond. Proteomics analysis proved that the myosin tail was the main target of MDA attack, meanwhile, lysine residues were the major modification sites. Taken together, the above results imply that MDA induces protein oxidation, aggregation, and blockage of hydrolysis sites, consequently leading to the decrease in both gastric and gastrointestinal digestibility of MP.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3390/foods11152176DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9330876PMC
July 2022

Genome-Wide Association Analysis and Genetic Parameters for Feed Efficiency and Related Traits in Yorkshire and Duroc Pigs.

Animals (Basel) 2022 Jul 26;12(15). Epub 2022 Jul 26.

College of Animal Science and Technology, China Agricultural University, Beijing 100193, China.

Feed efficiency (FE) traits are key factors that can influence the economic benefits of pig production. However, little is known about the genetic architecture of FE and FE-related traits. This study aimed to identify SNPs and candidate genes associated with FE and FE-related traits, namely, average daily feed intake (ADFI), average daily gain (ADG), the feed conversion ratio (FCR), and residual feed intake (RFI). The phenotypes of 5823 boars with genotyped data (50 K BeadChip) from 1365 boars from a nucleus farm were used to perform a genome-wide association study (GWAS) of two breeds, Duroc and Yorkshire. Moreover, we performed a genetic parameter estimation for four FE and FE-related traits. The heritabilities of the FE and FE-related traits ranged from 0.13 to 0.36, and there were significant genetic correlations (-0.69 to 0.52) of the FE and FE-related traits with two growth traits (age at 100 kg and backfat thickness at 100 kg). A total of 61 significant SNPs located on eight different chromosomes associated with the four FE and FE-related traits were identified. We further identified four regions associated with FE and FE-related traits that have not been previously reported, and they may be potential novel QTLs for FE. Considering their biological functions, we finally identified 35 candidate genes relevant for FE and FE-related traits, such as the widely reported and genes. A gene enrichment analysis showed that FE and FE-related traits were highly enriched in the biosynthesis, digestion, and metabolism of biomolecules. This study deepens our understanding of the genetic mechanisms of FE in pigs and provides valuable information for using marker-assisted selection in pigs to improve FE.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3390/ani12151902DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9329986PMC
July 2022

Photoluminescence and Fluorescence Quenching of Graphene Oxide: A Review.

Nanomaterials (Basel) 2022 Jul 17;12(14). Epub 2022 Jul 17.

School of Chemical Engineering and Technology, Sun Yat-Sen University, Zhuhai 519082, China.

In recent decades, photoluminescence (PL) material with excellent optical properties has been a hot topic. Graphene oxide (GO) is an excellent candidate for PL material because of its unique optical properties, compared to pure graphene. The existence of an internal band gap in GO can enrich its optical properties significantly. Therefore, GO has been widely applied in many fields such as material science, biomedicine, anti-counterfeiting, and so on. Over the past decade, GO and quantum dots (GOQDs) have attracted the attention of many researchers as luminescence materials, but their luminescence mechanism is still ambiguous, although some theoretical results have been achieved. In addition, GO and GOQDs have fluorescence quenching properties, which can be used in medical imaging and biosensors. In this review, we outline the recent work on the photoluminescence phenomena and quenching process of GO and GOQDs. First, the PL mechanisms of GO are discussed in depth. Second, the fluorescence quenching mechanism and regulation of GO are introduced. Following that, the applications of PL and fluorescence quenching of GO-including biomedicine, electronic devices, material imaging-are addressed. Finally, future development of PL and fluorescence quenching of GO is proposed, and the challenges exploring the optical properties of GO are summarized.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3390/nano12142444DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9319665PMC
July 2022

The Flow-Induced Degradation and Vascular Cellular Response Study of Magnesium-Based Materials.

Front Bioeng Biotechnol 2022 7;10:940172. Epub 2022 Jul 7.

School of Materials Science and Engineering, Southwest Jiaotong University, Chengdu, China.

Magnesium (Mg)-based materials are considered as potential materials for biodegradable vascular stents, and some Mg-based stents have obtained regulatory approval. However, the development and application of Mg-based stents are still restricted by the rapid degradation rate of Mg and its alloys. In order to screen out the desirable Mg-based materials for stents, the degradation behavior still needs further systematic study, especially the degradation behavior under the action of near-physiological fluid. Currently, the commonly used Mg-based vascular stent materials include pure Mg, AZ31, and WE43. In this study, we systematically evaluated their corrosion behaviors in a dynamic environment and studied the effect of their degradation products on the behavior of vascular cells. The results revealed that the corrosion rate of different Mg-based materials was related to the composition of the elements. The dynamic environment accelerated the corrosion of Mg-based materials. All the same, AZ31 still shows good corrosion resistance. The effect of corrosive products on vascular cells was beneficial to re-endothelialization and inhibition of smooth muscle cell proliferation at the implantation site of vascular stent materials.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3389/fbioe.2022.940172DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9301134PMC
July 2022

Ginsenoside Rb1 Ameliorated Bavachin-Induced Renal Fibrosis via Suppressing Bip/eIF2α/CHOP Signaling-Mediated EMT.

Front Pharmacol 2022 8;13:872474. Epub 2022 Jul 8.

Department of Pharmaceutical Sciences, Beijing Institute of Radiation Medicine, Beijing, China.

The nephrotoxicity of , an effective traditional Chinese medicine for vitiligo treatment, has been reported. As one of the main toxic components in , bavachin (BV) was considered to be related to -caused adverse outcomes, but the direct evidence and molecular mechanism underlying BV-induced nephrotoxicity are not well elucidated. Therefore, this study was designed to confirm whether BV would cause toxic effects on the kidney and explore the possible mode of action. Our results demonstrated that days' treatment with 0.5 μM BV indeed caused obvious renal fibrosis in the zebrafish kidney. The obvious E- to N-cadherin switch and the expressions of proteins promoting epithelial-mesenchymal transition (EMT) were observed in BV-treated human renal tubular epithelial and zebrafish kidneys. In addition, elevated reactive oxygen species (ROS) levels and Bip/eIF2α/CHOP-mediated endoplasmic reticulum (ER) stress and the unfolded protein response (UPR) were caused by BV, both of which could be reversed by ROS scavenger N-acetyl-L-cysteine (NAC). Also, blocking ER stress-caused cytoplasmic Ca overload with 4-PBA notably alleviated BV-induced alterations in key molecular events related to EMT and renal fibrosis. Furthermore, of the natural compounds subjected to screening, ginsenoside Rb1 significantly downregulated BV-induced ER stress by inhibiting ROS generation and following the activation of Bip/eIF2α/CHOP signaling in HK2 cells. Subsequently, BV-triggered EMT and renal fibrosis were both ameliorated by ginsenoside Rb1. In summary, our findings suggested that BV-induced ROS promoted the appearance of EMT and renal fibrosis mainly via Bip/eIF2α/CHOP-mediated ER stress. This ER stress-related toxic pathway might be a potential intervention target for BV-caused renal fibrosis, and ginsenoside Rb1 would be a promising drug against BV- or -induced nephrotoxicity.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3389/fphar.2022.872474DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9304982PMC
July 2022

Viral evasion of PKR restriction by reprogramming cellular stress granules.

Proc Natl Acad Sci U S A 2022 Jul 11;119(29):e2201169119. Epub 2022 Jul 11.

Key Laboratory of Animal Epidemiology of the Ministry of Agriculture and Rural Affairs, College of Veterinary Medicine, China Agricultural University, Beijing 100193, People's Republic of China.

Protein kinase R (PKR) is a critical host restriction factor against invading viral pathogens. However, this molecule is inactivated in the cells infected with porcine reproductive and respiratory syndrome virus (PRRSV), an economically devastating pathogen to the world swine industry. Here, we report that this event is to suppress cellular inflammation and is mediated by the viral replicase protein nsp1β. We show that nsp1β is a stress-responsive protein, enters virus-induced stress granules (SGs) during infection, and repurposes SGs into a proviral platform, where it co-opts the SG core component G3BP1 to interact with PKR in a regulated manner. RNA interference silencing of G3BP1 or mutation of specific nsp1β residues (VS19GG) can abolish the antagonization of PKR activation. The viral mutant carrying the corresponding mutations induces elevated level of PKR phosphorylation and pronounced production of inflammatory cytokines (e.g., tumor necrosis factor-α, interleukin [IL]-6, and IL-8), whereas small-interfering RNA knockdown of PKR or treatment with C16, a PKR inhibitor, blocks this effect. Thus, PRRSV has evolved a unique strategy to evade PKR restriction to suppress host inflammatory responses.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1073/pnas.2201169119DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9303852PMC
July 2022

Albumin-assembled copper-bismuth bimetallic sulfide bioactive nanosphere as an amplifier of oxidative stress for enhanced radio-chemodynamic combination therapy.

Regen Biomater 2022 5;9:rbac045. Epub 2022 Jul 5.

Advanced Biomaterials and Tissue Engineering Center, Huazhong University of Science and Technology, Wuhan 430074, China.

The tumor microenvironment with overexpressed hydrogen peroxide (HO) and reinforced antioxidative system (glutathione, GSH) becomes a double-edged sword for the accessibility of nano-therapy. Since reactive oxygen species (ROS) are easily quenched by the developed antioxidative network, ROS-based treatments such as chemodynamic therapy (CDT) and radiotherapy (RT) for killing cancer cells are severely attenuated. To overcome such limitations, a bioactive nanosphere system is developed to regulate intracellular oxidative stress for enhanced radio-chemodynamic combination therapy by using bovine serum albumin (BSA) based bioactive nanospheres that are BSA assembled with generated copper-bismuth sulfide nanodots and diallyl trisulfide (DATS). The copper-bismuth sulfide nanodots react with HO to produce •OH and release Cu. Then, the Cu further depletes GSH to generate Cu for more •OH generation in the way of Fenton-like reaction. Such a cascade reaction can initiate •OH generation and GSH consumption to realize CDT. The elevation of ROS triggered by the DATS from BBCD nanospheres further augments the breaking of redox balance for the increased oxidative stress in 4T1 cells. With the sensitization of increased oxidative stress and high Z element Bi, an enhanced radio-chemodynamic combination therapy is achieved. The current work provides an enhanced radio-chemodynamic combination treatment for the majority of solid tumors by using the co-assembled bioactive nanospheres as an amplifier of oxidative stress.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1093/rb/rbac045DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9290530PMC
July 2022

Identification of three different phenotypes in anti-MDA5 antibody-positive dermatomyositis patients: implications for rapidly progressive interstitial lung disease prediction.

Arthritis Rheumatol 2022 Jul 18. Epub 2022 Jul 18.

Department of Rheumatology, The First Affiliated Hospital of Nanjing Medical University, China, Nanjing, Jiangsu, China.

Objective: Substantial phenotypic heterogeneity exists in anti-melanoma differentiation-associated gene 5 antibody-positive (anti-MDA5 ) dermatomyositis patients, hindering disease assessment and management. This study aimed to identify distinct phenotypic groups in anti-MDA5 patients and determine their utility in outcome prediction.

Methods: A total of 265 patients with anti-MDA5 DM were enrolled retrospectively. An unsupervised analysis was performed to characterize the phenotypes.

Results: Three clusters with markedly different features and outcomes (all-cause mortality rates of 60%, 9.7%, and 3.7% for clusters 3, 2 and 1 (p < 0.0001)) were identified. Cluster 1 (n = 108) corresponded to mild risk of rapidly progressive ILD (RPILD) with the non-RPILD cumulative incidence being 85.2%. Cluster 2 (n = 72) corresponded to moderate risk of RPILD with a non-RPILPD cumulative incidence of 73.6%. Cluster 3 (n = 85), corresponding to high risk of RPILD with a non-RPILD cumulative incidence of 32.9%, had the highest possibility for anti-Ro52 antibodies to coexist with high titers of anti-MDA5 antibodies among the 3 subgroups. Decision tree analysis indicated a simple algorithm comprising of eight variables (age > 50 years, disease course < 3 months, myasthenia (proximal muscle weakness), arthritis, CRP level, CK level, anti-Ro52 and anti-MDA5 antibody titers), which could place patients into the appropriate clusters with 78.5% and 70.0% accuracies in the development and external validation cohorts.

Conclusion: Cluster analysis identified 3 distinct clinical patterns and outcomes in our large cohort of anti-MDA5 DM patients. Classification of these patients into phenotypes with prognostic values may help physicians to improve the efficacy of clinical decisions.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/art.42308DOI Listing
July 2022

The description of neuromyelitis optica spectrum disorder: Patient registry in Yangtze River Delta area of China.

Mult Scler Relat Disord 2022 Jul 5;66:104023. Epub 2022 Jul 5.

Department of Neurology and Rare Disease Center, Huashan Hospital, Shanghai Medical College, Fudan University, , 12 Wulumuqi Road (Mid), Shanghai 200040, China; National Center for Neurological Disorders (NCND), China. Electronic address:

Objective: To describe the clinical features of neuromyelitis optica spectrum disorder (NMOSD) through patient registry in Yangtze River Delta area of China.

Methods: A total of 502 consecutive patients diagnosed with aquaporin-4 antibody (AQP4-ab)-positive NMOSD were registered between December 2018 to January 2021 in multiple tertiary referral centers within the framework of Yangtze River Delta of China. Their baseline data were reviewed, and follow-up clinical information were collected prospectively.

Results: The mean age at onset was 37.3 (range 3-80 years) years and the female-to-male ratio was 8.1:1. The median disease duration was 47 months (interquartile range [IQR] 25-84 months). A total of 1372 attacks of the 502 patients were recorded till the last follow-up, with a median annualized relapse rate of 0.4 (IQR 0.3-0.6). Nearly one-fourth (24.5%, 336/1372) of the attacks had prodromic events, including upper respiratory tract infection (36.3%, 122/336), fever (20.2%, 68/336) and pregnancy-related issues (17.9%, 60/336), etc. Myelitis was the most common attack type throughout the disease course (51.4%, 705/1372), followed by optic neuritis (ON, 43.1%, 592/1372). As for onset phenotype, ON (37.3%, 187/502) prevailed over myelitis (28.3%, 142/502). The median time to first relapse was 12 months (IQR 5-25 months). Patients with brainstem encephalitis at onset were more likely to have other anatomical region involved in subsequent attacks (p < 0.001), compared to other onset type. The median serum AQP4-ab titer measured by cell-based assays was 1:100 (IQR 1:32-1:320, range 1:10-1:10,000). The baseline AQP4-ab titer in cerebrospinal fluid (r = 0.542, p <0.001), overall ARR (r = 0.232, p< 0.001) and the EDSS scores at last follow-up (r = 0.119, p = 0.022) significantly correlated with baseline serum AQP4-ab titer. Antinuclear antibodies (48.4%), thyroid peroxidase antibodies (30.7%), and anti-SSA antibodies (26.2%) represented the most frequent concomitant antibodies, while autoimmune thyroid disorders (13.1%, 66/502) and Sjogren's syndrome (10.8%, 54/502) were the most common accompanying autoimmune diseases. Till the last follow-up, 403 patients received preventive treatments. Azathioprine represented the most common initial treatment, mycophenolate mofetil and rituximab was the most common second and third-line treatment, respectively. The EDSS score at the last follow-up ranged from 0 to 8.5 with a median of 2 (IQR 1-3).

Conclusions: A comprehensive clinical picture of patients with AQP4-ab-positive NMOSD in Yangtze River Delta area of China was presented. More information on disease tragedy and predictive prognostic factors could be generated through long-term observations.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.msard.2022.104023DOI Listing
July 2022

Polyphenol oxidase inhibited by 4-hydroxycinnamic acid and naringenin: Multi-spectroscopic analyses and molecular docking simulation at different pH.

Food Chem 2022 Jul 9;396:133662. Epub 2022 Jul 9.

State Key Laboratory of Food Science and Technology, Nanchang University, Nanchang 330047, China; National R&D Center for Freshwater Fish Processing, Jiangxi Normal University, Nanchang 330022, China.

It is still unclear how pH affects the inhibitory effects of phenolic acids and flavonoids on polyphenol oxidase (PPO). In this study, 4-hydroxycinnamic acid and naringenin were selected to investigate their interactions with PPO from pH 6.8 to 5.0. Results showed that acidic pH could enhance the inhibitory effect of inhibitors and a greater enhancement effect was observed in 4-hydroxycinnamic acid. Fluorescence emission spectra indicated that 4-hydroxycinnamic acid and naringenin interacted with PPO and quenched its intrinsic fluorescence, which was also enhanced by acidic pH. Circular dichroism suggested that 4-hydroxycinnamic acid and naringenin could reversibly bind to PPO molecules and transform α-helix into β-sheet. Molecular docking results revealed that 4-hydroxycinnamic acid and naringenin interacted with PPO through hydrogen bond and hydrophobic interaction, and more interactions were observed near the carboxyl group. These results indicated that acidic pH could significantly enhance the inhibitory effect of phenolic acid on PPO.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.foodchem.2022.133662DOI Listing
July 2022

ZBTB46 defines and regulates ILC3s that protect the intestine.

Nature 2022 Jul 13. Epub 2022 Jul 13.

Joan and Sanford I. Weill Department of Medicine, Division of Gastroenterology & Hepatology, Weill Cornell Medicine, Cornell University, New York, NY, USA.

RORγt is a lineage-specifying transcription factor that is expressed by immune cells that are enriched in the gastrointestinal tract and promote immunity, inflammation and tissue homeostasis. However, fundamental questions remain with regard to the cellular heterogeneity among these cell types, the mechanisms that control protective versus inflammatory properties and their functional redundancy. Here we define all RORγt immune cells in the intestine at single-cell resolution and identify a subset of group 3 innate lymphoid cells (ILC3s) that expresses ZBTB46, a transcription factor specifying conventional dendritic cells. ZBTB46 is robustly expressed by CCR6 lymphoid-tissue-inducer-like ILC3s that are developmentally and phenotypically distinct from conventional dendritic cells, and its expression is imprinted by RORγt, fine-tuned by microbiota-derived signals and increased by pro-inflammatory cytokines. ZBTB46 restrains the inflammatory properties of ILC3s, including the OX40L-dependent expansion of T helper 17 cells and the exacerbated intestinal inflammation that occurs after enteric infection. Finally, ZBTB46 ILC3s are a major source of IL-22, and selective depletion of this population renders mice susceptible to enteric infection and associated intestinal inflammation. These results show that ZBTB46 is a transcription factor that is shared between conventional dendritic cells and ILC3s, and identify a cell-intrinsic function for ZBTB46 in restraining the pro-inflammatory properties of ILC3s and a non-redundant role for ZBTB46 ILC3s in orchestrating intestinal health.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1038/s41586-022-04934-4DOI Listing
July 2022

Two-Dimensional Metal-Organic Framework with Ultrahigh Water Stability for Separation of Acetylene from Carbon Dioxide and Ethylene.

ACS Appl Mater Interfaces 2022 Jul 12. Epub 2022 Jul 12.

School of Materials Science and Engineering, National Institute for Advanced Materials, Nankai University, Tianjin 300350, China.

Highly selective separation and purification of acetylene (CH) from ethylene (CH) and carbon dioxide (CO) are daunting challenges in light of their similar molecule sizes and physical properties. Herein, we report a two-dimensional (2D) stable metal-organic framework (MOF), ([Cu(Hmpba)]·1.5DMF) (Hmpba = 4-(3,5-dimethyl-1-pyrazol-4-yl)benzoic acid), with topology, stacked together through π-π interactions for efficient separation of CH from CH and CO. The 2D-MOF material offers high hydrolytic stability and good purification capacity; especially, it could survive in water for 7 months, even longer. This stable MOF selectively captures CH from mixtures containing CH and CO, as determined by adsorption isotherms. The ideal adsorbed solution theory selectivity calculations and transient breakthrough experiments were performed to verify the separation capacity. The low isosteric heat of - (desolvated -) (18.24 kJ mol for CH) validates the feasibility of adsorbent regeneration with low energy footprint consumption. Furthermore, Grand Canonical Monte Carlo simulations confirmed that the pore surface of the - framework enabled preferential binding of CH over CH and CO via multiple C-H···O, C-H···π, and C-H···C interactions. This work provides some insights to prepare stable MOF materials toward the purification of CH, and the water-stable structure, low isosteric heat, and good cycling stability of - make it very promising for practical industrial application.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1021/acsami.2c09917DOI Listing
July 2022

Circulating miR-627-5p and miR-199a-5p are promising diagnostic biomarkers of colorectal neoplasia.

World J Clin Cases 2022 Jun;10(16):5165-5184

Graduate school, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100730, China.

Background: Early detection of colorectal neoplasms, including colorectal cancers (CRCs) and advanced colorectal adenomas (AAs), is crucial to improve patient survival. Circulating microRNAs (miRNAs) in peripheral blood are emerging as noninvasive diagnostic markers for multiple cancers, but their potential for screening colorectal neoplasms remains ambiguous.

Aim: To identify candidate circulating cell-free miRNAs as diagnostic biomarkers in patients with colorectal neoplasms.

Methods: The study was divided into three phases: (1) Candidate miRNAs were selected from three public miRNA datasets using differential gene expression analysis methods; (2) an independent set of serum samples from 60 CRC patients, 60 AA patients and 30 healthy controls (HCs) was included and analyzed by quantitative real-time polymerase chain reaction for miRNAs, and their diagnostic power was detected by receiver operating characteristic (ROC) analysis; and (3) the origin and function of miRNAs in cancer patients were investigated in cancer cell lines and tumor tissues.

Results: Based on bioinformatics analysis, miR-627-5p and miR-199a-5p were differentially expressed in both the serum and tissues of patients with colorectal neoplasms and HCs and were selected for further study. Further validation in an independent cohort revealed that both circulating miR-627-5p and miR-199a-5p were sequentially increased from HCs and AAs to CRCs. The diagnostic power of miR-672-5p yielded an area under the curve (AUC) value of 0.90, and miR-199a-5p had an AUC of 0.83 in discriminating colorectal neoplasms from HCs. A logistic integrated model combining miR-199a-5p and miR-627-5p exhibited a higher diagnostic performance than either miRNA. Additionally, the levels of serum miR-627-5p and miR-199a-5p in CRC patients were significantly lower after surgery than before surgery and the expression of both miRNAs was increased with culture time in the culture media of several CRC cell lines, suggesting that the upregulated serum expression of both miRNAs in CRC might be tumor derived. Furthermore, experiments revealed that miR-627-5p and miR-199a-5p acted as tumor suppressors in CRC cells.

Conclusion: Serum levels of miR-199a-5p and miR-627-5p were markedly increased in patients with colorectal neoplasms and showed strong potential as minimally invasive biomarkers for the early screening of colorectal neoplasms.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.12998/wjcc.v10.i16.5165DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9210874PMC
June 2022

Cyclic-di-AMP Phosphodiesterase Elicits Protective Immune Responses Against H37Ra Infection in Mice.

Front Cell Infect Microbiol 2022 22;12:871135. Epub 2022 Jun 22.

Department of Microbiology and Pathogen Biology, Basic Medical School, Air Force Medical University, Xi'an, China.

Many antigens from have been demonstrated as strong immunogens and proved to have application potential as vaccine candidate antigens. Cyclic di-AMP (c-di-AMP) as a bacterial second messenger regulates various bacterial processes as well as the host immune responses. Rv2837c, the c-di-AMP phosphodiesterase (CnpB), was found to be relative to virulence of and interference with host innate immune response. In this study, recombinant CnpB was administered subcutaneously to mice. We found that CnpB had strong immunogenicity and induced high levels of humoral response and lung mucosal immunity after intranasally infection. CnpB immunization stimulated splenocyte proliferation and the increasing number of activated NK cells but had little effects on Th1/Th2 cellular immune responses in spleens. However, CnpB induced significant Th1/Th2 cellular immune responses with a decreased number of T and B cells in the lungs, and significantly recruits of CD4 and CD8 T cells after attenuated strain H37Ra infection. Besides, we first reported that CnpB could stimulate IFN-β expression transitorily and inhibit the autophagy of macrophages . In mice intranasally infection model, CnpB immunization alleviated pathological changes and reduced H37Ra loads in the lungs. Thus, our results suggested that CnpB interferes with host innate and adaptive immune responses and confers protection against respiratory infection, which should be considered in vaccine development as well as a drug target.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3389/fcimb.2022.871135DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9256937PMC
June 2022

Zanubrutinib versus bendamustine and rituximab in untreated chronic lymphocytic leukaemia and small lymphocytic lymphoma (SEQUOIA): a randomised, controlled, phase 3 trial.

Lancet Oncol 2022 08 7;23(8):1031-1043. Epub 2022 Jul 7.

Medical University of Lodz, Lodz, Poland.

Background: Zanubrutinib is a next-generation, selective Bruton tyrosine kinase inhibitor with efficacy in relapsed chronic lymphocytic leukemia (CLL) and small lymphocytic lymphoma (SLL). We compared zanubrutinib with bendamustine-rituximab to determine its effectiveness as frontline therapy in patients with CLL or SLL.

Methods: We conducted an open-label, multicentre, phase 3 study at 153 academic or community hospitals in 14 countries and regions. Eligible patients had untreated CLL or SLL requiring treatment as per International Workshop on CLL criteria; were aged 65 years or older, or 18 years or older and had comorbidities; and had an Eastern Cooperative Oncology Group performance status score of 0-2. A central interactive web response system randomly assigned patients without del(17)(p13·1) to zanubrutinib (group A) or bendamustine-rituximab (group B) by sequential block method (permutated blocks with a random block size of four). Patients with del(17)(p13·1) were enrolled in group C and received zanubrutinib. Zanubrutinib was administered orally at 160 mg twice per day (28-day cycles); bendamustine at 90 mg/m of body surface area on days 1 and 2 for six cycles plus rituximab at 375 mg/m of body surface area the day before or on day 1 of cycle 1, and 500 mg/m of body surface area on day 1 of cycles 2-6, were administered intravenously. The primary endpoint was progression-free survival per independent review committee in the intention-to-treat population in groups A and B, with minimum two-sided α of 0·05 for superiority. Safety was analysed in all patients who received at least one dose of study treatment. The study is registered with ClinicalTrials.gov, NCT03336333, and is closed to recruitment.

Findings: Between Oct 31, 2017, and July 22, 2019, 590 patients were enrolled; patients without del(17)(p13·1) were randomly assigned to zanubrutinib (group A; n=241) or bendamustine-rituximab (group B; n=238). At median follow-up of 26·2 months (IQR 23·7-29·6), median progression-free survival per independent review committee was not reached in either group (group A 95% CI not estimable [NE] to NE; group B 28·1 months to NE). Progression-free survival was significantly improved in group A versus group B (HR 0·42 [95% CI 0·28 to 0·63]; two-sided p<0·0001). The most common grade 3 or worse adverse event was neutropenia (27 [11%] of 240 patients in group A, 116 [51%] of 227 in group B, and 17 [15%] of 111 patients in group C). Serious adverse events occurred in 88 (37%) of 240 patients in group A, 113 (50%) of 227 patients in group B, and 45 (41%) of 111 patients in group C. Adverse events leading to death occurred in 11 (5%) of 240 patients in group A, 12 (5%) of 227 patients in group B, and three (3%) of 111 patients in group C, most commonly due to COVID-19 (four [2%] of 240 patients in group A), diarrhoea, and aspiration pneumonia (two each [1%] of 227 patients in group B).

Interpretation: Zanubrutinib significantly improved progression-free survival versus bendamustine-rituximab, with an acceptable safety profile consistent with previous studies. These data support zanubrutinib as a potential new treatment option for untreated CLL and SLL.

Funding: BeiGene.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/S1470-2045(22)00293-5DOI Listing
August 2022
-->