Publications by authors named "Rong Li"

2,068 Publications

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Manipulating the soil microbiomes during a community recovery process with plant beneficial species for the suppression of Fusarium wilt of watermelon.

AMB Express 2021 Jun 12;11(1):87. Epub 2021 Jun 12.

Jiangsu Provincial Key Lab for Solid Organic Waste Utilization, National Engineering Research Center for Organic-Based Fertilizers, Jiangsu Collaborative Innovation Center for Solid Organic Waste Resource Utilization, Nanjing Agricultural University, Nanjing, 210095, China.

Fusarium wilt is a devastating disease which impacts watermelon production. Soil fumigation using dazomet followed by biological organic fertilizer was applied to suppress the Fusarium wilt disease. We propose that fumigation suppresses the soil indigenous community, especially the soil-borne pathogens, while the utilization of bio-organic fertilizer facilitates the recovery of the soil microbiome to a beneficial, suppressive state through the introduction of plant growth-promoting microorganisms. Greenhouse experiment showed that applied biological organic fertilizer after dazomet fumigation effective restrain the disease incidence with a 93.6% disease control. Fumigation strongly decreased soil microbial diversity and altered relative taxa abundances, suggesting the possibility of niche release by the resident soil microbial community. Fumigation followed by bio-fertilizer transformed the soil microbial community composition and resulted in higher relative abundances of beneficial microbial groups such as Bacillus (8.5%) and Trichoderma (13.5%), coupled with lower Fusarium abundance compared to other treatments. Network analysis illustrated that soil fumigation decreased interactions within the soil microbial community with less nodes and links while bio-fertilizer addition promoted node interactions. In addition, bio-fertilizer addition after fumigation resulted in the beneficial species becoming the key network connectors. Collectively, fumigation appears to release the resident soil niche resulting in lower diversity while the beneficial microbes introduced by bio-fertilizer addition colonize these niches, leading to a more complex community with fewer pathogens that suppresses Fusarium wilt disease incidence.
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http://dx.doi.org/10.1186/s13568-021-01225-5DOI Listing
June 2021

The stemness of hepatocytes is maintained by high levels of lipopolysaccharide via YAP1 activation.

Stem Cell Res Ther 2021 Jun 10;12(1):342. Epub 2021 Jun 10.

Tumor Immunology and Gene Therapy Center, Third Affiliated Hospital of Second Military Medical University, Shanghai, 200438, China.

Background: The liver possesses a powerful regeneration ability, which is correlated with the stemness of hepatocytes in the portal vein (PV). However, the mechanism underlying the maintenance of hepatocyte stemness has not been elucidated. Here, we hypothesized that high levels of lipopolysaccharide from the portal vein might maintain the stemness of hepatocytes in the PV area.

Methods: First, we examined the location of hepatic stem cells and the concentration of lipopolysaccharide (LPS) in the portal vein and inferior vena cava. Then, we assessed the effect of LPS on stemness maintenance in mice by using antibiotics to eliminate LPS and knocking out the LPS receptor, TLR4. In vitro, the effect of LPS on the stemness of hepatocytes was investigated by colony and sphere formation assays and assessment of pluripotent and stem cell marker expression. Furthermore, we studied the mechanism by which LPS regulates the stemness of hepatocytes. Finally, we ligated the portal vein branch to further verify the effect of LPS.

Results: We found that a high level of LPS from the portal vein was correlated with the location of hepatic stem cells in the PV area, and elimination of LPS by antibiotics inhibited the expression of the stemness marker. LPS promoted colony and sphere formation and induced the upregulation of pluripotent and stem cell markers in AML12 cells. Furthermore, in the reprogramming medium, LPS facilitated the dedifferentiation of mature hepatocytes into hepatic progenitor-like cells, which exhibited a bipotent differentiation capacity in vivo and in vitro. Mechanistically, LPS bound TLR4 to regulate stemness of hepatocytes via the activation of YAP1 signaling, and blockade of YAP1 abolished the LPS-induced cell stemness and upregulation of pluripotent markers.

Conclusions: Our study implies a correlation between LPS/TLR4/YAP1 signaling and cell stemness, and LPS was shown to be involved in stemness maintenance of hepatocytes in the PV area. LPS might be used to induce the dedifferentiation of mature hepatocytes into progenitor-like cells for repair of liver injury.
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http://dx.doi.org/10.1186/s13287-021-02421-7DOI Listing
June 2021

Comparison of Long-Term Outcomes of Monotherapy and Polytherapy in Seizure-Free Patients With Epilepsy Following Antiseizure Medication Withdrawal.

Front Neurol 2021 24;12:669703. Epub 2021 May 24.

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

The objectives of this study were to compare the risk and timing of seizure relapse in seizure-free patients with epilepsy following the withdrawal of monotherapy or polytherapy and to identify relevant influencing factors. Patients who had achieved at least a 2-year seizure remission and started the withdrawal of antiseizure medication (ASM) were enrolled in this study. All patients were followed for at least 3 years or until seizure relapse. According to the number of ASMs at the time of withdrawalwas about twice than that, patients were divided into two groups: monotherapy group and polytherapy group. The Cox proportional hazards model was used to compare the recurrence risk of the two groups. Univariate analysis and multiple logistic regression analysis were used to analyze potential confounding variables between patients treated with monotherapy and polytherapy. A total of 188 patients (119 males and 69 females) were included. The average prescribed daily dose of most ASMs at the time of withdrawal was moderate or low (30-50% defined daily dose). The recurrence of most patients (89.2%) occurred within the first 3 years after withdrawal. The recurrence risk in patients treated with polytherapy at the time of withdrawal was about twice than that of the monotherapy group [ = 0.001, hazard ratio (HR) = 2.152, 95% confidence interval (CI) = 1.350-3.428]. Multivariate analysis showed that patients treated with polytherapy were significantly older at seizure onset [ = 0.024, odd ratio (OR) = 1.027, 95% CI = 1.004-1.052] and had a significantly longer duration of epilepsy before treatment ( = 0.004, OR = 1.009, 95% CI = 1.003-1.015) compared to patients in the monotherapy group. In addition, a history of perinatal injury was found to be an independent risk factor of seizure relapse in patients with ASM withdrawal. The average prescribed daily dose of most ASMs at the time of withdrawal was moderate or low. Patients who received polytherapy at the time of withdrawal, particularly those with later seizure onset age and longer epilepsy duration before treatment, had a higher recurrence risk after ASMs withdrawal compared to patients treated with monotherapy.
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http://dx.doi.org/10.3389/fneur.2021.669703DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8182048PMC
May 2021

Potential roles of N6-methyladenosine (m6A) in immune cells.

J Transl Med 2021 Jun 8;19(1):251. Epub 2021 Jun 8.

Department of Biochemistry and Molecular Biology, School of Life Sciences, China Medical University, No. 77 Puhe Road, Shenyang North New Area, Shenyang, 110122, Liaoning, China.

N6-methyl-adenosine (m6A) is one of the most common internal modifications on RNA molecules present in mammalian cells. Deregulation of m6A modification has been recently implicated in many types of human diseases. Therefore, m6A modification has become a research hotspot for its potential therapeutic applications in the treatment of various diseases. The immune system mostly involves different types of immune cells to provide the first line of defense against infections. The immunoregulatory network that orchestrate the immune responses to new pathogens plays a pivotal role in the development of the disease. And m6A modification has been demonstrated to be a major post-transcriptional regulator of immune responses in cells. In this review, we summarize the participants involved in m6A regulation and try to reveal how m6A modification affects the immune responses via changing the immunoregulatory networks.
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http://dx.doi.org/10.1186/s12967-021-02918-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8186046PMC
June 2021

Renal protective effects and mechanisms of the angiotensin receptor-neprilysin inhibitor LCZ696 in mice with cardiorenal syndrome.

Life Sci 2021 Jun 5:119692. Epub 2021 Jun 5.

Tianjin Key Laboratory of Ionic-Molecular Function of Cardiovascular Disease, Department of Cardiology, Tianjin Institute of Cardiology, Second Hospital of Tianjin Medical University, Tianjin, China. Electronic address:

Aims: This study investigated the renal protective effects and mechanisms of angiotensin receptor-neprilysin inhibitor LCZ696 in mice with cardiorenal syndrome.

Materials And Methods: Mice were divided into abdominal aortic ligation alone, or treatment with LCZ696 or valsartan, whilst those undergoing sham surgery served as controls. Rat proximal renal tubular epithelial cells from the NRK-52E line were treated with control solution, LCZ696 or valsartan, in the presence or absence of Ang II for 24 h.

Key Findings: Compared to controls, abdominal aortic ligation significantly increased plasma NT-proBNP and urine neutrophil gelatinase-associated lipocalin (NGAL), which were associated with reduced renal length and velocity time integral on ultrasonography. Histology revealed wrinkling of the glomerular capillary wall and sclerosis of the glomerulus, dilatation of the Bowman's capsule, accompanied by diffuse renal tubular atrophy and fibrosis, accompanied by lower kidney index and higher percentage area of fibrosis. Increases in NGAL and decreased ANP protein and mRNA expression levels were observed. These abnormalities were significantly prevented by LCZ696 and to a lesser extent by valsartan. Cellular experiments demonstrated a central role of Ang II/transforming growth factor-β1/Smad2/3/connective tissue growth factor-dependent signaling leading to type IV collagen deposition. This upregulation was reversed by LCZ696 in a greater extent than valsartan treatment alone, accompanied by a significant improvement in NGAL.

Significance: LCZ696 can reduce kidney injury to a level beyond valsartan therapy alone in mice with cardiorenal syndrome, which can be speculated by effects on epithelial-mesenchymal transition and fibrosis through downregulating the TGF-β1/Smad2/3/CTGF/Collagen IV pathway.
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http://dx.doi.org/10.1016/j.lfs.2021.119692DOI Listing
June 2021

Penta-acetyl Geniposide Suppresses Migration, Invasion, and Inflammation of TNF-α-Stimulated Rheumatoid Arthritis Fibroblast-Like Synoviocytes Involving Wnt/β-Catenin Signaling Pathway.

Inflammation 2021 Jun 8. Epub 2021 Jun 8.

Inflammation and Immune Mediated Diseases Laboratory of Anhui Province, School of Pharmacy, Anhui Medical University, 81 Meishan Road, Hefei, 230032, Anhui Province, People's Republic of China.

We previously reported that penta-acetyl geniposide ((Ac)GP, an active derivative of geniposide) showed anti-arthritic effect on adjuvant-induced arthritis (AIA) rats by promoting the apoptosis of AIA fibroblast-like synoviocyte (FLS). This study aimed to demonstrate the effects of (Ac)GP on migration, invasion, and inflammation of TNF-α-stimulated rheumatoid arthritis (RA) FLS (MH7A cell) and to explore the involved mechanisms. MTT assay was used to determine the applied non-cytotoxic doses of (Ac)GP (12.5, 25, 50 μM) in vitro. Results of wound-healing, transwell, and phalloidin staining assays indicated that (Ac)GP reduced the migration, invasion, and F-actin cytoskeletal reorganization of TNF-α-stimulated MH7A. Results of ELISA and western blot assays confirmed that (Ac)GP reduced TNF-α-induced production of pro-inflammatory cytokines (like IL-1β, IL-6, IL-8) and matrix metalloproteinases (MMPs, such as MMP-2 and MMP-9). Moreover, (Ac)GP inhibited TNF-α-induced activation of Wnt/β-catenin pathway, evidenced by reducing the protein levels of Wnt1, p-GSK-3β (Ser9), and β-catenin and preventing β-catenin nuclear translocation. Importantly, the combination of XAV939 (an inhibitor of Wnt/β-catenin) promoted the actions of (Ac)GP on TNF-α-induced migration, invasion, and inflammation, further revealing the involvement of Wnt/β-catenin pathway underlying the therapeutic effects of (Ac)GP on TNF-α-stimulated MH7A. In vivo, (Ac)GP relieved the progression and severity of rat collagen-induced arthritis, related to reducing the levels of IL-1β, IL-6, IL-8, MMP-2, and MMP-9 as well as inhibiting Wnt/β-catenin pathway in synovial tissues. Collectively, (Ac)GP could suppress TNF-α-induced migration, invasion, and inflammation in RA FLS involving Wnt/β-catenin pathway and (Ac)GP might be as a candidate agent for RA treatment.
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http://dx.doi.org/10.1007/s10753-021-01495-yDOI Listing
June 2021

CD38 deficiency up-regulated IL-1β and MCP-1 through TLR4/ERK/NF-κB pathway in sepsis pulmonary injury.

Microbes Infect 2021 Jun 4:104845. Epub 2021 Jun 4.

Department of Clinical Laboratory and Laboratory of Infection & Immunity, Jiangxi Provincial People's Hospital&People's Hospital Affiliated to Nanchang University, Nanchang 330006, China. Electronic address:

As a disease with high mortality,many cytokines and signaling pathways are associated with sepsis.The pro-inflammatory cytokines and chemokines are participating in the pathogenesis of sepsis, especially in early stage. Moreover, the releases and expressions of cytokines are regulated by numerous signaling pathways, including TLR4/ERK pathway. But despite many studies have expounded the pathogenesis of sepsis and the regulation of cytokines in sepsis, how CD38 influence the expressions of related molecules in sepsis are still unknown. The aim of this study is illuminating the alteration of cytokines and signaling pathways in CD38 mice injected with Escherichia coli.Compared with WT mice, E. coli infection results in more severe pulmonary injuries and higher mRNA expressions of cytokines. Compared with E. coli infected WT mice,CD38 knockout leads to aggravated pulmonary injury, increasedphosphorylated ERK1/2, p38 and NF-κB p65, and enhancedlevels of IL-1β, iNOS and MCP-1.While compared with E. coli infected CD38 mice, TLR4 mutation results in alleviated pulmonary injury, down-regulated phosphorylated ERK1/2 and NF-κB p65, and decreased expressions of IL-1β and MCP-1.CD38 deficiency increased the expressions of IL-1β andMCP-1and aggravated pulmonary injury through TLR4/ERK/NF-κB pathway in sepsis.
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http://dx.doi.org/10.1016/j.micinf.2021.104845DOI Listing
June 2021

DevOmics: an integrated multi-omics database of human and mouse early embryo.

Brief Bioinform 2021 Jun 7. Epub 2021 Jun 7.

Center for Reproductive Medicine, Department of Obstetrics and Gynecology, Peking University Third Hospital, Beijing 100191, China.

Transcriptomic and epigenetic alterations during early embryo development have been proven to play essential roles in regulating the cell fate. Nowadays, advances in single-cell transcriptomics and epigenomics profiling techniques provide large volumes of data for understanding the molecular regulatory mechanisms in early embryos and facilitate the investigation of assisted reproductive technology as well as preimplantation genetic testing. However, the lack of integrated data collection and unified analytic procedures greatly limits their usage in scientific research and clinical application. Hence, it is necessary to establish a database integrating the regulatory information of human and mouse early embryos with unified analytic procedures. Here, we introduce DevOmics (http://devomics.cn/), which contains normalized gene expression, DNA methylation, histone modifications (H3K4me3, H3K9me3, H3K27me3, H3K27ac), chromatin accessibility and 3D chromatin architecture profiles of human and mouse early embryos spanning six developmental stages (zygote, 2cell, 4cell, 8cell, morula and blastocyst (ICM, TE)). The current version of DevOmics provides Search and Advanced Search for retrieving genes a researcher is interested in, Analysis Tools including the differentially expressed genes (DEGs) analysis for acquiring DEGs between different types of samples, allelic explorer for displaying allele-specific gene expression as well as epigenetic modifications and correlation analysis for showing the dynamic changes in different layers of data across developmental stages, as well as Genome Browser and Ortholog for visualization. DevOmics offers a user-friendly website for biologists and clinicians to decipher molecular regulatory mechanisms of human and mouse early embryos.
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http://dx.doi.org/10.1093/bib/bbab208DOI Listing
June 2021

Analysis of related factors affecting cumulative live birth rates of the first ovarian hyperstimulation in vitro fertilization or intracytoplasmic sperm injection cycle: a population-based study from 17,978 women in China.

Chin Med J (Engl) 2021 Jun 4. Epub 2021 Jun 4.

Center for Reproductive Medicine, Peking University Third Hospital, Beijing 100191, China National Clinical Research Center for Obstetrics and Gynecology, Beijing 100191, China Key Laboratory of Assisted Reproduction (Peking University), Ministry of Education, Beijing 100191, China Beijing Key Laboratory of Reproductive Endocrinology and Assisted Reproductive Technology, Beijing 100191, China Department of Obstetrics and Gynecology, Peking University Third Hospital, Beijing 100191, China.

Background: More and more scholars have called for the cumulative live birth rate (CLBR) of a complete ovarian stimulation cycle as a key indicator for assisted reproductive technology. This research aims to study the CLBR of the first ovarian hyperstimulation cycles and analyze the related prognosis factors that might affect the CLBR.

Methods: Our retrospective study included first in vitro fertilization or intracytoplasmic sperm injection (IVF/ICSI) cycles performed between January 2013 to December 2014. A total of 17,978 couples of first ovarian hyperstimulation IVF/ICSI cycles were included. The study was followed up for 4 years to observe the CLBR. The multivariable logistic regression model was used to analyze the prognosis factor, P value of <0.05 was considered statistically significant.

Results: The cumulative pregnancy rate was 58.14% (10,452/17,978), and the CLBR was 49.66% (8928/17,978). The female age was younger in the live birth group when compared with the non-live birth group (30.81 ± 4.05 vs. 33.09 ± 5.13, P < 0.001). The average duration of infertility was shorter than the non-live birth cohort (4.22 ± 3.11 vs. 5.06 ± 4.08, P < 0.001). The preliminary gonadotropin used and the total number of gonadotropin used were lower in the live birth group when compared with the non-live birth group (both P < 0.001). Meanwhile, the number of oocytes retrieved and transferrable embryos were both significantly higher in the live birth group (15.35 ± 7.98 vs. 11.35 ± 7.60, P < 0.001; 6.66 ± 5.19 vs. 3.62 ± 3.51, P < 0.001, respectively).

Conclusions: The women's age, body mass index, duration of infertility years, infertility factors, controlled ovarian hyperstimulation protocol, the number of acquired oocytes, and number of transferrable embryos are the prognosis factors that significantly affected the CLBR.
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http://dx.doi.org/10.1097/CM9.0000000000001586DOI Listing
June 2021

Impact of Chinese Respiratory Physicians Participating in Smoking Cessation and Mobile Health: A Randomized Feasibility Trial.

Clin Respir J 2021 Jun 4. Epub 2021 Jun 4.

Department of Gerontology and Geriatrics, The First Hospital of China Medical University, Shenyang, China.

Introduction: People who are eager to quit smoking often lack long-term, daily smoking cessation guidance. In addition, advances in mobile communication technology offer promising ways for providing tobacco dependence treatment. However, it is unclear whether the doctor-WeChat network can improve the smoking cessation rate of nicotine-dependent patients.

Methods: In this prospective single-blind cohort study, 250 smokers were enrolled from May 2018 to October 2018. They were randomly divided into two groups, with or without doctors' active smoking cessation service, and followed up for 6 months. The smoking cessation rate and characteristics of successful smoking cessation groups were compared. The reasons for relapse were also analyzed.

Results: After smoking cessation for 3 months, the success rate of the group involving active respiratory physicians was 65.0% (80/123); the success rate of the control group was 34.7% (34/98). After 6 months, the success rate of the group involving active respiratory physicians was 55.3% (68/123), while that of the control group was only 11.2% (11/98). There was no difference in the weight change of the participants between the two groups. Subgroup analysis showed that doctors' participation had a greater impact on the success of smoking cessation on men younger than 45 years or unemployed.

Conclusions: Doctors in mobile smoking cessation services played a very important role in improving quit rates. Our research provided methodological guidance for further clinical trials and a template for further real-world applications of smoking cessation services.
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http://dx.doi.org/10.1111/crj.13404DOI Listing
June 2021

Effect of early whole lung lavage at different time-points for promoting the removal of depleted uranium from the lung.

Int J Radiat Biol 2021 Jun 7:1-9. Epub 2021 Jun 7.

Emergency Department, The Southwest Hospital of Third Military Medical University, Chongqing, China.

Purpose: This study compared the effect of whole lung lavage (WLL) at different time-points early after exposure of the respiratory system to insoluble radioactive particles.

Materials And Methods: Forty adult beagles were randomized into a control group and the 3-h, 8-h, 24-h, and 48-h lavage groups ( = 8). A canine model of acute lung injury was established by spraying a depleted uranium (DU) suspension using a superfine fiber bronchoscope, at a dose of 20 mg/kg. The lavage groups were subjected to WLL at 3 h, 8 h, 24 h, and 48 h post-DU exposure, while the control group received no treatment after exposure. Measurement of U in serum was performed using inductively coupled plasma mass spectrometry; measurements in the lavage fluid and left lung tissue were performed using inductively coupled plasma atomic emission spectrometry. The color of the lavage fluid was analyzed using colorimetry, and shadow changes in the lung were observed using chest computed tomography (CT).

Results: The lavage groups showed similarly increasing trends for serum U levels from DU exposure to 3 and 7 days after exposure; however, these values were significantly lower than those in the control group ( < .01). The U content in the lavage fluid was significantly higher in the 3-h group than in the 8-h, 24-h, and 48-h groups ( < .01), while that in the 8-h group was markedly higher than those in the 24-h and 48-h groups ( < .05). The average clearance rate of DU in the lungs varied in the range of 0.63‒7.06%. The U content in the left lung tissue of each lavage group was significantly lower than that in the control group ( < .01), while the content in the 8-h, 24-h, and 48-h groups was significantly higher than that in the 3-h group ( < .05). The colorimetric score of the lavage fluid in the 3-h group was significantly lower than those in the 8-h, 24-h, and 48-h groups ( < .05). Chest CT showed different degrees of consolidation and ground glass shadow changes in all groups. The score of the left lung shadow volume in the 3-h group was significantly lower than in the control, 8-h, 24-h, and 48-h groups ( < .01), while the score in the 8-h group was significantly higher than those in the 48-h and control groups ( < .05).

Conclusions: The best effect of WLL after exposure of the respiratory system to insoluble radioactive particles was achieved at 3 h, followed by 8 h; there was no difference in the effectiveness of lung lavage at 24 h and 48 h.
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http://dx.doi.org/10.1080/09553002.2021.1928783DOI Listing
June 2021

LXN deficiency regulates cytoskeleton remodelling by promoting proteolytic cleavage of Filamin A in vascular endothelial cells.

J Cell Mol Med 2021 Jun 3. Epub 2021 Jun 3.

State Key Laboratory for the Chemistry and Molecular Engineering of Medicinal Resources, School of Chemistry and Pharmacy, Guangxi Normal University, Guilin, China.

Endothelial cells (ECs) respond to blood shear stress by changing their morphology is important for maintaining vascular homeostasis. Studies have documented a relationship between endothelial cell shape and the stress flow, and however, the mechanism underlying this cytoskeletal rearrangement due to shear stress remains uncertain. In this paper, we demonstrate that laminar shear stress (LSS) significantly reduces latexin (LXN) expression in ECs. By using siRNA and cell imaging, we demonstrated that LXN knockdown results in the morphologic change and F-actin remodelling just like what LSS does in ECs. We further demonstrate that LXN interacts with Filamin A (FLNA) and regulates FLNA proteolytic cleavage and nuclei translocation. By constructing LXN mice and ApoE LXN double knockout mice, we evaluated the effect of LXN knockout on aortic endothelium damage in mice. We found that LXN deficiency significantly improves vascular permeability, vasodilation and atherosclerosis in mice. Our findings provide confident evidence, for the first time, that LXN is a novel regulator for morphological maintenance of ECs, and LXN deficiency has a protective effect on vascular homeostasis. This provides new strategies and drug targets for the treatment of vascular diseases.
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http://dx.doi.org/10.1111/jcmm.16685DOI Listing
June 2021

Thalidomide Attenuates Colitis and Is Associated with the Suppression of M1 Macrophage Polarization by Targeting the Transcription Factor IRF5.

Dig Dis Sci 2021 Jun 3. Epub 2021 Jun 3.

Department of Gastroenterology, The Second Xiangya Hospital, Central South University, Changsha, 410011, Hunan, China.

Background: Ulcerative colitis (UC) is a chronic inflammatory bowel disease. The TNF-α inhibitor thalidomide is reported to be effective for inducing remission in pediatric Crohn's disease (CD) and adults with refractory CD. The mechanisms underlying the immunomodulatory and anti-inflammatory properties of thalidomide are unclear.

Methods: Histological assessments were firstly performed in thalidomide treated UC patients. Then the effect of thalidomide in vivo was detected in DSS-induced murine colitis. The mechanism involving IRF5, and M1 macrophage polarization was investigated by using plasmid transfection, western blotting, and real-time PCR. Finally, AOM/DSS model was used to detect the role of thalidomide in colitis associated cancer.

Results: We first found that treatment with thalidomide could ameliorate colon inflammation for 8 weeks and promote mucosal healing in human UC. Moreover, treatment with thalidomide protected mice from dextran sodium sulfate (DSS)-induced acute colitis, with treated mice presenting with a higher body weight, lower histological score, and lower DAI. Concomitantly, in comparison with control mice, mice treated with thalidomide showed accelerated recovery following colitis after 10 days of thalidomide treatment. Mechanistically, we observed that thalidomide could increase epithelial cell self-renewal capacity and modulate M1/M2 polarization by decreasing M1 markers CD86 and CCR7 and increasing M2 protein signatures CD206 and Arg-1. Thalidomide controls M1 macrophage polarization by targeting the transcription factor IRF5. Finally, by using the classical AOM/DSS model, we found that thalidomide-treated mice presented with a lower incidence and growth of colitis-associated carcinoma (CAC) than negative control mice.

Conclusions: In summary, thalidomide suppresses M1 polarization in the inflammatory microenvironment, which not only attenuates colonic inflammation to facilitate mucosal healing after DSS-induced injury but also represses the progression of CAC.
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http://dx.doi.org/10.1007/s10620-021-07067-2DOI Listing
June 2021

Effects of WNT1 c.110 T>C and c.505G>T mutations on osteoblast differentiation via the WNT1/β-catenin signaling pathway.

J Orthop Surg Res 2021 Jun 2;16(1):359. Epub 2021 Jun 2.

Clinical Laboratory, Affiliated Dongguan People's Hospital, Southern Medical University, No.3 Xinguchong Wandao South Road, Wangjiang District, Dongguan, 523059, China.

Background: WNT1 c.110 T>C and c.505G>T missense mutations have been identified in patients with osteogenesis imperfecta (OI). Whether these mutations affect osteoblast differentiation remains to be determined. This study aimed to investigate the effects of WNT1 c.110 T>C and c.505G>T mutations on osteoblast function, gene expression, and pathways involved in OI.

Methods: Empty vector (negative control), wild-type WNT1, WNT1 c.110 T>C, WNT1 c.505G>T, and WNT1 c.884C>A (positive control) mutant plasmids were constructed and transfected into preosteoblast (MC3T3-E1) cells to investigate their effect on osteoblast differentiation. The expressions of osteoblast markers, including BMP2, RANKL, osteocalcin, and alkaline phosphatase (ALP), were determined using quantitative real-time polymerase chain reaction (RT-qPCR), western blotting (WB), enzyme-linked immunosorbent assay, and ALP staining assay, respectively. The mRNA and protein expression levels of WNT1 or the expression levels of the relevant proteins involved in the WNT1/β-catenin signaling pathway were also determined using RT-qPCR, WB, and immunofluorescence (IF) assays after the different plasmids were transfected into MC3T3-E1 cells.

Results: Compared with those in the wild-type group, in the mutation groups, the mRNA and protein expression levels of BMP2 were suppressed, the expressions of osteocalcin and ALP were inhibited, and the mRNA and protein expression levels of RANKL were enhanced in MC3T3-E1 cells. WB and IF assays revealed that the protein expression levels of WNT1 in MC3T3-E1 cells were downregulated in the mutation groups compared with those in the wild-type WNT1 group. Furthermore, the expression levels of nonphosphorylated β-catenin (non-p-β-catenin) and phosphorylated GSK-3β (p-GSK-3β) were downregulated in the mutation groups compared with those in the wild-type group. However, no significant changes in the expression level of non-p-β-catenin or p-GSK-3β were observed in the mutation groups.

Conclusions: WNT1 c.110 T>C and c.505G>T mutations may alter the proliferation and osteogenic phenotype of MC3T3-E1 linked to the progression of OI via the inhibition of the WNT1/β-catenin signaling pathway. This is the first study to confirm the effect of WNT1 c.110 T>C and c.505G>T missense mutations on osteoblast differentiation and propose a new molecular mechanism for OI development.
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http://dx.doi.org/10.1186/s13018-021-02495-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8170984PMC
June 2021

SiC-Coated Carbon Nanotubes with Enhanced Oxidation Resistance and Stable Dielectric Properties.

Materials (Basel) 2021 May 24;14(11). Epub 2021 May 24.

State Key Laboratory of Solidification Processing, School of Materials Science and Engineering, Northwestern Polytechnical University, Xi'an 710072, China.

Carbon nanotubes (CNTs) coated with SiC coating was successfully prepared by pyrolysis of polycarbosilane (PCS) used as a precursor. The function of pyrolysis temperature on the oxidation resistance and the dielectric properties of CNTs/SiC were studied in X-band. The results demonstrate that the obtained dense SiC film can prevent the oxidation of CNTs when the pyrolysis temperature reaches 600 °C. Correspondingly, after heat treatment is at 400 °C for 200 h, the mass loss of P-600 is less than 1.86%, and the real and imaginary parts of the dielectric constant nearly keep constant (ε' from 14.2 to 14, and ε″ from 5.7 to 5.5). SiC-coated CNTs have a better oxidation resistance than pristine CNTs. Therefore, this work, with a facile preparation process, enhances the oxidation resistance of CNTs at high temperature for a long time and maintains a stable dielectric property, which means CNTs/SiC composites can be good candidates for applications in the field of high-temperature absorbers.
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http://dx.doi.org/10.3390/ma14112770DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8197107PMC
May 2021

Intrauterine insemination (IUI) with or without letrozole for unexplained or mild male factor infertility: A randomized pilot study.

Eur J Obstet Gynecol Reprod Biol 2021 May 15;262:216-220. Epub 2021 May 15.

Department of Obstetrics and Gynaecology, School of Clinical Sciences at Monash Health, Monash University, Clayton, Australia.

Objective: To study the feasibility of a randomized controlled trial (RCT) comparing intrauterine insemination (IUI) with and without letrozole in couples with unexplained or mild male factor infertility STUDY DESIGN: We performed a randomized pilot study including 100 couples with unexplained or mild male factor infertility in the Reproductive Medicine Centre of Peking University Third Hospital in China. The couples scheduled for IUI were randomized to IUI with or without ovarian stimulation (letrozole) for up to 3 cycles within a time horizon of 4 months. Women in the letrozole group received 5 mg oral letrozole daily starting from cycle day 3-5 for 5 days. Women in the natural cycle IUI group did not receive any ovarian stimulation before IUI. The primary outcome is ongoing pregnancy leading to live birth. The study was registered under trial number NCT03455426 RESULTS: Between March 2018 and January 2019, 158 couples were eligible to participate after initial screening and 100 (63.3 %) couples agreed to participate. Of the 100 recruited couples, 50 were randomly allocated to IUI with letrozole and 50 to natural cycle IUI. Live birth occurred in 12 women (24.0 %) in the letrozole group and 10 women (20.0 %) in the natural cycle group (RR 1.20 (95 % CI 0.57-2.52)). Clinical pregnancy rates were 28 % and 26 % in the letrozole group and natural cycle group respectively (RR 1.08 (95 % CI 0.56-2.05). There were no multiple pregnancies in both groups. Patients were willing to be randomized and useful information was gained to plan a definitive trial.

Conclusions: We showed that an RCT comparing IUI with letrozole versus natural cycle IUI in couples with unexplained or mild male factor infertility is feasible and acceptable.
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http://dx.doi.org/10.1016/j.ejogrb.2021.05.029DOI Listing
May 2021

Effect of Workplace Fun on Chinese Nurse Innovative Behavior: The Intermediary Function of Affective Commitment.

J Nurs Manag 2021 May 30. Epub 2021 May 30.

Sichuan Academy of Medical Sciences & Sichuan Provincial People's Hospital, China.

Aim: To assess the effects of workplace fun on nurse innovative behavior and to confirm the intermediary function of affective commitment.

Background: Employee innovative behavior has a crucial function in survival and development of an organization. On the basis of the theory of social exchange, there has been inadequate study of the influence of workplace fun on nurse innovative behavior mediated by affective commitment.

Methods: A cross-sectional, descriptive correlational research design was conducted for 331 Chinese nurses from five public hospitals. The measurements were obtained from a questionnaire on workplace fun, affective commitment, nurse innovative behavior, and a sociodemographic datasheet. Descriptive statistics were used to analyze the personal profile, and inferential statistics were used to test hypotheses.

Results: We identified a positive correlation between workplace fun and nurse innovative behavior. Affective commitment had a mediating effect.

Conclusions: Workplace fun and affective commitment can promote nurse innovative behavior.

Implications For Practice: Managers need to provide measures that promote workplace fun and affective commitment to enhance nurse innovative behavior.
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http://dx.doi.org/10.1111/jonm.13387DOI Listing
May 2021

Knife-edged crown fabricated by 3-dimensional gel deposition and soft milling.

J Prosthet Dent 2021 May 26. Epub 2021 May 26.

Professor, Center of Digital Dentistry, Department of Prosthodontics, Peking University School and Hospital of Stomatology, National Engineering Laboratory for Digital and Material Technology of Stomatology, Research Center of Engineering and Technology for Digital Dentistry of Ministry of Health, Beijing Key Laboratory of Digital Stomatology & National Clinical Research Center for Oral Disease, Beijing, PR China. Electronic address:

Statement Of Problem: Restorations with knife-edge margins are more prone to margin chipping during the manufacturing process. Three-dimensional gel deposition shows potential for fabricating zirconia restorations with good margin quality, but studies on its performance in fabricating knife-edged crowns are lacking.

Purpose: The purpose of this in vitro study was to compare the 3-dimensional trueness, surface morphology, and margin quality of self-glazed zirconia and soft-milled zirconia crowns with knife-edge margins.

Material And Methods: An abutment with a knife-edge finish line design was prepared and scanned with a laboratory scanner. Anatomic contour crowns were designed and fabricated by 3-dimensional gel deposition and soft milling (n=5). The crowns were digitalized, and the scan data were superimposed on the computer-aided design (CAD) data for 3-dimensional deviation analysis. Surface morphology and margin quality were characterized with microscopic examination.

Results: The self-glazed zirconia crowns showed a smooth and glossy appearance. The soft-milled crowns showed traces left by the removal of support bars and numerous micropits of various sizes. In internal areas, no significant difference was found in root mean square values between the 2 groups (P>.05). For the external surface, self-glazed zirconia showed statistically lower root mean square values than the soft-milled crowns (P<.05). When observed at ×5 magnification, all the self-glazed zirconia crowns showed smooth edges with no defects, whereas small or large margin defects were found in the soft-milled crowns. When characterized at ×200 magnification, minor margin flaws were observed in the self-glazed zirconia crowns. More and larger margin defects were found in the soft-milled crowns.

Conclusions: Three-dimensional gel deposition forms a smoother and more homogeneous surface than soft milling. Knife-edged self-glazed zirconia crowns have good dimensional accuracy and margin quality.
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http://dx.doi.org/10.1016/j.prosdent.2021.04.011DOI Listing
May 2021

Detection of the : c.393T>G Mutation in Two Patients with Hypochromic Microcytic Anemia.

Hemoglobin 2021 May 25:1-4. Epub 2021 May 25.

Department of Obstetrics and Gynecology, The First Affiliated Hospital of Chongqing Medical University, Chongqing, Chongqing Municipality, People's Republic of China.

A novel mutation, : c.393T>G on the gene, was detected in two hypochromic microcytic anemia patients from Yulin, in the Guangxi Province of the People's Republic of China (PRC), by next-generation sequencing (NGS). It is a nonsense mutation causing a stop codon at amino acid 131 in exon 3 of the gene. It was found in a heterozygous state in two patients who both presented severe anemia during pregnancy and moderate anemia before pregnancy; Hb A levels were slightly increased (more than 4.0%) in both patients. It was also detected in the father of one of the patients. This mutation was pathogenic, and caused the dominant thalassemia-like phenotypes in the two patients.
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http://dx.doi.org/10.1080/03630269.2021.1929307DOI Listing
May 2021

Autophagy deficiency downregulates Omethylguanine-DNA methyltransferase and increases chemosensitivity of liver cancer cells.

Aging (Albany NY) 2021 05 24;13(10):14289-14303. Epub 2021 May 24.

Tumor Immunology and Gene Therapy Center, Shanghai Eastern Hepatobiliary Surgery Hospital, Shanghai 200438, China.

It is known that autophagy-deficient cells are prone to DNA damage, but the specific role of autophagy in DNA damage repair is not fully known. Here, we show that autophagy-deficient liver cancer cells exhibit increased DNA damage caused by the chemotherapeutic agent epirubicin. Autophagy deficiency promotes downregulation of the DNA repair enzyme Omethylguanine-DNA methyltransferase (MGMT) in liver cancer cells. However, autophagy induction with epirubicin had no impact on MGMT gene or protein expression in liver cancer cells. In the absence of autophagy, the chemosensitivity of liver cancer cells was increased, but this was reversed by MGMT overexpression, indicating that autophagy mediates resistance to chemotherapy in liver cancer cells via MGMT. These findings demonstrate a direct link between autophagy, MGMT, and DNA damage repair in liver cancer cells, and show that MGMT not only regulates chemosensitivity to alkylating agents, but may also be involved in other DNA damage repair processes in autophagy-deficient cells.
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http://dx.doi.org/10.18632/aging.203044DOI Listing
May 2021

OP-IVM: Combining In vitro Maturation after Oocyte Retrieval with Gynecological Surgery.

J Vis Exp 2021 May 9(171). Epub 2021 May 9.

Center for Reproductive Medicine, Department of Obstetrics and Gynecology, Peking University Third Hospital; National Clinical Research Center for Obstetrics and Gynecology; Key Laboratory of Assisted Reproduction, Ministry of Education; Beijing Key Laboratory of Reproductive Endocrinology and Assisted Reproduction; Research Units of Comprehensive Diagnosis and Treatment of Oocyte Maturation Arrest, Chinese Academy of Medical Sciences;

The use of in vitro maturation (IVM) before gynecological operation (OP-IVM) is an extension of conventional IVM that combines IVM following oocyte retrieval with routine gynecological surgery. OP-IVM is suitable for patients undergoing benign gynecological surgery who have the need for fertility preservation (FP) or infertility treatments such as in vitro fertilization and embryo transfer (IVF-ET). In the operating room, patients undergoing benign gynecological surgery are first anesthetized and receive ultrasound-guided immature follicle aspiration (IMFA) treatment. As the subsequent gynecological surgery is performed, the cumulus-oocyte complexes (COCs) are examined, and the immature COCs are transferred into the IVM medium and cultured for 28-32 hours in the IVF laboratory. After assessment, mature oocytes in the MII stage will be selected and cryopreserved in liquid nitrogen for FP or fertilized by intracytoplasmic sperm injection (ICSI) for IVF-ET. By combining IVM with gynecological surgery, immature oocytes that would have been discarded can be saved and used for assisted reproductive technology (ART). The procedure, significance and critical aspects of OP-IVM are described in this article.
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http://dx.doi.org/10.3791/61647DOI Listing
May 2021

The ORF8 protein of SARS-CoV-2 mediates immune evasion through down-regulating MHC-Ι.

Proc Natl Acad Sci U S A 2021 06;118(23)

Institute of Human Virology, Key Laboratory of Tropical Disease Control of Ministry of Education, Guangdong Engineering Research Center for Antimicrobial Agent and Immunotechnology, Zhongshan School of Medicine, Sun Yat-sen University, 510080, Guangzhou, Guangdong, China;

COVID-19, caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has become a global pandemic and has claimed over 2 million lives worldwide. Although the genetic sequences of SARS-CoV and SARS-CoV-2 have high homology, the clinical and pathological characteristics of COVID-19 differ significantly from those of SARS. How and whether SARS-CoV-2 evades (cellular) immune surveillance requires further elucidation. In this study, we show that SARS-CoV-2 infection leads to major histocompability complex class Ι (MHC-Ι) down-regulation both in vitro and in vivo. The viral protein encoded by open reading frame 8 (ORF8) of SARS-CoV-2, which shares the least homology with SARS-CoV among all viral proteins, directly interacts with MHC-Ι molecules and mediates their down-regulation. In ORF8-expressing cells, MHC-Ι molecules are selectively targeted for lysosomal degradation via autophagy. Thus, SARS-CoV-2-infected cells are much less sensitive to lysis by cytotoxic T lymphocytes. Because ORF8 protein impairs the antigen presentation system, inhibition of ORF8 could be a strategy to improve immune surveillance.
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http://dx.doi.org/10.1073/pnas.2024202118DOI Listing
June 2021

One-step synthesis of amorphous nickel iron phosphide hierarchical nanostructures for water electrolysis with superb stability at high current density.

Dalton Trans 2021 May 21. Epub 2021 May 21.

Chemical Synthesis and Pollution Control key Laboratory of Sichuan Province, College of Chemistry and Chemical Engineering, China West Normal University, Nanchong 637000, P. R. China.

The development of noble-metal-free high-performance bifunctional catalysts for both the oxygen evolution reaction (OER) and hydrogen evolution reaction (HER) is essential but challenging for hydrogen production from water electrolysis. Herein, amorphous bimetallic nickel-iron phosphide hierarchical nanostructures enrooted on nickel-iron alloy foam (NiFeP/NFF) are facilely fabricated via direct phosphidation of NFF at low temperature and developed as an efficient self-supporting bifunctional electrocatalyst to catalyze both the OER and HER with high activity, fast kinetics and excellent stability. Moreover, an alkaline water electrolyzer simultaneously utilizing NiFeP/NFF as the cathode and anode only needs a cell voltage of 1.58 V to afford a current density of 10 mA cm-2, overpassing most of the reported bifunctional electrocatalysts and comparable to noble metal-based ones. Impressively, the NiFeP/NFF-based symmetric electrolyzer can work well without appreciable performance degradation at a high current density of 500 mA cm-2 for over 1000 h for continuous hydrogen production with 100% faradaic efficiency, showing superb durability and great promise for industrial application.
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http://dx.doi.org/10.1039/d1dt00852hDOI Listing
May 2021

Evidence-based nursing combined with cognitive function training can reduce the incidence of delirium in ICU patients and improve their cognitive function.

Am J Transl Res 2021 15;13(4):3262-3269. Epub 2021 Apr 15.

School of Nursing, Southern Medical University Guangzhou, Guangdong Province, China.

Objective: To explore whether evidence-based nursing combined with cognitive function training can reduce the incidences of delirium in intensive care unit (ICU) patients and improve their cognitive function.

Methods: ICU patients in our hospital were randomly divided into an evidence-based nursing group (the E group) and an evidence-based nursing combined with cognitive function training group (the EC group). The incidences of delirium, the Pittsburgh Sleep Quality Index (PSQI) scores, the Mini-Mental State Exam (MMSE) scores, the National Institutes of Health Stroke Scale (NIHSS) scores, the Barthel Index levels, and the nursing satisfaction rates were compared between the two groups.

Results: Before the nursing, there were no significant differences in the MMSE scores, the NIHSS scores, the Barthel Index levels or the PSQI scores between the E group and the EC group (P>0.05). After one week of treatment, the incidences of delirium in the EC group were significantly lower than they were in the E group (P<0.05). The PSQI scores and the NIHSS scores in the EC group were significantly lower than they were in the E group (P<0.001). The MMSE scores and the Barthel Index levels in the EC group were significantly higher than they were in the E group (P<0.01). There was no significant difference in the nursing satisfaction rates between the two groups (P>0.05).

Conclusion: Compared with using evidence-based nursing only, the combined application of evidence-based nursing and cognitive function training has a significantly better effect on the improvement of neurological function, sleep quality and normal living conditions in ICU patients.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8129389PMC
April 2021

Lentivirus-Mediated Overexpression or Silencing of Aquaporin 1 Affects the Proliferation, Migration and Invasion of TNF-α-Stimulated Rheumatoid Arthritis Fibroblast-Like Synoviocytes by Wnt/β-Catenin Signaling Pathway.

J Inflamm Res 2021 14;14:1945-1957. Epub 2021 May 14.

Inflammation and Immune Mediated Diseases Laboratory of Anhui Province, School of Pharmacy, Anhui Medical University, Hefei, 230032, Anhui Province, People's Republic of China.

Introduction: Previous studies have confirmed the pathologic role of synovial aquaporin 1 (AQP1) in rheumatoid arthritis (RA), but its associations with the abnormal biologic behaviors of fibroblast-like synoviocytes (FLS) remain unclear. Herein, we examined the roles of AQP1 in the proliferation, migration and invasion of TNF-α-stimulated RA FLS (MH7A cells) and explored the underlying mechanisms.

Materials And Methods: Lentivirus-mediated AQP1 overexpression or silencing MH7A cells was constructed. Assays of MTT, flow cytometry (PI staining and Annexin V-PE/7-AAD staining), TMRM staining, wound-healing, transwell and phalloidin staining were performed to detect cell proliferation, cycle distribution, apoptosis, migration and invasion. The involvement of Wnt/β-catenin pathway was revealed by Western blot and β-catenin immunofluorescence staining.

Results: AQP1 overexpression promoted cell proliferation of TNF-α-stimulated MH7A by facilitating transformation from G0/G1 to S phase and inhibiting cell apoptosis (ie, reduced apoptosis rates, raised mitochondrial membrane potential, increased Bcl-2 protein level and decreased levels of Bax and cleaved caspase 3 protein). Also, AQP1 overexpression increased the migration index as well as the numbers of migrated and invasive cells. Furthermore, AQP1 overexpression promoted the activation of Wnt/β-catenin pathway, and XAV939, an inhibitor of Wnt/β-catenin, canceled the above effects of AQP1 overexpression on MH7A cells. As expected, AQP1 silencing exhibited the opposite effects on TNF-α-stimulated MH7A cells, which could be reversed by LiCl, an activator of Wnt/β-catenin.

Conclusion: AQP1 can affect the proliferation, migration and invasion of MH7A cells by Wnt/β-catenin signaling pathway, and AQP1 can be as a crucial determiner that can regulate RA FLS biologic behaviors.
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http://dx.doi.org/10.2147/JIR.S312783DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8131072PMC
May 2021

Analysis of the proportion and clinical characteristics of obstructive sleep apnea in women with polycystic ovary syndrome.

Sleep Breath 2021 May 19. Epub 2021 May 19.

Reproductive Medical Center, Peking University Third Hospital, No. 49 North Garden Road, Haidian District, Beijing, 100191, China.

Purpose: To investigate the proportion and clinical characteristics of obstructive sleep apnea (OSA) in Chinese patients with polycystic ovarian syndrome (PCOS) through home sleep apnea test (HSAT) and to evaluate the reproductive endocrine and metabolic characteristics in these patients.

Methods: The study was a cross-sectional analysis of infertile PCOS patients who underwent sleep respiratory monitoring between January and December 2019 at Peking University Third Hospital Reproductive Medical Center and respiratory and critical care medicine department. The prevalence of OSA, body mass index (BMI), menstruation, reproductive endocrine, and metabolic characteristics were collected in patients with PCOS. Logistic regression was performed to identify significant relationships among these factors and OSA.

Results: Amont 328 patients with PCOS, the prevalence of OSA was 40% (131/328), and six cases (5%) were severe. Univariate analysis showed that BMI and blood pressure were significantly higher in patients with OSA than in those without OSA (P < 0.05), whereas the anti-Mullerian hormone was lower than that in patients without OSA. In terms of glucose and lipid metabolism, the glycosylated hemoglobin (HbA1c), fasting plasma glucose, and fasting insulin levels were significantly higher in patients with PCOS and comorbid OSA than in those without OSA (all P < 0.05). Patients with OSA also had higher triglyceride, low-density lipoprotein cholesterol, and high-sensitivity C-reactive protein levels and lower high-density lipoprotein cholesterol levels (P < 0.05). Logistic regression analysis revealed that higher BMI, elevated serum testosterone, and decreased high-density lipoprotein cholesterol (HDL-C) are correlated with occurrence of OSA (P < 0.05).

Conclusion: OSA in patients with PCOS was associated with multiple alterations in indexes of reproductive endocrine and metabolic disorders.
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http://dx.doi.org/10.1007/s11325-021-02376-2DOI Listing
May 2021

Neutrophil extracellular traps promote gastric cancer metastasis by inducing epithelial‑mesenchymal transition.

Int J Mol Med 2021 Jul 20;48(1). Epub 2021 May 20.

The Second Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang 150086, P.R. China.

The risks of tumor recurrence following the successful resection of the primary tumor have been known for decades; however, the precise mechanisms underlying treatment failures remain unknown. The formation of neutrophil extracellular traps (NETs) has increasingly been demonstrated to be associated with thrombi formation in cancer patients, as well as with the development and metastasis of cancer. The present study demonstrated that the level of peripheral blood NETs in patients with gastric cancer (GC) was associated with tumor progression, and patients with stage III/IV disease exhibited significant differences compared with the healthy controls and patients with stage I/II disease, which may be associated with an increased risk of metastasis. In addition, plasma from patients with stage III/IV GC was more prone to stimulate neutrophils to form NETs; thus, it was hypothesized that the formation of NETs may be affected by the tumor microenvironment. A higher deposition of NETs in GC tissues compared with normal resection margins was also identified. , following treatment with phorbol myristate acetate, which promotes the formation of NETs, or with DNAse‑1/GSK‑484, which inhibits the formation of NETs, it was found that the tumor migratory ability was altered; however, no significant changes were observed in cell proliferation and cell cycle progression. Epithelial‑mesenchymal transition (EMT) is a key event associated with dissemination and metastasis in GC pathogenesis. Finally, the present study demonstrated that NETs promote a more aggressive mesenchymal phenotype and promote the progression of GC and . On the whole, to the best of our knowledge, the present study reports a previously unknown role of NETs in the regulation of GC, which is associated with EMT and migration. Therefore, targeting NETs may prove to be therapeutically beneficial.
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http://dx.doi.org/10.3892/ijmm.2021.4960DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8128417PMC
July 2021

Strategic Design of Catalytic Lysine-Targeting Reversible Covalent BCR-ABL Inhibitors.

Angew Chem Int Ed Engl 2021 May 19. Epub 2021 May 19.

National University of Singapore, Department of Chemistry, 3 Science Dr., 117543, Singapore, SINGAPORE.

Targeted covalent inhibitors have re-emerged as validated drugs to overcome acquired resistance in cancer treatment. Herein, by using a carbonyl boronic acid (CBA) warhead, we report the structure-based design of BCR-ABL inhibitors via reversible covalent targeting of the catalytic lysine with improved potency against both wild-type and mutant ABL kinases, especially ABLT315I bearing the gatekeeper residue mutation. We show the evolutionarily conserved lysine can be targeted selectively, and the selectivity depends largely on molecular recognition of the non-covalent pharmacophore in this class of inhibitors, probably due to the moderate reactivity of the warhead. We report the first co-crystal structures of covalent inhibitor-ABL kinase domain complexes, providing insights into the interaction of this warhead with the catalytic lysine. We also employed label-free mass spectrometry to evaluate off-targets of our compounds at proteome-wide level in different mammalian cells.
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http://dx.doi.org/10.1002/anie.202105383DOI Listing
May 2021

Phylogenetic relatedness of woody angiosperm assemblages and its environmental determinants along a subtropical elevational gradient in China.

Authors:
Juan Yue Rong Li

Plant Divers 2021 Apr 10;43(2):111-116. Epub 2020 Sep 10.

CAS Key Laboratory for Plant Diversity and Biogeography of East Asia, Kunming Institute of Botany, Chinese Academy of Sciences, Kunming, 650201, China.

The species composition of plant communities is determined by a number of factors, including current environmental conditions as well as biogeographical and evolutionary history. Despite evidence that plant diversity decreases and species relatedness increases along latitudinal and environmental gradients (e.g., low temperatures), it remains unclear whether these same patterns occur along elevational gradients, especially in the subtropical mountainous areas harboring rich biodiversity. In this study, we explored the pattern of phylogenetic relatedness of woody angiosperm assemblages and examined the effects of temperature variables on the phylogenetic relatedness among angiosperm woody plants using generalized linear model in subtropical forest communities along a broad elevational gradient in the Dulong Valley of Yunnan Province, China. Our results showed that woody angiosperm species in local forest plots tend to be more phylogenetically related at higher elevations and in areas with lower temperatures. Additionally, winter average temperature, rather than mean annual temperature, is a major predictor of the pattern of increasing phylogenetic relatedness with increasing elevation. This finding is consistent with the prediction of 'Tropical Niche Conservatism' hypothesis, which highlights the role of niche constraints in driving phylogenetic community assembly along an elevational gradient.
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http://dx.doi.org/10.1016/j.pld.2020.08.003DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8103416PMC
April 2021

Effect of seasonal thermal stress on oxidative status, immune response and stress hormones of lactating dairy cows.

Anim Nutr 2021 Mar 4;7(1):216-223. Epub 2021 Jan 4.

Department of Animal Nutrition and Feed Science, College of Animal Science and Technology, Huazhong Agricultural University, Wuhan, 430070, China.

This study aimed to assess the impact of seasonal thermal stress on oxidative stress, immune response, and stress hormones of lactating dairy cows in subtropical regions with different levels of temperature-humidity index (THI). A total of 32 healthy lactating Holstein dairy cows experienced 4 seasons (8 cows/season). The physiological parameters were categorized into low THI (LTHI, THI = 42.97 ± 0.95) in winter, moderate THI (MTHI, THI = 61.84 ± 0.42) in spring and autumn, and high THI period (HTHI, THI = 86.09 ± 0.23) in summer. The blood samples were collected twice in each season to measure oxidative stress, inflammatory and hormonal parameters. Our results showed THI had a positive correlation with the rectal temperature ( = 0.821,  < 0.001) and respiratory rate ( = 0.816,  < 0.001). Dry matter intake, milk yield and fat percentage also significantly differed among groups ( < 0.05). Compared with the MTHI group, the LTHI group exhibited a significant increase in malondialdehyde (MDA) level ( < 0.001), and the HTHI group displayed a significant increase in levels of cortisol, interleukin (IL)-10, IL-1β and tumor necrosis factor-α ( < 0.001). Opposite changes in serum endotoxin and immunoglobulin G levels were observed with the increasing THI ( < 0.001). LTHI notably increased the triiodothyronine level, although the thyroxine level was reduced by LTHI and HTHI compared with the MTHI group. In conclusion, LTHI and HTHI conditions may induce different degrees of oxidative stress, inflammation response, and stress hormone imbalances on lactating dairy cows, therefore environmental management is necessary for the health of dairy cows in extreme weather conditions.
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http://dx.doi.org/10.1016/j.aninu.2020.07.006DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8110863PMC
March 2021