Publications by authors named "Jin Zhou"

1,243 Publications

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Artificial neural network for cytocompatibility and antibacterial enhancement induced by femtosecond laser micro/nano structures.

J Nanobiotechnology 2022 Aug 6;20(1):365. Epub 2022 Aug 6.

Advanced Manufacturing Center, Ningbo Institute of Technology, Beihang University, Ningbo, 315100, China.

The failure of orthopedic and dental implants is mainly caused by biomaterial-associated infections and poor osseointegration. Surface modification of biomedical materials plays a significant role in enhancing osseointegration and anti-bacterial infection. In this work, a non-linear relationship between the micro/nano surface structures and the femtosecond laser processing parameters was successfully established based on an artificial neural network. Then a controllable functional surface with silver nanoparticles (AgNPs) to was produced to improve the cytocompatibility and antibacterial properties of biomedical titanium alloy. The surface topography, wettability, and Ag release were carefully investigated. The effects of these characteristics on antibacterial activity and cytocompatibilty were also evaluated. Results show that the prepared surface is hydrophobic, which can prevent the burst release of Ag in the initial stage. The prepared surface also shows both good cytocompatibility toward the murine calvarial preosteoblasts MC3T3-E1 cells (derived from Mus musculus (mouse) calvaria) and good antibacterial effects against Gram-negative (E. coli) and Gram-positive (S. aureus) bacteria, which is caused by the combined effect of appropriate micro/nano-structured feature and reasonable Ag release rate. We do not only clarify the antibacterial mechanism but also demonstrate the possibility of balancing the antibacterial and osteointegration-promoting properties by micro/nano-structures. The reported method offers an effective strategy for the patterned surface modification of implants.
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http://dx.doi.org/10.1186/s12951-022-01578-4DOI Listing
August 2022

Learner satisfaction-based research on the application of artificial intelligence science popularization kits.

Front Psychol 2022 19;13:901191. Epub 2022 Jul 19.

College of Educational Science and Technology, Zhejiang University of Technology, Hangzhou, China.

The application of artificial intelligence science popularization kits in maker courses has promoted the rapid development of maker education. However, there exist few theoretical and empirical studies on the application of artificial intelligence science popularization kits in maker education. The theory of learner satisfaction can be used to explain learner motivation and outcomes with regard to participation in maker education using the artificial intelligence suite. Therefore, taking advantage of the opportunity the Zhejiang Action Plan for Promoting the Development of New Generation Artificial Intelligence (2019-2022) has provided, this study first conducted semi-structured interviews based on the results of a literature review and a questionnaire survey and then performed Pearson correlation analysis and regression analysis using SPSS 24.0 to explore the influencing factors of students' satisfaction with the use of artificial intelligence science popularization kits in education. The following results were obtained. (1) The correlation between grades and learners' satisfaction is not significant. (2) The use of a high-quality artificial intelligence science suite in the classroom will positively impact learners' satisfaction. (3) The degree of interaction with the artificial intelligence suite is negatively correlated with learners' satisfaction. (4) Teaching adaptability is significantly positively correlated with learner satisfaction. (5) Learners' individual characteristics have no significant positive correlation with learner satisfaction. Therefore, this study recommends focusing on suite quality, improving human-computer interaction, adopting a student-centered strategy, and aiming at improving the suitability of the curriculum.
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http://dx.doi.org/10.3389/fpsyg.2022.901191DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9343763PMC
July 2022

Comprehensive Analysis Identifies and Validates the Tumor Microenvironment Subtypes to Predict Anti-Tumor Therapy Efficacy in Hepatocellular Carcinoma.

Front Immunol 2022 18;13:838374. Epub 2022 Jul 18.

Cancer Center, Renmin Hospital of Wuhan University, Wuhan, China.

Objective: The objective of this study was to explore and verify the subtypes in hepatocellular carcinoma based on the immune (lymphocyte and myeloid cells), stem, and stromal cells in the tumor microenvironment and analyze the biological characteristics and potential relevance of each cluster.

Methods: We used the xCell algorithm to calculate cell scores and got subtypes by k-means clustering. In the external validation sets, we verified the conclusion stability by a neural network model. Simultaneously, we speculated the inner connection between clusters by pseudotime trajectory analysis and confirmed it by pathway enrichment, TMB, CNV, etc., analysis.

Result: According to the results of the consensus cluster, we chose k = 4 as the optimal value and got four different subtypes (C1, C2, C3, and C4) with different biological characteristics based on infiltrating levels of 48 cells in TME. In univariable Cox regression, the hazard ratio (HR) value of C3 versus C1 was 2.881 (95% CI: 1.572-5.279); in multivariable Cox regression, we corrected the age and TNM stage, and the HR value of C3 versus C1 was 2.510 (95% CI: 1.339-4.706). C1 and C2 belonged to the immune-active type, C3 and C4 related to the immune-insensitive type and the potential conversion relationships between clusters. We established a neural network model, and the area under the curves of the neural network model was 0.949 in the testing cohort; the same survival results were also observed in the external validation set. We compared the differences in cell infiltration, immune function, pathway enrichment, TMB, and CNV of four clusters and speculated that C1 and C2 were more likely to benefit from immunotherapy and C3 may benefit from FGF inhibitors.

Discussion: Our analysis provides a new approach for the identification of four tumor microenvironment clusters in patients with liver cancer and identifies the biological differences and predicts the immunotherapy efficacy between the four subtypes.
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http://dx.doi.org/10.3389/fimmu.2022.838374DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9339643PMC
August 2022

Changing Effects of Minimally Invasive Surgical Intervention on ALT, AST, and UA in Patients with Obstructive Sleep Apnea-Hypopnea Syndrome.

Int J Clin Pract 2022 14;2022:3622896. Epub 2022 Jul 14.

Department of Occupational Health, Sleep Medicine Center and ENT, West China School of Public Health and West China Forth Hospital, Sichuan University, Chengdu 610041, Sichuan, China.

Background: This study aims at exploring the effect of obstructive sleep apnea-hypopnea syndrome (OSAHS) on the liver and kidney function indexes of patients and analyze the changes in these indexes after minimally invasive surgery.

Method: Patients with OSAHS ( = 51) who were diagnosed via polysomnography (PSG) and received minimally invasive surgery in the sleep disorders diagnosis and treatment center of the West China Fourth Hospital of Sichuan University from January 2017 to January 2019 were selected as test subjects and placed in the OSAHS group. At the same time, 79 healthy people with no snoring or breathing difficulties were selected from the medical examination center of the hospital as the control group (tested as normal by PSG). These two groups were used to compare the differences in the related indexes of serum liver and kidney function and evaluate the changes in sleep monitoring and related liver and kidney function indexes in patients with OSAHS after minimally invasive surgery.

Results: The alanine aminotransferase (ALT), aspartate aminotransferase (AST), and uric acid (UA) levels were higher in the OSAHS group (48.98 ± 36.34, 28.88 ± 14.80, and 422.30 ± 98.65, respectively) than in the control group (21.91 ± 11.61, 22.18 ± 6.19, and 330.49 ± 64.45 and  = 6.514, 3.549, and 6.373, respectively; < 0.05). Of the patients with OSAHS, 17 were followed up for one year. After minimally invasive surgery, ALT decreased from 44.29 ± 20.61 to 26.47 ± 9.91 ( = 4.395), AST decreased from 27.71 ± 8.32 to 21.82 ± 4.81 ( = 3.673), and UA decreased from 397.35 ± 92.14 umol/L to 362.94 ± 106.76 umol/L ( = 2.580), and these differences were statistically significant ( < 0.05).The changes in ALT ( = -0.635) and AST ( = -0.504) were related to the difference in the lowest blood oxygen saturation ( < 0.05), and the change in UA was related to the difference in the apnea-hypopnea index ( = -0.532, < 0.05).

Conclusion: There are some abnormalities in liver- and kidney-function-related indexes in patients with OSAHS, and minimally invasive surgery can help to improve liver and kidney function in these patients.
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http://dx.doi.org/10.1155/2022/3622896DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9303076PMC
August 2022

Study on Inflammatory Factors in Aneurysmal Perimembranous Ventricular Septal Defect in Congenital Heart Disease.

Biomed Res Int 2022 19;2022:8282624. Epub 2022 Jul 19.

Anhui Provincial Children's Hospital, Hefei 230000, China.

To detect the expression of inflammatory factors such as interleukin-1 (IL-1), interleukin-6 (IL-6), transforming growth factor (TGF-), and tumor necrosis factor (TNF-) in the tumor tissue of ventricular septal defect (VSD) in congenital heart disease and to explore the role of inflammatory response in the formation of aneurysmal perimembranous VSD(APVSD). Children with APVSD of congenital heart disease treated by surgery were selected and divided into true aneurysmal perimembranous group (TAP group) and pseudoaneurysmal perimembranous group (PAP group) according to echocardiography and surgical findings. There were 15 children in the TAP group and 31 in the PAP group. The aneurysmal perimembranous tissue of the two groups of children was collected during the operation. IL-1, IL-6, TGF-, and TNF- were positively expressed in the aneurysmal perimembranous tissue of the two groups, and the expression levels of all inflammatory factors in the PAP group were higher than those in the TAP group, and the difference was statistically significant ( < 0.05). The expression levels of IL-1, IL-6, TGF-, and TNF- in the aneurysmal perimembranous tissue of the two groups were negatively correlated with the width of the APVSD breach. IL-1, IL-6, TGF-, and TNF- may be involved in the occurrence and development of APVSD through inflammatory mechanism.
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http://dx.doi.org/10.1155/2022/8282624DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9325631PMC
August 2022

The Role of Amnioreduction in Emergency Cervical Cerclage with Bulging Membranes: A Retrospective Comparative Study.

Front Surg 2022 12;9:928322. Epub 2022 Jul 12.

Department of Obstetrics and Gynecology, Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, China.

The purpose of this study was to investigate the role of amnioreduction in patients who underwent emergency cervical cerclage (ECC) with bulging membranes during the second trimester. This retrospective comparative study included 46 singleton pregnant women who had cervical dilation at least 1 cm with bulging membranes beyond the external cervical os and underwent ECC at the Third Affiliated Hospital of Sun Yat-sen University between December 2016 and December 2021. Cases were categorized as amnioreduction group ( = 16) and non-amnioreduction group ( = 30) according to whether amnioreduction was performed prior to ECC. The gestational age and cervical dilation at cerclage, operative time, prolongation of pregnancy, and outcomes of pregnancy were compared between the two groups. All 46 patients underwent successful ECC excepted one case with intraoperative rupture of membrane in non-amnioreduction group. In the amnioreduction group, the cervical dilation at cerclage was larger than that in the non-amnioreduction group (4.5 ± 2.2 vs. 2.2 ± 1.2 cm,  < 0.001), and had more patients with cervical dilation ≥4 cm (50.0% vs. 10.0%,  = 0.004). However, the gestational age at cerclage, operative time, prolongation of pregnancy, gestational age at delivery were not significantly different between the two groups (22.9 ± 2.8 vs. 22.9 ± 3.2 weeks, 31.1 ± 9.2 vs. 27.9 ± 11.4 min, 21.3 ± 21.5 vs. 38.7 ± 40.2 days, 25.9 ± 4.5 vs. 28.4 ± 6.1 weeks;  > 0.05). The rates of delivery ≥28 weeks, ≥32 weeks, and live birth were 20.0% vs. 80.0%, 12.5% vs. 26.7%, 56.3% vs. 66.7% ( > 0.05) in amnioreduction group and non-amnioreduction group, respectively. In conclusion, even in cases with larger cervical dilation, the application of amnioreduction with ECC is possible to get the acceptable pregnancy outcomes. These findings suggested that amnioreduction may be a safe and feasible option to be applied before ECC, especially for those with advanced cervical dilation and bulging membranes.
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http://dx.doi.org/10.3389/fsurg.2022.928322DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9314748PMC
July 2022

Human liver microsomes study on the inhibitory effect of plantainoside D on the activity of cytochrome P450 activity.

BMC Complement Med Ther 2022 Jul 23;22(1):197. Epub 2022 Jul 23.

Clinical Research Center, Shanghai Baoshan Luodian Hospital, No.121 Luoxi Road, Baoshan District, Shanghai, 201908, China.

Background: Plantainoside D is widely existed in the herbs and possesses various pharmacological activities, making it possible to co-administrate with other herbs. Its effect on cytochrome P450 enzymes (P450) is a risk factor for inducing adverse drug-drug interactions. To assess the effect of plantainoside D on the activity of major P450 isoenzymes in human liver microsomes.

Methods: The Cocktail method was conducted in human liver microsomes in the presence of probe substrates. The activity of P450 isoenzymes was evaluated by the production of corresponding metabolites. The concentration-dependent and time-dependent inhibition assays were performed in the presence of 0, 2.5, 5, 10, 25, 50, and 100 μM plantainoside D to characterize the inhibitory effect of plantainoside D.

Results: Significant inhibition was observed in the activity of CYP1A2, 2D6, and 3A, which was concentration-dependent with the IC values of 12.83, 8.39, and 14.66 μM, respectively. The non-competitive manner and competitive manner were observed in the CYP3A inhibition (Ki = 7.16 μM) and CYP1A2 (Ki = 6.26 μM) and 2D6 inhibition (Ki = 4.54 μM), respectively. Additionally, the inhibition of CYP3A was found to be time-dependent with the KI of 1.28 μM and K of 0.039 min.

Conclusions: Weak inhibitory effects of plantainoside D on the activity of CYP1A2, 2D6, and 3A were revealed in vitro, implying its potential of inducing interactions with CYP1A2-, 2D6-, and 3A-metabolized drugs. Although further in vivo validations are needed, the feasibility of the Cocktail method in evaluating P450 activity has been verified.
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http://dx.doi.org/10.1186/s12906-022-03671-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9308932PMC
July 2022

Effectiveness, immunogenicity, and safety of the quadrivalent HPV vaccine in women and men aged 27-45 years.

Hum Vaccin Immunother 2022 Jul 19:2078626. Epub 2022 Jul 19.

Merck & Co., Inc, Rahway, NJ, USA.

Among women aged 27-45 years, the quadrivalent human papillomavirus (qHPV; HPV6/11/16/18) vaccine was generally well tolerated, efficacious, and immunogenic in the placebo-controlled FUTURE III study (NCT00090220; n = 3253). The qHPV vaccine was also generally well tolerated and highly immunogenic in men aged 27-45 years who participated in the single-cohort mid-adult male (MAM) study (NCT01432574; n = 150). Here, we report results of a long-term follow up (LTFU) extension of FUTURE III with up to 10 years follow-up. To understand the relevance of the mid-adult women LTFU study in the context of mid-adult men vaccination, we report results from post-hoc, cross-study immunogenicity analyses conducted to compare immunogenicity (geometric mean titers; GMTs) at 1-month post-qHPV vaccine dose 3 in women and men aged 27-45 years versus women and men aged 16-26 years from prior efficacy studies. The qHPV vaccine demonstrated durable protection against the combined endpoint of HPV6/11/16/18-related high-grade cervical dysplasia and genital warts up to 10 years (median 8.9) post-dose 3 and sustained HPV6/11/16/18 antibody responses through approximately 10 years in women aged 27-45 years. Efficacy of qHPV vaccine in men aged 27-45 years was inferred based on the cross-study analysis of qHPV vaccine immunogenicity demonstrating non-inferior HPV6/11/16/18 antibody responses in men aged 27-45 years versus 16-26 years. In conclusion, durable effectiveness of the qHPV vaccine was demonstrated in women 27-45 years of age, and vaccine efficacy was inferred in men 27-45 years of age based on the serological results.
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http://dx.doi.org/10.1080/21645515.2022.2078626DOI Listing
July 2022

Complete Genome Sequence of BH16, a Siderophore-Producing Mutualistic Bacterium Isolated from Diatom .

Mol Plant Microbe Interact 2022 Jul 13:MPMI01220025A. Epub 2022 Jul 13.

Shenzhen Public Platform for Screening and Application of Marine Microbial Resources, Institute for Ocean Engineering, Shenzhen International Graduate School, Tsinghua University, Shenzhen 518055, Guangdong Province, P. R. China.

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http://dx.doi.org/10.1094/MPMI-01-22-0025-ADOI Listing
July 2022

Effects of anthropogenic nitrogen additions and elevated CO on microbial community, carbon and nitrogen content in a replicated wetland.

Environ Monit Assess 2022 Jul 11;194(8):575. Epub 2022 Jul 11.

Soil Research Centre, Department of Geography and Environmental Sciences, University of Reading, Reading, RG6 6AB, UK.

Anthropogenic deposition of nitrogen (N) and elevated CO (CO) are expected to increase continuously and rapidly in the near future and influence global carbon cycling. These parameters affect the ecosystem by regulating the microbial community and contribute to soil organic matter decomposition. The study was performed to understand the effects of N additions (4 and 6mgl) and CO (700 ppm) on carbon (C)/nitrogen (N) content in the soil, microbial community, and plant biomass (Alternanthera philoxeroides species). The results showed that when the atmospheric CO concentration was raised, the total organic carbon (TOC) in the soil statistically increased (P < 0.05) by 4% and 3% under low and high N additions respectively, while the inorganic carbon content also increased by 1% and 3% (P > 0.05) under the same conditions. The increase in the soil TOC content was a result of the movement of carbon from water to the soil due to the presence of vascular tissues of plants in the water. The redundancy analysis (RDA) results revealed that the presence of plant species was responsible for the carbon content increment in the soil. The plant biomass content increased by 30.96% (P = 0.081) and 31.36%, (P = 0.002) under low and high N addition respectively due to the increment in atmospheric CO. The nitrogen content in the plant species decreased (p > 0.05) by 8.62% and 6.25% at low and high N addition respectively when atmospheric CO was raised. This suggests that soil microbes competed with the plants for inorganic nitrogen in the soil and the microbes used up the inorganic nitrogen before it got to the plants. The gram-positive bacteria and fungi population decreased under high N addition and CO while gram-negative bacteria increased, suggesting that N additions and CO affected the microbial function and correlated with the nitrogen reduction in the soil. The results from this study serve as a guide to researchers and stakeholders in making policies with regard to the constant increasing CO concentration in the atmosphere.
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http://dx.doi.org/10.1007/s10661-022-10229-yDOI Listing
July 2022

Multiscale biomechanics and mechanotransduction from liver fibrosis to cancer.

Adv Drug Deliv Rev 2022 Jul 9;188:114448. Epub 2022 Jul 9.

Center for Biomechanics and Bioengineering, Key Laboratory of Microgravity (National Microgravity Laboratory), and Beijing Key Laboratory of Engineered Construction and Mechanobiology, Institute of Mechanics, Chinese Academy of Sciences, Beijing 100190, China; School of Engineering Sciences, University of Chinese Academy of Sciences, Beijing 100049, China. Electronic address:

A growing body of multiscale biomechanical studies has been proposed to highlight the mechanical cues in the development of hepatic fibrosis and cancer. At the cellular level, changes in mechanical microenvironment induce phenotypic and functional alterations of hepatic cells, initiating a positive feedback loop that promotes liver fibrogenesis and hepatocarcinogenesis. Tumor mechanical microenvironment of hepatocellular carcinoma facilitates tumor cell growth and metastasis, and hinders the drug delivery and immunotherapy. At the molecular level, mechanical forces are sensed and transmitted into hepatic cells via allosteric activation of mechanoreceptors on the cell membrane, leading to the activation of various mechanotransduction pathways including integrin and YAP signaling and then regulating cell function. Thus, the application of mechanomedicine concept in the treatment of liver diseases is promising for rational design and cell-specific delivery of therapeutic drugs. This review mainly discusses the correlation between biomechanical cues and liver diseases from the viewpoint of mechanobiology.
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http://dx.doi.org/10.1016/j.addr.2022.114448DOI Listing
July 2022

Vitamin B and folate decrease inflammation and fibrosis in NASH by preventing Syntaxin 17 homocysteinylation.

J Hepatol 2022 Jul 9. Epub 2022 Jul 9.

Laboratory of Hormonal Regulation, Cardiovascular and Metabolic Disorders, Duke-NUS Medical School, Singapore 169857; Duke Molecular Physiology Institute, Duke University School of Medicine, 300 N Duke St, Durham, NC 27701, USA; Endocrinology, Diabetes, and Metabolism Division, Duke University School of Medicine, 300 N Duke St, Durham, NC 27701, USA. Electronic address:

Background And Aims: The relationship between hyperhomocysteinemia (HHcy) and non-alcoholic steatohepatitis (NASH) is poorly understood.

Methods: We examined the effects of HHcy on NASH progression, metabolism, and autophagy in dietary and genetic mouse models, patients, and primates. We employed vitamin B (B) and folate (Fol) to reverse NASH features in mice and cell culture.

Results: Serum homocysteine (Hcy) correlated with hepatic inflammation and fibrosis in NASH. Elevated hepatic Hcy induced and exacerbated NASH. Gene expression of hepatic Hcy-metabolizing enzymes was down-regulated in NASH. Surprisingly, we found increased homocysteinylation (Hcy-lation) and ubiquitination of multiple hepatic proteins in NASH including the key autophagosome/lysosome fusion protein, Syntaxin 17 (Stx17). This protein was Hcy-lated and ubiquitinated, and its degradation led to autophagy block. Genetic manipulation of Stx17 revealed its critical role in regulating autophagy, inflammation and fibrosis during HHcy. Remarkably, dietary B/Fol, which promotes enzymatic conversion of homocysteine to methionine, decreased HHcy and hepatic Hcy-lated protein levels, restored Stx17 expression and autophagy, stimulated β-oxidation of fatty acids, and improved hepatic histology in mice with pre-established NASH.

Conclusions: HHcy plays a key role in the pathogenesis of NASH via Stx17 homocysteinylation. B/folate also may represent a novel first-line therapy for NASH.

Lay Summary: The roles of high serum homocysteine levels (HHcy) and intrahepatic homocysteine on the development of non-alcoholic seatohepatitis (NASH) are not known. We found HHcy increased with NASH severity and showed that homocysteinylation of the key autophagy protein STX17 led to autophagy block during NASH and NASH progression. Vitmains B and folate supplementation restored autophagy and reduced NASH progression and could be a new first-line therapy for NASH.
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http://dx.doi.org/10.1016/j.jhep.2022.06.033DOI Listing
July 2022

Bladder Acellular Matrix Prepared by a Self-Designed Perfusion System and Adipose-Derived Stem Cells to Promote Bladder Tissue Regeneration.

Front Bioeng Biotechnol 2022 22;10:794603. Epub 2022 Jun 22.

Department of Urology, The Third Medical Centre, Chinese PLA General Hospital, Beijing, China.

The bladder patch constructed with the bladder acellular matrix (BAM) and adipose-derived stem cells (ASCs) was incubated with the omentum for bladder reconstruction in a rat model of bladder augmentation cystoplasty. A self-designed perfusion system and five different decellularization protocols were used to prepare the BAM. Finally, an optimal protocol (group C) was screened out by comparing the cell nucleus residue, collagen structure preservation and biologically active components retention of the prepared BAM. ASCs-seeded (BAM-ASCs group) and unseeded BAM (BAM group) were incubated with the omentum for 7 days to promote neovascularization and then perform bladder reconstruction. Hematoxylin and eosin and Masson's trichrome staining indicated that the bladder patches in the BAM-ASCs group could better regenerate the bladder wall structure compared to the BAM group. Moreover, immunofluorescence analyses demonstrated that the ASCs could promote the regeneration of smooth muscle, neurons and blood vessels, and the physiological function (maximal bladder capacity, max pressure prior to voiding and bladder compliance) restoration in the BAM-ASCs group. The results demonstrated that the self-designed perfusion system could quickly and efficiently prepare the whole bladder scaffold and confirmed that the prepared BAM could be used as the scaffold material for functional bladder tissue engineering applications.
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http://dx.doi.org/10.3389/fbioe.2022.794603DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9257038PMC
June 2022

Comprehensive Analysis of VCAN Expression Profiles and Prognostic Values in HCC.

Front Genet 2022 24;13:900306. Epub 2022 Jun 24.

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

Hepatocellular carcinoma (HCC) is the world's most common cause of cancer death. Therefore, more molecular mechanisms need to be clarified to meet the urgent need to develop new detection and treatment strategies. We used TCGAportal, Kaplan-Meier Plotter, the Cistrome DB Toolkit Database, MExpress, GEPIA2, and other databases to discuss the expression profiles, possible biological function, and potential prognostic value of versican (VCAN) in HCC. We conducted cell experiments such as Transwell migration and invasion assays, wound healing assay, and CCK8 experiment to explore the function of VCAN in HCC. We selected three HCC transcriptome databases GSE124535, GSE136247, and GSE144269 and analyzed the overexpressed genes contained in them. The overlapping genes were found by the Venn map, and two interacting network modules were found by Mcode. Module 1 was mainly related to mitosis and cell cycle, and module 2 was mainly related to EMT, angiogenesis, glycolysis, and so on. We found that the seed gene in module 2 is VCAN. Data from TCGAportal showed that compared with normal tissues, the expression of VCAN was up-regulated in HCC tissues. The patients with high expression of VCAN had shorter distant recurrence-free survival and overall survival. Multiple possible VCAN interactions had also been identified. These results revealed that the level of VCAN was higher in the subtypes of HCC with higher malignant degree and was connected to the poor prognosis. In addition, the treatment of VCAN with DNA methyltransferase inhibitors and transcription factor inhibitors may improve the prognosis of patients with HCC. Our findings systematically elucidated the expression profile and different prognostic values of VCAN in HCC, which may provide new therapeutic targets and potential prognostic biomarkers for HCC patients.
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http://dx.doi.org/10.3389/fgene.2022.900306DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9263583PMC
June 2022

Differential diagnosis of B-mode ultrasound Breast Imaging Reporting and Data System category 3-4a lesions in conjunction with shear-wave elastography using conservative and aggressive approaches.

Quant Imaging Med Surg 2022 Jul;12(7):3833-3843

Department of Ultrasonography, Fudan University Shanghai Cancer Center, Shanghai, China.

Background: The high false-positive rates of US Breast Imaging Reporting and Data System (BI-RADS) category 3-4a breast lesions leads to excessive biopsies of many benign lesions, and our aim was to investigate the diagnostic performance achieved by adding a maximum elasticity (Emax) of shear-wave elastography (SWE) to ultrasound (US) to evaluate US BI-RADS category 3-4a breast lesions using conservative and aggressive approaches. We explored the capacity of using this method to avoid unnecessary biopsies without increasing the probability of missing breast cancers.

Methods: A total of 123 breast lesions of 120 patients classified as BI-RADS category 3 or 4a were enrolled from January 2019 to December 2019. The US features were evaluated according to the US BI-RADS lexicon. The maximum diameter measured on the US was defined as the size of the lesion. The Emax was assessed by SWE, and the average Emax of breast lesions on two images were calculated and recorded as the final maximum Young's modulus. The diagnostic performance of the combined B-mode US and SWE approach for BI-RADS category 3-4a breast lesions was tested using a conservative approach and an aggressive approach. In the conservative approach, the lesions were downgraded with Emax of 30 kPa or less and upgraded with Emax of 160 kPa or more. In the aggressive approach, the lesions were downgraded with Emax of 80 kPa or less and upgraded with Emax of 160 kPa or more. Pathologic results were defined as the reference standard.

Results: Among all 123 breast lesions, there were 60 lesions classified as BI-RADS category 3 and 63 lesions classified as BI-RADS category 4a. Compared to the B-mode US, the sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), accuracy, and area under the receiver operating characteristic (ROC) curve (AUC) of the combined B-mode US and SWE with a conservative approach changed from 88.9% to 94.4%, 55.2% to 60.0%, 25.4% to 28.8%, 96.7% to 98.4%, 60.2% to 65.0%, and 0.721 to 0.772, respectively. The specificity, PPV, and accuracy of combined B-mode US and SWE with an aggressive approach increased from 55.2% to 72.4%, 25.4% to 29.3%, and 60.2% to 71.5%, respectively, but this was accompanied with decreases in the sensitivity from 88.9% to 66.7%, the NPV from 96.7% to 92.7%, and the AUC from 0.721 to 0.695.

Conclusions: The addition of SWE improves the diagnostic performance of breast US. Adding the diagnostic criteria of SWE to the BI-RADS assessment of B-mode US, downgrading the lesions with Emax 30 kPa or less, and upgrading the lesions with Emax 160 kPa or more helped discriminate low suspicion lesions from benign lesions in order to decrease false-positive findings and avoid missing cancer diagnosis.
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http://dx.doi.org/10.21037/qims-21-916DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9246754PMC
July 2022

Ammonium stress promotes the conversion to organic nitrogen and reduces nitrogen loss based on restructuring of bacterial communities during sludge composting.

Bioresour Technol 2022 Jun 28;360:127547. Epub 2022 Jun 28.

College of Life Science, Northeast Agricultural University, Harbin 150030, China.

This study aimed to clarify the conversion relationship between organic and inorganic nitrogen. The NHCl was used to enhance the inorganic nitrogen content. The key role of bacterial conversion of ammonium to organic nitrogen under ammonium stress was explored. Studies had shown that ammonium stress increased the amide nitrogen and bioavailable nitrogen content by 36.95% and 32.25%, respectively. Network and regression analyses showed that the microbial community structure was restructured by high ammonium and more bacteria were involved in the conversion of inorganic nitrogen to organic nitrogen(i.e., amide nitrogen, unknown nitrogen). Variation partition analysis and structural equation model showed that the bacterial community was the main contributor to organic nitrogen production(up to 67.4%), which reduced the nitrogen loss by 6.03%. These findings shed light on the poorly understood interaction between inorganic and organic nitrogen by clarifying the role of core bacterial communities in nitrogen conversion.
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http://dx.doi.org/10.1016/j.biortech.2022.127547DOI Listing
June 2022

Risk Factors and Timing of Additional Surgery after Noncurative ESD for Early Gastric Cancer.

Can J Gastroenterol Hepatol 2022 21;2022:3421078. Epub 2022 Jun 21.

Department of General Surgery, The First Affiliated Hospital of Soochow University, Suzhou, Jiangsu 215006, China.

Background: Patients with early gastric cancer undergoing noncurative endoscopic submucosal dissection (ESD) have a risk of tumor recurrence and metastasis, and some patients need additional surgery. The purpose of this study was to explore the risk factors of cancer residue and lymph node (LN) metastasis after noncurative ESD for early gastric cancer and to compare the short outcome of early and delayed additional surgery.

Methods: The clinicopathological characteristics of 30 early gastric cancer patients who received noncurative ESD and additional surgery were studied retrospectively. Multivariable regression was utilized to examine the independent risk factors for residual cancer and LN metastasis. Receiver operating characteristic curve was used to analyze the multivariable model's predictive performance. Furthermore, the perioperative safety and radical tumor performance of early surgery (≤30 days,  = 11), delayed surgery (>30 days,  = 11) after ESD, and upfront surgery ( = 59) were compared.

Results: Multivariable regression showed that diffuse type of Lauren classification, submucosal invasion, and positive human epidermal growth factor receptor-2 (HER-2) were risk factors for residual cancer. Undifferentiated carcinoma, vascular invasion, and positive vertical margin were risk factors for LN metastasis. The area under the curve (AUC) of the multifactor model predicting cancer residue and LN metastasis was 0.761 and 0.792, respectively. The early surgery group experienced higher intraoperative blood loss and a longer operation time than the delayed surgery and upfront surgery groups. There was no significant difference in the number of LN dissections, LN metastasis rate, and postoperative complications among the three groups.

Conclusion: Diffuse type of Lauren classification, submucosal invasion, and positive HER-2 are risk factors for residual cancer, while undifferentiated carcinoma, vascular invasion, and positive vertical margin are risk factors for LN metastasis. Delayed additional surgery after ESD (>30 days) has higher intraoperative safety, without affecting the radical resection in early gastric cancer patients.
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http://dx.doi.org/10.1155/2022/3421078DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9239820PMC
July 2022

A MUC5B Gene Polymorphism, rs35705950-T Confers Protective Effects Against COVID-19 Hospitalization but not Severe Disease or Mortality.

Am J Respir Crit Care Med 2022 Jun 30. Epub 2022 Jun 30.

Vanderbilt University Medical Center, 12328, Division of Cardiovascular Medicine, Department of Medicine, Nashville, Tennessee, United States.

Rationale: A common MUC5B gene polymorphism, rs35705950-T, is associated with idiopathic pulmonary fibrosis (IPF), but its role in SARS-CoV-2 infection and disease severity is unclear.

Objectives: To assess whether rs35705950-T confers differential risk for clinical outcomes associated with COVID-19 infection among participants in the Million Veteran Program (MVP).

Methods: The MUC5B rs35705950-T allele was directly genotyped among MVP participants; clinical events and comorbidities were extracted from the electronic health records. Associations between the incidence or severity of COVID-19 and rs35705950-T were analyzed within each ancestry group in the MVP followed by trans-ancestry meta-analysis. Replication and joint meta-analysis were conducted using summary statistics from the COVID-19 Host Genetics Initiative (HGI). Sensitivity analyses with adjustment for additional covariates (BMI, Charlson comorbidity index, smoking, asbestosis, rheumatoid arthritis with interstitial lung disease and IPF) and associations with post-COVID-19 pneumonia were performed in MVP subjects.

Measurements And Main Results: The rs35705950-T allele was associated with fewer COVID-19 hospitalizations (Ncases=4,325/, Ncontrols=507,640; OR=0.89 [0.82-0.97], p=6.86 x 10-03) in trans-ancestry meta-analysis within MVP and joint meta-analyses with the HGI (Ncases=13,320, Ncontrols=1,508,841; OR=0.90 [0.86-0.95], p =8.99 x 10-05). The rs35705950-T allele was not associated reduced COVID-19 positivity in trans-ancestry meta-analysis within MVP (Ncases=19,168/Ncontrols=492,854; OR=0.98 [0.95-1.01], p=0.06) but was nominally significant (p<0.05) in the joint meta-analysis with HGI (Ncases=44,820/Ncontrols=1,775,827; OR=0.97 [0.95-1]; p=0.03). We did not observe associations with severe outcomes or mortality. Among MVP individuals of European ancestry, rs35705950-T was associated with fewer post-COVID-19 pneumonia events (OR=0.82 [0.72-0.93], p=0.001).

Conclusions: The MUC5B variant rs35705950-T may confer protection in COVID-19 hospitalizations. This article is open access and distributed under the terms of the Creative Commons Attribution Non-Commercial No Derivatives License 4.0 (http://creativecommons.org/licenses/by-nc-nd/4.0/).
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http://dx.doi.org/10.1164/rccm.202109-2166OCDOI Listing
June 2022

Effect of Carbetocin on Postpartum Hemorrhage after Vaginal Delivery: A Meta-Analysis.

Comput Math Methods Med 2022 20;2022:6420738. Epub 2022 Jun 20.

Department of Obstetrics and Gynecology, Hainan Modern Women and Children's Hospital, Haikou, Hainan 571100, China.

Background: The efficacy of oxytocin and carbetocin in preventing postpartum hemorrhage (PPH) in women with vaginal delivery has been controversial. This study is aimed at conducting a meta-analysis that compares the efficacy of carbetocin and oxytocin in the prevention of PPH among women with vaginal delivery.

Methods: Literature was retrieved from PubMed, Medline, Embase, CENTRAL, and CNKI databases. The randomized controlled trials (RCTs) that compare the efficacy of carbetocin and oxytocin to prevent PPH were searched. Data from the included literatures were extracted by two researchers, including author, title, publication date, study type, study number, the incidence of PPH, number of patients requiring additional uterotonics, and number of patients requiring blood transfusion. Jadad scale was used to evaluate the quality of the included RCTs. The Chi-square test was adopted for the heterogeneity test. A fixed-effect model was used for analysis if heterogeneity did not exist between literatures. If heterogeneity exists between literatures, a random-effect model was used for analysis. The source of heterogeneity was explored by subgroup analysis and sensitivity analysis.

Results: The incidence of PPH in the carbetocin group was lower than that in the oxytocin group (OR = 0.62, 95% CI (0.46, 0.84), = 3.14, = 0.002). There was no heterogeneity among studies ( = 7.29, = 0.12, = 45%) and no significant publication bias ( > 0.05). The proportion of women requiring additional uterotonics in the carbetocin group was lower than that in the oxytocin group (OR = 0.41, 95% CI (0.29, 0.56), = 5.34, < 0.00001). There was no heterogeneity among studies ( = 0.82, = 0.84, = 0%) and no significant publication bias ( > 0.05). There was no significant difference in the proportion of women needing blood transfusion between the carbetocin group and the oxytocin group (OR = 0.92, 95% CI (0.66, 1.29), = 0.46, = 0.64). There was no heterogeneity among studies ( = 3.06, = 0.55, = 0%) and no significant publication bias ( > 0.05).

Conclusion: Carbetocin is superior to oxytocin in preventing PPH among women with vaginal delivery and can be widely used in clinical practice.
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http://dx.doi.org/10.1155/2022/6420738DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9236811PMC
July 2022

The genetic heterogeneity and drug resistance mechanisms of relapsed refractory multiple myeloma.

Nat Commun 2022 06 29;13(1):3750. Epub 2022 Jun 29.

Michigan Center for Translational Pathology, University of Michigan, Ann Arbor, MI, USA.

Multiple myeloma is the second most common hematological malignancy. Despite significant advances in treatment, relapse is common and carries a poor prognosis. Thus, it is critical to elucidate the genetic factors contributing to disease progression and drug resistance. Here, we carry out integrative clinical sequencing of 511 relapsed, refractory multiple myeloma (RRMM) patients to define the disease's molecular alterations landscape. The NF-κB and RAS/MAPK pathways are more commonly altered than previously reported, with a prevalence of 45-65% each. In the RAS/MAPK pathway, there is a long tail of variants associated with the RASopathies. By comparing our RRMM cases with untreated patients, we identify a diverse set of alterations conferring resistance to three main classes of targeted therapy in 22% of our cohort. Activating mutations in IL6ST are also enriched in RRMM. Taken together, our study serves as a resource for future investigations of RRMM biology and potentially informs clinical management.
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http://dx.doi.org/10.1038/s41467-022-31430-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9243087PMC
June 2022

Assessing the contribution of rare genetic variants to phenotypes of chronic obstructive pulmonary disease using whole-genome sequence data.

Hum Mol Genet 2022 Jun 29. Epub 2022 Jun 29.

Channing Division of Network Medicine, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, USA.

Rationale: Genetic variation has a substantial contribution to chronic obstructive pulmonary disease (COPD) and lung function measurements. Heritability estimates using genome-wide genotyping data can be biased if analyses do not appropriately account for the non-uniform distribution of genetic effects across the allele frequency and linkage disequilibrium spectrum. In addition, the contribution of rare variants has been unclear.

Objectives: We sought to assess the heritability of COPD and lung function using whole-genome sequence data from the Trans-Omics for Precision Medicine program.

Methods: Using the genome-based restricted maximum likelihood method, we partitioned the genome into bins based on minor allele frequency and linkage disequilibrium scores and estimated heritability of COPD, FEV1% predicted, and FEV1/FVC ratio in 11 051 European ancestry and 5853 African-American participants.

Measurements And Main Results: In European ancestry participants, the estimated heritability of COPD, FEV1% predicted, and FEV1/FVC ratio were 35.5%, 55.6% and 32.5%, of which 18.8%, 19.7%, 17.8% were from common variants, and 16.6%, 35.8%, and 14.6% were from rare variants. These estimates had wide confidence intervals, with common variants and some sets of rare variants showing a statistically significant contribution (P-value < 0.05). In African-Americans, common variant heritability was similar to European ancestry participants, but lower sample size precluded calculation of rare variant heritability.

Conclusions: Our study provides updated and unbiased estimates of heritability for COPD and lung function, and suggests an important contribution of rare variants. Larger studies of more diverse ancestry will improve accuracy of these estimates.
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http://dx.doi.org/10.1093/hmg/ddac117DOI Listing
June 2022

An oncogenic JMJD6-DGAT1 axis tunes the epigenetic regulation of lipid droplet formation in clear cell renal cell carcinoma.

Mol Cell 2022 Jun 15. Epub 2022 Jun 15.

Department of Pathology, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA; Kidney Cancer Program, Simmons Comprehensive Cancer Center, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA. Electronic address:

Characterized by intracellular lipid droplet accumulation, clear cell renal cell carcinoma (ccRCC) is resistant to cytotoxic chemotherapy and is a lethal disease. Through an unbiased siRNA screen of 2-oxoglutarate (2-OG)-dependent enzymes, which play a critical role in tumorigenesis, we identified Jumonji domain-containing 6 (JMJD6) as an essential gene for ccRCC tumor development. The downregulation of JMJD6 abolished ccRCC colony formation in vitro and inhibited orthotopic tumor growth in vivo. Integrated ChIP-seq and RNA-seq analyses uncovered diacylglycerol O-acyltransferase 1 (DGAT1) as a critical JMJD6 effector. Mechanistically, JMJD6 interacted with RBM39 and co-occupied DGAT1 gene promoter with H3K4me3 to induce DGAT1 expression. JMJD6 silencing reduced DGAT1, leading to decreased lipid droplet formation and tumorigenesis. The pharmacological inhibition (or depletion) of DGAT1 inhibited lipid droplet formation in vitro and ccRCC tumorigenesis in vivo. Thus, the JMJD6-DGAT1 axis represents a potential new therapeutic target for ccRCC.
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http://dx.doi.org/10.1016/j.molcel.2022.06.003DOI Listing
June 2022

Association of Kidney Comorbidities and Acute Kidney Failure With Unfavorable Outcomes After COVID-19 in Individuals With the Sickle Cell Trait.

JAMA Intern Med 2022 Aug;182(8):796-804

Department of Psychiatry, Division of Human Genetics, Yale School of Medicine, New Haven, Connecticut.

Importance: Sickle cell trait (SCT), defined as the presence of 1 hemoglobin beta sickle allele (rs334-T) and 1 normal beta allele, is prevalent in millions of people in the US, particularly in individuals of African and Hispanic ancestry. However, the association of SCT with COVID-19 is unclear.

Objective: To assess the association of SCT with the prepandemic health conditions in participants of the Million Veteran Program (MVP) and to assess the severity and sequelae of COVID-19.

Design, Setting, And Participants: COVID-19 clinical data include 2729 persons with SCT, of whom 353 had COVID-19, and 129 848 SCT-negative individuals, of whom 13 488 had COVID-19. Associations between SCT and COVID-19 outcomes were examined using firth regression. Analyses were performed by ancestry and adjusted for sex, age, age squared, and ancestral principal components to account for population stratification. Data for the study were collected between March 2020 and February 2021.

Exposures: The hemoglobin beta S (HbS) allele (rs334-T).

Main Outcomes And Measures: This study evaluated 4 COVID-19 outcomes derived from the World Health Organization severity scale and phenotypes derived from International Classification of Diseases codes in the electronic health records.

Results: Of the 132 577 MVP participants with COVID-19 data, mean (SD) age at the index date was 64.8 (13.1) years. Sickle cell trait was present in 7.8% of individuals of African ancestry and associated with a history of chronic kidney disease, diabetic kidney disease, hypertensive kidney disease, pulmonary embolism, and cerebrovascular disease. Among the 4 clinical outcomes of COVID-19, SCT was associated with an increased COVID-19 mortality in individuals of African ancestry (n = 3749; odds ratio, 1.77; 95% CI, 1.13 to 2.77; P = .01). In the 60 days following COVID-19, SCT was associated with an increased incidence of acute kidney failure. A counterfactual mediation framework estimated that on average, 20.7% (95% CI, -3.8% to 56.0%) of the total effect of SCT on COVID-19 fatalities was due to acute kidney failure.

Conclusions And Relevance: In this genetic association study, SCT was associated with preexisting kidney comorbidities, increased COVID-19 mortality, and kidney morbidity.
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http://dx.doi.org/10.1001/jamainternmed.2022.2141DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9237798PMC
August 2022

Case Report: Pericardial Tamponade and Hemothorax After Superior Vena Cava Filter Removal.

Front Cardiovasc Med 2022 3;9:863732. Epub 2022 Jun 3.

Department of Emergency, Peking University Shenzhen Hospital, Shenzhen, China.

A 67-year-old male patient was admitted to receive surgical treatment because of lumbar spinal stenosis. Ultrasonography showed a thrombus in the middle and lower segment of the left internal jugular vein. Superior vena cava filter implantation was performed and removed on day 7 after its implantation. The patient suddenly had dyspnea, and his blood pressure decreased 9 h after filter removal. Examinations showed pericardial tamponade and hemothorax. In addition, aortic dissection occurred approximately 20 days after superior vena cava filter removal. This case aimed to provide information to clinicians about the complications of the implantation and removal of superior vena cava filter implantation. The safety and possible complications of superior vena cava filter implantation and removal should be evaluated to identify their actual clinical benefit and cost-effectiveness ratio.
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http://dx.doi.org/10.3389/fcvm.2022.863732DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9204137PMC
June 2022

A Global Regulatory Network for Dysregulated Gene Expression and Abnormal Metabolic Signaling in Immune Cells in the Microenvironment of Graves' Disease and Hashimoto's Thyroiditis.

Front Immunol 2022 26;13:879824. Epub 2022 May 26.

Department of Endocrinology, Affiliated Yantai Yuhuangding Hospital of Qingdao University Medical College, Yantai, China.

Background: Although the pathogenetic mechanisms of Hashimoto's thyroiditis (HT) and Graves' disease (GD) have been elucidated, the molecular mechanisms by which the abnormal immune function of cellular subpopulations trigger an autoimmune attack on thyroid tissue largely remains unexplained.

Methods: The study included 2 HT patients, 2 GD patients, and 1 control donor. The thyroid samples were extracted for single-cell RNA sequencing, whole transcriptome, full-length transcriptome (Oxford Nanopore Technologies), and metabolome sequencing. Identification of immune cells with dysregulated gene expression and abnormal metabolic signaling was performed in the microenvironment, both at the bulk and single-cell levels. Based on functional enrichment analysis, the biological processes and pathways involved in abnormal immune cells were further explored. Finally, according to cell communication analysis, the global regulatory network of immune cells was constructed.

Results: CD4 T cells, CD8 T cells, and macrophages were abnormally increased in patients with HT and GD. The differentially expressed genes of these cells were significantly involved in signaling pathways, including Th1 and Th2 cell differentiation, Th17 cell differentiation, cytokine-cytokine receptor interaction, and NF-kappa B signaling pathway. Moreover, in HT, CD4 T cells interact with macrophages the IL16-CCR5/FGF10-FGFR1/CXCL13-CXCR3 axis, and macrophages interact with CD8 T cells the CD70-CD27 axis, thereby activating the T-cell receptor signaling pathway and NF-kappa B signaling pathway. In GD, CD4 T cells interact with macrophages the CXCR3-CXCL10/PKM-CD44/MHCII-NFKBIE axis, and macrophages interact with CD8 T cells the IFNG-IFNGR1/CCR7-CCL21 axis, thereby activating T-cell receptor signaling pathway, Th1 and Th2 cell differentiation, and chemokine signaling pathway.

Conclusion: In HT and GD, immune dysregulated cells interact and activate relevant immune pathways and further aggravate the immune response. This may trigger the immune cells to target the thyroid tissue and influence the development of the disease.
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http://dx.doi.org/10.3389/fimmu.2022.879824DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9204353PMC
May 2022

Identification of a novel prognostic signature for HCC and analysis of costimulatory molecule-related lncRNA AC099850.3.

Sci Rep 2022 Jun 15;12(1):9954. Epub 2022 Jun 15.

Department of Histology and Embryology, Anhui Medical College, Hefei, 230601, Anhui, China.

Costimulatory molecules are involved in initiation of anti-tumor immune responses while long non-coding RNAs (lncRNAs) regulate the development of various cancers. However, the roles of lncRNA in hepatocellular carcinoma (HCC) have not been fully established. In this study, we aimed at identifying lncRNAs-related costimulatory molecules in HCC and to construct a prognostic signature for predicting the clinical outcomes for HCC patients. Data were downloaded from The Cancer Genome Atlas database for bioinformatics analyses. Costimulatory molecules were obtained from published literature. The R software, SPSS, and GraphPad Prism were used for statistical analyses. A risk model that is based on five costimulatory molecule-related lncRNAs was constructed using lasso and Cox regression analyses. Multivariate regression analysis revealed that the risk score could predict the prognostic outcomes for HCC. Samples in high- and low-risk groups exhibited significant differences in gene set enrichment and immune infiltration levels. Through colony formation and CCK8 assays, we found that AC099850.3 was strongly associated with HCC cell proliferation. We identified and validated a novel costimulatory molecule-related survival model. In addition, AC099850.3 was found to be closely associated with clinical stages and proliferation of HCC cells, making it a potential target for HCC treatment.
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http://dx.doi.org/10.1038/s41598-022-13792-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9200812PMC
June 2022

Prefrontal GABA(δ)R Promotes Fear Extinction through Enabling the Plastic Regulation of Neuronal Intrinsic Excitability.

J Neurosci 2022 07 15;42(29):5755-5770. Epub 2022 Jun 15.

Laboratory of Fear and Anxiety Disorders, Institutes of Life Science, Nanchang University, Nanchang 330031, People's Republic of China

Extinguishing the previously acquired fear is critical for the adaptation of an organism to the ever-changing environment, a process requiring the engagement of GABA receptors (GABARs). GABARs consist of tens of structurally, pharmacologically, and functionally heterogeneous subtypes. However, the specific roles of these subtypes in fear extinction remain largely unexplored. Here, we observed that in the medial prefrontal cortex (mPFC), a core region for mood regulation, the extrasynaptically situated, δ-subunit-containing GABARs [GABA(δ)Rs], had a permissive role in tuning fear extinction in male mice, an effect sharply contrasting to the established but suppressive role by the whole GABAR family. First, the fear extinction in individual mice was positively correlated with the level of GABA(δ)R expression and function in their mPFC. Second, knockdown of GABA(δ)R in mPFC, specifically in its infralimbic (IL) subregion, sufficed to impair the fear extinction in mice. Third, GABA(δ)R-deficient mice also showed fear extinction deficits, and re-expressing GABA(δ)Rs in the IL of these mice rescued the impaired extinction. Further mechanistic studies demonstrated that the permissive effect of GABA(δ)R was associated with its role in enabling the extinction-evoked plastic regulation of neuronal excitability in IL projection neurons. By contrast, GABA(δ)R had little influence on the extinction-evoked plasticity of glutamatergic transmission in these cells. Altogether, our findings revealed an unconventional and permissive role of extrasynaptic GABA receptors in fear extinction through a route relying on nonsynaptic plasticity. The medial prefrontal cortex (mPFC) is one of the kernel brain regions engaged in fear extinction. Previous studies have repetitively shown that the GABA receptor (GABAR) family in this region act to suppress fear extinction. However, the roles of specific GABAR subtypes in mPFC are largely unknown. We observed that the GABAR-containing δ-subunit [GABA(δ)R], a subtype of GABARs exclusively situated in the extrasynaptic membrane and mediating the tonic neuronal inhibition, works oppositely to the whole GABAR family and promotes (but does not suppress) fear extinction. More interestingly, in striking contrast to the synaptic GABARs that suppress fear extinction by breaking the extinction-evoked plasticity of glutamatergic transmission, the GABA(δ)R promotes fear extinction through enabling the plastic regulation of neuronal excitability in the infralimbic subregion of mPFC. Our findings thus reveal an unconventional role of GABA(δ)R in promoting fear extinction through a route relying on nonsynaptic plasticity.
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http://dx.doi.org/10.1523/JNEUROSCI.0689-22.2022DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9302468PMC
July 2022

The Role of Activated Monocyte IFN/SIGLEC1 Signalling in Graves' Disease.

J Endocrinol 2022 Jun 1. Epub 2022 Jun 1.

S Wang, Department of Endocrine and Metabolic Diseases, Shanghai Jiao Tong University School of Medicine, Shanghai, China, Shanghai Institute of Endocrine and Metabolic Disease, Shanghai, China.

Context: Graves' disease (GD) is characterized by dysregulation of the immune system with aberrant immune cell function. However, there have been few previous studies on the role of monocytes in the pathology of GD. The object of this study was to investigate whether and how monocytes participate in GD pathology. CD14+ monocytes were isolated from untreated initial GD patients and healthy controls. Then RNA-seq was performed to investigate changes in global mRNA expression in monocytes. We found that Type I interferon (IFN) signalling was among the top upregulated signalling pathways in GD monocytes. Type I IFN-induced Sialic acid-binding immunoglobulin-like lectin1 (SIGLEC1) expression was significantly upregulated in untreated GD patients and correlated with thyroid parameters. Patient serum SIGLEC1 concentrations were reduced after anti-thyroid drug treatment. Inhibiting SIGLEC1 expression could inhibit proinflammatory cytokine (IL-1β, IL-6, IL-8, IL-10 and M-CSF) expression in monocytes. In conclusion,our study suggested that type I IFN-mediated monocyte activation could have a deleterious effect on the pathogenesis of GD. These observations indicated that the inhibition of type I IFN-activated monocytes/macrophages could have a therapeutic effect on GD remission.
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http://dx.doi.org/10.1530/JOE-21-0453DOI Listing
June 2022

Transfer-Learning-Based Gaussian Mixture Model for Distributed Clustering.

IEEE Trans Cybern 2022 Jun 10;PP. Epub 2022 Jun 10.

Distributed clustering based on the Gaussian mixture model (GMM) has exhibited excellent clustering capabilities in peer-to-peer (P2P) networks. However, more iterative numbers and communication overhead are required to achieve the consensus in existing distributed GMM clustering algorithms. In addition, the truth that it cannot find a closed form for the update of parameters in GMM causes the imprecise clustering accuracy. To solve these issues, by utilizing the transfer learning technique, a general transfer distributed GMM clustering framework is exploited to promote the clustering performance and accelerate the clustering convergence. In this work, each node is treated as both the source domain and the target domain, and these nodes can learn from each other to complete the clustering task in distributed P2P networks. Based on this framework, the transfer distributed expectation-maximization algorithm with the fixed learning rate is first presented for data clustering. Then, an improved version is designed to obtain the stable clustering accuracy, in which an adaptive transfer learning strategy is adopted to adjust the learning rate automatically instead of a fixed value. To demonstrate the extensibility of the proposed framework, a representative GMM clustering method, the entropy-type classification maximum-likelihood algorithm, is further extended to the transfer distributed counterpart. Experimental results verify the effectiveness of the presented algorithms in contrast with the existing GMM clustering approaches.
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http://dx.doi.org/10.1109/TCYB.2022.3177242DOI Listing
June 2022

Pharmacogenetic variants and risk of remdesivir-associated liver enzyme elevations in Million Veteran Program participants hospitalized with COVID-19.

Clin Transl Sci 2022 Jun 9. Epub 2022 Jun 9.

Tennessee Valley Healthcare System Nashville VA and Vanderbilt University Medical Center, Nashville, Tennessee, USA.

Remdesivir is the first US Food and Drug Administration (FDA)-approved drug for the treatment of coronavirus disease 2019 (COVID-19). We conducted a retrospective pharmacogenetic study to examine remdesivir-associated liver enzyme elevation among Million Veteran Program participants hospitalized with COVID-19 between March 15, 2020, and June 30, 2021. Pharmacogene phenotypes were assigned using Stargazer. Linear regression was performed on peak log-transformed enzyme values, stratified by population, adjusted for age, sex, baseline liver enzymes, comorbidities, and 10 population-specific principal components. Patients on remdesivir had higher peak alanine aminotransferase (ALT) values following treatment initiation compared with patients not receiving remdesivir. Remdesivir administration was associated with a 33% and 24% higher peak ALT in non-Hispanic White (NHW) and non-Hispanic Black (NHB) participants (p < 0.001), respectively. In a multivariable model, NHW CYP2C19 intermediate/poor metabolizers had a 9% increased peak ALT compared with NHW normal/rapid/ultrarapid metabolizers (p = 0.015); this association was not observed in NHB participants. In summary, remdesivir-associated ALT elevations appear to be multifactorial, and further studies are needed.
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http://dx.doi.org/10.1111/cts.13313DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9347806PMC
June 2022
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