Publications by authors named "Hao Geng"

115 Publications

Novel variants in helicase for meiosis 1 lead to male infertility due to non-obstructive azoospermia.

Reprod Biol Endocrinol 2021 Aug 24;19(1):129. Epub 2021 Aug 24.

Reproductive Medicine Center, Department of Obstetrics and Gynecology, the First Affiliated Hospital of Anhui Medical University, No 218 Jixi Road, Hefei, 230022, Anhui, China.

Background: Non-obstructive azoospermia (NOA) is the most severe form of male infertility; more than half of the NOA patients are idiopathic. Although many NOA risk genes have been detected, the genetic factors for NOA in majority of the patients are unknown. In addition, it is difficult to retrieve sperm from these patients despite using the microsurgical testicular sperm extraction (microTESE) method. Therefore, we conducted this genetic study to identify the potential genetic factors responsible for NOA and investigate the sperm retrieval rate of microTESE for genetically deficient NOA patients.

Methods: Semen analyses, sex hormone testing, and testicular biopsy were performed to categorize the patients with NOA. The chromosome karyotypes and Y chromosome microdeletion analyses were used to exclude general genetic factors. Whole exome sequencing and Sanger sequencing were performed to identify potential genetic variants in 51 patients with NOA. Hematoxylin and eosin staining (H&E) and anti-phosphorylated H2AX were used to assess the histopathology of spermatogenesis. Quantitative real time-polymerase chain reaction, western blotting, and immunofluorescence were performed to verify the effects of gene variation on expression.

Results: We performed whole exome sequencing in 51 NOA patients and identified homozygous helicase for meiosis 1(HFM1) variants (NM_001017975: c.3490C > T: p.Q1164X; c.3470G > A: p.C1157Y) in two patients (3.9%, 2/51). Histopathology of the testis showed that spermatogenesis was completely blocked at metaphase in these two patients carrying the HFM1 homozygous variants. In comparison with unaffected controls, we found a significant reduction in the levels of HFM1 mRNA and protein expression in the testicular tissues from these two patients. The patients were also subjected to microTESE treatment, but the sperms could not be retrieved.

Conclusions: This study identified novel homozygous variants of HFM1 that are responsible for spermatogenic failure and NOA, and microTESE did not aid in retrieving sperms from these patients.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1186/s12958-021-00815-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8383409PMC
August 2021

Endogenous Deficiency of Brain-Derived Neurotrophic Factor Induces the Downregulation of Tryptophan Hydroxylase-2 Expression in Raphe Nuclei of Rapid Ejaculator Rats.

J Sex Med 2021 09 9;18(9):1491-1499. Epub 2021 Aug 9.

Department of Urology, The First Affiliated Hospital of Anhui Medical University, Hefei, China. Electronic address:

Background: Premature ejaculation (PE) is one of the most common ejaculatory disorders. Recent studies have suggested a close relationship between the serotonin (5-hydroxytryptamine [5-HT]) system and brain-derived neurotrophic factor (BDNF), raising the question of whether BDNF plays a role in ejaculation regulation. To our knowledge, no previous studies have explored BDNF level of the central nervous system in ejaculatory disorders. At the same time, the interaction of central BDNF and 5-HT systems has not been undertaken in ejaculation regulation field.

Aim: The aim of this study was to investigate the interaction between BDNF and 5-HT levels in raphe nuclei which contains the serotonergic neurons in a rat animal model with different ejaculatory behavior.

Methods: Eighteen male rats were selected and classified as "sluggish," "normal," and "rapid" ejaculators on the basis of ejaculation frequency during copulatory behavioral testing. BDNF and 5-HT levels were determined by enzyme-linked immunosorbent assay (ELISA). Real-Time Quantitative PCR and Western blot analyses were used to measure the mRNA level of Tryptophan Hydroxylase-2 (TPH2) gene and the expression of TPH2 protein (the rate-limiting enzyme in central 5-HT synthesis) in raphe nuclei, respectively.

Outcomes: Male rat sexual behavior, the levels of BDNF and 5-HT in raphe nuclei of rats with different ejaculatory behavior, the mRNA level of gene encoding TPH2 and the expression of TPH2 protein in raphe nuclei.

Results: The primary finding of our study was that BDNF concentration was significantly decreased in raphe nuclei of rapid ejaculators. There was a strong positive correlation between the levels of BDNF and 5-HT (r = 0.944, P < .001). Further results showed that decreased TPH2 gene expression accompanied by TPH2 protein was shown in rapid ejaculators with lower BDNF level.

Clinical Implications: With refinement of current knowledge, BDNF may eventually serve as a promising biomarker in patients with PE.

Strengths & Limitations: There are no previous studies examining the interaction of the brain BDNF and 5-HT in ejaculation regulation field. The main limitation is the limited sample size.

Conclusion: BDNF may act via increasing the synthesis of central 5-HT in the process of ejaculation regulation. Our results suggest lack of endogenous BDNF induces the downregulation of TPH2 gene expression and the decrease of 5-HT synthesis in raphe nuclei of rapid ejaculator rats. Huang Y, Peng D, Geng H, et al. Endogenous Deficiency of Brain-Derived Neurotrophic Factor Induces the Downregulation of Tryptophan Hydroxylase-2 Expression in Raphe Nuclei of Rapid Ejaculator Rats. J Sex Med 2021;18:1491-1499.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.jsxm.2021.07.009DOI Listing
September 2021

Acquisition of the L452R mutation in the ACE2-binding interface of Spike protein triggers recent massive expansion of SARS-CoV-2 variants.

J Clin Microbiol 2021 Aug 11:JCM0092121. Epub 2021 Aug 11.

University of Washington, Seattle, WA.

We report that there is a recent global expansion of numerous independent SARS-CoV-2 variants with mutation L452R in the receptor-binding domain (RBD) of the Spike protein. The massive emergence of L452R variants was first linked to lineage B.1.427/B.1.429 (clade 21C) that has been spreading in California since November-December 2020, originally named CAL.20C and currently variant of interest Epsilon. By PCR amplification and Sanger sequencing of a 541 base fragments coding for amino acids 414-583 of RBD from a collection of clinical specimens, we identified a separate L452R variant that also recently emerged in California but derives from the lineage B.1.232, clade 20A (named CAL.20A). Notably, CAL.20A caused an infection in gorillas in the San Diego Zoo, reported in January 2021. Unlike the Epsilon variant that carries two additional mutations in the N-terminal domain of Spike protein, L452R is the only mutation found in the Spike proteins of CAL.20A. Based on genome-wide phylogenetic analysis, emergence of both viral variants was specifically triggered by acquisition of L452R, suggesting a strong positive selection for this mutation. Global analysis revealed that L452R is nearly omnipresent in a dozen independently emerged lineages, including the most recent variants of concern/interest Delta, Kappa, Epsilon and Iota, with the Lambda variant carrying L452Q. L452 is in immediate proximity to the ACE2 interaction interface of RBD. It was reported that the L452R mutation is associated with immune escape and could result in a stronger cell attachment of the virus, with both factors likely increasing viral transmissibility, infectivity and pathogenicity.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1128/JCM.00921-21DOI Listing
August 2021

[Bidirectional regulation of acupuncture: a subgroup analysis of multicenter randomized controlled trial of acupuncture with for irritable bowel syndrome].

Zhongguo Zhen Jiu 2021 Aug;41(8):845-50

Department of Acupuncture-Moxibustion and Rehabilitation, Affiliated Hospital of Nanjing University of Chinese Medicine, Nanjing 210029, Jiangsu Province, China.

Objective: To explore the bidirectional regulation of acupuncture based on a subgroup analysis of multicenter randomized controlled trial of acupuncture with for irritable bowel syndrome (IBS).

Methods: A total of 519 patients were included in the analysis, including 137 patients with constipation type irritable bowel syndrome (IBS-C) (92 cases in the acupuncture group and 45 cases in the polyethylene glycol [PEG] group), and 382 patients with diarrhea type irritable bowel syndrome (IBS-D) (252 cases in the acupuncture group and 130 cases in the pinaverium group). The patients in the acupuncture group were given acupuncture at Baihui (GV 20), Yintang (GV 29), Tianshu (ST 25), Shangjuxu (ST 37), Zusanli (ST 36), Sanyinjiao (SP 6) and Taichong (LR 3) once every other day, 3 times a week. The patients in the PEG group received polyethylene glycol 4000 powder orally, and the pinaverium group received pinaverium bromide tablets orally. All were treated for 6 weeks. The IBS symptom severity score (IBS-SSS) was assessed at baseline, treatment period (2, 4, 6 weeks of treatment) and 12 weeks of follow-up, and the IBS quality of life (IBS-QOL) score was evaluated at the baseline period, 6 weeks of treatment and 12 weeks of follow-up.

Results: The total IBS-SSS scores of the two groups of IBS-C patients at 2, 4, 6 weeks of treatment and follow-up of 12 weeks were lower than those in the baseline period (<0.01). The total IBS-SSS score in the IBS-C acupuncture group was lower than that in the PEG group at 12 weeks of follow-up (<0.05). The total IBS-SSS scores of the two groups of IBS-D patients at 2, 4, 6 weeks of treatment and 12 weeks of follow-up were lower than those in the baseline period (<0.01). The total IBS-SSS scores in the IBS-D acupuncture group were lower than those in the pinaverium group at 2, 4, 6 weeks of treatment and 12 weeks of follow-up (<0.05). The total IBS-QOL scores at 6 weeks of treatment and 12 weeks of follow-up were higher than those in the baseline period in both groups of patients with IBS-C (<0.01). The total IBS-QOL scores at 6 weeks of treatment and 12 weeks of follow-up were higher than those in the baseline period in both groups in patients with IBS-D (<0.01). The total IBS-QOL score in the IBS-D acupuncture group was higher than that in the pinaverium group at 18 weeks of follow-up (<0.05).

Conclusion: Acupuncture with can improve the clinical symptoms and quality of life of patients with IBS-C and IBS-D, which can regulate different functional states (constipation and diarrhea) of the same disease (irritable bowel syndrome), reflecting the bidirectional regulation of acupuncture.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.13703/j.0255-2930.20201111-k0001DOI Listing
August 2021

Identifying Sequence Variants of 18 Hereditary Ovarian Cancer-Associated Genes in Chinese Epithelial Ovarian Cancer Patients.

Biomed Res Int 2021 24;2021:5579543. Epub 2021 Jul 24.

Department of Obstetrics and Gynecology, Anhui Provincial Hospital affiliated to Anhui Medical University, Hefei, Anhui, China.

Objectives: The causes of ovarian cancer (OC) have been confirmed to be closely related to genetic factors. Identifying sequence variants of hereditary ovarian cancer (HOC) susceptibility genes can increase clinical surveillance, facilitate early detection, and provide personalized treatment for patients. This study is aimed at investigating the variation frequency of HOC susceptibility genes in the Chinese population and providing information for the etiology and genetics of OC.

Methods: 118 epithelial OC patients were recruited in this clinical study. Variants of 18-gene panel were detected in blood samples by next-generation sequencing (NGS) technology.

Results: Overall, 36.44% (43/118) of patients carried at least one pathogenic variant. Among these, pathogenic variants were detected in 31 (26.27%) patients, and 5 (4.24%) patients carried pathogenic variants of . Moreover, 27.12% (32/118) of patients carried variants of unknown significance (VUSs). Importantly, we detected eight variants that were not reported previously.

Conclusions: Our study enlarged the spectrum of HOC-associated gene sequence variants in the Chinese population and also proved the necessity of multigene testing in epithelial OC patients. The identification of patients with HOC will allow family members to undergo cascade testing where identification of unaffected carriers can facilitate early detection, risk reduction, or prevention of OC and ultimately improve long-term outcomes.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1155/2021/5579543DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8328723PMC
September 2021

Reproductive and hormonal factors and risk of incident rosacea among US White women.

J Am Acad Dermatol 2021 Jul 15. Epub 2021 Jul 15.

Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Department of Cancer Epidemiology, Peking University Cancer Hospital & Institute, Beijing, People's Republic of China; Department of Dermatology, Warren Alpert Medical School, Brown University, Providence, Rhode Island; Department of Epidemiology, School of Public Health, Brown University, Providence, Rhode Island. Electronic address:

View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.jaad.2021.06.865DOI Listing
July 2021

Regulation of serum microRNA expression by acupuncture in patients with diarrhea-predominant irritable bowel syndrome.

Acupunct Med 2021 Jul 7:9645284211027892. Epub 2021 Jul 7.

Department of Acupuncture and Rehabilitation, Jiangsu Province Hospital of Chinese Medicine, Nanjing, China.

Objective: To screen for differentially expressed serum microRNAs (miRNAs) in patients with diarrhea-predominant irritable bowel syndrome (IBS-D) compared with healthy participants and explore the mechanism of acupuncture in the treatment of IBS-D based on miRNAs.

Methods: IBS-D patients that met the Rome III diagnostic criteria and age- and sex-matched healthy participants were enrolled between April 2017 and December 2017. Serum miRNA levels were initially determined using a TaqMan low-density array (TLDA) in pooled samples. Markedly altered miRNAs in IBS-D patients were subsequently validated using quantitative real-time polymerase chain reaction (qRT-PCR) on individual samples. All IBS-D patients accepted the acupuncture therapy for 6 weeks. The disease severity was assessed using the IBS symptom severity scale (IBS-SSS) questionnaire before and after treatment. After acupuncture, the patients' serum was re-analyzed for altered expression of the miRNAs by qRT-PCR.

Results: TLDA and qRT-PCR analysis revealed six upregulated miRNAs (miR-1305, miR-575, miR-149-5p, miR-190a-5p, miR-135a-5p, and miR-148a-3p;  < 0.05) and two downregulated miRNAs (miR-194-5p, miR-127-5p;  < 0.05) in IBS-D patients compared with healthy controls. Post acupuncture treatment, total IBS-SSS scores, severity of abdominal pain, duration of abdominal pain, severity of abdominal distention, dissatisfaction with bowel habits and disruption in quality of life decreased significantly ( < 0.001). Furthermore, the upregulated miR-148a-3p levels in IBS-D patients also decreased significantly after acupuncture ( < 0.05).

Conclusions: The over-expression or reduced expression of several miRNAs may contribute to IBS-D pathogenesis. Acupuncture might downregulate miR-148a-3p through multiple pathways to alleviate or relieve IBS-D symptoms.

Trial Registration Number: ChiCTR-IOR-17010860 (Chinese Clinical Trials Registry).
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1177/09645284211027892DOI Listing
July 2021

An Efficient Sharing Grouped Convolution via Bayesian Learning.

IEEE Trans Neural Netw Learn Syst 2021 Jun 10;PP. Epub 2021 Jun 10.

Compared with traditional convolutions, grouped convolutional neural networks are promising for both model performance and network parameters. However, existing models with the grouped convolution still have parameter redundancy. In this article, concerning the grouped convolution, we propose a sharing grouped convolution structure to reduce parameters. To efficiently eliminate parameter redundancy and improve model performance, we propose a Bayesian sharing framework to transfer the vanilla grouped convolution to be the sharing structure. Intragroup correlation and intergroup importance are introduced into the prior of the parameters. We handle the Maximum Type II likelihood estimation problem of the intragroup correlation and intergroup importance by a group LASSO-type algorithm. The prior mean of the sharing kernels is iteratively updated. Extensive experiments are conducted to demonstrate that on different grouped convolutional neural networks, the proposed sharing grouped convolution structure with the Bayesian sharing framework can reduce parameters and improve prediction accuracy. The proposed sharing framework can reduce parameters up to 64.17%. For ResNeXt-50 with the sharing grouped convolution on ImageNet dataset, network parameters can be reduced by 96.875% in all grouped convolutional layers, and accuracies are improved to 78.86% and 94.54% for top-1 and top-5, respectively.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1109/TNNLS.2021.3084900DOI Listing
June 2021

Expression of brain-derived neurotrophic factor in rapid ejaculator rats: A further study.

Andrologia 2021 Sep 8;53(8):e14134. Epub 2021 Jun 8.

Department of Urology, First Affiliated Hospital of Anhui Medical University, Hefei, China.

Limited evidence has indicated that brain-derived neurotrophic factor (BDNF) may be involved in the neurobiology of premature ejaculation (PE). This study aimed to investigate BDNF levels in the central and peripheral nervous systems of a rapid ejaculation model. Eighteen male rats were selected and classified as 'sluggish', 'normal' and 'rapid' ejaculators on the basis of ejaculation frequency during copulatory behavioural tests. BDNF levels in specific brain regions, spinal cord and serum were determined by enzyme-linked immunosorbent assay (ELISA). Consistent with the results in PE patients, the concentration of serum BDNF decreased significantly from the sluggish rats to normal and rapid rats. Besides, in both brain regions and spinal cord, the sluggish group had the highest BDNF levels, while the rapid group had the lowest BDNF levels. Regression analyses of the expression of BDNF presented positive correlations between serum and brain (r = 0.958, p < .001), and between serum and spinal cord (r = 0.967, p < .001) respectively. Our findings suggested insufficient BDNF in the nervous system and serum may lead to rapid ejaculation. The current study adds to the evidence that BDNF is involved in the regulation of ejaculation.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1111/and.14134DOI Listing
September 2021

A Bibliometric Analysis of Research Trends of Acupuncture Therapy in the Treatment of Migraine from 2000 to 2020.

J Pain Res 2021 25;14:1399-1414. Epub 2021 May 25.

Jiangsu Province Hospital of Chinese Medicine, Nanjing, Jiangsu Province, People's Republic of China.

Background: Migraine is the second-leading cause of disability worldwide. It is often characterized by attacks of severe, mostly unilateral, pulsating headache associated with symptoms such as photophobia, phonophobia, nausea, vomiting, and cutaneous allodynia. Acupuncture therapy has been used worldwide for the treatment of migraine. However, no visual bibliometric analysis has been conducted on the effects of acupuncture on migraine over the past 20 years. Therefore, this study aimed to explore the current status and trends on the use of acupuncture in the treatment of migraine from 2000 to 2020.

Purpose: The objective of this study is to identify the current status and emerging trends of the global use of acupuncture on migraine from 2000 to 2020 using CiteSpace and VOSviewer.

Methods: Web of Science databases were searched for publications related to acupuncture therapy for treating migraine between 2000 and 2020. CiteSpace and VOSviewer were used to analyze the number of publications per year, countries, institutions, authors, journals, references, and keywords.

Results: A total of 572 publications were included in the final analysis. The total number of publications has continued to increase with some fluctuations over the past 20 years. The most productive country and institution in this field were the USA, and Chengdu University of Traditional Chinese Medicine, respectively. The most active and cited authors were Liang FR and Linde K, respectively. was the most productive, cited, and co-cited journal. The Linde K (2005) had the highest co-citation, citation number and centrality. The keywords "migraine" ranked first in frequency. The common type of migraine (tension-type headache), research method (randomized controlled trial, multicenter, double-blind), acupuncture's role (prophylactic, quality of life, pain), and evaluation (meta-analysis, systematic review) were the hotspots and frontier trends of acupuncture therapy on migraine between 2000 and 2020.

Conclusion: The present study examined the research-related trend in acupuncture therapy on migraine using bibliometric methods and identified the statement and research frontiers over the past two decades. This may help researchers to identify potential hotspots and new directions for future research in this field.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.2147/JPR.S306594DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8164719PMC
May 2021

Exosomes in bladder cancer: novel biomarkers and targets.

J Zhejiang Univ Sci B 2021 May;22(5):341-347

Jiangsu Key Laboratory of Medical Science and Laboratory Medicine, School of Medicine, Jiangsu University, Zhenjiang 212013, China.

Exosomes are nanometer-sized vesicles that contain various types of biologically active components, including proteins, nucleic acids, carbohydrates, and lipids, which vary with the type and physiological state of the cell. In recent years, several studies have showed that exosomes can provide new non-invasive diagnostic and prognostic biomarkers in patients affected by cancers, including bladder cancer (BC), and the lipid bilayer membrane structure makes exosomes as promising delivery vehicles for therapeutic applications. Exosomes have the characteristics of high abundance, high stability, tissue specificity, and wide distribution in body fluids, and are secreted as various types by cells in different states, thereby possessing great potential as biomarkers for BC. Herein, we briefly summarize the functions and roles of exosomes in the occurrence and development of BC and the current progress of research on exosomes in BC, while focusing on potential clinical applications of the diagnosis, treatment, and prognosis of BC.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1631/jzus.B2000711DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8110466PMC
May 2021

[Mind-regulating and spleen-strengthening needling technique improves abdominal hypersensitivity and emotion by enhancing functional connectivity between hippocampus and brain regions in diarrhea-predominant irritable bowel syndrome patients].

Zhen Ci Yan Jiu 2021 Apr;46(4):318-25

Department of Acupuncture and Rehabilitation, The Affiliated Hospital of Nanjing University of Chinese Medicine, Nanjing 210029, China.

Objective: To compare the difference of brain functional connectivity between diarrhea-predominant irritable bowel syndrome (IBS-D) patients and healthy volunteers and changes after acupuncture intervention, so as to investigate the underlying mechanism of acupuncture in regulating functional activities of IBS-D patients by using seed point correlation analysis.

Methods: A total of 25 IBS-D patients and 25 healthy volunteers were recruited in the present study and respectively attributed to acupuncture group and control group. The IBS-D patients received manual acupuncture stimulation of Baihui (GV20), Yintang (EX-HN3), and bilateral Tianshu (ST25), Zusanli (ST36), Shangjuxu (ST37), Sanyinjiao (SP6) and Taichong (LR3) with mind-regulating and spleen-strengthening technique for 30 min, once a day, 3 days a week for 6 weeks. Before and after the intervention, the IBS symptom severity scale (IBS-SSS) was used to assess the patients' state of abdominal pain, distention and defecation, and Hamilton Anxiety Rating Scale (HAMA) employed to evaluate the patients' anxiety severity. The resting state functional magnetic resonance imaging (rs-fMRI) data were acquired and preprocessed by using SPM8 and DPARSE soft-wares. Seeds (bilate-ral hippocampus regions) to whole-brain analysis was performed to obtain the mean time series of the left and right seed regions, followed by making Pearson correlation analysis to obtain the correlation coefficient (time series from each seed region with the rest of the voxels in the brain), and making a multivariate comparative correction to get data of functional connectivity (FC) of bilateral hippocampus regions and to find the related difference in the brain regions. Then, the differences of the FC of brain regions between IBS-D patients and healthy volunteers were compared.

Results: Following acupuncture treatment, both the HAMA and IBS-SSS scores were significantly reduced in the acupuncture group compared with its pre-treatment (<0.01). Compared with the healthy volunteers, there were a reduction in the functional connectivity between the left hippocampus seed region and the right inferior temporal gyrus, left fusiform gyrus and left superior gyrus, and between the right hippocampus region and the right fusiform gyrus, left inferior temporal gyrus, left inferior occipital gyrus, left rectus gyrus, left insula, left precuneus, right angular gyrus, left middle occipital gyrus, right precuneus, and the left superior temporal gyrus, and an increase in the FC between the left hippocampus and left superior temporal gyrus was increased in ISB-D patients. Self-comparison showed that after the treatment, the FC was increased between the left hippocampus seed region and the right inferior temporal gyrus, left fusiform gyrus, bilateral lingual gyrus, left amygdala, right inferior occipital gyrus, right insula, right middle frontal gyrus, left middle frontal gyrus and the left middle occipital gyrus; and between the right hippocampus seed region and the posterior inferior cerebellar lobe, left inferior temporal gyrus, left suboccipital gyrus, right fusiform gyrus, left insula, right inferior frontal gyrus, left superior temporal gyrus, left middle occipital gyrus, right middle frontal gyrus, left supplementary motor area and right supplementary motor area, and decreased between the left hippocampus region and the left anterior cingulate, paracingulate gyrus and the right posterior central gyrus in IBS-D patients.

Conclusion: Mind-regulating and spleen-strengthening acupuncture intervention may improve the abdominal pain and distension and emotional state in IBS-D patients, which is possibly associated with its effect in enhancing FC between the hippocampus and brain regions.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.13702/j.1000-0607.200569DOI Listing
April 2021

[Correlation between curative effect and 5-HTTLPR polymorphism in treatment of diarrhea-predominant irritable bowel syndrome with acupuncture for regulating and strengthening spleen].

Zhongguo Zhen Jiu 2021 Apr;41(4):365-70

Department of Acupuncture-Moxibustion and Rehabilitation, Affiliated Hospital of Nanjing University of Chinese Medicine, Nanjing 210029, Jiangsu Province, China.

Objective: To compare the curative effect on diarrhea-predominant irritable bowel syndrome (IBS-D) between acupuncture for regulating and strengthening spleen and pinaverium bromide, and explore the relevant mechanism of curative effect of acupuncture in view of polymorphism of 5-hydroxytryptamine transporter gene-linked polymorphic region (5-HTTLPR).

Methods: A total of 231 patients with IBS-D were randomized into an acupuncture group (154 cases) and a western medication group (77 cases) at the ratio of 2 to 1. In the acupuncture group, acupuncture was applied to acupoint regimen for regulating and strengthening spleen, i.e. Baihui (GV 20), Yintang (GV 29), Tianshu (ST 25), Shangjuxu (ST 37) and Zusanli (ST 36), etc. The treatment was given once every 2 days, 3 times a week. In the western medication group, pinaverium bromide was prescribed for oral administration, 50 mg each time, 3 times daily. The duration of treatment was 6 weeks in each group. Separately, before treatment, after treatment and in 3-month follow-up, the IBS symptom severity scale (IBS-SSS) and IBS quality of life scale (IBS-QOL) scores were adopted in assessment. After treatment, the curative effect and safety were compared between the two groups. Before treatment, 5-HTTLPR genotypes were determined in the patients.

Results: After treatment and in follow-up, the total scores of IBS-SSS in the patients of the two groups were all reduced as compared with those before treatment (<0.01) and the scores in the acupuncture group were lower than those in the western medication group (<0.01). After treatment and in follow-up, the total scores of IBS-QOL in the two groups were all increased as compared with those before treatment (<0.01) and the score in the acupuncture group was higher than the western medication group in follow-up (<0.01). The total effective rate was 79.2% (122/154) in the acupuncture group, higher than 58.4% (45/77) in the western medication group (<0.01). There was no severe adverse reaction found in the two groups. The difference in the total score of IBS-SSS before and after treatment in the patients with LS and SS genotypes was greater than that in the patients with LL in the acupuncture group (<0.01). The difference in the total score of ISB-SSS before and after treatment in the patients with SS genotype was greater than that in the patients with LL in the western medication group (<0.01). The difference in the total score of IBS-SSS before and after treatment in the patients with LS and SS genotypes in the acupuncture group was greater than that in the patients with the same genotypes in the western medication group (<0.01).

Conclusion: Acupuncture for regulating and strengthening spleen achieves the more curative effect on IBS-D as compared with pinaverium bromide. The acupuncture regimen effectively relieves the clinical symptoms and improves the quality of life in patients as well as presents a satisfactory long-term effect and safety. The clinical curative effect of acupuncture is correlated with 5-HTTLPR polymorphism, in which, the curative effect of acupuncture may be more effective in the patients with LS and SS genotypes.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.13703/j.0255-2930.20200313-k0002DOI Listing
April 2021

[Effect of acupuncture therapy on gut microbiota and fecal short-chain fatty acids in patients with diarrhea type irritable bowel syndrome].

Zhongguo Zhen Jiu 2021 Feb;41(2):137-41

Department of Acupuncture-Moxibustion and Rehabilitation, Affiliated Hospital of Nanjing University of Chinese Medicine, Nanjing 210029, Jiangsu Province, China.

Objective: To observe the clinical therapeutic effect of acupuncture therapy (acupuncture for regulating the mind and strengthening the spleen) on the gut microbiota and the content of fecal short-chain fatty acids (SCFAs) in patients with diarrhea type irritable bowel syndrome (IBS-D).

Methods: A total of 20 patients with IBS-D and 20 healthy subjects were included. The patients with IBS-D were treated with acupuncture therapy at Baihui (GV 20), Yintang (GV 29), Tianshu (ST 25), Shangjuxu (ST 37), Zusanli (ST 36), Sanyinjiao (SP 6) and Taichong (LR 3). The treatment was given once every two days, 3 times weekly, consecutively for 6 weeks. No intervention was provided for the healthy subjects. Before and after treatment, the IBS symptom severity score (IBS-SSS) was observed in the patients. The fecal samples were collected before and after treatment separately in the patients and in the healthy subjects. Using 16S rRNA sequencing technique, the structure and diversity of gut microbiota were analyzed. Using high-performance liquid chromatography, the content of SCFAs was detected.

Results: After treatment, the abdominal pain severity score, the abdominal pain days score, the satisfaction in bowel movement score, the life interference score and the total IBS-SSS score were all lower than those before treatment in the patients with IBS-D (<0.05). Compared with the healthy subjects, Firmicutes was increased (<0.05), Bacteroidetes and Proteobacteria were decreased (<0.05), and Shannon index was reduced (<0.05) and Simpson index was increased in patients with IBS-D before treatment (<0.05). Compared before treatment, Firmicutes was decreased (<0.05), Bacteroidetes and Proteobacteria were increased (<0.05), and Shannon index was increased (<0.05) and Simpson index was reduced in the patients with IBS-D after treatment (<0.05). Besides, the content of SCFAs was reduced after treatment (<0.05).

Conclusion: acupuncture therapy relieves abdominal pain and diarrhea, which may be related to regulating the structure and diversity of gut microbiota and reducing the content of fecal SCFAs in the patients with IBS-D.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.13703/j.0255-2930.20200205-k0002DOI Listing
February 2021

LMNB2 promotes the progression of colorectal cancer by silencing p21 expression.

Cell Death Dis 2021 03 29;12(4):331. Epub 2021 Mar 29.

Department of General Surgery, The Affiliated Hospital of Xuzhou Medical University, Jiangsu, 221002, Xuzhou, China.

Colorectal cancer is the second common cause of death worldwide. Lamin B2 (LMNB2) is involved in chromatin remodeling and the rupture and reorganization of nuclear membrane during mitosis, which is necessary for eukaryotic cell proliferation. However, the role of LMNB2 in colorectal cancer (CRC) is poorly understood. This study explored the biological functions of LMNB2 in the progression of colorectal cancer and explored the possible molecular mechanisms. We found that LMNB2 was significantly upregulated in primary colorectal cancer tissues and cell lines, compared with paired non-cancerous tissues and normal colorectal epithelium. The high expression of LMNB2 in colorectal cancer tissues is significantly related to the clinicopathological characteristics of the patients and the shorter overall and disease-free cumulative survival. Functional analysis, including CCK8 cell proliferation test, EdU proliferation test, colony formation analysis, nude mouse xenograft, cell cycle, and apoptosis analysis showed that LMNB2 significantly promotes cell proliferation by promoting cell cycle progression in vivo and in vitro. In addition, gene set enrichment analysis, luciferase report analysis, and CHIP analysis showed that LMNB2 promotes cell proliferation by regulating the p21 promoter, whereas LMNB2 has no effect on cell apoptosis. In summary, these findings not only indicate that LMNB2 promotes the proliferation of colorectal cancer by regulating p21-mediated cell cycle progression, but also suggest the potential value of LMNB2 as a clinical prognostic marker and molecular therapy target.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1038/s41419-021-03602-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8007612PMC
March 2021

Acquisition of the L452R mutation in the ACE2-binding interface of Spike protein triggers recent massive expansion of SARS-Cov-2 variants.

bioRxiv 2021 Mar 11. Epub 2021 Mar 11.

The recent rise in mutational variants of SARS-CoV-2, especially with changes in the Spike protein, is of significant concern due to the potential ability for these mutations to increase viral infectivity, virulence and/or ability to escape protective antibodies. Here, we investigated genetic variations in a 414-583 amino acid region of the Spike protein, partially encompassing the ACE2 receptor-binding domain (RBD), across a subset of 570 nasopharyngeal samples isolated between April 2020 and February 2021, from Washington, California, Arizona, Colorado, Minnesota and Illinois. We found that samples isolated since November have an increased number of amino acid mutations in the region, with L452R being the dominant mutation. This mutation is associated with a recently discovered CAL.20C viral variant from clade 20C, lineage B.1.429, that since November-December 2020 is associated with multiple outbreaks and is undergoing massive expansion across California. In some samples, however, we found a distinct L452R-carrying variant of the virus that, upon detailed analysis of the GISAID database genomes, is also circulating primarily in California, but emerged even more recently. The newly identified variant derives from the clade 20A (lineage B.1.232) and is named CAL.20A. We also found that the SARS-CoV-2 strain that caused the only recorded case of infection in an ape - gorillas in the San Diego Zoo, reported in January 2021 - is CAL.20A. In contrast to CAL.20C that carries two additional to L452R mutations in the Spike protein, L452R is the only mutation found in CAL.20A. According to the phylogenetic analysis, however, emergence of CAL.20C was also specifically triggered by acquisition of the L452R mutation. Further analysis of GISAID-deposited genomes revealed that several independent L452R-carrying lineages have recently emerged across the globe, with over 90% of the isolates reported between December 2020 - February 2021. Taken together, these results indicate that the L452R mutation alone is of significant adaptive value to SARS-CoV-2 and, apparently, the positive selection for this mutation became particularly strong only recently, possibly reflecting viral adaptation to the containment measures or increasing population immunity. While the functional impact of L452R has not yet been extensively evaluated, leucine-452 is positioned in the receptor-binding motif of RBD, in the interface of direct contact with the ACE2 receptor. Its replacement with arginine is predicted to result in both a much stronger binding to the receptor and escape from neutralizing antibodies. If true, this in turn might lead to significantly increased infectivity of the L452R variants, warranting their close surveillance and in-depth functional studies.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1101/2021.02.22.432189DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7987020PMC
March 2021

No significant long-term complications from inadvertent exposure to gonadotropin-releasing hormone agonist during early pregnancy in mothers and offspring: a retrospective analysis.

Reprod Biol Endocrinol 2021 Mar 20;19(1):46. Epub 2021 Mar 20.

Reproductive Medicine Center, Department of Obstetrics and Gynecology, The First Affiliated Hospital of Anhui Medical University, No. 218 Jixi Road, Hefei, 230022, China.

Background: Administration of gonadotropin-releasing hormone agonist (GnRH-a) in the luteal phase is commonly used for pituitary suppression during in vitro fertilisation (IVF). There is an ineluctable risk of inadvertent exposure of spontaneous pregnancy to GnRH-a. However, little is known about the pregnancy complications and repregnancy outcomes of the affected women and the neurodevelopmental outcomes of the GnRH-a-exposed children.

Methods: Retrospective analysis was used to determine obstetric and repregnancy outcomes after natural conception in 114 women who naturally conceived while receiving GnRH-a during their early pregnancy over the past 17 years. The GnRH-a-exposed children were evaluated to determine their neonatal characteristics and long-term neurodevelopmental outcomes. The outcomes were compared to those of relevant age-matched control groups.

Results: Sixty-five women had 66 live births. The neonatal health outcomes and the incidence of maternal complications were similar in the GnRH-a-exposed and control groups. Thirty-one GnRH-a-exposed children, aged 2-8 years, were available for investigation of neurodevelopment. Except for one case of autism spectrum disorder, the full-scale intelligence quotient score was within the normal range and similar to that of the control group. Most mothers with successful pregnancies and about one-third of the women who had spontaneous abortions were subsequently able to conceive naturally again. IVF is recommended for repregnancy in women who have experienced ectopic pregnancies.

Conclusions: Accidental exposure to GnRH-a in early pregnancy might be safe. Reproductive treatment suggestions for repregnancy should be made with consideration of the outcomes of the previously GnRH-a-exposed spontaneous pregnancy.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1186/s12958-021-00732-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7980339PMC
March 2021

Diallyl trisulfide inhibited tobacco smoke-mediated bladder EMT and cancer stem cell marker expression via the NF-κB pathway .

J Int Med Res 2021 Mar;49(3):300060521992900

Department of Urology, Second Affiliated Hospital of Anhui Medical University, Hefei, China.

Objective: This study examined the effect of the NF-κB pathway on tobacco smoke-elicited bladder epithelial-mesenchymal transition (EMT) and cancer stem cell (CSC) marker expression . The effect of diallyl trisulfide (DATS) treatment was also examined.

Methods: BALB/c mice were exposed to tobacco smoke and treated with an NF-κB inhibitor and DATS. Western blotting, quantitative real-time PCR, and immunohistochemical staining were used to detect the changes of relevant indices.

Results: Phosphorylated inhibitor of kappa-B kinase alpha/beta expression and p65 and p50 nuclear transcription were increased by tobacco smoke exposure, whereas inhibitor of kappa-B expression was decreased. In addition, tobacco smoke reduced the expression of epithelial markers but increased that of mesenchymal and CSC markers. Our study further demonstrated that tobacco smoke-mediated EMT and CSC marker expression were attenuated by inhibition of the NF-κB pathway. Moreover, DATS reversed tobacco smoke-induced NF-κB pathway activation, EMT, and the acquisition of CSC properties in bladder tissues.

Conclusions: These data suggested that the NF-κB pathway regulated tobacco smoke-induced bladder EMT, CSC marker expression, and the protective effects of DATS.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1177/0300060521992900DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8166398PMC
March 2021

Differences in the Gut Microbiome of Women With and Without Hypoactive Sexual Desire Disorder: Case Control Study.

J Med Internet Res 2021 02 25;23(2):e25342. Epub 2021 Feb 25.

Reproductive Medicine Center, Department of Obstetrics and Gynecology, The First Affiliated Hospital of Anhui Medical University, Hefei, China.

Background: The gut microbiome is receiving considerable attention as a potentially modifiable risk factor and therapeutic target for numerous mental and neurological diseases.

Objective: This study aimed to explore and assess the difference in the composition of gut microbes and fecal metabolites between women with hypoactive sexual desire disorder (HSDD) and healthy controls.

Methods: We employed an online recruitment method to enroll "hard-to-reach" HSDD populations. After a stringent diagnostic and exclusion process based on DSM-IV criteria, fecal samples collected from 24 women with HSDD and 22 age-matched, healthy controls underwent microbiome analysis using 16S ribosomal RNA gene sequencing and metabolome analysis using untargeted liquid chromatography-mass spectrometry.

Results: We found a decreased abundance of Ruminococcaceae and increased abundance of Bifidobacterium and Lactobacillus among women with HSDD. Fecal samples from women with HSDD showed significantly altered metabolic signatures compared with healthy controls. The abundance of Bifidobacterium, Lactobacillus, and several fecal metabolites correlated negatively with the sexual desire score, while the number of Ruminococcaceae correlated positively with the sexual desire score in all subjects.

Conclusions: Our analysis of fecal samples from women with HSDD and healthy controls identified significantly different gut microbes and metabolic signatures. These preliminary findings could be useful for developing strategies to adjust the level of human sexual desire by modifying gut microbiota.

Trial Registration: Chinese Clinical Trial Registry ChiCTR1800020321; http://www.chictr.org.cn/showproj.aspx?proj=34267.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.2196/25342DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7952237PMC
February 2021

Novel variants in DNAH9 lead to nonsyndromic severe asthenozoospermia.

Reprod Biol Endocrinol 2021 Feb 20;19(1):27. Epub 2021 Feb 20.

Reproductive Medicine Center, Department of Obstetrics and Gynecology, the First Affiliated Hospital of Anhui Medical University, No 218 Jixi Road, Hefei, 230022, Anhui, China.

Background: Asthenozoospermia is one of the most common causes of male infertility, and its genetic etiology is poorly understood. DNAH9 is a core component of outer dynein arms in cilia and flagellum. It was reported that variants of DNAH9 (OMIM: 603330) might cause primary ciliary dyskinesia (PCD). However, variants in DNAH9 lead to nonsyndromic severe asthenozoospermia have yet to be reported.

Methods: Whole exome sequencing (WES) was performed for two individuals with nonsyndromic severe asthenozoospermia from two non-consanguineous families, and Sanger sequencing was performed to verify the identified variants and parental origins. Sperm routine analysis, sperm vitality rate and sperm morphology analysis were performed according the WHO guidelines 2010 (5th edition). Transmission electron microscopy (TEM, TECNAI-10, 80 kV, Philips, Holland) was used to observe ultrastructures of sperm tail. Quantitative realtime-PCR and immunofluorescence staining were performed to detect the expression of DNAH9-mRNA and location of DNAH9-protein. Furthermore, assisted reproductive procedures were applied.

Results: By WES and Sanger sequencing, compound heterozygous DNAH9 (NM_001372.4) variants were identified in the two individuals with nonsyndromic severe asthenozoospermia (F1 II-1: c.302dupT, p.Leu101fs*47 / c.6956A > G, p.Asp2319Gly; F2 II-1: c.6294 T > A, p.Phe2098Leu / c.10571 T > A, p.Leu3524Gln). Progressive rates less than 1% with normal sperm morphology rates and normal vitality rates were found in both of the two subjects. No respiratory phenotypes, situs inversus or other malformations were found by detailed medical history, physical examination and lung CT scans etc. Moreover, the expression of DNAH9-mRNA was significantly decreased in sperm from F1 II-1. And expression of DNAH9 is lower in sperm tail by immunofluorescence staining in F1 II-1 compared with normal control. Notably, by intracytoplasmic sperm injection (ICSI), F1 II-1 and his partner successfully achieved clinical pregnancy.

Conclusions: We identified DNAH9 as a novel pathogenic gene for nonsyndromic severe asthenospermia, and ICSI can contribute to favorable pregnancy outcomes for these patients.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1186/s12958-021-00709-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7896388PMC
February 2021

Benzidine promotes the stemness of bladder cancer stem cells via activation of the Sonic hedgehog pathway.

Oncol Lett 2021 Feb 23;21(2):146. Epub 2020 Dec 23.

Department of Nutrition and Food Safety, Center for Global Health, School of Public Health, Nanjing Medical University, Nanjing, Jiangsu 211166, P.R. China.

Substantial evidence suggests that cancer stem cells (CSCs) are the main cause of the initiation, progression and recurrence of tumors. Benzidine has been identified as a risk factor for bladder cancer. The aim of the present study was to investigate the effects of benzidine on bladder CSCs (BCSCs) and the possible mechanism underlying its action. The bladder cancer cell lines UM-UC-3 and EJ were maintained in serum-free medium and cells forming three-dimensional spheres were characterized as BCSCs. The sphere-forming cells were exposed to different concentrations of benzidine and vismodegib, and western blotting was performed to evaluate the expression of markers associated with CSCs and the Sonic hedgehog (SHH) signaling pathway. Flow cytometry was used to detect the distribution of cells in different phases of the cell cycle, and immunofluorescence staining was used to detect the protein expression of CD44. The results revealed that the levels of BCSC markers, namely CD133, CD44, aldehyde dehydrogenase 1-A1, Nanog and octamer-binding transcription factor-4, in the cell spheres were markedly elevated compared with those in cells cultured in serum-supplemented medium. Furthermore, benzidine increased the expression of BCSC markers and promoted the sphere-forming ability of the cells. In addition, it was observed that benzidine activated the SHH pathway, while inhibition of the Shh pathway using vismodegib diminished the promoting effects of benzidine on BCSCs. The findings of the present study indicate that benzidine promoted the stemness of BCSCs via activation of the SHH pathway, which may support further exploration of the molecular basis of the association between benzidine exposure and bladder oncogenesis.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3892/ol.2020.12407DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7798036PMC
February 2021

Prevalence of SARS-CoV-2 Contamination on Food Plant Surfaces as Determined by Environmental Monitoring.

J Food Prot 2021 03;84(3):352-358

Institute for Environmental Health, 15300 Bothell Way N.E., Lake Forest Park, Washington 98155, USA (ORCID: https://orcid.org/0000-0001-5840-353X [Z.M.]).

Abstract: The SARS-CoV-2 pandemic has presented new challenges to food manufacturers. During the early phase of the pandemic, several large outbreaks of coronavirus disease 2019 (COVID-19) occurred in food manufacturing plants resulting in deaths and economic loss, with approximately 15% of personnel diagnosed as asymptomatic for COVID-19. Spread by asymptomatic and presymptomatic individuals has been implicated in large outbreaks of COVID-19. In March 2020, we assisted in implementation of environmental monitoring programs for SARS-CoV-2 in zones 3 and 4 of 116 food production facilities. All participating facilities had already implemented measures to prevent symptomatic personnel from coming to work. During the study period, from 17 March to 3 September 2020, 1.23% of the 22,643 environmental samples tested positive for SARS-CoV-2, suggesting that infected individuals were actively shedding virus. Virus contamination was commonly found on frequently touched surfaces such as doorknobs, handles, table surfaces, and sanitizer dispensers. Most processing plants managed to control their environmental contamination when they became aware of the positive findings. Comparisons of positive test results for plant personnel and environmental surfaces in one plant revealed a close correlation. Our work illustrates that environmental monitoring for SARS-CoV-2 can be used as a surrogate for identifying the presence of asymptomatic and presymptomatic personnel in workplaces and may aid in controlling infection spread.

Highlights:
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.4315/JFP-20-465DOI Listing
March 2021

A novel homozygous mutation in the meiotic gene leading to male infertility due to non-obstructive azoospermia.

Am J Transl Res 2020 15;12(12):8185-8191. Epub 2020 Dec 15.

Reproductive Medicine Center, Department of Obstetrics and Gynecology, The First Affiliated Hospital of Anhui Medical University No 218 Jixi Road, Hefei 230022, Anhui, China.

Non-obstructive azoospermia (NOA) is the most severe form of male infertility. Although some causes have been established, including genetic causes, the etiology in most cases remains idiopathic. Mutations in (OMIM: 602105), an important gene involved in meiosis, may be related to female infertility due to primary ovarian insufficiency (POI) and male NOA. Here, we report a novel homozygous stop-gain mutation of associated with NOA. Whole exome sequencing (WES) and bioinformatic analysis were performed in a patient with NOA from a consanguineous family (F1 II-1). A rare homozygous stop-gain mutation (c.1552C>T:p.Q518X) was observed in the patient, and his parents were heterozygous carriers, as verified by Sanger sequencing. Testicular biopsy and hematoxylin and eosin staining of testicular tissue suggested meiotic arrest (MA), and no sperm were observed. was detected in other 50 separate cases with same pathological results of MA using the same procedures, but only one heterozygous mutation was observed. Subsequent real-time quantitative polymerase chain reaction and immunohistochemistry were performed to examine mRNA expression levels and the localization of the MSH4 protein in the testicular tissue. Furthermore, the expression of MSH4 mRNA was significantly decreased compared with normal control. MSH4 protein was highly expressed in spermatocytes in the seminiferous tubules of the normal control, while no obvious expression was observed in F1 II-1. In this present study, was identified as a candidate gene of male infertility causing NOA. A novel mutation of MSH4 (c.1552C>T:p.Q518X) is associated with the MA phenotype during spermatogenesis.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7791528PMC
December 2020

Tunnel Intergrowth Li MnO Nanosheet Arrays as 3D Cathode for High-Performance All-Solid-State Thin Film Lithium Microbatteries.

Adv Mater 2021 Feb 18;33(5):e2003524. Epub 2020 Dec 18.

School of Materials Science and Engineering, Nanjing University of Science and Technology, Nanjing, 210094, China.

All-solid-state thin film lithium batteries (TFBs) are proposed as the ideal power sources for microelectronic devices. However, the high-temperature (>500 °C) annealing process of cathode films, such as LiCoO and LiMn O restricts the on-chip integration and potential applications of TFBs. Herein, tunnel structured Li MnO nanosheet arrays are fabricated as 3D cathode for TFBs by a facile electrolyte Li ion infusion method at very low temperature of 180 °C. Featuring an interesting tunnel intergrowth structure consisting of alternating 1 × 3 and 1 × 2 tunnels, the Li MnO cathode shows high specific capacity with good structural stability between 2.0 and 4.3 V (vs. Li /Li). By utilizing the 3D Li MnO cathode, all-solid-state Li MnO /LiPON/Li TFB (3DLMO-TFB) has been successfully constructed with prominent advantages of greatly enriched cathode/electrolyte interface and shortened Li diffusion length in the 3D structure. Consequently, the 3DLMO-TFB device exhibits large specific capacity (185 mAh g at 50 mA g ), good rate performance, and excellent cycle performance (81.3% capacity retention after 1000 cycles), outperforming the TFBs using spinel LiMn O thin film cathodes fabricated at high temperature. Importantly, the low-temperature preparation of high-performance cathode film enables the fabrication of TFBs on various rigid and flexible substrates, which could greatly expand their potential applications in microelectronics.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/adma.202003524DOI Listing
February 2021

A Novel Missense Variant of Heterozygously Present in Split-Hand/Foot Malformation.

Biomed Res Int 2020 26;2020:4215632. Epub 2020 Nov 26.

Reproductive Medicine Center, Department of Obstetrics and Gynecology, The First Affiliated Hospital of Anhui Medical University, No. 218 Jixi Road, Hefei, 230022 Anhui, China.

Background: Split-hand/foot malformation (SHFM) is a severe congenital disability mainly characterized by the absence or hypoplasia of the central ray of the hand/foot. To date, several candidate genes associated with SHFM have been identified, including , , , , and . Herein, we report a novel variant of heterozygously present in affected members of a family with SHFM.

Methods: This study investigated a Chinese family, in which the proband and his son suffered from SHFM. The peripheral blood sample of the proband was used to perform whole-exome sequencing (WES) to explore the possible genetic causes of this disease. Postsequencing bioinformatic analyses and Sanger sequencing were conducted to verify the identified variants and parental origins on all family members in the pedigree.

Results: By postsequencing bioinformatic analyses and Sanger sequencing, we identified a novel missense variant (NM_003722.4:c.948G>A; p.Met316Ile) of in this family that results in a substitution of methionine with isoleucine, which is probably associated with the occurrence of SHFM.

Conclusion: A novel missense variant (NM_003722.4:c.948G>A; p.Met316Ile) of in SHFM was thus identified, which may enlarge the spectrum of known variants and also provide new approaches for genetic counselling of families with SHFM.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1155/2020/4215632DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7714569PMC
May 2021

Inhibition and disaggregation of amyloid β protein fibrils through conjugated polymer-core thermoresponsive micelles.

J Mater Chem B 2020 11;8(44):10126-10135

School of Materials Science and Engineering, Hebei University of Technology, Tianjin 300401, P. R. China.

Excess aggregation of amyloid β peptide (Aβ) is a fatal cause of Alzheimer's disease (AD), which leads to physiological toxicity. Inhibiting and disaggregating the Aβ aggregates is an effective strategy to reduce physiological toxicity in neuronal cells. Herein, conjugated polymer-based thermoresponsive micelles (CPMs) were designed with an efficient thermoresponsive surface and a reactive-oxygen-species (ROS)-generating core. In this work, the CPMs exhibited a strong capability to capture the toxic Aβ aggregates at physiological temperature. Under white-light irradiation, ROS was generated in the CPMs, and the toxic Aβ aggregates were efficiently disaggregated through the oxidation of ROS, leading to appropriate Aβ homeostasis between aggregation and disaggregation and reduced the Aβ-induced cytotoxicity. Therefore, the multifunctional micelles of CPMs with both capturing shells and ROS functional cores present a promising strategy to reduce Aβ fibrillation-induced cytotoxicity.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1039/d0tb01863eDOI Listing
November 2020

Curcumin Negatively Regulates Cigarette Smoke-Induced Renal Cell Carcinoma Epithelial-Mesenchymal Transition Through the ERK5/AP-1 Pathway.

Onco Targets Ther 2020 29;13:9689-9700. Epub 2020 Sep 29.

Department of Urologic Surgery, The Second Affiliated Hospital of Anhui Medical University, Hefei 230032, People's Republic of China.

Background: So far, little research has been conducted regarding the underlying mechanism of renal carcinogenesis at molecular level. Epithelial-mesenchymal transition (EMT) exerts an important part during tumor genesis as well as the development through mitogen-activated protein kinase (MAPK) pathways. Therefore, we hypothesized that EMT could promote renal cell carcinoma (RCC) progression via the ERK5/AP-1pathway.

Materials And Methods: The RCC cell lines were utilized to be the models with in vitro exposure to cigarette smoke extract (CSE). We used the curcumin for the EMT intervention study. In the present study, immunohistochemistry (IHC), Western blotting, and real-time quantitative reverse transcription PCR had been used to determine the experimental results. EMT phenotypic alterations were assessed by changes in cell morphology, invasion and transfer ability, as well as expression of epithelial and mesenchymal markers.

Results: In human renal cell carcinoma tissue, E-cadherin expression within the smoking renal cancer patients was down-regulated compared with that among the non-smokers. However, Vimentin, N-cadherin, and TWIST levels increased (<0.05). Significantly, we clarified that ERK5/AP-1 exerted positive regulation on the renal cell carcinoma EMT mediated by CS, which was suggested based on the results of CS activating the ERK5/AP-1 pathway, as well as ERK5 inhibition via XMD8-92 reversed AP-1 protein levels and the EMT process. Furthermore, curcumin showed the same inhibitory effect as XMD8-92 and significantly reversed CS-induced EMT through inhibiting the ERK5/AP-1 signaling pathway.

Conclusion: The above results indicated that ERK5/AP-1 signaling pathway exerts a vital part for CS-associated RCC development and cancer intervention.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.2147/OTT.S265847DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7532894PMC
September 2020

First measurements of the radiation dose on the lunar surface.

Sci Adv 2020 Sep 25;6(39). Epub 2020 Sep 25.

18th Research Institute, China Electronics Technology Group Corporation, Tianjin, PR China.

Human exploration of the Moon is associated with substantial risks to astronauts from space radiation. On the surface of the Moon, this consists of the chronic exposure to galactic cosmic rays and sporadic solar particle events. The interaction of this radiation field with the lunar soil leads to a third component that consists of neutral particles, i.e., neutrons and gamma radiation. The Lunar Lander Neutrons and Dosimetry experiment aboard China's Chang'E 4 lander has made the first ever measurements of the radiation exposure to both charged and neutral particles on the lunar surface. We measured an average total absorbed dose rate in silicon of 13.2 ± 1 μGy/hour and a neutral particle dose rate of 3.1 ± 0.5 μGy/hour.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1126/sciadv.aaz1334DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7518862PMC
September 2020

[Exploration on the relationship between acupuncture for mind-regulation and flow theory].

Zhongguo Zhen Jiu 2020 Sep;40(9):1003-5

Department of Acupuncture and Rehabilitation, Affiliated Hospital of Nanjing University of Chinese Medicine, Nanjing 210029, Jiangsu Province, China.

Based on the story of Chinese idiom, (a magical and skilled form of craftsmanship) as the breakthrough point, this paper discusses the both (cook) and the experienced acupuncture practitioner have the same high skills and explores the potential relationship between mind-regulation in treatment with acupuncture and flow theory. It is believed that the skills of ancient acupuncture practitioner in mind-regulation with acupuncture is not only a kind of "Tao" mode, but also a state of "flow". By the discussion on mind-regulation and flow theory, modern people may have more clear recognition on the mind regulation in treatment with acupuncture so as to better determine the therapeutic methods of acupuncture for mind-regulation.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.13703/j.0255-2930.20191231-k0006DOI Listing
September 2020

Gandou decoction, a Chinese medicinal formula, in the treatment of hepatic injury by Wnt/β-catenin pathway regulation in models of Wilson disease.

Ann Palliat Med 2020 Sep 10;9(5):2872-2885. Epub 2020 Aug 10.

Anhui University of Chinese Medicine, Hefei, China.

Background: Gandou decoction (GDD) has been widely used in the treatment of Wilson disease (WD) for decades. It is optimized from the Dahuanghuanglianxiexin decoction, Yinchenhao decoction, and Huanglianjiedu decoction. It was first reported in the Treatise on Febrile and Miscellaneous Diseases and A Handbook of Prescriptions for Emergencies published in the Eastern Han Dynasty and the Eastern Jin Dynasty respectively. Hepatic injury is one of the most severe complications of WD. The current study aimed to explore the hepatic-protection effects of GDD and its exact therapeutic target, with a particular focus on the expression of oxidative stress and the Wnt/β-catenin pathway.

Methods: Hepatic injury was induced in a copper-loaded rat model using the intragastric administration of copper(II) sulfate pentahydrate (CuSO4·5H2O). The water extract of GDD (0.4 g/kg/d) was administered twice a day for 4 weeks. Copper content and alanine aminotransferase (ALT) level, structural observation under the microscope, and immunohistochemical analysis of liver tissue were performed after the final administration. Moreover, the expression of β-catenin, GSK3β, Dishevelled-3, c-Myc, and p-GSK3β of liver tissue were detected to explore the relationship between the hepatic protection of GDD and the Wnt/ β-catenin signal pathway of GDD. We also stimulated the rat hepatic cell line BRL-3A with CuSO4·5H2O to establish a hepatic injury cytomodel. GDD serum at a concentration of 20% was administered into the model cell for 24 h. 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) assay and flow cytometry were performed to detect cell viability, mitochondrial membrane potential (MMP), and the expression of reactive oxygen species (ROS). Meanwhile, the expression of the Wnt/β-catenin signal pathway-related proteins was evaluated.

Results: GDD reduced copper and ALT while inhibiting oxidative stress and the degeneration and necrosis of liver tissue and hepatocytes. Treatment with GDD improved cell viability and MMP while suppressing the ROS level. Furthermore, GDD rectified the expression of Wnt/β-catenin signal pathway-related proteins in both livers of the copper-loaded and copper-stimulated BRL-3A cell lines.

Conclusions: GDD had apparent therapeutic effects on the hepatic injury of copper-loaded rats and copper-stimulated BRL-3A cells. Its mechanism is related to its regulatory effect on the Wnt/β-catenin pathway rectification and oxidative stress antagonism.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.21037/apm-20-301DOI Listing
September 2020
-->