High-frequency rTMS over bilateral primary motor cortex improves freezing of gait and emotion regulation in patients with Parkinson's disease: a randomized controlled trial.

Background: Freezing of gait (FOG) is a common and disabling phenomenon in patients with Parkinson's disease (PD), but effective treatment approach remains inconclusive. Dysfunctional emotional factors play a key role in FOG. Since primary motor cortex (M1) connects with prefrontal areas via the frontal longitudinal system, where are responsible for emotional regulation, we hypothesized M1 may be a potential neuromodulation target for FOG therapy. The purpose of this study is to explore whether high-frequency rTMS over bilateral M1 could relieve FOG and emotional dysregulation in patients with PD. Methods: This study is a single-center, randomized double-blind clinical trial. Forty-eight patients with PD and FOG from the Affiliated Hospital of Xuzhou Medical University were randomly assigned to receive 10 sessions of either active (N = 24) or sham (N = 24) 10 Hz rTMS over the bilateral M1. Patients were evaluated at baseline (T0), after the last session of treatment (T1) and 30 days after the last session (T2). The primary outcomes were Freezing of Gait Questionnaire (FOGQ) scores, with Timed Up and Go Test (TUG) time, Standing-Start 180° Turn (SS-180) time, SS-180 steps, United Parkinson Disease Rating Scales (UPDRS) III, Hamilton Depression scale (HAMD)-24 and Hamilton Anxiety scale (HAMA)-14 as secondary outcomes. Results: Two patients in each group dropped out at T2 and no serious adverse events were reported by any subject. Two-way repeated ANOVAs revealed significant group × time interactions in FOGQ, TUG, SS-180 turn time, SS-180 turning steps, UPDRS III, HAMD-24 and HAMA-14. Post-hoc analyses showed that compared to T0, the active group exhibited remarkable improvements in FOGQ, TUG, SS-180 turn time, SS-180 turning steps, UPDRS III, HAMD-24 and HAMA-14 at T1 and T2. No significant improvement was found in the sham group. The Spearman correlation analysis revealed a significantly positive association between the changes in HAMD-24 and HAMA-14 scores and FOGQ scores at T1. Conclusion: High-frequency rTMS over bilateral M1 can improve FOG and reduce depression and anxiety in patients with PD.

Compound heterozygous mutations in CFTR causing congenital bilateral absence of the vas deferens in a Chinese pedigree.

BACKGROUND: Cystic fibrosis (CF) is an autosomal recessive disorder rarely found in Asian populations. Most males with CF are infertile because of obstructive azoospermia (OA) caused by congenital bilateral absence of the vas deferens (CBAVD). Compound heterozygous mutations of cystic fibrosis transmembrane conductance regulator (CFTR) are among the most common pathogenic factors in CBAVD. However, few genealogical analyses have been performed. METHODS: In this study, whole-exome sequencing and cosegregation analysis were performed in a Chinese pedigree involving two siblings with CBAVD. Moreover, in vitro gene expressions were used to analyze the pathogenicity of a novel CFTR mutation. RESULTS: We identified compound heterozygous mutations of CFTR comprising the known disease-causing variant c.1210-11T>G (also known as IVS9-5 T) and c.2144delA;p.q715fs in two siblings with CBAVD. To verify the effects in vitro, we transfected vectors expressing wild-type and mutated CFTR into 293T cells. The results showed that the CFTR protein containing the frameshift mutation (c.2144delA) was 60 kD smaller. With testicular sperm aspiration/intracytoplasmic sperm injection-embryo transfer (TESA/ICSI-ET), both CBAVD patients fathered healthy offspring. CONCLUSION: Our study revealed that compound heterozygous mutations of CFTR are involved in CBAVD, expanding the known CFTR gene mutation spectrum of CBAVD patients and providing more evidence that compound heterozygous mutations can cause familial CBAVD.

Utility of labial salivary gland biopsy in the histological diagnosis of neuronal intranuclear inclusion disease.

BACKGROUND AND PURPOSE: Neuronal intranuclear inclusion disease (NIID) poses a diagnostic challenge because of its diverse clinical manifestations. Detection of intranuclear inclusions remains the primary diagnostic criterion for NIID. Skin biopsies have traditionally been used, but concerns exist regarding postoperative complications and scarring. We sought to investigate the diagnostic utility of labial salivary gland biopsy, a less invasive alternative. METHODS: This study included a total of 19 patients and 11 asymptomatic carriers who underwent labial gland biopsies, while 10 patients opted for skin biopsies. All these individuals were confirmed to have pathogenic GGC repeat expansions in the NOTCH2NLC gene. The control group comprised 20 individuals matched for age and sex, all with nonpathogenic GGC repeat expansions, and their labial gland tissue was sourced from oral surgery specimens. RESULTS: Labial gland biopsies proved to be a highly effective diagnostic method in detecting eosinophilic intranuclear inclusions in NIID patients. The inclusions showed positive staining for p62 and ubiquitin, confirming their pathological significance. The presence of uN2CpolyG protein in the labial gland tissue further supported the diagnosis. Importantly, all patients who underwent lip gland biopsy experienced fast wound healing without any noticeable scarring. In contrast, skin biopsies led to varying degrees of scarring and one instance of a localized infection. CONCLUSION: Labial salivary gland biopsy emerged as a minimally invasive, efficient diagnostic method for NIID, with rapid healing and excellent sensitivity.

A prediction model for high ovarian response in the GnRH antagonist protocol.

Backgrounds: The present study was designed to establish and validate a prediction model for high ovarian response (HOR) in the GnRH antagonist protocol. Methods: In this retrospective study, the data of 4160 cycles were analyzed following the in vitro fertilization (IVF) at our reproductive medical center from June 2018 to May 2022. The cycles were divided into a training cohort (n=3121) and a validation cohort (n=1039) using a random sampling method. Univariate and multivariate logistic regression analyses were used to screen out the risk factors for HOR, and the nomogram was established based on the regression coefficient of the relevant variables. The area under the receiver operating characteristic curve (AUC), the calibration curve, and the decision curve analysis were used to evaluate the performance of the prediction model. Results: Multivariate logistic regression analysis revealed that age, body mass index (BMI), follicle-stimulating hormone (FSH), antral follicle count (AFC), and anti-mullerian hormone (AMH) were independent risk factors for HOR (all P< 0.05). The prediction model for HOR was constructed based on these factors. The AUC of the training cohort was 0.884 (95% CI: 0.869-0.899), and the AUC of the validation cohort was 0.884 (95% CI:0.863-0.905). Conclusion: The prediction model can predict the probability of high ovarian response prior to IVF treatment, enabling clinicians to better predict the risk of HOR and guide treatment strategies.

Effects of assisted reproductive technology on gene expression in heart and spleen tissues of adult offspring mouse.

Objectives: Assisted reproductive technology (ART) is an important part of reproductive medicine, whose possible effects on offspring's health have drawn widespread attention in recent years. However, relevant studies are limited to postnatal short-term follow-up and lack of diverse sample sources analysis other than blood. Methods: In this study, a mouse model was used to explore the effects of ART on fetal development and gene expression in the organs of offspring in the adulthood using next-generation sequencing. The sequencing results were then analyzed. Results: The results showed that it caused abnormal expression in 1060 genes and 179 genes in the heart and spleen, respectively. Differentially expressed genes (DEGs) in the heart are mainly enriched in RNA synthesis and processing, and the cardiovascular system development also shows enrichment. STRING analysis identified Ccl2, Ptgs2, Rock1, Mapk14, Agt, and Wnt5a as the core interacting factors. DEGs in the spleen are significantly enriched in anti-infection and immune responses, which include the core factors Fos, Jun and Il1r2. Further exploration revealed the abnormal expression of 42 and 5 epigenetic modifiers in the heart and spleen, respectively. The expression of the imprinted genes Dhcr7, Igf2, Mest and Smoc1 decreased in the hearts of ART offspring, and the DNA methylation levels of Igf2- and Mest-imprinting control regions (ICRs) increased abnormally. Conclusion: In the mouse model, ART can interfere with the gene expression pattern in the heart and spleen of the adult offspring and that these changes are related to the aberrant expression of epigenetic regulators.

Correlation between CFTR variants and outcomes of ART in patients with CAVD in Central China.

Biallelic variants in Cystic Fibrosis Transmembrane Conductance Regulator (CFTR) are the main pathogenic factor of congenital absence of the vas deferens (CAVD), including congenital bilateral absence of the vas deferens (CBAVD) and congenital unilateral absence of the vas deferens (CUAVD). However, there are few reports about the correlation between CFTR variant and outcomes of assisted reproductive technology (ART) in CAVD patients of China. In this study, 104 patients with CAVD were recruited in Central China, and provided gene detection by the whole-exome sequencing, among them 69% (72/104) carried at least one variant in CFTR and one carried adhesion G protein-coupled receptor G2 (ADGRG2) variant. A total of 81 CAVD patients were treated with ART, of which 21 and 60 carried none or at least one variant in CFTR, respectively. The fertilization rate, cleavage rate, effective embryo rate, implantation rate, clinical pregnancy rate and live birth rate per fresh embryo transfer were compared between patients with and without CFTR variants. It was found that the ART outcomes had no significant difference whether the patients carried the CFTR variant or not. In addition, all of the offspring were healthy after follow-up. In conclusion, rare CFTR variants may play a major role in patients with CAVD in Central China, which were greatly different from other descent. There was no significant difference in ART outcomes in CAVD patients with or without CFTR variants. The limitations of this study were that there was no statistical analysis of the sperm quality through TESA and conclusions were relatively limited due to the small sample size of the study.

Effects of oocyte vitrification on gene expression in the liver and kidney tissues of adult offspring.

Oocyte vitrification is an important assisted reproductive technology (ART) that preserves the fertility of unmarried patients with malignant tumors, and promotes the development of the oocyte donation program. In recent years, the effects of ART, including the vitrification of oocytes and embryos on the health of offspring, have attracted much attention; however, it is difficult to conduct long-term follow-up and biochemical evaluation in humans. In this study, we detected the effect of oocyte vitrification on gene expression in the organs of adult mice offspring by RNA sequencing for the first time. Our results showed that only a small amount of gene expression was significantly affected. Seven genes (Tpm3, Hspe1-rs1, Ntrk2, Cyp4a31, Asic5, Cyp4a14, Retsat) were abnormally expressed in the liver, and ten genes (Lbp, Hspe1-rs1, Prxl2b, Pfn3, Gm9008, Bglap3, Col8a1, Hmgcr, Ero1lb, Ifi44l) were abnormal in the kidney. Several genes were related to metabolism and disease occurrence in the liver or kidney. Besides, we paid special attention to the expression of known imprinted genes and DNA methylation-related genes in adult organs, which are susceptible to oocyte cryopreservation in the preimplantation stage. As a result, some of these transcripts were detected in adult organs, but they were not affected by oocyte vitrification. In conclusion, we first report that oocyte vitrification did not significantly change the global gene expression in offspring organs; nonetheless, it can still influence the transcription of a few functional genes. The potential adverse effects caused by oocyte vitrification need attention and further study.

LncRNA NEAT1 affects endometrial receptivity by regulating HOXA10 promoter activity.

In vitro fertilization and embryo transfer (IVF-ET) is one of the effective methods to treat female infertility. Poor endometrial receptivity (ER) is an important factor leading to embryo implantation dysfunction, which can reduce pregnancy rate of IVF-ET. The mice model with embryo implantation dysfunction in vivo and attachment model of trophoblast (JAR) spheroids in vitro were constructed. The levels of lncRNA NEAT1, HOXA10, CTCF and markers of ER were detected. The cell proliferation was measured. The interaction between lncRNA NEAT1 and CTCF, HOXA10 promoter and CTCF were confirmed. LncRNA NEAT1 and HOXA10 levels in infertile patients and mice model with embryo implantation dysfunction were increased. In vitro experiments showed that down-regulation of lncRNA NEAT1 improved EECs proliferation and ER marker expressions. LncRNA NEAT1 could bind to CTCF, and CTCF could bind to HOXA10 promoter and down-regulate HOXA10 gene expression by regulating histone modification level. The lncRNA NEAT1/CTCF/HOXA10 signaling pathway regulated EECs proliferation and ER establishment in vitro and in vivo. Our study suggested that lncRNA NEAT1 could up-regulate HOXA10 promoter activity and its expression by combining with CTCF, thus improving EECs proliferation and ER establishment, and ultimately facilitating embryo implantation.

Novel exon mutation in SYCE1 gene is associated with non-obstructive azoospermia.

Non-obstructive azoospermia (NOA) is a common cause of male infertility, and genetic problems, such as chromosomal abnormalities and gene mutations, are important causes of NOA. Our centre received a case of NOA, in which no mature sperm was found during microdissection testicular sperm extraction. A postoperative pathological examination revealed that testicular spermatogenesis was blocked. Target region capture combined with high-throughput sequencing was used to screen for male infertility-related gene mutations. Sanger sequencing further confirmed that the SYCE1 gene, a central component of the synaptonemal complex (SC) during meiosis, had a homozygous deletion mutation in the tenth exon (c.689_690del; p.F230fs). Through molecular biological studies, we discovered altered expression and nuclear localization of the endogenous mutant SYCE1. To verify the effects in vitro, wild- and mutated-type SYCE1 vectors were constructed and transfected into a human cell line. The results showed that the expression and molecular weight were decreased for SYCE1 containing c.689_690del. In addition, mutated SYCE1 was abnormally located in the cytoplasm rather than in the nucleus. In summary, our research suggests that the novel homozygous mutation (c.689_690del; p.F230fs) altered the SYCE1 expression pattern and may have disturbed SC assembly, leading to male infertility and to a barrier to gamete formation. We reported for the first time that a frameshift mutation occurred in the exon region of SYCE1 in an NOA patient. This study is beneficial for accurate NOA diagnosis and the development of corresponding gene therapy strategies.

Tylvalosin Tartrate Improves the Health Status of Swine Herds during Immunization with Porcine Reproductive and Respiratory Syndrome Virus-Inactivated Vaccine.

Porcine reproductive and respiratory syndrome (PRRS) is a devastating disease that affects pigs and is responsible for severe economic losses. The commercial PRRSV-inactivated vaccine (CH-1a strain) in China was recently selected to control PRRS in large populations of PRRS-positive sows and was found to effectively reduce the rate of stillbirth abortion based on clinical observations. However, stress from vaccine inoculation (e.g., fever, anorexia, abortions, and slow body weight gain) usually appears after immunization on many swine farms. In this study, we fed piglets a diet medicated with tylvalosin tartrate during PRRSV-inactivated vaccine immunization. We found that tylvalosin tartrate attenuated the increase in total white blood cells induced by immunization at day one post-immunization (DPI) and induced an increase in monocyte counts after seven DPI. There was also attenuation in the intensity of the inflammatory response induced by vaccination and elevation of serum IFN-γ concentrations at three and seven DPI after immunization. The administration of tylvalosin tartrate could also attenuate the reduction in the percentage of CD8+ T cells induced by PRRSV-inactivated vaccine immunization at seven DPI. These results demonstrated that in addition to tylvalosin tartrate being able to control respiratory and enteric bacterial infections in swine farms, it can also improve the stress status of swine herds during PRRSV-inactivated vaccine immunization.

Relationships between plasma expression levels of microRNA-146a and microRNA-132 in epileptic patients and their cognitive, mental and psychological disorders.

We aimed to explore the relationships between the plasma expression levels of microRNA (miR)-146a and miR-132 in epileptic patients and cognitive, mental and psychological disorders. Eighty epileptic patients and seventy healthy subjects as controls were evaluated with Montreal Cognitive Assessment (MoCA), Hamilton Anxiety Rating (HAMA) and Hamilton Depression Rating (HAMD) scales, and plasma samples were collected. MiR-146a and miR-132 levels were detected by real-time quantitative PCR. The total incidence rate of cognitive dysfunction, anxiety and depression in epilepsy group was 62.5%. Cognitive dysfunction was correlated positively with educational level, but negatively with disease course, duration and type of administration. The frequency and duration of seizures were positively correlated with anxiety. Depression was correlated negatively with educational level, whereas positively with course of disease and number of used drugs. Epileptic patients had significantly higher miR-146a and miR-132 levels than those of healthy controls. The miR-146a and miR-132 levels of patients with complications were significantly higher than those of cases without complications. Their expressions were correlated negatively with total MoCA scale score, but positively with type of complications. MiR-132 expression was positively correlated with the total scores of HAMA and HAMD scales. Plasma miR-146a and miR-132 expressions increased in epileptic patients, and miR-132 expression reflected the severity of epilepsy and predicted the risks of complications.

Comparative Analysis of Acute Levodopa Challenge Test and the Outcomes of Deep Brain Stimulation in Parkinson's Disease.

BACKGROUND: We study the correlation between the preoperative levodopa challenge test and the efficacy of deep brain stimulation (DBS) surgery in Parkinson's disease (PD). METHODS: Fifty patients with PD who underwent DBS treatment in our hospital from October 2016 to October 2017 were enrolled in this study. Using the Unified Parkinson Disease Rating Scale-III (UPDRS-III) as an indicator, we analyzed the improvement in motor symptoms on the levodopa challenge test and by DBS surgery. We also discussed the correlation between the effects of the levodopa challenge test and DBS surgery. RESULTS: There was no correlation between the results of the levodopa challenge test and DBS surgery. There was a linear correlation between muscle rigidity and bradykinesia, whereas the linear correlation between other symptoms was weak. CONCLUSION: The levodopa challenge test can be used as a screening tool for patients undergoing DBS surgery, and can predict the degree of improvement in muscle rigidity and bradykinesia surgery. However, the prediction of the degree of improvement of total motor symptoms is poor.

Prevalence and associated factors of infertility among 20-49 year old women in Henan Province, China.

BACKGROUND: Infertility is a reproductive health problem which affects not only individuals, families and social populations. Recently, the infertility rate in China has a trend of increase year by year, and few studies have reported the infertility rate in Henan Province, China. The aim of this study was to investigate the current prevalence and associated factors of infertility among women of childbearing age in Henan Province, China. METHODS: This cross-sectional study was conducted from March 2019 to October 2019. We sampled 765 women who were 20-49 years old in eight hospitals of four cities in Henan Province, China. This survey included a questionnaire, physical examination, vaginal ultrasound examinations, and serum anti-Mullerian hormone (AMH) assessment, all of which were conducted under uniform standards by trained personnel. According to the data collected from questionnaire, participants were divided into infertile and fertile groups and analyzed associated factors. RESULTS: Among all the 765 participants in this study, the prevalence of infertility was 24.58%. The prevalence of primary infertility was 6.54%, and the prevalence of secondary infertility was 18.04%. In logistic multivariate regression analyses, infertility was associated with age (p < 0.001), history of gynecological surgery (p < 0.001), sweet food (p = 0.003) and decreased ovarian reserve (DOR) (p < 0.001). After further analyses, factors associated with primary infertility were age of marriage (p = 0.006), age of first sexual intercourse (p = 0.003), long-term air-conditioning environment (p < 0.001), decreased ovarian reserve (p = 0.005) and age (p = 0.002). And factors associated with secondary infertility were history of gynecological surgery (p < 0.001), decreased ovarian reserve (p = 0.002), waist-to-hip ratio (WHR) above 0.85 (p = 0.043), delivery times (p = 0.001) and ages (p < 0.001). CONCLUSION: The prevalence of infertility among women aged 20-49 was 24.58% and only 61.17% infertile women sought medical help in Henan Province, China. Age, history of gynecological surgeries and DOR may increase the risk of infertility. Local public health departments and medical professionals need to discharge their duty of reducing the high incidence of infertility and protecting women's reproductive health.

Infertility prevalence rate has increased in the past 30 years. Infertility plagues thousands of women of childbearing age. Although not life-threatening, the detrimental influence of infertility to patients, their families, and society should not be underestimated, especially in China. In order to investigate the prevalence of infertility, determine the associated factors, and promote disease prevention and treatment, we conducted a cross-sectional study among 20­49 year old women in Henan, one of the central provinces of China.This study distributed 920 questionnaires and collected 803 completed questionnaires. Interviews, questionnaires, and physical and ultrasound examinations were done.Among all the 765 participants in this study, the prevalence of infertility was 24.58%. The prevalence of primary infertility was 6.54%, and the secondary infertility was 18.04%. Age, history of gynecological surgeries and DOR may increase the risk of infertility.In conclusion, among women aged 20­49 years in Henan Province, China, the prevalence of infertility in 2019 was 24.58% and 61.17% of infertile women sought medical help.

A Multi-Phase Based Multi-Application Mapping Approach for Many-Core Networks-on-Chip.

More and more attention is being paid to the use of massive parallel computing performed on many-core Networks-on-Chip (NoC) in order to accelerate performance. Simultaneously deploying multiple applications on NoC is one feasible way to achieve this. In this paper, we propose a multi-phase-based multi-application mapping approach for NoC design. Our approach began with a rectangle analysis, which offered several potential regions for application. Then we mapped all tasks of the application into these potential regions using a genetic algorithm, and identified the one which exhibited the strongest performance. When the packeted regions for each application were identified, a B*Tree-based simulated annealing algorithm was used to generate the optimal placement for the multi-application mapping regions. The experiment results show that the proposed approach can achieve a considerable reduction in network power consumption (up to 23.45%) and latency (up to 24.42%) for a given set of applications.

Identification of small extracellular vesicle-linked miRNA specifically derived from intrafollicular cells in women with polycystic ovary syndrome.

RESEARCH QUESTION: This study aimed to identify small extracellular vesicle (sEV)-linked microRNAs (miRNA) specifically derived from intrafollicular cells in women with polycystic ovary syndrome (PCOS) and to investigate their biological functions. DESIGN: A total of 120 women were recruited from September 2017 to October 2018. To investigate miRNA profiles in sEV derived from follicular fluid and serum, 30 women with PCOS and 30 without PCOS were included for a miRNA microarray containing probes interrogating 2549 human miRNA. To study the expression levels of differentially expressed miRNA, sEV in follicular fluid obtained from another 30 PCOS and 30 non-PCOS patients were used for quantitative real-time polymerase chain reaction analysis. RESULTS: A total of 281 sEV-linked miRNA specifically derived from intrafollicular cells were identified, 179 of which were expressed in both the PCOS and non-PCOS groups. Twenty-six of the 179 intrafollicle-specific sEV-linked miRNA were predicted to target 1537 genes. Functional analysis suggested that these genes were involved in pathways related to folliculogenesis, including the MAPK, and PI3K-Akt signalling pathways. Quantitative real-time polymerase chain reaction analysis showed that the expression of seven intrafollicle-specific sEV-linked miRNA was significantly higher in follicular fluid-derived sEV in women with PCOS than in women without it. These miRNA and their corresponding target genes were identified as being involved in the MAPK signalling pathway and oocyte meiosis. CONCLUSIONS: The data suggest that the aberrantly expressed miRNA and their target genes might be associated with PCOS, providing novel insights into the molecular mechanisms underlying regulation of folliculogenesis and oocyte maturation in PCOS.

Strain Characterization of Streptococcus suis Serotypes 28 and 31, Which Harbor the Resistance Genes optrA and ant(6)-Ia.

Streptococcus suis causes disease in pigs and is implicated increasingly in human disease worldwide. Although most clinical cases are associated with serotype 2, infections by other serotypes have sometimes been reported. Here, we sequenced the genome of a multidrug-resistant S. suis serotype 28 (strain 11313) and a multidrug-resistant S. suis serotype 31 (strain 11LB5). Strain 11313 was apathogenic in mouse infection models, whereas strain 11LB5 displayed ganglion demyelination, meningeal thickening, congestion, mononuclear cell infiltration, massive proliferation of cortical glial cells, and bacteria (>104 CFU/g) in the spinal cord and ganglia in mice. Furthermore, immunohistochemistry found that the heavily infiltrated glial cells were astrocytes. Strain 11313 harbored the resistance genes ant(6)-Ia, erm(B), optrA, tet(l), tet(o), and strain 11LB5 harbored the resistance genes ant(6)-Ia, erm(B), tet(40), tet(o/w/32/o), aac(6')-aph(2″). Mouse studies showed that strain 11LB5 exhibited a similar virulence to serotype 2 strain 700794, highlighting the need for surveillance of the other serotype S. suis isolates, in addition to serotype 2, in farms. This is the first report of the aminoglycoside resistance gene ant(6)-Ia in S. suis from animals. This suggests that S. suis might serve as an antibiotic resistance reservoir, which spreads the resistance gene ant(6)-Ia or optrA to other streptococcal pathogens on farms.

The role of miRNAs in polycystic ovary syndrome with insulin resistance.

PURPOSE: This review aims to summarize the key findings of several miRNAs and their roles in polycystic ovary syndrome with insulin resistance, characterize the disease pathogenesis, and establish a new theoretical basis for diagnosing, treating, and preventing polycystic ovary syndrome. METHODS: Relevant scientific literature was covered from 1992 to 2020 by searching the PubMed database with search terms: insulin/insulin resistance, polycystic ovary syndrome, microRNAs, and metabolic diseases. References of relevant studies were cross-checked. RESULTS: The related miRNAs (including differentially expressed miRNAs) and their roles in pathogenesis, and possible therapeutic targets and pathways, are discussed, highlighting controversies and offering thoughts for future directions. CONCLUSION: We found abundant evidence on the role of differentially expressed miRNAs with its related phenotypes in PCOS. Considering the essential role of insulin resistance in the pathogenesis of PCOS, the alterations of associated miRNAs need more research attention. We speculate that race/ethnicity or PCOS phenotype and differences in methodological differences might lead to inconsistencies in research findings; thus, several miRNA profiles need to be investigated further to qualify for the potential therapeutic targets for PCOS-IR.

Amorphous manganese oxide as highly active catalyst for soot oxidation.

A series of highly active amorphous manganese oxide catalysts for soot combustion were synthesized using colloidal solution combustion synthesis (CSCS) method. The surface morphological and structural properties were systematically tested via various techniques: X-ray diffraction, N2 adsorption-desorption, temperature-programmed reduction, scanning electron microscopy, and X-ray photoelectron spectroscopy. Manganese precursors and calcination temperatures affect the crystal structure, redox properties, and surface properties of MnOx. With the calcination temperature increasing from 550 to 850 °C, the crystalline structure of manganese oxides changed from amorphous phase to crystal phase. In general, the amorphous MnOx with a hierarchical porous structure showed better catalytic activity for soot oxidation than the crystal ones (T10 as indicator), which can be ascribed to the improved low-temperature reducibility, more surface active oxygen species, and abundant surface Mn4+ ions. The presence of NO in O2 also promoted soot oxidation which follows the NO2-assisted mechanism. Our work may provide a rational comparison between high-efficient amorphous and crystal MnOx catalysts for soot oxidation.

Exosomes derived from human umbilical cord mesenchymal stem cells repair injured endometrial epithelial cells.

PURPOSE: To investigate whether exosomes derived from human umbilical cord mesenchymal stem cells (hucMSC-derived exosomes) can repair injured endometrial epithelial cells (EECs). METHODS: HucMSC-derived exosomes and mouse primary EECs were isolated and purified. EECs were exposed to oxygen and glucose deprivation for 2 h followed by reoxygenation to mimic injury. After oxygen and glucose deprivation/reoxygenation (OGD/R), hucMSC-derived exosomes were added to the EEC culture medium. After 24 h of co-treatment, cell viability and cell death were tested by 3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium assay and lactate dehydrogenase (LDH) assay, respectively. The expression of proinflammatory cytokines was tested by real-time PCR, enzyme-linked immunosorbent assay (ELISA), and Western blot to investigate the potential mechanism. RESULTS: Compared with the control group, 5, 10, and 15 µg/mL of hucMSC-derived exosomes significantly attenuated cell viability decrease and inhibited LDH release of injured EECs, but 1 µg/mL of hucMSC-derived exosomes had no effect on either cell viability or LDH release. Real-time PCR and ELISA analysis revealed that 10 µg/mL of hucMSC-derived exosomes significantly inhibited the release of interleukin-6 (IL-6) and interleukin-1 beta (IL-1ß) and increased tumor necrosis factor alpha (TNFA) in injured EECs. In addition, 10 µg/mL of hucMSC-derived exosomes significantly inhibited toll-like receptor 4 (TLR4) and v-rel reticuloendotheliosis viral oncogene homolog A (RelA) expression in injured EECs. CONCLUSIONS: In OGD/R-induced injured EECs, hucMSC-derived exosomes efficiently improved the cell viability, reduced cell death, and exhibited anti-inflammatory properties against OGD/R.

Silencing of microRNA-146a alleviates the neural damage in temporal lobe epilepsy by down-regulating Notch-1.

This study aimed to evaluate the specific regulatory roles of microRNA-146a (miRNA-146a) in temporal lobe epilepsy (TLE) and explore the related regulatory mechanisms. A rat model of TLE was established by intraperitoneal injection of lithium chloride-pilocarpine. These model rats were injected intracerebroventricularly with an miRNA-146a inhibitor and Notch-1 siRNA. Then, neuronal damage and cell apoptosis in the cornu ammonis (CA) 1 and 3 regions of the hippocampus were assessed. SOD and MDA levels in the hippocampus were detected by chromatometry, and IL-1ß, IL-6, and IL-18 levels were detected by ELISA. Then, we evaluated the expression levels of caspase-9, GFAP, Notch-1, and Hes-1 in the hippocampus. The interaction between Notch-1 and miRNA-146a was assessed by a dual luciferase reporter gene assay. A rat model of TLE was successfully established, which exhibited significantly increased miRNA-146a expression in the hippocampus. Silencing of miRNA-146a significantly alleviated the neuronal damage and cell apoptosis in the CA1 and CA3 regions of the hippocampus in TLE rats and decreased MDA, IL-1ß, IL-6, and IL-18 levels and increased SOD levels in the hippocampus of TLE rats. In addition, silencing of miRNA-146a significantly decreased the expression levels of caspase-9, GFAP, Notch-1, and Hes-1 in the hippocampus of TLE rats. Notch-1 was identified as a target of miRNA-146a and silencing of Notch-1 aggravated the neuronal damage in the CA1 and CA3 regions. Silencing of miRNA-146a alleviated the neuronal damage in the hippocampus of TLE rats by down-regulating Notch-1.