The crucial role of HFM1 in regulating FUS ubiquitination and localization for oocyte meiosis prophase I progression in mice.

BACKGROUND: Helicase for meiosis 1 (HFM1), a putative DNA helicase expressed in germ-line cells, has been reported to be closely associated with premature ovarian insufficiency (POI). However, the underlying molecular mechanism has not been clearly elucidated. The aim of this study was to investigate the function of HFM1 in the first meiotic prophase of mouse oocytes. RESULTS: The results suggested that the deficiency of HFM1 resulting in increased apoptosis and depletion of oocytes in mice, while the oocytes were arrested in the pachytene stage of the first meiotic prophase. In addition, impaired DNA double-strand break repair and disrupted synapsis were observed in the absence of HFM1. Further investigation revealed that knockout of HFM1 promoted ubiquitination and degradation of FUS protein mediated by FBXW11. Additionally, the depletion of HFM1 altered the intranuclear localization of FUS and regulated meiotic- and oocyte development-related genes in oocytes by modulating the expression of BRCA1. CONCLUSIONS: These findings elaborated that the critical role of HFM1 in orchestrating the regulation of DNA double-strand break repair and synapsis to ensure meiosis procession and primordial follicle formation. This study provided insights into the pathogenesis of POI and highlighted the importance of HFM1 in maintaining proper meiotic function in mouse oocytes.

Excessive fatty acids activate PRMT5/MDM2/Drosha pathway to regulate miRNA biogenesis and lipid metabolism.

BACKGROUND: Excessive fatty acids in the liver lead to the accumulation of lipotoxic lipids and then cellular stress to further evoke the related disease, like non-alcoholic fatty liver disease (NAFLD). As reported, fatty acid stimulation can cause some specific miRNA dysregulation, which caused us to investigate the relationship between miRNA biogenesis and fatty acid overload. METHODS: Gene expression omnibus (GEO) dataset analysis, miRNA-seq, miRNA cleavage assay, RT-qPCR, western blotting, immunofluorescence and co-immunoprecipitation (co-IP) were used to reveal the change of miRNAs under pathological status and explore the relevant mechanism. High fat, high fructose, high cholesterol (HFHFrHC) diet-fed mice transfected with AAV2/8-shDrosha or AAV2/8-shPRMT5 were established to investigate the in vivo effects of Drosha or PRMT5 on NAFLD phenotype. RESULTS: We discovered that the cleavage of miRNAs was inhibited by analysing miRNA contents and detecting some representative pri-miRNAs in multiple mouse and cell models, which was further verified by the reduction of the Microprocessor activity in the presence of palmitic acid (PA). In vitro, PA could induce Drosha, the core RNase III in the Microprocessor complex, degrading through the proteasome-mediated pathway, while in vivo, knockdown of Drosha significantly promoted NAFLD to develop to a more serious stage. Mechanistically, our results demonstrated that PA can increase the methyltransferase activity of PRMT5 to degrade Drosha through MDM2, a ubiquitin E3 ligase for Drosha. The above results indicated that PRMT5 may be a critical regulator in lipid metabolism during NAFLD, which was confirmed by the knocking down of PRMT5 improved aberrant lipid metabolism in vitro and in vivo. CONCLUSIONS: We first demonstrated the relationship between miRNA dosage and NAFLD and proved that PA can activate the PRMT5-MDM2-Drosha signalling pathway to regulate miRNA biogenesis.

A comprehensive metabolomics analysis of volatile and non-volatile compounds in matcha processed from different tea varieties.

Tea varieties play a crucial role on the quality formation of matcha. This research aimed to examine the impact of four specific tea plant varieties (Okumidori, Longjing 43, Zhongcha108, and E'Cha 1) on various aspects of matcha, including sensory evaluation, major components, color quality, volatile and non-volatile metabolomic profiles. The findings revealed that the levels of tea polyphenols, ester catechins, nonester catechins, and amino acids varied among these four varieties. Notably, 177 significant different metabolites, such as phenolic acids, flavonoids, tannins, alkaloids were identified among 1383 non-volatile compounds. In addition, 97 key aroma-active compounds were identified based on their odor activity value exceeding 1. Aldehydes, heterocyclic compounds, and ketones were closely associated with the formation of volatile metabolites. Overall, this study enhances our understanding of how different tea plant varieties impact the quality of matcha, and can provide valuable guidance for improving matcha varieties in a favorable direction.

Stem cell therapy for premature ovarian insufficiency: a systematic review and meta-analysis of animal and clinical studies.

PURPOSE: The aim of this systematic review and meta-analysis is to evaluate the efficacy of stem cell therapy in mouse models of POI and patients with POI. METHODS: The PubMed, Web of Science, and Embase databases were searched from inception to February 2022 for relevant animal and clinical studies. The reference lists of the included reviews were manually searched to identify additional eligible studies. Data were independently extracted by two investigators, and disagreements were resolved by discussion. SYRCLE's risk of bias tool and the MINORS tool were used to assess the quality of animal and clinical studies by two independent investigators. All statistical analyses were conducted using Review Manager 5.3 software. RESULTS: A total of twenty animal studies and six clinical studies were included in this meta-analysis. In animal studies, the results showed that stem cells could improve hormone levels, follicle count, estrous cycle and pregnancy outcome. For hormone levels, stem cells increased serum E2 and AMH levels and decreased serum FSH and LH levels compared with the control group (serum E2 level: SMD: 5.05, 95% CI 4.21-5.90, P < 0.00001; serum AMH level: SMD: 4.42, 95% CI 3.06-5.79, P < 0.00001; serum FSH level: SMD: - 3.79, 95% CI - 4.87 to -  2.70, P < 0.00001; serum LH level: SMD: - 1.31, 95% CI - 1.65 to - 0.96, P < 0.00001). All follicle counts, except for the antral follicle count, were significantly changed compared with the control group. (primordial follicle count: SMD: 4.61, 95% CI 3.65-5.56, P < 0.00001; primary follicle count: SMD: 3.35, 95% CI 1.08-5.63, P = 0.004; secondary follicle count: SMD: 3.23, 95% CI 1.92-4.55, P < 0.00001; total follicle count: SMD: 4.84, 95% CI 2.86-6.83, P < 0.00001; oocyte count: SMD: 7.56, 95% CI 5.92-9.20, P < 0.00001; atretic follicle count: SMD: - 1.79, 95% CI - 2.59 to - 1.00, P < 0.00001). For the estrous cycle, stem cell therapy increased the number of estrous cycles (WMD: 2.72, 95% CI 2.07-3.37, P < 0.00001) and decreased the duration of the estrous cycle (WMD: - 1.26, 95% CI - 1.84 to - 0.69, P < 0.0001) compared with the control group. For pregnancy outcomes, stem cell therapy increased the fertility rate (RR: 3.00, 95% CI 1.74-5.17, P < 0.0001) and litter size (WMD: 3.82, 95% CI 0.36-7.28, P = 0.03) compared with the control group. In animal studies, the asymmetric funnel plot of serum E2 and FSH levels indicated the possibility of publication bias. Unpublished and negative studies may be the source of publication bias. In clinical studies, the results showed that stem cell therapy could decrease serum FSH level (MD: - 30.32, 95% CI - 59.03 to - 1.01, P = 0.04) and increase AFC (MD: 1.07, 95% CI 0.70-1.43, P < 0.00001), pregnancy rate (RD: 0.19, 95% CI 0.04-0.34, P = 0.01) and live birth rate (RD: 0.19, 95% CI 0.07-0.31, P = 0.001) in POI patients. In addition, there was no significant difference in menstrual function regained (RD: 0.22, 95% CI - 0.03-0.46, P = 0.09), oocytes retrieved (MD: 1.00, 95% CI - 0.64-2.64, P = 0.23) and embryos (MD: 0.80, 95% CI - 0.15-1.76, P = 0.10) between different groups. CONCLUSION: This meta-analysis suggested that stem cell therapy might be effective in POI mouse models and patients and could be considered a potential treatment to restore fertility capability in POI patients.

MiR-337-3p improves metabolic-associated fatty liver disease through regulation of glycolipid metabolism.

Epigenetic regulations play crucial roles in the pathogenesis of metabolic-associated fatty liver disease; therefore, elucidating the biological functions of differential miRNAs helps us to understand the pathogenesis. Herein, we discovered miR-337-3p was decreased in patients with NAFLD from Gene Expression Omnibus dataset, which was replicated in various cell and mouse models with lipid disorders. Subsequently, overexpression of miR-337-3p in vivo could ameliorate hepatic lipid accumulation, reduce fasting blood glucose, and improve insulin resistance. Meanwhile, we determined miR-337-3p might influence multiple genes involved in glycolipid metabolism through mass spectrometry detection, bioinformatics analysis, and experimental verification. Finally, we selected HMGCR as a representative example to investigate the molecular mechanism of miR-337-3p regulating these genes, where the seed region of miR-337-3p bound to 3'UTR of HMGCR to inhibit HMGCR translation. In conclusion, we discovered a new function of miR-337-3p in glycolipid metabolism and that might be a new therapeutic target of MAFLD.

Suicidal ideation in Chinese patients with chronic schizophrenia: prevalence, clinical correlates, and relationship with alexithymia.

Suicidal ideation (SI) is common among people with schizophrenia. However, it has received less attention than suicide attempts (SA), especially in the Chinese population. Alexithymia is a well-established risk factor for SI across different populations. Nevertheless, very few studies evaluated their relationship in schizophrenia patients. We aimed to determine the prevalence and clinical correlates of SI and its relationship with alexithymia in 812 Chinese chronic schizophrenia inpatients. We assessed SI, clinical symptoms, and alexithymia by the Beck Scale for Suicidal Ideation, the Positive and Negative Syndrome Scale (PANSS), and the Toronto Alexithymia Scale, respectively. A multiple logistic regression model was conducted to identify independent correlates of SI. Receiver operating characteristic (ROC) curves and area under the curve (AUC) were performed to determine the ability of our model to distinguish between patients with and without SI. 10% (n = 84) reported current SI. Lifetime SA (OR, 4.68; 95% CI 2.76-7.94, p < 0.001), PANSS depressive factor (OR, 1.24; 95% CI 1.12-1.38, p < 0.001), PANSS positive subscale (OR, 1.055; 95% CI 1.004-1.108, p = 0.035), and difficulty identifying emotions (OR, 1.07; 95% CI 1.03-1.12, p = 0.002) were associated with SI. The AUC value was 0.80, indicating excellent distinguishing capabilities. Timely assessments of these factors may help identify schizophrenia patients who are at risk for SI.

CLPP inhibition triggers apoptosis in human ovarian granulosa cells via COX5A abnormality-Mediated mitochondrial dysfunction.

Premature ovarian insufficiency (POI) is characterized by early loss of ovarian function before the age of 40 years. It is confirmed to have a strong and indispensable genetic component. Caseinolytic mitochondrial matrix peptidase proteolytic subunit (CLPP) is a key inducer of mitochondrial protein quality control for the clearance of misfolded or damaged proteins, which is necessary to maintain mitochondrial function. Previous findings have shown that the variation in CLPP is closely related to the occurrence of POI, which is consistent with our findings. This study identified a novel CLPP missense variant (c.628G > A) in a woman with POI who presented with secondary amenorrhea, ovarian dysfunction, and primary infertility. The variant was located in exon 5 and resulted in a change from alanine to threonine (p.Ala210Thr). Importantly, Clpp was mainly localized in the cytoplasm of mouse ovarian granulosa cells and oocytes, and was relatively highly expressed in granulosa cells. Moreover, the overexpression of c.628G > A variant in human ovarian granulosa cells decreased the proliferative capacity. Functional experiments revealed that the inhibition of CLPP decreased the content and activity of oxidative respiratory chain complex IV by affecting the degradation of aggregated or misfolded COX5A, leading to the accumulation of reactive oxygen species and reduction of mitochondrial membrane potential, ultimately activating the intrinsic apoptotic pathways. The present study demonstrated that CLPP affected the apoptosis of granulosa cells, which might be one of the mechanisms by which CLPP aberrations led to the development of POI.

The benefits of hesperidin in central nervous system disorders, based on the neuroprotective effect.

Disorders of central nervous system (CNS) disorders are considered serious health issues. The most common CNS diseases include neurodegenerative diseases, mental disorders, demyelinating disease, ischemia-reperfusion injury, and neuroinflammation. As a natural phenolic compound, hesperidin is a flavanone glycoside with various biological effects. Increasing evidence show that the growth of CNS diseases is hindered by hesperidin. Here, we have reviewed the related literature on neuropharmacological mechanisms for the preventive and therapeutic effects of hesperidin on CNS diseases. Several cellular and animal models have been developed to evaluate the underlying neuropharmacological mechanisms of hesperidin. Additionally, clinical evidence has confirmed its neuroprotective function. Hesperidin exerts its neuroprotective properties by decreasing neuro-inflammatory and apoptotic pathways. Hesperidin function has been studied in preclinical models for CNS diseases, but little is known about its definite effect in humans. Hesperidin can effectively alleviate depression and improve cognition and memory. It is urgent to explore and discover clinical trials for further confirmation of the neuroprotective efficacy of hesperidin and to evaluate its safety profile.

Prevalence of non-alcoholic fatty liver disease in pediatric mental disorder inpatients: a tertiary mental health referral hospital study.

BACKGROUND AND AIM: Studies have revealed a high prevalence of non-alcoholic fatty liver disease (NAFLD) among adult patients with mental disorders, as well as its associate risk factors, however little is known about these in pediatric population. The aim of the present study is to investigate the prevalence of NAFLD in pediatric inpatients with mental disorder, as well as to explore the risk factors. METHODS: In this retrospective study, we included 1156 pediatric inpatients with mental disorder admitted to our hospital between January 2020 and December 2021, including inpatients with schizophrenia, bipolar disorder, depressive disorder and other mental disorders. Relevant clinical data were obtained from the electronic medical records. We calculated the prevalence rate of NAFLD, and compared NAFLD prevalence between gender, mental disorders types, antipsychotics use, and comorbidities. Multivariable logistic regression was used to examine risk factors associated with NAFLD. RESULTS: The prevalence of NAFLD in pediatric inpatients with mental disorders was 7.35% (85/1156). Patients with NAFLD had senior age than those without NAFLD (15.33±1.75 vs 14.21±1.95 year-old, P<0.001). The NAFLD prevalence in participants with schizophrenia (12.11%) was higher than in participants with bipolar disorder (8.45%), depressive disorder (7.06%) and other mental disorders (2.97%)(p=0.002). The NAFLD prevalence was higher in participants who used antipsychotics (8.70%) than those who didn't (5.45%) (p=0.038). Multivariate analysis revealed that senior age, body weight (overweight/obese) and dyslipidemia were independent risk factors for NAFLD in pediatric inpatients with mental disorders. CONCLUSIONS: The NAFLD prevalence was is higher in those patients with schizophrenia and receiving antipsychotic medication. Metabolic factors and longer evolution may explain these differences.

Prevalence of non-alcoholic fatty liver disease in pediatric mental disorder inpatients: a tertiary mental health referral hospital study

Background and aim: Studies have revealed a high prevalence of non-alcoholic fatty liver disease (NAFLD) among adult patients with mental disorders, as well as its associate risk factors, however little is known about these in pediatric population. The aim of the present study is to investigate the prevalence of NAFLD in pediatric inpatients with mental disorder, as well as to explore the risk factors. Methods: In this retrospective study, we included 1156 pediatric inpatients with mental disorder admitted to our hospital between January 2020 and December 2021, including inpatients with schizophrenia, bipolar disorder, depressive disorder and other mental disorders. Relevant clinical data were obtained from the electronic medical records. We calculated the prevalence rate of NAFLD, and compared NAFLD prevalence between gender, mental disorders types, antipsychotics use, and comorbidities. Multivariable logistic regression was used to examine risk factors associated with NAFLD. Results: The prevalence of NAFLD in pediatric inpatients with mental disorders was 7.35% (85/1156). Patients with NAFLD had senior age than those without NAFLD (15.33±1.75 vs 14.21±1.95 year-old, P<0.001). The NAFLD prevalence in participants with schizophrenia (12.11%) was higher than in participants with bipolar disorder (8.45%), depressive disorder (7.06%) and other mental disorders (2.97%)(p=0.002). The NAFLD prevalence was higher in participants who used antipsychotics (8.70%) than those who didn't (5.45%) (p=0.038). Multivariate analysis revealed that senior age, body weight (overweight/obese) and dyslipidemia were independent risk factors for NAFLD in pediatric inpatients with mental disorders. Conclusions: The NAFLD prevalence was is higher in those patients with schizophrenia and receiving antipsychotic medication. Metabolic factors and longer evolution may explain these differences (AU)

Use of an Application to Increase Self-Care Ability, Improve Quality of Life, and Decrease Stoma Complications in Patients With Ileocystoplasty or Ureterostomy Due to Bladder Cancer.

BACKGROUND: Quality of life for patients after ileocystoplasty or ureterostomy due to a urinary bladder neoplasm can be limited after discharge from the hospital. PURPOSE: To add the real-time communication ability of an application (app) to the daily care of this patient population to enhance communication between doctors and patients and provide improved nursing interventions, thus improving patients' self-care abilities and quality of life while decreasing stoma complications. METHODS: A total of 67 patients who underwent urinary tract diversion after total cystectomy were randomly divided into 2 groups. Patients in the control group (n = 32) received regular telephone follow-ups when they were discharged from the hospital, once a week for the first 2 months and then once a month for the next 22 months; patients in the intervention group (n = 35) used an app in addition to receiving regular telephone follow-ups. After 24 months of the intervention, multivariate analyses were conducted regarding self-care ability, complication rate, and quality of life. RESULTS: Self-care ability and quality of life scores in the intervention group were significantly improved during the 24-month period, and the complication rate was significantly reduced. CONCLUSION: Interaction via an app improved patients' self-care ability and quality of life. In addition, stoma complications were reduced. Future studies with larger sample sizes and patients of different ages are needed.

CSAD Ameliorates Lipid Accumulation in High-Fat Diet-Fed Mice.

Non-alcoholic fatty liver disease (NAFLD) is a chronic metabolic disease manifested in hepatic steatosis, inflammation, fibrosis, etc., which affects over one-quarter of the population around the world. Since no effective therapeutic drugs are available to cope with this widespread epidemic, the functional research of genes with altered expression during NAFLD helps understand the pathogenesis of this disease and the development of new potential therapeutic targets for drugs. In the current work, we discovered via the analysis of the Gene Expression Omnibus (GEO) dataset that cysteine sulfinic acid decarboxylase (CSAD) decreased significantly in NAFLD patients, which was also confirmed in multiple NAFLD mouse models (HFD-fed C57BL/6J, db/db and HFHFrHC-fed C57BL/6J mice). Next, CSAD's function in the progression of NAFLD was explored using AAV-mediated liver-directed gene overexpression in an HFD-fed mouse model, where the overexpression of CSAD in the liver could alleviate NAFLD-associated pathologies, including body weight, liver/body weight ratio, hepatic triglyceride and total cholesterol, and the degree of steatosis. Mechanically, we found that the overexpression of CSAD could increase the expression of some genes related to fatty acid ß-oxidation (Acad1, Ppara, and Acox1). Furthermore, we also detected that CSAD could improve mitochondrial injury in vitro and in vivo. Finally, we proposed that the effect of CSAD on lipid accumulation might be independent of the taurine pathway. In conclusion, we demonstrated that CSAD is involved in the development of NAFLD as a protective factor, which suggested that CSAD has the potential to become a new target for drug discovery in NAFLD.

Association between Folic Acid Supplementation and Hypertensive Disorder Complicating Pregnancy in Jiangsu Province: A Cross-Sectional Study.

Objectives: To investigate the association of folic acid (FA) supplementation with hypertensive disorder complicating pregnancy (HDCP) and preeclampsia in Jiangsu Province, China. Materials and Methods: In this cross-sectional study, a total of 10,662 women with infants born between January 2017 and December 2018 were enrolled in Jiangsu Province, China. Maternal women with and without FA supplement intake were compared in this study. FA supplementation included 0.4 mg FA (0.4 FA), multivitamins with 0.4 mg FA (multivitamin (MV)+0.4 FA), and multivitamins with 0.8 mg FA (MV + 0.8 FA). Associations between FA intake, FA supplement dose or duration, (MV + FA) dosage per weight, and HDCP were analysed using ANOVA, the chi-square test, and logistic regression analysis. Results: Over the study follow-up period, the incidences of HDCP and preeclampsia were 3.5%, 1.4%, and 2.2%, 0.6% in the non-FA supplementation and FA supplementation groups, but only 1.5% and 0.1% in the MV + 0.8 FA group in early pregnancy. Compared with the non-FA group, HDCP and preeclampsia had the lowest risk in the MV + 0.8 FA group among the seven FA supplementation groups (HDCP: RR = 0.42, 95% CI = 0.27-0.68, P=0.001; preeclampsia: RR = 0.09, 95% CI = 0.03-0.33, P=0.001) in early pregnancy. Compared with the 0.4 FA alone group, the risk of HDCP and preeclampsia in women taking MV + 0.8 FA was significantly reduced (RR = 0.60, 95% CI = 0.41-0.87, P=0.008; preeclampsia: RR = 0.18, 95% CI = 0.06-0.60, P=0.005) in early pregnancy. (MV + FA)/BMI supplementation was associated with the risk of HDCP in early pregnancy (P trend = 0.002). Conclusions: MV supplement with 0.8 mg FA during early pregnancy may be effective in reducing HDCP and preeclampsia risk. The study provided the viewpoint that (MV + FA)/BMI could be used as a reference for FA intake in pregnant women of different weights.

Association of methylenetetrahydrofolate reductase ( MTHFR ) gene polymorphisms (C677T and A1298C) with thyroid dysfunction: A meta-analysis and trial sequential analysis

ABSTRACT Recent studies have shown that two common methylenetetrahydrofolate reductase ( MTHFR ) gene polymorphisms (C677T and A1298C) might correlate with thyroid dysfunction, but the results remain inconsistent. We carried out a meta-analysis aiming to assess the relationship of both polymorphisms with thyroid dysfunction. The PubMed, EMBASE, CNKI (China National Knowledge Infrastructure), CBMdisc (China Biology Medicine disc), WeiPu and Wanfang databases were searched up to September 2021. Case-control and cohort studies on MTHFR polymorphism and thyroid dysfunction were identified. Eight studies from six publications were finally included in our meta-analysis, including 817 patients and 566 controls. After pooled analysis, we found that the MTHFR C677T polymorphism was associated with an increased risk of hypothyroidism (TT vs. CC+CT/recessive model: OR = 2.07, 95% CI: 1.02-4.20, P = 0.04; TT vs. CC/homozygote model: OR = 2.35, 95% CI: 1.13-4.86, P = 0.02), while trial sequential analysis (TSA) revealed that it could be a false positive result. The MTHFR A1298C polymorphism was related to a decreased risk of hypothyroidism (C vs. A/allele model: OR = 0.63, 95% CI: 0.44-0.92, P = 0.02; CC vs. AC+AA/recessive model: OR = 0.42, 95% CI: 0.22-0.79, P = 0.007; CC vs. AA/homozygote model: OR = 0.43, 95% CI: 0.25-0.85, P = 0.02), which was conclusive according to TSA. The results of this meta-analysis suggest that MTHFR A1298C seems to be a protective factor for hypothyroidism, while the MTHFR C677T polymorphism may be a risk factor. However, more well-designed studies with larger sample sizes are needed to obtain more reliable results of the association between the MTHFR C677T polymorphism and hypothyroidism.

Association of methylenetetrahydrofolate reductase (MTHFR) gene polymorphisms (C677T and A1298C) with thyroid dysfunction: A meta-analysis and trial sequential analysis.

Recent studies have shown that two common methylenetetrahydrofolate reductase (MTHFR) gene polymorphisms (C677T and A1298C) might correlate with thyroid dysfunction, but the results remain inconsistent. We carried out a meta-analysis aiming to assess the relationship of both polymorphisms with thyroid dysfunction. The PubMed, EMBASE, CNKI (China National Knowledge Infrastructure), CBMdisc (China Biology Medicine disc), WeiPu and Wanfang databases were searched up to September 2021. Case-control and cohort studies on MTHFR polymorphism and thyroid dysfunction were identified. Eight studies from six publications were finally included in our meta-analysis, including 817 patients and 566 controls. After pooled analysis, we found that the MTHFR C677T polymorphism was associated with an increased risk of hypothyroidism (TT vs. CC+CT/recessive model: OR = 2.07, 95% CI: 1.02-4.20, P = 0.04; TT vs. CC/homozygote model: OR = 2.35, 95% CI: 1.13-4.86, P = 0.02), while trial sequential analysis (TSA) revealed that it could be a false positive result. The MTHFR A1298C polymorphism was related to a decreased risk of hypothyroidism (C vs. A/allele model: OR = 0.63, 95% CI: 0.44-0.92, P = 0.02; CC vs. AC+AA/recessive model: OR = 0.42, 95% CI: 0.22-0.79, P = 0.007; CC vs. AA/homozygote model: OR = 0.43, 95% CI: 0.25-0.85, P = 0.02), which was conclusive according to TSA. The results of this meta-analysis suggest that MTHFR A1298C seems to be a protective factor for hypothyroidism, while the MTHFR C677T polymorphism may be a risk factor. However, more well-designed studies with larger sample sizes are needed to obtain more reliable results of the association between the MTHFR C677T polymorphism and hypothyroidism.

Corrigendum to: Emergence and evolution of highly pathogenic porcine epidemic diarrhea virus by natural recombination of a low pathogenic vaccine isolate and a highly pathogenic strain in the spike gene.

[This corrects the article DOI: 10.1093/ve/veaa049.].

Transcriptomic responses to aluminum stress in tea plant leaves.

Tea plant (Camellia sinensis) is a well-known Al-accumulating plant, showing a high level of aluminum (Al) tolerance. However, the molecular mechanisms of Al tolerance and accumulation are poorly understood. We carried out transcriptome analysis of tea plant leaves in response to three different Al levels (0, 1, 4 mM, for 7 days). In total, 794, 829 and 585 differentially expressed genes (DEGs) were obtained in 4 mM Al vs. 1 mM Al, 0 Al vs. 1 mM Al, and 4 mM Al vs. 0 Al comparisons, respectively. Analysis of genes related to polysaccharide and cell wall metabolism, detoxification of reactive oxygen species (ROS), cellular transport, and signal transduction were involved in the Al stress response. Furthermore, the transcription factors such as zinc finger, myeloblastosis (MYB), and WRKY played a critical role in transcriptional regulation of genes associated with Al resistance in tea plant. In addition, the genes involved in phenolics biosynthesis and decomposition were overwhelmingly upregulated in the leaves treated with either 0 Al and 4 mM Al stress, indicating they may play an important role in Al tolerance. These results will further help us to understand mechanisms of Al stress and tolerance in tea plants regulated at the transcriptional level.

Association of forkhead box P3 gene polymorphisms with premature ovarian insufficiency in Chinese women.

OBJECTIVE: Forkhead box P3 (FOXP3), a transcription factor, is regarding critical regulator of the function of regulatory T (Treg) cells and plays a crucial role in the development of autoimmune diseases. Premature ovarian insufficiency (POI) is an autoimmune disease; however, little is known about the association between FOXP3 variants and the susceptibility to POI. METHODS: Long-range polymerase chain reaction was used to analyze complete FOXP3 gene sequences from 153 patients with POI. The frequencies of genotypes and alleles of the FOXP3 gene were compared between patients with POI and 269 East Asian women from the Genome Aggregation (gnomAD) database. RESULTS: Forty-three single-nucleotide polymorphisms (SNPs) were detected, including 25 known SNPs and 18 novel SNPs. The genotype distributions and allele frequencies of two known SNPs (rs17847094 and rs76798919) and three novel SNPs (NC_000023.11:g.49112832G > A, NC_000023.11:g.49112833G > A, and NC_000023.11:g.49120479CT > C) were significantly different between the two groups. Linkage disequilibrium and haplotype analyses of the rs57734889, rs2232365, rs3761548, and rs34629506 SNPs in FOXP3 were performed and compared, and the high D' (standardized disequilibrium coefficients) value indicated that these polymorphisms may contribute to the risk of POI. CONCLUSIONS: This study is the first to show that genetic variants in the regulatory regions of FOXP3 play a vital role in idiopathic POI in the Chinese population.

Comparison between open reduction and internal fixation and minimally invasive surgery in management of Sanders type II calcaneal fracture: A randomized controlled trial protocol.

BACKGROUND: The minimally invasive surgery possesses an essential and growing function in treating the calcaneal fractures, but the related literature on this topic is limited. For our study, the main purpose was to compare the early prognosis of a group of the patients with Sanders type II fracture of calcaneus treated via minimally invasive surgery and open reduction and internal fixation (ORIF). METHODS: This is a prospective randomized controlled trial in the patients who suffer from displaced intra-articular calcaneal fractures. This current study was carried out in accordance with the guidelines of "CONSORT statement" for the randomized controlled studies. All patients were randomly assigned into 2 groups on the basis of a random number table, namely the minimally invasive treatment group and the ORIF group using conventional methods. Inclusion criteria included the followings: aged between 18 to 59 years old; closed and unilateral fracture; patients with displaced intra-articular calcaneal fracture (>2 mm) involving Sanders Type IIC and Type IIB; and patients have enough mental capacity to understand and answer questions in the evaluation scale. In the process of outpatient follow-up, the radiographs were taken at 1, 3, 6, and 12 months. The functional results involved the American Orthopaedic Foot and Ankle Score, Foot Function Index, and the pain score. CONCLUSIONS: This protocol will give us research directions in future work. TRIAL REGISTRATION: This study protocol was registered in Research Registry (researchregistry6261).

Efficacy of autologous platelet-rich plasma use for arthroscopic meniscal repair: A randomized trial protocol.

BACKGROUND: Meniscus tear is one of the most familiar orthopedic injury, and it is also the leading cause of the dysfunction of knee joint. Recent efforts to improve the success rate of the meniscus repair surgery involve the addition of platelet-rich plasma (PRP). The aim of our experiment is to assess the clinical effects of arthroscopic repair of meniscal tears without or with PRP. METHODS: This is a randomized and parallel-group superiority study. The study protocol is approved through the review committee of the corresponding institutions in PLA Army 80th Group Military Hospital. All patients will provide written informed consent to participate in the study. We implement our investigation on the basis of the ethical standards outlined in the Helsinki Declaration of 1964 and then report our outcomes according to the CONSORT statement of 2010. All the patients follow a same rehabilitation program. Patients are assessed at baseline (day before operation), 12 months and 24 months after the last time of injection; outcome assessments involve Ikeuchi score, Lysholm score, and the visual analogue scales for failure and pain rate. P value less than .05 indicates that there is statistical significance. RESULTS: We suppose that arthroscopic PRP repair of meniscus tears results in improved pain and functional results owing to the release of bioactive molecules that may affect the healing of meniscus. TRIAL REGISTRATION: This study protocol was registered in Research Registry (researchregistry6175).