Novel KCNQ2 missense variant expands the genotype spectrum of DEE7.

BACKGROUND: KCNQ is a voltage-gated K + channel that controls neuronal excitability and is mutated in epilepsy and autism spectrum disorder (ASD). We focus on the KV7.2 voltage-gated potassium channel gene (KCNQ2), which is known for its association with developmental delay and various seizures (including self-limited benign familial neonatal epilepsy and epileptic encephalopathy). But the pathogenicity of many variants remains unproven, potentially leading to misinterpretation of their functional consequences. METHODS: In this study, we studied a patient who visited Nanhua Hospital. Targeted next-generation sequencing and Sanger sequencing were used to identify the pathogenic variants. Meanwhile, computational models, including hydrogen bonding and docking analyses, suggest that variants cause functional impairment. In addition, functional validation was performed in the drosophila to further evaluate the missense variant in the KCNQ2 gene as the cause of this patient. RESULTS: A new missense variant in the KCNQ2 gene was identified: NM_172107.4:c.1007C > A(p.ALa336Glu), which resulted in the change from alanine to glutamate at amino acid position 336 in the KCNQ2 gene. After computational modeling, including hydrogen bond analysis and docking analysis, it is indicated that the variants cause functional impairment. Furthermore, RNAi-mediated KCNQ knockout in flies led to the onset of epileptic behavior, lifespan and climbing capacity were affected, expression of the normal human KCNQ2 rescues the in flies RNAi-mediated KCNQ knockout behavioral abnormalities. CONCLUSION: Our findings expands the genetic profile of KCNQ2 and enhances the genotype - phenotype link.

Critical thinking disposition of medical students in Anhui Province, China: a cross-sectional investigation.

OBJECTIVE: To investigate the critical thinking disposition of medical undergraduates. METHODS: This cross-sectional study was performed on 426 students from four majors, including preventive medicine, maternal and children's health care medicine, health inspection and quarantine, and food quality and safety. The survey was completed in May 2019 using the California Critical Thinking Dispositions Inventory-Chinese version (CTDI-CV). RESULTS: A total of 435 questionnaires were distributed and 426 valid questionnaires were collected, with an effective rate of 97.93%. The CTDI-CV overall average score was 262.02 ± 34.74 points indicating an ambivalent disposition in medical undergraduate students. Only one of the subscales (maturity in judgment) had mean scores of 43.35 ± 8.23 indicating the positive disposition of students. Among them, males scored 257.42 ± 35.06 lower than females' 264.82 ± 34.32, the difference was statistically significant. The target scores of preventive medicine, maternal and children's health medicine, health inspection and quarantine, and food quality and safety were 265.17 ± 30.10, 260.26 ± 37.05, 271.73 ± 33.55, and 252.11 ± 39.87, respectively. The difference was statistically significant. Among the three dimensions of seeking truth, open mind, and cognitive maturity, the scores of males were 38.26 ± 7.48, 38.78 ± 6.46 and 41.03 ± 8.69, which were lower than females' 39.97 ± 7.11, 40.48 ± 6.48 and 44.91 ± 7.60, respectively. The scores of food quality and safety students were 37.23 ± 7.08, 36.61 ± 7.41 and 40.57 ± 8.60, respectively, which were lower than the preventive medicine (39.98 ± 7.07, 40.60 ± 5.96 and 44.44 ± 6.97, respectively). CONCLUSION: Most medical students were found to have an ambivalent disposition which meant they were not disposed toward critical thinking. These findings suggested that more effective teaching methods should be taken to facilitate critical thinking disposition and problem-solving ability.

Environmental and occupational exposure to cadmium associated with male reproductive health risk: a systematic review and meta-analysis based on epidemiological evidence.

There is an abundance of epidemiological evidence and animal experiments concerning the correlation between cadmium exposure and adverse male reproductive health outcomes. However, the evidence remains inconclusive. We conducted a literature search from PubMed, Embase, and Web of Science over the past 3 decades. Pooled r and 95% confidence intervals (CIs) were derived from Cd levels of the type of biological materials and different outcome indicators to address the large heterogeneity of existing literature. Cd was negatively correlated with semen parameters (r = - 0.122, 95% CI - 0.151 to - 0.092) and positively correlated with sera sex hormones (r = 0.104, 95% CI 0.060 to 0.147). Among them, Cd in three different biological materials (blood, semen, and urine) was negatively correlated with semen parameters, while among sex hormones, only blood and urine were statistically positively correlated. In subgroup analysis, blood Cd was negatively correlated with semen density, sperm motility, sperm morphology, and sperm count. Semen Cd was negatively correlated with semen concentration. As for serum sex hormones, blood Cd had no statistical significance with three hormones, while semen Cd was negatively correlated with testosterone. In summary, cadmium exposure might be associated with the risk of a decline in sperm quality and abnormal levels of sex hormones.

Vitamin C supplementation rescued meiotic arrest of spermatocytes in Balb/c mice exposed to BDE-209.

Deca-brominated diphenyl ether (BDE-209) is a ubiquitous industrial chemical as brominated flame retardant (BFRs). Exposure to BDE-209 has been clearly associated with male reproductive disorders. However, the meiotic arrest mechanism of spermatocytes exposed to BDE-209 is still unclear. The present work aimed to explore the protective effect of vitamin C on BDE-209-induced meiotic arrest of spermatocytes and its possible mechanism. Vitamin C (100 mg/kg BW) was administered to BDE-209-exposed (80 mg/kg BW) male Balb/c mice once daily by intraperitoneal injection for 2 weeks. Our results showed that vitamin C played male reproductive protection effects as showed by attenuated BDE-209-induced testicular damage, and reduced sperm abnormality rate. Vitamin C also attenuated BDE-209-induced increase in SOD and MDA in testes and GC-2 spd cells. Moreover, vitamin C promoted meiotic prophase in BDE-209-induced mice, with suppressed γ-H2AX, restored DMC1, RAD51, and crossover marker MLH1 levels, and prevented BDE-209-induced DNA impairment. In addition, vitamin C supplementation also interfered with BDE-209-induced upregulation of testicular H3K4me3 through inhibition of KDM5s capacity and decreasing ferrous ion concentration. Furthermore, ferrous sulfate pretreatment could partially restore the expression of H3K4me3 via maintaining the concentration of ferrous ions. Taken together, vitamin C exerts a potential therapeutic agent for preventing BDE-209-induced reproductive toxicity with meiotic arrest, which is attributed to its antioxidant and electron donor properties, as well as, modulation of ferrous ion levels and demethylation of H3K4me3.

Impact of ambient temperature on hospital admissions for cardiovascular disease in Hefei City, China.

Many studies have quantified the hospitalization risk for cardiovascular disease (CVD) caused by temperature, but the results of most studies are not consistent. In this study, we evaluate the effect of temperature on CVD hospitalizations. We use a quasi-Poisson regression with a distributed-lag nonlinear model (DLNM) to evaluate the effect of temperature on CVD hospitalizations between July 1, 2015, and October 31, 2017, in Hefei City, China. We found that the cold effect and heat effect of temperature can impact CVD hospital admissions. Compared with the 25th percentile of temperature (10.3 °C), the cumulative relative risk (RR) of extremely low temperature (first percentile of temperature, 0.075 °C) over lags 0-27 days was 0.616 (95% CI 0.423-0.891), and the cumulative RR of moderate low temperature (10th percentile of temperature, 5.16 °C) was 1.081 (95% CI 1.019-1.147) over lags 0-7 days. Compared with the 75th percentile of temperature (25.6 °C), the cumulative RR of extremely high temperature (99th percentile of temperature, 33.7 °C) was 1.078 (95% CI 0.752-1.547) over lags 0-27 days, and the cumulative RR of moderate-high temperature (90th percentile of temperature, 29.0 °C) was 1.015 (95% CI 0.988-1.043) over lag 0 day. In the subgroup, the < 65-year group and male were more susceptible to low temperature; however, the ≥ 65-year group and female were more vulnerable to high temperature. The high temperature's impact on CVD hospital admissions was found to be more obvious in female and the ≥ 65-year group compared to male and the < 65-year group. However, the < 65-year group and men are more sensitive to low temperature.

Effects of diurnal temperature range on mortality in Hefei city, China.

Although several studies indicated an association between diurnal temperature range (DTR) and mortality, the results about modifiers are inconsistent, and few studies were conducted in developing inland country. This study aims to evaluate the effects of DTR on cause-specific mortality and whether season, gender, or age might modify any association in Hefei city, China, during 2007-2016. Quasi-Poisson generalized linear regression models combined with a distributed lag non-linear model (DLNM) were applied to evaluate the relationships between DTR and non-accidental, cardiovascular, and respiratory mortality. We observed a J-shaped relationship between DTR and cause-specific mortality. With a DTR of 8.3 °C as the reference, the cumulative effects of extremely high DTR were significantly higher for all types of mortality than effects of lower or moderate DTR in full year. When stratified by season, extremely high DTR in spring had a greater impact on all cause-specific mortality than other three seasons. Male and the elderly (≥ 65 years) were consistently more susceptible to extremely high DTR effect than female and the youth (< 65 years) for non-accidental and cardiovascular mortality. To the contrary, female and the youth were more susceptible to extremely high DTR effect than male and the elderly for respiratory morality. The study suggests that extremely high DTR is a potential trigger for non-accidental mortality in Hefei city, China. Our findings also highlight the importance of protecting susceptible groups from extremely high DTR especially in the spring.

[The mechanisms of hippocampal neurons exposed to PBDE-209 induce oxidative stress and apoptosis].

OBJECTIVE: To determine the potential mechanisms of PBDE-209 induce apoptosis of the hippocampal neurons. METHODS: The primary fetal hippocampal neurons and hippocampus neurons cell line HT-22 were exposed to the concentrations of 0( solvent control), 6. 25, 12. 5, 25, 50 and 100 µg/mL PBDE-209 for 24 h. The SOD activity, MDA, NO and GSH contents in primary fetal hippocampal neurons were examined. The apoptosis of hippocampus neurons cell line HT-22 was observed using Annexin V/PI. The expressions of Bax, Bcl-2, CHOP, GRP78, PERK, Caspase-12 were measured by Western blot. RESULTS: The results showed that the difference was significant( P < 0. 05)of neuronal survival between the experimental groups and control groups and the difference was more obvious with the increasing dose of PBDE-209 which was observed in primary fetal hippocampal neurons and HT-22 cell lines. The increasing of Bax/Bcl-2( P < 0. 05), expression of CHOP and Caspase-12 in primary fetal hippocampal neurons( P < 0. 05), malondialdehyde( MDA) content and NO content( P < 0. 01) were also observed. Additionally, the results also indicated that PBDE-209 deceased activity of superoxidedismutase( SOD) and glutathione( GSH)( P < 0. 05). Meanwhile, the experiments of the HT-22 cell line showed that PBDE-209 could increase the expression of GRP78, PERK and Caspase-12 and apoptosis. CONCLUSION: The oxidative stress and endoplasmic reticulum stress may involve in the apoptosis of nerve cells caused by PBDE-209.

[Protective effects of n-acetylcysteine against decabromodiphenyl ether-induced brain oxidative injury in mice].

OBJECTIVE: To study the protective effects of N-acetylcysteine (NAC) against oxidative injury in the brain tissue of mice induced by decabromodiphenyl ether (PBDE-209) and the expression of mitogen activated protein kinase (MAPK)-related proteins in the hippocampus. METHODS: Twenty-one male BALB/c mice were randomly divided into three groups with seven mice in each group: solvent control group, PBDE-209 group with gavage of 500 mg/kg PBDE-209, and PBDE-209 +NAC group which received intraperitoneal injection of 100 mg/kg NAC 0.5 h before exposure to PBDE-209. Mice were sacrificed 6 weeks after exposure. Malondialdehyde (MDA) level, superoxide dismutase (SOD) activity, and glutathione (GSH) level in the cerebral cortex, hippocampus, cerebellum, and striatum, as well as the protein expression of extracellular signal-regulated kinase (ERK), phosphorylated ERK (p-ERK), p38 MAPK (p38), and phosphorylated p38 (p-p38) in the hippocampus, were determined by Western blot. RESULTS: Compared with the hippocampal and cerebellar levels of MDA in control group [(4.91±1.60) and (2.42±1.41) nmol/mg pro] and PBDE-209+NAC group [(6.16±1.03) and (2.83±0.85) nmol/mg pro], the MDA levels in PBDE-209 group [(12.12±6.39) and (4.24±1.15) nmol/mg pro] were significantly increased (P < 0.05). The striatum MDA level in PBDE-209 group [(12.92±4.30) nmol/mg pro] was significantly increased as compared with that of the control group [(4.05±2.23) nmol/mg pro] (P < 0.05). The hippocampal SOD activity of PBDE-209 group [(59.29±37.09) U/mg pro] was reduced significantly as compared with those of the control group [(93.28±21.75) U/mg pro] and PBDE-209+NAC group [(98.92±21.54) U/mgpro] (P < 0.05). The GSH levels in the cerebral cortex, striatum, and cerebellum in PBDE-209 group [(40.98±13.19), (24.46±11.30), and (3.55±1.55) mg GSH/g pro] were significantly reduced as compared with those of the control group [(75.79±26.51), (44.52±13.15) and (8.01±3.23) mg GSH/g pro] and the PBDE-209+NAC group [(89.86±28.39), (39.01±9.05) and (10.34±2.58) mg GSH/g pro] (P < 0.05). Western blot results showed that the ratios of p-p38/p38 and p-ERK/ERK in the hippocampus were significantly higher in the PBDE-209 group than in the control group and PBDE-209+NAC group (P < 0.05). CONCLUSION: Antioxidant NAC has a protective effect against PBDE-209-induced brain injury in mice to some extent, and reduces the expression of MAPK-related proteins.

Lipid metabolism: Novel approaches for managing idiopathic epilepsy.

Epilepsy is a common neurological condition characterized by abnormal neuronal activity, often leading to cellular damage and death. There is evidence to suggest that lipid imbalances resulting in cellular death play a key role in the development of epilepsy, including changes in triglycerides, cholesterol, sphingolipids, phospholipids, lipid droplets, and bile acids (BAs). Disrupted lipid metabolism acts as a crucial pathological mechanism in epilepsy, potentially linked to processes such as cellular ferroptosis, lipophagy, and immune modulation of gut microbiota (thus influencing the gut-brain axis). Understanding these mechanisms could open up new avenues for epilepsy treatment. This study investigates the association between disturbances in lipid metabolism and the onset of epilepsy.

Research progress on the relationship between epilepsy and circRNA.

OBJECTIVE: This review aims to provide a comprehensive summary of the latest research progress regarding the relationship between epilepsy and circular RNA (circRNA). METHODS: Relevant literature from the PubMed database was meticulously searched and reviewed. The selected articles focused on investigating the association between epilepsy and circRNA, including studies on expression patterns, diagnostic markers, therapeutic targets, and functional mechanisms. RESULTS: Epilepsy, characterized by recurrent seizures, is a neurological disorder. Numerous studies have demonstrated significant alterations in the expression profiles of circRNA in epileptic brain tissues, animal models, and peripheral blood samples. These differential expressions of circRNA are believed to be closely linked with the occurrence and development of epilepsy. Moreover, circRNA has shown promising potential as diagnostic markers for epilepsy, as well as prognostic indicators for predicting disease outcomes. Furthermore, circRNA has emerged as a potential therapeutic target for epilepsy treatment, offering prospects for gene therapy interventions. CONCLUSION: The dysregulation of circRNA expression in epilepsy suggests its potential involvement in the pathogenesis and progression of this disorder. Identifying specific circRNA molecules associated with epilepsy may pave the way for novel diagnostic approaches and therapeutic strategies. However, further investigations are imperative to elucidate the precise functional mechanisms of circRNA in epilepsy and validate its clinical utility.

Comparison of the impact of team-based learning and lecture-based learning on nursing students' core competencies: A systematic review and meta-analysis.

AIM: This study aims to evaluate the effect of team-based learning on the core competence of nursing students compared with traditional teaching methods. BACKGROUND: In recent years, team-based learning has been widely used as a learning and teaching method in the world. Not only the necessary knowledge, skills and attitudes, but also the core competence is necessary to cope with various clinical situations for nursing students. However, the effect of this new teaching method on core competence of nursing students is not consistent. DESIGN: The study was designed according to the preferred reporting entries guidelines statement for systematic reviews and meta-analyses and population, intervention, comparison, outcome and study. METHODS: Data were collected from PubMed, Embase, Web of Science, ScienceDirect and Scopus. The quality of studies was assessed using "The Newcastle Ottawa scale". A random-effect model of meta-analyses was conducted to generate pooled standardized mean differences (SMD) for core competence using Rev Man 5.4.1 software and STATASE 15. Moreover, subgroup, heterogeneity, sensitivity and publication bias analyses were conducted. RESULTS: A total of 14 articles with 1942 participants were included in the meta-analysis. Compared with the traditional pedagogy among nursing students, team-based learning pedagogy significantly increased theoretical performance, professional effects (self-directed learning ability and communication ability) but did not affect practice skills. In addition, one study found that learning attitudes were not improved in students with high or low academic performance. This might mean that the teaching model should be implemented for a long time, which essentially changed students' learning attitudes to improve students' self-directed learning ability and core competence, especially for students with low scores. CONCLUSIONS: In summary, findings indicated that team-based learning pedagogical approaches might be beneficial to improve teaching quality in nursing education. However, practice skills might not be sensitive to team-based learning because of the seriation of the original course. Nursing educators need to explore teaching strategies to cultivate high-quality nursing talents to cultivate nursing students with core competence and ensure that they are successfully qualified for new employment.

NIR-responsive micropatterned nanocomposite functionalized implant for sequential antibacterial and osteogenesis.

The long-term durability of the implant is influenced by two significant clinical challenges, namely bacterial infection and fixation loosening. Conventional implant materials have failed to meet the demands of the dynamic process of infectious bone repair, which necessitates early-stage bacterial sterilization and a conducive environment for late-stage osteogenesis. Consequently, there is an urgent requirement for an implant material that can sequentially regulate antibacterial properties and promote osteogenesis. The study aimed to develop a micropatterned graphene oxide nanocomposite on titanium implant (M-NTO/GO) for the sequential management of bacterial infection and osteogenic promotion. M-NTO/GO exhibited a micropattern nanostructure surface and demonstrated responsiveness to near-infrared (NIR) light. Upon NIR light irradiation, M-NTO/GO exhibited effective antibacterial properties, achieving antibacterial rates of 96.9% and 98.6% against E. coli and S. aureus, respectively. Under no-light condition, the micropatterned topography of M-NTO/GO exhibited the ability to induce directed cell growth, enhance cell adhesion and spreading, and facilitate osteogenic differentiation. These findings suggest the successful development of a functionalized micropatterned nanocomposite implant capable of sequentially regulating antibacterial and osteogenesis activity. Consequently, this highly effective strategy holds promise for expanding the potential applications of orthopedic implants.

Hydrogel Coatings of Implants for Pathological Bone Repair.

Hydrogels are well-suited for biomedical applications due to their numerous advantages, such as excellent bioactivity, versatile physical and chemical properties, and effective drug delivery capabilities. Recently, hydrogel coatings have developed to functionalize bone implants which are biologically inert and cannot withstand the complex bone tissue repair microenvironment. These coatings have shown promise in addressing unique and pressing medical needs. This review begins with the major functionalized performance and interfacial bonding strategy of hydrogel coatings, with a focus on the novel external field response properties of the hydrogel. Recent advances in the fabrication strategies of hydrogel coatings and their use in the treatment of pathologic bone regeneration are highlighted. Finally, challenges and emerging trends in the evolution and application of physiological environment-responsive and external electric field-responsive hydrogel coatings for bone implants are discussed.

Piezo-enhanced near infrared photocatalytic nanoheterojunction integrated injectable biopolymer hydrogel for anti-osteosarcoma and osteogenesis combination therapy.

Preventing local tumor recurrence while promoting bone tissue regeneration is an urgent need for osteosarcoma treatment. However, the therapeutic efficacy of traditional photosensitizers is limited, and they lack the ability to regenerate bone. Here, a piezo-photo nanoheterostructure is developed based on ultrasmall bismuth/strontium titanate nanocubes (denoted as Bi/SrTiO3), which achieve piezoelectric field-driven fast charge separation coupling with surface plasmon resonance to efficiently generate reactive oxygen species. These hybrid nanotherapeutics are integrated into injectable biopolymer hydrogels, which exhibit outstanding anticancer effects under the combined irradiation of NIR and ultrasound. In vivo studies using patient-derived xenograft models and tibial osteosarcoma models demonstrate that the hydrogels achieve tumor suppression with efficacy rates of 98.6 % and 67.6 % in the respective models. Furthermore, the hydrogel had good filling and retention capabilities in the bone defect region, which exerted bone repair therapeutic efficacy by polarizing and conveying electrical stimuli to the cells under mild ultrasound radiation. This study provides a comprehensive and clinically feasible strategy for the overall treatment and tissue regeneration of osteosarcoma.

Reprint of: Recessive APC2 missense variants associated with epilepsies without neurodevelopmental disorders.

OBJECTIVES: The APC2 gene, encoding adenomatous polyposis coli protein-2, is involved in cytoskeletal regulation in neurons responding to endogenous extracellular signals and plays an important role in brain development. Previously, the APC2 variants have been reported to be associated with cortical dysplasia and intellectual disability. This study aims to explore the association between APC2 variants and epilepsy. METHODS: Whole-exome sequencing (WES) was performed in cases (trios) with epilepsies of unknown causes. The damaging effects of variants were predicted by protein modeling and in silico tools. Previously reported APC2 variants were reviewed to analyze the genotype-phenotype correlations. RESULTS: Four pairs of compound heterozygous missense variants were identified in four unrelated patients with epilepsy without brain malformation/intellectual disability. All variants presented no or low allele frequencies in the controls. The missense variants were predicted to be damaging by silico tools, and affect hydrogen bonding with surrounding amino acids or decreased protein stability. Patients with variants that resulted in significant changes in protein stability exhibited more severe and intractable epilepsy, whereas patients with variants that had minor effect on protein stability exhibited relatively mild phenotypes. The previously reported APC2 variants in patients with complex cortical dysplasia with other brain malformations-10 (CDCBM10; MIM: 618677) were all truncating variants; in contrast, the variants identified in epilepsy in this study were all missense variants, suggesting a potential genotype-phenotype correlation. SIGNIFICANCE: This study suggests that APC2 is potentially associated with epilepsy without brain malformation/intellectual disability. The genotype-phenotype correlation helps to understand the underlying mechanisms of phenotypic heterogeneity.

CTLA-4 polymorphisms and systemic lupus erythematosus (SLE): a meta-analysis.

The aim of this study was to summarize results on the association of cytotoxic T-lymphocyte antigen-4 (CTLA-4) promoter exon-1 +49 and 1722T/C polymorphism with systemic lupus erythematosus (SLE) susceptibility by using the meta-analysis. We searched all the publications about the association between CTLA-4) promoter exon-1 +49 and 1722T/C polymorphism and SLE from PubMed, Elsevier Science Direct, Chinese Biomedical Literature Database (CBM), Chinese National Knowledge Infrastructure (CNKI), and Wanfang (Chinese). Previous CTLA-4 association studies with SLE, however, have produced inconsistent results. We have performed a meta-analysis to better assess the purported associations. A total of 17 independent studies (to June 2012) testing association between one or more CTLA-4 polymorphisms and SLE were used in this analysis. We have compared allele and genotype frequencies at two polymorphic sites found in exon-1 (at +49) and the promoter region (at -1722). The data demonstrate that the exon-1 +49 polymorphism is associated with SLE susceptibility in Asian population. The overall risk, measured by odds ratio (OR), stratification by ethnicity indicates the exon-1 +49 GG+GA genotype is associated with SLE, at least in Asians (OR = 0.85, 95 % CI = 0.73-0.99, P = 0.04 for GG+GA vs. AA; OR = 0.85, 95 % CI = 0.72-1.00, P = 0.05 for AG vs. AA). Similar trends are found in allele-specific risk estimates and disease association. Overall, there was significant association between the 1722T/C polymorphism and overall SLE risks (OR = 0.78, 95 % CI = 0.63-0.97, P = 0.04 for GG+GA vs. AA, OR = 0.87, 95 % CI = 0.76-0.99, P = 0.04 for G vs. A) in Asian population.In summary, this meta-analysis demonstrates that the CTLA-4 promoter +49A/G and promoter -1722C/T polymorphism may confer susceptibility to SLE, especially in Asian-derived population.

Polychlorinated biphenyls and risk of metabolic syndrome and comparison with the risk of diabetes: A systematic review and meta-analysis.

With the increasing incidence of metabolic syndrome (MetS) worldwide and no consistent results on PCBs and MetS. A meta-analysis to explore their relationship was conducted. Given the high correlation and overlap of MetS with diabetes, analysis of diabetes risk, was used as a supplement to compare with MetS. Seven studies included MetS, 15 studies for diabetes, and one study included both outcomes. It was found that PCBs may not be a risk factor for MetS, but their high heterogeneity indicates that they are under-represented. In addition, our results showed that total PCBs might be a protective factor against diabetes. In the whole blood subgroup, which can reflect the accumulation of more than one body load, heterogeneity was reduced, and its OR value suggested that PCBs increased the risk of MetS in the whole blood biomaterial. DL-PCBs were positively associated with MetS and diabetes, while NDL-PCBs were negatively associated with diabetes. In the subgroup analysis of PCBs homologs, DL-PCB-126 and DL-PCB-118 were risk factors for MetS and diabetes, respectively. In addition, PCB-153 and 180 showed a dose-response relationship between them and diabetes mellitus, respectively. The results of total analysis of MetS and diabetes mellitus and subgroup analysis of PCBs were mixed, and this reason might be attributed to the different mechanisms of action and effect sizes of different PCBs, so based on subgroup results and in vivo and in vitro experiments, we considered PCBs to be a risk factor for MetS and diabetes. Due to various reasons, there are still many shortcomings in the evaluation of PCBs impact on human health, and more high-quality research are needed to further explore the role of PCBs of different species and congeners in MetS and diabetes.

Do phthalates and their metabolites cause poor semen quality? A systematic review and meta-analysis of epidemiological studies on risk of decline in sperm quality.

A systematic review and meta-analysis were conducted to understand the association of phthalates and their metabolites with sperm quality in humans. By June 30, 2022, relevant literature on the effects of phthalates and their metabolites on sperm quality were searched and collected using three English-language databases including PubMed, EMbase, and Web of Science. Two researchers independently screened literature, extracted data, and assessed risk of bias. Stata 11 and RevMan 5.3 were used to conduct meta-analysis, test publication bias, and sensitivity analysis. A total of 12 literature were included for meta-analysis, excluding literature with different effect sizes. The results of meta-analysis indicated that monobutyl phthalate (MBP) and monobenzyl phthalate (MBzP) in urine were negatively correlated with semen concentration, and the results were statistically significant (MBP, pooled odds ratio (OR), 95% confidence interval (CI): 2.186 (1.471, 3.248), P < 0.05) and (MBzP, pooled OR (95%CI): 1.882 (1.471, 3.248), P < 0.05). Furthermore, the level of Di-(2-ethylhexyl) phthalate (DEHP) in semen was negatively correlated with semen concentration and the combined effect size was (pooled correlation coefficients (r) (95%CI): -0.225 (-0.319, -0.192), P < 0.05). However, the associations between MBP and MBzP with sperm motility and sperm morphology were not statistically significant (P > 0.05). And there was also no significant correlation between monoethyl phthalate (MEP), monomethyl phthalate (MMP), and mono-2-ethylhexyl phthalate (MEHP) and semen parameters, including semen concentration, sperm motility, and sperm morphology (P > 0.05). In summary, this current study provides moderate-certainty evidence for the data demonstrated that is a negative correlation between urine MBP levels, urine MBzP levels, and semen DEHP levels with semen concentration. In the future, more longitudinal cohort studies are needed to help elucidate the overall association.

N-acetylcysteine rescues meiotic arrest during spermatogenesis in mice exposed to BDE-209.

Deca-bromodiphenyl ethers (BDE-209) has been widely used in electronic devices and textiles as additives to flame retardants. Growing evidence showed that BDE-209 exposure leads to poorer sperm quality and male reproductive dysfunction. However, the underlying mechanisms of BDE-209 exposure caused a decline in sperm quality remains unclear. This study aimed to evaluate the protective effects of N-acetylcysteine (NAC) on meiotic arrest in spermatocytes and decreased sperm quality in BDE-209-exposed mice. In the study, mice were treated with NAC (150 mg/kg BW) 2 h before administrated with BDE-209 (80 mg/kg BW) for 2 weeks. For the in vitro studies, spermatocyte cell line GC-2spd cells were pretreated with NAC (5 mM) 2 h before treated with BDE-209 (50 µM) for 24 h. We found that pretreatment with NAC attenuated the oxidative stress status induced by BDE-209 in vivo and in vitro. Moreover, pretreatment with NAC rescued the testicular histology impairment and decreased the testicular organ coefficient in BDE-209-exposed mice. In addition, NAC supplement partially promoted meiotic prophase and improved sperm quality in BDE-209-exposed mice. Furthermore, NAC pretreatment effectively improved DNA damage repair by recovering DMC1, RAD51, and MLH1. In conclusion, BDE-209 caused spermatogenesis dysfunction related to the meiotic arrest medicated by oxidative stress, decreasing sperm quality.

Gut Microbiota Metabolites Mediate Bax to Reduce Neuronal Apoptosis via cGAS/STING Axis in Epilepsy.

The beneficial effects of gut flora on reducing nerve cell apoptosis and inflammation and improving epilepsy (EP) symptoms have been reported, but the specific mechanism of action is still unclear. A series of in vitro and in vivo experiments revealed the relationship between gut microbiota metabolites and the cGAS/STING axis and their role in EP. These results suggest that antibiotic-induced dysbiosis of gut microbiota exacerbated epileptic symptoms, probiotic supplements reduced epileptic symptoms in mice. Antibiotics and probiotics altered the diversity and composition of gut microbiota. The changes in gut bacteria composition, such as in the abundance of Firmicutes, Bacteroidetes, Lactobacillus and Ruminococcus, were associated with the production of short-chain fatty acids (SCFA) in the gut. The concentrations of propionate, butyrate and isovalerate were changed after feeding antibiotics and probiotics, and the increase in butyrate levels reduced the expression of cGAS/STING in nerve cell further reduced Bax protein expression. The reduction of Bax protein attenuated the hippocampal neuron cell apoptosis in PTZ-induced EP and EP progression. Our findings provide new insights into the roles and mechanisms of action of the gut microbiota in attenuating EP symptoms and progression.