Four and a half LIM domains 2 (FHL2) attenuates tumorigenesis of gastrointestinal stromal tumors (GISTs) by negatively regulating KIT signaling.

Gastrointestinal stromal tumors (GISTs) are predominately induced by KIT mutants. In this study, we found that four and a half LIM domains 2 (FHL2) was highly expressed in GISTs and KIT signaling dramatically increased FHL2 transcription while FHL2 inhibited KIT transcription. In addition, our results showed that FHL2 associated with KIT and increased the ubiquitination of both wild-type KIT and primary KIT mutants in GISTs, leading to decreased expression and activation of KIT although primary KIT mutants were less inhibited by FHL2 than wild-type KIT. In the animal experiments, loss of FHL2 expression in mice carrying germline KIT/V558A mutation which can develop GISTs resulted in increased tumor growth, but increased sensitivity of GISTs to imatinib treatment which is used as the first-line targeted therapy of GISTs, suggesting that FHL2 plays a role in the response of GISTs to KIT inhibitor. Unlike wild-type KIT and primary KIT mutants, we further found that FHL2 didn't alter the expression and activation of drug-resistant secondary KIT mutants. Taken together, our results indicated that FHL2 acts as the negative feedback of KIT signaling in GISTs while primary KIT mutants are less sensitive and secondary KIT mutants are resistant to the inhibition of FHL2.

Association between CYP2C9 and VKORC1 genetic polymorphisms and efficacy and safety of warfarin in Chinese patients.

OBJECTIVES: Genetic variation has been a major contributor to interindividual variability of warfarin dosage requirement. The specific genetic factors contributing to warfarin bleeding complications are largely unknown, particularly in Chinese patients. In this study, 896 Chinese patients were enrolled to explore the effect of CYP2C9 and VKORC1 genetic variations on both the efficacy and safety of warfarin therapy. METHODS AND RESULTS: Univariate analyses unveiled significant associations between two specific single nucleotide polymorphisms rs1057910 in CYP2C9 and rs9923231 in VKORC1 and stable warfarin dosage ( P  < 0.001). Further, employing multivariate logistic regression analysis adjusted for age, sex and height, the investigation revealed that patients harboring at least one variant allele in CYP2C9 exhibited a heightened risk of bleeding events compared to those with the wild-type genotype (odds ratio = 2.16, P  = 0.04). Moreover, a meta-analysis conducted to consolidate findings confirmed the associations of both CYP2C9 (rs1057910) and VKORC1 (rs9923231) with stable warfarin dosage. Notably, CYP2C9 variant genotypes were significantly linked to an increased risk of hemorrhagic complications ( P  < 0.00001), VKORC1 did not demonstrate a similar association. CONCLUSION: The associations found between specific genetic variants and both stable warfarin dosage and bleeding risk might be the potential significance of gene detection in optimizing warfarin therapy for improving patient efficacy and safety.

Biphasic regulation of miR-17∼92 transcription during hypoxia: roles of HIF1 and p53 hyperphosphorylation at ser15.

We have reported previously that during hypoxia exposure, the expression of mature miR-17∼92 was first upregulated and then downregulated in pulmonary artery smooth muscle cells (PASMC) and in mouse lungs in vitro and in vivo. Here, we investigated the mechanisms regulating this biphasic expression of miR-17∼92 in PASMC in hypoxia. We measured the level of primary miR-17∼92 in PASMC during hypoxia exposure and found that short-term hypoxia exposure (3% O2, 6 h) induced the level of primary miR-17∼92, whereas long-term hypoxia exposure (3% O2, 24 h) decreased its level, suggesting a biphasic regulation of miR-17∼92 expression at the transcriptional level. We found that short-term hypoxia-induced upregulation of miR-17∼92 was hypoxia-inducible factor 1α (HIF1α) and E2F1 dependent. Two HIF1α binding sites on miR-17∼92 promoter were identified. We also found that long-term hypoxia-induced suppression of miR-17∼92 expression could be restored by silencing of p53. Mutation of the p53-binding sites in the miR-17∼92 promoter increased miR-17∼92 promoter activity in both normoxia and hypoxia. Our findings suggest that the biphasic transcriptional regulation of miR-17∼92 during hypoxia is controlled by HIF1/E2F1 and p53 in PASMC: during short-term hypoxia exposure, stabilization of HIF1 and induction of E2F1 induce the transcription of miR-17∼92, whereas during long-term hypoxia exposure, hyperphosphorylation of p53 suppresses the expression of miR-17∼92.NEW & NOTEWORTHY We showed that the biphasic transcriptional regulation of miR-17∼92 during hypoxia is controlled by two distinct mechanisms: during short-term hypoxia exposure, induction of HIF1 and E2F1 upregulates miR-17∼92. Longer hypoxia exposure induces hyperphosphorylation of p53 at ser15, which leads to its binding to miR-17∼92 promoter and inhibition of its expression. Our findings provide novel insights into the spatiotemporal regulation of miR-17∼92 that may play a role in the development of human lung diseases including pulmonary hypertension (PH).

Benefit finding in individuals undergoing maintenance hemodialysis in Shanghai: a latent profile analysis.

Objective: This multi-center cross-sectional study aimed to delineate latent profiles of benefit finding (BF) in individuals undergoing maintenance hemodialysis (MHD) in Shanghai and examine associations between these BF profiles, social support, and coping style. Methods: A total of 384 individuals undergoing MHD (mean age = 57.90, SD = 13.36) were assessed using the Benefit Finding Scale, Simplified Coping Style Questionnaire, and Perceived Social Support Scale. Latent profile analysis (LPA) identified distinct BF categories. Analysis of variance (ANOVA) evaluated the correlation between BF groups and demographic variables, while the relationship between BF, social support, and coping style was tested through correlation and multiple regression analyses. Results: LPA identified three BF groups: rich BF (54.17%), moderate BF (41.14%), and poor BF (4.69%). Regression analyses indicated that positive coping and social support are protective factors for BF. Additionally, older age and heightened understanding of MHD correlated with higher BF levels. Conclusion: The findings highlighted the importance of recognizing different BF profiles in individuals on MHD and working toward promoting BF levels in the rich BF and moderate BF groups, while helping the poor BF group to identify and address their challenges. Medical professionals should consider interventions tailored to individual psychological profiles to improve mental health and quality of life outcomes in this population.

Novel underlying genetic markers for asthenozoospermia due to abnormal spermatogenesis and reproductive organ inflammation.

Asthenozoospermia, a male fertility disorder, has a complex and multifactorial etiology. Moreover, the effectiveness of different treatments for asthenozoospermia remains uncertain. Hence, by using bioinformatics techniques, the present study aimed to determine the underlying genetic markers and pathogenetic mechanisms associated with asthenozoospermia due to abnormal spermatogenesis and inflammation of the reproductive tract. GSE160749 dataset was downloaded from the Gene Expression Omnibus database, and the data were filtered to obtain 1336 differentially expressed genes (DEGs) associated with asthenozoospermia. These DEGs were intersected with the epithelial mesenchymal transition datasets to yield 61 candidate DEGs. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathway enrichment analyses were performed, and the results revealed that these candidate DEGs were significantly enriched in the enzyme-linked receptor pathway and the thyroid hormone pathway. A protein-protein interaction network was constructed to identify the key genes of asthenozoospermia. A total of five key genes were identified, among which SOX9 was significantly upregulated, while HSPA4, SMAD2, HIF1A and GSK3B were significantly downregulated. These findings were validated by conducting reverse transcription-quantitative PCR for clinical semen samples. To determine the underlying molecular mechanisms, a regulatory network of transcription factors and miRNA-mRNA interactions was predicted. The expression levels of HSPA4, SMAD2 and GSK3B were positively associated with several related etiological genes of asthenozoospermia. In total, five key genes were closely associated with the level and type of immune cells; higher levels of activated B cells and CD8 T cells were observed in asthenozoospermia. Thus, the findings of the present study may provide clues to determine the underlying novel diagnostic genetic markers and treatment strategies for asthenozoospermia.

Benefit finding in chronic kidney disease patients receiving hemodialysis: a cross-sectional study.

BACKGROUND AND OBJECTIVES: The psychological problems of hemodialysis (HD) patients are prominent, and benefit finding (BF) have been proven beneficial to physical and mental health, fewer researchers explored BF in HD patients. The aim of this study was to investigate the current status of BF in patients with chronic kidney disease and to analyze the factors influencing it in order to provide a reference for subsequent interventions. METHODS: A cross-sectional study was done on 246 HD patients by convenience sampling in the hemodialysis center of a 3 A hospital in Shanghai from March to September 2019. The measures include General Information Questionnaire, Benefit Finding Scale, Perceived Social Support Scale, General Self-efficacy Scale, and Simplified Coping Style scale. RESULTS: The median (interquartile range, IQR) score of BF was 66 (IQR = 19) and it was lower compared with other chronic diseases. Significant differences in BF scores were found between different age groups, HD duration categories, and understanding degrees of HD. Taking BF as the dependent variable, the results of multiple linear regression analysis showed that age, duration of HD, family support, other support, positive coping, and self-efficacy entered the regression equation to explain 43.8% of the total variation. Social support played an indirect effect in the relationship between positive coping and BF, accounting for 54.1% of the total effect. CONCLUSION: The BF of HD patients is worrisome and affected by many factors. Medical staff could pay attention to the positive psychology of HD patients, and construct individualized interventions according to the influencing factors to improve their BF level and achieve physical and mental health.

Male infertility risk and gut microbiota: a Mendelian randomization study.

Background: In recent decades, the decline of male sperm quality has become a worldwide phenomenon, with sperm quality of critical importance for the ability to conceive naturally. Recent studies suggest that male fertility function is closely linked to the gut microbiota, however, the cause-and-effect association between the gut microbiota and male infertility risk is currently unclear. Methods: We performed one two-sample Mendelian randomization (MR) study, which uses summary data on human gut microbiota from the MiBioGen consortium as factors of exposure. FinnGen Consortium R8 data was used to obtain GWAS data for male infertility. To evaluate cause-and-effect associations linking gut microbiota and male infertility risk with multiple Mendelian randomization methods, we included inverse variance weighted (IVW), MR-Egger, and Maximum Likelihood (ML) Ratio. The heterogeneity of instrumental variables was evaluated through Cochran's Q, Rucker's Q, and leave-one-out analysis methods. Results: We found a positive association between Allisonella, Anaerotruncus, Barnesiella, Intestinibacter, and Lactococcus with male infertility risk according to the MR analysis results. Bacteroides Romboutsia, Ruminococcaceae (NK4A2140group), and Ruminococcaceae (UCG011) play a protective function in male infertility pathogenesis. Conclusion: It was found that gut microbiota and infertility are causally related in this study. In subsequent studies, there is a need to build a larger and more comprehensive GWAS database on male infertility, which will reveal the underlying mechanisms for gut microbiota and male infertility. There is a need for randomized controlled trials for validating the protective effect of the associated gut microbiota against male infertility risk, and for exploring the associated mechanisms.

Integrative preimplantation genetic testing analysis for a Chinese family with hereditary spherocytosis caused by a novel splicing variant of SPTB.

Hereditary spherocytosis (HS), the most common inherited hemolytic anemia disorder, is characterized by osmotically fragile microspherocytic red cells with a reduced surface area on the peripheral blood smear. Pathogenic variants in five erythrocyte membrane structure-related genes ANK1 (Spherocytosis, type 1; MIM#182900), SPTB (Spherocytosis, type 2; MIM#616649), SPTA1 (Spherocytosis, type 3; MIM#270970), SLC4A1 (Spherocytosis, type 4; MIM#612653) and EPB42 (Spherocytosis, type 5; MIM#612690) have been confirmed to be related to HS. There have been many studies on the pathogenic variants and mechanisms of HS, however, studies on how to manage the transmission of HS to the next-generation have not been reported. In this study, we recruited a patient with HS. Targeted next-generation sequencing with a panel of 208 genes related to blood system diseases detected a novel heterozygous variant in the SPTB: c.300+2dup in the proband. Sanger sequencing of variant alleles and haplotype linkage analysis of single nucleotide polymorphism (SNP) based on next-generation sequencing were performed simultaneously. Five embryos were identified with one heterozygous and four not carrying the SPTB variant. Single-cell amplification and whole genome sequencing showed that three embryos had varying degrees of trisomy mosaicism. One of two normal embryos was transferred to the proband. Ultimately, a healthy boy was born, confirmed by noninvasive prenatal testing for monogenic conditions (NIPT-M) to be disease-free. This confirmed our successful application of PGT in preventing transmission of the pathogenic variant allele in the HS family.

Colorimetric miRNA detection based on self-primer-initiated CRISPR-Cas12a-assisted amplification.

miRNAs alter significantly throughout pregnancy to support the development of the fetus. However, sensitive detection of miRNA remains a challenge. Herein, a reliable miRNA detection approach integrating self-assembly-triggered signal amplification and CRISPR-Cas12a-system cleavage-based color generation is described. The colorimetric approach contains three signal amplification processes. The first signal amplification is formed by the released miRNA in a chain extension process. The produced sequence that is similar to the target miRNA initiates the second signal recycle. Finally, CRISPR-Cas12a-based transcleavage on linker sequences induces the third signal amplification. The method exhibits high sensitivity and a low limit of detection of 254 aM, showing promising prospects in disease diagnosis.

Retrospective study of influencing factors on the outcomes of luteal phase stimulation in patients with dual stimulation.

Background: Dual/double stimulation (DS) is an ovarian stimulation strategy that has emerged in recent years; it is characterized by two rounds of ovarian stimulation and oocyte retrieval in the same menstrual cycle. DS can greatly shorten the time required to obtain valid embryos in assisted reproduction. For fertility preservation, DS can speed up oocyte storage process. However, factors influencing luteal phase ovarian stimulation (LPS) outcomes in DS have not been elucidated. Methods: A total of 156 cycles from 78 cases were studied. Patients were grouped and analyzed according to their follicular phase ovarian stimulation (FPS) types. Female ages, ovarian stimulation protocols, number of oocytes retrieved, embryo quality were recorded. Comparisons of outcomes were conducted between different groups. Results: Our study found that LPS obtained similar outcomes to follicular phase stimulation (FPS), and that the choice of FPS protocol affected the efficiency of LPS, the antagonist protocol and progestin-primed ovarian stimulation (PPOS) protocol resulted in better embryo outcomes in LPS. In LPS of DS, sufficient stimulation duration was the guarantee of embryo quality (number of available embryos: ß = 0.145, 95% CI [0.078-0.211], P = 0.000; number of high-quality embryos: ß = 0.114, 95% CI [0.057-0.171], P = 0.000). Discussion: This study provided ideas for the precise use of DS. We suggest to further expand the sample size of DS in the future, conduct prospective controlled studies, unify the sample size of each subgroup, include the ovarian reserve of patients in the grouping basis, and exclude the influence of male factors. We hope that this study will help further refinement of DS so as to maximize patient benefits from it. Conclusion: When the DS strategy is considered in the follicular phase, the antagonist protocol and PPOS protocol are more recommended for better embryo outcomes in LPS. During LPS, adequate ovarian stimulation duration is the most important guarantee for LPS efficiency.

Sensitive and reliable analysis of endometrial cancer related microRNA using ternary hybridization hairpin probe.

MicroRNA (miRNA), as a kind of small non-coding ribonucleic acid (RNA) that plays a crucial role in regulating transcriptional activities, is a potential biomarker for EC diagnosis. However, reliable detection of miRNA remains a huge challenge, especially for these methods that require multiple probes for signal amplifications, due to the detective deviation caused by variation of probe concentrations. Herein, we present a novel approach for miRNA-205 identification and quantification by employing simply a ternary hairpin probe (TH probe). The ternary hybridization of three sequences results in the construction of the TH probe, which combines high-efficient signal amplification and specific target recognition. A significant number of G-rich sequences have been produced as a result of the enzymes assisted signal amplification process. The G-rich sequences can fold into G-quadruplexes, which can then be detected in a label-free manner by a common fluorescent dye (thioflavin T). Eventually, the approach exhibits a low limit of detection of 278 aM with a wide detection range of 7 orders of magnitude. In summary, the proposed approach possesses a great potential for both clinical diagnosis of EC and fundamental biomedical researches.

Caregiver Perceptions of Children's and Adolescents' Psychosocial Functioning During the Stringent COVID-19 Lockdown Restrictions in Shanghai: Cross-sectional Study.

BACKGROUND: The COVID-19 pandemic represents a global health crisis. The Shanghai municipal government in China implemented strict and comprehensive pandemic control strategies in the first half of 2022 to eliminate a wave of COVID-19 infection. The pandemic and the resulting government responses have led to abrupt changes to families' daily lives, including the mental health of children and adolescents. OBJECTIVE: The aim of this paper is to examine the impact of COVID-19 exposure and the stringent lockdown measures on the daily life and mental health of children and adolescents and to provide suggestions on maintaining their mental health when similar public health emergencies occur in the future. METHODS: In this cross-sectional study, an anonymous survey was distributed online in May 1-15, 2022, in Shanghai. Individuals were eligible to participate if they were currently the caregiver of a child or adolescent (aged 4-17 years). Outcomes were psychosocial functioning of children and adolescents, as reported by parents, using the Pediatric Symptom Checklist-17. COVID-19 exposure and life changes were also reported. Multivariate logistic regression was used to analyze risk factors for poor psychosocial functioning. RESULTS: In total, 2493 valid questionnaires were analyzed. The rate of positive scores on the global Pediatric Symptom Checklist-17 scale was 16.5% (n=411). Internalizing, attention, and externalizing problem subscale positivity rates were 17.3% (n=431), 10.9% (n=272), and 8.9% (n=221), respectively. Caregivers reported that 64.2% (n=1601) and 20.7% (n=516) of the children's interactions with friends or peers and parents deteriorated, respectively. Compared with male caregivers, female caregivers were less likely to report psychosocial problems in children and adolescents (adjusted odds ratio [aOR] 0.68; 95% CI 0.53-0.88). Older children and those with lower COVID-19 Exposure and Family Impact Scales scores were less likely to have psychological problems (aOR 1.15; 95% CI 1.10-1.21). Compared with children with screen times <1 hour per day for recreation, those using screens for >3 hours had higher odds of psychological distress (aOR 2.09; 95% CI 1.47-1.97). Children who spent 1-2 hours exercising and had better interactions with friends or peers and parents showed a trend toward lower odds of psychological problems. Children and adolescents with worse sleep compared with preclosure were more likely to have psychological problems. CONCLUSIONS: The prevalence of psychosocial problems among children and adolescents is relatively high. Being young, having more COVID-19 exposure, and having more screen times (>3 h/day), less exercise time (<30 min), worse sleep, and deteriorated interactions with friends or peers and parents were risk factors for poor psychosocial functioning. It is necessary for governments, communities, schools, and families to take appropriate countermeasures to reduce the negative impact of the stringent control measures on caregivers' parenting and psychosocial functioning of children and adolescents.

Transcriptomic and metabolomic studies on the protective effect of molecular hydrogen against nuclear electromagnetic pulse-induced brain damage.

Background: Excessive doses of electromagnetic radiation pose a negative impact on the central nervous system and lead to mental disorders. Molecular hydrogen can scavenge intracellular hydroxyl radicals, acting as an antioxidant, anti-apoptotic and anti-inflammatory agent. We seek to assess the capability of molecular hydrogen to ameliorate brain damage induced by electromagnetic radiation. Methods: NEMP (nuclear electromagnetic pulse), a subset of electromagnetic pulse with high voltage value that could cause severe brain injury, was applied to this study. Male wild-type rats were divided into four groups: the control group, the H2 (Molecular hydrogen) group, the NEMP group and the NEMP+H2 group. Rats in the H2 group and the NEMP+H2 group were fed with saturated hydrogen-rich water from 3 days before NEMP exposure (electromagnetic field intensity 400 kV/m, rising edge 20 ns and pulse width 200 ns) to the day of sacrifice. One day after exposure, animal behavior experiments were performed, and samples for transcriptomics and metabolomics analysis were collected. Seven days after exposure, histopathological experiments were conducted. Results: The data from the elevated plus maze and the open field test showed that NEMP exposure elicited anxiety-like behavior in rats, which could be alleviated by H2 treatment. Histopathological results manifested that NEMP exposure-induced injuries of the neurons in the hippocampus and amygdala could be attenuated by H2 treatment. Transcriptomic results revealed that NEMP exposure had a profound effect on microtubule structure in the brain. And the combined analysis of transcriptomics and metabolomics showed that H2 has a significant impact on the neuroactive ligand-receptor interaction, synaptic vesicle cycle and synapse etc. Moreover, it was indicated that the glutathione metabolic pathway played a vital role in the NEMP exposure-induced damage and the protective activity of H2. Conclusions: H2 is identified as a potent agent against NEMP exposure-induced brain damage and has the potential to be a promising electromagnetic radiation protectant.

Development and Psychometric Assessment of the Benefit Finding Scale for Chinese Older Adults With Chronic Diseases.

The current study sought to develop an instrument for measuring benefit finding in Chinese older adults with chronic diseases and establish its psychometric characteristics. Scale items were drafted based on a literature review, theoretical learning, the Benefit Finding Scale (BFS), the Post-Traumatic Growth Inventory, and results of interviews with 24 older adults with chronic diseases. The preliminary scale draft was constructed by performing a Delphi expert consultation and pretest with a small sample. Using the first draft of the scale, we surveyed 380 older adults with chronic diseases. The BFS for older adults with chronic diseases comprised 26 items. Using exploratory factor analysis, we identified six common factors that explained 66.86% of the variance. Item content validity index ranged from 0.818 to 1.000 and scale content validity index was 0.91. Cronbach's alpha of the scale was 0.924 and test-retest reliability was 0.902. The BFS for older adults with chronic diseases showed good validity and reliability and can be used as a measurement tool for benefit finding in the aforementioned population. [Research in Gerontological Nursing, 16(1), 44-52.].

Effects of Various Marine Toxins on the Mouse Intestine Organoid Model.

Because of their trace existence, exquisite structure and unique role, highly toxic marine biotoxins have always led to the development of natural product identification, structure and function research, chemistry and biosynthesis, and there are still many deficiencies in the injury and protection of highly toxic organisms, toxin biosynthesis, rapid detection, poisoning and diagnosis and treatment. In this study, a mouse intestine organoid (MIO) model was constructed to explore the effects of the marine toxins okadaic acid (OA) and conotoxin (CgTx) on MIO. The results showed that the cell mortality caused by the two toxins at middle and high concentrations was significantly higher than the cell mortality of the control group, the ATPase activity in each group exposed to OA was significantly lower than the ATPase activity of the control group, all the CgTx groups were significantly higher than that of the control group, and the number of apoptotic cells was not significantly higher than the number of apoptotic cells of the control group. Through RNA-Seq differential genes, Gene Ontology (GO) and pathway analysis, and Gene Set Enrichment Analysis (GSEA) experimental results, it was demonstrated that OA reduced cell metabolism and energy production by affecting cell transcription in MIO. Ultimately, cell death resulted. In contrast, CgTx upregulated the intracellular hormone metabolism pathway by affecting the nuclear receptor pathway of MIO, which resulted in cell death and the generation of energy in large amounts.

Feasibility Analysis and Implementation of Head-Mounted Electrical Impedance Respiratory Monitoring.

The respiratory rate is one of the crucial indicators for monitoring human physiological health. The purpose of this paper was to introduce a head-mounted respiratory monitoring solution based on electrical impedance sensing. Firstly, we constructed a finite element model to analyze the feasibility of using head impedance for respiratory sensing based on the physiological changes in the pharynx. After that, we developed a circuit module that could be integrated into a head-mounted respiratory monitoring device using a bioelectrical impedance sensor. Furthermore, we combined adaptive filtering and respiratory tracking algorithms to develop an app for a mobile phone. Finally, we conducted controlled experiments to verify the effectiveness of this electrical impedance sensing system for extracting respiratory rate. We found that the respiration rates measured by the head-mounted electrical impedance respiratory monitoring system were not significantly different from those of commercial respiratory monitoring devices by a paired t-test (p > 0.05). The results showed that the respiratory rates of all subjects were within the 95% confidence interval. Therefore, the head-mounted respiratory monitoring scheme proposed in this paper was able to accurately measure respiratory rate, indicating the feasibility of this solution. In addition, this respiratory monitoring scheme helps to achieve real-time continuous respiratory monitoring, which can provide new insights for personalized health monitoring.

Electroacupuncture improves cognitive impairment in diabetic cognitive dysfunction rats by regulating the mitochondrial autophagy pathway.

BACKGROUND: Diabetes-associated cognitive dysfunction has become a major public health concern. However, the mechanisms driving this disease are elusive. Herein, we explored how electroacupuncture improves learning and memory function in diabetic rats. METHODS: The diabetic model was established by intraperitoneal injection of streptozotocin (STZ) in adult Sprague-Dawley rats. Rats were fed on high-fat and high-sugar diets. Learning and memory functions were assessed using behavioral tests. The hematoxylin and eosin (H&E) staining, Western blotting, real-time PCR, ELISA, immunohistochemistry, and transmission electronic microscopy (TEM) was performed to test related indicators. RESULTS: High-fat and high-sugar diets impaired learning and memory function in rats, while electroacupuncture treatment reversed these changes. The model group presented highly prolonged escape latency compared to the control group, indicating impaired learning and memory functions. The TEM examination showed that electroacupuncture enhanced Aß clearance and mitochondrial autophagy in hippocampal neuronal cells by increasing DISC1 expression. CONCLUSIONS: Electroacupuncture improves learning and memory function in diabetic rats by increasing DISC1 expression to promote mitophagy. This enhanced Aß clearance, alleviating cytotoxicity in hippocampal neuronal cells.

Molecular Hydrogen Reduces Electromagnetic Pulse-Induced Male Rat Reproductive System Damage in a Rodent Model.

Infertility has got to be a broadly concerned social issue these days, in which the malefactor cannot be overlooked. Numerous studies have shown that electromagnetic pulse (EMP) radiation may have seriously damaging effects on reproductive health, through nonthermal effects and oxidative stress. Molecular hydrogen, a selective hydroxyl radical scavenger, explains the protective effects against many diseases closely associated with oxidative damage, such as ionizing radiation (IR). We sought to characterize the beneficial effects of molecular hydrogen on the male reproductive system in a rodent EMP exposure model. The 8-week-old male Sprague-Dawley rats were exposed to EMP (peak intensity 1000 kV/m, pulse edge 20 ns, pulse width 200 ns, 1 Hz, and 200 pulses), with or without hydrogen-rich water. The pathological structure of the testis, the rate of apoptosis of the testis, the serum testosterone level, the sperm parameters, and the activity of the antioxidant enzymes of the testis were measured. Then, transcriptomic and untargeted metabolomic analyses were applied to uncover the underlying mechanism. Exposure to EMP increased testicular apoptosis rate and apoptosis protein level, decreased sperm viability and motility, decreased serum testosterone levels, and diminished testicular antioxidant capacity. Molecular hydrogen-alleviated damage decreased the testicular apoptosis rate and apoptosis protein level, increased sperm motility, increased serum testosterone levels, and improved antioxidative capacity. Omics results showed that molecular hydrogen has a strong influence on metabolic pathways, and EMP affects mainly oxidative phosphorylation, TNF signaling pathways, and cytokine-receptor interactions. The mechanism of molecular hydrogen's effect may be related to the reversal of some metabolite levels. These observations warrant molecular hydrogen as an innovative approach for potential protection against EMP.