Intricate role of intestinal microbe and metabolite in schizophrenia.

BACKGROUND: The brain-gut axis has gained increasing attention due to its contribution to the etiology of various central nervous system disorders. This study aims to elucidate the hypothesis that schizophrenia is associated with disturbances in intestinal microflora and imbalance in intestinal metabolites. By exploring the intricate relationship between the gut and the brain, with the goal of offering fresh perspectives and valuable insights into the potential contribution of intestinal microbial and metabolites dysbiosis to the etiology of schizophrenia. METHODS: In this study, we used a 16S ribosomal RNA (16S rRNA) gene sequence-based approach and an untargeted liquid chromatography-mass spectrometry-based metabolic profiling approach to measure the gut microbiome and microbial metabolites from 44 healthy controls, 41 acute patients, and 39 remission patients, to evaluate whether microbial dysbiosis and microbial metabolite biomarkers were linked with the severity of schizophrenic symptoms. RESULTS: Here, we identified 20 dominant disturbances in the gut microbial composition of patients compared with healthy controls, with 3 orders, 4 families, 9 genera, and 4 species. Several unique bacterial taxa associated with schizophrenia severity. Compared with healthy controls, 145 unusual microflora metabolites were detected in the acute and remission groups, which were mainly involved in environmental information processing, metabolism, organismal systems, and human diseases in the Kyoto encyclopedia of genes and genomes pathway. The Sankey diagram showed that 4 abnormal intestinal and 4 anomalous intestinal microbial metabolites were associated with psychiatric clinical symptoms. CONCLUSIONS: These findings suggest a possible interactive influence of the gut microbiota and their metabolites on the pathophysiology of schizophrenia.

The global burden and trends of maternal sepsis and other maternal infections in 204 countries and territories from 1990 to 2019.

BACKGROUND: Maternal sepsis and other maternal infections (MSMI) have considerable impacts on women's and neonatal health, but data on the global burden and trends of MSMI are limited. Comprehensive knowledge of the burden and trend patterns of MSMI is important to allocate resources, facilitate the establishment of tailored prevention strategies and implement effective clinical treatment measures. METHODS: Based on data from the Global Burden of Disease database, we analysed the global burden of MSMI by the incidence, death, disability-adjusted life year (DALY) and maternal mortality ratio (MMR) in the last 30 years. Then, the trends of MSMI were assessed by the estimated annual percentage change (EAPC) of MMR as well as the age-standardized rate (ASR) of incidence, death and DALY. Moreover, we determined the effect of sociodemographic index (SDI) on MSMI epidemiological parameters. RESULTS: Although incident cases almost stabilized from 1990 to 2015, the ASR of incidence, death, DALY and MMR steadily decreased globally from 1990 to 2019. The burden of MSMI was the highest in the low SDI region with the fastest downward trends. MSMI is still one of the most important causes of maternal death in the developed world. Substantial diversity of disease burden and trends occurred in different regions and individual countries, most of which had reduced burden and downward trends. The MMR and ASR were negatively correlated with corresponding SDI value in 2019 in 204 countries/territories and 21 regions. CONCLUSION: These findings highlight significant improvement in MSMI care in the past three decades, particularly in the low and low-middle SDI regions. However, the increased burden and upward trends of MSMI in a few countries and regions are raising concern, which poses a serious challenge to maternal health. More tailored prevention measures and additional resources for maternal health are urgently needed to resolve this problem.

Association Between Abundance of Haemophilus in the Gut Microbiota and Negative Symptoms of Schizophrenia.

Increasing evidence indicates an interaction between dysbiosis of the microbiota and the pathogenesis of schizophrenia. However, limited information is available on the specific microbial communities associated with symptoms of schizophrenia. Therefore, this study aimed to investigate gut microbiota dysbiosis and its relationship with psychopathologies in schizophrenia. We recruited 126 participants and divided them into three groups according to the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition, criteria-acute group (patients with acute schizophrenia), remission group (patients with schizophrenia in remission), and control group (healthy controls). Psychotic symptoms were evaluated using the Positive and Negative Syndrome Scale. Microbiota compositions, diversity and community structure were evaluated using 16S rRNA sequencing. Pearson's correlation analysis was used to evaluate the association between bacterial taxa and psychotic symptoms. The beta-diversity of microbiota composition in the acute group was distinct from that in the remission and control groups (PC1 = 21.11% vs. PC2 = 12.86%, P = 0.021). Furthermore, Pearson's correlation analysis revealed that abundance of Haemophilus was positively correlated with negative psychiatric symptoms (r = 0.303, P = 0.021), while abundance of Coprococcus was negatively correlated with negative psychiatric symptoms (r = -0.285, P = 0.025). Moreover, abundance of Haemophilus was positively correlated with cognition (r = 0.428, P = 0.009), excitement (r = 0.266, P = 0.037), and depression (r = 0.295, P = 0.020). The study findings suggest that alterations in certain gut microbiota may interfere with psychological symptoms in schizophrenia. Our results provide evidence that may help in the development of therapeutic strategies using microbial-based targets. The data that support the findings of this study have been deposited in the NCBI (https://submit.ncbi.nlm.nih.gov/) with accession number SUB9453991.

LncRNA TONSL-AS1 regulates miR-490-3p/CDK1 to affect ovarian epithelial carcinoma cell proliferation.

BACKGROUND: LncRNA TONSL-AS1 has been characterized as a critical player in gastric cancer. By analyze the TCGA dataset, we observed the upregulation of TONSL-AS1 in ovarian epithelial carcinoma (EOC). We therefore investigated the involvement of TONSL-AS1 in EOC. METHODS: The differential expression of TONSL-AS1 in EOC was first explored by analyzing the TCGA dataset. The effects of overexpression of TONSL-AS1 and miR-490-3p on the expression of CDK1 mRNA and protein in OVCAR3 cells were evaluated by qPCR and western blot, respectively. CCK-8 assay was performed to investigate the effects of overexpression of TONSL-AS1, miR-490-3p and CDK1 on proliferation of OVCAR3 cells. RESULTS: We observed that TONSL-AS1 was upregulated in EOC tumor tissues from EOC patients, and its high expression level was correlated with poor survival. Dual luciferase assay and RNA interaction prediction showed the direct interaction between TONSL-AS1 and miR-490-3p. However, overexpression of miR-490-3p did not affect the expression of TONSL-AS1. Instead, overexpression of TONSL-AS1 resulted in the upregulation of CDK1, a target of miR-490-3p, in EOC cells. Overexpression of TONSL-AS1 and CDK1 resulted in increased proliferation rate of EOC cells. Overexpression of miR-490-3p played an opposite role and reduced the effects of overexpression of TONSL -AS1 and CDK1. CONCLUSIONS: Therefore, TONSL-AS1 may regulate miR-490-3p/CDK1 to affect EOC cell proliferation.

Study on buffer characteristics of air cushion used as hip protector.

INTRODUCTION: In order to develop a good hip protector to prevent in the elderly hip fracture as a result of a fall, we studied the buffer characteristics of sponges and air cushions. METHODS: The buffer rate of material was defined, and the absorption ability of the material to instantaneous impact was evaluated. An experimental device was developed and used to measure the buffer rates of sponges and leak-allowed air cushions with orifice(s). RESULTS: According to the experimental results, the buffer rate largely depended on the hardness of the sponge materials, and on the total area of the orifice(s) for the leak-allowed air cushions. Compared with the sponge with correct hardness and thickness, the buffer characteristic of the air cushion seems slightly inferior. CONCLUSIONS: Nevertheless, the air cushion's overall performance, including the better buffer rate, ultra-lightness, flexibility, and low cost, makes it a potentially useful material for hip protectors and other sport protectors.

Study on electromagnetic characteristics of the magnetic coupling resonant coil for the wireless power transmission system.

BACKGROUND: The resonant coil design is taken as the core technology in the magnetic coupling resonant wireless power transmission system, which achieves energy transmission by the coupling of the resonant coil. This paper studies the effect of the resonant coil on energy transmission and the efficiency of the system. Combining a two-coil with a three-coil system, the optimum design method for the resonant coil is given to propose a novel coil structure. METHODS: First, the co-simulation methods of Pspice and Maxwell are used. When the coupling coefficient of the resonant coil is different, the relationship between system transmission efficiency, output power, and frequency is analyzed. When the self-inductance of the resonant coil is different, the relationship between the performance and frequency of the system transmission is analyzed. Then, two-coil and three-coil structure models are built, and the parameters of the magnetic field of the coils are calculated and analyzed using the finite element method. In the end, a dual E-type simulation circuit model is used to optimize the design of the novel resonance coil. RESULTS: The co-simulation results show that the coupling coefficients of the two-coil, three-coil, and novel coil systems are 0.017, 0.17 and 0.0126, respectively. The power loss of the novel coil is 16.4 mW. CONCLUSIONS: There is an obvious improvement in the three-coil system, which shows that the magnetic leakage of the field and the energy coupling are relatively small. The new structure coil has better performance, and the load loss is lower; it can improve the system output power and transmission efficiency.

[Involvement of miR-199a in cisplatin resistance of ovarian cancer cell through modulating expression of mTOR].

OBJECTIVE: To study the effect of miR-199a on the sensitivity of OV2008 and C13* cells to cisplatin and investigate its mechanism of action. METHODS: Real-time polymerase chain reaction(PCR) and Western blot were applied to detect the expression level changes of mammalian target of rapamycin (mTOR) in OV2008 and C13* cells before and after transfecting the cells with the mimics and inhibitor of miR-199a with Lipofectamine 2000.We constructed luciferase reporter vectors of mTOR and then transfected OV2008 cells with the mimics of miR-199a with Lipofectamine 2000 to study the regulation of miR-199a's downstream target genes. RESULTS: The expression level of mTOR was significantly higher in C13* than OV2008 cells (P<0.05). After OV2008 and C13* cells were transfected with the mimics and inhibitor of miR-199a, real-time PCR and Western blot showed that the mimics of miR-199a repressed the expression of mTOR; and the inhibitor of miR-199a promoted the expression of mTOR. After transfecting OV2008 cells with the mimics of miR-199a and luciferase reporter vectors of mTOR, renillaluciferase reporter gene analysis indicated the expression level of mTOR was negatively regulated by miR-199a. CONCLUSION: miR-199a regulates the sensitivity of ovarian cancer cells to cisplatin through modulating expression of mTOR, and involves in the cisplatin resistance process of ovarian cancer cells.

microRNA-199a is able to reverse cisplatin resistance in human ovarian cancer cells through the inhibition of mammalian target of rapamycin.

microRNAs (miRNAs/miRs) may have a crucial function in tumor metastasis through the regulation of a plethora of signaling pathways. Increasing evidence has shown that miR-199a is important in regulating the tumor metastasis of ovarian cancer, although the precise biological function of miR-199a is unclear at present. In the current study, it was observed that the expression levels of miR-199a were higher in OV2008 cells compared with C13* cells. However, lower levels of mammalian target of rapamycin (mTOR) protein were detected by western blotting in the OV2008 cells compared with the C13* cells. The miR-199a levels were increased in the C13* cells using miR-199a mimics and the mTOR levels were observed to decrease. This may have resulted in a reversal of cisplatin resistance in the C13* cells. To test this hypothesis, the Renilla luciferase reporter gene system was used to analyze the mTOR levels. The results indicated that the expression levels of mTOR were significantly blocked by the increased miR-199a levels. When the miR-199a inhibitor was applied to decrease the miR-199a levels, it was observed that the mTOR expression levels were increased, while cisplatin-induced apoptosis was decreased in the OV2008 cells. The study concludes that miR-199a is able to reverse cisplatin resistance in human ovarian cancer cells through the inhibition of mTOR and that mTOR may be the target of miR-199a during this process.

miR-125b confers resistance of ovarian cancer cells to cisplatin by targeting pro-apoptotic Bcl-2 antagonist killer 1.

Chemotherapy is the preferred therapeutic approach for advanced ovarian cancer, but a successful long-term treatment is prevented by the development of drug resistance. Recent works have underlined the involvement of non-coding RNAs, microRNAs (miRNAs) in cancer development, with several conjectures regarding their possible involvement in the evolution of drug resistance. This study is to investigate the promoting effects and mechanism of miR-125b involved in the development of chemoresistance in ovarian cancer. The different expression of miR-125b in cisplatin-sensitive ovarian cancer cell line (OV2008) and its resistant variant (C13*) was identified by real-time PCR. An in vitro cytotoxicity assay and apoptosis assay using CCK-8 assay and flow cytometry, were carried out to detect the effect of miR-125b and Bak1 on cisplatin resistance of cells. Real-time PCR, Western blotting and luciferase reporter assay were used to detect whether Bak1 is a target of miR-125b. As compared with OV2008 cells, the expression levels of miR-125b in C13* cells were increased. It was found that the up-regulation of microRNA-125b caused a marked inhibition of cisplatin-induced cytotoxicity and apoptosis and a subsequent increase in the resistance to cisplatin in OV2008 and C13* cells. Moreover, Bak1 was a direct target of miR-125b, and down-regulation of Bak1 suppressed cisplatin-induced apoptosis and led to an increased resistance to cisplatin. Our study indicates that miR-125b has a significantly promoting effect on chemoresistance of C13* cells and up-regulation of miR-125b expression contributes to cisplatin resistance through suppression of Bak1 expression. This finding has important implications in the development of targeted therapeutics for overcoming cisplatin resistance in ovarian cancer.

miR-125b Confers Resistance of Ovarian Cancer Cells to Cisplatin by Targeting Pro-apoptotic Bcl-2 Antagonist Killer 1 / 华中科技大学学报（医学）（英德文版）

Chemotherapy is the preferred therapeutic approach for advanced ovarian cancer,but a suceessful long-term treatment is prevented by the development of drug resistance.Recent works have underlined the involvement of non-coding RNAs,microRNAs (miRNAs) in cancer development,with several conjectures regarding their possible involvement in the evolution of drug resistance.This study is to investigate the promoting effects and mechanism of miR-125b involved in the development of chemoresistance in ovarian cancer.The different expression of miR-125b in cisplatin-sensitive ovarian cancer cell line (OV2008) and its resistant variant (C13*) was identified by real-time PCR.An in vitro cytotoxicity assay and apoptosis assay using CCK-8 assay and flow cytometry,were carried out to detect the effect of miR-125b and Bak1 on cisplatin resistance of cells.Real-time PCR,Western blotting and luciferase reporter assay were used to detect whether Bak1 is a target of miR-125b.As compared with OV2008 cells,the expression levels of miR-125b in C13* cells were increased.It was found that the up-regulation of microRNA-125b caused a marked inhibition of cisplatin-induced cytotoxicity and apoptosis and a subsequent increase in the resistance to cisplatin in OV2008 and C13* cells.Moreover,Bakl was a direct target of miR-125b,and down-regulation of Bak1 suppressed cisplatin-induced apoptosis and led to an increased resistance to cisplatin.Our study indicates that miR-125b has a significantly promoting effect on chemoresistance of C13* cells and up-regulation of miR-125b expression contributes to cisplatin resistance through suppression of Bakl expression.This finding has important implications in the development of targeted therapeutics for overcoming cisplatin resistance in ovarian cancer.