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.

The PP2A Inhibitor LB-100 Mitigates Lupus Nephritis by Suppressing Tertiary Lymphoid Structure Formation.

Systemic lupus erythematosus (SLE) is an autoimmune disease characterized by multi-organ involvement and autoantibody production. Patients with SLE face a substantial risk of developing lupus nephritis (LN), which imposes a substantial burden on both patients and their families. Protein phosphatase 2A (PP2A) is a widely distributed serine/threonine phosphatase participated in regulating multiple signaling pathways and immune responses. Inhibition of PP2A is implicated in the treatment of diseases. LB-100, a small molecule inhibitor of PP2A, is currently undergoing preclinical trials for its therapeutic potential against tumors. However, the role of PP2A and its inhibitor has been insufficiently studied in LN. In this study, we assessed the potential effects of LB-100 in both MRL/lpr mice and R848-induced BALB/c mice. Our findings indicated that LB-100 administration led to reduced spleen enlargement, decreased deposition of immune complexes, ameliorated renal damage, and improved kidney function in two distinct lupus mouse models. Importantly, we observed the formation of tertiary lymphoid structures (TLS) in the kidneys of both spontaneous and induced lupus mouse models. The levels of chemokines inducing T cell infiltration were elevated in the kidneys of lupus mice, whereas LB-100 mitigated chemokines production and inhibited TLS formation. In summary, our study identified the role of PP2A in LN and highlighted the renal protective potential of the PP2A inhibitor LB-100 in two distinct lupus mouse models, suggesting its potential as a novel strategy for LN and other autoimmune diseases.

Compound prebiotics as prophylactic and adjunctive treatments ameliorate DSS-induced colitis through gut microbiota modulation effects.

The prophylactic and adjunctive impacts of compound prebiotics (CP), comprising galacto-oligosaccharides, fructo-oligosaccharides, and isomalto-oligosaccharides, on colitis remain unclear. This study aimed to elucidate the effects of CP on dextran sodium sulfate (DSS)-induced colitis via modulation of the gut microbiota. Mice received prophylactic CP (PCP) for three weeks and DSS in the second week. In the third week, therapeutic CP, mesalazine, and a combination of CP and mesalazine (CPM) were administered to mice with DSS-induced colitis. The administration of PCP and CPM was found to ameliorate colitis, as evidenced by increases in body weight and colon length, elevation of the anti-inflammatory cytokine IL-10, and reductions in the disease activity index, histological scores, and levels of pro-inflammatory cytokines in mice with DSS-induced colitis on days 14 or 21. Furthermore, an increase in the relative abundance of probiotics (Ligilactobacillus, Bifidobacterium, and Limosilactobacillus), alpha diversity indices, short-chain fatty acids (SCFA) contents, and microbial network complexity was observed following PCP or CPM treatment. Correlation analysis revealed positive associations between these probiotics and both SCFA and IL-10, and negative associations with pro-inflammatory cytokines. This study highlighted the potential of CP as novel prophylactic and adjunctive treatments for alleviating DSS-induced intestinal inflammation and maintaining gut microbiota homeostasis.

RNA-seq analysis-based study on the effects of gestational diabetes mellitus on macrosomia.

Background: Both the mother and the infant are negatively impacted by macrosomia. Macrosomia is three times as common in hyperglycemic mothers as in normal mothers. This study sought to determine why hyperglycemic mothers experienced higher macrosomia. Methods: Hematoxylin and Eosin staining was used to detect the placental structure of normal mother(NN), mothers who gave birth to macrosomia(NM), and mothers who gave birth to macrosomia and had hyperglycemia (DM). The gene expressions of different groups were detected by RNA-seq. The differentially expressed genes (DEGs) were screened with DESeq2 R software and verified by qRT-PCR. The STRING database was used to build protein-protein interaction networks of DEGs. The Cytoscape was used to screen the Hub genes of the different group. Results: The NN group's placental weight differed significantly from that of the other groups. The structure of NN group's placenta is different from that of the other group, too. 614 and 3207 DEGs of NM and DM, respectively, were examined in comparison to the NN group. Additionally, 394 DEGs of DM were examined in comparison to NM. qRT-PCR verified the results of RNA-seq. Nucleolar stress appears to be an important factor in macrosomia, according on the results of KEGG and GO analyses. The results revealed 74 overlapped DEGs that acted as links between hyperglycemia and macrosomia, and 10 of these, known as Hub genes, were key players in this process. Additionally, this analysis believes that due of their close connections, non-overlapping Hubs shouldn't be discounted. Conclusion: In diabetic mother, ten Hub genes (RPL36, RPS29, RPL8 and so on) are key factors in the increased macrosomia in hyperglycemia. Hyperglycemia and macrosomia are linked by 74 overlapping DEGs. Additionally, this approach contends that non-overlapping Hubs shouldn't be ignored because of their tight relationships.

Establishment and validation of a nomogram model for predicting ovulation in the PCOS women.

BACKGROUND: The mechanisms underlying ovulatory dysfunction in PCOS remain debatable. This study aimed to identify the factors affecting ovulation among PCOS patients based on a large sample-sized randomized control trial. METHODS: Data were obtained from a multi-centered randomized clinical trial, the PCOSAct, which was conducted between 2011 and 2015. Univariate and multivariate analysis using binary logistic regression were used to construct a prediction model and nomogram. The accuracy of the model was assessed using receiver operating characteristic (ROC) curves and calibration curves. RESULTS: The predictive variables included in the training dataset model were luteinizing hormone (LH), free testosterone, body mass index (BMI), period times per year, and clomiphene treatment. The ROC curve for the model in the training dataset was 0.81 (95% CI [0.77, 0.85]), while in the validation dataset, it was 0.7801 (95% CI [0.72, 0.84]). The model showed good discrimination in both the training and validation datasets. Decision curve analysis demonstrated that the nomogram designed for ovulation had clinical utility and superior discriminative ability for predicting ovulation. CONCLUSIONS: The nomogram composed of LH, free testosterone, BMI, period times per year and the application of clomiphene may predict the ovulation among PCOS patients.

HiMIC-Monthly: A 1 km high-resolution atmospheric moisture index collection over China, 2003-2020.

Near-surface atmospheric moisture is a key environmental and hydro-climatic variable that has significant implications for the natural and human systems. However, high-resolution moisture data are severely lacking for fine-scale studies. Here, we develop the first 1 km high spatial resolution dataset of monthly moisture index collection in China (HiMIC-Monthly) over a long period of 2003~2020. HiMIC-Monthly is generated by the light gradient boosting machine algorithm (LightGBM) based on observations at 2,419 weather stations and multiple covariates, including land surface temperature, vapor pressure, land cover, impervious surface proportion, population density, and topography. This collection includes six commonly used moisture indices, enabling fine-scale assessment of moisture conditions from different perspectives. Results show that the HiMIC-Monthly dataset has a good performance, with R2 values for all six moisture indices exceeding 0.96 and root mean square error and mean absolute error values within a reasonable range. The dataset exhibits high consistency with in situ observations over various spatial and temporal regimes, demonstrating broad applicability and strong reliability.

Impact of C-reactive protein on the effect of Roxadustat for the treatment of anemia in chronic kidney disease: a systematic review of randomized controlled trials.

BACKGROUND: Chronic inflammation, reflected by an increased blood C-reactive protein (CRP) level, is common in patients with chronic kidney disease (CKD) and is involved in the development of renal anemia. This systematic review aims to investigate the impacts of CRP on the efficacy of hypoxia-inducible factor-prolyl hydroxylase inhibitors (HIF-PHIs) in the treatment of renal anemia in patients with CKD. METHODS: We conducted a comprehensive search of electronic databases including Pubmed, Web of Science, Embase, Cochrane Library, CNKI, Wanfang, and the International Clinical Trials Registry Platform (ICTRP), from their inception to May 19, 2022. We systematically reviewed evidence from randomized controlled trials using HIF-PHIs for renal anemia treatment. The mean difference (MD) in changes in hemoglobin concentration (∆Hb) before and after treatment served as the meta-analysis outcome, utilizing a random-effects model. We compared groups with CRP levels greater than or equal to the upper limit of normal (ULN) and less than the ULN. Additionally, further analysis was conducted in the CRP ≥ ULN group comparing HIF-PHIs and erythropoiesis-stimulating agents (ESA). RESULTS: A total of 7 studies from 6 publications were included in the analysis. In the comparison between the CRP ≥ ULN group and the CRP < ULN group, 524 patients from 4 studies were incorporated into the analysis. All patients received roxadustat as the primary intervention. The pooled results revealed no significant difference in ΔHb between patients with CRP ≥ ULN and CRP < ULN at baseline (Mean Difference: 0.00, 95% Confidence Interval: -0.32 to 0.33, P = 0.99). Moreover, within the CRP ≥ ULN group, three studies involving 1399 patients compared the efficacy of roxadustat and erythropoiesis-stimulating agents (ESAs). The results indicated no significant difference in ΔHb between patients treated with ESAs and HIF-PHIs (Mean Difference: 0.24, 95% Confidence Interval: -0.08 to 0.56, P = 0.14). In terms of medication dosage, an increase in ESA dose over time was observed across various studies, particularly evident in the CRP ≥ ULN group, while the dose of roxadustat remains constant over time and is not influenced by the baseline levels of CRP. CONCLUSIONS: Our systematic review demonstrates that roxadustat exhibits similar efficacy across different CRP levels. Moreover, within the CRP ≥ ULN group, roxadustat can maintain efficacy comparable to ESA without the necessity for dose escalation. TRIAL REGISTRATION: CRD42023396704.

Comparative efficacy and tolerability of probiotic, prebiotic, and synbiotic formulations for adult patients with mild-moderate ulcerative colitis in an adjunctive therapy: A network meta-analysis.

BACKGROUND & AIMS: Probiotics, prebiotics, and synbiotics (PPS) have been widely used as adjuvant treatments in patients with ulcerative colitis (UC) in recent years. However, the most effective formulations of PPS have yet to be identified. We thus aimed to compare the efficacy and tolerability of different PPS formulations for mild-moderate UC. METHODS: We searched PubMed, Embase, Web of Science, and Cochrane CENTRAL from inception to June 24, 2023 for double-blind randomized controlled trials. We used a frequentist approach in random-effects models for network meta-analysis and the Grading of Recommendations Assessment, Development, and Evaluation approach to evaluate the certainty of evidence. RESULTS: We analysed data from 20 trials involving 1153 patients. The combinations of specific strains of Lactobacillus and Bifidobacterium (CLB) (odds ratio (OR), 3.85; 95 % confidence interval (CI), 1.40-10.60; low certainty) and combinations of specific strains of Lactobacillus, Bifidobacterium, and Streptococcus (CLBS) (OR, 2.20; 95 % CI, 1.47-3.28; low certainty) significantly increased the clinical remission rate in intention-to-treat analysis (ITT) when compared to placebo. Similarly, compared with placebo, the two combinations significantly reduced clinical activity scores (standardized mean difference (SMD), -1.17 (95 % CI, -1.68 to -0.65), low certainty; and SMD, -1.33 (95 % CI, -1.81 to -0.86), low certainty, respectively). Hierarchical cluster analyses showed the two combinations formed clusters with high efficacy (clinical remission in ITT and clinical activity score) and tolerability (withdrawal due to worsening symptoms) within 12 weeks. CONCLUSION: In this systematic review, we found CLB and CLBS demonstrated a clinical benefit in adjuvant treatments, with a comparable tolerability and safety profile to placebo. Further trials are needed. TRIAL REGISTRATION NUMBER: CRD42022344905.

Identifying And Unveiling the Role of Multivalent Metal States for Bidirectional UOR and HER Over Ni, Mo-Trithiocyanuric Based Coordination Polymer.

Urea oxidation reaction (UOR), an ideal alternative to oxygen evolution reaction (OER), has received increasing attention for realizing energy-saving H2 production and relieving pollutant degradation. Normally, most studied Ni-based UOR catalysts pre-oxidate to NiOOH and then act as active sites. However, the unpredictable transformation of the catalyst's structure and its dissolution and leaching, may complicate the accuracy of mechanism studies and limit its further applications. Herein, a novel self-supported bimetallic Mo-Ni-C3 N3 S3 coordination polymers (Mo-NT@NF) with strong metal-ligand interactions and different H2 O/urea adsorption energy are prepared, which realize a bidirectional UOR/hydrogen evolution reaction (HER) reaction pathway. A series of Mo-NT@NF is prepared through a one-step mild solvothermal method and their multivalent metal states and HER/UOR performance relationship is evaluated. Combining catalytic kinetics, in situ electrochemical spectroscopic characterization, and density-functional theory (DFT) calculations, a bidirectional catalytic pathway is proposed by N, S-anchored Mo5+ and reconstruction-free Ni3+ sites for catalytic active center of HER and UOR, respectively. The effective anchoring of the metal sites and the fast transfer of the intermediate H* by N and S in the ligand C3 N3 S3 H3 further contribute to the fast kinetic catalysis. Ultimately, the coupled HER||UOR system with Mo-NT@NF as the electrodes can achieve energy-efficient overall-urea electrolysis for H2 production.

Acupuncture and Doxylamine-Pyridoxine for Nausea and Vomiting in Pregnancy : A Randomized, Controlled, 2 × 2 Factorial Trial.

BACKGROUND: An effective and safe treatment for nausea and vomiting of pregnancy (NVP) is lacking. OBJECTIVE: To assess the efficacy and safety of acupuncture, doxylamine-pyridoxine, and a combination of both in women with moderate to severe NVP. DESIGN: Multicenter, randomized, double-blind, placebo-controlled, 2 × 2 factorial trial. (ClinicalTrials.gov: NCT04401384). SETTING: 13 tertiary hospitals in mainland China from 21 June 2020 to 2 February 2022. PARTICIPANTS: 352 women in early pregnancy with moderate to severe NVP. INTERVENTION: Participants received daily active or sham acupuncture for 30 minutes and doxylamine-pyridoxine or placebo for 14 days. MEASUREMENTS: The primary outcome was the reduction in Pregnancy-Unique Quantification of Emesis (PUQE) score at the end of the intervention at day 15 relative to baseline. Secondary outcomes included quality of life, adverse events, and maternal and perinatal complications. RESULTS: No significant interaction was detected between the interventions (P = 0.69). Participants receiving acupuncture (mean difference [MD], -0.7 [95% CI, -1.3 to -0.1]), doxylamine-pyridoxine (MD, -1.0 [CI, -1.6 to -0.4]), and the combination of both (MD, -1.6 [CI, -2.2 to -0.9]) had a larger reduction in PUQE score over the treatment course than their respective control groups (sham acupuncture, placebo, and sham acupuncture plus placebo). Compared with placebo, a higher risk for births with children who were small for gestational age was observed with doxylamine-pyridoxine (odds ratio, 3.8 [CI, 1.0 to 14.1]). LIMITATION: The placebo effects of the interventions and natural regression of the disease were not evaluated. CONCLUSION: Both acupuncture and doxylamine-pyridoxine alone are efficacious for moderate and severe NVP. However, the clinical importance of this effect is uncertain because of its modest magnitude. The combination of acupuncture and doxylamine-pyridoxine may yield a potentially larger benefit than each treatment alone. PRIMARY FUNDING SOURCE: The National Key R&D Program of China and the Project of Heilongjiang Province "TouYan" Innovation Team.

Development of The Chinese Version of Ultra-Low Vision Visual Functioning Questionnaire-150.

Purpose: The purpose of this study was to develop the Chinese version of Ultra-Low Vision Visual Functioning Questionnaire-150 (ULV-VFQ-150) and evaluate its psychometric function. Methods: A standardized procedure for the translation of ULV-VFQ-150 was carried out, including the forward translation, consistency check, back translation, back review, and coordination. Participants with ultra-low vision (ULV) were recruited for the questionnaire survey. Psychometric characteristics were evaluated using Rasch analysis based on Item Response Theory (IRT), and some items were revised and proofread accordingly. Results: In total, 70 out of 74 responders completed the Chinese ULV-VFQ-150, of which 10 were excluded because their vision did not meet the criterion of ULV. Therefore, 60 valid questionnaires were analyzed (valid response rate = 81.1%). The average age of eligible responders was 49.0 years (standard deviation = 16.0), with 35% female subjects (21/60). The person measures (ability) ranged from -1.7 to +4.9 logits, and the item measures (difficulty) ranged from -1.6 to +1.2 logits. The mean value of item difficulty and personnel ability were 0.00 and 0.62 logits, respectively. The reliability index was 0.87 for items and 0.99 for persons, and the overall fit is good. The items conform to unidimensionality as indicated by principal component analysis of the residuals. Conclusions: The Chinese version of ULV-VFQ-150 is a reliable questionnaire for evaluating both visual function and functional vision in people with ULV in China. Translational Relevance: The Chinese version of ULV-VFQ-150 is a new assessment of the visual function of people with ULV in China.

Identification and analysis of autism spectrum disorder via large-scale dynamic functional network connectivity.

Autism spectrum disorder (ASD) is a prevalent neurodevelopmental disorder with severe cognitive impairment. Several studies have reported that brain functional network connectivity (FNC) has great potential for identifying ASD from healthy control (HC) and revealing the relationships between the brain and behaviors of ASD. However, few studies have explored dynamic large-scale FNC as a feature to identify individuals with ASD. This study used a time-sliding window method to study the dynamic FNC (dFNC) on the resting-state fMRI. To avoid arbitrarily determining the window length, we set a window length range of 10-75 TRs (TR = 2 s). We constructed linear support vector machine classifiers for all window length conditions. Using a nested 10-fold cross-validation framework, we obtained a grand average accuracy of 94.88% across window length conditions, which is higher than those reported in previous studies. In addition, we determined the optimal window length using the highest classification accuracy of 97.77%. Based on the optimal window length, we found that the dFNCs were located mainly in dorsal and ventral attention networks (DAN and VAN) and exhibited the highest weight in classification. Specifically, we found that the dFNC between DAN and temporal orbitofrontal network (TOFN) was significantly negatively correlated with social scores of ASD. Finally, using the dFNCs with high classification weights as features, we construct a model to predict the clinical score of ASD. Overall, our findings demonstrated that the dFNC could be a potential biomarker to identify ASD and provide new perspectives to detect cognitive changes in ASD.

Protective effects of electroacupuncture on polycystic ovary syndrome in rats: Down-regulating Alas2 to inhibit apoptosis, oxidative stress, and mitochondrial dysfunction in ovarian granulosa cells.

Polycystic ovary syndrome (PCOS) is a heterogeneous endocrine disorder affecting women at reproductive age. The therapeutic effect of electroacupuncture (EA) on PCOS has been revealed, while the anti-PCOS mechanisms of EA have not been fully explored. In this study, PCOS were induced in rats by daily injection with dehydroepiandrosterone (DHEA) for 20 days and EA treatment was performed for 5 weeks. The mRNA expression profiles in ovarian tissues from control, PCOS, and EA-treated rats were examined by high-throughput mRNA sequencing. 5'-aminolevulinate synthase 2 (Alas2), a vital rate-limiting enzyme of the heme synthesis pathway, was selected to be further studied. PCOS led to the upregulation of Alas2 mRNA, whereas EA treatment restored this change. In vitro, primary ovarian granulosa cells (GCs) were challenged with H2O2 to mimic the oxidative stress (OS) state in PCOS. H2O2 induced apoptosis, OS, mitochondrial dysfunction, as well as Alas2 overexpression in GCs, while lentivirus-mediated Alas2 knockdown evidently restrained the above impairments. In summary, this study highlights the crucial role of Alas2 in cell apoptosis, OS, and mitochondrial dysfunction of PCOS GCs and provides potential therapeutic candidates for further investigation on PCOS treatment.

Effects of compound prebiotics as prophylactic and therapeutic supplementation in a mouse model of acute colitis.

Compound prebiotics (CP) have been explored in modulation of intestinal microbiota and remission of inflammatory responses in the acute colitis (AC). Yet, research on the roles of simultaneous prophylactic and therapeutic CP intervention in relation to AC remains lacking. Here, CP were pre-fed to examine preventive effects. CP, CP combined with mesalazine (5-aminosalicylic acid) (CPM), and mesalazine were used to evaluate therapeutic effects on the dextran sulfate sodium (DSS)-induced AC. Results showed that prophylactic CP and therapeutic CPM alleviated AC, evidenced by variations of body weight, colon length, spleen index, disease activity index score, histological score, and intestinal mucosa. Ruminococcus and Bifidobacterium were detected in significant abundance in the prophylactic CP and therapeutic CPM groups, respectively. Phylogenetic ecological network analysis revealed that therapeutic CPM probably had the strongest coupling between microbes in changing intestinal microbiota to influence treatment. However, changes in short-chain fatty acids (SCFAs) seemed to have no persuasive results, probably due to reduced SCFA level in feces and variability in transit, absorption, and utilization. Furthermore, therapeutic CP exerted higher value in terms of observed species and Shannon diversity, as well as a more concentrated distribution by principal coordinates analysis. Together, the favorable roles of CP in colitis provide directions for prebiotics in designing effective prophylactic functional diets and treatment strategies. KEY POINTS: • Prebiotics as prophylactic intervention effectively inhibited acute colitis. • Prebiotics as prophylactic and therapeutic interventions had distinct effects on gut microbiota. • Prebiotics combined with drug intervention had higher efficacy in treating acute colitis.

Fecal microbiota transplantation for induction of remission in Crohn's disease: a systematic review and meta-analysis.

PURPOSE: Fecal microbiota transplantation (FMT) has been found to be a potential treatment for Crohn's disease (CD). We sought to perform a systematic review and meta-analysis to evaluate the efficacy and safety of FMT in CD. METHODS: Electronic databases were searched for studies until January 2023. Clinical remission was established as the primary outcome. The secondary outcome was clinical response, endoscopic remission, minor adverse events, serious adverse events, and changes in disease activity indices, biochemical indicators, and microbial diversities. Pooled effect sizes and 95% confidence intervals (CIs) were calculated under the random effects model. RESULTS: Eleven cohort studies and one randomized controlled trial involving 228 patients were included. In a meta-analysis, the pooled proportion of adult patients with active CD that achieved clinical remission 2 to 4 weeks after FMT was 57% (95% CI = 49-64%) with a low risk of heterogeneity (I2 = 37%). Furthermore, our results showed that FMT significantly (standardized mean difference = -0.66; 95% CI = -1.12 to -0.20; I2 = 0) reduced Crohn's disease activity index scores 4 to 8 weeks after FMT. Subgroup analyses showed no difference between FMT methodologies, except for pre-FMT treatment with antibiotics (P = 0.02). Most adverse events were self-limiting and disappeared spontaneously within hours or days after FMT. Microbiota analysis showed an increased Shannon diversity and a shift toward donor-like microbiome after FMT. CONCLUSION: FMT could be a promising therapy in the short-term treatment of active CD. More placebo-controlled randomized trials with a long-term follow-up treatment are necessary. TRIAL REGISTRATION: https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42022322694 No. CRD42022322694.

JAK/STAT signaling pathway and its regulation on insect immunity.

JAK/STAT signaling pathway is involved in important biological processes, such as cell growth, differentiation, apoptosis and immune regulation, and is one of the most important signal transduction pathways mediated by cytokines. JAK/STAT is a relatively conserved signaling pathway in insects, which is the main immune pathway together with Toll signaling pathway and Imd signaling pathway to resist the invasion of pathogens. It plays a vital role in insect immunity, hormone regulation and other physiological regulation processes. In this review, we summarize the cytokine receptor superfamily, JAKs family, STATs family, JAK/STAT signaling pathway and its mechanism of negative feedback regulation. We analyze the important functions and the latest research progress of JAK/STAT signaling pathway in insect infected by parasites, viruses and fungi. Finally, we propose the remaining problems in the study of JAK/STAT signaling pathway, so as to provide direction and reference for further research in this field.

Identification and functional analysis of Dmrt1 gene and the SoxE gene in the sexual development of sea cucumber, Apostichopus japonicus.

Members of the Doublesex and Mab-3-related transcription factor (Dmrt) gene family handle various vital functions in several biological processes, including sex determination/differentiation and gonad development. Dmrt1 and Sox9 (SoxE in invertebrates) exhibit a very conserved interaction function during testis formation in vertebrates. However, the dynamic expression pattern and functional roles of the Dmrt gene family and SoxE have not yet been identified in any echinoderm species. Herein, five members of the Dmrt gene family (Dmrt1, 2, 3a, 3b and 5) and the ancestor SoxE gene were identified from the genome of Apostichopus japonicus. Expression studies of Dmrt family genes and SoxE in different tissues of adult males and females revealed different expression patterns of each gene. Transcription of Dmrt2, Dmrt3a and Dmrt3b was higher expressed in the tube feet and coelomocytes instead of in gonadal tissues. The expression of Dmrt1 was found to be sustained throughout spermatogenesis. Knocking-down of Dmrt1 by means of RNA interference (RNAi) led to the downregulation of SoxE and upregulation of the ovarian regulator foxl2 in the testes. This indicates that Dmrt1 may be a positive regulator of SoxE and may play a role in the development of the testes in the sea cucumber. The expression level of SoxE was higher in the ovaries than in the testes, and knocking down of SoxE by RNAi reduced SoxE and Dmrt1 expression but conversely increased the expression of foxl2 in the testes. In summary, this study indicates that Dmrt1 and SoxE are indispensable for testicular differentiation, and SoxE might play a functional role during ovary differentiation in the sea cucumber.

Elevated baseline LH/FSH ratio is associated with poor ovulatory response but better clinical pregnancy and live birth in Chinese women with PCOS after ovulation induction.

Background: What is the association between elevated baseline LH/FSH ratio and reproductive outcomes, especially ovulatory response, among Chinese women with polycystic ovary syndrome (PCOS) after ovulation induction. Methods: This was a secondary analysis of a multicenter randomized trial in 1000 women with PCOS from 21 sites (27 hospitals) in Mainland China. LH and FSH levels before ovulation induction and the main outcomes including ovulation, biochemical pregnancy, clinical pregnancy, miscarriage, and live birth were measured. A linear regression model, logistic regression models and Cox proportional hazard regression model were used to estimate the association between LH/FSH ratios and reproductive outcomes in PCOS. Results: LH/FSH ratio was significantly associated with age, body mass index (BMI), total testosterone (TT), estradiol (E2), free testosterone (FT), and antimullerian hormone (AMH). Anovulatory women had significantly higher LH/FSH ratio than ovulatory women (P = 0.003), especially in women with young age (P = 0.023), high BMI (P = 0.002), low E2 (P = 0.002), FT (P = 0.010), TT (P < 0.001) and AMH(P = 0.032). Women with elevated LH/FSH ratio were associated with lower ovulation (LH/FSH≥1 OR = 0.42, 95% CI, 0.26-0.68; LH/FSH≥2 OR = 0.32, 95% CI, 0.20-0.54; LH/FSH≥3 OR = 0.40, 95% CI 0.21-0.74) when compared with LH/FSH<1. The association was held after adjustment for treatment with or without the confounding factors. Although no association between LH/FSH ratio and biochemical pregnancy, women with 1 ≤ LH/FSH<2 were associated with higher clinical pregnancy (OR = 1.71; 95% CI, 1.09-2.67) and live birth (OR = 1.73; 95% CI, 1.09-2.75) compared to women with LH/FSH<1. Women with 2 ≤ LH/FSH<3 were associated with lower miscarriage rate (OR = 0.38; 95% CI, 0.16-0.93). Conclusions: Elevated baseline LH/FSH ratio in women with PCOS was associated with poor ovulatory response, but women were more likely to achieve clinical pregnancy and live birth than women with normal LH/FSH. It suggests LH and FSH in women with PCOS may play a role in successful pregnancy despite of negative impact in ovulation.

Altered default mode network causal connectivity patterns in autism spectrum disorder revealed by Liang information flow analysis.

Autism spectrum disorder (ASD) is a pervasive developmental disorder with severe cognitive impairment in social communication and interaction. Previous studies have reported that abnormal functional connectivity patterns within the default mode network (DMN) were associated with social dysfunction in ASD. However, how the altered causal connectivity pattern within the DMN affects the social functioning in ASD remains largely unclear. Here, we introduced the Liang information flow method, widely applied to climate science and quantum mechanics, to uncover the brain causal network patterns in ASD. Compared with the healthy controls (HC), we observed that the interactions among the dorsal medial prefrontal cortex (dMPFC), ventral medial prefrontal cortex (vMPFC), hippocampal formation, and temporo-parietal junction showed more inter-regional causal connectivity differences in ASD. For the topological property analysis, we also found the clustering coefficient of DMN and the In-Out degree of anterior medial prefrontal cortex were significantly decreased in ASD. Furthermore, we found that the causal connectivity from dMPFC to vMPFC was correlated with the clinical symptoms of ASD. These altered causal connectivity patterns indicated that the DMN inter-regions information processing was perturbed in ASD. In particular, we found that the dMPFC acts as a causal source in the DMN in HC, whereas it plays a causal target in ASD. Overall, our findings indicated that the Liang information flow method could serve as an important way to explore the DMN causal connectivity patterns, and it also can provide novel insights into the nueromechanisms underlying DMN dysfunction in ASD.

The relationships between dynamic resting-state networks and social behavior in autism spectrum disorder revealed by fuzzy entropy-based temporal variability analysis of large-scale network.

Autism spectrum disorder (ASD) is a common neurodevelopmental disorder characterized by a core deficit in social processes. However, it is still unclear whether the core clinical symptoms of the disorder can be reflected by the temporal variability of resting-state network functional connectivity (FC). In this article, we examined the large-scale network FC temporal variability at the local region, within-network, and between-network levels using the fuzzy entropy technique. Then, we correlated the network FC temporal variability to social-related scores. We found that the social behavior correlated with the FC temporal variability of the precuneus, parietal, occipital, temporal, and precentral. Our results also showed that social behavior was significantly negatively correlated with the temporal variability of FC within the default mode network, between the frontoparietal network and cingulo-opercular task control network, and the dorsal attention network. In contrast, social behavior correlated significantly positively with the temporal variability of FC within the subcortical network. Finally, using temporal variability as a feature, we construct a model to predict the social score of ASD. These findings suggest that the network FC temporal variability has a close relationship with social behavioral inflexibility in ASD and may serve as a potential biomarker for predicting ASD symptom severity.