Associations between 25 hydroxyvitamin D concentration and spontaneous abortion.

BACKGROUND: Spontaneous abortion is a common complication of pregnancy that can lead to adverse physical and psychological outcomes for women. Vitamin D is reported to be associated with reproductive functions, whereas its casual effects on abortion remains unclear. MATERIALS AND METHODS: In this study, a two-sample Mendelian randomization (MR) analysis was performed to systematically assess the causal relationships between serum 25 hydroxyvitamin D [25(OH)D] concentration and the risk of spontaneous abortion. GWAS summary data of 25(OH)D were used as exposure, and data of spontaneous abortion was considered as outcome. A retrospective study was additionally conducted to verify the MR results. RESULTS: MR estimates showed that a higher 25(OH)D level was potentially associated with decreased risk of spontaneous abortion (IVW, OR = 0.98, 95%CI = 0.90-1.06; MR Egger, OR = 0.94, 95%CI = 0.84-1.05; Weighted median, OR = 0.93, 95%CI = 0.82-1.06; Weighted mode, OR = 0.93, 95%CI = 0.84-1.03), though the P-value was not statistically significant. The retrospective study also produced consistent result of Vitamin D's protective role to spontaneous abortion. The P-value was very close to statistical significance (P = 0.053). CONCLUSIONS: This study reports the potential protective role of serum 25(OH)D concentration to spontaneous abortion, suggesting that increased vitamin D levels may decrease the risk of abortion. Further larger prospective studies and/or even randomized controlled trials are needed to confirm causal relationship between vitamin D and abortion.

Identification and Regulation of Hypoxia-Tolerant and Germination-Related Genes in Rice.

In direct seeding, hypoxia is a major stress faced by rice plants. Therefore, dissecting the response mechanism of rice to hypoxia stress and the molecular regulatory network is critical to the development of hypoxia-tolerant rice varieties and direct seeding of rice. This review summarizes the morphological, physiological, and ecological changes in rice under hypoxia stress, the discovery of hypoxia-tolerant and germination-related genes/QTLs, and the latest research on candidate genes, and explores the linkage of hypoxia tolerance genes and their distribution in indica and japonica rice through population variance analysis and haplotype network analysis. Among the candidate genes, OsMAP1 is a typical gene located on the MAPK cascade reaction for indica-japonica divergence; MHZ6 is involved in both the MAPK signaling and phytohormone transduction pathway. MHZ6 has three major haplotypes and one rare haplotype, with Hap3 being dominated by indica rice varieties, and promotes internode elongation in deep-water rice by activating the SD1 gene. OsAmy3D and Adh1 have similar indica-japonica varietal differentiation, and are mainly present in indica varieties. There are three high-frequency haplotypes of OsTPP7, namely Hap1 (n = 1109), Hap2 (n = 1349), and Hap3 (n = 217); Hap2 is more frequent in japonica, and the genetic background of OsTPP7 was derived from the japonica rice subpopulation. Further artificial selection, natural domestication, and other means to identify more resistance mechanisms of this gene may facilitate future research to breed superior rice cultivars. Finally, this study discusses the application of rice hypoxia-tolerant germplasm in future breeding research.

Meta-analysis of correlation between sleep duration and gender difference in adults with type 2 diabetes.

OBJECTIVE: To explore the correlation between sleep duration and type II diabetes in adults. METHOD: Computer databases searches were carried out through October 1, 2022, including PubMed, Cochrane Library, Embase, and Web of Science. Relevant literature was collected, and the Newcastle-Ottawa Scale (NOS) and extracted data were used to exclude studies and evaluate quality on the basis of inclusion and exclusion criteria. Meta-analysis was conducted using RevMan 5.4.1 software with random/fixed effects models. RESULTS: A total of 5 studies with 74,226 subjects (31,611 in the male study group, 42,615 in the female study group) were included. The meta-analysis revealed that women with long sleep duration (LSD) have a higher risk for developing type II diabetes than men, OR = 0.70; 95% CI 0.59-0.84, Z = 4.00 and P < 0.001. Men with short sleep duration (SSD) tended to have a higher risk in developing type II diabetes than women though the difference between men and women did not reach statistical significance, OR = 1.09, 95% CI 0.73-1.62, Z = 0.42 and P = 0.68. Further subgroup analysis by regional populations suggested that men in Europe and America with SSD had a higher risk of type II diabetes OR = 1.52, 95% CI 1.04-2.21, Z = 2.18 and P = 0.03. CONCLUSION: Women with LSD may have a higher risk for type II diabetes, and men in Europe and America with SSD may have a higher risk for type II diabetes than men of other regions.

Phylogeography of Artemisia frigida (Anthemideae, Asteraceae) based on genotyping-by-sequencing and plastid DNA data: Migration through Beringia.

Artemisia frigida is a temperate grassland species that has the largest natural range among its genus, with occurrences across the temperate grassland biomes of Eurasia and North America. Despite its wide geographic range, we know little about the species' distribution history. Hence, we conducted a phylogeographical study to test the hypothesis that the species' distribution pattern is related to a potential historical migration over the 'Bering land bridge'. We applied two molecular approaches: genotyping-by-sequencing (GBS) and Sanger sequencing of the plastid intergenic spacer region (rpl32 - trnL) to investigate genetic differentiation and relatedness among 21 populations from North America, Middle Asia, Central Asia and the Russian Far East. Furthermore, we identified the ploidy level of individuals based on GBS data. Our results indicate that A. frigida originated in Asia, spread northwards to the Far East and then to North America across the Bering Strait. We found a pronounced genetic structuring between Middle and Central Asian populations with mixed ploidy levels, tetraploids in the Far East, and nearly exclusively diploids in North America except for one individual. According to phylogenetic analysis, two populations of Kazakhstan (KZ2 and KZ3) represent the most likely ancestral diploids that constitute the basally branching lineages, and subsequent polyploidization has occurred on several occasions independently. Mantel tests revealed weak correlations between genetic distance and geographical distance and climatic conditions, which indicates that paleoclimatic fluctuations may have more profoundly influenced A. frigida's spatial genetic structure and distribution than the current environment.

Development and validation of a simple clinical nomogram for predicting obstructive sleep apnea.

Obstructive sleep apnea is the most common type of sleep breathing disorder. Therefore, the purpose of our research is to construct and verify an objective and easy-to-use nomogram that can accurately predict a patient's risk of obstructive sleep apnea. In this study, we retrospectively collected the data of patients undergoing polysomnography at the Sleep Medicine Center of the First Affiliated Hospital of Guangzhou Medical University. Participants were randomly assigned to a training cohort (50%) and a validation cohort (50%). Logistic regression and Lasso regression models were used to reduce data dimensions, select factors and construct the nomogram. C-index, calibration curve, decision curve analysis and clinical impact curve analysis were used to evaluate the identification, calibration and clinical effectiveness of the nomogram. Nomograph validation was performed in the validation cohort. The study included 1035 people in the training cohort and 1078 people in the validation cohort. Logistic and Lasso regression analysis identified age, gender, diastolic blood pressure, body mass index, neck circumference and Epworth Sleepiness Scale as the predictive factors included in the nomogram. The training cohort (C-index = 0.741) and validation cohort (C-index = 0.745) had better identification and calibration effects. The areas under the curve of the nomogram and STOP-Bang were 0.741 (0.713-0.767) and 0.728 (0.700-0.755), respectively. Decision curve analysis and clinical impact curve analysis showed that the nomogram is clinically useful. We have established a concise and practical nomogram that will help doctors better determine the priority of patients referred to the sleep centre.

Efficacy and safety of selexipag, an oral prostacyclin receptor agonist for the treatment of pulmonary hypertension: A meta-analysis.

BACKGROUND AND OBJECTIVE: This meta-analysis was performed to evaluate the effect and safety of selexipag in the treatment of pulmonary hypertension and to explore the effect of selexipag on cardiac function indexes in PAH patients. METHODS: Electronic databases, including the Cochrane Library, EMBASE, and PubMed databases, were searched. Endnote software X9 was used for study selection, and the Cochrane Risk of Bias Tool was used for literature screening and quality assessment. Data analysis was performed using RevMan 5.3 software, and GRADE was used to assess the evidence level. RESULTS: Ten studies were finally selected in accordance with the standard. A total of 10 papers were included. A total of 1322 patients were included, including 723 in the trial group and 599 in the control group. Patients with PAH treated with selexipag were included in the trial group, and patients with PAH treated with placebo were included in the control group. The results of the study showed that selexipag was effective in reducing mortality in patients (WMD=0.70, 95% CI: 0.53-0.94, P = 0.02). Selexipag effectively increased the 6-min walk distance (WMD=33.79, 95% CI: 2.69-64.90, P=0.03). Selexipag also effectively increased the 6-min distance between baseline and follow-up (WMD = 15.28, 95% CI: 7.76-22.80, P < 0.0001). Selexipag effectively reduced PVR (WMD = -230.96, 95% CI: 445.94 to -15.97, P = 0.04). Selexipag significantly reduced PVR between baseline and follow-up (WMD = -139.62, 95% CI: 215.32 to -63.91, P = 0.0003). The adverse reactions of selexipag were mild with headache, diarrhea and nausea reported as the main symptoms. CONCLUSION: Selexipag is a new drug with mild adverse reactions and is safe for the treatment of PAH. This drug significantly prolongs the level of 6MWD in PAH patients, reduces the fatality rate, improves WHO FC and reduces PVR. The effects of this drug on CI, mPAP, MRAP, SvO2 and other indicators still need to be further confirmed. PROSPERO REGISTRATION: CRD42021245557.

A meta-analysis of the diagnostic value of NoSAS in patients with sleep apnea syndrome.

OBJECTIVE: The NoSAS score is a new tool widely used in recent years to screen for obstructive sleep apnea. A number of studies have shown that the NoSAS score is more accurate than previous tools, such as the Berlin, STOP-Bang, and STOP questionnaires. Therefore, this meta-analysis assessed the diagnostic value of the NoSAS score for sleep apnea syndrome in comparison to polysomnography. METHODS: Two researchers searched the PubMed, EMBASE, Cochrane, and Web of Science databases through November 13, 2020. This paper used Endnote9.3 software to manage the literature and RevMan 5.3 and STATA12.0 software to perform the meta-analysis. RESULTS: A total of 10 studies were included in this meta-analysis, including 14,510 patients. The meta-analysis showed that the pooled sensitivity was 0.798 (95% CI 0.757, 0.833), the pooled specificity was 0.582 (95% CI 0.510, 0.651), the positive likelihood ratio was 1.909 (95% CI 1.652, 2.206), the negative likelihood ratio was 0.347 (95% CI 0.300, 0.403), the diagnostic OR was 5.495 (95% CI 4.348, 6.945), and the area under the SROC curve was 0.77 (95% CI 0.73, 0.80). The NoSAS score has good efficacy in identifying patients likely to have obstructive sleep apnea. CONCLUSION: The NoSAS score can accurately identify patients likely to have obstructive sleep apnea. Therefore, in the absence of polysomnography, one should use the NoSAS score to evaluate patients with suspected sleep apnea syndrome.

Reproductive outcome of hysteroscopic metroplasty for women with T-shaped uterus: a retrospective study.

BACKGROUND: T-shaped uterus is a Müllerian malformation with unapparent clinical manifestations. Intrauterine adhesion and tuberculosis may lead to T-shaped uterus, too. Hysteroscopic metroplasty is a treatment option for T-shaped uterus, while the postoperative reproductive outcomes have not been thoroughly investigated. The aim of this study was to determine the reproductive outcome in Chinese women with T-shaped uterus who had hysteroscopic metroplasty with cold scissors. METHODS: This retrospective cohort study was conducted in the reproductive surgery unit of a university-affiliated hospital. One hundred and eleven patients with T-shaped uterus who underwent hysteroscopic metroplasty from Jan. 2017 to Sept. 2019 were followed-up by telephone in Apr. 2021. All patients received hysteroscopic metroplasty using microcissors, followed by estrogen-progesterone sequential treatment, with or without intrauterine device (IUD) implantation. According to whether they had had history of intrauterine operation, patients were divided into congenital group and acquired group. The main outcome measure was postoperative live birth rate. χ2 test and t test were used for comparison between groups. Cochran-Mantel-Haenszel test were used for stratified analysis. P < 0.05 was considered statistically significant. RESULTS: One hundred and eleven patients were included in total, with 46 in congenital group and 65 in acquired group. After hysteroscopic metroplasty, in the congenital group, the pregnancy rate increased from 28.3% to 87.0% (P < 0.001) and the live birth rate increased from 23.1% to 79.5% (P = 0.001); in the acquired group, the pregnancy rate slightly dropped from 98.5% to 72.3% (P < 0.001) while the live birth rate increased from 20.8% to 74.5% (P < 0.001). No statistically significant difference was observed in postoperative reproductive outcome indicators between the two subgroups except mode of conception. CONCLUSIONS: For both groups, hysteroscopic metroplasty may improve reproductive outcomes for patients with T-shaped uterus.

As a Müllerian malformation, T-shaped uterus is named for the shape of the uterine cavity. According to cause of the disease and patients' intrauterine operation history, T-shaped uterus can be divided into congenital and acquired types.This study was conducted in the reproductive surgery unit in a university-affiliated hospital. Data were collected from medical records, and patients were followed up via telephone.One hundred and eleven patients were included in this study, with 46 in congenital group and 65 in acquired group. Whether infertility/subfertility patients had had intrauterine operation history or not, their rates of giving live birth increased after the hysteroscopic metroplasty.In conclusion, hysteroscopic metroplasty is an effective intervention for T-shaped uterus patients with fertility intention.

Toll-Like Receptor 3 in Cardiovascular Diseases.

Toll-like receptor 3 (TLR3) is an important member of the innate immune response receptor toll-like receptors (TLRs) family, which plays a vital role in regulating immune response, promoting the maturation and differentiation of immune cells, and participating in the response of pro-inflammatory factors. TLR3 is activated by pathogen-associated molecular patterns and damage-associated molecular patterns, which support the pathophysiology of many diseases related to inflammation. An increasing number of studies have confirmed that TLR3, as a crucial medium of innate immunity, participates in the occurrence and development of cardiovascular diseases (CVDs) by regulating the transcription and translation of various cytokines, thus affecting the structure and physiological function of resident cells in the cardiovascular system, including vascular endothelial cells, vascular smooth muscle cells, cardiomyocytes, fibroblasts and macrophages. The dysfunction and structural damage of vascular endothelial cells and proliferation of vascular smooth muscle cells are the key factors in the occurrence of vascular diseases such as pulmonary arterial hypertension, atherosclerosis, myocardial hypertrophy, myocardial infarction, ischaemia/reperfusion injury, and heart failure. Meanwhile, cardiomyocytes, fibroblasts, and macrophages are involved in the development of CVDs. Therefore, the purpose of this review was to explore the latest research published on TLR3 in CVDs and discuss current understanding of potential mechanisms by which TLR3 contributes to CVDs. Even though TLR3 is a developing area, it has strong treatment potential as an immunomodulator and deserves further study for clinical translation.

Drought and heat wave impacts on grassland carbon cycling across hierarchical levels.

Droughts and heat waves are increasing in magnitude and frequency, altering the carbon cycle. However, understanding of the underlying response mechanisms remains poor, especially for the combination (hot drought). We conducted a 4-year field experiment to examine both individual and interactive effects of drought and heat wave on carbon cycling of a semiarid grassland across individual, functional group, community and ecosystem levels. Drought did not change below-ground biomass (BGB) or above-ground biomass (AGB) due to compensation effects between grass and non-grass functional groups. However, consistently decreased BGB under heat waves limited such compensation effects, resulting in reduced AGB. Ecosystem CO2 fluxes were suppressed by droughts, attributed to stomatal closure-induced reductions in leaf photosynthesis and decreased AGB of grasses, while CO2 fluxes were little affected by heat waves. Overall the hot drought produced the lowest leaf photosynthesis, AGB and ecosystem CO2 fluxes although the interactions between heat wave and drought were usually not significant. Our results highlight that the functional group compensatory effects that maintain community-level AGB rely on feedback of root system responses, and that plant adjustments at the individual level, together with shifts in composition at the functional group level, co-regulate ecosystem carbon sink strength under climate extremes.

Terrestrial N2 O emissions and related functional genes under climate change: A global meta-analysis.

Nitrous oxide (N2 O) emissions from soil contribute to global warming and are in turn substantially affected by climate change. However, climate change impacts on N2 O production across terrestrial ecosystems remain poorly understood. Here, we synthesized 46 published studies of N2 O fluxes and relevant soil functional genes (SFGs, that is, archaeal amoA, bacterial amoA, nosZ, narG, nirK and nirS) to assess their responses to increased temperature, increased or decreased precipitation amounts, and prolonged drought (no change in total precipitation but increase in precipitation intervals) in terrestrial ecosystem (i.e. grasslands, forests, shrublands, tundra and croplands). Across the data set, temperature increased N2 O emissions by 33%. However, the effects were highly variable across biomes, with strongest temperature responses in shrublands, variable responses in forests and negative responses in tundra. The warming methods employed also influenced the effects of temperature on N2 O emissions (most effectively induced by open-top chambers). Whole-day or whole-year warming treatment significantly enhanced N2 O emissions, but daytime, nighttime or short-season warming did not have significant effects. Regardless of biome, treatment method and season, increased precipitation promoted N2 O emission by an average of 55%, while decreased precipitation suppressed N2 O emission by 31%, predominantly driven by changes in soil moisture. The effect size of precipitation changes on nirS and nosZ showed a U-shape relationship with soil moisture; further insight into biotic mechanisms underlying N2 O emission response to climate change remain limited by data availability, underlying a need for studies that report SFG. Our findings indicate that climate change substantially affects N2 O emission and highlights the urgent need to incorporate this strong feedback into most climate models for convincing projection of future climate change.

Ecological responses to heavy rainfall depend on seasonal timing and multi-year recurrence.

Heavy rainfall events are expected to increase in frequency and severity in the future. However, their effects on natural ecosystems are largely unknown, in particular with different seasonal timing of the events and recurrence over multiple years. We conducted a 4 yr manipulative experiment to explore grassland response to heavy rainfall imposed in either the middle of, or late in, the growing season in Inner Mongolia, China. We measured hierarchical responses at individual, community and ecosystem levels. Surprisingly, above-ground biomass remained stable in the face of heavy rainfall, regardless of seasonal timing, whereas heavy rainfall late in the growing season had consistent negative impacts on below-ground and total biomass. However, such negative biomass effects were not significant for heavy rainfall in the middle of the growing season. By contrast, heavy rainfall in the middle of the growing season had greater positive effects on ecosystem CO2 exchanges, mainly reflected in the latter 2 yr of the 4 yr experiment. This two-stage response of CO2 fluxes was regulated by increased community-level leaf area and leaf-level photosynthesis and interannual variability of natural precipitation. Overall, our study demonstrates that ecosystem impacts of heavy rainfall events crucially depend on the seasonal timing and multiannual recurrence. Plant physiological and morphological adjustment appeared to improve the capacity of the ecosystem to respond positively to heavy rainfall.

Petroclostridium xylanilyticum gen. nov., sp. nov., a xylan-degrading bacterium isolated from an oilfield, and reclassification of clostridial cluster III members into four novel genera in a new Hungateiclostridiaceae fam. nov.

A rod-shaped, Gram-stain-positive, obligately anaerobic, xylan-degrading bacterium, SK-Y3T, was isolated from oily-sludge of Shengli oilfield, China. Optimum growth occurred at 50 °C, at pH 7.5 and without addition of NaCl. The predominant cellular fatty acids of strain SK-Y3T were iso-C15 : 0, anteiso-C15 : 0 and iso-C17 : 0, and the main polar lipids were glycolipids (GL), lipids (L), phosphatidylglycerol (PG) and diphosphatidylglycerol (DPG); no respiratory quinones were detected. The genomic DNA G+C content was 37.2 mol%. Phylogenetic analysis of 16S rRNA gene sequences showed that strain SK-Y3T belongs to clostridial cluster III, exhibiting 91-92% sequence similarity to the most closely related species, namely Clostridium clariflavum, Clostridium straminisolvens and Acetivibrio cellulolyticus. Based on distinct physiological and phylogenetic differences from the aforementioned described taxa, strain SK-Y3T (=DSM 103557T=ACCC 19952T) is proposed as the type strain of a novel species of a new genus, Petroclostridium xylanilyticum gen. nov., sp. nov. Furthermore, analysis through 16S rRNA gene, ribosomal protein and whole genome sequences indicated that clostridial cluster III members should be reclassified into four novel genera for which the names Hungateiclostridium gen. nov., Thermoclostridium gen. nov., Ruminiclostridium gen. nov. and Pseudoclostridium gen. nov. are proposed. In combination with the genera Anaerobacterium, Cellulosibacter, Ercella, Fastidiosipila, Mageeibacillus, Pseudobacteroides, Petroclostridium and Saccharofermentans, clostridial cluster III members formed a monophyletic clade within the order Clostridiales but that was clearly distinguished from other Ruminococcaceae members, which is proposed as a novel family, Hungateiclostridiaceae fam. nov.

Sequential combination therapy of ovarian cancer with cisplatin and γ-secretase inhibitor MK-0752.

OBJECTIVE: Ovarian cancer is one of the most lethal of women cancers and lack potent therapeutic options. There have many evidences demonstrate the Notch signaling has deregulation in variety of human malignancies.MK-0752 is a novel potent γ-secretase inhibitor and now assessed in clinical trial for treatment of several types of cancer, our objective was to investigate the anticancer effects and mechanisms of MK-0752 alone or combined with cisplatin in ovarian cancer. METHODS: Cell lines used: A2780, OVCAR3, SKOV3, HO8910PM, the effects of MK-0752 and cisplatin on cell proliferation were measured by MTT assay. The effect of combination treatment was examined by isobologram analysis. The distribution of cell cycle and cell apoptosis were analyzed using PI and Annexin V-FITC/PI staining by flow cytometric analysis. The mechanism in biochemistry was analyzed by using Western blot. Mouse xenograft model of A2780 was established to observe the anti-ovarian cancer effects in vivo setting, nude mice were randomized into four groups (n=6 per group) and treated every 4 days with control (solvent) group, MK-0752(25mg/kg) group, cisplatin (2mg/kg)group, combination group (both of MK-0752 and cisplatin). RESULTS: MK-0752 alone actively induced cell growth inhibition, G2/M phase cell cycle arrest and apoptosis with down-regulation of Notch1 and its downstream effectors including Hes1, XIAP, c-Myc and MDM2 in a dose- and time-dependent manner. Moreover, sequential combination of cisplatin prior to MK-0752 significantly promoted cell apoptosis and inhibited the subcutaneous xenograft growth of ovarian cancer in nude mice. CONCLUSION: Our data supports the sequential combination of cisplatin prior to MK-0752 is a highly promising novel experimental therapeutic strategy against ovarian cancer.