Birth weight and premature ovarian insufficiency: a systematic review and meta-analysis.

OBJECTIVE: To comprehensively evaluate the effect of low birth weight on premature ovarian insufficiency. METHODS: We performed a systematic review of the literature by searching MEDLINE, EMBASE, Web of Science, Scopus, Wanfang and CNKI up to August 2023. All cohort and case-control studies that included birth weight as an exposure and premature ovarian insufficiency as an outcome were included in the analysis. Data were combined using inverse-variance weighted meta-analysis with fixed and random effects models and between-study heterogeneity evaluated. We evaluated risk of bias using the Newcastle Ottawa Scale and using Egger's method to test publication bias. All statistical analyses were performed with the use of R software. RESULTS: Five articles were included in the review. A total of 2,248,594 women were included, including 21,813 (1%) cases of premature ovarian insufficiency, 150,743 cases of low birth weight, and 220,703 cases of macrosomia. We found strong evidence that changed the results of the previous review that low birth weight is associated with an increased risk of premature ovarian insufficiency (OR = 1.15, 95%CI 1.09-1.22) in adulthood compared with normal birth weight. No effect of macrosomia on premature ovarian insufficiency was found. CONCLUSIONS: Our meta-analysis showed strong evidence of an association between low birth weight and premature ovarian insufficiency. We should reduce the occurrence of low birth weight by various methods to avoid the occurrence of premature ovarian insufficiency.

Flexible and Energy-Efficient Synaptic Transistor with Quasi-Linear Weight Update Protocol by Inkjet Printing of Orientated Polar-Electret/High-k Oxide Composite Dielectric.

Inkjet printing artificial synapse is cost-effective but challenging in emulating synaptic dynamics with a sufficient number of effective weight states under ultralow voltage spiking operation. A synaptic transistor gated by inkjet-printed composite dielectric of polar-electret polyvinylpyrrolidone (PVP) and high-k zirconia oxide (ZrOx) is proposed and thus synthesized to solve this issue. Quasi-linear weight update with a large variation margin is obtained through the coupling effect and the facilitation of dipole orientation, which can be attributed to the orderly arranged molecule chains induced by the carefully designed microfluidic flows. Crucial features of biological synapses including long-term plasticity, spike-timing-dependence-plasticity (STDP), "Learning-Experience" behavior, and ultralow energy consumption (<10 fJ/pulse) are successfully implemented on the device. Simulation results exhibit an excellent image recognition accuracy (97.1%) after 15 training epochs, which is the highest for printed synaptic transistors. Moreover, the device sustained excellent endurance against bending tests with radius down to 8 mm. This work presents a very viable solution for constructing the futuristic flexible and low-cost neural systems.

Rotor-based image-guided therapy of glioblastoma.

Glioblastoma (GBM), deep in the brain, is more challenging to diagnose and treat than other tumors. Such challenges have blocked the development of high-impact therapeutic approaches that combine reliable diagnosis with targeted therapy. Herein, effective cyanine dyes (IRLy) with the near-infrared two region (NIR-II) adsorption and aggregation-induced emission (AIE) have been developed via an "extended conjugation & molecular rotor" strategy for multimodal imaging and phototherapy of deep orthotopic GBM. IRLy was synthesized successfully through a rational molecular rotor modification with stronger penetration, higher signal-to-noise ratio, and a high photothermal conversion efficiency (PCE) up to ∼60%, which can achieve efficient NIR-II photo-response. The multifunctional nanoparticles (Tf-IRLy NPs) were further fabricated to cross the blood-brain barrier (BBB) introducing transferrin (Tf) as a targeting ligand. Tf-IRLy NPs showed high biosafety and good tumor enrichment for GBM in vitro and in vivo, and thus enabled accurate, efficient, and less invasive NIR-II multimodal imaging and photothermal therapy. This versatile Tf-IRLy nanosystem can provide a reference for the efficient, precise and low-invasive multi-synergistic brain targeted photo-theranostics. In addition, the "extended conjugation & molecular rotor" strategy can be used to guide the design of other photothermal agents.

Bifunctional ligand Co metal-organic framework derived heterostructured Co-based nanocomposites as oxygen electrocatalysts toward rechargeable zinc-air batteries.

Rational construction of efficient and robust bifunctional oxygen electrocatalysts is key but challenging for the widespread application of rechargeable zinc-air batteries (ZABs). Herein, bifunctional ligand Co metal-organic frameworks were first explored to fabricate a hybrid of heterostructured CoOx/Co nanoparticles anchored on a carbon substrate rich in CoNx sites (CoOx/Co@CoNC) via a one-step pyrolysis method. Such a unique heterostructure provides abundant CoNx and CoOx/Co active sites to drive oxygen reduction reaction (ORR) and oxygen evolution reaction (OER), respectively. Besides, their positive synergies facilitate electron transfer and optimize charge/mass transportation. Consequently, the obtained CoOx/Co@CoNC exhibits a superior ORR activity with a higher half-wave potential of 0.88 V than Pt/C (0.83 V vs. RHE), and a comparable OER performance with an overpotential of 346 mV at 10 mA cm-2 to the commercial RuO2. The assembled ZAB using CoOx/Co@CoNC as a cathode catalyst displays a maximum power density of 168.4 mW cm-2, and excellent charge-discharge cyclability over 250 h at 5 mA cm-2. This work highlights the great potential of heterostructures in oxygen electrocatalysis and provides a new pathway for designing efficient bifunctional oxygen catalysts toward rechargeable ZABs.

Effects of temperature anomaly on sperm quality: A multi-center study of 33,234 men.

Backgrounds: Global fertility rates continue to decline and sperm quality is a prime factor affecting male fertility. Both extreme cold and heat have been demonstrated to be associated with decreased sperm quality, but no epidemiological studies have considered human adaptation to long-term temperature. Our aim was to conduct a multi-center retrospective cohort study to investigate exposure-response relationship between temperature anomaly (TA) that deviate from long-term climate patterns and sperm quality. Methods: A total of 78,952 semen samples measured in 33,234 donors from 6 provincial human sperm banks in China were collected. This study considered heat and cold acclimatization to prolonged exposure in humans and explored the exposure-response relationship between TAs and sperm quality parameters (sperm concentrations, sperm count, progressive motility, progressive sperm count, total motility and total motile sperm count) during the hot and cold seasons, respectively. Linear mixed models and generalized linear models were built separately for specific centers to pool in a meta-analysis to obtain the pooled effect of TA on sperm quality, considering repeated measurements data structure and spatial heterogeneity. Results: We identified an inverted U-shaped exposure-response relationship between TA and sperm quality during the hot season. Significant negative effect of anomalous cold on sperm quality during the hot season was found after additional adjustment for Body mass index, marital status and childbearing history. The heat-related TA in hot season was significantly negatively associated with sperm concentration, progressive sperm count and total motile sperm count (all P-values<0.05). After adjusting the relative humidity, the cold-related TA in cold season was negatively associated with the sperm total motility (P-values<0.05). Conclusions: Our results suggest both heat-related and cold-related TAs are associated with decreased sperm quality. The findings highlight the importance of reducing exposure to anomalous temperatures to protect male fertility.

[Mechanisms of changes of active components in Chinese medicinal materials during drying: a review].

Drying is an indispensable processing step for Chinese medicinal materials after harvesting. It often leads to significant changes in the active components of these materials, thus impacting their medicinal values. Understanding the mechanisms behind the changes during the drying process is of great importance for regulating the transformation of key active components. Therefore, this paper reviews the available studies and comprehensively expounds the mechanisms underlying the changes in active components during the drying process. The aim is to offer insights for the development of regulatory strategies and the improvement of drying techniques for Chinese medicinal materials.

Low levels of Cd2+ combined with procymidone may cause ovarian damage in mice via unfolded protein response.

As no study about the combined effect of low levels of Cd2+ with procymidone (PCM) on organs and organisms, we investigated their actions on mouse-ovary in vivo and in vitro. Four-week mice were treated with corn oil for the control group, corn oil + 0.0045 mg/L Cd2+ (CdCl2 was dissolved in ultrapure water and freely consumed by mice) for Cd2+ group, 50 mg/kg/d PCM (suspended in corn oil and administered orally to mice) for PCM group, and 50 mg/kg/d PCM + 0.0015 (0.0045 and 0.0135) mg/L Cd2+ for L+ (M+ and H+) PCM group for 21 days. For in vitro experiment, the cultured ovaries were treated with acetone for the control group, 0.1% acetone + 8.4 µg/L Cd2+ for the Cd2+ group, 0.63 mg/L PCM (dissolved in acetone) for the PCM-group, and 0.63 mg/L PCM + 2.8 (8.4 and 25.2) µg/L Cd2+ for L+ (M+ and H+) PCM group for 7 days. Mouse body weight in each treatment group, the weight and volume of ovaries in all PCM groups were lower than the control. Both in vivo and in vitro, all-stage follicle numbers were lower in M+PCM and H+PCM groups, whereas the atretic follicles and CASPASE3/8 were higher; meanwhile, lower estradiol and progesterone and higher unfolded protein response (UPR) members in all PCM groups. L+, M+, and H+PCM groups had further ovarian damage and stronger UPR than PCM groups, as did M+PCM groups over Cd2+ groups. It is hypothesized low-level PCM and Cd2+ may mutually promote each other's triggered UPR and exacerbate ovarian damage.

TEAD1, MYO7A and NDUFC2 are novel functional genes associated with glucose metabolism in BXD recombinant inbred population.

AIM: The liver is an important metabolic organ that governs glucolipid metabolism, and its dysfunction may cause non-alcoholic fatty liver disease, type 2 diabetes mellitus, dyslipidaemia, etc. We aimed to systematic investigate the key factors related to hepatic glucose metabolism, which may be beneficial for understanding the underlying pathogenic mechanisms for obesity and diabetes mellitus. MATERIALS AND METHODS: Oral glucose tolerance test (OGTT) phenotypes and liver transcriptomes of BXD mice under chow and high-fat diet conditions were collected from GeneNetwork. QTL mapping was conducted to pinpoint genomic regions associated with glucose homeostasis. Candidate genes were further nominated using a multi-criteria approach and validated to confirm their functional relevance in vitro. RESULTS: Our results demonstrated that plasma glucose levels in OGTT were significantly affected by both diet and genetic background, with six genetic regulating loci were mapped on chromosomes 1, 4, and 7. Moreover, TEAD1, MYO7A and NDUFC2 were identified as the candidate genes. Functionally, siRNA-mediated TEAD1, MYO7A and NDUFC2 knockdown significantly decreased the glucose uptake and inhibited the transcription of genes related to insulin and glucose metabolism pathways. CONCLUSIONS: Our study contributes novel insights to the understanding of hepatic glucose metabolism, demonstrating the impact of TEAD1, MYO7A and NDUFC2 on mitochondrial function in the liver and their regulatory role in maintaining in glucose homeostasis.

Donor engineering of a benzothiadiazole-based D-A-D-type molecular semiconductor for perovskite solar cells: a theoretical study.

Due to the easy formation of compact molecular packing arrangements and the favorable photophysical and electrochemical properties, donor-acceptor-donor (D-A-D)-type small molecule hole-transporting materials (HTMs) have been widely synthesized and researched to improve the efficiency and stability of perovskite solar cells (PSCs). The main approach in recent experiments has been to seek good acceptors, whereas the influence of the electron-donating units has been less reported. In this work, six new benzothiadiazole-based D-A-D-type HTMs are tailored by employing the ethyl-substituted phenoxazine (POZ), phenothiazine (PTZ) and carbazole (CZ) as the donors. To obtain an elementary understanding of new HTMs, the electronic, optical, hole-transporting and interfacial properties are simulated with quantum chemistry methods. The results indicate that all tailored HTMs exhibit suitable energy alignment compared with the band structures of the perovskite, and the continuous highest occupied molecular orbital (HOMO) levels will be helpful for interfacial energy regulation. In comparison with the YN1, the maximum absorption wavelengths of the newly designed HTMs are red-shifted due to the decreased excitation energies from the ground-state to the first singlet excited-state. Importantly, the hole mobilities of all designed HTMs are distinctly higher than the referenced YN1, which is contributed by the better planarity of the molecular skeleton and the easier orbital overlapping between adjacent molecules. The interfacial simulations manifest that the FAPbI3/SM37 system displays a more stable adsorption configuration and greater charge redistributions at the interface compared to YN1, which further promotes the separation of photogenerated electron-hole pairs. Moreover, larger Stokes shifts and better solubility are also acquired for the new HTMs. In summary, our calculations not only propose several potential highly efficient HTMs, but also provide useful insights at the atomic level for the experimental synthesis of new D-A-D-type HTMs.

Glutathione S-transferase activity facilitates rice tolerance to the barnyard grass root exudate DIMBOA.

BACKGROUND: In paddy fields, the noxious weed barnyard grass secretes 2,4-dihydroxy-7-methoxy-2H-1,4-benzoxazin-3(4H)-one (DIMBOA) to interfere with rice growth. Rice is unable to synthesize DIMBOA. Rice cultivars with high or low levels of allelopathy may respond differently to DIMBOA. RESULTS: In this study, we found that low concentrations of DIMBOA (≤ 0.06 mM) promoted seedling growth in allelopathic rice PI312777, while DIMBOA (≤ 0.08 mM) had no significant influence on the nonallelopathic rice Lemont. DIMBOA treatment caused changes in the expression of a large number of glutathione S-transferase (GST) proteins, which resulting in enrichment of the glutathione metabolic pathway. This pathway facilitates plant detoxification of heterologous substances. The basal levels of GST activity in Lemont were significantly higher than those in PI312777, while GST activity in PI312777 was slightly induced by increasing DIMBOA concentrations. Overexpression of GST genes (Os09g0367700 and Os01g0949800) in these two cultivars enhanced rice resistance to DIMBOA. CONCLUSIONS: Taken together, our results indicated that different rice accessions with different levels of allelopathy have variable tolerance to DIMBOA. Lemont had higher GST activity, which helped it tolerate DIMBOA, while PI312777 had lower GST activity that was more inducible. The enhancement of GST expression facilitates rice tolerance to DIMBOA toxins from barnyard grass root exudates.

Association of sleep characteristics with cardiovascular disease risk in adults over 40 years of age: a cross-sectional survey.

Background: The relationship between sleep characteristics and cardiovascular disease (CVD) risk has yet to reach a consistent conclusion, and more research needs to be carried out. This study aimed to explore the relationship between snoring, daytime sleepiness, bedtime, sleep duration, and high-risk sleep patterns with CVD risk. Methods: Data from the National Health and Nutrition Examination Survey (NHANES) 2015-2018 were collected and analyzed. Multivariable logistic regression was used to evaluate the relationship between snoring, daytime sleepiness, bedtime, sleep duration, high-risk sleep patterns, and CVD risk. Stratified analysis and interaction tests were carried out according to hypertension, diabetes and age. Results: The final analysis contained 6,830 participants, including 1,001 with CVD. Multivariable logistic regression suggested that the relationship between snoring [OR = 7.37,95%CI = (6.06,8.96)], daytime sleepiness [OR = 11.21,95%CI = (9.60,13.08)], sleep duration shorter than 7 h [OR = 9.50,95%CI = (7.65,11.79)] or longer than 8 h [OR = 6.61,95%CI = (5.33,8.19)], bedtime after 0:00 [OR = 13.20,95%CI = (9.78,17.80)] compared to 22:00-22:59, high-risk sleep patterns [OR = 47.73,95%CI = (36.73,62.04)] and CVD risk were statistically significant. Hypertension and diabetes interacted with high-risk sleep patterns, but age did not. Conclusions: Snoring, daytime sleepiness, excessive or short sleep duration, inappropriate bedtime, and high-risk sleep patterns composed of these factors are associated with the CVD risk. High-risk sleep patterns have a more significant impact on patients with hypertension and diabetes.

Association between different insulin resistance surrogates and all-cause mortality in patients with coronary heart disease and hypertension: NHANES longitudinal cohort study.

BACKGROUND: Studies on the relationship between insulin resistance (IR) surrogates and long-term all-cause mortality in patients with coronary heart disease (CHD) and hypertension are lacking. This study aimed to explore the relationship between different IR surrogates and all-cause mortality and identify valuable predictors of survival status in this population. METHODS: The data came from the National Health and Nutrition Examination Survey (NHANES 2001-2018) and National Death Index (NDI). Multivariate Cox regression and restricted cubic splines (RCS) were performed to evaluate the relationship between homeostatic model assessment of IR (HOMA-IR), triglyceride glucose index (TyG index), triglyceride glucose-body mass index (TyG-BMI index) and all-cause mortality. The recursive algorithm was conducted to calculate inflection points when segmenting effects were found. Then, segmented Kaplan-Meier analysis, LogRank tests, and multivariable Cox regression were carried out. Receiver operating characteristic (ROC) and calibration curves were drawn to evaluate the differentiation and accuracy of IR surrogates in predicting the all-cause mortality. Stratified analysis and interaction tests were conducted according to age, gender, diabetes, cancer, hypoglycemic and lipid-lowering drug use. RESULTS: 1126 participants were included in the study. During the median follow-up of 76 months, 455 participants died. RCS showed that HOMA-IR had a segmented effect on all-cause mortality. 3.59 was a statistically significant inflection point. When the HOMA-IR was less than 3.59, it was negatively associated with all-cause mortality [HR = 0.87,95%CI (0.78, 0.97)]. Conversely, when the HOMA-IR was greater than 3.59, it was positively associated with all-cause mortality [HR = 1.03,95%CI (1.00, 1.05)]. ROC and calibration curves indicated that HOMA-IR was a reliable predictor of survival status (area under curve = 0,812). No interactions between HOMA-IR and stratified variables were found. CONCLUSION: The relationship between HOMA-IR and all-cause mortality was U-shaped in patients with CHD and hypertension. HOMA-IR was a reliable predictor of all-cause mortality in this population.

In vitro study of miRNA-369-3p targeting TCF4 regulating the malignant biological behavior of colon cancer cells.

Background: Colorectal carcinoma (CRC) is a common malignant tumor of the digestive tract. It is characterized by a high degree of malignancy, early metastasis and poor prognosis. Studies have shown the effect of miR-369-3p on the biological function of a variety of tumors. However, the mechanism by which miR-369-3p and its potential target genes participate in the pathogenesis of CRC has not been elucidated. This study aims to study the relationship between miR-369-3p and transcription factor 4 (TCF4), to reveal the mechanism of the occurrence and development of CRC, and to provide a promising target for the treatment of CRC. Methods: Real-time quantitative polymerase chain reaction (RT-qPCR) was used to detect the miR-369-3p levels in CRC tissues and cells. miR-369-3p mimics and/or TCF4 overexpression vectors were transfected into SW480 cells. The expression of miR-369-3p and TCF4 mRNA was detected using RT-qPCR. Bioinformatics analysis predicted the binding site of miR-369-3p to the TCF4 3'UTR, and the targeting relationship was verified by a dual luciferase reporter gene assay. Cell proliferation and invasion were investigated by labeled immunofluorescence assay using BrdU antibody and Transwell assay. The oxidative stress ability of cells was determined by commercial kits. The levels of proteins related to cell proliferation and invasion were measured by western blotting. Results: The level of miR-369-3p was significantly down-regulated in CRC tissues and cell lines, especially in SW480 cells (P<0.05). The expression of TCF4 was negatively correlated with that of miR-369-3p. High levels of miR-369-3p targeting TCF4 suppressed cell proliferation and downregulated the protein expression of Ki67 and PCNA (P<0.05). Overexpressed miR-369-3p binding TCF4 inhibited cell invasion and decreased the protein levels of vascular endothelial growth factor (VEGF) and E-cadherin (P<0.05). Furthermore, upregulation of miR-369-3p increased the activity of superoxide dismutase (SOD) while decreasing the content of malondialdehyde (MDA) and activity of lactate dehydrogenase (LDH) by blocking the expression of TCF4 (P<0.05). Conclusions: MiR-369-3p inhibits the proliferation, invasion and oxidative stress of CRC cells by targeting TCF4, thus defining miR-369-3p as a potential target for the diagnosis and treatment of CRC.

Amino-Functionalized Zirconium-Based Metal-Organic Frameworks as Bifunctional Nanomaterials to Treat Bone Tumors and Promote Osteogenesis.

Bone tumor patients often encounter challenges associated with cancer cell residues and bone defects postoperation. To address this, there is an urgent need to develop a material that can enable tumor treatment and promote bone repair. Metal-organic frameworks (MOFs) have attracted the interest of many researchers due to their special porous structure, which has great potential in regenerative medicine and drug delivery. However, few studies explore MOFs with dual antitumor and bone regeneration properties. In this study, we investigated amino-functionalized zirconium-based MOF nanoparticles (UiO-66-NH2 NPs) as bifunctional nanomaterials for bone tumor treatment and osteogenesis promotion. UiO-66-NH2 NPs loading with doxorubicin (DOX) (DOX@UiO-66-NH2 NPs) showed good antitumor efficacy both in vitro and in vivo. Additionally, DOX@UiO-66-NH2 NPs significantly reduced lung injury compared to free DOX in vivo. Interestingly, the internalized UiO-66-NH2 NPs notably promoted the osteogenic differentiation of preosteoblasts. RNA-sequencing data revealed that PI3K-Akt signaling pathways or MAPK signaling pathways might be involved in this enhanced osteogenesis. Overall, UiO-66-NH2 NPs exhibit dual functionality in tumor treatment and bone repair, making them highly promising as a bifunctional material with broad application prospects.

The effect of subcutaneous dulaglutide on weight loss in patients with Type 2 diabetes mellitus: Systematic review and meta-analysis of randomized controlled trials.

BACKGROUND: Dulaglutide, a subcutaneously administered glucagon-like peptide 1 receptor agonist, has been hypothesized to lead to weight loss in patients with Type 2 diabetes mellitus (T2DM). However, the consequences of its prescription on body weight (BW) and other anthropometric indices, for example, body mass index (BMI) or waist circumference (WC), have not been completely clarified. Therefore, we aimed to assess the effects of subcutaneous dulaglutide administration on BW, BMI and WC values in T2DM subjects by means of a systematic review and meta-analysis of RCTs. METHODS: We computed a literature search in five databases (PubMed/Medline, Web of Science, EMBASE, Scopus and Google Scholar) from their inception to February 2023 to identify RCTs that examined the influence of subcutaneous dulaglutide on obesity indices. We calculated effect sizes using the random-effects model (using DerSimonian-Laird method). Results were derived across weighted mean differences (WMD) and 95% confidence intervals (CI). Subgroup analyses were applied to explore possible sources of heterogeneity among the RCTs. The current systematic review and meta-analysis was conducted in compliance with The Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement. RESULTS: In total, 18 studies with 33 RCT arms (BW = 33 RCT arms, 14,612 participants, 7869 cases and 6743 controls; BMI = 10 RCT arms, 14,612 subjects, 7869 cases and 6743 controls; WC = 10 RCT arms, 1632 participants, 945 cases and 687 cases) were included in the meta-analysis. BW (WMD: -0.86 kg, 95% CI: -1.22, -0.49, p < 0.001), BMI (WMD: -0.68 kg/m2 , 95% CI: -0.88, -0.49, p < 0.001) and WC (WMD: -1.23 cm, 95% CI: -1.82, -0.63, p < 0.001) values decreased notably following subcutaneous dulaglutide administration versus placebo. BW notably decreased in RCTs lasting >18 weeks (WMD: -1.42 kg, 95% CI: -1.90, -0.94, p < 0.001), whereas notable reductions in WC were seen in RCTs lasting ≤18 weeks (WMD: -1.78 cm, 95% CI: -2.59, -0.98, p < 0.001). Dulaglutide dosages >1 mg/day significantly decreased BW (WMD: -1.94 kg, 95% CI: -2.54, -1.34, p < 0.001), BMI (WMD: -0.80 kg/m2 , 95% CI: -1.07, -0.54, p < 0.001) and WC (WMD: -1.47 cm, 95% CI: -1.80, -1.13, p < 0.001). BW decreased particularly following dulaglutide prescription in individuals with obesity (WMD: -1.05 kg, 95% CI: -1.28, -0.82, p < 0.001) versus overweight. The dose-response meta-analysis revealed that BW decreased significantly when dulaglutide was prescribed in doses ≤3 mg/day versus >3 mg/day. CONCLUSIONS: Subcutaneous dulaglutide administration in T2DM reduces BW, BMI and WC. The decrease in BW and WC was influenced by the dose and the duration of dulaglutide administration. The reduction in BMI was only influenced by the dosage of dulaglutide. Moreover, T2DM patients who suffered from obesity experienced a notable decrease in BW versus T2DM subjects without obesity.

Depletion of gut microbiota influents glucose metabolism and hyperandrogenism traits of mice with PCOS induced by letrozole.

Background: Polycystic ovary syndrome (PCOS) is a multifaceted disorder that impacts metabolism, reproduction, as well as endocrine function, characterized by excessive levels of androgen and insulin resistance. The gut microbiota has been implicated in the pathogenesis of PCOS. However, the precise mechanisms through which the gut microbiota influences PCOS still require further elucidation. Methods: The PCOS mouse model was established through the administration of letrozole to both conventional and antibiotics-treated mice. The evaluation of glucose metabolism, sex hormone levels, and ovarian morphology was conducted. Furthermore, the fecal samples from each group of mice were subjected to 16S rRNA gene sequencing, and functional prediction of gut microbiota was proceeded using PICRUSt2 to explore potential mechanisms. Results: By using letrozole-induced PCOS mice model, we manifested that antibiotic intervention significantly reduced the serum total testosterone level and ameliorated glucose intolerance. Antibiotic treatment reduced the number of amplicon sequence variants (ASVs), as well as the Shannon and Simpson index. Meanwhile, letrozole induced a significant increase in the Shannon and Simpson index instead of ASVs. Through random forest model analysis, the results revealed significant alterations in three distinct groups of microbiota, namely Clostridia_vadinBB60_group, Enterorhabdus, and Muribaculaceae after letrozole treatment. Further correlation analysis revealed a positive association between alterations in these microbiota and both serum total testosterone levels and the area under the curve (AUC) of blood glucose in IPGTT. The administration of antibiotics led to a decrease in the absolute abundance of 5 ASVs belonging to unclassified Clostridia_vadinBB60_group, unclassified Enterorhabdus, and unclassified Muribaculaceae, which exhibited a positive correlation with the levels of total testosterone in mice serum, as well as the area under the curve of blood glucose in IPGTT. Moreover, 25 functional pathways of gut microbiome were significantly discrepant between the letrozole-treated mice with and without antibiotics. Conclusion: These results suggest that disturbance of the gut microbiota may take participate in the progression of PCOS and manipulating the composition of the gut microbiota may be a therapeutic approach for managing PCOS.

Circulating bile acid profile characteristics in PCOS patients and the role of bile acids in predicting the pathogenesis of PCOS.

Background: The metabolic profile of bile acids and their potential role as biomarkers in the pathogenesis of polycystic ovary syndrome (PCOS) have not been thoroughly characterized. Assessing their predictive value for PCOS is of significant importance. Methods: In this study, we enrolled 408 women with PCOS and 204 non-PCOS controls. The serum bile acid profile was measured using high-performance liquid chromatography-tandem mass spectrometry (LC/MS). We analyzed the differences in serum bile acid profiles between PCOS patients using the OPLS-DA model. Additionally, we examined the relationship between bile acid profiles and parameters related to glucose metabolism and hyperandrogenism. ROC analysis was employed to identify potential biomarkers for PCOS pathogenesis. XGboost was utilized for cross-validation. Results: The bile acid profile was found to be altered in PCOS patients. Specifically, the primary and secondary unconjugated bile acid fractions were significantly higher in the PCOS population. We identified five bile acid metabolite candidates that exhibited the most significant differences between PCOS and non-PCOS controls. DCA was associated with deposition index, fasting and postprandial insulin but was influenced by testosterone. CDCA and LCA combined with testosterone showed potential as biomarkers for the pathogenesis of PCOS. Conclusion: The circulating bile acid profile undergoes changes in PCOS. DCA is associated with deposition index, fasting and postprandial insulin and its level is influenced by testosterone. CDCA and LCA combined with testosterone have the potential to serve as biomarkers for the pathogenesis of PCOS.

Exposure to Fine Particulate Matter Constituents and Human Semen Quality Decline: A Multicenter Study.

Exposure to fine particulate matter (PM < 2.5 µm in diameter [PM2.5]) may accelerate human sperm quality decline, although research on this association is limited. Our objective was to investigate the relationship between exposure to the chemical constituents of PM2.5 air pollution and decreased sperm quality and to further explore the exposure-response relationship. We conducted a multicenter population-based cohort study including 78,952 semen samples from 33,234 donors at 6 provincial human sperm banks (covering central, northern, southern, eastern, and southwestern parts of China) between 2014 and 2020. Daily exposure to PM2.5 chemical composition was estimated using a deep learning model integrating a density ground-based measure network at a 1 km resolution. Linear mixed models with subject- and center-specific intercepts were used to quantify the harmful impacts of PM2.5 constituents on semen quality and explore their exposure-response relationships. Per interquartile range (IQR) increase in PM2.5 exposure levels during spermatogenesis was significantly associated with decreased sperm concentration, progressive motility, and total motility. For PM2.5 constituents, per IQR increment in Cl- (ß: -0.02, 95% CI: [-0.03, -0.00]) and NO3- (ß: -0.05, 95% CI: [-0.08, -0.02]) exposure was negatively associated with sperm count, while NH4+ (ß: -0.03, 95% CI: [-0.06, -0.00]) was significantly linked to decreased progressive motility. These results suggest that exposure to PM2.5 chemical constituents may adversely affect human sperm quality, highlighting the urgent need to reduce PM2.5 exposure.

Characterising Biosecurity Initiatives Globally to Support the Development of a Progressive Management Pathway for Terrestrial Animals: A Scoping Review.

While biosecurity is of increasing importance globally, there is still limited evidence of the factors or elements that support the progressive and sustainable scaling up of biosecurity along the value chains from the local to the global level. To gain insight into the current body of literature on biosecurity, a mixed-methods approach was used based on a scoping literature review and an online survey with subject matter experts. Six databases were searched for published literature, and textual information from titles and abstracts of all included records (n = 266) were analysed through inductive content analysis to build biosecurity-relevant categories and identify strengths, weaknesses, opportunities, and threats (SWOT) of existing biosecurity systems or initiatives (such as projects or programs). Most records focused on initiatives in high-income countries, traditional livestock species (pigs, poultry, and large ruminants), and the production stage and had a disease-specific focus. No records described a comprehensive or global framework to progressively scale up biosecurity. Overall, the findings highlight the need for initiatives such as the FAO Progressive Management Pathway for Terrestrial Animal Biosecurity (FAO-PMP-TAB), which is a stepwise approach for strengthening biosecurity management along value chains to enhance the health, resilience, and sustainability of animal sectors. The findings highlight important elements and provide recommendations useful for developing approaches or a global framework to progressively improve biosecurity management.