Changes in the serum metabolomics of polycystic ovary syndrome before and after compound oral contraceptive treatment.

Background: Polycystic ovary syndrome (PCOS) is both a common endocrine syndrome and a metabolic disorder that results in harm to the reproductive system and whole-body metabolism. This study aimed to investigate differences in the serum metabolic profiles of patients with PCOS compared with healthy controls, in addition to investigating the effects of compound oral contraceptive (COC) treatment in patients with PCOS. Materials and methods: 50 patients with PCOS and 50 sex-matched healthy controls were recruited. Patients with PCOS received three cycles of self-administered COC treatment. Clinical characteristics were recorded, and the laboratory biochemical data were detected. We utilized ultra-performance liquid chromatography-high-resolution mass spectrometry to study the serum metabolic changes between patients with PCOS, patients with PCOS following COC treatment, and healthy controls. Result: Patients with PCOS who received COC treatment showed significant improvements in serum sex hormone levels, a reduction in luteinising hormone levels, and a significant reduction in the levels of biologically active free testosterone in the blood. Differential metabolite correlation analysis revealed differences between PCOS and healthy control groups in N-tetradecanamide, hexadecanamide, 10E,12Z-octadecadienoic acid, and 13-HOTrE(r); after 3 months of COC treatment, there were significant differences in benzoic acid, organic acid, and phenolamides. Using gas chromatography-mass spectrometry to analyse blood serum in each group, the characteristic changes in PCOS were metabolic disorders of amino acids, carbohydrates, and purines, with significant changes in the levels of total cholesterol, uric acid, phenylalanine, aspartic acid, and glutamate. Conclusion: Following COC treatment, improvements in sex hormone levels, endocrine factor levels, and metabolic levels were better than in the group of PCOS patients receiving no COC treatment, indicating that COC treatment for PCOS could effectively regulate the levels of sex hormones, endocrine factors, and serum metabolic profiles.

Exploring the workplace factors and their influence on the employment outcomes for people with multiple sclerosis.

BACKGROUND: High unemployment rate of people with multiple sclerosis (PwMS) is associated with substantial economic costs. Whilst the impact of MS symptoms and other disease-related factors on employment outcomes of PwMS has been assessed, limited evidence exists on the impacts of workplace factors. OBJECTIVE: To investigate the most common individual and group workplace factors associated with unemployment or a perceived risk of unemployment in PwMS, and to identify patient subgroups that are more susceptible to changes in employment status due to such factors. METHODS: Data from the Australian MS Longitudinal Study (AMSLS) on employment status and workplace factors were used. Fifteen workplace factors were classified under four groups: organisational, commuting, moving around at work, and equipment usage factors. Participants answered 'Yes' to each factor if it related to their unemployment and/or perceived risk of becoming unemployed and a group factor was considered "Yes" if at least one individual factor within it was answered as "Yes". The proportions of "Yes" responses were calculated for both individual and group factors. Total number of individual factors was calculated and descriptive analyses and ordered logistic regression were used to summarize the total number of factors affecting each participant, and their association with participants' occupations, sex, disability severity and disease duration. RESULTS: Common workplace factors influencing employment were organisational (39.8 % perceived risk, 44.0 % lost employment), commuting (28.9 % perceived risk) and equipment usage difficulty (30.9 % lost employment). Common individual factors included inflexible working conditions, lack of suitable work, commuting difficulties, architectural barriers, and requirement to stand for long periods to use equipment. Professionals, blue-collar workers, and those with moderate/severe disability were more likely to report a higher number of workplace factors risking their employment. CONCLUSIONS: Workplace factors undermine PwMS employment, with variations among subgroups based on occupation and disability severity. Understanding these barriers is crucial for supporting PwMS in the workforce.

Ratiometric fluorescence and smartphone-assisted sensing platform based on dual-emission carbon dots for brilliant blue detection.

In this study, an innovative ratiometric fluorescence and smartphone-assisted visual sensing platform based on blue-yellow dual-emission carbon dots (BY-CDs) was constructed for the first time to determine brilliant blue. The BY-CDs was synthesized via a facile one-step hydrothermal process involving propyl gallate and o-phenylenediamine. The synthesized BY-CDs exhibit favorable water solubility and exceptional fluorescence stability. Under excitation at 370 nm, BY-CDs show two distinguishable fluorescence emission bands (458 and 558 nm). Upon addition of brilliant blue, the fluorescence intensity at 558 nm exhibited a significant quenching effect attributed to fluorescence resonance energy transfer (FRET), while the fluorescence intensity at 458 nm was basically unchanged. The prepared BY-CDs can effectively serve as a ratiometric nanosensor for determining brilliant blue with the ratio of fluorescence intensities at 458 and 558 nm (F458/F558) as response signal. In addition, the developed ratiometric fluorescence sensor exhibits a noticeable alteration in color from yellow to green under UV light with a wavelength of 365 nm upon addition of varying concentrations of brilliant blue, which provides the possibility of visual detection of brilliant blue by a smartphone application. Finally, the BY-CDs based dual-mode sensing platform successfully detected brilliant blue in actual food samples and achieved a desirable recovery rate. This study highlights the merits of fast, convenient, economical, real-time, visual, high accuracy, excellent precision, good selectivity and high sensitivity for brilliant blue detection, and paves new paths for the monitoring of brilliant blue in real samples.

Effects of CYP3A4 genetic polymorphisms on the pharmacokinetics and efficacy of perampanel in Chinese pediatric patients with epilepsy.

OBJECTIVE: This study was the first to evaluate the effect of CYP3A4 gene polymorphisms on the plasma concentration and effectiveness of perampanel (PER) in Chinese pediatric patients with epilepsy. METHODS: We enrolled 102 patients for this investigation. The steady-state concentration was determined after patients maintained a consistent PER dosing regimen for at least 21 days. Plasma PER concentrations were measured using liquid chromatography-tandem mass spectrometry. Leftover samples from standard therapeutic drug monitoring were allocated for genotyping analysis. The primary measure of efficacy was the rate of seizure reduction with PER treatment at the final check-up. RESULTS: The CYP3A4×10 GC phenotype exhibited the highest average plasma concentration of PER at 491.1 ±â€¯328.1 ng/mL, in contrast to the CC phenotype at 334.0 ±â€¯161.1 ng/mL. The incidence of adverse events was most prominent in the CYP3A4×1 G TT and CYP3A4×10 GC groups, with rates of 77.8 % (7 of 9 patients) and 50.0 % (46 of 92 patients), respectively. Moreover, the percentage of patients for whom PER was deemed ineffective was least in the CYP3A4×1 G TT and CYP3A4×10 CC groups, recorded at 11.1 % (1 of 9 patients) and 10.0 % (1 of 10 patients), respectively. There was a significant correlation between PER plasma concentration and either exposure or toxicity (both with p < 0.05). We suggest a plasma concentration range of 625-900 ng/mL as a suitable reference for PER in Chinese patients with epilepsy. CONCLUSION: The CYP3A4×10 gene's genetic polymorphisms influence plasma concentrations of PER in Chinese pediatric patients with epilepsy. Given that both efficacy and potential toxicity are closely tied to plasma PER levels, the CYP3A4 genetic phenotype should be factored in when prescribing PER to patients with epilepsy.

Gold nanoparticles-conjugation of irisin enhances therapeutic effect by improving cardiac function and attenuating inflammation in sepsis.

Irisin is considered to be a promising therapeutic approach for cardiac depression and inflammatory disorders. The short half-life of irisin impeded its use and drug efficacy in the treatment. This study aimed to examine if pegylated gold nanoparticles-conjugated to irisin would improve therapeutic effects in cecal ligation and puncture (CLP)-induced sepsis in mice. Recombinant irisin were conjugated to a pegylated gold nanoparticle, which was given to mice exposed to CLP. The cecal ligation procedure and sham on mice were operated and assigned to one of following five groups: (I) CLP group: The mouse models underwent the CLP surgical procedure and received only vehicle saline treatment (n = 5); (II) CLP + soluble Irisin: The mouse underwent the CLP and received an intramuscular injection (i.m) (TA) injection of 1 ug of soluble irisin into each tibialis anterior (TA) leg (n = 5); (III) CLP + Gold nanoparticle-conjugated to Irisin: The mouse models underwent the CLP and received an i.m (TA) injection of 1 µg of Gold nanoparticle-irisin via intramuscular injection (TA) into each leg (n = 5); (IV) CLP + Gold nanoparticles- conjugated to IgG: The mouse underwent the CLP and received an i.m (TA) injection of gold nanoparticles conjugated to IgG (n = 5). (V) Sham: The mouse underwent the surgical operation without conducting the CLP (n = 10). The post-operated animals were observed for one week, and survival rates were estimated. Echocardiography was performed to measure cardiac function at 12 h following CLP. TUNEL was employed to detect apoptosis in both cardiac and skeletal muscles; histology was conducted to assess tissue injury in muscles. Enzyme linked immunosorbent assay (ELISA) was conducted to examine release of interleukin 6 (IL6) and the tumor necrosis factor (TNF) alpha. Compared to the CLP control, soluble irisin treatment improved cardiac function recovery, as indicated by the fractional shortening (FS) and ejection fraction (EF). Irisin treatment exhibited reduced IL6 and TNF-alpha release in association with less apoptosis, lower muscle injury index and improved survival post-CLP. However, compared to soluble irisin treatment, gold nanoparticles-conjugated to irisin showed a significant improvement in cardiac function, suppression of apoptosis, reduced IL6 and TNF-alpha releases, decreased muscle injury and an improved survival rate of post-CLP. This study reveals that gold nanoparticles-conjugated irisin can serve to improve irisin's therapeutic effects over a longer course of treatment.

Structural basis for the H2AK119ub1-specific DNMT3A-nucleosome interaction.

Isoform 1 of DNA methyltransferase DNMT3A (DNMT3A1) specifically recognizes nucleosome monoubiquitylated at histone H2A lysine-119 (H2AK119ub1) for establishment of DNA methylation. Mis-regulation of this process may cause aberrant DNA methylation and pathogenesis. However, the molecular basis underlying DNMT3A1-nucleosome interaction remains elusive. Here we report the cryo-EM structure of DNMT3A1's ubiquitin-dependent recruitment (UDR) fragment complexed with H2AK119ub1-modified nucleosome. DNMT3A1 UDR occupies an extensive nucleosome surface, involving the H2A-H2B acidic patch, a surface groove formed by H2A and H3, nucleosomal DNA, and H2AK119ub1. The DNMT3A1 UDR's interaction with H2AK119ub1 affects the functionality of DNMT3A1 in cells in a context-dependent manner. Our structural and biochemical analysis also reveals competition between DNMT3A1 and JARID2, a cofactor of polycomb repression complex 2 (PRC2), for nucleosome binding, suggesting the interplay between different epigenetic pathways. Together, this study reports a molecular basis for H2AK119ub1-dependent DNMT3A1-nucleosome association, with important implications in DNMT3A1-mediated DNA methylation in development.

Immune-mediated disruption of the blood-brain barrier after intracerebral hemorrhage: Insights and potential therapeutic targets.

AIMS: Intracerebral hemorrhage (ICH) is a condition that arises due to the rupture of cerebral blood vessels, leading to the flow of blood into the brain tissue. One of the pathological alterations that occurs during an acute ICH is an impairment of the blood-brain barrier (BBB), which leads to severe perihematomal edema and an immune response. DISCUSSION: A complex interplay between the cells of the BBB, for example, pericytes, astrocytes, and brain endothelial cells, with resident and infiltrating immune cells, such as microglia, monocytes, neutrophils, T lymphocytes, and others accounts for both damaging and protective mechanisms at the BBB following ICH. However, the precise immunological influence of BBB disruption has yet to be richly ascertained, especially at various stages of ICH. CONCLUSION: This review summarizes the changes in different cell types and molecular components of the BBB associated with immune-inflammatory responses during ICH. Furthermore, it highlights promising immunoregulatory therapies to protect the integrity of the BBB after ICH. By offering a comprehensive understanding of the mechanisms behind BBB damage linked to cellular and molecular immunoinflammatory responses after ICH, this article aimed to accelerate the identification of potential therapeutic targets and expedite further translational research.

[Study on anti-inflammatory activity of phenolic acids from Leucas ciliata].

The chemical constituents from Leucas ciliata belonging to Leucas genus in Lamiaceae were systematically explored by silica gel column chromatography, ODS column chromatography, Sephadex LH-20 gel column chromatography, and preparative high performance liquid chromatography, and seventeen phenolic acids were isolated. The chemical structures of the compounds were identified by their physicochemical properties, spectroscopic data, and literature. They were 4-hydroxyphenethyl ethyl succinate(1), 4-hydroxyphenethyl methyl succinate(2), 2-(4-hydroxyphenyl) ethyl acetate(3), p-hydroxyphenylethyl anisate(4), cassia cis-trans diphenylpropanoid(5), p-coumaric acid(6), 3,4-dihydroxybenzenepropionic acid methyl ester(7), caffeic acid(8), trans-p-hydroxyl ethyl cinnamate(9), methyl p-hydroxybenzeneacetate(10), 4-hydroxyphenethyl alcohol(11), syringic acid(12), vanillin(13), protocatechuic acid(14), salicylic acid(15), p-hydroxybenzaldehyde(16), and diorcinol(17). Among them, compound 1 was new, and compounds 2-10, 12, 14, and 16-17 were isolated from the plants belonging to Leucas genus for the first time. All compounds were obtained from L. ciliata for the first time. The anti-inflammatory activity of compounds 1-17 on NO production in lipopolysaccharide(LPS)-induced mouse leukemia cells of monocyte macrophage(RAW264. 7) cells was evaluated. The results showed that compounds 5, 7, and 9 exhibited significant anti-inflammatory activity, with IC50values of(10. 14±0. 36)-(21. 17±0. 11) µmol·L~(-1).

Effects of Freeze-Thaw Pretreatment Combined with Hot Air on Snake Gourd (Trichosanthes anguina L.).

Snake gourd is a seasonal vegetable with a high water content and medicinal value, but the short harvest period limits the large-scale application of snake gourd. Therefore, the effects of freeze-thaw pretreatment (FT) combined with hot air (HD) on the drying characteristics, active ingredients and bioactivities of snake gourd were investigated. The results showed that FT pretreatment reduced browning and shortened the drying time by 44%; the Page model was the best fit for describing the drying process. The polysaccharide contents (21.70% in alcoholic extract (TG1) and 44.34% in water extract (TG2)) and total phenol contents (1.81% in TG1 and 0.88% in TG2) of snake gourd pretreated by FT-HD were higher than those of snake gourd pretreated by the corresponding HD treatment. The FT pretreatment decreased the molecular weight of snake gourd polysaccharides and increased the molar ratio of glucose. The extracts pretreated by FT-HD showed greater chemical, cellular antioxidant capacity and α-amylase and α-glucosidase inhibition than those pretreated by HD. FT-HD can be recommended for achieving a short drying time and high quality of snake gourd and can be used for the drying of other fruits and vegetables.

Responses of soil organic carbon compounds to phosphorus addition between tropical monoculture and multispecies forests.

Tropical forests are sensitive to nitrogen (N) and phosphorus (P) availability, and under nutrient application the variation of soil organic carbon (SOC) preserving mechanism remains to be explored. To reveal the forest-specific SOC preservation via biochemical selection in response to nutrient application, we investigated a monoculture (Acacia plantation) and a multispecies forest both with chronic fertilization in subtropical regions, and measured specific fingerprints of plant- and microbial-derived C compounds. In addition, to quantify the effect of P application on SOC content among tropical forests, we conducted a meta-analysis by compiling 125 paired measurements in field experiments from 62 studies. In our field experiment, microbial community composition and activity mediated forest-specific responses of SOC compounds to P addition. The shift of community composition from fungi towards Gram-positive bacteria in the Acacia plantation by P addition led to the consumption of microbial residual C (MRC) as C source; in comparison, P addition increased plant species with less complex lignin substrates and induced microbial acquisition for N sources, thus stimulated the decomposition of both plant- and microbial-derived C. Same with our field experiment, bulk SOC content had neutral response to P addition among tropical forests in the meta-analysis, although divergences could happen among experimental durations and secondary tree species. Close associations among SOC compounds with biotic origins and mineral associated organic C (MAOC) in the multispecies forest suggested contributions of both plant- and microbial-derive C to SOC stability. Regarding that fungal MRC closely associated with MAOC and consisted of soil N pool which tightly coupled to SOC pool, the reduce of fungal MRC by chronic P addition was detrimental to SOC accumulation and stability in tropical forests.

Efficient recovery of gold from solution with a thiocyanate-modified Zr-MOF: adsorption properties and DFT calculations.

The design and development of new large-capacity and selective materials for extracting rare precious metals via electronic waste is practically essential. In this paper, a new efficient UiO-66-NCS has been obtained as a consequence of the modification of the classical Zr-MOF (UiO-66-NH2), and its ability to recover gold has been investigated. These batch results adequately illustrated that UiO-66-NCS exhibited good adsorption capacity (675.5 mg g-1) and exceptional selectivity. In addition, UiO-66-NCS achieved faster adsorption equilibrium times of about 120 min. Adsorption kinetics and isotherms demonstrated that the pseudo-second-order adsorption scheme and a Langmuir-type procedure were shown by the adsorption of Au(III) on UiO-66-NCS. Characterized by pH effect experiments, TEM, XRD, and XPS, the adsorption of UiO-66-NCS with Au(III) relies on coordination, which further results in reduction, and the generated Au(0) is uniformly dispersed in the MOF. The adsorbent has considerable advantages for cyclic regeneration. Finally, DFT fitting results showed that the adsorption binding energy of UiO-66-NCS with [AuCl4]- was -8.63 kcal mol-1 for the adsorption process. UiO-66-NCS is likely to be an ideal substance for gold recovery.

DNA polymerase κ participates in early S-phase DNA replication in human cells.

Cycling cells replicate their DNA during the S phase through a defined temporal program known as replication timing. Mutation frequencies, epigenetic chromatin states, and transcriptional activities are different for genomic regions that are replicated early and late in the S phase. Here, we found from ChIP-Seq analysis that DNA polymerase (Pol) κ is enriched in early-replicating genomic regions in HEK293T cells. In addition, by feeding cells with N 2-heptynyl-2'-deoxyguanosine followed by click chemistry-based enrichment and high-throughput sequencing, we observed elevated Pol κ activities in genomic regions that are replicated early in the S phase. On the basis of the established functions of Pol κ in accurate and efficient nucleotide insertion opposite endogenously induced N 2-modified dG lesions, our work suggests that active engagement of Pol κ may contribute to diminished mutation rates observed in early-replicating regions of the human genome, including cancer genomes. Together, our work expands the functions of Pol κ and offered a plausible mechanism underlying replication timing-dependent mutation accrual in the human genome.

Epigenetic maintenance of adult neural stem cell quiescence in the mouse hippocampus via Setd1a.

Quiescence, a hallmark of adult neural stem cells (NSCs), is required for maintaining the NSC pool to support life-long continuous neurogenesis in the adult dentate gyrus (DG). Whether long-lasting epigenetic modifications maintain NSC quiescence over the long term in the adult DG is not well-understood. Here we show that mice with haploinsufficiency of Setd1a, a schizophrenia risk gene encoding a histone H3K4 methyltransferase, develop an enlarged DG with more dentate granule cells after young adulthood. Deletion of Setd1a specifically in quiescent NSCs in the adult DG promotes their activation and neurogenesis, which is countered by inhibition of the histone demethylase LSD1. Mechanistically, RNA-sequencing and CUT & RUN analyses of cultured quiescent adult NSCs reveal Setd1a deletion-induced transcriptional changes and many Setd1a targets, among which down-regulation of Bhlhe40 promotes quiescent NSC activation in the adult DG in vivo. Together, our study reveals a Setd1a-dependent epigenetic mechanism that sustains NSC quiescence in the adult DG.

Overview of deltamethrin residues and toxic effects in the global environment.

Pyrethroids are synthetic organic insecticides. Deltamethrin, as one of the pyrethroids, has high insecticidal activity against pests and parasites and is less toxic to mammals, and is widely used in cities and urban areas worldwide. After entering the natural environment, deltamethrin circulates between solid, liquid and gas phases and enters organisms through the food chain, posing significant health risks. Increasing evidence has shown that deltamethrin has varying degrees of toxicity to a variety of organisms. This review summarized worldwide studies of deltamethrin residues in different media and found that deltamethrin is widely detected in a range of environments (including soil, water, sediment, and air) and organisms. In addition, the metabolism of deltamethrin, including metabolites and enzymes, was discussed. This review shed the mechanism of toxicity of deltamethrin and its metabolites, including neurotoxicity, immunotoxicity, endocrine disruption toxicity, reproductive toxicity, hepatorenal toxicity. This review is aim to provide reference for the ecological security and human health risk assessment of deltamethrin.

Chitosan-modified dihydromyricetin liposomes promote the repair of liver injury in mice suffering from diabetes mellitus.

Liver injury caused by type-II diabetes mellitus (DM) is a significant public-health concern worldwide. We used chitosan (CS) to modify dihydromyricetin (DHM)-loaded liposomes (DL) through charge interaction. The effect of CS-modified DL (CDL) on liver injury in mice suffering from DM was investigated in vivo and in vitro. CDL exhibited superior antioxidant capacity and stability. Pharmacokinetic analyses revealed a 3.23- and 1.92-fold increase in the drug concentration-time curve (953.60 ± 122.55 ng/mL/h) in the CDL-treated group as opposed to the DHM-treated group (295.15 ± 25.53 ng/mL/h) and DL-treated group (495.31 ± 65.21 ng/mL/h). The maximum drug concentration in blood (Tmax) of the CDL group saw a 2.26- and 1.21-fold increase compared with that in DHM and DL groups. We observed a 1.49- and 1.31-fold increase in the maximum drug concentration in blood (Cmax) in the CDL group compared with that in DHM and DL groups. Western blotting suggested that CDL could alleviate liver injury in mice suffering from DM by modulating inflammatory factors and the transforming growth factor-ß1/Smad2/Smad3 signaling pathway. In conclusion, modification of liposomes using CS is a viable approach to address the limitations of conventional liposomes and insoluble drugs.

Association between Unsaturated Fatty Acid-Type Diet and Systemic Lupus Erythematosus: A Systematic Review with Meta-Analyses.

BACKGROUND: Systemic lupus erythematosus (SLE) is a complex autoimmune disorder that affects multiple organ systems, with a higher prevalence among women in their reproductive years. The disease's multifactorial etiology involves genetic, environmental, and hormonal components. Recent studies have highlighted the potential impact of dietary factors, particularly unsaturated fatty acids, on the modulation of SLE due to their anti-inflammatory properties. This meta-analysis aims to evaluate the association between unsaturated fatty acid consumption and the risk, progression, and clinical manifestations of SLE, providing evidence-based guidance for dietary management. METHODS: We conducted a comprehensive search across major medical databases up to January 2024, focusing on studies that examined the intake of unsaturated fatty acids and the impact of such intake on SLE. Using the PICOS (population, intervention, comparator, outcomes, study design) framework, we included randomized controlled trials and case-control studies, assessing outcomes such as SLE activity, measured by SLE Disease Activity Index (SLEDAI) or the British Isles Lupus Assessment Group (BILAG) index, inflammation biomarkers. Studies were analyzed using either a fixed- or random-effects model based on heterogeneity (I2 statistic), with sensitivity analyses performed to assess the robustness of the findings. RESULTS: Our search included 10 studies, encompassing a wide variety of designs and populations. The meta-analysis showed that a diet rich in unsaturated fatty acids is significantly associated with a reduction in SLEDAI scores (pooled SMD) of -0.36, 95% CI: -0.61 to -0.11, p = 0.007, indicating a beneficial effect on disease activity. Additionally, we found that unsaturated fatty acid intake has a significant impact on HDL levels, suggesting a positive effect on lipid profiles. However, no significant effects were observed on levels of the inflammatory marker IL-6 or other lipid components (LDL and cholesterol). With minimal heterogeneity among studies (I2 ≤ 15%), sensitivity analysis confirmed the stability and reliability of these results, highlighting the potential role of unsaturated fatty acids in SLE management. CONCLUSIONS: This meta-analysis suggests that dietary intake of unsaturated fatty acids may play a positive role in reducing SLE activity and may significantly affect HDL levels without having significant effects on inflammation markers or other lipid profiles. These findings support the inclusion of unsaturated fatty acids in the dietary management of SLE patients, although further research is required to refine dietary recommendations and explore the mechanisms underlying these associations.

YTHDF2 regulates MSS51 expression contributing to mitochondria dysfunction of granulosa cells in polycystic ovarian syndrome patients.

RESEARCH QUESTION: Granulosa cells (GCs) dysfunction plays a crucial role in the pathogenesis of polycystic ovary syndrome (PCOS). It is reported that YTH domain-containing family protein 2 (YTHDF2) is upregulated in mural GCs of PCOS patients. What effect does the differential expression of YTHDF2 have in PCOS patients? DESIGN: Mural GCs and cumulus GCs from 15 patients with PCOS and 15 ovulatory controls and 4 cases of pathological sections in each group were collected. Real-time PCR, Western Blot, immunohistochemistry, and immunofluorescence experiments were conducted to detect gene and protein expression. RNA immunoprecipitation assay was performed to evaluate the binding relationship between YTHDF2 and MSS51. Mitochondrial morphology, cellular ATP and ROS levels and glycolysis-related gene expression were detected after YTHDF2 overexpression or MSS51 inhibition. RESULTS: In the present study, we found that YTHDF2 was upregulated in GCs of PCOS patients while MSS51 was downregulated. YTHDF2 protein can bind to MSS51 mRNA and affect MSS51 expression. The reduction of MSS51 expression or the increase in YTHDF2 expression can lead to mitochondrial damage, reduced ATP levels, increased ROS levels and reduced expression of LDHA, PFKP and PKM. CONCLUSIONS: YTHDF2 may regulate the expression of MSS51, affecting the structure and function of mitochondria in GCs and interfering with cellular glycolysis, which may disturb the normal biological processes of GCs and follicle development in PCOS patients.

An explanation of the role of pyroptosis playing in epilepsy.

Epilepsy is a severe central nervous system disorder characterized by an imbalance between neuronal excitation and inhibition, resulting in heightened neuronal excitability, particularly within the hippocampus. About one-third of individuals with epilepsy experience difficult-to-manage seizures, known as refractory epilepsy. Epilepsy is closely linked to inflammatory immune response, with elevated levels of inflammatory mediators observed in individuals with this condition. This inflammation of the brain can lead to seizures of various types and is further exacerbated by the release of inflammatory factors, which heighten the excitability of peripheral neurons and worsen the progression of epilepsy. Pyroptosis is an inflammatory programmed cell death which has been shown to be involved in the pathological process of epilepsy. Inflammatory factors released during pyroptosis increase neuronal excitability and promote abnormal discharge in epilepsy, increasing susceptibility to epilepsy. This article provides an overview of the current knowledge on cell pyroptosis and its potential mechanisms, including both canonical and noncanonical pathways. Additionally, we discuss the potential mechanisms of pyroptosis occurrence in epilepsy and the potential therapeutic drugs targeting pyroptosis as a treatment strategy. In summary, this review highlights the promising potential of pyroptosis as a target for developing innovative therapies for epilepsy.

Association between patent foramen ovale morphology and clinical outcomes following transcatheter closure.

BACKGROUND: Anatomic variations of the patent foramen ovale (PFO) are commonly observed, yet limited research has investigated their impact on clinical outcomes following transcatheter closure. We aimed to explore the association between PFO morphology and clinical outcomes. METHODS: Consecutive patients with cryptogenic stroke who underwent PFO closure were prospectively enrolled at a single center from September 2019 to April 2023. Patients were categorized into simple and complex groups based on PFO morphology. Composite events were compared between the two groups during a median follow-up of 24 months, including all-cause mortality, recurrent stroke, residual moderate or severe shunt, and symptomatic atrial fibrillation. RESULTS: A total of 247 patients were enrolled, with a mean age of 41.9 ± 13.0 years and 45.3% males. Ninety-one (36.8%) patients had complex PFO. These individuals were older (45.4 ± 12.5 years vs. 39.9 ± 12.9 years; P = 0.001), more males (56.0% vs. 39.1%; P = 0.010), had longer procedure times (54 ± 32 min vs 46 ± 29 min; P = 0.044), and had a higher rate of using delivery sheath-assisted crossing of the PFO (22.0% vs 12.8%; P = 0.040) than those with simple PFO. The estimated event rates were 27.9% and 11.3% (P = 0.006) in the complex and simple PFO groups, respectively (12.9 events and 5.2 events per 100 person-years; P = 0.001). After adjusting for age, sex, hypertension, diabetes, smoking, device type, and left atrial diameters, complex PFO remained independently associated with composite events (HR 2.10, 95%CI 1.06-4.17, P = 0.034). CONCLUSIONS: Patients with complex PFO may suffer from a higher risk of adverse events following transcatheter PFO closure.

Comparative transcriptomic analysis provides insights into the genetic networks regulating oil differential production in oil crops.

BACKGROUND: Plants differ more than threefold in seed oil contents (SOCs). Soybean (Glycine max), cotton (Gossypium hirsutum), rapeseed (Brassica napus), and sesame (Sesamum indicum) are four important oil crops with markedly different SOCs and fatty acid compositions. RESULTS: Compared to grain crops like maize and rice, expanded acyl-lipid metabolism genes and relatively higher expression levels of genes involved in seed oil synthesis (SOS) in the oil crops contributed to the oil accumulation in seeds. Here, we conducted comparative transcriptomics on oil crops with two different SOC materials. In common, DIHYDROLIPOAMIDE DEHYDROGENASE, STEAROYL-ACYL CARRIER PROTEIN DESATURASE, PHOSPHOLIPID:DIACYLGLYCEROL ACYLTRANSFERASE, and oil-body protein genes were both differentially expressed between the high- and low-oil materials of each crop. By comparing functional components of SOS networks, we found that the strong correlations between genes in "glycolysis/gluconeogenesis" and "fatty acid synthesis" were conserved in both grain and oil crops, with PYRUVATE KINASE being the common factor affecting starch and lipid accumulation. Network alignment also found a conserved clique among oil crops affecting seed oil accumulation, which has been validated in Arabidopsis. Differently, secondary and protein metabolism affected oil synthesis to different degrees in different crops, and high SOC was due to less competition of the same precursors. The comparison of Arabidopsis mutants and wild type showed that CINNAMYL ALCOHOL DEHYDROGENASE 9, the conserved regulator we identified, was a factor resulting in different relative contents of lignins to oil in seeds. The interconnection of lipids and proteins was common but in different ways among crops, which partly led to differential oil production. CONCLUSIONS: This study goes beyond the observations made in studies of individual species to provide new insights into which genes and networks may be fundamental to seed oil accumulation from a multispecies perspective.