Identification of two flavonoids antiviral inhibitors targeting 3C-like protease of porcine epidemic diarrhea virus.

Porcine epidemic diarrhea virus (PEDV) has caused severe damage to the global pig industry in the past 20 years, creating an urgent demand for the development of associated medications. Flavonoids have emerged as promising candidates for combating coronaviruses. It is believed that certain flavonoids can directly inhibit the 3C-like protease (3CLpro), thus displaying antiviral activity against coronaviruses. In this investigation, we applied a flavonoid library to screen for natural compounds against PEDV 3CLpro. Baicalein and baicalin were found to efficiently inhibit PEDV 3CLproin vitro, with the IC50 value of 9.50 ± 1.02 µM and 65.80 ± 6.57 µM, respectively. A docking analysis supported that baicalein and baicalin might bind to the active site and binding pocket of PEDV 3CLpro. Moreover, both baicalein and baicalin successfully suppressed PEDV replication in Vero and LLC-PK1 cells, as indicated by reductions in viral RNA, protein, and titer. Further investigation revealed that baicalein and baicalin mainly inhibited the early viral replication of the post-entry stage. Furthermore, baicalein showed potential effects on the attachment or invasion step of PEDV. Collectively, our findings provide experimental proof for the inhibitory effects of baicalein and baicalin on PEDV 3CLpro activity and PEDV infection. These discoveries may introduce novel therapeutic strategies for controlling porcine epidemic diarrhea (PED).

Mitigation of inflammatory bowel disease-related osteoporosis by oxyberberine: Insights into the RANKL/NF-κB signaling pathway.

Inflammatory bowel disease is linked to a higher occurrence of bone loss. Oxyberberine can effectively improve experimental inflammatory bowel disease. However, no study has shown the effect of oxyberberine on inflammatory bowel disease induced bone loss. The present study was performed to investigate the role of oxyberberine in inflammatory bowel disease induced osteoporosis in chronic inflammatory bowel disease mice model. The inflammatory bowel disease mice were orally given two doses of oxyberberine daily. Blood, colon, and bone specimens were collected for biomarker assessments and histological examinations. Bone biomechanical properties and key proteins and genes involved in the receptor activator of nuclear factor kappa-B ligand/nuclear factor kappa-B signaling pathway were evaluated. Additionally, the binding characteristics of oxyberberine and receptor activator of nuclear factor kappa-B ligand were evaluated by in silico simulation. Results indicated that oxyberberine treatment significantly attenuated the macroscopic damage, colonic shortening, and histological injury from the colon. Furthermore, oxyberberine decreased serum inflammatory cytokine levels. The intervention with oxyberberine significantly mitigated the deterioration of bone mass, biomechanical properties, and microstructural parameters. Moreover, the upregulated osteoclast formation factors in model mice were significantly abolished by oxyberberine. In silico simulation results also showed that oxyberberine was firmly bound with target protein. Hence, our findings indicated that oxyberberine had the potential to mitigate inflammatory bowel disease induced inflammation in bone, inhibit osteoclast formation through regulating the receptor activator of nuclear factor kappa-B ligand/nuclear factor kappa-B signaling pathway, and might be a valuable approach in preventing bone loss associated with inflammatory bowel disease.

First-principles prediction of one-dimensional conductive metallic organic polymers as ultrahigh energy density anode for lithium-ion batteries.

Metal-Organic Polymers (MOPs) have attracted growing attention for lithium-ion battery (LIB) applications due to their merits in orderly ionic transportation and robust structure stability in electrochemical reactions. However, they suffer from poor electronic conductivity. In this work, we apply first-principles density functional theory to explore the potential of three one-dimensional (1D) electrically conductive C6H2S4TM (TM = Fe, Co, and Ni) MOPs with the π-d conjugated coordination as anode materials for Li+ ions storage. Our theoretical results reveal that these 1D MOPs possess a superior theoretical capacity of over 748 mA h g-1. In particular, the 1D C6H2S4Ni MOP shows an exceptional theoretical specific capacity of 1110 mA h g-1 based on the three-electron transferring reaction, which significantly outperforms the traditional graphite-based anode material in LIBs. Moreover, the resonant charge transfer between Ni metal and ligand within the 1D C6H2S4Ni MOP reduces the diffusion energy barrier of the Li atoms when they migrate on the surface of the MOP. The ultrahigh theoretical specific capacity of the C6H2S4Ni MOP predicts that it can be a promising anode material for LIBs.

The association of blood eosinophil counts and FEV1 decline: a cohort study.

BACKGROUND: Accelerated lung function decline is characteristic of chronic obstructive pulmonary disease (COPD). However, the association between blood eosinophil counts and lung function decline, accounting for current smoking status, in young individuals without prevalent lung disease is not fully understood. METHODS: This is a cohort study of 629 784 Korean adults without COPD or a history of asthma at baseline who participated in health screening examinations including spirometry and differential white blood cell counts. We used linear mixed effects model to estimate the annual change in FEV1 (mL) by baseline blood eosinophil count, adjusting for covariates including smoking status. We also performed a stratified analysis by baseline and time-varying smoking status. RESULTS: During a mean follow-up of 6.5 years (maximum of 17.8 years), the annual change in FEV1 (95% confidence interval [CI]) in participants with eosinophil counts <100, 100-199, 200-299, 300-499, and ≥500 cells/µL in the fully adjusted model were -23.3 (-23.9, -22.7), -24.3 (-24.9, -23.7), -24.8 (-25.5, -24.2), -25.5 (-26.2, -24.8), and -26.8 (-27.7, -25.9) mL, respectively. When stratified by smoking status, participants with higher eosinophil count had a faster decline in FEV1 than those with lower eosinophil count in both never- and ever-smokers, which persisted when time-varying smoking status was used. CONCLUSIONS: Blood eosinophil counts were associated with a faster lung function decline among healthy individuals without lung disease, independent of smoking status. The findings suggest that blood eosinophil counts contribute to the risk of faster lung function decline, particularly among younger adults without a history of lung disease.

Effect of Isocaloric, Time-Restricted Eating on Body Weight in Adults With Obesity : A Randomized Controlled Trial.

BACKGROUND: Time-restricted eating (TRE) lowers body weight in many studies. Whether TRE induces weight loss independent of reductions in calorie intake, as seen in rodent studies, is unknown. OBJECTIVE: To determine the effect of TRE versus a usual eating pattern (UEP) on body weight in the setting of stable caloric intake. DESIGN: Randomized, isocaloric feeding study. (ClinicalTrials.gov: NCT03527368). SETTING: Clinical research unit. PARTICIPANTS: Adults with obesity and prediabetes or diet-controlled diabetes. INTERVENTION: Participants were randomly assigned 1:1 to TRE (10-hour eating window, 80% of calories before 1 p.m.) or UEP (≤16-hour window, ≥50% of calories after 5 p.m.) for 12 weeks. Both groups had the same nutrient content and were isocaloric with total calories determined at baseline. MEASUREMENTS: Primary outcome was change in body weight at 12 weeks. Secondary outcomes were fasting glucose, homeostatic model assessment for insulin resistance (HOMA-IR), glucose area under the curve by oral glucose tolerance test, and glycated albumin. We used linear mixed models to evaluate the effect of interventions on outcomes. RESULTS: All 41 randomly assigned participants (mean age, 59 years; 93% women; 93% Black race; mean BMI, 36 kg/m2) completed the intervention. Baseline weight was 95.6 kg (95% CI, 89.6 to 101.6 kg) in the TRE group and 103.7 kg (CI, 95.3 to 112.0 kg) in the UEP group. At 12 weeks, weight decreased by 2.3 kg (CI, 1.0 to 3.5 kg) in the TRE group and by 2.6 kg (CI, 1.5 to 3.7 kg) in the UEP group (average difference TRE vs. UEP, 0.3 kg [CI, -1.2 to 1.9 kg]). Change in glycemic measures did not differ between groups. LIMITATION: Small, single-site study; baseline differences in weight by group. CONCLUSION: In the setting of isocaloric eating, TRE did not decrease weight or improve glucose homeostasis relative to a UEP, suggesting that any effects of TRE on weight in prior studies may be due to reductions in caloric intake. PRIMARY FUNDING SOURCE: American Heart Association.

Comparative Pharmacokinetics Research of 13 Bioactive Components of Jieyu Pills in Control and Attention Deficit Hyperactivity Disorder Model Rats Based on UPLC-Orbitrap Fusion MS.

Jieyu Pills (JYPs), a Chinese medicine consisting of 10 herbal elements, have displayed promising clinical effectiveness and low by-effects in the treatment of depression. Prior investigations mostly focused on elucidating the mechanism and therapeutic efficacy of JYPs. In our earlier study, we provided an analysis of the chemical composition, serum pharmacochemistry, and concentrations of the main bioactive chemicals found in JYPs. However, our precise understanding of the pharmacokinetics and metabolism remained vague. This study involved a comprehensive and meticulous examination of the pharmacokinetics of 13 bioactive compounds in JYPs. Using UPLC-Orbitrap Fusion MS, we analyzed the metabolic characteristics and established the pharmacokinetic parameters in both control rats and model rats with attention deficit hyperactivity disorder (ADHD) following oral administration of the drug. Before analysis, plasma samples that were collected at different time intervals after the administration underwent methanol pre-treatment with Puerarin used as the internal standard (IS) solution. Subsequently, the sample was chromatographed on a C18 column employing gradient elution. The mobile phase consisted of methanol solution containing 0.1% formic acid in water. The electrospray ionization source (ESI) was utilized for ionization, whereas the scanning mode employed was selected ion monitoring (SIM). The UPLC-Orbitrap Fusion MS method was subjected to a comprehensive validation process to assess its performance. The method demonstrated excellent linearity (r ≥ 0.9944), precise measurements (RSD < 8.78%), accurate results (RE: -7.88% to 8.98%), and appropriate extraction recoveries (87.83-102.23%). Additionally, the method exhibited minimal matrix effects (87.58-101.08%) and satisfactory stability (RSD: 1.52-12.42%). These results demonstrated adherence to the criteria for evaluating and determining biological material. The 13 bioactive compounds exhibited unique pharmacokinetic patterns in vivo. In control rats, all bioactive compounds except Ferulic acid exhibited linear pharmacokinetics within the dose ranges. In the ADHD model, the absorption rate and amount of most of the components were both observed to have increased. Essentially, this work is an important reference for examining the metabolism of JYPs and providing guidelines for clinical therapy.

Tissue-specific silencing of integrated transgenes achieved through endogenous RNA interference in Caenorhabditis elegans.

Transgene silencing is a common phenomenon observed in Caenorhabditis elegans, particularly in the germline, but the precise mechanisms underlying this process remain elusive. Through an analysis of the transcription factors profile of C. elegans, we discovered that the expression of several transgenic reporter lines exhibited tissue-specific silencing, specifically in the intestine of C. elegans. Notably, this silencing could be reversed in mutants defective in endogenous RNA interference (RNAi). Further investigation using knock-in strains revealed that these intestine-silent genes were indeed expressed in vivo, indicating that the organism itself regulates the intestine-specific silencing. This tissue-specific silencing appears to be mediated through the endo-RNAi pathway, with the main factors of this pathway, mut-2 and mut-16, are significantly enriched in the intestine. Additionally, histone modification factors, such as met-2, are involved in this silencing mechanism. Given the crucial role of the intestine in reproduction alongside the germline, the transgene silencing observed in the intestine reflects the self-protective mechanisms employed by the organisms. In summary, our study proposed that compared to other tissues, the transgenic silencing of intestine is specifically regulated by the endo-RNAi pathway.

Effects of Dietary l-Glutamine Supplementation on the Intestinal Function and Muscle Growth of Piglets.

The aim of this study was to investigate the effects of dietary l-glutamine (Gln) supplementation on the morphology and function of the intestine and the growth of muscle in piglets. In this study, sixteen 21-day-old piglets were randomly divided into two groups: the Control group (fed a basal diet) and the Gln group (fed a basal diet supplemented with 0.81% Gln). Blood, gut, and muscle samples were collected from all piglets on Day 20 of the trial. Compared with the Control group, the supplementation of Gln increased (p < 0.05) the villus height, villus width, villus surface area, and villus height/crypt depth ratio of the small intestine. Furthermore, the supplementation of Gln increased (p < 0.05) total protein, total protein/DNA, and RNA/DNA in both the jejunum and ileum. It also increased (p < 0.05) the concentrations of carnosine and citrulline in the jejunal mucosa, as well as citrulline and cysteine concentrations in the ileum. Conversely, Gln supplementation decreased (p < 0.05) Gln concentrations in both the jejunum and ileum, along with ß-aminoisobutyric acid and 1-Methylhistidine concentrations, specifically in the ileum. Subsequent research revealed that Gln supplementation increased (p < 0.05) the mRNA levels for glutathione-S-transferase omega 2 and interferon-ß in the duodenum. In addition, Gln supplementation led to an increase (p < 0.05) in the number of Lactobacillus genus in the colon, but a decrease (p < 0.05) in the level of HSP70 in the jejunum and the activity of diamine oxidase in plasma. Also, Gln supplementation reduced (p < 0.05) the mRNA levels of glutathione-S-transferase omega 2 and interferon stimulated genes, such as MX1, OAS1, IFIT1, IFIT2, IFIT3, and IFIT5 in both the jejunum and ileum, and the numbers of Clostridium coccoides, Enterococcus genus, and Enterobacterium family in the colon. Moreover, Gln supplementation enhanced (p < 0.05) the concentrations of total protein, RNA/DNA, and total protein/DNA ratio in the longissimus dorsi muscle, the concentrations of citrulline, ornithine, arginine, and hydroxyproline, and the mRNA level of peptide transporter 1, while reducing the contents of hydrogen peroxide and malondialdehyde and the mRNA level of glutathione-S-transferase omega 2 in the longissimus dorsi muscle. In conclusion, dietary Gln supplementation can improve the intestinal function of piglets and promote the growth of the longissimus dorsi muscle.

Early-onset vasomotor symptoms and development of depressive symptoms among premenopausal women.

BACKGROUND: We investigated the association between vasomotor symptoms (VMSs) and the onset of depressive symptoms among premenopausal women. METHODS: This cross-sectional study included 4376 premenopausal women aged 42-52 years, and the cohort study included 2832 women without clinically relevant depressive symptoms at baseline. VMSs included the symptoms of hot flashes and night sweats. Depressive symptoms were evaluated using the Center for Epidemiological Studies Depression Scale; a score of ≥16 was considered to define clinically relevant depressive symptoms. RESULTS: Premenopausal Women with VMSs at baseline exhibited a higher prevalence of depressive symptoms compared with women without VMSs at baseline (multivariable-adjusted prevalence ratio 1.76, 95 % confidence interval [CI] 1.47-2.11). Among the 2832 women followed up (median, 6.1 years), 406 developed clinically relevant depressive symptoms. Women with versus without VMSs had a significantly higher risk of developing clinically relevant depressive symptoms (multivariable-adjusted hazard ratio, 1.72; 95 % CI 1.39-2.14). VMS severity exhibited a dose-response relationship with depressive symptoms (P for trend <0.05). LIMITATIONS: Self-reported questionnaires were only used to obtain VMSs and depressive symptoms, which could have led to misclassification. We also could not directly measure sex hormone levels. CONCLUSIONS: Even in the premenopausal stage, women who experience hot flashes or night sweats have an increased risk of present and developed clinically relevant depressive symptoms. It is important to conduct mental health screenings and provide appropriate support to middle-aged women who experience early-onset VMSs.

Association between quality of life and resilience in infertile patients: a systematic review.

This systematic review was carried out to describe QoL and resilience in infertile patients, as well as the relationship between them, and to give a theoretical foundation for clinical practice. The databases of CNKI, Wanfang data, VIP database, PubMed, Web of Science, and Embase were searched without a time limit. A narrative synthesis of relevant articles was undertaken. This systematic review was registered on PROSPERO in advance. Of 21 studies eligible for inclusion in this review, 13 focused on the relationship between QoL and resilience, 5 on QoL influencing factors (resilience included), and 3 on mediation effect analysis on mental health (resilience as a mediator). Resilience can significantly predict the QoL of infertile patients. It seems plausible that more resilient couples will be less vulnerable to the stress of infertility. A global consortium of infertile population research could make cross-cultural comparisons of QoL and resilience possible. Future research should focus on resilience therapies. Systematic review registration: This systematic review was registered on PROSPERO in advance (CRD42023414706).

Inclusion complexes of ß-cyclodextrin with isomeric ester aroma compounds: Preparation, characterization, mechanism study, and controlled release.

Cyclodextrins (CDs) have been discovered to provide an efficient solution to the limited application of ester aroma molecules used in food, tobacco, and medication due to their strong smell and unstable storage. This work combined molecular modeling and experimental to analyze the conformation and controlled release of isomeric ester aroma compounds/ß-CD inclusion complexes (ICs). The investigation revealed that ester aroma compounds could be effectively encapsulated within the ß-CD cavity, forming ICs with low binding affinity. Furthermore, the key driving forces in ICs were identified as hydrogen bonds and van der Waals interactions through theoretical simulation. Results from the Fourier transform infrared (FTIR), nuclear magnetic resonance (NMR) and Isothermal titration calorimetry (ITC) experiments confirmed the intermolecular interaction predicted by the molecular model. Notably, the release rate of aroma compounds from L-menthyl acetate/ß-CD (LMA/ß-CD) IC exceeded that of terpinyl acetate/ß-CD (TA/ß-CD) IC. This difference is attributed to the length of the chain of aroma molecules and the variation in the position of functional groups, influencing the stable formation of ICs with ß-CD. These findings hold potential implications for refining the application of ICs across diverse industries.

Bibliometric Analysis of Brain Stimulation Technologies in Sleep Disorders.

BACKGROUND Sleep disorders are a common disease faced by people today and can lead to fatigue, lack of concentration, impaired memory, and even death. In recent years, the development of brain stimulation techniques has provided a new perspective for the treatment of sleep disorders. However, there is a lack of bibliometric analyses related to sleep disorders and brain stimulation techniques. Therefore, this study analyzed the application status and trend of brain stimulation technology in sleep disorder research. MATERIAL AND METHODS Articles and reviews published between 1999 and 2023 were retrieved from the Web of Science. CiteSpace was used to visually analyze the publications, countries, institutions, journals, authors, references, and keywords. RESULTS A total of 459 publications were obtained. The number of studies was shown to be on a general upward trend. The country with the largest number of publications was the United States; UDICE-French Research Universities had the highest number of publications; Neurology had the highest citation frequency; 90% of the top 10 references cited were from Journal Citation Reports Q1; Brigo was the author with the highest number of publications; and the most frequent keywords were "transcranial magnetic stimulation", "deep brain stimulation", and "Parkinson disease". CONCLUSIONS Our study used CiteSpace software to analyze 459 studies published since 1999 on brain stimulation techniques for the treatment of sleep disorders, revealing research trends and the current state of the field. Our results will help researchers to understand the existing research quickly and provide direction for future research.

Protective effect of exosomes derived from bone marrow mesenchymal stem cells on hypoxia reperfusion injury of cardiomyocytes.

We aimed to investigate the cardiomyocyte-protective effects of bone marrow mesenchymal stem cells (BMSCs)-derived exosomes on ischemia/reperfusion (I/R)-injured rats and to explore the mechanisms. Cardiomyocytes were divided into control group, ischemia/reperfusion group (I/R group), ischemia/reperfusion+exosome group (I/R+Exo group) or ischemia/reperfusion+exosomes transfected with miR-101a-3p inhibitor group (I/R+Exo inhibitor group). MiR-101a-3p levels were lower in I/R and I/R+Exo inhibitor groups than in control and I/R+Exo groups. Apoptosis rate and cleaved caspase 3 expression were higher in I/R and I/R+Exo inhibitor groups. The levels of superoxide dismutase (SOD) in cardiomyocytes of I/R group and I/R+Exo inhibitor group were lower than those of control group and I/R+Exo group, and the levels of malondialdehyde (MDA) and the relative production of oxygen species clusters (ROS) in cardiomyocytes of I/R group and I/R+Exo inhibitor group were higher than those of control group and I/R+Exo group. The levels of interleukin-10 (IL-10), interleukin-6 (IL-6), tumour necrosis factor α (TNF-α), and nuclear factor κB (NF-κB) were higher in the I/R group and the I/R +Exo inhibitor group than in the control group and the I/R+Exo group. Bioinformatics analysis suggested that Pik3c3 is the most promising gene involved in miR-101a-3p-mediated apoptosis in cardiomyocytes, and in vitro experiments confirmed that low expression of miR-101a-3p significantly up-regulated the mRNA and protein expression levels of Pik3c3. BMSCs-derived exosomes have a protective effect on cardiomyocytes from I/R-injured rats, and the mechanism may be related to the inhibition of oxidative stress and inflammatory responses in cardiomyocytes by exosome-delivered miR-101a-3p.

Gastrointestinal Characteristics of Constipation from the Perspectives of Microbiome and Metabolome.

BACKGROUND: Constipation is one of the most common gastrointestinal complaints. Yet, the underlying mechanisms of constipation remain to be explored deeply. Integration of microbiome and metabolome is powerful and promising to demonstrate characteristics of constipation. AIM OF STUDY: This study aimed to characterize intestinal microbiome and metabolome of constipation. In addition, this study revealed the correlations among behaviors, intestinal microbiota, and metabolites interrupted by constipation. METHODS: Firstly, the constipation model was successfully applied. At the macro level, the ability of learning, memory, locomotor activity, and the defecation index of rats with constipation-like phenotype were characterized. At the micro-level, 16S rRNA sequencing was applied to analyze the intestinal microbiota in rats with constipation-like phenotype. 1H nuclear magnetic resonance (NMR)-based metabolomics was employed to investigate the metabolic phenotype of constipation. In addition, we constructed a correlation network, intuitively showing the correlations among behaviors, intestinal microbiota, and metabolites. RESULTS: Constipation significantly attenuated the locomotor activity, memory recognition, and frequency of defecation of rats, while increased the time of defecation. Constipation significantly changed the diversity of intestinal microbial communities, which correspondingly involved in 5 functional pathways. Besides, 28 fecal metabolites were found to be associated with constipation, among which 14 metabolites were further screened that can be used to diagnose constipation. On top of this, associated networks intuitively showed the correlations among behaviors, intestinal microbiota, and metabolites. CONCLUSIONS: The current findings are significant in terms of not only laying a foundation for understanding characteristics of constipation, but also providing accurate diagnosis and treatments of constipation clinically.

GPR41 deficiency aggravates type 1 diabetes in streptozotocin-treated mice by promoting dendritic cell maturation.

Disturbances in intestinal immune homeostasis predispose susceptible individuals to type 1 diabetes (T1D). G-protein-coupled receptor 41 (GPR41) is a receptor for short-chain fatty acids (SCFAs) mainly produced by gut microbiota, which plays key roles in maintaining intestinal homeostasis. In this study, we investigated the role of GPR41 in the progression of T1D. In non-obese diabetic (NOD) mice, we found that aberrant reduction of GPR41 expression in the pancreas and colons was associated with the development of T1D. GPR41-deficient (Gpr41-/-) mice displayed significantly exacerbated streptozotocin (STZ)-induced T1D compared to wild-type mice. Furthermore, Gpr41-/- mice showed enhanced gut immune dysregulation and increased migration of gut-primed IFN-γ+ T cells to the pancreas. In bone marrow-derived dendritic cells from Gpr41-/- mice, the expression of suppressor of cytokine signaling 3 (SOCS) was significantly inhibited, while the phosphorylation of STAT3 was significantly increased, thus promoting dendritic cell (DC) maturation. Furthermore, adoptive transfer of bone marrow-derived dendritic cells (BMDC) from Gpr41-/- mice accelerated T1D in irradiated NOD mice. We conclude that GPR41 is essential for maintaining intestinal and pancreatic immune homeostasis and acts as a negative regulator of DC maturation in T1D. GPR41 may be a potential therapeutic target for T1D.

Network structure of complex interactions of premenstrual syndrome and influencing factors in young adult women.

BACKGROUND: In the transition phase from adolescence to adulthood, premenstrual syndrome (PMS) occurs more commonly, with a variety of symptoms. The occurrence of PMS may be the result of a combination of demographic, physiological, psychological and sociological factors. This study aimed to identify the central symptoms of PMS, and explored the complex influencing factors especially the one-to-one inter-relationships factors with specific symptoms. METHOD: This is a cross-sectional study conducted in mainland China. 3458 young adult women were assessed. Using the Premenstrual Syndrome Scale (PSS) to assess the PMS, and PSS score was over 6 divided into PMS group, and vice versa. Influencing factors were assessed by a set of self-reported questionnaire. Network analysis was used to examined the interplay of PMS, whilst also considering the influencing factors of PMS. RESULTS: In summary, 1479 participants were in PMS group. Anxiety had the highest strength centrality (1.12/1.09), shown higher centrality in the both network. Swelling of the hands or feet also shown higher strength centrality (0.89) in PMS group. PMS is associated with a higher history of dysmenorrhea, and neurotic personality. Neurotic personality - depressed mood/nervousness (0.27/0.23), history of dysmenorrhea - abdominal distension (0.21), had significantly higher weight than other edges in PMS group. CONCLUSION: Anxiety was the most central symptom in the network, and was closely associated with other symptoms like depressed mood, which provided additional evidence for the centrality of emotional features in PMS. Moreover, the influencing factors of PMS combined demographic, physiological, psychological, and sociological factors. According to the central symptoms and factors affecting the specific PMS symptoms in young adult women, targeted intervention is helpful to prevent and alleviate PMS. LIMITATION: Cross-sectional design cannot infer the directionality of the associations between variables. All data is self-reported with recall bias and the edge weights across the constructs of influencing factors and PMS were fairly small.

Boosting the Luminescence of a Europium(III)-ß-Diketonate Complex-Nanoclay Aqueous Solution by Acetylcholine.

It is a challenging task to prepare lanthanide complex-based luminescent materials with high quantum efficiency in aqueous solution, since the excited state of Ln3+ can be significantly quenched by water through the excitation of the O-H vibrations. Herein, we present a simple and environmentally friendly strategy to prepare strongly red-light-emitting lanthanide complex-based luminescent materials by loading 2-thenoyltrifluoroacetate (TTA) on the Eu3+-exchanged nanoclay (Eu3+(TTAn)-NC, NC = nanoclay) and coadsorption of choline chloride (ChCl) or acetylcholine chloride (AChCl) in water. The coadsorbed molecules remarkably boosted the luminescence of Eu3+(TTAn)-NC, which is tentatively ascribed to the removal of waters coordinated in the Eu3+ coordination sphere via the complete coordination of TTA mediated by ChCl or AChCl. Highly luminescent films were facilely prepared by mixing a Eu3+(TTAn)-NC aqueous solution with PVA-ChCl (PVA-AChCl) deep eutectic solvents. This work provides a simple and environmentally friendly way for preparing highly luminescent emitting luminescent materials in aqueous solution.

GSTP alleviates acute lung injury by S-glutathionylation of KEAP1 and subsequent activation of NRF2 pathway.

Oxidative stress plays an important role in the pathogenesis of acute lung injury (ALI). As a typical post-translational modification triggered by oxidative stress, protein S-glutathionylation (PSSG) is regulated by redox signaling pathways and plays diverse roles in oxidative stress conditions. In this study, we found that GSTP downregulation exacerbated LPS-induced injury in human lung epithelial cells and in mice ALI models, confirming the protective effect of GSTP against ALI both in vitro and in vivo. Additionally, a positive correlation was observed between total PSSG level and GSTP expression level in cells and mice lung tissues. Further results demonstrated that GSTP inhibited KEAP1-NRF2 interaction by promoting PSSG process of KEAP1. By the integration of protein mass spectrometry, molecular docking, and site-mutation validation assays, we identified C434 in KEAP1 as the key PSSG site catalyzed by GSTP, which promoted the dissociation of KEAP1-NRF2 complex and activated the subsequent anti-oxidant genes. In vivo experiments with AAV-GSTP mice confirmed that GSTP inhibited LPS-induced lung inflammation by promoting PSSG of KEAP1 and activating the NRF2 downstream antioxidant pathways. Collectively, this study revealed the novel regulatory mechanism of GSTP in the anti-inflammatory function of lungs by modulating PSSG of KEAP1 and the subsequent KEAP1/NRF2 pathway. Targeting at manipulation of GSTP level or activity might be a promising therapeutic strategy for oxidative stress-induced ALI progression.

Formation processes of groundwater in a non-ferrous metal mining city of China: Insights from hydrochemical and strontium isotope analyses.

Tongling is a significant non-ferrous metal mining city in China, which produces waste that negatively impacts the area's water environment. It is essential to comprehend the hydrochemical properties and formation processes of groundwater to safeguard and utilize it efficiently. We explored major ions, strontium, and its isotopes in water and river-bottom samples from the northern (i.e., A-A' section) and southern (i.e., B-B' section) areas. The hydrochemical facies show the mining activities have a greater impact on surface water than on groundwater. Groundwater hydrochemical formation results from several factors, with water-rock interaction and ion exchange being primary. Additionally, the dissolution of calcite, dolomite, and feldspar, oxidation of pyrite, and hydrolysis of carbonate minerals also impact the formation of groundwater chemistry. Our analysis of strontium and its isotopes indicates that carbonate dissolution primarily occurred in the recharge area; the runoff from the recharge to the discharge area results in the dissolution of certain silicate rocks; calcite dissolution sources account for > 70% contribution in both surface water and groundwater water-rock interactions, whereas silicate rock dissolution sources and dolomite dissolution sources account for < 30%. Due to changed order of dissolved carbonate and silicate minerals during groundwater flow, the distribution of strontium and its isotopes in the A-A' section is opposite to that in the B-B' section. The findings provide a basis for developing, utilizing, managing, and protecting groundwater resources, especially in similar mining areas.

Quercetin: A promising therapy for diabetic encephalopathy through inhibition of hippocampal ferroptosis.

BACKGROUND: The pathophysiology of diabetic encephalopathy (DE), a significant diabetes-related pathological complication of the central nervous system, is poorly understood. Ferroptosis is an iron-dependent regulated necrotic cell death process that mediates the development of neurodegenerative and diabetes-related lesions. Quercetin (QE) exerts anti-ferroptotic effects in various diseases. However, the roles of ferroptosis in DE and the potential anti-ferroptotic mechanisms of QE are unclear. PURPOSE: This study aimed to investigate if quercetin can ameliorate DE by inhibiting ferroptosis and to elucidate the potential anti-ferroptotic mechanisms of QE, thus providing a new perspective on the pathogenesis and prevention of DE. METHODS: The spontaneously type 2 diabetic Goto-Kakizak rats and high glucose (HG)-induced PC12 cells were used as animal and in vitro models, respectively. The Morris water maze test was performed to evaluate the cognition of rats. Pathological damage was examined using hematoxylin and eosin staining. Mitochondrial damage was assessed using transmission electron microscopy. Lipid peroxidation was evaluated by examining the levels of malondialdehyde, superoxide dismutase, and glutathione. Additionally, the contents of iron ions were quantified. Immunofluorescence and western blotting were carried out to poke the protein levels. Network pharmacology analysis was conducted to construct a protein-protein interaction network for the therapeutic targets of QE in DE. Additionally, molecular docking and cellular thermal shift assay was performed to examine the target of QE. RESULTS: QE alleviated cognitive impairment, decreased lipid peroxidation and iron deposition in the hippocampus, and upregulated the Nrf2/HO-1 signaling pathway. HG-induced ferroptosis in PC12 cells resulted in decreased cell viability accompanied by lipid peroxidation and iron deposition. QE mitigated HG-induced ferroptosis by upregulating the Nrf2/HO-1 pathway, which was partially suppressed upon Nrf2 inhibition. Network pharmacology analysis further indicated that the Nrf2/HO-1 signaling pathway is a key target of QE. Molecular docking experiments revealed that QE binds to KEAP1 through four hydrogen bonds. Moreover, QE altered the thermostability of KEAP1. CONCLUSION: These results indicated that QE inhibits ferroptosis in the hippocampal neurons by binding to KEAP1 and subsequently upregulating the Nrf2/HO-1 signaling pathway.