Flavonoids: Potential therapeutic agents for cardiovascular disease.

Flavonoids are found in the roots, stems, leaves, and fruits of many plant taxa. They are related to plant growth and development, pigment formation, and protection against environmental stress. Flavonoids function as antioxidants and exert anti-inflammatory effects in the cardiovascular system by modulating classical inflammatory response pathways, such as the TLR4-NF-ĸB, PI3K-AKT, and Nrf2/HO-1 signalling pathways. There is increasing evidence for the therapeutic effects of flavonoids on hypertension, atherosclerosis, and other diseases. The potential clinical value of flavonoids for diseases of the cardiovascular system has been widely explored. For example, studies have evaluated the roles of flavonoids in the regulation of blood pressure via endothelium-dependent and non-endothelium-dependent pathways and in the regulation of myocardial systolic and diastolic functions by influencing calcium homeostasis and smooth muscle-related protein expression. Flavonoids also have hypoglycaemic, hypolipidemic, anti-platelet, autophagy, and antibacterial effects. In this paper, the role and mechanism of flavonoids in cardiovascular diseases were reviewed in order to provide reference for the clinical application of flavonoids in the future.

Efficacy and prognosis of HER2-Low and HER2-Zero in triple-negative breast cancer after neoadjuvant chemotherapy.

Mounting evidence showed that HER2-Low breast cancer patients could benefit from the novel anti-HER2 antibody-drug conjugates (ADCs) treatment, which pointed the way towards better therapy for HER2-Low patients. The purpose of this study was to describe the clinicopathological features, along with chemotherapeutic effects and survival outcomes of HER2-Low and HER2-Zero in TNBC who received neoadjuvant chemotherapy (NACT). We retrospectively evaluated 638 triple-negative breast cancer patients who were treated with neoadjuvant chemotherapy between August 2014 and August 2022. Pathologic complete response (pCR) and survival outcomes were analyzed in HER2-Low cohort, HER2-Zero cohort and the overall patients, respectively. In the entire cohort, 342 (53.6%) patients were HER2-Low and 296 (46.4%) patients were HER2-Zero. No significant difference was found between HER2-Low and HER2-Zero patients based on all the clinical-pathological characteristics. 143 cases (22.4%) achieved pCR after NACT in the overall TNBC patients. The pCR rate of the HER2-Low patients and the HER2-Zero patients was 21.3% and 23.6%, respectively, exhibiting no statistical difference (p = 0.487). The survival of pCR group after NACT significantly improved compared to non-pCR group either in HER2-Low patients or in HER2-Zero patients. Although we found that patients with HER2-Low had longer DFS than patients with HER2-Zero, there was no considerable difference (p = 0.068). However, HER2-Low patients had a dramatically longer OS than HER2-Zero patients (p = 0.012). The data from present study confirmed the clinical importance of HER2-Low expression in TNBC. Further effort is needed to determine whether HER2-Low could be a more favorable prognostic marker for individual treatment.

Hsa_circ_0043532 contributes to PCOS through upregulation of CYP19A1 by acting as a ceRNA for hsa-miR-1270.

BACKGROUND: Polycystic ovarian syndrome (PCOS) accounts for about 75% of anovulatory infertility. The cause of PCOS is not clear. CircRNAs acting as miRNA sponges mediate the post-transcriptional regulation of multiple genes. CYP19A1 is a limiting enzyme in the ovarian steroidogenesis pathway. However, the mechanism of circRNAs regulating granulosa cell (GC) estradiol secretion in PCOS remains to be elucidated. METHODS: Bioinformatics was used to predict the potential target miRNAs of circ_0043532 and target genes of miR-1270. Target miRNAs and mRNA expression were verified by qRT-PCR in GCs from 45 women with PCOS and 65 non-PCOS. Western blot, ELISA and dual-luciferase reporter assays were applied to confirm the substrate of miR-1270. RESULTS: Circ_0043532 and CYP19A1 were significant up-regulation in GCs from patients with PCOS. The predicted target miRNAs of circ_0053432, miR-1270, miR-576-5p, miR-421 and miR-142-5p, were notably decreased in GCs from patients with PCOS. Mechanistic experiments showed that circ_0043532 specifically binds to miR-1270. MiR-1270 was negatively regulated by circ_0043532. Concomitantly, miR-1270 inhibited CYP19A1 expression and estradiol production, which could be reversed by circ_0043532 over-expression. CONCLUSION: We identified that circ_0043532/miR-1270/CYP19A1 axis contributes to the aberrant steroidogenesis of GCs from patients with PCOS. This study broadens the spectrum of pathogenic factors of PCOS, and circ_0043532 might be a potential therapeutic target for PCOS.

The development and implementation of pathological parameters and molecular testing impact prognosis of colorectal adenocarcinoma.

Objective: This study aims to analyze how changes in pathological diagnosis practice and molecular detection technology have affected clinical outcomes for colorectal cancer (CRC) patients in Fudan University Shanghai Cancer Center (FUSCC). Methods: This retrospective cohort study analyzed 21,141 pathologically confirmed CRC cases diagnosed at FUSCC from 2008 to 2020. Patients were divided into five groups for different analytical purposes: (1) the before vs. since 2014 groups to analyze the influence of the changes in the classification criteria of pT3 and pT4 staging on the survival of patients; (2) the partial vs. total mesorectal excision (TME) groups to analyze whether evaluation of completeness of the mesorectum have impact on the survival of patients; (3) the tumor deposit (TD)(+)N0 vs. TD(+)N1c groups to analyze the influence of the changes in the pN staging on the survival of patients with positive TD and negative regional lymph node metastasis (LNM); (4) the before vs. since 2013 groups to analyze the influence of the changes in the testing process of deficient mismatch repair on the survival of patients; and (5) the groups with vs. without RAS/BRAF gene mutation testing to analyze the influence of these testing on the survival of patients. Patients' clinicopathological parameters, including age at diagnosis, sex, tumor size, location, differentiation, mucinous subtype, TD, lymphovascular invasion, perineural invasion, tumor depth, LNM and distant metastasis, and tumor-node-metastasis (TNM) stage, were compared between groups. Kaplan-Meier analysis with log rank method was performed for patients' overall survival (OS) and disease-free survival (DFS) analyses. Results: In pathological reports, there were three parameter changes that impacted patient outcomes. Firstly, changes in the pT staging criteria led to a shift of the ratio of patients with stage pT3 to stage pT4 from 1: 110.9 to 1: 0.26. In comparison to patients admitted before 2014 (n = 4,754), a significant difference in prognosis between pT3 and pT4 stages was observed since 2014 (n = 9,965). Secondly, we began to evaluate the completeness of the mesorectum since 2016. As a result, 91.0% of patients with low rectal cancer underwent TME (n = 4,111) surgery, and patients with TME had significantly better OS compared with partial mesorectal excision (PME, n = 409). Thirdly, we began to stage TD (+) LNM (-) as N1c since 2017. The results showed that N1c (n = 127) but not N0 (n = 39) can improve the prognosis of patients without LNM and distal metastasis. In molecular testing, there have been three and five iterations of updates regarding mismatch repair (MMR)/microsatellite instability (MSI) status and RAS/BRAF gene mutation detection, respectively. The standardization of MMR status testing has sharply decreased the proportion of deficient MMR (dMMR) patients (from 32.5% to 7.4%) since 2013. The prognosis of patients underwent MMR status testing since 2013 (n = 867) were significantly better than patients before 2013 (n = 1,313). In addition, detection of RAS/BRAF gene mutation status (n = 5,041) resulted in better DFS but not OS, for patients with stage I-III disease (n = 16,557). Conclusion: Over the past few decades, updates in elements in pathological reports, as well as the development of standardized tests for MMR/MSI status and RAS/BRAF gene mutations have significantly improved patient outcomes.

A Glimpse of Research Trends and Frontiers in the Etiology of Premature Ovarian Insufficiency via Bibliometric Analysis.

INTRODUCTION: Premature Ovarian Insufficiency (POI) is the most common reproductive aging disorder in women of reproductive age, which is characterized by decreased ovarian function in women before the age of 40. Etiology research of POI has garnered interest and attention from scholars worldwide over the past decades. METHOD: However, to the best of our knowledge, no comprehensive survey with bibliometric analysis has been conducted yet on the research trends of POI etiology. This article aimed to analyze current scientific findings on the etiology of POI, offering innovative ideas for further research. Research articles on the etiology of POI from 1994 to 2023 were collected from the Web of Science Core Collection. A total of 456 research articles were included, and the total number of publications increased annually. We used VOSviewer and bibliometric.com to analyze the keywords, terms, institution, publication country/region, author name, publication journal, and the sum of times the articles have been cited. RESULTS: This study has shown that a research hotspot is the genetic etiology of POI; however, there is still a lack of research on the impact of epigenetic alterations, iatrogenic injuries, environmental pollution, social stress, and unhealthy lifestyles on the pathogenesis of POI. CONCLUSION: The factors illustrated here represent potential future directions for POI etiology research and warrant more attention from researchers.

Unlocking the crucial role of cancer-associated fibroblasts in tumor metastasis: Mechanisms and therapeutic prospects.

BACKGROUND: Tumor metastasis represents a stepwise progression and stands as a principal determinant of unfavorable prognoses among cancer patients. Consequently, an in-depth exploration of its mechanisms holds paramount clinical significance. Cancer-associated fibroblasts (CAFs), constituting the most abundant stromal cell population within the tumor microenvironment (TME), have garnered robust evidence support for their pivotal regulatory roles in tumor metastasis. AIM OF REVIEW: This review systematically explores the roles of CAFs at eight critical stages of tumorigenic dissemination: 1) extracellular matrix (ECM) remodeling, 2) epithelial-mesenchymal transition (EMT), 3) angiogenesis, 4) tumor metabolism, 5) perivascular migration, 6) immune escape, 7) dormancy, and 8) premetastatic niche (PMN) formation. Additionally, we provide a compendium of extant strategies aimed at targeting CAFs in cancer therapy. KEY SCIENTIFIC CONCEPTS OF REVIEW: This review delineates a structured framework for the interplay between CAFs and tumor metastasis while furnishing insights for the potential therapeutic developments. It contributes to a deeper understanding of cancer metastasis within the TME, facilitating the utilization of CAF-targeting therapies in anti-metastatic approaches.

Finding the minimum number of retrieved lymph nodes and negative lymph nodes in gastric cancer surgery: a real-world study.

BACKGROUND: Lymph node retrieval deficiency can lead to understagement and postoperative cancer recurrence, it is crucial to establish the standard number of retrieved lymph nodes (rLNs) and negative lymph nodes (nLNs) for patients undergoing gastrectomy. METHODS: Patients who has gastric adenocarcinoma and underwent either radical subtotal gastrectomy (RSG) or radical total gastrectomy (RTG) between 2000 and 2022 were retrospectively included. We utilized restricted cubic spline (RCS) analysis to determine the ideal threshold for rLNs and nLNs. Survival analysis was conducted using Kaplan-Meier (KM) curves, log-rank tests and forest plots. Propensity score matching (PSM) was utilized to balance parameters between two groups. The median follow-up time for this study was 3,095 days. RESULTS: Our study found that there are significant tumor characteristic differences between RSG and RTG. For patients with N0-N3a stage undergoing RSG, retrieving≥24 lymph nodes intraoperatively were associated with better prognosis both before and after PSM (OS: P<0.001, P=0.019); whereas for N3b stage, at least 32 rLNs were required (OS: P=0.006, P=0.023). Similarly, for patients with N0-N3a stage undergoing RTG, retrieving≥27 lymph nodes intraoperatively were associated with better prognosis both before and after PSM (OS: P<0.001, P=0.047); whereas for N3b stage, at least 34 rLNs were required (OS: P<0.001, P=0.003). Additionally, for patients undergoing RSG, having ≥21 nLNs (OS: P<0.001, P=0.013), and for those undergoing RTG, having ≥22 nLNs (OS: P<0.001, P<0.001), were also associated with better prognosis both before and after PSM. CONCLUSIONS: For patients receiving RSG, rLNs should reach 24 when lymph nodes are limited, and 32 when lymph node metastasis is more extensive, with a minimum number of nLNs ideally reaching 21. Similarly, for patients receiving RTG, rLNs should reach 27 when lymph nodes are limited, 34 when lymph node metastasis is more extensive, and a minimum number of nLNs ideally reaching 22.

Study on the Effect of Different Concentrations of SO2 on the Volatile Aroma Components of 'Beibinghong' Ice Wine.

SO2 plays an important role in wine fermentation, and its effects on wine aroma are complex and diverse. In order to investigate the effects of different SO2 additions on the fermentation process, quality, and flavor of 'Beibinghong' ice wine, we fermented 'Beibinghong' picked in 2019. We examined the fermentation rate, basic physicochemical properties, and volatile aroma compound concentrations of 'Beibinghong' ice wine under different SO2 additions and constructed a fingerprint of volatile compounds in ice wine. The results showed that 44 typical volatile compounds in 'Beibinghong' ice wine were identified and quantified. The OAV and VIP values were calculated using the threshold values of each volatile compound, and t the effect of SO2 on the volatile compounds of 'Beibinghong' ice wine might be related to five aroma compounds: ethyl butyrate, ethyl propionate, ethyl 3-methyl butyrate-M, ethyl 3-methyl butyrate-D, and 3-methyl butyraldehyde. Tasting of 'Beibinghong' ice wine at different SO2 additions revealed that the overall flavor of 'Beibinghong' ice wine was the highest at an SO2 addition level of 30 mg/L. An SO2 addition level of 30 mg/L was the optimal addition level. The results of this study are of great significance for understanding the effect of SO2 on the fermentation of 'Beibinghong' ice wine.

Synergistic Development of Natural Rubber/Butyl Rubber Composites for Improved Interfacial Bonding and Enhanced Shock-Absorbing Capabilities.

Shock-absorbing materials play a vital role in various industrial sectors, including construction and transportation. Among these materials, natural rubber (NR) stands out due to its exceptional elastic and mechanical properties, coupled with its robust crack resistance. Nevertheless, with the rising demand for enhanced damping capacities, there is a need to further optimize the damping performance of NR. One direct approach is to blend it with high-damping rubber. Butyl rubber (IIR) is a prominent member of the high-damping rubber category. Integrating IIR effectively with the NR, however, presents challenges. These challenges arise from IIR's inherent characteristics, such as its low unsaturation, slower vulcanization rate, and restricted compatibility with NR. Addressing these challenges, our study employed isoprene and isobutene to synthesize a variant of butyl rubber with a higher degree of unsaturation-achieving an unsaturation level between 4 and 6 mol %. Notably, this heightened unsaturation significantly expedited the curing time of IIR and facilitated the concurrent vulcanization of both IIR and NR. Utilizing atomic force microscopy, we observed that the introduction of unsaturated double bonds ameliorated the compatibility between NR and IIR, leading to an interfacial region extending up to 1000 nm. Our tests using a dynamic mechanical analyzer and rubber processing analyzer demonstrated the material's damping temperature range. Furthermore, there was a noticeable rise in the loss factor (tan δ) at ambient temperature, which remains over 0.1 across both a frequency window of 0.2 to 5 Hz and a strain spectrum of 10 to 200%. This tan δ enhancement ensured the potential of these rubber composites for shock-absorbing applications.

Efficacy, tolerability, and safety of the oral phosphate binder VS-505 (AP301).

BACKGROUND: VS-505 (AP301), an acacia and ferric oxyhydroxide polymer, is a novel fiber-iron-based phosphate binder. This two-part phase 2 study evaluated the tolerability, safety, and efficacy of oral VS-505 administered three times daily with meals in treating hyperphosphatemia in chronic kidney disease (CKD) patients receiving maintenance hemodialysis (MHD). METHODS: In Part 1, patients received dose-escalated treatment with VS-505 2.25, 4.50, and 9.00 g/day for 2 weeks each, guided by serum phosphorus levels. In Part 2, patients received randomized, open-label, fixed-dosage treatment with VS-505 (1.50, 2.25, 4.50, or 6.75 g/day) or sevelamer carbonate 4.80 g/day for 6 weeks. The primary efficacy endpoint was the change in serum phosphorus. RESULTS: The study enrolled 158 patients (Part 1: 25; Part 2: 133), with 130 exposed to VS-505 in total. VS-505 was well tolerated. The most common adverse events were gastrointestinal disorders, mainly feces discolored (56%) and diarrhea (15%; generally during weeks 1‒2 of treatment). Most gastrointestinal disorders resolved without intervention, and none were serious. In Part 1, serum phosphorus significantly improved (mean change -2.0 mg/dL; 95% confidence interval -2.7, -1.4) after VS-505 dose escalation. In Part 2, serum phosphorus significantly and dose-dependently improved in all VS-505 arms, with clinically meaningful reductions with VS-505 4.50 and 6.75 g/day, and sevelamer carbonate 4.80 g/day (mean change -1.6 (-2.2, -1.0), -1.8 (-2.4, -1.2), and -1.4 (-2.2, -0.5) mg/dL, respectively). In both Parts, serum phosphorus reductions occurred within 1 week of VS-505 initiation, returning to baseline within 2 weeks of VS-505 discontinuation. CONCLUSION: VS-505, a novel phosphate binder, was well tolerated with a manageable safety profile, and effectively and dose-dependently reduced serum phosphorus in CKD patients with hyperphosphatemia receiving MHD. Clinical Trial registration number: NCT04551300.

Exposure to Short- and Medium-Chain Chlorinated Paraffins and the Risk of Gestational Diabetes Mellitus: A Nested Case-Control Study in Eastern China.

Toxicological studies have indicated that exposure to chlorinated paraffins (CPs) may disrupt intracellular glucose and energy metabolism. However, limited information exists regarding the impact of human CP exposure on glucose homeostasis and its potential association with an increased risk of developing gestational diabetes mellitus (GDM). Here, we conducted a prospective study with a nested case-control design to evaluate the link between short- and medium-chain CP (SCCPs and MCCPs) exposures during pregnancy and the risk of GDM. Serum samples from 102 GDM-diagnosed pregnant women and 204 healthy controls were collected in Hangzhou, Eastern China. The median (interquartile range, IQR) concentration of SCCPs was 161 (127, 236) ng/mL in the GDM group compared to 127 (96.9, 176) ng/mL in the non-GDM group (p < 0.01). For MCCPs, the GDM group had a median concentration of 144 (117, 174) ng/mL, while the control group was 114 (78.1, 162) ng/mL (p < 0.01). Compared to the lowest quartile as the reference, the adjusted odds ratios (ORs) of GDM were 7.07 (95% CI: 2.87, 17.40) and 3.34 (95% CI: 1.48, 7.53) in the highest quartile of ∑SCCP and ∑MCCP levels, respectively, with MCCPs demonstrating an inverted U-shaped association with GDM. Weighted quantile sum regression evaluated the joint effects of all CPs on GDM and glucose homeostasis. Among all CP congeners, C13H23Cl5 and C10H16Cl6 were the crucial variables driving the positive association with the GDM risk. Our results demonstrated a significant positive association between CP concentration in maternal serum and GDM risk, and exposure to SCCPs and MCCPs may disturb maternal glucose homeostasis. These findings contribute to a better understanding of the health risks of CP exposure and the role of environmental contaminants in the pathogenesis of GDM.

Diversity of Endophytes of Actinidia arguta in Different Seasons.

The seasonal changes in environmental conditions can alter the growth states of host plants, thereby affecting the living environment of endophytes and forming different endophytic communities. This study employs Illumina MiSeq next-generation sequencing to analyze the 16SrRNA and ITS rDNA of endophytes in 24 samples of Actinidia arguta stem tissues across different seasons. The results revealed a high richness and diversity of endophytes in Actinidia arguta, with significant seasonal variations in microbial community richness. This study identified 897 genera across 36 phyla for bacteria and 251 genera across 8 phyla for fungi. Notably, 69 bacterial genera and 19 fungal genera significantly contributed to the differences in community structure across seasons. A distinctive feature of coexistence in the endophytic community, both specific and conservative across different seasons, was observed. The bacterial community in winter demonstrated significantly higher richness and diversity compared to the other seasons. Environmental factors likely influence the optimal timing for endophyte colonization. Solar radiation, temperature, precipitation, and relative humidity significantly impact the diversity of endophytic bacteria and fungi. In addition, seasonal variations show significant differences in the nutritional modes of fungal endophytes and the degradation, ligninolysis, and ureolysis functions of bacterial endophytes. This study elucidates the potential role of endophytes in assisting Actinidia arguta in adapting to seasonal changes and provides a theoretical basis for further exploration of functional microbial strains.

ED-71 ameliorates bone regeneration in type 2 diabetes by reducing ferroptosis in osteoblasts via the HIF1α pathway.

Eldecalcitol (ED-71), a novel active form of vitamin D, shows potential in treating osteoporosis. However, its underlying mechanisms of action remain to be determined. This study aimed to investigate the effect of ED-71 on bone regeneration and to illustrate its mode of action. The in-vitro model was developed using rat primary osteoblasts cultured under high-glucose conditions, and these cells were treated with ED-71. Additionally, an in vivo model of cranial bone defects was established in type 2 diabetic rats, and ED-71 was administered by gavage. The results demonstrated that ED-71 prevented osteoblast cell death, enhanced rat primary osteoblasts' osteogenic capacity, and attenuated the overexpression of hypoxia-inducible factor 1α (HIF1α) induced by high glucose levels. Furthermore, ED-71 increased glutathione peroxidase 4 (GPX4) levels and inhibited ferroptosis in response to hyperglycemic stimulation. Notably, interference with the HIF1α activator and ferroptosis activator Erastin significantly reduced the therapeutic effects of edetate osteolysis. These findings were further tested in vivo experiments. These results suggest that ED-71 activates the HIF1α pathway in vivo and in vitro, effectively relieving the ferroptosis induced by high glucose. Significantly, ED-71 may improve osteogenic disorders caused by diabetes.

Ferroptosis in cardiovascular diseases: role and mechanism.

In multicellular organisms, regulatory cell death is a crucial aspect of growth and development. Ferroptosis, which was postulated roughly ten years ago, is a mode of cell death that differs from apoptosis, autophagy, and pyrodeath. This distinct pattern of cell death is triggered by an imbalance between oxidants and antioxidants and strongly associated with the metabolism of iron, lipids, amino acids, and glutathione. A growing body of research has implicated ferroptosis in the incidence and progression of many organ traumas and degenerative diseases. Recently, ferroptosis has gained attention as a crucial regulatory mechanism underlying the initiation and development of a variety of cardiovascular diseases, including myocardial ischemia/reperfusion injury, cardiomyopathy, arrhythmia, chemotherapy, and Corona Virus-2-induced cardiac injury. Pharmacological therapies that inhibit ferroptosis have great potential for the management of cardiovascular disorders. This review discusses the prevalence and regulatory mechanisms of ferroptosis, effect of ferroptosis on the immune system, significance of ferroptosis in cardiovascular diseases, and potential therapeutic value of regulating ferroptosis in a variety of heart diseases.

Protein Disulfide Isomerase A2 Is Correlated with Immune Infiltrates and Is a Novel Prognostic Biomarker in Glioma Patients.

OBJECTIVE: Protein disulfide isomerase A2 (PDIA2), a member of the protein disulfide isomerase family, plays a key role in the folding of nascent proteins in the endoplasmic reticulum by forming disulfide bonds, together with enzymes such as thiol isomerase, oxidase, and reductase. This study investigated the clinical significance and potential functions of PDIA2 in glioma. METHODS: The expression of PDIA2 in gliomas was explored using The Cancer Genome Atlas and Gene Expression Omnibus databases. We analyzed the clinical characteristics of glioma patients and the prognostic and diagnostic value of PDIA2 expression. Kaplan-Meier and Cox regression analyses were used to examine the effect of PDIA2 expression on overall survival, progression-free interval, and disease-specific survival. Furthermore, we performed Gene Set Enrichment Analysis and immune infiltration analysis to investigate the functions of PDIA2. PDIA2 mRNA and protein expression was evaluated in cell lines and glioma tissues. RESULTS: PDIA2 was expressed at low levels in glioma patients. Kaplan-Meier survival analysis showed that glioma patients with low PDIA2 levels had a worse prognosis than those with high PDIA2 levels. Receiver operating characteristic curve analysis indicated the diagnostic and prognostic ability of PDIA2 (area under the curve = 0.918). Pathways associated with PD1, PI3K/AKT, cancer immunotherapy via PD1 blockade, Fceri-mediated NF-kB activation, FOXM1, and DNA repair were enriched in glioma patients with low levels of PDIA2. PDIA2 expression levels were negatively correlated with immune cell infiltrate levels. CONCLUSION: PDIA2 levels are significantly downregulated in glioma. PDIA2 expression may be a potential biomarker for the diagnosis and prognosis of glioma patients.

Deterministic factors modulating assembly of groundwater microbial community in a nitrogen-contaminated and hydraulically-connected river-lake-floodplain ecosystem.

The river-lake-floodplain system (RLFS) undergoes intensive surface-groundwater mass and energy exchanges. Some freshwater lakes are groundwater flow-through systems, serving as sinks for nitrogen (N) entering the lake. Despite the threat of cross-nitrogen contamination, the assembly of the microbial communities in the RLFS was poorly understood. Herein, the distribution, co-occurrence, and assembly pattern of microbial community were investigated in a nitrogen-contaminated and hydraulically-connected RLFS. The results showed that nitrate was widely distributed with greater accumulation on the south than on the north side, and ammonia was accumulated in the groundwater discharge area (estuary and lakeshore). The heterotrophic nitrifying bacteria and aerobic denitrifying bacteria were distributed across the entire area. In estuary and lakeshore with low levels of oxidation-reduction potential (ORP) and high levels of total organic carbon (TOC) and ammonia, dissimilatory nitrate reduction to ammonium (DNRA) bacteria were enriched. The bacterial community had close cooperative relationships, and keystone taxa harbored nitrate reduction potentials. Combined with multivariable statistics and self-organizing map (SOM) results, ammonia, TOC, and ORP acted as drivers in the spatial evolution of the bacterial community, coincidence with the predominant deterministic processes and unique niche breadth for microbial assembly. This study provides novel insight into the traits and assembly of bacterial communities and potential nitrogen cycling capacities in RLFS groundwater.

Prenatal exposure to emerging and traditional organophosphate flame retardants: Regional comparison, transplacental transfer, and birth outcomes.

During gestation, organophosphate flame retardants (OPFRs) have the potential to pose health risks to fetuses due to their ability to cross the placental barrier. However, data are scarce regarding the transplacental transfer of these compounds, particularly concerning emerging OPFRs and regional variations. In this study, we analyzed 14 traditional OPFRs and 5 emerging OPFRs in maternal and cord serum samples from Mianyang and Hangzhou, two cities in eastern and western China, respectively. The results revealed marked disparities in the overall levels of OPFRs between the two cities (p < 0.05), with the average concentration in maternal serum being higher in Hangzhou (14.55 ng/mL) than in Mianyang (8.28 ng/mL). The most abundant compounds found in both cities were tris (2-chloroethyl) phosphate (TCEP), Triphenyl phosphate (TPHP), and Tri-n-butyl phosphate (TnBP). Additionally, this study marked the first detection of novel OPFRs, including resorcinol bis (diphenyl phosphate) (RDP), isodecyl diphenyl phosphate (IDDPP), cresyl diphenyl phosphate (CDP), and bisphenol A bis (diphenyl phosphate) (BPA-BDPP) in maternal and cord serum simultaneously with the detection frequencies higher than 45%. This study also found that transplacental transfer efficiencies for OPFRs varied by ester group, with Aryl-OPFRs exhibiting the highest transfer rates (0.90-1.11) and Alkyl-OPFRs exhibiting the lowest (0.66-0.83). Transfer efficiencies exhibited a positive correlation with log Kow values (p < 0.05), suggesting that hydrophobic OPFRs with higher log Kow values are more likely to permeate the placental barrier. Moreover, the exposure levels of Tris (1,3-dichloro-2-propyl) phosphate (TDCIPP), Tri (Chloropropyl) Phosphate (TCIPP), TPHP, and CDP in cord serum were negatively associated (p < 0.05) with birthweight of newborns. This research adds to our understanding of the transplacental transfer of OPFRs and the possible health risks associated with prenatal exposure.

Navy Sailors Health Behavior: A Multi-Factor Analysis of Circadian Rhythm on Naval Operational Capability.

Objective: The objective of this research was to determine the impact of circadian rhythm disorders on sleep disorders, fatigue and health problems of navy sailors from the perspective of their health behavior. During its voyage, navy crews have obvious problems such as sleep disorders and fatigue, among which the circadian rhythm disorder was the most common. Warning system, special environment at sea, pressure and other factors can lead to the occurrence of circadian rhythm disorders. Methods: The primary data was used in this research with a sample size of 278 and Smart PLS was used for statistical analysis. Results: According to empirical data, the impact of circadian rhythm disorders was significant on sleep disorders, fatigue and health problems of navy sailors. The research is novel in the literature because very few studies have discussed the circadian rhythm disorders in the context of navy sailors. Conclusion: The research implications in the theory are reliable to enhance the body of knowledge of circadian in the significant way. Furthermore, the study has some practical implications to work on to enhance the practices to improve the health of navy sailors during their long time in the sea.

Heterogeneous organization of Locus coeruleus: An intrinsic mechanism for functional complexity.

Locus coeruleus (LC) is a small nucleus located deep in the brainstem that contains the majority of central noradrenergic neurons, which provide the primary source of noradrenaline (NA) throughout the entire central nervous system (CNS).The release of neurotransmitter NA is considered to modulate arousal, sensory processing, attention, aversive and adaptive stress responses as well as high-order cognitive function and memory, with the highly ramified axonal arborizations of LC-NA neurons sending wide projections to the targeted brain areas. For over 30 years, LC was thought to be a homogeneous nucleus in structure and function due to the widespread uniform release of NA by LC-NA neurons and simultaneous action in several CNS regions, such as the prefrontal cortex, hippocampus, cerebellum, and spinal cord. However, recent advances in neuroscience tools have revealed that LC is probably not so homogeneous as we previous thought and exhibits heterogeneity in various aspects. Accumulating studies have shown that the functional complexity of LC may be attributed to its heterogeneity in developmental origin, projection patterns, topography distribution, morphology and molecular organization, electrophysiological properties and sex differences. This review will highlight the heterogeneity of LC and its critical role in modulating diverse behavioral outcomes.

Nitrogen species and microbial community coevolution along groundwater flowpath in the southwest of Poyang Lake area, China.

Nitrate and ammonia overload in groundwater can lead to eutrophication of surface water in areas where surface water is recharged by groundwater. However, this process remained elusive due to the complicated groundwater N cycling, which is governed by the co-evolution of hydrogeochemical conditions and N-cycling microbial communities. Herein, this process was studied along a generalized groundwater flowpath in Ganjing Delta, Poyang Lake area, China. From groundwater recharge to the discharge area near the lake, oxidation-reduction potential (ORP), NO3-N, and NO2-N decreased progressively, while NH3-N, total organic carbon (TOC), Fe2+, sulfide, and TOC/NO3- ratio accumulated in the lakeside samples. The anthropogenic influences such as sewage and agricultural activities drove the nitrate distribution, as observed by Cl- vs. NO3-/Cl- ratio and isotopic composition of nitrate. The hydrogeochemical evolution was intimately coupled with the changes in microbial communities. Variations in microbial community structures was significantly explained by Fe2+, NH3-N, and sulfide, while TOC/NO3- controlled the distribution of predicted N cycling gene. The absence of NH3-N in groundwater upstream was accompanied by the enrichment in Acinetobacter capable of nitrification and aerobic denitrification. These two processes were also supported by Ca2+ + Mg2+ vs. HCO3- ratio and isotopic composition of NO3-. The DNRA process downstream was revealed by both the presence of DNRA-capable microbes such as Arthrobacter and the isotopic composition of NH4+ in environments with high concentrations of NH3-N, TOC/NO3-, Fe2+, and sulfide. This coupled evolution of N cycling and microbial community sheds new light on the N biogeochemical cycle in areas where surface water is recharged by groundwater.