Network pharmacology screening, in vitro and in vivo evaluation of antianxiety and antidepressant drug-food analogue.

BACKGROUND: Depression and anxiety disorders are prevalent psychiatric conditions, and currently utilized chemical drugs typically come with significant adverse effects. China boasts a wealth of medicinal and food herbs known for their safe and effective properties. PURPOSE: This study aimed to develop novel formulations with improved antidepressant and anxiolytic effects derived from medicinal and food herbs. STUDY DESIGN: Screening combinations with antidepressant and anxiolytic effects using techniques such as network pharmacology and validating their effects in vitro and in vivo experiments. METHODS: Utilizing network pharmacology and molecular docking, we identified the top ten medicinal herbs with anxiolytic and antidepressant potential. Herbs with cytoprotective effects and non-toxic characteristics were further screened to formulate the herbal blends. Subsequently, we established a PC12 cell injury model and a chronic unpredictable mild stress (CUMS) model in mice to assess the effects of our formulations. RESULTS: Ten medicinal herbs were initially screened, and six of them were deemed suitable for formulating the blend, namely Gancao, Dazao, Gouqizi, Sangye, Huangqi, and Jinyinhua (GDGSHJ). The GDGSHJ formulation reduced Lactate Dehydrogenase (LDH) leakage, decreased apoptosis, and demonstrated a favorable antidepressant and antianxiety effect in the CUMS mouse model. Besides, GDGSHJ led to the upregulation of serum 5-Hydroxytryptamine (5-HT) content and brain tissue 5-HT, Gamma-aminobutyric acid (GABA), and Dopamine (DA) levels. It also downregulated the expression of SLC6A4 and SLC6A3 genes in the mouse hippocampus while upregulating HTR1A, DRD1, DRD2, and GABRA1 genes. CONCLUSION: Our formulation exhibited robust antidepressant and antianxiety effects without inducing substantial toxicity. This efficacy appears to be mediated by the expression of relevant genes within the hippocampus of mice. The formulation achieved this effect by balancing 5-HT levels in the serum and DA, GABA, and 5-HT levels within brain tissue.

The role of dysbiotic gut mycobiota in modulating risk for abdominal aortic aneurysm.

Abdominal aortic aneurysm (AAA) is a large-vessel disease with high mortality, characterized by complex pathogenic mechanisms. Current therapeutic approaches remain insufficient to halt its progression. Fungi are important members of the gut microbiota. However, their characteristic alterations and roles in AAA remain unclear. This study investigated the role of gut fungal communities in the development of AAA through metagenomic sequencing of fecal samples from 31 healthy individuals and 33 AAA patients. We observed significant dysbiosis in the gut mycobiomes of AAA patients compared to healthy individuals, characterized by an increase in pathogenic fungi like Candida species and a decrease in beneficial yeasts such as Saccharomyces cerevisiae. The changes in fungal populations correlated strongly with clinical indicators of AAA, highlighting their potential for diagnosing and predicting AAA progression. Furthermore, our animal experiments demonstrated that Saccharomyces cerevisiae significantly ameliorated pathological alterations in AAA mice, suggesting a protective role for specific yeast strains against AAA development. These findings underscore the significant impact of gut mycobiomes on AAA and suggest that modulating these fungal communities could offer a novel therapeutic approach. Our research advances the understanding of the influence of gut microbiome on vascular diseases and suggests potential non-surgical approaches for managing AAA. By elucidating the diagnostic and therapeutic potential of gut fungi in AAA, this study provided important clues for future clinical strategies and therapeutic developments in the field of vascular medicine. IMPORTANCE: Our research highlights the crucial role of gut fungi in abdominal aortic aneurysm (AAA) development. By analyzing fecal samples from AAA patients and healthy controls, we discovered significant dysbiosis in gut fungal communities, characterized by an increase in harmful Candida species and a decrease in beneficial yeasts like Saccharomyces cerevisiae. This dysbiosis was correlated with the severity of AAA. Importantly, in animal experiments, supplementing with Saccharomyces cerevisiae significantly slowed AAA progression. These findings suggest that modulating gut fungi may offer a novel, non-surgical approach to the diagnosis and treatment of AAA, potentially reducing the need for invasive procedures.

Regional distribution differences of antibiotics in tropical marine aquaculture area: Insights into antibiotic management and risk assessment.

In recent years, global demand for marine aquaculture products has led to a significant rise in antibiotic use, particularly in tropical coastal aquaculture areas However, research on antibiotic residues in these environments remains limited, hindering a comprehensive understanding of their environmental presence and associated risks. This study investigates the regional distribution, ecological risks, and sources of 44 antibiotics in seawater across four coastal aquaculture areas in Hainan island (Wenchang, Sanya, Danzhou, and Wanning). Among the 44 antibiotics tested across 42 sampling sites, all were detected with a 100 % detection rate. Antibiotics such as Trimethoprim (TMP), Sulfanitran (APNPS), Sulfaquinoxaline (SQ), Sulfadimethoxine (SDT), Chloramphenicol (CHP), and Florfenicol (FLO) were consistently detected across all sampling sites. Total concentrations of detected antibiotics ranged from 0 to 818.79 ng.L-1, with sulfonamide antibiotics ranging from 0 to 629.49 ng.L-1, chloramphenicol antibiotics from 0 to 87.39 ng.L-1, tetracyclines from 0 to 221.39 ng.L-1, and fluoquinolones from 0 to 272.08 ng.L-1. The highest levels of antibiotic pollution were observed at the W5 sampling site in Wenchang, attributed to aquaculture wastewater discharge, while no antibiotics were found at D12 in Danzhou. In these regions, source analysis identified aquaculture and domestic sewage as the primary contributors to antibiotic pollution in these regions. Correlation analysis with environmental factors revealed significant influences of factors such as SAL, kPa, TN, SPC, and pH on sulfonamide and chloramphenicol antibiotics. Health risk assessment indicated moderate to high risks to aquatic organisms from antibiotics like NOR, CIP, ENR, OFL, TMP, and SMX in the study areas, underscoring the need for preventive measures, stricter regulation of antibiotic use, and enhanced ecological risk monitoring in aquaculture regions. This study provides critical insights into antibiotic contamination in Hainan's coastal aquaculture areas, highlighting the urgent need for further research into the occurrence and ecological impacts of these emerging pollutants in marine environments.

Synergistically activating nucleophile strategy enabled organocatalytic asymmetric P-addition of cyclic imines.

Herein, we present an attractive organocatalytic asymmetric addition of P-nucleophiles to five-membered cyclic N-sulfonyl imines facilitated by phosphonium salt catalysis, enabling the highly enantioselective synthesis of tri- and tetra-substituted cyclic phosphorus-containing benzosultams. With this protocol, various cyclic α-aminophosphonates were efficiently synthesized with high yields and exceptional enantioselectivities (up to >99% ee) under mild reaction conditions. The utility and practicality of this method were demonstrated through gram-scale reactions and straightforward elaborations. Notably, the success of this approach relies on the deliberate selection of a synergistic organocatalytic system, which helps circumvent foreseeable side effects while handling secondary phosphine oxides (SPOs). Systematic mechanistic studies, incorporating experiments and DFT calculations, have revealed the critical importance of judiciously selecting bifunctional phosphonium salt catalysts for effectively activating P-nucleophiles while stereoselectively controlling the P-attack process.

Complete mitochondrial genome and phylogenetic analysis of Mancinella alouina.

BACKGROUND: The Muricidae family in the Class Gastropoda comprises numerous species with a vast range of morphological features and a worldwide presence. The phylogeny of the Muricidae has been analyzed in previous studies; however, the evolutionary relationships among the main branches of the Muricidae remain unknown. METHODS AND RESULTS: In the present study, the mitochondrial genome of Mancinella alouina was sequenced. The mitochondrial genome was found to be 16,671 bp in length and made up of 37 genes (13 protein-coding genes, 22 transfer RNA and 2 ribosomal RNA genes). The genome has an A-T-rich region (66.5% A + T content) and all of the PCGs use the ATN start codon and the TAG or TAA stop codons. The mitochondrial gene arrangement of Mancinella alouina is similar to that of other Muricidae, except for Ocinebrellus inornatus and Ceratostoma burnetti. On the basis of a flexible molecular clock model, time-calibrated phylogenetic results indicate that the genus Mancinella diverged roughly 18.09 Mya, and that the family Muricidae emerged in the Late Cretaceous. CONCLUSIONS: This study reveals the structural and sequence information features of the mitochondrial genome of Mancinella alouina. This study provides evidence for the relationships within the family Muricidae at the molecular level, and infer the divergence time. The results of phylogenetic analyses strongly support the current classification.

Tracking-seq reveals the heterogeneity of off-target effects in CRISPR-Cas9-mediated genome editing.

The continued development of novel genome editors calls for a universal method to analyze their off-target effects. Here we describe a versatile method, called Tracking-seq, for in situ identification of off-target effects that is broadly applicable to common genome-editing tools, including Cas9, base editors and prime editors. Through tracking replication protein A (RPA)-bound single-stranded DNA followed by strand-specific library construction, Tracking-seq requires a low cell input and is suitable for in vitro, ex vivo and in vivo genome editing, providing a sensitive and practical genome-wide approach for off-target detection in various scenarios. We show, using the same guide RNA, that Tracking-seq detects heterogeneity in off-target effects between different editor modalities and between different cell types, underscoring the necessity of direct measurement in the original system.

Gender differences in the relationship between medical students' emotional intelligence and stress coping: a cross-sectional study.

BACKGROUND: Given the increasing stress levels among medical students due to the impact of COVID-19, it is crucial to effectively reduce their stress levels for their future development. To better understand medical students' stress coping, this study investigated how their emotional intelligence is related to stress coping and whether this relationship is moderated by gender differences. METHODS: A cross-sectional study was conducted. A random sample of 744 medical students from Hebei Province, China, was investigated via an emotional intelligence scale and stress coping questionnaire from March-May 2023. The response rate was 93%. SPSS and Mplus statistical software were used for the data analysis. RESULTS: The self-emotional appraisal of medical students had a significant negative effect on avoidant coping (ß = -0.173, CI 95% = [-0.243, -0.099], p < .001). However, the other dimensions of emotional intelligence (others' emotional appraisal, use of emotion, and regulation of emotion) had a significant positive impact on the active coping of female medical students (ß = 0.146, CI 95% = [0.082,0.214], p < .001; ß = 0.235, CI 95% = [0.167,0.304], p < .001; ß = 0.165, CI 95% = [0.084,0.247], p < .001). In contrast to those of female medical students, other dimensions of emotional intelligence had a significant positive impact on the avoidant coping of male medical students (ß = -0.161, CI 95% = [-0.284, -0.062]; p < 0.01; ß = 0.126, CI 95% = [0.043,0.246], p < 0.001; ß = 0.159, CI 95% = [0.054,0.277], p < 0.05; ß = -0.221, CI 95% = [-0.363, -0.129], p < 0.001). Moreover, the use of emotion had a significant positive impact on the active coping of male medical students (ß = 0.272, CI 95% = [0.182,0.382], p < .001). Furthermore, gender differences had a moderating effect on the relationship between emotional intelligence dimensions and stress coping (ß = 0.178; CI 95% = [0.068,0.292]; p < 0.05). Others' emotional appraisal has a greater impact on female students' active coping. In addition, with increasing regulation of emotion ability, female medical students reduce avoidant coping (ß = 0.169, CI 95% = [0.002,0.326]; p < 0.05). CONCLUSIONS: The current study revealed that gender is a significant moderator of the relationship between medical students' emotional intelligence and stress coping. These findings may help medical colleges focus on gender differences when improving medical students' ability to cope with stress.

Organophosphate esters uptake, translocation and accumulation in rice (Oryza sativa L.): impacts of lipid transporters and chemical properties.

To explore key factors involved in the uptake, translocation and accumulation of organophosphate esters (OPEs), computer simulation analysis and hydroponic experiments were executed. Lipid transporters with stocky-like active (SAC) cavities usually showed stronger binding affinities with the OPEs, especially when the SAC cavities belong to the Fish Trap model according to molecular docking. In our hydroponic trial, the binding affinity and gene expression of the lipid transporters and log Kow of the OPEs could be charged to the uptake, translocation and accumulation of the OPEs; however, these three factors played various important roles in roots and shoots. In detail, the effect of gene expression and binding affinity were stronger than log Kow in roots uptake and accumulation, but the result was the opposite in the shoots translocation. Transporters OsTIL and OsLTPL1 among all investigated transporters could play key roles in transporter-mediated OPE uptake, translocation and accumulation in the roots and shoots. OsMLP could be involved in the bidirected vertical translocation of the OPEs. OsLTP2 and OsLTP4 mainly acted as transporters of the OPEs in roots.

Single-Cell Landscape and a Macrophage Subset Enhancing Brown Adipocyte Function in Diabetes.

BACKGRUOUND: Metabolic dysregulation is a hallmark of type 2 diabetes mellitus (T2DM), in which the abnormalities in brown adipose tissue (BAT) play important roles. However, the cellular composition and function of BAT as well as its pathological significance in diabetes remain incompletely understood. Our objective is to delineate the single-cell landscape of BAT-derived stromal vascular fraction (SVF) and their characteristic alterations in T2DM rats. METHODS: T2DM was induced in rats by intraperitoneal injection of low-dose streptozotocin and high-fat diet feeding. Single-cell mRNA sequencing was then performed on BAT samples and compared to normal rats to characterize changes in T2DM rats. Subsequently, the importance of key cell subsets in T2DM was elucidated using various functional studies. RESULTS: Almost all cell types in the BAT-derived SVF of T2DM rats exhibited enhanced inflammatory responses, increased angiogenesis, and disordered glucose and lipid metabolism. The multidirectional differentiation potential of adipose tissue-derived stem cells was also reduced. Moreover, macrophages played a pivotal role in intercellular crosstalk of BAT-derived SVF. A novel Rarres2+macrophage subset promoted the differentiation and metabolic function of brown adipocytes via adipose-immune crosstalk. CONCLUSION: BAT SVF exhibited strong heterogeneity in cellular composition and function and contributed to T2DM as a significant inflammation source, in which a novel macrophage subset was identified that can promote brown adipocyte function.

Exosomes in diagnostic and therapeutic applications of ovarian cancer.

Ovarian cancer accounts for more deaths than any other female reproductive tract cancer. The major reasons for the high mortality rates include delayed diagnoses and drug resistance. Hence, improved diagnostic and therapeutic options for ovarian cancer are a pressing need. Extracellular vesicles (EVs), that include exosomes provide hope in both diagnostic and therapeutic aspects. They are natural lipid nanovesicles secreted by all cell types and carry molecules that reflect the status of the parent cell. This facilitates their potential use as biomarkers for an early diagnosis. Additionally, EVs can be loaded with exogenous cargo, and have features such as high stability and favorable pharmacokinetic properties. This makes them ideal for tumor-targeted delivery of biological moieties. The International Society of Extracellular Vesicles (ISEV) based on the Minimal Information for Studies on Extracellular Vesicles (MISEV) recommends the usage of the term "small extracellular vesicles (sEVs)" that includes exosomes for particles that are 30-200 nm in size. However, majority of the studies reported in the literature and relevant to this review have used the term "exosomes". Therefore, this review will use the term "exosomes" interchangeably with sEVs for consistency with the literature and avoid confusion to the readers. This review, initially summarizes the different isolation and detection techniques developed to study ovarian cancer-derived exosomes and the potential use of these exosomes as biomarkers for the early diagnosis of this devastating disease. It addresses the role of exosome contents in the pathogenesis of ovarian cancer, discusses strategies to limit exosome-mediated ovarian cancer progression, and provides options to use exosomes for tumor-targeted therapy in ovarian cancer. Finally, it states future research directions and recommends essential research needed to successfully transition exosomes from the laboratory to the gynecologic-oncology clinic.

Sedentary behavior patterns and bone health among overweight/obesity older women: a cross-sectional study.

Background: Recent studies have indicated an association between sedentary behavior (SB), particularly patterns of SB, and bone health. However, it remains uncertain how different patterns of SB in overweight/obesity older women impact their bone health. This study aimed to investigate the association between objectively measured SB patterns and bone health in Chinese community-dwelling overweight/obesity older women. Methods: Cross-sectional data were obtained from a baseline survey of Physical Activity and Health in Older Women Study. Quantitative ultrasound was used to measure speed of sound (SOS), broadband ultrasound attenuation (BUA), bone quality index (BQI) and T value to evaluate bone health. SB patterns were measured using triaxial accelerometers, including sedentary time in SB bouts of ≥ 10, 30, and 60 min, number of SB bouts ≥ 10, 30, and 60 min. Multiple linear regression was used to examine the associations of different SB patterns with bone health. Results: After adjusting for confounders, sedentary time in SB bouts ≥ 60 min, number of SB bouts ≥ 60 min were significantly associated with bone health, with a lower SOS [ß = -2.75, 95% confidence interval (CI): -4.96 to -0.53, P = 0.015], BUA (ß = -1.20, 95% CI: -2.14 to -0.26, P = 0.013), BQI (ß = -1.56, 95% CI: -2.63 to -0.49, P = 0.004), T value (ß = -0.08, 95% CI: -0.14 to -0.03, P = 0.004) per 60 min increase of sedentary time in SB bouts ≥ 60 min, and a lower SOS (ß = -3.97, 95% CI: -7.54 to -0.40, P = 0.029), BUA (ß = -1.80, 95% CI: -3.44 to -0.16, P = 0.031), BQI (ß = -2.28, 95% CI: -4.08 to -0.47, P = 0.014) and T value (ß = -0.12, 95% CI: -0.22 to -0.03, P = 0.013) per bout increase of SB bouts ≥ 60 min, respectively. Conclusion: Limiting the duration of prolonged sedentary bouts and minimizing the occurrence of number of SB bouts ≥ 60 min could be essential in bone health management, especially for those older people who are overweight/obesity.

Effects of Miscut on Step Instabilities in Homo-Epitaxially Grown GaN.

The rough morphology at the growth surface results in the non-uniform distribution of indium composition, intentionally or unintentionally doped impurity, and thus impacts the performance of GaN-based optoelectronic and vertical power electronic devices. We observed the morphologies of unintentionally doped GaN homo-epitaxially grown via MOCVD and identified the relations between rough surfaces and the miscut angle and direction of the substrate. The growth kinetics under the effect of the Ehrlich-Schwoebel barrier were studied, and it was found that asymmetric step motions in samples with a large miscut angle or those grown at high temperature were the causes of step-bunching. Meandering steps were believed to be caused by surface free energy minimization for steps with wide terraces or deviating from the [11¯00] m-direction.

Organocatalyzed Asymmetric Conjugate Addition of Alcohols to ß-Fluoroalkyl Vinylsulfones by Bifunctional Phosphonium Salt Catalyst.

Chiral secondary alcohols, serving as essential structural motifs, hold significant potential for diverse applications. The exploration of effective synthetic strategies toward these compounds is both attractive and challenging. Herein, we present an asymmetric oxa-Michael reaction involving aliphatic alcohols as nucleophiles and ß-fluoroalkyl vinylsulfones catalyzed by bifunctional phosphonium salt (BPS), achieving high yields and excellent enantioselectivities (up to 98 % yield and 98 % ee). Additionally, a sequential process including asymmetric oxa-Michael and debenzylation, facilitated by BPS/Lewis acid cooperation, was revealed for synthesizing diverse chiral secondary alcohol compounds in high yields (81-88 %) with consistent stereoselectivities. Furthermore, mechanistic explorations and subsequent results unveiled that the enantioselectivity originates from hydrogen-bonding and ion-pair interactions between the BPS catalyst and the substrates.

Association between per- and poly-fluoroalkyl substances and nonalcoholic fatty liver disease: A nested case-control study in northwest China.

Per- and poly-fluoroalkyl substances (PFAS) have been reported to have hepatotoxic effects. However, it is unclear whether they are linked to non-alcoholic fatty liver disease (NAFLD). This nested case-control study focused on the epidemiological links between PFAS and the prevalence of NAFLD. We selected 476 new cases of NAFLD and 952 age- and sex-matched controls from the Jinchang cohort population between 2014 and 2019. Serum concentrations of PFAS were measured using high-performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS). Only PFAS with a detection rate of ≥90 % were included for analysis, which included PFPeA, PFOA, PFNA, PFHxS, PFOS, and 9Cl-PF3ONS. The relationship between single and co-exposure to PFAS and the occurrence of NAFLD was evaluated using conditional logistic regression, Quantile g-computation (QgC), and Bayesian kernel machine regression (BKMR) model. Logistic regression indicated that PFPeA, PFOA, and 9Cl-PF3ONS were positive correlation with the incidence of NAFLD after adjusting for confounders, with odds ratios (OR) and 95 % confidence interval (CI) of 3.13 (95 % CI: 2.53, 3.86), 1.39 (95 % CI: 1.12, 1.73), and 1.41 (95 % CI: 1.20, 1.66), respectively. PFNA, PFHxS, and PFOS were nonlinearly and negatively associated with the incidence of NAFLD, with OR (95 % CI) of 0.53 (0.46, 0.62), 0.83 (0.73, 0.95), and 0.52 (0.44, 0.61), respectively. QgC showed a significant joint effect of PFAS mixture on NAFLD onset (OR: 1.52, 95 % CI: 1.24, 1.88). BKMR showed a weak positive trend between PFAS mixtures and NAFLD incidence. Positive correlations were primarily driven by PFPeA and 9Cl-PF3ONS, while negative correlations were mainly influenced by PFNA and PFOS. The BKMR model also suggested that there was an interaction between PFOS and PFNA and other four PFAS compounds. In conclusion, our findings suggest that individual and co-exposure to PFAS is associated with a risk of NAFLD onset.

Site-Selective Polyfluoroaryl Modification and Unsymmetric Stapling of Unprotected Peptides.

Peptide stapling is recognized as an effective strategy for improving the proteolytic stability and cell permeability of peptides. In this study, we present a novel approach for the site-selective unsymmetric perfluoroaryl stapling of Ser and Cys residues in unprotected peptides. The stapling reaction proceeds smoothly under very mild conditions, exhibiting a remarkably rapid reaction rate. It can furnish stapled products in both liquid and solid phases, and the presence of nucleophilic groups other than Cys thiol within the peptide does not impede the reaction, resulting in uniformly high yields. Importantly, the chemoselective activation of Ser ß-C(sp3)-H enables the unreacted -OH to serve as a reactive handle for subsequent divergent modification of the staple moiety with various therapeutic functionalities, including a clickable azido group, a polar moiety, a lipid tag, and a fluorescent dye. In our study, we have also developed a visible-light-induced chemoselective C(sp3)-H polyfluoroarylation of the Ser ß-position. This reaction avoids interference with the competitive reaction of Ser -OH, enabling the precise late-stage polyfluoroarylative modification of Ser residues in various unprotected peptides containing other highly reactive amino acid residues. The biological assay suggested that our peptide stapling strategy would potentially enhance the proteolytic stability and cellular permeability of peptides.

Novel Stereo-Induction Pattern in Pudovik Addition/Phospha-Brook Rearrangement Towards Chiral Trisubstituted Allenes.

Despite the significance of chiral allene skeletons in catalysis, organic synthesis and medicinal chemistry et al., there is a scarcity of reports on axially chiral allenyl phosphorus compounds. Here, we disclosed an efficient and straightforward cascade reaction between ethynyl ketones and phosphine oxides, resulting in a broad array of trisubstituted allenes incorporating a phosphorus moiety in high yields with excellent stereoselectivities facilitated by peptide-mimic phosphonium salt (PPS) catalysis, Additionally, comprehensive series of mechanistic experiments have been conducted to elucidate that this cascade reaction proceeds via an asymmetric Pudovik addition reaction followed by a subsequent phospha-Brook rearrangement that occurs concomitantly with kinetic resolution, representing a stereospecific rearrangement and protonation process facilitating central-to-axial chirality transfer in a cascade manner. We anticipate that our research will pave the way for a promising exploration of novel stereo-induction pattern in the Pudovik addition/phospha-Brook rearrangement cascade reaction.

Transport pathway of the Ag+ following artificial precipitation enhancement activities.

Artificial precipitation enhancement (APE) activities have been applied extensively around the world to enhance water resources. However, the transport way of the silver iodide catalyst utilized remains completely unknown. To address this issue, in this study, we monitored the content of silver ions (Ag+) in a water body under the influence of APE for a period of 16 years (2004-2019). Additionally, we monitored the content of silver ions in the multi-period rainfall and soil. Our findings indicate that after the APE operation, the detected silver content in the precipitation initially demonstrated an upward trend and then decreased to 0. Furthermore, we observed that some of the silver ions remained in the air for a period extending from the time of artificial rain till the next rain. The silver ion content in the soil during the flood season was elevated by 44 % in comparison to the non-operation period; the concentration of silver ions in the water body during the operation period was 42.86 % higher than that in the non-operation period. During the long-term study, spanning 16 years, the water body played a leading role in regulating the content of silver ions released by the APE, resulting in an increase in silver ion content by 3.3 %. Our results revealed the presence of silver in the precipitation after the APE operation, indicating that silver iodide initially entered the precipitation after catalysis. Furthermore, upon the comparison of the soil and surface water during the operation period and non-operation period, the silver content during the operation period was observed to be higher than that in the non-operation period, indicating that silver iodide was incorporated into the underlying surface from the precipitation. Therefore, we have concluded that the transport pathway of silver involves its initial entry into precipitation after sowing, subsequently descending with the precipitation to reach the soil and surface water. The findings of this study establish a scale ruler for the impact of increasing global APE activities on the environment, as well as first-hand data for preventing possible future environmental risks.

Association between physical activity, sedentary behavior patterns with bone health among Chinese older women.

INTRODUCTION: We examined the association between physical activity (PA) and sedentary behavior (SEB) time with bone health and whether it changes depending on different patterns. MATERIALS AND METHODS: Cross-sectional data were derived from the baseline of the Physical Activity and Health in Older Women Study. PA and SEB were measured using Actigraph wGT3X-BT accelerometers. Bone mineral density (BMD) was derived from the SONOST-2000 ultrasound bone densitometer, with unhealthy bone defined as a BMD T-score of <2.5 standard deviation a young adult reference population's mean. A 10 min-bouted SEB was defined as an SEB duration of >10 min (allow 2 min 0 counts), similar to 30 min-bouted and 60 min-bouted SEBs. Sporadic and bouted PAs were defined by PA duration of <10 min or ≥ 10 min. Multivariate logistic regression analysis investigated the associations between PA and SEB patterns with bone health. RESULTS: Among 1111 female participants, 42.12 % had unhealthy bones. In a fully-adjusted model, increasing 30 min/day of SEB was associated with a higher odds ratio (OR) for an unhealthy bone (OR, 1.08; P = 0.005), similar to the 10 (OR, 1.06; P = 0.012), 30 (OR, 1.06; P = 0.043), and 60 min-bouted (OR 1.08, P = 0.032) SEBs. Total light PA (LPA) time (OR, 0.97; P = 0.005) had a lower OR for unhealthy bone. After adjusting for sporadic LPA time, bouted LPA (OR, 0.97; P = 0.005) retained this association. No association was observed between total moderate-to-vigorous PA (MVPA) and bone health, sporadic MVPA, and bouted MVPA. CONCLUSIONS: Performing bouted LPA and reducing 10 min-bouted SEB may maintain bone health.

Hemodynamic study on the therapeutic effects of varying diameter embolic coils in the treatment of intracranial aneurysms.

Endovascular coiling is the predominant method for treating cerebral aneurysms. Extensive reports on selecting coil length, hardness, and material are available. However, the impact of coil diameter on postoperative outcomes remains unclear. This study enrolled six personalized geometric models of intracranial aneurysms: three bifurcation aneurysms and three sidewall aneurysms. Four coil models were constructed by changing the coil diameter. Coil embolization was simulated using the finite element method. Computational fluid dynamics was used to characterize hemodynamics in the aneurysms after embolization. Evaluation parameters included velocity reduction, wall shear stress (WSS), low WSS (LWSS), oscillatory shear index (OSI), relative residence time (RRT), and residual flow volume in the aneurysms. At the peak time (t = 0.17 s), the proportion of LWSS area in bifurcation aneurysms increase with the rise in coil diameter: 0.8D, 71.28 ± 12.62% versus 1D, 74.97 ± 19.17% versus 1.2D, 78.88 ± 18.56% versus 1.4D, 84.00 ± 11.53% (mean ± SD). The proportion of high OSI area decreases as the coil diameter increases: 0.8D, 4.41% ± 2.82% versus 1.0D, 3.78 ± 3.33% versus 1.2D, 2.28% ± 1.77% versus 1.4D, 1.58% ± 1.11% (mean ± SD). The proportion of high RRT area increases as the coil diameter rises: 0.8D, 3.40% ± 1.68% versus 1.0D, 7.67 ± 4.12% versus 1.2D, 9.84% ± 9.50% versus 1.4D, 22.29% ± 14.28% (mean ± SD). Side wall aneurysms do not exhibit the aforementioned trend. Bifurcation aneurysms plugged with a coil of 1.4 times the diameter have the largest RFVs (<10 mm/s) within the group. Aforementioned patterns are not found in sidewall aneurysms. In the treatment of aneurysms with coiling, varying coil diameters can result in different hemodynamic environments within the aneurysm. Larger coil diameters have improved hemodynamic performance for bifurcation aneurysms. However, coil diameter and embolization effectiveness have no significant relationship for sidewall aneurysms.

Loss of Myo19 increases metastasis by enhancing microenvironmental ROS gradient and chemotaxis.

Tumor metastasis involves cells migrating directionally in response to external chemical signals. Reactive oxygen species (ROS) in the form of H2O2 has been demonstrated as a chemoattractant for neutrophils but its spatial characteristics in tumor microenvironment and potential role in tumor cell dissemination remain unknown. Here we investigate the spatial ROS distribution in 3D tumor spheroids and identify a ROS concentration gradient in spheroid periphery, which projects into a H2O2 gradient in tumor microenvironment. We further reveal the role of H2O2 gradient to induce chemotaxis of tumor cells by activating Src and subsequently inhibiting RhoA. Finally, we observe that the absence of mitochondria cristae remodeling proteins including the mitochondria-localized actin motor Myosin 19 (Myo19) enhances ROS gradient and promotes tumor dissemination. Myo19 downregulation is seen in many tumors, and Myo19 expression is negatively associated with tumor metastasis in vivo. Together, our study reveals the chemoattractant role of tumor microenvironmental ROS and implies the potential impact of mitochondria cristae disorganization on tumor invasion and metastasis.