Preparation, Mechanical Properties, and Degradation Behavior of Zn-1Fe-xSr Alloys for Biomedical Applications.

As biodegradable materials, zinc (Zn) and zinc-based alloys have attracted wide attention owing to their great potential in biomedical applications. However, the poor strength of pure Zn and binary Zn alloys limits their wide application. In this work, a stir casting method was used to prepare the Zn-1Fe-xSr (x = 0.5, 1, 1.5, 2 wt.%) ternary alloys, and the phase composition, microstructure, tensile properties, hardness, and degradation behavior were studied. The results indicated that the SrZn13 phase was generated in the Zn matrix when the Sr element was added, and the grain size of Zn-1Fe-xSr alloy decreased with the increase in Sr content. The ultimate tensile strength (UTS) and Brinell hardness increased with the increase in Sr content. The UTS and hardness of Zn-1Fe-2Sr alloy were 141.65 MPa and 87.69 HBW, which were 55.7% and 58.4% higher than those of Zn-1Fe alloy, respectively. As the Sr content increased, the corrosion current density of Zn-1Fe-xSr alloy increased, and the charge transfer resistance decreased significantly. Zn-1Fe-2Sr alloy had a degradation rate of 0.157 mg·cm-2·d-1, which was 118.1% higher than the degradation rate of Zn-1Fe alloy. Moreover, the degradation rate of Zn-1Fe-xSr alloy decreased significantly with the increase in immersion time.

Research on advanced photoresponsive azobenzene hydrogels with push-pull electronic effects: a breakthrough in photoswitchable adhesive technologies.

Smart materials that adapt to various stimuli, such as light, hold immense potential across many fields. Photoresponsive molecules like azobenzenes, which undergo E-Z photoisomerization when exposed to light, are particularly valuable for applications in smart coatings, light-controlled adhesives, and photoresists in semiconductors and integrated circuits. Despite advances in using azobenzene moieties for stimuli-responsive adhesives, the role of push-pull electronic effects in regulating reversible adhesion remains largely unexplored. In this study, we investigate for the first time photo-controlled hydrogel adhesives of azobenzene with different push-pull electronic groups. We synthesized the monomers 4-methoxyazobenzene acrylate (ABOMe), azobenzene acrylate (ABH), and 4-nitroazobenzene acrylate (ABNO2), and examined their effects on reversible adhesion properties. By incorporating these azobenzene monomers into acrylamide, dialdehyde-functionalized poly(ethylene glycol), and [3-(methacryloylamino)propyl]-trimethylammonium chloride, we prepared ABOMe, ABH, and ABNO2 ionic hydrogels. Our research findings demonstrate that only the ABOMe ionic hydrogel exhibits reversible adhesion. This is due to its distinct transition state mechanism compared to ABH and ABNO2, which enables efficient E-Z photoisomerization and drives its reversible adhesion properties. Notably, the ABOMe ionic hydrogel reveals an outstanding skin adhesion strength of 360.7 ± 10.1 kPa, surpassing values reported in current literature. This exceptional adhesion is attributed to Schiff base reactions, monopole-quadrupole interactions, π-π interactions, and hydrogen bonding with skin amino acids. Additionally, the ABOMe hydrogel exhibits excellent reversible self-healing capabilities, significantly enhancing its potential for injectable medical applications. This research underscores the importance of integrating multifunctional properties into a single system, opening new possibilities for innovative and durable adhesive materials.

Inhalation of Microplastics Induces Inflammatory Injuries in Multiple Murine Organs via the Toll-like Receptor Pathway.

Previous studies have detected microplastics (MPs) in human biological samples, such as lungs, alveolar lavage fluid, and thrombus. However, whether MPs induce health effects after inhalation are unclear. In this study, fluorescent polystyrene microplastics (PS-MPs) were found in the thymus, spleen, testes, liver, kidneys, and brain on day 1 or day 3 after one intratracheal instillation. Furthermore, mice showed inflammation in multiple organs, manifested as obvious infiltration of neutrophils and macrophages, increased Toll-like receptors (TLRs), myeloid differentiation primary response protein 88 (MyD88) and nuclear factor-κB (NF-κB), as well as proinflammatory cytokines (tumor necrosis factor (TNF)-α and interleukin (IL)-1ß) in the lungs, thymus, spleen, liver, and kidneys after four intratracheal instillations of PS-MPs at once every 2 weeks. Hepatic and renal function indexes were also increased. Subsequently, the inflammatory response in multiple murine organs was significantly alleviated by TLR2 and TLR4 inhibitors. Unexpectedly, we did not find any elevated secretion of monocyte chemotactic protein (MCP)-1 or TNF-α by RAW264.7 macrophages in vitro. Thus, PS-MPs induced inflammatory injuries in multiple murine organs via the TLRs/MyD88/NF-κB pathway in vivo, but not macrophages in vitro. These results may provide theoretical support for healthy protection against PS-MPs and their environmental risk assessment.

Multi-Target Mechanisms of Si-Ni-San on Anxious Insomnia: An Example of Network-pharmacology and Molecular Docking Analysis.

BACKGROUND AND OBJECTIVE: Based on comprehensive network-pharmacology and molecular docking analysis, this study was intended to unveil the multiple mechanisms of Si-Ni-San (SNS) in treating anxious insomnia. METHODS: The compounds of SNS were meticulously analyzed, selected and standardized with references to their pharmacological attributes. The components included chaihu (Bupleurum chinense DC.), baishao (Paeonia lactiflora Pall.), zhishi (Citrus aurantium L.) and gancao (Glycyrrhiza uralensis Fisch. ex DC.). We used the Traditional Chinese Medicine System Pharmacology (TCMSP) Database, Traditional Chinese Medicines Integrated Database (TCMID), GeneCards database, therapeutic target database (TTD) and comparative toxicogenomic database (CTD) to construct the components-compounds-targets networks and used Cytoscape 3.9.1 software to visualize the outcome. Afterwards, the STRING database and Cytoscape 3.9.1 software were utilized to construct and visualize the protein-protein interaction (PPI) network analysis. In addition, the Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis were also conducted through the Database for Annotation, Visualization, and Integrated Discovery (DAVID). The molecular docking program was carried out using AutoDock 4.2 software to understand interactions between target receptors and compound ligands selected for study. RESULTS: We thoroughly sorted and filtered 31 pharmacologically active compounds from SNS. Subsequently, several potential target genes were predicted, of which there were 59 target genes distinctly associated with anxious insomnia. The PPI analysis indicated that the core target proteins included AKT1, IL6, TNF, SLC6A4, MAOA and GABRA2. The results of our study indicated that SNS potentially remediates anxious insomnia by reducing inflammation, neurodegeneration, and cell apoptosis of neurons. In addition, GO and KEGG enrichment analysis results indicated that SNS could modulate multiple aspects of anxious insomnia through mechanisms related to pathways of neuroactive ligand-receptor interaction. These pathways include various kinds of synaptic transmission pathways, and anti-inflammatory activity associated with response pathways. When we compared the components-compounds-targets networks and the compounds-targets-synaptic pathways networks, the five active compounds, including beta-Sitosterol, Kaempferol, Tetramethoxyluteolin, Isorhamnetin and Shinpterocarpin, were selected to conduct molecular docking experiments. Eleven target proteins, (AKT1, SLC6A4, ADRB2, MAOA, ACHE, ESR1, CYP3A4, CHRNA7, GABRA2, HTR2A and NOS3), which also play significant roles in regulating serotonergic, cholinergic, dopaminergic and GABAergic systems in the PPI network, were selected to act as receptors in molecular docking trials. The results showed that docking pairs isorhamnetin-AKT1, isorhamnetin-SLC6A4, ß-sitosterol-MAOA, ß- sitosterol-ACHE, isorhamnetin-CHRNA7 and shinpterocarpin-GABRA2 provided the most stable conformations of ligand-receptor binding between key compounds and core target proteins in the SNS. CONCLUSION: In the study, we offer a computational result, revealing that SNS may alleviate sleep disorders associated with anxiety through a "multi-compounds, multi-targets, and multi-pathways" mechanism. The network-pharmacology and molecular docking outcomes could theoretically confirm the anti-anxiety and anti-insomnia effects of SNS. Although this research is purely statistical and systematic without empirical validation, it serves as a stepping stone and cornerstone for subsequent experimental investigations.

Isomalto-Oligosaccharide Potentiates Alleviating Effects of Intermittent Fasting on Obesity-Related Cognitive Impairment during Weight Loss and the Rebound Weight Gain.

Obesity-related cognitive dysfunction poses a significant threat to public health. The present study demonstrated mitigating effects of intermittent fasting (IF) and its combination with isomalto-oligosaccharides and IF (IF + IMO) on cognitive impairments induced by a high-fat-high-fructose (HFHF) diet in mice, with IF + IMO exhibiting superior effects. Transcriptomic analysis of the hippocampus revealed that the protective effects on cognition might be attributed to the suppression of toll-like receptor 4 (TLR4)/NFκB signaling, oxidative phosphorylation, and neuroinflammation. Moreover, both IF and IF + IMO modulated the gut microbiome and promoted the production of short-chain fatty acids, with IF + IMO displaying more pronounced effects. IF + IMO-modulated gut microbiota, metabolites, and molecular targets associated with cognitive impairments were further corroborated using human data from public databases Gmrepo and gutMgene. Furthermore, the fecal microbiome transplantation confirmed the direct impacts of IF + IMO-derived microbiota on improving cognition functions by suppressing TLR4/NFκB signaling and increasing BDNF levels. Notably, prior exposure to IF + IMO prevented weight-regain-induced cognitive decline, suppressed TLR4/NFκB signaling and inflammatory cytokines in the hippocampus, and mitigated weight regain-caused gut dysbacteriosis without altering body weight. Our study underscores that IMO-augmented alleviating effects of IF on obesity-related cognitive impairment particularly during weight-loss and weight-regain periods, presenting a novel nutritional strategy to tackle obesity-related neurodegenerative disorders.

Ninth Version of the AJCC and UICC Nasopharyngeal Cancer TNM Staging Classification.

Importance: Accurate staging is a fundamental step in treating patients with nasopharyngeal carcinoma (NPC) worldwide; this is crucial not only for prognostication, but also for guiding treatment decisions. The American Joint Committee on Cancer (AJCC)/Union for International Cancer Control (UICC) tumor-node-metastasis (TNM) system is the global language for clinicians, researchers, and cancer registries. Continual improvement that aligns with contemporary pattern of care is essential. Objective: To improve the prognostic accuracy and clinical applicability of the eighth edition (TNM-8) for NPC. Design, Setting, and Participants: This multicenter study analyzed patients with NPC with detailed tumor features during January 2014 and December 2015 and was reviewed by experienced radiologists. The data analysis was completed in December 2023. The findings were further confirmed with internal and external validation. Statistical analyses and clinical considerations were reviewed by the AJCC/UICC multidisciplinary head and neck panels and attained consensus. The recommendations were evaluated by the AJCC Evidence-Based Medicine Committee before final endorsement as the ninth version (TNM-9). Main Outcomes and Measures: The primary end point was overall survival. Adjusted hazard ratios of different subgroups were then assessed for confirmation of optimal stage grouping. Results: Of the 4914 patients analyzed, 1264 (25.7%) were female and 3650 (74.3%) were male; the median (SD) age was 48.1 (12.0) years. Advanced radiological extranodal extension (with involvement of adjacent muscles, skin, and/or neurovascular bundles) was identified as an independent adverse factor for all end points: this was added as a criterion for N3. Patients with nonmetastatic disease were regrouped into stages I to III instead of TNM-8 stages I to IVA. Significant hazard discrimination was achieved by grouping T1-2N0-1 as stage I, T3/N2 as stage II, and T4/N3 as stage III. Although the T1-2N0-1 subgroups had comparable 5-year overall survival, subdivisions into IA (T1-T2N0) and IB (T1-T2N1) were recommended due to the distinction in adjusted hazard ratios following adjustment for chemotherapy use. Metastatic disease was exclusively classified as stage IV, and prognostication was further refined by subdivision into IVA (M1a, ≤3 lesions) and IVB (M1b, >3 lesions). TNM-9 demonstrated superiority compared with TNM-8 in major statistical aspects. Conclusion and Relevance: The results of this diagnostic study suggest that the ninth version of TNM staging for NPC, based on robust analyses and a comprehensive review by the AJCC/UICC staging committees, provides an improved staging system for global application and a framework for future incorporation of nonanatomical factors. This will be launched for global application in January 2025.

The protective effects of annexin A1 against oxidized-LDL-induced monocytes adhesion to endothelial cells: implication in atherosclerosis.

Oxidized low-density lipoprotein (ox-LDL)-associated endothelial dysfunction is a critical factor in the initiation and progression of Atherosclerosis (AS). Annexin A1 is an important member of the annexin family. Despite its wide range of biological functions across various tissues and cells, the role of Annexin A1 in AS remains largely unexplored. In this study, we demonstrate that Annexin A1 treatment effectively reduced the expression of LOX-1 at both the mRNA and protein levels in HUVECs exposed to ox-LDL. Annexin A1 also ameliorated oxidative stress (OS) by decreasing mitochondrial ROS levels and restoring reduced GSH levels. Moreover, Annexin A1 decreased the expression of pro-inflammatory cytokines, including IL-6 and MCP-1. Importantly, Annexin A1 inhibited ox-LDL-induced expressions of the endothelial adhesion molecules, such as E-selectin and VCAM-1 in HUVECs, which leads to reduced attachment of THP-1 monocytes to HUVECs. Mechanically, we found that Annexin A1 reversed the expression of KLF2 against ox-LDL mediated by the PI3K/Akt axis. Notably, the silencing of KLF2 abrogated the protective effects of Annexin A1 on E-selectin and VCAM-1 expression and the attachment of THP-1 monocytes to HUVECs. Our findings suggest that Annexin A1 is a potential therapeutic agent for atherosclerosis, offering a novel approach to mitigate endothelial dysfunction and inflammation.

Triglyceride glucose-body mass index as a mediator of hypertension risk in obstructive sleep apnoea syndrome: a mediation analysis study.

The aim of this study was to investigate whether triglyceride glucose-body mass index (TyG-BMI) plays a mediating role between obstructive sleep apnoea syndrome (OSAS) and hypertension. The study analyzed clinical data from a total of 840 OSAS patients at Wuhan Union Hospital between January 2020 to December 2023. The association between TyG-BMI and hypertension was examined using restricted cubic spline regression and logistic regression. Mediation effect analysis was conducted to explore the relationship between OSAS, TyG-BMI, and the risk of hypertension. Severe OSAS was associated with a significantly increased risk of hypertension compared to mild OSAS (OR = 1.752, p = 0.013). There was a positive linear relationship between TyG-BMI and the risk of hypertension (P-non-linear = 0.535). The risk of hypertension increased with increasing TyG-BMI, with a significantly higher risk of hypertension in the fourth quartile (OR = 3.407, p < 0.001) than in the third quartile (OR = 2.457, p < 0.001) and in the second quartile (OR = 1.576, p = 0.043). TyG-BMI mediated the association between OSAS and hypertension with a mediation effect of 41.3% (p < 0.001). TyG-BMI is important for assessing the risk of hypertension in patients with OSAS.

Relationship Between Growth Mindset and Self-Control Amongst Chinese Primary School Students: A Longitudinal Study.

Purpose: Growth mindset and self-control, both recognized as pivotal qualities with significant impacts on personal success, possess respective robust predictive power for academic achievement and broader life outcomes. However, the bidirectional relationship between them remains largely unexplored. This study aims to investigate whether growth mindset, conceptualized as the belief that abilities can be developed through effort and support, prospectively predicts the development of self-control over time. Additionally, it endeavors to explore whether self-control, a crucial positive psychological trait, exerts an influence on the fostering of growth mindset. In summary, our research focuses on elucidating the bidirectional relationship between growth mindset and self-control among Chinese primary school students. Participants and Methods: The current research recruited a sample of 428 primary school students, aged 9-12, from China (214 females, mean age = 9.64 ± 1.21) to participate in a longitudinal study. Participants underwent two follow-up assessments of growth mindset and self-control over a six-month period. Results: The correlation analysis revealed significant associations between growth mindset at T1 and self-control at T2, as well as between self-control at T1 and growth mindset at T2(r = 0.23 to 0.25, ps < 0.01). Cross-lagged analysis found that growth mindset at T1 positively predicted self-control at T2 (ß = 0.11, p = 0.04), while self-control at T1 did not significantly predict growth mindset at T2. Conclusion: The results suggest that growth mindset exerts a direct impact on self-control among primary school students. This finding extends the scope of research concerning growth mindset and provides important theoretical inspiration and practical guidance for educators, parents and counselling professionals in assisting students to enhance self-control.

Large language multimodal models for new-onset type 2 diabetes prediction using five-year cohort electronic health records.

Type 2 diabetes mellitus (T2DM) is a prevalent health challenge faced by countries worldwide. In this study, we propose a novel large language multimodal models (LLMMs) framework incorporating multimodal data from clinical notes and laboratory results for diabetes risk prediction. We collected five years of electronic health records (EHRs) dating from 2017 to 2021 from a Taiwan hospital database. This dataset included 1,420,596 clinical notes, 387,392 laboratory results, and more than 1505 laboratory test items. Our method combined a text embedding encoder and multi-head attention layer to learn laboratory values, and utilized a deep neural network (DNN) module to merge blood features with chronic disease semantics into a latent space. In our experiments, we observed that integrating clinical notes with predictions based on textual laboratory values significantly enhanced the predictive capability of the unimodal model in the early detection of T2DM. Moreover, we achieved an area greater than 0.70 under the receiver operating characteristic curve (AUC) for new-onset T2DM prediction, demonstrating the effectiveness of leveraging textual laboratory data for training and inference in LLMs and improving the accuracy of new-onset diabetes prediction.

[Niche and interspecific association of main woody plants in Cunninghamia lanceolata plantation community in Jianfengling, China]. / 尖峰岭杉木人工林群落主要木本植物的生态位和种间联结.

Studies on niche and interspecific association can reveal plant interspecific relationship in the community, and provide theoretical support for promoting the transformation and development of plantation to natural forest. Based on Cunninghamia lanceolata investigation data of permanent plots of plantation in Jianfengling area of Hainan Tropical Rainforest National Park, we analyzed niche and interspecific association of the top 20 woody species in the community according to their importance values. The results showed that there were 163 species of woody species belonging to 101 genera and 55 families in the C. lanceolata plantation community, with complex species composition. As a constructive species, C. lanceolata had the highest importance value and niche breadth, and thus was the absolute dominant species in the community. It had a large niche overlap and niche similarity with many other species, among which the highest was observed in Adinandra hainanensis. The average niche overlap and niche similarity of the community were 0.54 and 0.49, respectively. The change trends of those two niche indicators were basically the same, indicating that some species were similar in resource demands. The overall association of main woody species was significantly positive. The χ2 test, association coefficient, Pearson correlation coefficient, and Spearman rank correlation coefficient suggested that the amounts of pairs with positive association were more than that with negative ones. The proportion of significant association species pairs was relatively low, indicating that the community stability was strong, species could coexist stably, and most species did not form close ties. On the whole, C. lanceolata had inhibited the regeneration of original tree species, and A. hainanensis, Garcinia oblongifolia, and Heptapleurum heptaphyllum could be used in natural transformation and restoration of C. lanceolata plantation in the Hainan Tropical Rainforest National Park.

[Pharmacovigilance guidelines for clinical application of oral Chinese patent medicines].

Oral Chinese patent medicine is the essence of effective prescriptions created and summarized by Chinese medical scientists through thousands of years of medical practice. It is portable and convenient, with an obvious curative effect and other characteristics. However, at present, oral Chinese patent medicine is rich in dosage forms, various in types, complex in mechanism of action, and broad in clinical positioning. In clinical application, there are often cases of drug use without reference to instructions,repeated drug use, and prolonged drug use, which highlights safety problems such as adverse reactions and hepatorenal toxicity. Oral Chinese patent medicine pharmacovigilance is facing challenges. World Health Organization(WHO) has issued the WHO guidelines on safety monitoring of herbal medicines in pharmacovigilance systems, and International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use(ICH) has issued the ICH E2 pharmacovigilance guidelines. The United States has issued the Pharmacovigilance management standards and pharmacoepidemiological assessment guidelines, and the European Union has issued the Guidelines on good pharmacovigilance practices. Japan, South Korea, and other countries in the Asia Pacific region have established their own pharmacovigilance systems, but currently, there are no pharmacovigilance guidelines related to oral Chinese patent medicine in China. Therefore, experts from many disciplines and fields in China were invited to jointly develop the Pharmacovigilance guidelines for clinical application of oral Chinese patent medicines, which aims to develop pharmacovigilance guidelines for clinical application that are consistent with China's national conditions and highlight the characteristics of oral Chinese patent medicine, and provide guidance for clinically safe and rational drug application in medical institutions.

A Highly Atom-Efficient Prodrug Approach to Generate Synergy between H2S and Nonsteroidal Anti-inflammatory Drugs and Improve Safety.

Efforts to synergize hydrogen sulfide (H2S) with NSAIDs have faced challenges due to complex structural entities and independent release kinetics. This study presents a highly atom-efficient approach of using a thiocarboxylic acid (thioacid) as a novel H2S releasing precursor and successfully employs it to modify NSAIDs, which offers several critical advantages. First, thioacid-modified NSAID is active in inhibiting cyclooxygenase, sometimes with improved potency. Second, this prodrug approach avoids introducing extra structural moieties, allowing for the release of only the intended active principals. Third, the release of H2S and NSAID is concomitant, thus optimally synchronizing the concentration profiles of the two active principals. The design is based on our discovery that esterases can directly and efficiently hydrolyze thiocarboxylic acids, enabling controlled release H2S. This study demonstrates the proof of principle through synthesizing analogs, assesses release kinetics, enzyme inhibition, and pharmacological efficacy, and evaluates toxicity and gut microbiota regulation in animal models.

Maternal dietary practices during pregnancy and obesity of neonates: a machine learning approach towards hierarchical and nested relationships in a Tibet Plateau cohort study.

Studies on obesity and risk factors from a life-course perspective among residents in the Tibet Plateau with recent economic growth and increasing obesity are important and urgently needed. The birth cohort in this area provides a unique opportunity to examine the association between maternal dietary practice and neonatal obesity. The study aims to detect the prevalence of obesity among neonates, associated with maternal diet and other factors, supporting life-course strategies for obesity control. A cohort of pregnant women was enrolled in Tibet Plateau and followed till childbirth. Dietary practice during pregnancy was assessed using the Chinese FFQ - Tibet Plateau version, food items and other variables were associated with the risk for obesity of neonates followed by logistic regression, classification and regression trees (CART) and random forest. Of the total 1226 mother-neonate pairs, 40·5 % were Tibetan and 5·4 % of neonates with obesity. Consuming fruits as a protective factor for obesity of neonates with OR (95 % CI) = 0·61 (0·43, 0·87) from logistic regression; as well as OR = 0·20 (0·12, 0·35) for consuming fruits (≥ weekly) from CART. Removing fruit consumption to avoid overshadowing effects of other factors, the following were influential from CART: maternal education (more than middle school, OR = 0·22 (0·13, 0·37)) and consumption of Tibetan food (daily, OR = 3·44 (2·08, 5·69). Obesity among neonates is prevalent in the study population. Promoting healthy diets during pregnancy and strengthening maternal education should be part of the life-course strategies for obesity control.

Negative prognostic impact of tumor deposits in stage III colorectal cancer patients.

BACKGROUND: The prognostic value of tumor deposits (TDs) in stage III colorectal cancer (CRC) patients is poorly described based on the current tumor node metastasis (TNM) stage system. MATERIALS AND METHODS: Based on the data from the Surveillance, Epidemiology, and End Result (SEER) database between 2010 to 2020 and local hospital between 2006 to 2022, the clinicopathological features of stage III CRC patients with TDs were screened by Chi-square test. Kaplan-Meier curves were performed to describe the significant difference in overall survival (OS) among the different groups, and log-rank tests were used to compare the cumulative survival distributions. RESULT: Patients with TDs exhibited more aggressive tumors, characterized by advanced T staging (T3&T4), N staging (N2), perineural invasion, and more advanced TNM stage. The presence of TDs was identified as a negative prognostic factor in stage III CRC patients, with the co-existence of TDs and lymph node metastasis associated the poorest prognosis. A pairwise comparison revealed no statistically significant difference between TD+N1a/b and N1c groups, while the OS of TD-LN+ (TD- N1a/b) patients was the most favorable within the N1 stage. Notably, patients with a single lymph node positive had a significantly better OS than those with a single TD positive. CONCLUSION: The presence of tumor deposits was a negative prognostic factor in stage III colorectal cancer patients, and the significance of tumor deposits was underestimated in the current TNM staging system.

Subway Fine Particles (PM2.5)-Induced Pro-Inflammatory Response Triggers Airway Epithelial Barrier Damage Through the TLRs/NF-κB-Dependent Pathway In Vitro.

Subways are widely used in major cities around the world, and subway fine particulate matter (PM2.5) is the main source of daily PM2.5 exposure for urban residents. Exposure to subway PM2.5 leads to acute inflammatory damage in humans, which has been confirmed in mouse in vivo studies. However, the concrete mechanism by which subway PM2.5 causes airway damage remains obscure. In this study, we found that subway PM2.5 triggered release of pro-inflammatory cytokines such as interleukin 17E, tumor necrosis factor α, transforming growth factor ß, and thymic stromal lymphopoietin from human bronchial epithelial cells (BEAS-2B) in a dose-effect relationship. Subsequently, supernatant recovered from the subway PM2.5 group significantly increased expression of the aforementioned cytokines in BEAS-2B cells compared with the subway PM2.5 group. Additionally, tight junctions (TJs) of BEAS-2B cells including zonula occludens-1, E-cadherin, and occludin were decreased by subway PM2.5 in a dose-dependent manner. Moreover, supernatant recovered from the subway PM2.5 group markedly decreased the expression of these TJs compared with the control group. Furthermore, inhibitors of toll-like receptors (TLRs) and nuclear factor-kappa B (NF-κB), as well as chelate resins (e.g., chelex) and deferoxamine, remarkably ameliorated the observed changes of cytokines and TJs caused by subway PM2.5 in BEAS-2B cells. Therefore, these results suggest that subway PM2.5 induced a decline of TJs after an initial ascent of cytokine expression, and subway PM2.5 altered expression of both cytokines and TJs by activating TLRs/NF-κB-dependent pathway in BEAS-2B cells. The metal components of subway PM2.5 may contribute to the airway epithelial injury.

The anti-COVID-19 drug nirmatrelvir crosses the blood‒brain barrier and exhibits herb-drug pharmacokinetic interactions with Scutellaria baicalensis formulations.

Aim of the study: Our hypothesis is that nirmatrelvir can penetrate the blood‒brain barrier and reach effective concentrations in the brain. Furthermore, herbal formulations can help maintain nirmatrelvir levels in the body, suggesting potential interactions between these medications. Materials and methods: To investigate this hypothesis, an animal model combining multisite microdialysis, ultrahigh-performance liquid chromatography and tandem mass spectrometry (UHPLC-MS/MS) methods was developed to monitor nirmatrelvir levels in the blood and brain of rats. Results: The pharmacokinetic results showed that the area under the curve (AUC) of nirmatrelvir in the blood and brain was 798.3 ± 58.56 and 187.2 ± 23.46 min µg/mL, respectively, after the administration of nirmatrelvir alone (15 mg/kg, iv). When the Scutellaria baicalensis formulations were administered for five consecutive days prior to drug administration, the AUC of nirmatrelvir in the blood increased. Conclusions: These results provide constructive preclinical information that the concentrations of nirmatrelvir in the blood and brain were greater than the effective concentration (EC90) for more than 6 h, and the Scutellaria baicalensis formulations had synergistic pharmacokinetic effects by increasing the concentration of nirmatrelvir in the blood.

Exploring influencing factors and predictive analysis of sarcopenia in the Chinese population using the body composition analyzer.

OBJECTIVE: Employing body composition analysis, this study aims to examine the influencing factors and conduct predictive analysis regarding sarcopenia incidence in the middle-aged and elderly population in China. METHODS: This study recruited inpatients from the General Medicine Department of Tongji Medical College Affiliated Union Hospital, Huazhong University of Science and Technology, as the subjects for a single-center retrospective study. Diagnosis was conducted according to the 2019 criteria from the Asian Working Group for Sarcopenia. Binary logistic regression analysis was utilized to identify factors influencing sarcopenia, and predictive modeling for sarcopenia occurrence was performed based on the area under the ROC curve (AUC). RESULTS: This study comprised 1258 hospitalized patients, of whom 340 were diagnosed with sarcopenia and 918 were not, resulting in a prevalence of 27%. The baseline characteristics showed statistically significant differences between the two groups. Binary logistic regression analysis revealed that low protein, low total body water, low minerals, low basal metabolic rate, and age were risk factors for sarcopenia (OR > 1, P < 0.05). Conversely, being male, having a higher BMI, greater fat-free mass index, and a higher InBody score were identified as protective factors against sarcopenia (OR < 1, P < 0.05). The AUC values for predicting sarcopenia occurrence based on low protein, low total body water, low minerals, low basal metabolic rate, and age were 0.871, 0.846, 0.757, 0.645, and 0.649, respectively, indicating their significance as predictive indicators. Combining these five indicators into a new predictive model for sarcopenia yielded an area under the curve (AUC) value of 0.932, demonstrating excellent sensitivity and specificity concurrently. CONCLUSION: The results of body composition analysis indicate that sarcopenia occurrence in the middle-aged and elderly population in China is associated with factors such as low protein, low total body water, low minerals, low basal metabolic rate, age, gender, BMI, fat-free mass index, and InBody score. The combination of specific body composition indicators facilitates the effective prediction of sarcopenia. Clinical practitioners should proactively identify the risk factors influencing sarcopenia, accurately predict.

[Identification and expression pattern analysis of Trihelix transcription factor family genes of ginseng].

The function of the Trihelix transcription factor is that it plays an important role in many abiotic stresses, especially in the signaling pathway of low temperature, drought, flood, saline, abscisic acid, methyl jasmonate, and other abiotic stresses. However, there are few studies on the Trihelix gene family of ginseng. In this study, 41 Trihelix gene family members were identified and screened from the ginseng genome database, and their physicochemical properties, cis-acting elements, subcellular localization, chromosomal assignment, and abiotic stress-induced expression patterns were analyzed by bioinformatics methods. The results showed that 85% of Trihelix family members of ginseng were located in the nucleus, and the main secondary structure of Trihelix protein was random coil and α helix. In the promoter region of Trihelix, cis-acting regulatory elements related to various abiotic stresses such as low temperature, hormone response, and growth and development were identified. Through the collinearity analysis of interspecific Trihelix transcription factors of model plants Arabidopsis thaliana and ginseng, 19 collinear gene pairs were found between A. thaliana and ginseng, and no collinear gene pairs existed on chromosomes 3, 6, and 12 only. qRT-PCR analysis showed that the expression of GWHGBEIJ010320.1 was significantly up-regulated under low temperature stress, a significant response to low temperature stress. This study lays a foundation for further research on the role of the Trihelix transcription factor of ginseng in abiotic stress, as well as the growth and development of ginseng.

Biomechanical analysis of the tandem spinal external fixation in a multiple-level noncontiguous lumbar fractures model: a finite element analysis.

Objective: This study aimed to investigate the biomechanical characteristics of the tandem spinal external fixation (TSEF) for treating multilevel noncontiguous spinal fracture (MNSF) using finite element analysis and provide a theoretical basis for clinical application. Methods: We constructed two models of L2 and L4 vertebral fractures that were fixed with the TSEF and the long-segment spinal inner fixation (LSIF). The range of motion (ROM), maximum stresses at L2 and L4 vertebrae, the screws and rods, and the intervertebral discs of the two models were recorded under load control. Subsequently, the required torque, the maximum stress at L2 and L4 vertebrae, the screws and rods, and the intervertebral discs were analyzed under displacement control. Results: Under load control, the TSEF model reserved more ROM than the LSIF model. The maximum stresses of screws in the TSEF model were increased, while the maximum stresses of rods were reduced compared to the LSIF model. Moreover, the maximum stresses of L2 and L4 vertebrae and discs in the TSEF model were increased compared to the LSIF model. Under displacement control, the TSEF model required fewer moments (N·mm) than the LSIF model. Compared to the LSIF model, the maximum stresses of screws and rods in the TSEF model have decreased; the maximum stresses at L2 and L4 in the TSEF model were increased. In the flexion condition, the maximum stresses of discs in the TSEF model were less than the LSIF model, while the maximum stresses of discs in the TSEF model were higher in the extension condition. Conclusion: Compared to LSIF, the TSEF has a better stress distribution with higher overall mobility. Theoretically, it reduces the stress concentration of the connecting rods and the stress shielding of the fractured vertebral bodies.