Serum klotho associated with thyroid hormone in adults: A population-based cross-sectional research.

BACKGROUND AND STUDY AIM: The klotho protein, a multifunctional protein, has been shown to be associated with a wide range of endocrine diseases and has been linked to thyroid tumourigenesis. However, the relationship between serum klotho levels and thyroid hormones remains poorly understood. This study aimed to explore the correlation between serum klotho levels and thyroid hormones. METHODS: Data was obtained from the NHANES cycles 2007-2008, 2009-2010, and 2011-2012. A total of 4674 participants were recruited for this study. Statistical analysis was using multiple linear regression analyses, and restricted cubic spline plots (RCS) to investigate the association between serum klotho levels and serum levels of thyroid hormones. RESULTS: In the unadjusted covariate model, ln(klotho) significantly positively correlated with tT3, tT4, fT3, tT4/fT4, and tT3/fT3 (all P<0.01) and negatively correlated with TSH, tT4/tT3, and fT4/fT3 (all P<0.05). Furthermore, tT3, tT4, fT3and tT3/fT3 (P < 0.05) were still significant in the adjusted model. And it is worth noting that there is an approximately L-shaped nonlinear relationship between ln(klotho) and fT3,tT3 with a cut-off point of 6.697 (P-non-linear < 0.05). The stratification analysis showed gender and iodine level differences in the relationship between serum Klotho levels and thyroid hormones. CONCLUSION: There is an L-shaped nonlinear relationship between ln(klotho) and fT3, tT3, suggesting that klotho could be involved in the physiological regulation of thyroid function.

A regressive analysis of the main environmental risk factors of human echinococcosis in 370 counties in China.

BACKGROUND: Echinococcosis is a natural focal, highly prevalent disease in China. Factors influencing the spread of echinococcosis are not only related to personal exposure but also closely related to the environment itself. The purpose of this study was to explore the influence of environmental factors on the prevalence of human echinococcosis and to provide a reference for prevention and control of echinococcosis in the future. METHODS: Data were collected from 370 endemic counties in China in 2018. By downloading Modis, DEM and other remote-sensing images in 2018. Data on environmental factors, i.e., elevation, land surface temperature (LST) and normalized difference vegetation index (NDVI) were collected. Rank correlation analysis was conducted between each environmental factor and the prevalence of echinococcosis at the county level. Negative binomial regression was used to analyze the impact of environmental factors on the prevalence of human echinococcosis at the county level. RESULTS: According to rank correlation analysis, the prevalence of human echinococcosis in each county was positively correlated with elevation, negatively correlated with LST, and negatively correlated with NDVI in May, June and July. Negative binomial regression showed that the prevalence of human echinococcosis was negatively correlated with annual LST and summer NDVI, and positively correlated with average elevation and dog infection rate. The prevalence of human cystic echinococcosis was inversely correlated with the annual average LST, and positively correlated with both the average elevation and the prevalence rate of domestic animals. The prevalence of human alveolar echinococcosis was positively correlated with both NDVI in autumn and average elevation, and negatively correlated with NDVI in winter. CONCLUSION: The prevalence of echinococcosis in the population is affected by environmental factors. Environmental risk assessment and prediction can be conducted in order to rationally allocate health resources and improve both prevention and control efficiency of echinococcosis.

Enzymatic Reaction Enhanced Diffusion Accelerates Cargo Transport through Micro/Nano-Channels.

Energy conversion and transfer of enzyme-catalyzed reactions at molecular level are an interesting and challenging scientific topic that helps understanding biological processes in nature. In this study, it is demonstrated that enzyme-catalyzed reactions can enhance diffusion of surrounding molecules and thus accelerate cargo transport within 1D micro/nanochannels. Specifically, urease is immobilized on the inner walls of silica micro/nano-tubes to construct bio-catalytically active micro/nanochannels. The catalytic reaction inside the channels drives a variety of cargoes, including small dye molecules, polymers, and rigid nanoparticles (e.g., quantum dots, QDs), to pass through these micro/nanochannels much faster than they will by free diffusion. The enhanced diffusion of molecular species inside the channels is validated by direct observation of the Brownian motion of tracer particles, and further confirmed by significantly enhanced Raman intensity of reporter molecules. Finite element and Brownian dynamics simulations provide a theoretical understanding of these experimental observations. Furthermore, the effect of the channels' size on the diffusion enhancement is examined. The acceleration effect of the cargo transport through these enzymatically active micro/nanochannels can be turned on or off via chemical activators or inhibitors. This study provides valuable insights on the design of biomimetic channels capable of controlled and efficient transmembrane transport.

Trailblazing in Adjuvant Research: Succinate's Uncharted Territory with Neutrophils.

The purpose of this study is to investigate the previously unknown connection that succinate has with neutrophils in the setting of adjuvant-mediated immunological enhancement. It has been discovered that succinates stimulate the recruitment of neutrophils in immunization sites, which in turn induces the expression of what is known as neutrophil-derived B cell-activating factor (BAFF). Further amplification of vaccine-induced antibody responses is provided via the SUCNR1-IRF5-BAFF signaling pathway, which provides insights into a unique mechanism for immunological enhancement.

Potential mechanisms of traditional Chinese medicine in treating insomnia: A network pharmacology, GEO validation, and molecular-docking study.

The purpose of this study is to investigate the potential mechanisms of Chinese herbs for the treatment of insomnia using a combination of data mining, network pharmacology, and molecular-docking validation. All the prescriptions for insomnia treated by the academician Qi Wang from 2020 to 2022 were collected. The Ancient and Modern Medical Case Cloud Platform v2.3 was used to identify high-frequency Chinese medicinal herbs and the core prescription. The Traditional Chinese Medicine Systems Pharmacology and UniProt databases were utilized to predict the effective active components and targets of the core herbs. Insomnia-related targets were collected from 4 databases. The intersecting targets were utilized to build a protein-protein interaction network and conduct gene ontology enrichment analysis and Kyoto Encyclopedia of Genes and Genomes pathway enrichment analysis using the STRING database, Cytoscape software, and clusterProfiler package. Gene chip data (GSE208668) were obtained from the Gene Expression Omnibus database. The limma package was applied to identify differentially expressed genes (DEGs) between insomnia patients and healthy controls. To create a "transcription factor (TF)-miRNA-mRNA" network, the differentially expressed miRNAs were entered into the TransmiR, FunRich, Targetscan, and miRDB databases. Subsequently, the overlapping targets were validated using the DEGs, and further validations were conducted through molecular docking and molecular dynamics simulations. Among the 117 prescriptions, 65 herbs and a core prescription were identified. Network pharmacology and bioinformatics analysis revealed that active components such as ß-sitosterol, stigmasterol, and canadine acted on hub targets, including interleukin-6, caspase-3, and hypoxia-inducible factor-1α. In GSE208668, 6417 DEGs and 7 differentially expressed miRNAs were identified. A "TF-miRNA-mRNA" network was constructed by 4 "TF-miRNA" interaction pairs and 66 "miRNA-mRNA" interaction pairs. Downstream mRNAs exert therapeutic effects on insomnia by regulating circadian rhythm. Molecular-docking analyses demonstrated good docking between core components and hub targets. Molecular dynamics simulation displayed the strong stability of the complex formed by small molecule and target. The core prescription by the academician Qi Wang for treating insomnia, which involves multiple components, targets, and pathways, showed the potential to improve sleep, providing a basis for clinical treatment of insomnia.

ROS-Responsive and Self-Tumor Curing Methionine Polymer Library Based Nanoparticles with Self-Accelerated Drug Release and Hydrophobicity/Hydrophilicity Switching Capability for Enhanced Cancer Therapy.

The applications of amino acid-based polymers are impeded by their limited structure and functions. Herein, a small library of methionine-based polymers (Met-P) with programmed structure and reactive oxygen species (ROS)-responsive properties is developed for tumor therapy. The Met-P can self-assemble into sub-100 nm nanoparticles (NPs) and effectively load anticancer drugs (such as paclitaxel (PTX) (P@Met-P NPs)) via the nanoprecipitation method. The screened NPs with superior stability and high drug loading are further evaluated in vitro and in vivo. When encountering with ROS, the Met-P polymers will be oxidized and then switch from a hydrophobic to a hydrophilic state, triggering the rapid and self-accelerated release of PTX. The in vivo results indicated that the screened P@2Met10 NPs possessed significant anticancer performance and effectively alleviated the side effects of PTX. More interestingly, the blank 2Met10 NPs displayed an obvious self-tumor inhibiting efficacy. Furthermore, the other Met-P NPs (such as 2Met8, 4Met8, and 4Met10) are also found to exhibit varied self-anti-cancer capabilities. Overall, this ROS-responsive Met-P library is a rare anticancer platform with hydrophobic/hydrophilic switching, controlled drug release, and self-anticancer therapy capability.

Impact of the COVID-19 pandemic on mental health and viral suppression among persons living with HIV in western Washington.

The COVID-19 pandemic and social distancing measures elevated stress levels globally, exacerbating mental health challenges for people with HIV (PWH). We examined the effect of COVID-19-related stress on mental health among PWH in western Washington, exploring whether social support and coping self-efficacy were protective. Data on COVID-19-related stress, mental health, social support, and coping self-efficacy were collected using online surveys during the pandemic. Pre-COVID-19 mental health data were available for a subset of participants and were linked with the survey data. In the total sample (N = 373), COVID-19-stress was associated with elevated depression (PHQ-8, ß = 0.21, 95%CI [0.10, 0.32]) and anxiety (GAD-7, ß = 0.28, 95%CI [0.17, 0.39]). Among the subset of respondents with pre-pandemic mental health data (N = 103), COVID-19-related stress was associated with elevated PHQ-8 scores (ß = 0.35, 95%CI [0.15, 0.56]) and GAD-7 scores (ß = 0.35, 95%CI [0.16, 0.54]), adjusted for baseline mental health and other confounders. Coping self-efficacy was negatively associated with GAD-7 scores (ß = -0.01, 95%CI [-0.01, 0.00]), while social support was negatively associated with PHQ-8 scores (ß = -0.06, 95%CI [-0.12, -0.01]). Viral suppression before and during the pandemic did not differ among participants with available data. While COVID-19-related stress predicted elevated depression and anxiety symptoms among PWH, social support and coping self-efficacy were protective.

The trogocytosis of neutrophils on initial transplanted tumor in mice.

The role of neutrophils in tumor initiation stage is rarely reported because of the lack of suitable models. We found that neutrophils recruited in early tumor nodules induced by subcutaneous inoculation of B16 melanoma cells were able to attack tumor cells by trogocytosis. The anti-tumor immunotherapy like peritoneal injection with TLR9 agonist CpG oligodeoxynucleotide combined with transforming growth factor ß2 inhibitor TIO3 could increase the trogocytic neutrophils in the nodules, as well as CD8+ T cells, natural killer (NK) cells, and their interferon-γ production. Local use of Cxcl2 small interfering RNA significantly reduced the number of neutrophils and trogocytic neutrophils in tumor nodules, as well as CD8+ T and NK cells, and also enlarged the nodules. These results suggest that neutrophils recruited early to the inoculation site of tumor cells are conducive to the establishment of anti-tumor immune microenvironment. Our findings provide a useful model system for studying the effect of neutrophils on tumors and anti-tumor immunotherapy.

Chinese patent medicine combined with calcium channel blockers in the treatment of essential hypertension:a Bayes network meta-analysis and systematic review.

Backgroud: The co-administration of Chinese patent medicine with calcium channel blockers (CCBs) is a prevalent practice in China for treating essential hypertension (EH). However, robust evidence supporting the efficacy and safety of tailored combinations of different Chinese patent medicines with CCBs, according to individual patient conditions, is still limited. This study sought to elucidate the efficacy and safety of these combinations using a systematic review and network meta-analysis. Materials and methods: Relevant studies were sourced from established databases, incorporating randomized controlled trials published up to 1 February 2023. The ROB2 tool from the Cochrane Collaborative Network was employed to independently assess and cross-verify the quality of the included literature. A network meta-analysis was conducted in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) 2020 and PRISMA-Network Meta-Analyses (PRISMA-NMA) guidelines. A Bayesian network meta-analysis was utilized to gauge the efficacy and safety of distinct integrations of Chinese patent medicine and CCBs. Primary outcomes were interpreted using a paired fixed-effect meta-analysis. Publication bias was appraised through Egger's test and represented with funnel plots. All statistical analyses were executed within the R statistical framework. Results: Following rigorous selection, data extraction, and bias evaluation, 36 articles were incorporated. Tianma Gouteng Granule, when combined with CCBs, displayed superior efficacy in reducing systolic blood pressure (SBP). In terms of diastolic blood pressure (DBP) reduction, Songling Xuemaikang Capsule combined with CCBs emerged as the most effective. Regarding enhancement of antihypertensive effective rates, Qinggan Jiangya Capsule paired with CCBs demonstrated optimal results. For diminishing Traditional Chinese Medicine syndrome scores, the Qiangli Dingxuan Tablet and CCBs combination proved most beneficial. When aiming to reduce total cholesterol (TC), triglycerides (TG), and low-density lipoprotein cholesterol (LDL-C) levels, Tianma Gouteng Granule and CCBs showcased superior results. In contrast, the combination of Songling Xuemaikang Capsule and CCBs was more effective in reducing LDL-C, tumor necrosis factor-alpha (TNF-α), and interleukin-6 (IL-6). Conclusion: This study underscores variability in outcomes from combining Chinese patent medicine and CCBs for hypertension, emphasizing the importance of personalized medicinal combinations, especially Tianma Gouteng Granule and Songling Xuemaikang Capsule. The results offer robust evidence to inform clinical guidelines for essential hypertention and significantly aid clinician in seleting appropriate Chinese patent medicines for treatment.

Lignin Derived Ultrathin All-Solid Polymer Electrolytes with 3D Single-Ion Nanofiber Ionic Bridge Framework for High Performance Lithium Batteries.

The lignin derived ultrathin all-solid composite polymer electrolyte (CPE) with a thickness of only 13.2 µm, which possess 3D nanofiber ionic bridge networks composed of single-ion lignin-based lithium salt (L-Li) and poly(vinylidene fluoride-co-hexafluoropropylene) (PVDF-HFP) as the framework, and poly(ethylene oxide)/lithium bis(trifluoromethanesulfonyl)imide (PEO/LiTFSI) as the filler, is obtained through electrospinning/spraying and hot-pressing. t. The Li-symmetric cell assembled with the CPE can stably cycle more than 6000 h under 0.5 mA cm-2 with little Li dendrites growth. Moreover, the assembled Li||CPE||LiFePO4 cells can stably cycle over 700 cycles at 0.2 C with a super high initial discharge capacity of 158.5 mAh g-1 at room temperature, and a favorable capacity of 123 mAh g-1 at -20 °C for 250 cycles. The excellent electrochemical performance is mainly attributed to the reason that the nanofiber ionic bridge network can afford uniformly dispersed single-ion L-Li through electrospinning, which synergizes with the LiTFSI well dispersed in PEO to form abundant and efficient 3D Li+ transfer channels. The ultrathin CPE induces uniform deposition of Li+ at the interface, and effectively inhibit the lithium dendrites. This work provides a promising strategy to achieve ultrathin biobased electrolytes for solid-state lithium ion batteries.

Maternal PFOS exposure in mice induces hepatic lipid accumulation and inflammation in adult female offspring: Involvement of microbiome-gut-liver axis and autophagy.

Perfluorooctane sulfonates (PFOS) are the persistent organic pollutants. In the present study, 0, 0.3, or 3-mg/kg PFOS were administered to pregnant mice from GD 11 to GD 18. The histopathology of liver and intestine, serum and hepatic lipid levels, lipid metabolism related genes, and gut microbiota were examined in adult female offspring. The results suggested that maternal PFOS exposure increased serum levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST), and induced F4/80+ macrophage infiltration in adult female offspring, in addition to the elevation of TNF-α and IL-1ß mRNA levels in low-dose and high-dose groups, respectively. Furthermore, maternal exposure to PFOS increased serum triglyceride (TG) and hepatic total cholesterol (TC) levels, which was associated with the alteration of the process of fatty acid transport and ß-oxidation, TG synthesis and transport, cholesterol synthesis and excretion in the liver. The AMPK/mTOR/autophagy signaling was also inhibited in the liver of adult female offspring. Moreover, changes in gut microbiota were also related to lipid metabolism, especially for the Desulfovibrio, Ligilactobacillus, Enterorhabdus, HT002 and Peptococcaceae_unclassified. Additionally, maternal exposure to PFOS decreased mRNA expressions of the tight junction protein and AB+ goblet cells in the colon, while increasing the overproduction of lipopolysaccharides (LPS) and F4/80+ macrophage infiltration. Collectively, maternal PFOS exposure induced liver lipid accumulation and inflammation, which strongly correlated with the disruption of the gut-liver axis and autophagy in adult female offspring, highlighting the persistent adverse effects in offspring exposed to PFOS.

Comparing ChatGPT's and surgeon's responses to thyroid-related questions from patients.

BACKGROUND: For some common thyroid-related conditions with high prevalence and long follow-up times, ChatGPT can be used to respond to common thyroid-related questions. In this cross-sectional study, we assessed the ability of ChatGPT (version GPT-4.0) to provide accurate, comprehensive, compassionate, and satisfactory responses to common thyroid-related questions. STUDY DESIGN: First, we obtained 28 thyroid-related questions from the Huayitong app, which together with the two interfering questions eventually formed 30 questions. Then, these questions were responded to by ChatGPT (on July 19, 2023), junior specialist and senior specialist (on July 20, 2023) separately. Finally, 26 patients and 11 thyroid surgeons evaluated those responses on four dimensions: accuracy, comprehensiveness, compassion, and satisfaction. RESULTS: Among the 30 questions and responses, ChatGPT's speed of response was faster than that of the junior specialist (8.69 [7.53-9.48] vs. 4.33 [4.05-4.60], P <.001) and senior specialist (8.69 [7.53-9.48] vs. 4.22 [3.36-4.76], P <.001). The word count of the ChatGPT's responses was greater than that of both junior specialist (341.50 [301.00-384.25] vs. 74.50 [51.75-84.75], P <0.001) and senior specialist (341.50 [301.00-384.25] vs. 104.00 [63.75-177.75], P <0.001). ChatGPT received higher scores than junior specialist and senior specialist in terms of accuracy, comprehensiveness, compassion and satisfaction in responding to common thyroid-related questions. CONCLUSIONS: ChatGPT performed better than junior specialist and senior specialist in answering common thyroid-related questions, but further research is needed to validate the logical ability of the ChatGPT for complex thyroid questions.

Characterization of the novel HLA-C*06:376N allele by Pacific Biosciences HiFi sequencing in a Chinese individual.

HLA-C*06:376N differs from HLA-C*06:02:01:01 by seven nucleotide changes in exon 2, intron 2, and exon 3.

Impact of the COVID-19 Pandemic on Persons Living with HIV in Western Washington: Examining Lived Experiences of Social Distancing Stress, Personal Buffers, and Mental Health.

Pandemic-related stressors may disproportionately affect the mental health of people with HIV (PWH). Stratified, purposive sampling was used to recruit 24 PWH who participated in a quantitative survey on COVID-19 experiences for in-depth interviews (IDIs). IDIs were conducted by Zoom, audio recorded and transcribed. Thematic analysis was used to develop an adapted stress-coping model. Participants experienced acute stress following exposure events and symptoms compatible with COVID-19. Social isolation and job loss were longer-term stressors. While adaptive coping strategies helped promote mental health, participants who experienced multiple stressors simultaneously often felt overwhelmed and engaged in maladaptive coping behaviors. Healthcare providers were important sources of social support and provided continuity in care and referrals to mental health and social services. Understanding how PWH experienced stressors and coped during the COVID-19 pandemic can help healthcare providers connect with patients during future public health emergencies, address mental health needs and support adaptive coping strategies.

Comparing urine point-of-care tests to screen preeclampsia: Congo-red dot paper test versus dipstick urinalysis.

To compare the urine Congo-red dot paper test (CRD) with dipstick urinalysis to screen preeclampsia (PE). A total of 409 paired spot urine samples were obtained prospectively from women with suspected pre-eclampsia attending for routine hospital visits. Congo-red dot paper test and dipstick urinalysis were examined and compared to screen pre-eclampsia. The agreement between the two urinary test is modest (kappa coefficient = 0.28, 95% CI 0.14-0.42). The specificity of CRD was higher than urinalysis (97.4% vs. 90.4%, p < .001). Urinalysis performed better in sensitivity (77.3% vs. 40.9%, p = .04) and the area under the receiver operating characteristic curves (AUC) (0.84 [95% CI 0.74-0.94] vs. 0.69 [95% CI 0.55-0.83], p = .04) than CRD, respectively. The sensitivity, specificity, AUC of the parallel test of them is 86.4% (64.0%-96.4%), 89.1% (85.5%-92.0%), and 0.88 (95% CI 0.79-0.96). And the serial test is 31.8% (14.7%-54.9%), 98.7% (96.8%-99.5%), 0.65 (95% CI 0.51-0.79), accordingly. The urinalysis is a better diagnosing test for preeclampsia. CRD could aid in the diagnosis of patients with preeclampsia. Combined the two tests in suspected patients may further improve the performance in the diagnosis of preeclampsia. Further study need to be made for its potential clinical practice.

A network meta-analysis on the effects of different exercise types on COPD patients.

Objective: This study aimed to compare and rank the effects of aerobic exercise (AE), resistance training (RT), endurance training (ET), and high-intensity interval training (HIIT) in chronic obstructive pulmonary disease (COPD) by network meta-analysis (NMA).Methods: PubMed, Cochrane, Embase, and Web of Science were searched to identify randomized controlled trials investigating the effects of exercise training on COPD. The search period began on the date of database establishment and ended in April 8, 2023. Two reviewers independently screened the retrieved articles, extracted relevant data, and assessed the risk of bias in the included studies. NMA was performed using Stata 15.1 and R 4.2.1.Results: This study included a total of 27 studies involving 1415 patients. The NMA findings indicated that HIIT was the most effective intervention for improving 6-Minute Walk Distance (6MWD) with a SUCRA (Surface Under the Cumulative Ranking) score of 87.68%. In addition, HIIT showed the highest efficacy in improving Forced Expiratory Volume in 1 second (FEV1) with a SUCRA score of 73.17%, FEV1/FVC% with a SUCRA score of 79.52%, and St. George's Respiratory Questionnaire (SGRQ) score with a SUCRA score of 73.88%. Conversely, ET was found to be the most effective for ameliorating Forced Vital Capacity (FVC) with a SUCRA score of 73.39%.Conclusion: The findings of this study suggest that HIIT may be more effective than endurance exercise, resistance exercise, and AE in improving the 6MWD, FEV1, FEV1/FVC ratio, and SGRQ scores in patients with COPD. Additionally, ET may be better than resistance exercise, AE, and HIIT in improving FVC in COPD patients. However, due to the limited number of studies conducted on HIIT, more high-quality randomized controlled trials (RCTs) are required to verify these conclusions.

Elucidating the anti-hypertensive mechanisms of Uncaria rhynchophylla-Alisma plantago-aquatica L: an integrated network pharmacology, cluster analysis, and molecular docking approach.

Background: With the increasing global prevalence of hypertension, a condition that can severely affect multiple organs, there is a growing need for effective treatment options. Uncaria rhynchophylla-Alisma plantago-aquatica L. (UR-AP) is a traditional drug pair used for treating hypertension based on the liver-kidney synergy concept. However, the detailed molecular mechanisms underlying its efficacy remain unclear. Methods: This study utilized an integrative approach combining network pharmacology, cluster analysis, and molecular docking to uncover the bioactive components and targets of UR-AP in the treatment of hypertension. Initially, we extracted data from public databases to identify these components and targets. A Protein-Protein Interaction (PPI) network was constructed, followed by enrichment analysis to pinpoint the bioactive components, core targets, and pivotal pathways. Cluster analysis helped in identifying key sub-networks and hypothesizing primary targets. Furthermore, molecular docking was conducted to validate the interaction between the core targets and major bioactive components, thus confirming their potential efficacy in hypertension treatment. Results: Network pharmacological analysis identified 58 bioactive compounds in UR-AP, notably quercetin, kaempferol, beta-sitosterol (from Uncaria rhynchophylla), and Alisol B, alisol B 23-acetate (from Alisma plantago-aquatica L.), as pivotal bioactives. We pinpointed 143 targets common to both UR-AP and hypertension, highlighting MAPK1, IL6, AKT1, VEGFA, EGFR, and TP53 as central targets involved in key pathways like diastolic and endothelial function, anti-atherosclerosis, AGE-RAGE signaling, and calcium signaling. Cluster analysis emphasized IL6, TNF, AKT1, and VEGFA's roles in atherosclerosis and inflammation. Molecular docking confirmed strong interactions between these targets and UR-AP's main bioactives, underscoring their therapeutic potential. Conclusion: This research delineates UR-AP's pharmacological profile in hypertension treatment, linking traditional medicine with modern pharmacology. It highlights key bioactive components and their interactions with principal targets, suggesting UR-AP's potential as a novel therapeutic option for hypertension. The evidence from molecular docking studies supports these interactions, indicating the relevance of these components in affecting hypertension pathways. However, the study acknowledges its limitations, including the reliance on in silico analyses and the need for in vivo validation. These findings pave the way for future clinical research, aiming to integrate traditional medicine insights with contemporary scientific approaches for developing innovative hypertension therapies.

Transmission dynamics of Zika virus with multiple infection routes and a case study in Brazil.

The Zika virus (ZIKV) is a serious global public health crisis. A major control challenge is its multiple transmission modes. This paper aims to simulate the transmission patterns of ZIKV using a dynamic process-based epidemiological model written in ordinary differential equations, which incorporates the human-to-mosquito infection by bites and sewage, mosquito-to-human infection by bites, and human-to-human infection by sex. Mathematical analyses are carried out to calculate the basic reproduction number and backward bifurcation, and prove the existence and stability of the equilibria. The model is validated with infection data by applying it to the 2015-2016 ZIKV epidemic in Brazil. The results indicate that the reproduction number is estimated to be 2.13, in which the contributions by mosquito bite, sex and sewage account for 85.7%, 3.5% and 10.8%, respectively. This number and the morbidity rate are most sensitive to parameters related to mosquito ecology, rather than asymptomatic or human-to-human transmission. Multiple transmission routes and suitable temperature exacerbate ZIKV infection in Brazil, and the vast majority of human infection cases were prevented by the intervention implemented. These findings may provide new insights to improve the risk assessment of ZIKV infection.

Gibberellins regulate masculinization through the SpGAI-SpSTM module in dioecious spinach.

The sex of dioecious plants is mainly determined by genetic factors, but it can also be converted by environmental cues such as exogenous phytohormones. Gibberellic acids (GAs) are well-known inducers of flowering and sexual development, yet the pathway of gibberellin-induced sex conversion in dioecious spinach (Spinacia oleracea L.) remains elusive. Based on sex detection before and after GA3 application using T11A and SSR19 molecular markers, we confirmed and elevated the masculinization effect of GA on a single female plant through exogenous applications of GA3 , showing complete conversion and functional stamens. Silencing of GIBBERELLIC ACID INSENSITIVE (SpGAI), a single DELLA family protein that is a central GA signaling repressor, results in similar masculinization. We also show that SpGAI can physically interact with the spinach KNOX transcription factor SHOOT MERISTEMLESS (SpSTM), which is a homolog of the flower meristem identity regulator STM in Arabidopsis. The silencing of SpSTM also masculinized female flowers in spinach. Furthermore, SpSTM could directly bind the intron of SpPI to repress SpPI expression in developing female flowers. Overall, our results suggest that GA induces a female masculinization process through the SpGAI-SpSTM-SpPI regulatory module in spinach. These insights may help to clarify the molecular mechanism underlying the sex conversion system in dioecious plants while also elucidating the physiological basis for the generation of unisexual flowers so as to establish dioecy in plants.