Fusible and Radiopaque Microspheres for Embolization.

In this work, fusible microspheres loaded with radiopaque agents as an embolic agent for transcatheter arterial embolization (TAE) are developed. A poly(ethylene glycol) (PEG) and poly(ε-caprolactone) (PCL) multi-block copolymer basing polyurethane (PCEU) is synthesized and fabricated into blank microspheres (BMs). The microspheres are elastic in compression test. A clinical contrast agent lipiodol is encapsulated in the microspheres to receive fusible radiopaque microspheres (FRMs). The sizes of FRMs are uniform and range from 142.2 to 343.1 µm. The encapsulated lipiodol acts as the plasticizer to reduce the melting temperature point (Tm) of PECU microspheres, thus, leading to the fusion of microspheres to exhibit efficient embolization in vivo. The performance of FRMs is carried out on a rabbit ear embolization model. Serious ischemic necrosis is observed and the radiopacity of FRMs sustains much longer time than that of commercial contrast agent Loversol in vivo. The fusible and radiopaque microsphere is promising to be developed as an exciting embolic agent.

Dietary flavonoid intake and risk of hormone-related cancers: A population-based prospective cohort study.

BACKGROUND: Dietary flavonoids may have potential effects on hormone-related cancers (HRCs) due to their anti-cancer properties via regulating hormones and suppressing inflammation and oxidative stress. We aimed to examine the association of flavonoid intake with risks of HRCs and whether this association was mediated by blood biomarkers involved in biological mechanisms. METHODS: This prospective cohort study from UK Biobank included 187,350 participants free of cancer when the last dietary recall was completed. The dietary intakes of flavonoids and subclasses were assessed using 24-hour dietary recalls. Venous blood was collected at baseline and assayed for biomarkers of inflammation, hormones, and oxidative stress. Hazard ratios (HR) and 95 % confidential intervals (CI) for the associations between flavonoid intake and HRCs risk were estimated by the cause-specific Cox proportional hazards model. The role of blood biomarkers in the flavonoids-HRCs association was investigated through mediation analysis. RESULTS: Over a median follow-up of 9.5 years, 3,392 female breast cancer, 417 ovarian cancer, 516 endometrial cancer, 4,305 prostate cancer, 45 testicular cancer, and 146 thyroid cancer cases were documented. Compared to the lowest quintile, multivariable-adjusted HRs (95 % CIs) in the highest quintile of total flavonoid intake were 0.89 (0.80-0.99) for breast cancer, 0.68 (0.50-0.92) for ovarian cancer, and 0.88 (0.80-0.98) for female-specific cancers. For subclasses, intakes of flavonols and anthocyanidins were inversely associated with the risk of female-specific cancers (Ptrend <0.05). Anthocyanidin intake was positively related to prostate cancer risk, whereas isoflavone intake was inversely linked to thyroid cancer risk (Ptrend <0.05). Additionally, certain biomarkers of inflammation, hormones and oxidative stress jointly mediated the association of flavonoid intake with the risk of female-specific cancers and prostate cancer. CONCLUSIONS: Our findings highlighted the importance of dietary flavonoids for the prevention of HRCs in the general population, providing epidemiological evidence for dietary guidelines.

The Link Between Temporomandibular Disorders and Jaw Functional Limitations Among Chinese Adolescents.

BACKGROUND: Currently, there is still controversy surrounding the relationship between temporomandibular disorders (TMDs) symptoms and jaw functional limitations. We investigated the distribution of TMDs in senior high school students, including both the number and types of symptoms, and assessed their association with jaw functional limitations. Furthermore, we explored sex differences in these associations. METHODS: This study was conducted at a public high school in Hefei, Anhui Province, China, with data collected from September to October 2022. All subjects completed questionnaires assessing the anamnestic symptoms of TMDs and the Jaw Functional Limitation Scale (JFLS), and examinations were performed by trained dentists according to the Diagnostic Criteria for TMD. Data were analysed using the Kruskal-Wallis, Mann-Whitney U, and Chi-square tests. RESULTS: The mean age of the participants (N = 2890) was 17.2 ± 0.14 years and 38.9% were females (61.1% were males). Limitations in self-assessed jaw function were associated with the presence of TMDs (P < .05). Participants with more symptoms reported significantly high levels of functional limitations (P < .05). Compared to male adolescents, female adolescents more commonly experienced TMDs pain and tended to have more symptoms (P < .05). However, no sex differences were observed in most associations between TMDs and jaw functional limitations. CONCLUSION: TMDs-positive symptoms are common in adolescents. Female adolescents were more affected by TMDs symptoms than male adolescents. Individuals with more TMDs symptoms have greater jaw functional limitations.

Are different generations of female employees trapped by work-family conflicts? A study on the impact of family-supportive supervisor behavior on thriving at work.

Introduction: With women's advancement in education and status, they drive corporate and social progress. However, traditional gender roles burden female employees with more family responsibilities, challenging work-life balance and affecting job performance. Organizations should supporting female employees to address these challenges. Thriving at work, a core aspect of positive work engagement, helps maintain enthusiasm and efficiency. This study explores the impact of family-supportive supervisor behavior (FSSB) on the thriving at work of female employees in China, considering generational differences in their work-family balance needs and the mediating mechanisms involved. Methods: The methodology adopted in this study utilized Amos 26.0 and SPSS 25.0 to analyze data obtained from a sample of 279 female employees in China. Specifically, the study examined the direct impact of FSSB on thriving at work, alongside the mediating influence of work-family balance. Moreover, the research aimed to discern variations in these effects across different generational cohorts. Results: This study highlights the direct impact of FSSB on female employees' thriving at work across different generational cohorts. Notably, the "post-90s" generation displayed the strongest direct effect of FSSB on thriving at work. Additionally, the impact of FSSB on work-family balance varied by generation, with the "post-90s" generation showing the weakest effect. Furthermore, the mediating role of work-family balance differed among generations, with complete mediation observed in the "post-80s" generation but no mediating effect in the "post-90s" generation, reflecting their distinct work-life balance priorities and needs. Discussion: This study uses a generational difference perspective to explore the main and mediating effects of FSSB on thriving at work, enriching the theoretical research on generational differences and providing valuable insights for future research. Practically, organizations should focus on the needs of different generations while encouraging FSSB, fostering a supportive work environment and enhancing outcomes.

ARID1A safeguards the canalization of the cell fate decision during osteoclastogenesis.

Chromatin remodeler ARID1A regulates gene transcription by modulating nucleosome positioning and chromatin accessibility. While ARID1A-mediated stage and lineage-restricted gene regulation during cell fate canalization remains unresolved. Using osteoclastogenesis as a model, we show that ARID1A transcriptionally safeguards the osteoclast (OC) fate canalization during proliferation-differentiation switching at single-cell resolution. Notably, ARID1A is indispensable for the transcriptional apparatus condensates formation with coactivator BRD4/lineage-specifying transcription factor (TF) PU.1 at Nfatc1 super-enhancer during safeguarding the OC fate canalization. Besides, the antagonist function between ARID1A-cBAF and BRD9-ncBAF complex during osteoclastogenesis has been validated with in vitro assay and compound mutant mouse model. Furthermore, the antagonistic function of ARID1A-"accelerator" and BRD9-"brake" both depend on coactivator BRD4-"clutch" during osteoclastogenesis. Overall, these results uncover sophisticated cooperation between chromatin remodeler ARID1A, coactivator, and lineage-specifying TF at super-enhancer of lineage master TF in a condensate manner, and antagonist between distinct BAF complexes in the proper and balanced cell fate canalization.

Near-infrared-II photocharging nanozyme for enhanced tumor immunotherapy.

In tumor therapy, copper (Cu)-based nanozymes with peroxidase-like activity play a crucial role in converting hydrogen peroxide into hydroxyl radicals (OH). This process induces immunogenic cell death, which in turn activates the body's immune response, enhancing the efficacy of tumor immunotherapy. Nonetheless, the efficiency of this reaction is curtailed due to the oxidation of Cu(I) to Cu(II), leading to the self-depletion of the nanozyme's activity and an insufficient yield of OH for effective immunotherapeutic activation. To surmount this challenge, our research introduces a photocharging self-doped semiconductor nanozyme, copper sulfide (Cu9S8). The photocharging effect enables the nanozyme to convert internal Cu(II) back to Cu(I) through charge transfer induced by near-infrared (NIR)-II photothermal energy, thereby effectively maintaining the enzyme-like activity of the nanozyme. Additionally, Cu9S8 is enhanced with a calcium sulfide (CaS) coating. This coating reacts in the acidic microenvironment of tumors to generate hydrogen sulfide (H2S) gas, which in turn suppresses the catalase activity inherent in tumor cells, ensuring a plentiful supply of H2O2 for the nanozyme's operation. This dual strategy of amplifying enzyme-like activity and substrate availability culminates in the generation of ample OH within tumor cells, leading to significant immunogenic cell death and thereby realizing potent immunotherapy.

Modulation of external and internal aluminum resistance by ALS3-dependent STAR1-mediated promotion of STOP1 degradation.

The ALMT1 transporter aids malate secretion, chelating Al3+ ions to form nontoxic Al-malate complexes, believed to exclude Al from the roots. However, the extent to which malate secreted by ALMT1 is solely used for the exclusion of Al3+ or can be reutilized by plant roots for internal Al tolerance remains uncertain. In our investigation, we explored the impact of malate secretion on both external and internal Al resistance in Arabidopsis thaliana. Additionally, we delved into the mechanism by which the tonoplast-localized bacterial-type ATP-binding cassette (ABC) transporter complex STAR1/ALS3 promotes the degradation of the Al resistance transcription factor STOP1 to regulate ALMT1 expression. Our study demonstrates that the level of secreted malate influences whether the Al-malate complex is excluded from the roots or transported into root cells. The nodulin 26-like intrinsic protein (NIP) subfamily members NIP1;1 and NIP1;2, located in the plasma membrane, coordinate with STAR1/ALS3 to facilitate Al-malate transport from root apoplasm to the symplasm and eventually to the vacuoles for the internal Al detoxification. ALS3-dependent STAR1 interacts with and promotes the degradation of STOP1, regulating malate exudation. Our findings demonstrate the dual roles of malate exudation in external Al exclusion and Al absorption for internal Al detoxification.

Natural variation in BnaA07.MKK9 confers resistance to Sclerotinia stem rot in oilseed rape.

Sclerotinia stem rot (SSR), caused by the necrotrophic fungus Sclerotinia sclerotiorum, is one of the most devastating diseases for several major oil-producing crops. Despite its impact, the genetic basis of SSR resistance in plants remains poorly understood. Here, through a genome-wide association study, we identify a key gene, BnaA07. MKK9, that encodes a mitogen-activated protein kinase kinase that confers SSR resistance in oilseed rape. Our functional analyses reveal that BnaA07.MKK9 interacts with BnaC03.MPK3 and BnaC03.MPK6 and phosphorylates them at the TEY activation motif, triggering a signaling cascade that initiates biosynthesis of ethylene, camalexin, and indole glucosinolates, and promotes accumulation of H2O2 and the hypersensitive response, ultimately conferring resistance. Furthermore, variations in the coding sequence of BnaA07.MKK9 alter its kinase activity and improve SSR resistance by ~30% in cultivars carrying the advantageous haplotype. These findings enhance our understanding of SSR resistance and may help engineer novel diversity for future breeding of oilseed rape.

Bacillus coagulans and Clostridium butyricum synergistically alleviate depression in a chronic unpredictable mild stress mouse model through altering gut microbiota and prefrontal cortex gene expression.

Introduction: The prevalence of major depressive disorder (MDD) has gradually increased and has attracted widespread attention. The aim of this study was to investigate the effect of a probiotic compound consisting of Bacillus coagulans and Clostridium butyricum, on a mouse depression model. Methods: Mice were subjected to chronic unpredictable mild stress (CUMS) and then treated with the probiotics at different concentrations. And mice received behavior test such as forced swimming test and tail suspension test. After that, all mice were sacrificed and the samples were collected for analysis. Moreover, prefrontal cortex (PFC) gene expression and the gut microbiota among different groups were also analyzed. Results: Probiotics improved depressive-like behavior in CUMS mice, as indicated by decreased immobility time (p < 0.05) in the forced swimming test and tail suspension test. probiotics intervention also increased the level of 5-hydroxytryptamine (5-HT) in the prefrontal cortex and decreased the adrenocorticotropic hormone (ACTH) level in serum. In addition, by comparing the PFC gene expression among different groups, we found that the genes upregulated by probiotics were enriched in the PI3K-Akt signaling pathway in the prefrontal cortex. Moreover, we found that downregulated genes in prefrontal cortex of CUMS group such as Sfrp5 and Angpt2, which were correlated with depression, were reversed by the probiotics. Furthermore, the probiotics altered the structure of the gut microbiota, and reversed the reduction of cob(II)yrinate a,c-diamide biosynthesis I pathway in CUMS group. Several species like Bacteroides caecimuris and Parabacteroides distasoni, whose abundance was significantly decreased in the CUMS group but reversed after the probiotics intervention, showed significantly positive correlation with depression associated genes such as Tbxas1 and Cldn2. Discussion: These findings suggested that CUMS-induced depression-like behavior can be alleviated by the probiotics, possibly through alterations in the PFC gene expression and gut microbiota.

A Causal Regulation Modeling Algorithm for Temporal Events with Application to Escherichia coli's Aerobic to Anaerobic Transition.

Time-series experiments are crucial for understanding the transient and dynamic nature of biological phenomena. These experiments, leveraging advanced classification and clustering algorithms, allow for a deep dive into the cellular processes. However, while these approaches effectively identify patterns and trends within data, they often need to improve in elucidating the causal mechanisms behind these changes. Building on this foundation, our study introduces a novel algorithm for temporal causal signaling modeling, integrating established knowledge networks with sequential gene expression data to elucidate signal transduction pathways over time. Focusing on Escherichia coli's (E. coli) aerobic to anaerobic transition (AAT), this research marks a significant leap in understanding the organism's metabolic shifts. By applying our algorithm to a comprehensive E. coli regulatory network and a time-series microarray dataset, we constructed the cross-time point core signaling and regulatory processes of E. coli's AAT. Through gene expression analysis, we validated the primary regulatory interactions governing this process. We identified a novel regulatory scheme wherein environmentally responsive genes, soxR and oxyR, activate fur, modulating the nitrogen metabolism regulators fnr and nac. This regulatory cascade controls the stress regulators ompR and lrhA, ultimately affecting the cell motility gene flhD, unveiling a novel regulatory axis that elucidates the complex regulatory dynamics during the AAT process. Our approach, merging empirical data with prior knowledge, represents a significant advance in modeling cellular signaling processes, offering a deeper understanding of microbial physiology and its applications in biotechnology.

Electro-oxidation of 5-hydroxymethylfurfural in a low-concentrated alkaline electrolyte by enhancing hydroxyl adsorption over a single-atom supported catalyst.

Electrocatalytic oxidation of 5-hydroxymethylfurfural (HMF) to 2,5-furandicarboxylic acid (FDCA), a sustainable strategy to produce bio-based plastic monomer, is always conducted in a high-concentration alkaline solution (1.0 mol L-1 KOH) for high activity. However, such high concentration of alkali poses challenges including HMF degradation and high operation costs associated with product separation. Herein, we report a single-atom-ruthenium supported on Co3O4 (Ru1-Co3O4) as a catalyst that works efficiently in a low-concentration alkaline electrolyte (0.1 mol L-1 KOH), exhibiting a low potential of 1.191 V versus a reversible hydrogen electrode to achieve 10 mA cm-2 in 0.1 mol L-1 KOH, which outperforms previous catalysts. Electrochemical studies demonstrate that single-atom-Ru significantly enhances hydroxyl (OH-) adsorption with insufficient OH- supply, thus improving HMF oxidation. To showcase the potential of Ru1-Co3O4 catalyst, we demonstrate its high efficiency in a flow reactor under industrially relevant conditions. Eventually, techno-economic analysis shows that substitution of the conventional 1.0 mol L-1 KOH with 0.1 mol L-1 KOH electrolyte may significantly reduce the minimum selling price of FDCA by 21.0%. This work demonstrates an efficient catalyst design for electrooxidation of biomass working without using strong alkaline electrolyte that may contribute to more economic biomass electro-valorization.

Pathogenic roles of follicular helper T cells in IgG4-related disease and implications for potential therapy.

IgG4-related disease (IgG4-RD) is a recently described autoimmune disorder characterized by elevated serum IgG4 levels and tissue infiltration of IgG4+ plasma cells in multiple organ systems. Recent advancements have significantly enhanced our understanding of the pathological mechanism underlying this immune-mediated disease. T cell immunity plays a crucial role in the pathogenesis of IgG4-RD, and follicular helper T cells (Tfh) are particularly important in germinal center (GC) formation, plasmablast differentiation, and IgG4 class-switching. Apart from serum IgG4 concentrations, the expansion of circulating Tfh2 cells and plasmablasts may also serve as novel biomarkers for disease diagnosis and activity monitoring in IgG4-RD. Further exploration into the pathogenic roles of Tfh in IgG4-RD could potentially lead to identifying new therapeutic targets that offer more effective alternatives for treating this condition. In this review, we will focus on the current knowledge regarding the pathogenic roles Tfh cells play in IgG4-RD and outline potential therapeutic targets for future clinical intervention.

Effect of endoscopic full-thickness resection assisted by distal serosal turnover with floss traction for gastric submucosal masses.

BACKGROUND: Complex and high-risk surgical complications pose pressing challenges in the clinical implementation and advancement of endoscopic full-thickness resection (EFTR). Successful perforation repair under endoscopy, thereby avoiding surgical intervention and postoperative complications such as peritonitis, are pivotal for effective EFTR. AIM: To investigate the effectiveness and safety of EFTR assisted by distal serosal inversion under floss traction in gastric submucosal tumors. METHODS: A retrospective analysis of patients with gastric and duodenal submucosal tumors treated with EFTR assisted by the distal serosa inversion under dental floss traction from January 2023 to January 2024 was conducted. The total operation time, tumor dissection time, wound closure time, intraoperative bleeding volume, length of hospital stay and incidence of complications were analyzed. RESULTS: There were 93 patients, aged 55.1 ± 12.1 years. Complete tumor resection was achieved in all cases, resulting in a 100% success rate. The average total operation time was 67.4 ± 27.0 min, with tumor dissection taking 43.6 ± 20.4 min. Wound closure times varied, with gastric body closure time of 24.5 ± 14.1 min and gastric fundus closure time of 16.6 ± 8.7 min, showing a significant difference (P < 0.05). Intraoperative blood loss was 2.3 ± 4.0 mL, and average length of hospital stay was 5.7 ± 1.9 d. There was no secondary perforation after suturing in all cases. The incidence of delayed bleeding was 2.2%, and the incidence of abdominal infection was 3.2%. No patient required other surgical intervention during and after the operation. CONCLUSION: Distal serosal inversion under dental-floss-assisted EFTR significantly reduced wound closure time and intraoperative blood loss, making it a viable approach for gastric submucosal tumors.

The formation and evolution of vulnerability risk of rural poor groups under the perspective of social support -- based on the analysis of "sensitivity-resilience".

The anticipated sensitivity and resilience practices of the poor groups expose them to significant vulnerability risks, with social support actions arising from the return to poverty posing additional interference. To comprehensively prevent and mitigate vulnerability risks, breakthroughs in corresponding social support are essential. This study, through questionnaire surveys and semi-structured interviews, collected original data from 750 impoverished households in Lantian County, northwest China. Using a bottom-up approach, it constructed a "sensitivity-resilience" framework to assess the vulnerability and resilience mechanisms of the relatively poor groups. The research reveals that vulnerability and resilience interact in response to risk shocks. The strong livelihood dependence, capital accumulation deficiency, and sensitivity characteristics of social marginalization among rural relatively poor groups, coupled with fragmented and inefficient social support, exacerbate the degree of vulnerability risks, leading to an amplification of sensitivity and a reduction in resilience. Based on these findings, targeted at the characteristics of vulnerability risks and the fatigue factors of social support, this study proposes policy recommendations at two levels: system reengineering to reduce sensitivity and long-term reengineering to enhance resilience, aiming to prevent large-scale return to poverty.

Comparison of Facial Aesthetic Evaluation Given by Patients with Cleft Lip and/or Palate and Professionals: A Systematic Review.

OBJECTIVE: To compare the differences of facial aesthetic evaluation between patients with Cleft Lip and/or Palate (CL/P) and professionals for the treatment outcome of CL/P. DESIGN: This systematic review was conducted on MedLine, Web of Science, Embase and Cochrane Library databases. The Risk of Bias in Non-randomized Studies of Intervention (ROBINS-I) tool was used to evaluate the included researches. SETTING: Not applicable. PATIENTS, PARTICIPANTS: Patients with CL/P and professionals. INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURES: The facial aesthetic evaluation of patients with CL/P and professionals. RESULTS: Among the 1695 literatures retrieved, 22 articles were included, including 974 patients with CL/P and 251 professionals. The bias risk assessment on 21 articles was rated "Moderate" and only one article was rated "Serious". Due to the high heterogeneity of the included studies, meta-analysis was not possible, so descriptive analysis was conducted. Among the included studies, two articles indicated similar views from both groups, 19 noted differences between the two groups, of which three articles indicated more positive evaluation by professionals and nine articles indicated more positive evaluation by patients. CONCLUSIONS: The available data indicate that there is a difference between patients with CL/P and professionals in the aesthetic evaluation, but it is not clear which group is more positive. During the treatment of patients with CL/P, apart from the objective aesthetic evaluation, professionals should fully consider subjective ideas and self-assessment of patients, in order to improve the quality of life for patients.

Apigenin alleviates doxorubicin-induced myocardial pyroptosis by inhibiting glycogen synthase kinase-3ß in vitro and in vivo.

Apigenin, a natural flavonoid compound found in chamomile (Matricaia chamomilla L.) from the Asteraceae family, has been shown in our previous study to possess antimyocardial hypertrophy and anti-cardiac fibrosis effects. However, its effects and mechanisms on the pyroptosis of cardiomyocytes induced by doxorubicin (DOX) are poorly understood. The objective of this study was to investigate the role of GSK-3ß and the effects of apigenin in DOX-induced cardiotoxicity. H9c2 cells stimulated with DOX were treated with SB216763 and apigenin. Additionally, a mouse model of DOX-induced cardiotoxicity was prepared and further treated with apigenin and SB216763 for 30 days. The findings revealed that treatment with SB216763 or apigenin resulted in a significant reduction in the levels of pyroptosis-related factors. Furthermore, the phosphorylation of GSK-3ß was enhanced while the phosphorylation of nuclear factor-kB (NF-κB) p65 was reduced following treatment with either SB216763 or apigenin. Conversely, the effects of apigenin treatment were nullified in siRNA-GSK-3ß-transfected cells. Results from computer simulation and molecular docking analysis supported that apigenin could directly target the regulation of GSK-3ß. Therefore, our study confirmed that the inhibition of GSK-3ß and treatment with apigenin effectively suppressed the pyroptosis of cardiomyocytes in both DOX-stimulated H9c2 cells and mice. These benefits may be attributed in part to the decrease in GSK-3ß expression and subsequent reduction in NF-κB p65 activation. Overall, our findings revealed that the pharmacological targeting of GSK-3ß may offer a promising therapeutic approach for alleviating DOX-induced cardiotoxicity.

3D Gaussian Splatting as New Era: A Survey.

3D Gaussian Splatting (3D-GS) has emerged as a significant advancement in the field of Computer Graphics, offering explicit scene representation and novel view synthesis without the reliance on neural networks, such as Neural Radiance Fields (NeRF). This technique has found diverse applications in areas such as robotics, urban mapping, autonomous navigation, and virtual reality/augmented reality, just name a few. Given the growing popularity and expanding research in 3D Gaussian Splatting, this paper presents a comprehensive survey of relevant papers from the past year. We organize the survey into taxonomies based on characteristics and applications, providing an introduction to the theoretical underpinnings of 3D Gaussian Splatting. Our goal through this survey is to acquaint new researchers with 3D Gaussian Splatting, serve as a valuable reference for seminal works in the field, and inspire future research directions, as discussed in our concluding section.

Long-term effects of climate factors on dengue fever over a 40-year period.

BACKGROUND: Dengue fever stands as one of the most extensively disseminated mosquito-borne infectious diseases worldwide. While numerous studies have investigated its influencing factors, a gap remains in long-term analysis, impeding the identification of temporal patterns, periodicity in transmission, and the development of effective prevention and control strategies. Thus, we aim to analyze the periodicity of dengue fever incidence and explore the association between various climate factors and the disease over an extended time series. METHODS: By utilizing monthly dengue fever cases and climate data spanning four decades (1978-2018) in Guangdong province, China, we employed wavelet analysis to detect dengue fever periodicity and analyze the time-lag relationship with climate factors. Additionally, Geodetector q statistic was employed to quantify the explanatory power of each climate factor and assess interaction effects. RESULTS: Our findings revealed a prolonged transmission period of dengue fever over the 40-year period, transitioning from August to November in the 1970s to nearly year-round in the 2010s. Moreover, we observed lags of 1.5, 3.5, and 3 months between dengue fever and temperature, relative humidity, and precipitation, respectively. The explanatory power of precipitation, temperature, relative humidity, and the Oceanic Niño Index (ONI) on dengue fever was determined to be 18.19%, 12.04%, 11.37%, and 5.17%, respectively. Dengue fever exhibited susceptibility to various climate factors, with notable nonlinear enhancement arising from the interaction of any two variables. Notably, the interaction between precipitation and humidity yielded the most significant effect, accounting for an explanatory power of 75.32%. CONCLUSIONS: Consequently, future prevention and control strategies for dengue fever should take into account these climate changes and formulate corresponding measures accordingly. In regions experiencing the onset of high temperatures, humidity, and precipitation, it is imperative to initiate mosquito prevention and control measures within a specific window period of 1.5 months.

Estrogen inhibits TGF­ß1­stimulated cardiac fibroblast differentiation and collagen synthesis by promoting Cdc42.

17ß­estradiol (E2) can inhibit cardiac fibrosis in female patients with heart failure (HF) and activate cell division cycle 42 (Cdc42), however it is unknown whether 17ß­estradiol (E2) can ameliorate differentiation and collagen synthesis in TGF­ß1­stimulated mouse cardiac fibroblasts (MCFs) by regulating cell division cycle 42 (Cdc42). The present study aimed to investigate the roles of estrogen and Cdc42 in preventing myocardial fibrosis and the underlying molecular mechanisms. An ELISA was used to measure the levels of E2 and Cdc42 in the serum of patients with heart failure (HF), and western blotting was used to measure the expression levels of Cdc42 in TGF­ß1­stimulated immortalized MCFs. MCFs were transfected with a Cdc42 overexpression (OE) lentivirus or small interfering RNA (siRNA), or treated with a Cdc42 inhibitor (MLS­573151), and the function of Cdc42 was assessed by western blotting, immunofluorescence staining, reverse transcription­quantitative PCR and dual­luciferase reporter assays. Western blotting and immunofluorescence staining were performed to verify the protective effect of E2 on TGF­ß1­stimulated MCFs, and the association between the protective effect and Cdc42. The results demonstrated that Cdc42 levels were increased in the serum of patients with HF and were positively correlated with the levels of E2; however, Cdc42 levels were decreased in TGF­ß1­stimulated MCFs. Cdc42 inhibited MCF differentiation and collagen synthesis, as indicated by the protein expression of α­smooth muscle actin, collagen I and collagen III. Mechanistically, Cdc42 inhibited the transcription of TGF­ß1 by promoting the expression of p21 (RAC1)­activated kinase 1 (Pak1)/JNK/c­Jun signaling pathway proteins and inhibiting the activity of the Tgfb1 gene promoter. In addition, E2 inhibited the differentiation and collagen synthesis of TGF­ß1­stimulated MCFs, and promoted the protein expression of Pak1, JNK and c­Jun, consistent with the effects of Cdc42, whereas the effects of E2 were abolished when Cdc42 was knocked down. The aforementioned findings suggested that E2 could inhibit differentiation and collagen synthesis in TGF­ß1­stimulated MCFs by regulating Cdc42 and the downstream Pak1/JNK/c­Jun signaling pathway.

SEC: A core hub during cell fate alteration.

Pol II pause release is a rate-limiting step in gene transcription, influencing various cell fate alterations. Numerous proteins orchestrate Pol II pause release, thereby playing pivotal roles in the intricate process of cellular fate modulation. Super elongation complex (SEC), a large assembly comprising diverse protein components, has garnered attention due to its emerging significance in orchestrating physiological and pathological cellular identity changes by regulating the transcription of crucial genes. Consequently, SEC emerges as a noteworthy functional complex capable of modulating cell fate alterations. Therefore, a comprehensive review is warranted to systematically summarize the core roles of SEC in different types of cell fate alterations. This review focuses on elucidating the current understanding of the structural and functional basis of SEC. Additionally, we discuss the intricate regulatory mechanisms governing SEC in various models of cell fate alteration, encompassing both physiological and pathological contexts. Furthermore, leveraging the existing knowledge of SEC, we propose some insightful directions for future research, aiming to enhance our mechanistic and functional comprehension of SEC within the diverse landscape of cell fate alterations.