Responsive Supramolecular Nanomicelles Formed through Self-Assembly of Acyclic Cucurbit[n]uril for Targeted Drug Delivery to Cancer Cells.

The supramolecular drug delivery systems (SDDSs) based on host-guest recognition through noncovalent interactions, capable of responsive behavior and dynamic switching to external stimuli, have attracted considerable attention in cancer therapy. In this study, a targeted dual-functional drug delivery system was designed and synthesized. A hydrophilic macrocyclic host molecule (acyclic cucurbit[n]uril ACB) was modified with folic acid (FA) as a targeting ligand. The guest molecule consists of a disulfide bond attached to adamantane (DA) and cannabidiol (CBD) at both ends of the response element of glutathione. Recognition and self-assembly of host and guest molecules successfully functionalize supramolecular nanomicelles (SNMs), targeting cancer cells and releasing drugs in a high glutathione environment. The interactions between host and guest molecules were investigated by using nuclear magnetic resonance (NMR), fluorescence titration, Fourier-transform infrared spectroscopy (FT-IR), and thermal analysis (TGA). Transmission electron microscopy (TEM) and dynamic light scattering (DLS) confirmed the nanostructure of the SNMs. Experimentation with 5,5'-dithiobis (2-nitrobenzoic acid) (DTNB) demonstrated the responsiveness of SNMs to glutathione (GSH). In vitro cytotoxicity assays demonstrated that SNMs had a greater targeting efficacy for four types of cancer cells (HeLa, HCT-116, A549, and HepG2) compared to normal 293T cells. Cellular uptake studies revealed that HeLa cells more readily absorbed SNMs, leading to their accumulation in the tumor cell cytoplasm. Fluorescence colocalization assays verified that SNMs efficiently accumulated in organelles related to energy metabolism and signaling, including mitochondria and the endoplasmic reticulum, affecting cellular metabolic death. Both flow cytometry and confocal nuclear staining assays confirmed that SNMs effectively induced apoptosis over time, ultimately resulting in the death of cancer cells. These findings demonstrate that SNMs exhibit excellent targeting ability, responsiveness, high bioavailability, and stability, suggesting significant potential in drug delivery applications.

Digital Technology Use in US Community-Dwelling Seniors With and Without Homebound Status.

OBJECTIVES: To examine (1) the prevalence of digital technology use, including information and communication technology devices, everyday technology use, and digital health technology use among community-dwelling older adults with or without homebound status and (2) the associations of digital technology use with homebound status. DESIGN: Cross-sectional study. SETTING AND PARTICIPANTS: We used the 2022 National Health and Aging Trends Study (NHATS) data that included 5510 community-dwelling older adults. METHODS: Digital technology use was assessed using self-reported outcomes of the technological environment component of the NHATS, including information and communication technology devices, everyday technology use, and digital health technology use. Homebound status was measured with 4 mobility-related questions regarding the frequency, independence, and difficulties of leaving home. Survey-weighted, binomial logistic regression was used to examine the associations of 17 technological-related outcomes and homebound status. RESULTS: Overall, the prevalence of homebound older adults was 5.2% (95% CI, 4.4%-6.1%), representing an estimated 2,516,403 people. The prevalence of digital technology use outcomes varied according to homebound status. The prevalence of any technology used in homebound, semi-homebound, and non-homebound populations was 88.5%, 93.3%, and 98.5%, respectively. Compared with non-homebound older adults, semi-homebound older adults had lower odds of emailing (OR, 0.71; 95% CI, 0.53-0.94), using the internet for any other reason (OR, 0.70; 95% CI, 0.49-0.99), visiting medical providers (OR, 0.68; 95% CI, 0.48-0.95), and handling insurance (OR, 0.75; 95% CI, 0.56-0.99); homebound older adults had lower odds of using a phone (OR, 0.41; 95% CI, 0.28-0.59), using any everyday technology (OR, 0.58; 95% CI, 0.38-0.89), visiting medical providers (OR, 0.52; 95% CI, 0.35-0.76), and handling insurance (OR, 0.57; 95% CI, 0.38-0.86). CONCLUSIONS AND IMPLICATIONS: Non-homebound older adults are more likely to use digital technology than those who are semi-homebound or homebound. Public health care providers should prioritize efforts to enhance digital inclusion to ensure that all older adults can benefit from the advantages of digital technology.

Cascade Cyclization of N-Cyanamide Alkenes for the Divergent Synthesis of Azido-, Nitro-, and Alkenyl-Containing Pyrroloquinazolinones.

Radical cascade cyclizations of N-cyanamide alkenes have been developed for the divergent synthesis of pyrroloquinazolinones bearing azido, alkenyl, and nitro groups by controlling the reaction conditions. The reaction temperature and the loading of the base play important roles in the different reaction pathways. These reactions are characterized by wide functional group compatibility and mild conditions.

Exploring the protective effects of Qiju Granule in a rat model of dry age-related macular degeneration.

AIM: The aim of this study was to evaluate the potential protective effect of Qiju Granule in a rat model of age-related macular degeneration (AMD) and investigate the underlying mechanisms involved. METHODS: Rats were injected intravenously with 40 mg/kg of sodium iodate (SI) to induce a dry AMD model. The rats in the treatment group received three different doses of Qiju Granule once a day via gavage, while the rats in the control group were given an equal volume of physiological saline. On day 14 and day 28 following the intervention, various methods were employed to evaluate retinal function and structure, including electroretinography (ERG), optical coherence tomography (OCT), and histological examination. The expression of glial fibrillary acidic protein (GFAP), basic fibroblast growth factor (bFGF), brain-derived neurotrophic factor (BDNF), and ciliary neurotrophic factor (CNTF) was assessed via immunofluorescence. Beyond immunofluorescence, the mRNA levels of bFGF, BDNF, and CNTF were quantitatively determined using real-time polymerase chain reaction (qRT-PCR). RESULTS: Rats treated with Qiju Granule exhibited significant improvements in both retinal function and structure compared to the model group. The most noteworthy effects were observed at a high dose of Qiju Granule. Furthermore, the expression levels of bFGF, BDNF, and CNTF were significantly unregulated in the treated groups compared to the model group. CONCLUSIONS: Qiju Granule demonstrated a protective effect on the retina in the SI-induced rat model of AMD. The protective mechanism may be attributed to the upregulation of retinal neurotrophic factors expression.

Experiences and needs of family members following sudden cardiac death: A meta-synthesis.

OBJECTIVE: This meta-synthesis of qualitative studies aimed to explore the experiences and needs of family members of victims of sudden cardiac death. DESIGN: A meta-synthesis was conducted. DATA SOURCES: Five databases (PubMed, CINAHL, EMBASE, Web of Science, and China National Knowledge Infrastructure) were searched from establishment to May 2024. From initial searches with essential keywords (sudden cardiac death, family members, and qualitative studies), 3021 articles were retrieved. There were eight studies in the meta-synthesis, selected on the basis of inclusion and exclusion criteria. REVIEW METHODS: We evaluated the quality of the included studies using the Critical Appraisal Skills Programme-Qualitative Research Checklist. RESULTS: Eight studies from six countries reported on the experiences and needs of family members who had lost someone to sudden cardiac death, and five analytical themes were synthesized: negative emotional reaction, finding cause of death, rebuilding life, meaning reconstruction and need for support. These experiences and needs fuse with each other and are relevant to the health and future of the family members. CONCLUSION: Negative emotional reaction is a necessary process for family members dealing with sudden cardiac death, and rebuilding life is a challenge that family members must face. In the process of family members rebuilding normal life, finding the cause of death is the foundation, and meaning reconstruction is the core. Many of the needs faced by these family members are not well met, and policymakers and bereavement teams should provide comprehensive and personalized interventions for them.

Technology of plant factory for vegetable crop speed breeding.

Sustaining crop production and food security are threatened by a burgeoning world population and adverse environmental conditions. Traditional breeding methods for vegetable crops are time-consuming, laborious, and untargeted, often taking several years to develop new and improved varieties. The challenges faced by a long breeding cycle need to be overcome. The speed breeding (SB) approach is broadly employed in crop breeding, which greatly shortens breeding cycles and facilities plant growth to obtain new, better-adapted crop varieties as quickly as possible. Potential opportunities are offered by SB in plant factories, where optimal photoperiod, light quality, light intensity, temperature, CO2 concentration, and nutrients are precisely manipulated to enhance the growth of horticultural vegetable crops, holding promise to surmount the long-standing problem of lengthy crop breeding cycles. Additionally, integrated with other breeding technologies, such as genome editing, genomic selection, and high-throughput genotyping, SB in plant factories has emerged as a smart and promising platform to hasten generation turnover and enhance the efficiency of breeding in vegetable crops. This review considers the pivotal opportunities and challenges of SB in plant factories, aiming to accelerate plant generation turnover and improve vegetable crops with precision and efficiency.

Urinary Equol and Equol-Predicting Microbial Genera Are Favorably Associated with Body Fat Measures among Chinese Adults.

BACKGROUND: Many studies have investigated the intake of dietary isoflavones in relation to obesity risk, whereas the association using objective biomarkers of isoflavones, particularly equol (a gut-derived metabolite of daidzein with greater bioavailability than other isoflavones) has been less studied. In addition, the associations between equol and gut microbiota profile at the population level remain to be fully characterized. OBJECTIVES: We aimed to identify equol-predicting microbial species and to investigate the associations of equol-predicting microbial species and urinary excretion of isoflavones including glycitein, genistein, daidzein, and equol with diverse obesity markers in free living-individuals. METHODS: In this 1-y longitudinal study of 754 community-dwelling adults, urinary isoflavones, fecal microbiota, height, weight, and circumferences of waist and hip were measured at baseline and again after 1 y. Liver fat [indicated by the controlled attenuation parameter (CAP)] and other body composition were also measured after 1 y. Linear models and linear mixed-effects models were used to analyze the associations for single measure and repeated measures, respectively. RESULTS: Among 305 participants (median age: 50 y, IQR, 37-59 y) including 138 males and 167 females, higher urinary excretion of equol was associated with lower CAP (ß = -0.013, P < 0.001) and body fat mass (ß= -0.014, P = 0.046). No association was found between any other urinary isoflavones and obesity markers (all P > 0.05). We identified 21 bacterial genera whose relative abundance were positively associated with urinary equol concentrations (all Pfalsediscovery rate < 0.05), and constructed an equol-predicting microbial score to reflect the overall equol-producing potential of host gut microbiota. This score was inversely associated with CAP (ß = -0.040, P = 0.011). CONCLUSIONS: High urinary equol concentrations and equol-predicting microbial species could be favorably associated with liver fat and other obesity markers.

Labor patterns of spontaneous first-stage labor in Chinese women with normal neonatal outcomes.

BACKGROUND: Friedman's standards, developed almost 50 years ago, may no longer align with the needs of today's obstetric population and current pregnancy management practices. This study aims to analyze contemporary labor patterns and estimate labor duration in China, focusing on first-stage labor data from Chinese parturients with a spontaneous onset of labor. METHODS: This retrospective observational study utilized data from electronic medical records of a tertiary hospital in Changsha, Hunan. Out of a total of 2,689 parturients, exclusions were made for multiple gestations, preterm, post-term, or stillbirth, cesarean delivery, non-vertex presentation, and neonatal intensive care unit admission. Average labor curves were constructed by parity using repeated-measure analysis, and labor duration was estimated through interval-censored regression, stratified by cervical dilation at admission. We performed an analysis to assess the impact of oxytocin augmentation and amniotomy on labor progression and conducted a sensitivity analysis using women with complicated outcomes. RESULTS: Nulliparous women take over 180 minutes for cervical dilation from 3 to 4 cm, and the duration from 5 to 6 cm exceeds 145 minutes. Multiparous women experience shorter labor durations than nulliparous. Labor acceleration is observed after 5 cm in nulliparous, but no distinct inflection point is evident in the average labor curve. In the second stage of labor, the 95th percentile for nulliparous, with and without epidural analgesia, is 142 minutes and 127 minutes, respectively. CONCLUSIONS: These findings provide valuable insights for the reassessment of labor and delivery processes in contemporary obstetric populations, including current Chinese obstetric practice.

Application progress of latent class growth models in dynamic prevention and control strategies for acquired immunodeficiency syndrome. / æ½œåˆ†ç±»å¢žé•¿æ¨¡åž‹åœ¨èŽ·å¾—æ€§å ç–«ç¼ºé™·ç»¼åˆå¾åŠ¨æ€é˜²æŽ§ç­–ç•¥ä¸­çš„åº”ç”¨è¿›å±•.

The prevention and control requirements for HIV/AIDS vary significantly among different populations, posing substantial challenges to the formulation and implementation of intervention strategies. Dynamically assessing the heterogeneity and disease progression trajectories of various groups is crucial. Latent class growth model (LCGM) serves as a statistical approach that fits a longitudinal data into N subgroups of individual development trajectories, identifying and analyzing the progression paths of different subgroups, thereby offering a novel perspective for disease control strategies. LCGM has shown significant advantages in the application of HIV/AIDS prevention and control, especially in gaining a deeper understanding and analysis of epidemiological characteristics, risk behaviors, psychological research, heterogeneity in testing, and dynamic changes. Summarizing the advantages and limitations of applying LCGM can provide a reliable basis for precise prevention and control of HIV/AIDS.

Association of screen-based activities and risk of self-harm and suicidal behaviors among young people: A systematic review and meta-analysis of longitudinal studies.

Emerging evidence suggests that screen-based activities are associated with self-harm and suicidal behaviors. This study aimed to examine these associations among young people through a meta-analysis. We systematically searched EBSCO pshyARTICLES, MEDLINE (via PubMed), EMBASE, and Web of Science from their inception to April 1, 2022, and updated on May 1, 2024. Longitudinal studies reporting the association between various screen-based activities and subsequent self-harm and suicidal behaviors in young people aged 10 to 24 were included. Nineteen longitudinal studies were included in the qualitative synthesis, and 13 studies comprising 43,489 young people were included in the meta-analysis, revealing that total screen use is significantly associated with the risks of self-harm and suicidal behaviors. Cyberbullying victimization was also related to these adverse outcomes. Subgroup analyses indicated that social media use and problematic screen use are significant risk factors for self-harm and suicidal behaviors. Study quality was appraised using the Newcastle-Ottawa Scale, and potential publication bias was deemed unlikely to affect the results significantly. These findings suggest that screen-based activities should be considered in the management and intervention strategies for self-harm and suicidal behaviors in young people.

Association Between the Hepatic Steatosis Index and Risk of Incident Type 2 Diabetes Mellitus in the Normoglycemic Population:A Longitudinal Prospective Study in Japan.

Purpose: The Hepatic Steatosis Index (HSI) is a reliable predictor of non-alcoholic fatty liver disease (NAFLD), which can increase the risk of type 2 diabetes mellitus (T2DM). However, limited research has directly predicted HSI's association with T2DM occurrence at normal blood glucose levels. Hence, this study aimed to assess the link between baseline HSI and T2DM development under euglycemic conditions while also exploring potential sex differences. Methods: Using data from the NAGALA cohort study, a Cox regression model analyzed the relationship between HSI and T2DM risk, calculating hazard ratios (HR) and 95% confidence intervals (CI). Subgroup analyses were conducted to investigate factors influencing HSI's prediction of incident T2DM. Results: During a mean 6.1-year follow-up, 238 individuals (1.65% of participants) developed T2DM. After adjusting for age, ethanol consumption, smoking status, SBP, DBP, TG, and TC, HSI showed a significant association with incident T2DM in individuals with normal glucose levels, consistent across sexes. Compared to the lowest quartile group (Q1), the HR and 95% CI for Q2, Q3, and Q4 were 1.09 (0.61, 1.93), 1.16 (0.68, 1.98), and 3.30 (2.04, 5.33), respectively (P for trend < 0.001). Subgroup analysis indicated that elevated HSI significantly increased the risk of incident T2DM in individuals with normal TG levels (P for interaction = 0.0170). Conclusion: This study highlights the significant association between elevated HSI levels and the likelihood of developing incident T2DM in individuals with normal glucose levels. Furthermore, it offers a simple and valuable screening tool for predicting T2DM.

Psychological Flexibility Profiles and Mental Health Among University Students with Left-Behind Experience: A Latent Profile Analysis.

The left-behind experience as an adverse childhood experience has a negative impact on the mental health of university students. Psychological inflexibility mediated the relationship between adverse childhood experiences and mental disorders, but no similar findings were drawn in psychological flexibility (PF). More research is needed to understand the relationship between PF and mental health of university students with left-behind experience. To investigate the relationship between PF profiles and mental health and sleep quality of university students with left-behind experience based on latent profile analysis. A sample of 1988 Chinese university students with left-behind experience were recruited to complete an online survey. Participants provided demographic information and completed validated measures of PF and mental health. Latent profile analysis was used to identify patterns of PF, and logistic regression analysis was used to examine the relationships among these variables. We found four PF profiles among participants, with the largest number being the moderately flexible profile (n = 808, 40.6%). The level of PF was positively correlated with mental health and sleep quality (all P < 0.001). Females, being left behind at a young age and for a long time, and having little contact with parents were associated with low PF (all P < 0.05). Our study highlights the importance of focusing on the PF of university students with left-behind experience and left-behind children, and the need for interventions to improve their PF and thus their mental health.

Curcumin protects against cadmium-induced germ cell death in the testis of rats.

Introduction: Cadmium (Cd) has been shown to disrupt the reproductive system. In this study, we evaluated the protective effects of Curcumin (Cur) against Cd-induced reproductive toxicity. Methods: Exploring the role of Cur in Cd-treated rat models. Results: The study demonstrated that Cd treatment impaired the seminiferous epithelium, leading to increased apoptosis of germ cells. Interestingly, pretreatment with Cur ameliorated the histological damage and decreased the germ cell apoptosis induced by Cd. Furthermore, after Cd exposure, B-cell lymphoma-2 expression was significantly decreased while Bax expression was increased. Pretreatment of rats with Cur protected against germ cell apoptosis by improving the expression of B-cell lymphoma-2 and reducing Bax. Additionally, Cd treatment increased reactive oxygen species, resulting in a decrease in antioxidant enzymes. However, pretreatment of rats with Cur followed by Cd administration led to a substantial decrease in reactive oxygen species levels and increased activities of antioxidant enzymes. Ultrastructural investigations revealed that damage to the mitochondrial structure was significantly ameliorated by Cur pretreatment in Cd-treated rats. Notably, Cur significantly activated the peroxisome proliferator-activated receptor gamma coactivator 1a/Sirtuins-3 signaling pathway. Conclusions: Overall, our data suggest that Cd induces germ cell apoptosis through mitochondrial-induced oxidative stress, but Cur pretreatment offers strong protection against Cd-induced reproductive toxicity.

Lung-Specific mRNA Delivery Enabled by Sulfonium Lipid Nanoparticles.

Among various mRNA carrier systems, lipid nanoparticles (LNPs) stand out as the most clinically advanced. While current clinical trials of mRNA/LNP therapeutics mainly address liver diseases, the potential of mRNA therapy extends far beyond─yet to be unraveled. To fully unlock the promises of mRNA therapy, there is an urgent need to develop safe and effective LNP systems that can target extrahepatic organs. Here, we report on the development of sulfonium lipid nanoparticles (sLNPs) for systemic mRNA delivery to the lungs. sLNP effectively and specifically delivered mRNA to the lungs following intravenous administration in mice. No evidence of lung and systemic inflammation or toxicity in major organs was induced by sLNP. Our findings demonstrated that the newly developed lung-specific sLNP platform is both safe and efficacious. It holds great promise for advancing the development of new mRNA-based therapies for the treatment of lung-associated diseases and conditions.

Urinary Equol and Equol-Predicting Microbial Species Are Favorably Associated With Cardiometabolic Risk Markers in Chinese Adults.

BACKGROUND: The association between soy isoflavones intake and cardiometabolic health remains inconclusive. We investigated the associations of urinary biomarkers of isoflavones including daidzein, glycitein, genistein, equol (a gut microbial metabolite of daidzein), and equol-predicting microbial species with cardiometabolic risk markers. METHODS AND RESULTS: In a 1-year study of 305 Chinese community-dwelling adults aged ≥18 years, urinary isoflavones, fecal microbiota, blood pressure, blood glucose and lipids, and anthropometric data were measured twice, 1 year apart. Brachial-ankle pulse wave velocity was also measured after 1 year. A linear mixed-effects model was used to analyze repeated measurements. Logistic regression was used to calculate the adjusted odds ratio (aOR) and 95% CI for the associations for arterial stiffness. Each 1 µg/g creatinine increase in urinary equol concentrations was associated with 1.47%, 0.96%, and 3.32% decrease in triglycerides, plasma atherogenic index, and metabolic syndrome score, respectively (all P<0.05), and 0.61% increase in high-density lipoprotein cholesterol (P=0.025). Urinary equol was also associated with lower risk of arterial stiffness (aOR, 0.28 [95% CI, 0.09-0.90]; Ptrend=0.036). We identified 21 bacterial genera whose relative abundance was positively associated with urinary equol (false discovery rate-corrected P<0.05) and constructed a microbial species score to reflect the overall equol-predicting capacity. This score (per 1-point increase) was inversely associated with triglycerides (percentage difference=-1.48%), plasma atherogenic index (percentage difference=-0.85%), and the risk of arterial stiffness (aOR, 0.27 [95% CI, 0.08-0.88]; all P<0.05). CONCLUSIONS: Our findings suggest that urinary equol and equol-predicting microbial species may improve cardiometabolic risk parameters in Chinese adults.

"Wheels stuck in the mud": A qualitative study of experiences of academic burnout in graduate nursing students.

BACKGROUND: Academic burnout is widespread in higher education, affecting academic achievements, professional development, and physical and mental health. Previous related research lacks qualitative studies on graduate nursing students. AIM: This study aims to provide valuable information to relevant authorities and stakeholders by identifying the key experiences associated with academic burnout in graduate nursing students. DESIGN: An exploratory qualitative research design. SETTINGS: This research was carried out at two medical universities located in the southern region of China. PARTICIPANTS: Nineteen enrolled graduate nursing students. METHODS: Data collection spanned from December 2023 to January 2024. After obtaining informed consent from the participants, the researchers conducted in-depth, semi-structured interviews. Data processing and analysis were based on Giorgi's phenomenological method. The reporting of this study strictly adhered to the Standards for Reporting Qualitative Research (SRQR). RESULTS: Nineteen participants completed the interviews, ranging in age from 22 to 42 years and including sixteen females and three males. "Wheels stuck in mud" was the core construct that explained graduate nursing students' academic burnout. Analyses revealed four themes: invisible hand, a battle with myself, two choices, find my way. CONCLUSION: The academic burnout of nursing graduate students is perceived as a psychological dilemma akin to being "wheels stuck in mud." It is driven by an invisible force composed of multiple components, leading to intense internal struggles for individuals. Individuals exhibit two distinct trends in their academic performance: either "remaining detached and indifferent to academics" or "overcommitting and self-exploiting." It is encouraged to conduct intervention using an integrative strategy based on acceptance and commitment therapy, self-disclosure, and mindfulness.

The role of TrkB signaling-mediated synaptic plasticity in the antidepressant properties of catalpol, the main active compound of Rehmannia glutinosa Libosch.

ETHNOPHARMACOLOGICAL RELEVANCE: Rehmannia glutinosa Libosch. (RGL) is a famous ethnic medicine contained in antidepressant Chinese medicine formulas and is traditionally clinically used for depression. We have recently confirmed that RGL enhanced synaptic plasticity in a mouse model of Chinese medical syndrome and that catalpol may be the representatively pharmacological component responsible for its improvement in synaptic plasticity and treatment of depression. Impaired synaptic plasticity is closely linked to major depression. Tyrosine kinase receptor B (TrkB) signaling has recently been discovered as a key pathway for synaptic plasticity improvement and antidepressant discovery. However, to date, it is unknown whether the target of catalpol to improve synaptic plasticity involves TrkB and whether its antidepressant mechanism involves synaptic plasticity mediated by TrkB signaling. AIM OF STUDY: This study aims to elucidate the potential antidepressant target and mechanisms of catalpol, the main active compound of RGL, through TrkB signaling-mediated synaptic plasticity. MATERIALS AND METHODS: We have recently predicted through molecular networking strategy (including network pharmacology, molecular docking, and molecular dynamics simulation) that catalpol may exert its antidepressant effects by regulating TrkB signaling and thus modulating essential synaptic plasticity proteins. Then, this study used classic behavioral tests, targeted diagnostic reagents, Nissl and Golgi staining, immunohistochemical analysis, immunofluorescence analysis, Western blot, enzyme-linked immunosorbent assay, and Real-time PCR to confirm the potential target and signaling of catalpol to improve synaptic plasticity for the treatment of depression. RESULTS: The data showed that catalpol could improve synaptic plasticity and depressive behaviors, and its action pathway was predicted to involve TrkB signaling. Subsequently, the blockade of TrkB abolished the improvement of synaptic plasticity by catalpol and its antidepressant properties, which validated that TrkB signaling was the key pathway for catalpol to improve synaptic plasticity and exert antidepressant properties. Inhibition of COX-2 was likely to be a necessary facilitator for the antidepressant efficacy of catalpol via the TrkB target and TrkB-mediated synaptic plasticity. CONCLUSION: TrkB signaling-mediated synaptic plasticity plays a key role in the antidepressant properties of catalpol. This study provides critical information for the development of new and targeted antidepressant therapies or treatment strategies by catalpol. However, considering the existence of sex differences in depression (female depression is 2-3 times than that of males) and not exploring the antidepressant sex specificity of catalpol is a limitation, we will investigate the sex specificity of the antidepressant effects and molecular mechanisms of catalpol on sex-specific animals in the future to provide a preclinical basis for more accurate and targeted medication of catalpol.

Urinary enterolignans and enterolignan-predicting microbial species are favourably associated with liver fat and other obesity markers.

Aims: Plant-derived lignans may protect against obesity, while their bioactivity needs gut microbial conversion to enterolignans. We used repeated measures to identify enterolignan-predicting microbial species and investigate whether enterolignans and enterolignan-predicting microbial species are associated with obesity. Methods: Urinary enterolignans, fecal microbiota, body weight, height, and circumferences of the waist (WC) and hips (HC) were repeatedly measured at the baseline and after 1 year in 305 community-dwelling adults in Huoshan, China. Body composition and liver fat [indicated by the controlled attenuation parameter (CAP)] were measured after 1 year. Multivariate-adjusted linear models and linear mixed-effects models were used to analyze single and repeated measurements, respectively. Results: Enterolactone and enterodiol levels were both inversely associated with the waist-to-hip ratio, body fat mass (BFM), visceral fat level (VFL), and liver fat accumulation (all P < 0.05). Enterolactone levels were also associated with lower WC (ß = -0.0035 and P = 0.013) and HC (ß = -0.0028 and P = 0.044). We identified multiple bacterial genera whose relative abundance was positively associated with the levels of enterolactone (26 genera) and enterodiol (22 genera, all P false discovery rate < 0.05), and constructed the enterolactone-predicting microbial score and enterodiol-predicting microbial score to reflect the overall enterolignan-producing potential of the host gut microbiota. Both these scores were associated with lower body weight and CAP (all P < 0.05). The enterolactone-predicting microbial score was also inversely associated with the BFM (ß = -0.1128 and P = 0.027) and VFL (ß = -0.1265 and P = 0.044). Conclusion: Our findings support that modulating the host gut microbiome could be a potential strategy to prevent obesity by enhancing the production of enterolignans.

Factors associated with clinical nurse's mental health: a qualitative study applying the social ecological model.

BACKGROUND: The prevalence of burnout, depression, and anxiety among Chinese nurses was 34%, 55.5%, and 41.8% respectively. Mental health problems have significant impacts on their personal well-being, work performance, patient care quality, and the overall healthcare system. Mental health is influenced by factors at multiple levels and their interactions. METHODS: This was a descriptive qualitative study using phenomenological approach. We recruited a total of 48 nurses from a tertiary hospital in Changsha, Hunan Province, China. Data were collected through focus group interviews. Audio-recorded data were transcribed and inductively analysed. RESULTS: Four major themes with 13 subthemes were identified according to the social ecological model: (1) individual-level factors, including personality traits, sleep quality, workplace adaptability, and years of work experience; (2) interpersonal-level factors, encompassing interpersonal support and role conflict; (3) organization-level factors, such as organizational climate, organizational support, career plateau, and job control; and (4) social-level factors, which included compensation packages, social status, and legislative provision and policy. CONCLUSIONS: Our study provides a nuanced understanding of the multifaceted factors influencing nurses' mental health. Recognizing the interconnectedness of individual, interpersonal, organizational, and social elements is essential for developing targeted interventions and comprehensive strategies to promote and safeguard the mental well-being of nurses in clinical settings. TRIAL AND PROTOCOL REGISTRATION: The larger study was registered with Chinese Clinical Trial Registry: ChiCTR2300072142 (05/06/2023) https://www.chictr.org.cn/showproj.html?proj=192676 . REPORTING METHOD: This study is reported according to the Consolidated Criteria for Reporting Qualitative Research (COREQ).