Radish (Raphanus sativus L.) represents a major root vegetable crop exhibiting remarkable variation in taproot morphology, yet the underlying genetic and molecular mechanisms remain poorly understood. Through a structural variant (SV)-based genome-wide association study (GWAS), we identified RsOFP2.3, encoding an OVATE Family Protein (OFP), as a major determinant of fleshy taproot shape. Comprehensive expression profiling and RNA in situ hybridization revealed that RsOFP2.3 is broadly expressed, with the highest transcript accumulation in cambial tissues. Notably, RsOFP2.3 expression was markedly higher in the round-rooted accession than in the long-rooted one. Population-wide analysis showed that RsOFP2.3 expression was negatively correlated with taproot length and shape index, but positively correlated with taproot width. A 312-bp transposable element (TE) insertion in the RsOFP2.3 promoter repressed its expression and was strongly associated with taproot shape variation, revealing a TE-mediated cis-regulatory mechanism underlying morphological divergence. Functional analyses showed that RsOFP2.3 overexpression (OE) promotes radial expansion by enhancing cambial cell division and xylem differentiation, resulting in thicker and shorter taproots, whereas silencing RsOFP2.3 produced opposite phenotypic effects. Mechanistically, RsOFP2.3 physically interacts with the TONNEAU1-recruiting motif (TRM) protein RsTRM4, recruiting it from microtubules to the cytoplasm. Downregulation of RsTRM4 reduced taproot length, while RsTRM4 OE partially alleviated the shortened organ phenotypes caused by RsOFP2.3 OE, indicating an antagonistic relationship that fine-tunes organ morphology. These findings uncover two coordinated regulatory mechanisms involving TE-mediated cis-regulatory variation and a conserved OFP-TRM interaction module that jointly shape the balance between radial and longitudinal growth during radish taproot development, providing valuable molecular targets for precision breeding of storage root crops.
The healthcare industry is the largest private employer in the United States, yet workforce shortages persist. The Health Resources and Services Administration (HRSA) estimates that 92 million people live in primary care health professional shortage areas (HPSAs), 64 million in dental HPSAs, and 137 million in mental health HPSAs. An aging population and rising chronic illness rates place a growing burden on the healthcare system, with projected shortages exceeding 140,000 physicians and 100,000 registered nurses by 2038. Recruiting younger learners into healthcare careers is therefore critical. This study evaluated whether a traditional informational presentation or a presentation combined with hands-on activities was more effective at increasing high school students' interest in healthcare careers. Two medical students visited eight high school chemistry classes, providing either a 30-minute informational presentation with time for questions, or a 10-minute presentation followed by 30 minutes of hands-on healthcare activities, including practicing vital signs and learning intubation techniques. Both presentations discussed motivations for working in healthcare and potential career paths. Students completed anonymous pre- and post-surveys assessing healthcare career interest. Surveys were paired using anonymous identifiers. Parental consent and student assent were obtained per institutional review board requirements. The study included 129 consented participants, primarily 10th-grade students (n=124). Prior healthcare exposure was reported by 54%, and 62% had previously considered a healthcare career. On a scale of 1-10, baseline interest averaged 4.29. Interest increased by 0.64 (±1.16) in the presentation-only group and by 0.68 (±1.27) in the presentation plus hands-on group. These changes were statistically significant (p<0.001), with no significant difference between groups. Overall, 44% of students reported increased interest, 43% no change, and 12% decreased interest. Both approaches were influential in reaffirming students' interest or disinterest in a healthcare career. However, they did not differ significantly in their effect on interest. Future studies including broader student populations and expanded hands-on activities may better clarify effective strategies for engaging undecided students.
Triple-negative breast cancer (TNBC) is an aggressive subtype lacking effective treatment options, and paclitaxel resistance remains a major clinical challenge. This study investigated the role of VASN in mediating paclitaxel resistance in TNBC by integrating transcriptomic and single-cell RNA sequencing data from public databases and clinical samples. Using paclitaxel-resistant TNBC cell lines (MDA-MB-231R and CAL-51R) and xenograft models, we revealed that VASN was significantly upregulated in resistant TNBC cells and tissues, correlating with poor prognosis. Mechanistically, CEBPB directly bound to the VASN promoter to activate its transcription, and VASN interacted with IGF2BP3 via its LRR domain, recruiting USP10 to deubiquitinate and stabilize IGF2BP3 by suppressing K48-linked polyubiquitination. Stabilized IGF2BP3 enhanced ABCB1 expression through m6A-dependent mRNA stabilization, activating the PI3K/AKT pathway and driving paclitaxel resistance. Genetic or pharmacological inhibition of VASN resensitized resistant cells to paclitaxel, and computational drug screening identified Trametinib as a candidate to downregulate VASN. Trametinib synergized with paclitaxel to effectively suppress tumor growth without obvious toxicity in resistant models. In summary, we uncovered a new CEBPB-VASN/IGF2BP3/USP10-ABCB1 axis responsible for paclitaxel resistance in TNBC. Targeting VASN with Trametinib in combination with paclitaxel represents a promising therapeutic strategy to overcome chemoresistance, offering a rationale for precision medicine in resistant TNBC.
Intervertebral disc degeneration (IVDD) is a degenerative disease characterized by degradation of the extracellular matrix (ECM) in the nucleus pulposus, disruption of the fibrous ring structure, and imbalance of the inflammatory microenvironment. It is the main cause of chronic low back pain. Its pathogenesis is closely related to cellular aging and immune inflammation. Aging nucleus pulposus cells release pro-inflammatory factors such as IL-6 and TNF-α through the secretion of senescence associated secretory phenotype (SASP), recruiting M1 macrophages to infiltrate and forming a vicious cycle of "aging inflammation matrix destruction." This study systematically analyzed the molecular mechanism by which kaempferol improves IVDD through multi-target regulation by integrating bioinformatics analysis, animal experiments, and cell models. Bioinformatics screening revealed significant abnormal expression of genes such as AURKB, CCNB1, AXL, NEK6, and PTK2 in IVDD degenerated tissues. Downregulation of CCNB1 induced G2/M phase arrest by inhibiting CDK1 activity, while activation of GSK3B inhibited the Wnt signaling pathway by phosphorylating β-catenin, exacerbating ECM catabolism. Proteomics further confirms that the NOX4 mediated ROS-p38 MAPK pathway promotes cell apoptosis and SASP secretion. Immune infiltration analysis showed that M1 macrophages were significantly enriched in degenerated intervertebral discs, and their secreted IL-6 and TNF-α amplified the inflammatory cascade by activating the NF-κ B pathway. Animal experiments have shown that intervention with kaempferol can partially restore the intervertebral disc height index (DHI), downregulate the levels of IL‑1β and TNF‑α, upregulate the expression of CCNB1 and AURKB (which were downregulated in the IVDD model), thereby alleviating G2/M phase arrest and promoting cell cycle progression, inhibit AXL and PTK2, and reduce macrophage infiltration. Mechanistically, kaempferol inhibits NOX4 activity by clearing ROS, blocking the vicious cycle of oxidative stress‑inflammation; by regulating the NEK6/NF‑κB axis, the expression of MMP‑3 and ADAMTS‑4 is reduced, delaying ECM degradation; and improve the immune microenvironment by promoting macrophage polarization towards the M2 phenotype. In addition, kaempferol can reverse the metabolic imbalance mediated by GSK3B. This study reveals for the first time that kaempferol upregulates core gene networks such as AURKB and CCNB1 while suppressing AXL through the "anti‑inflammatory anti‑aging" dual pathway, thereby breaking the "aging‑immunity" crosstalk and restoring cell cycle homeostasis, providing a new strategy for natural compound intervention in IVDD treatment.
Colorectal cancer (CRC) with microsatellite-stable (MSS)/pMMR status resists immune checkpoint blockade due to its immunologically "cold" tumor microenvironment. We developed Lipo-LPS-Rg3, a dual-functional nanoliposome co-delivering lipopolysaccharide (LPS) and ginsenoside Rg3, to simultaneously ignite pyroptosis and attenuate PD-L1-associated immune suppression. LPS triggered GSDMD-mediated pyroptosis, releasing DAMPs and recruiting CD8+ T cells, while Rg3 reduced PD-L1 expression in vitro, at least partly by inhibiting NFATc1 nuclear translocation. In vivo, Lipo-LPS-Rg3 decreased PD-L1 protein expression in tumor tissues and promoted both CD8+ T-cell infiltration and IFN-γ-producing effector function. The nanoplatform achieved tumor-targeted delivery, induced near-complete regression in colorectal cancer, and exhibited minimal systemic toxicity. By converting "cold" tumors into "hot" and supporting antitumor T-cell activity, Lipo-LPS-Rg3 offers a promising strategy for MSS/pMMR CRC immunotherapy.
Prior work demonstrates that earlier trauma exposure increases the risk of posttraumatic stress disorder (PTSD) after a subsequent trauma, and cross-sectional work has also identified sexual violence (SV) as the form of traumatic stressor with the greatest conditional risk for PTSD. However, little work explores these findings longitudinally with a comparison group with no history of SV. To examine the differences in PTSD symptoms after a new incident of trauma exposure in survivors with and without an earlier history of SV. In this case-control study, data from a longitudinal cohort sample of patients enrolled in the Advancing Understanding of Recovery After Trauma (AURORA) study were examined. Participants were admitted to emergency departments due to a traumatic injury (primarily motor vehicle crash), and they were followed up for 1 year after emergency department (ED) admission. They were recruited within 72 hours of ED admission and then assessed at 5 time points (2 weeks, 8 weeks, 3 months, 6 months, 12 months) after their injury. Participants were a diverse and heterogeneous sample of individuals admitted to EDs across the US. Study data were evaluated from January 2025 to March 2026. Earlier history of SV as assessed at ED admission using the Childhood Trauma Questionnaire and the Life Events Checklist. Symptoms of PTSD as assessed by the PTSD Checklist for DSM-5. The study sample included 2423 individuals (mean [SD] age, 36 [13] years; 1566 female [64.6%]), 1270 whom (52%) reported an earlier history of SV. At every time point, participants with a history of SV demonstrated significantly elevated symptoms of PTSD (β = 4.62; 95% CI, 3.09-6.21; P < .001) compared with those without a history of SV, even after controlling for earlier nonsexual trauma exposure. Within the group with prior SV, the PTSD symptoms that remained the highest across time points were hypervigilance symptoms (criterion E), although negative alterations in cognition and mood (criterion D) were the symptom cluster that recovered most slowly. Results of this case-control study indicate that having a history of SV was associated with elevated symptoms of PTSD and slower symptom recovery after a subsequent nonsexual trauma. These results raise important considerations for clinicians, regardless of whether or not they self-identify as working specifically with survivors of SV.
As a first-level discipline, nursing plays an increasingly important role in China's healthcare system, and its sustainable development has become a key focus of current nursing research. The existing research on nursing discipline development is mostly quantitative analysis and lacks depth, failing to fully explore the experiences of nursing managers in practice and the influencing factors. This study adopted a descriptive phenomenological qualitative research design to explore the obstacles and promoting factors in nursing discipline construction and used Herzberg's Two-Factor Theory as the theoretical basis for the research design and result interpretation. The research results can provide multi-dimensional references for policy formulation, talent cultivation, and clinical discipline construction, thereby promoting the high-quality and sustainable nursing discipline development. This study aimed to (1) understand the perceptions of nursing managers regarding the construction of nursing discipline, (2) assess barriers for nursing administrators in implementing the discipline of nursing on the unit in China, (3) explore how to promote the rapid and sustainable nursing discipline development in China. The study aims to provide effective theoretical support and practical guidance for future nursing discipline development. A descriptive phenomenological qualitative design was adopted. Purposive sampling was used to recruit nursing administrators receiving standardized discipline construction training from a tertiary hospital in Nanjing. Semi-structured interviews were implemented for data collection. Colaizzi's analytical approach was used for qualitative data coding and analysis, and Herzberg's two-factor theory guided the interview outline formulation and subsequent theme classification into hygiene and motivating factors. A total of 18 nursing managers were interviewed in this study. This study coded and categorized qualitative data. Three thematic clusters were formed, covering eight subthemes in total: Hygiene factors: (1) uneven development of subspecialties, (2) irrational allocation of human resources, (3) lack of specialized nursing talent, (4) deficiencies in nurses' scientific research competency, (5) lack of sustainability in development pathways, and (6) limitations in multispecialty integration. Adverse consequences of deficient hygiene conditions: (1) low subjective initiative, and (2) low engagement in scientific research and discipline construction. Motivators: No effective motivational factors were extracted from interview data. All eight subthemes constitute critical influencing factors restricting the construction and sustainable advancement of the nursing discipline. Semistructured interviews were conducted to explore the influencing factors and barriers to nursing discipline construction for healthcare professionals. While nursing discipline construction in China holds promising prospects, numerous issues remain to be addressed. A thorough understanding of the difficulties and obstacles in nursing discipline construction helped managers adopt targeted measures and advance the sustainable nursing discipline development.
to investigate maternal perspectives on the impacts of COVID-19 pandemic the daily lives and diabetes care of families of children and adolescents with type 1 diabetes. qualitative study guided by Morin's complexity paradigm. Remote, audio-recorded, semi-structured interviews were conducted with eight Brazilian mothers recruited through social media. Data were examined using inductive content analysis. three categories emerged: a) Intensifying care: between the fear of the unpredictable and infection-prevention routines; b) (Re)assuming control: maternal responsibilities over the disorder caused by the pandemic; and c) Reinventing family life: actions grounded in supportive care. maternal perspectives reveal multidimensional pandemic-related impacts on family routines and diabetes care and highlight challenges and coping strategies adopted. The findings can inform emotional support interventions and initiatives to strengthen care for these families.
Lung squamous cell carcinoma (LUSC) frequently metastasizes to lymph nodes, yet how tumor-intrinsic biomechanical cues influence nodal immune environments remains unclear. Here, we identify solid stress, generated during tumor expansion, as a key driver of pre-metastatic niche formation in tumor-draining lymph nodes (TDLNs). Using murine models with defined solid stress levels, we show that high-stress tumors induce early TDLN remodeling characterized by fibroblast activation and accumulation of immunosuppressive S100a8⁺ myeloid cells. Single-cell and spatial transcriptomics reveal that Col1a1⁺ fibroblasts upregulate STAT3 and YAP-dependent chemokines (CCL2, CSF1), establishing a fibroblast-myeloid signaling axis that supports myeloid recruitment and suppresses CD8⁺ T cell infiltration. Functional blockade of CCR2, CSF1R, STAT3, or YAP disrupts fibroblast-myeloid co-localization, restores antigen-presenting cell populations, and enhances CD8⁺ cytotoxic T cells activity, leading to reduced lymph node metastasis and improved survival. Mechanistically, chromatin accessibility and ChIP assays reveal direct binding of p-STAT3 and YAP at inflammatory enhancer elements in fibroblasts under mechanical strain. Cross-species spatial transcriptomic analysis confirms the inverse association between Col1a1⁺ fibroblast density and CD8A⁺ T cell presence in human LUSC tissues. Our findings uncover a mechano-immune circuit whereby tumor-derived solid stress activates fibroblast-STAT3/YAP signaling to remodel TDLNs into immunosuppressive, metastasis-permissive niches. Targeting this biomechanical axis offers a promising strategy to intercept early lymphatic dissemination in LUSC.
Leprosy is a chronic, granulomatous, and infectious disease caused by Mycobacterium leprae and Mycobacterium lepromatosis. The diagnosis of the disease is primarily clinical based on the observation of the characteristic signs and symptoms. Laboratory tests such as bacilloscopy and skin biopsy can also be used to aid in diagnosis. Due to the lack of complementary tests with 100% sensitivity, diagnosis is often made based on the combination of clinical, laboratory, and molecular criteria. Although M leprae has a tropism for nerves, no validated minimally invasive procedure exists to sample nerves for this disease. The investigation of the genetic material of the etiological agents that cause leprosy through perineural collection guided by ultrasound is a promising method for improving diagnostic accuracy. This study aims to evaluate the accuracy of ultrasound-guided perineural aspirate in the diagnosis of leprosy. The World Health Organization leprosy composite reference standard will be used as the benchmark for diagnostic accuracy. We will also perform the clinical, molecular, and ultrasonographic follow-up of patients. The study will be performed at the University Hospital of Brasília, a reference center for the treatment of leprosy in the central-west region of Brazil. This will be a diagnostic study with consecutive prospective recruitment of patients referred to the leprosy outpatient clinic of University Hospital of Brasília for diagnosis and treatment. During follow-up, clinical and molecular examinations will be performed, and their results will be compared to the sonographic findings, which will be collected monthly for 1 year. Patients will be evaluated clinically, via ultrasound, and molecularly in 2 stages of leprosy diagnosis and treatment: immediately after clinical diagnosis and 1 year after the start of treatment. Subcutaneous aspiration of the ulnar nerve will be performed in the ulnar tunnel guided by ultrasound. The aspirated material will be used for identification of bacillary DNA and RNA at the time of diagnosis and 1 year after the start of treatment. Grant funding for this study was received in May 2023, August 2023, and June 2026. As of October 2025, no patients have been enrolled in this study. Patient recruitment started in January 2026 and is expected to be concluded in December 2026. Collection of clinical and laboratorial data will follow the same schedule as that of recruitment. Analysis of the collected data will be conducted between February 2027 and July 2027, with results expected to be submitted to publication by August 2027. We believe that ultrasound-guided perineural aspirate will increase the accuracy of leprosy diagnosis and may demonstrate the viability of the bacillus before and after treatment via RNA identification. PRR1-10.2196/86421.
The effect of dietary quality trajectories on cognitive frailty in older adults has not been explored previously. This population-based study examines this association. Participants were recruited between 2011 and 2013 and followed through 2022 (median follow-up: 7.6 years). The study included 519 older adults, with dietary quality assessed at four time points and cognitive frailty evaluated at five time points. Dietary intake was assessed by food frequency questionnaires, and dietary quality trajectories were identified using growth mixture modeling based on the modified Alternative Healthy Eating Index. A battery of psychoneurological tests was used to evaluate global and domain-specific cognition. Physical frailty was measured using modified Fried's frailty phenotype. Cognitive frailty was defined as the coexistence of cognitive impairment and physical frailty and categorized into six ordinal levels according to combinations of cognitive and frailty status. Generalized linear mixed models were utilized to examine the relationship between trajectories of dietary quality and cognitive frailty adjusting for important covariates. Participants' baseline mean age was 72.7 years. Compared with Relatively Lower trajectory, Relatively Higher dietary quality trajectory was associated with traditional cognitive frailty (adjusted odds ratio (aOR) = 0.62) and impaired memory-frailty (aOR = 0.48-0.50), whereas Hill-Shaped trajectory was associated only with impaired memory-frailty (aOR = 0.60). Valley-Shaped trajectory was consistently associated with impaired memory-frailty (aOR = 0.48-0.56). Based on stratified analyses, these associations mainly became more evident in participants aged ≥ 75 years, men, those with normal body mass index (18.5-24 kg/m2), apolipoprotein E ε4 non-carriers, those without diabetes, hyperlipidemia, and those with hypertension. This study identified four dietary quality trajectories, and elevated dietary quality was associated with lower odds of traditional cognitive frailty and impaired memory-frailty in older adults. Our findings provide valuable insights for identifying vulnerable subpopulations and contribute to the early prevention of cognitive frailty.
Waning immunity and recurring COVID-19 waves point to the importance of sustained booster vaccination strategies. With repeated boosters needed to sustain population-level immunity, evaluating public preferences for COVID-19 booster vaccination is important for informing future vaccination strategies, as changing perceptions of urgency, threat, and motivation may alter willingness to receive vaccine boosters compared with initial uptake. This study aimed to explore the public's stated preferences and implicit willingness to pay for COVID-19 vaccine boosters in Singapore and to identify the sociodemographic factors and health-risk acceptance profiles associated with these outcomes. A discrete choice experiment survey was conducted among the general population in Singapore, recruited from an online panel in June 2022. Discrete choice experiment scenarios presented hypothetical scenarios varying by booster characteristics, including effectiveness, protection duration, and cost, and risks of COVID-19 infection, hospitalization, and death. A 2-stage discrete choice design was used: participants first selected between 2 hypothetical scenarios and then reported real-life booster acceptance of their chosen option. A mixed logit model was used for analyses. We also estimated implicit willingness to pay for vaccine boosters, as well as assessed the associations of sociodemographic factors and health-risk profiles with booster acceptance or hesitancy. A total of 1567 participants were included in the analysis. Overall, respondents preferred boosters that offered a longer duration of protection, particularly under higher risks of COVID-19 infection and death. Respondents were willing to pay S$1.43 for every percentage-point increase in booster effectiveness, S$4.95 (S$1=US $0.77 as of July 10, 2026) per additional month of protection, and an additional S$55.23 for a vaccine booster under the hypothetical worst-case scenario of COVID-19. Younger adults, women, individuals of non-Chinese ethnicity, those without children, people with higher socioeconomic status, individuals who had received 2 or fewer COVID-19 vaccine doses, and those with chronic conditions or on chronic disease medication were more likely to receive a booster. On the other hand, older adults, individuals with lower education or socioeconomic status, those with prior COVID-19 infection, and those exhibiting higher health-risk acceptance were less likely to accept booster vaccination. Our findings demonstrate how vaccine attributes, sociodemographic factors, and health-risk attitudes influence booster acceptance. These insights can guide policymakers in tailoring strategies and communication efforts that address population needs and behavioral drivers to improve booster uptake, address hesitancy, and support sustainable long-term immunization coverage, contributing to adaptive vaccination planning in the ongoing management of COVID-19.
Protein S-palmitoylation, the reversible thioesterification of cysteine side chains, is emerging as a druggable post-translational modification that couples membrane topology to oncogenic, metabolic, immune, and epigenetic networks in cancer. ZDHHC palmitoyltransferases and depalmitoylating enzymes, including acyl-protein thioesterases and palmitoyl-protein thioesterase 1, constitute a dynamic circuitry that governs the localization, stability, and signaling competence of key regulators of tumor growth, metabolic adaptation, and immune phenotype. Here, we synthesize recent structural and chemical biology advances that clarify how human ZDHHC enzymes achieve acyl-chain recognition and substrate engagement. Structural studies show that these enzymes adopt a four-transmembrane, "tent-like" fold, in which the helices create a membrane-embedded cavity for acyl-chain accommodation. We also discuss how ankyrin-repeat domains and accessory partners shape substrate recruitment and subcellular localization, and we highlight emerging high-throughput platforms that enable quantitative profiling of isoform- and site-selective modulators. We then discuss how ZDHHC-substrate circuits rewire canonical growth-factor signaling and epithelial-mesenchymal transition programs, metabolic and ferroptotic control nodes, innate immune sensing, and chromatin-linked regulation. These convergent mechanisms position ZDHHC-mediated S-palmitoylation as a context-dependent regulator of tumor progression, therapy response, ferroptosis sensitivity, and immune phenotype. Finally, we outline a translational framework encompassing clinical-stage PPT1 inhibitors, selective ABHD17 blockade, emerging ZDHHC modulators, substrate-competitive strategies targeting checkpoint palmitoylation, and selected comparator approaches affecting Wnt and Hedgehog ligand lipidation. Current evidence positions ZDHHC-mediated S-palmitoylation as a regulatory layer with potential biomarker and therapeutic relevance; however, not all reported ZDHHC-substrate associations carry equivalent evidentiary weight. Mechanisms supported by convergent site-directed, genetic, biochemical, functional, and in vivo evidence should be distinguished from associations inferred mainly from expression profiling, overexpression systems, single-model observations, or broad pharmacological perturbation. Clinical translation remains preliminary and is constrained by isoform selectivity, substrate redundancy, incomplete pharmacodynamic read-outs, and the absence of validated biomarker-guided patient stratification.
Human-held beliefs about the emotional capacity and experience of non-human animals appear to be related to attitudes concerning animal use, but direct links between such beliefs and consumer behaviors that affect animals have not been investigated. Two survey-based studies were conducted to test whether scores on the Beliefs about Animal Emotions Scale (BAES) are associated with self-reported consumer behaviors. In Study 1, beliefs about animal emotions statistically predicted reported frequency of non-dietary animal use avoidances (e.g., avoiding animal-tested products, animal-based competitions), over and above age, gender, and educational attainment in a U.S.-based sample. Study 2, which involved targeted recruitment of self-identified vegetarians and vegans, largely replicated these findings, and further showed that BAES scores predicted the number of reported animal-product food avoidances. Having established a link between beliefs about animal emotions and animal-related behavioral choices, additional analyses were conducted to investigate potential factors that contribute to such beliefs. Educational attainment was a consistent negative predictor of BAES scores across both studies: more highly educated participants attributed less emotional capacity and experience to animals. Exploratory analyses indicated that, based on self-report, there are numerous sources of information that contribute to beliefs about animal emotions including, most notably, direct interaction with pets and personal belief systems (e.g., moral, spiritual). Together, these results indicate that individual differences in beliefs about animal emotions, in particular beliefs concerning emotional complexity and authenticity, as well as beliefs about the moral relevance of animal emotions, are importantly related to self-reported consumer behaviors that have implications for animals.
Mucosal chemokines (eg, CCL25, CCL28, CXCL14, and CXCL17) play key roles in protecting mucosal surfaces against invading infectious pathogens. However, their specific contributions to protection against genital herpes remain to be fully elucidated. Here, we investigated the role of CXCL14 as a mediator of mucosal immunity against genital HSV-2 infection and disease. CXCL14 expression was analyzed in HSV-specific CD8+ T cells from HSV-2-infected asymptomatic and symptomatic women, in primary human vaginal epithelial cells, and in a murine genital HSV-2 infection model. CXCL14(-/-) deficient mice and wild-type (WT) mice were compared for genital disease severity, vaginal viral loads, survival, immune cell recruitment, and T-cell effector function following intravaginal HSV-2 infection. Chromatin immunoprecipitation assays were performed to identify transcription factors binding to the CXCL14 promoter after HSV-2 infection. CXCL14 was homeostatically expressed at the genital tract mucosal surface, and HSV-specific CD8+ T cells from HSV-2-infected asymptomatic women expressed significantly higher levels of CXCL14 than those from symptomatic women. HSV-2 infection rapidly induced CXCL14 transcription and production in primary human vaginal epithelial cells and in murine vaginal mucocutaneous tissue. CXCL14(-/-) mice developed more severe genital lesions, higher vaginal viral loads, and lower survival compared to WT mice. In addition, CXCL14 deficiency impaired the recruitment of natural killer (NK) cells, neutrophils, and CD44+CD62L- effector memory CD4+ and CD8+ T cells to the infected vaginal mucosa. It reduced T cell effector functions, including production of IFN-γ, TNF-α, and Granzyme B. Mechanistically, NF-κB and OCT-1 transcription factors bound to the CXCL14 promoter within hours of HSV-2 infection. Our findings demonstrate that NF-κB- and OCT-1-driven CXCL14 expression is crucial for orchestrating early innate and T-cell responses that protect against genital HSV-2 infection and disease. These results suggest that CXCL14 is an important immunoregulatory chemokine triggered early after epithelial viral infection, facilitating the induction of effective mucosal protective immunity against genital herpes.
Excess sugar intake in early life may affect long-term brain health, but evidence for dementia is limited. We used the abrupt end of UK sugar rationing in September 1953 as a natural experiment to test whether exposure to sugar rationing during different windows within the first 1,000 days from conception was associated with adult risk of all-cause dementia, Alzheimer disease (AD), and vascular dementia (VaD). We analyzed UK Biobank participants born around the end of UK sugar rationing. Exposure was classified as rationing in utero only, in utero plus the first year of life, in utero plus 1-2 years of life, or no exposure. Incident dementia was identified from linked ICD-10 records. MRI of the brain and cognitive function were assessed in the imaging subcohort. Adjusted Cox and Gompertz models estimated HRs and 95% CIs, Fine-Gray models accounted for competing risk, and mediation analyses evaluated type 2 diabetes and hypertension. Among 64,737 participants included in the analysis, the mean age at recruitment was 54.6 years, and 56.4% were women; 40,963 were exposed to sugar rationing during fetal and/or early-childhood life, and 23,774 were unexposed. Compared with unexposed individuals, sugar rationing in utero plus the first year of life was associated with lower hazards of all-cause dementia (HR, 0.79; 95% CI 0.66-0.94) and AD (HR, 0.77; 95% CI 0.59-1.00). Similar or slightly stronger associations were observed for exposure in utero plus 1-2 years (all-cause dementia: HR, 0.77; 95% CI 0.63-0.95; AD: HR, 0.72; 95% CI 0.53-0.98). Exposure in utero plus 1-2 years was associated with delayed onset of all-cause dementia by 2.55 years, AD by 2.87 years, and VaD by 2.49 years. Early-life sugar rationing was also associated with higher total gray matter volume (β, 3.27; 95% CI 0.46-6.07), lower white matter hyperintensity volume (β, -0.64; 95% CI -0.97 to -0.31), and better performance in processing speed and reasoning. Incident type 2 diabetes and hypertension jointly mediated 25.5% of the association. Sugar restriction in the first 1,000 days was associated with lower dementia hazards, delayed onset, and more favorable brain-health profiles. These results support early-life sugar reduction as a potential strategy for dementia prevention.
Introduction/ObjectivesLower urinary tract symptoms (LUTS) are prevalent and represent prominent health issues among community-dwelling older people globally. This study aimed to examine the association among psychological adaptation, socio-economic status (SES), symptom types, and quality of life in community-dwelling older women with LUTS.MethodsA cross-sectional study was conducted among 150 older women residing in communities in central Thailand, who were recruited using purposive sampling criteria. Data collection was conducted through structured interviews and questionnaires, including the Personal Information Questionnaire, the Thai Geriatric Depression Scale-15, the International Consultation on Incontinence Questionnaire Female Lower Urinary Tract Symptoms, and the King's Health Questionnaire. Descriptive statistics and multiple logistic regression analyses were performed.ResultsParticipants presented with multiple urinary tract symptoms; filling symptoms were found in 99.3% of participants, followed by incontinence (70%), and voiding symptoms (30%). For psychosocial adaptations, 23.3% suggested mild-moderate depressive symptoms, and 2.7% were classified as having moderate-severe depressive symptoms. Regarding SES, the majority of participants had completed primary school (73.3%), earned an average monthly income of 500-1,000 baht (52.7%), and were unemployed (56.7%). For quality of life, the mean total quality of life score was 16.45 ± 11.32. Participants with more than one lower urinary tract symptom were 3.81 times more likely to report poor quality of life than those with only filling symptoms (OR: 3.81, 95% CI: 1.53-9.47, p = 0.004).ConclusionThe findings from this study provide essential insights for healthcare personnel, particularly geriatric nurse practitioners, about the impact of LUTS on the quality of life of community-dwelling older women. Implementing systematic screening for LUTS may facilitate timely intervention, potentially delaying symptom progression, mitigating complications, and thereby enhancing the quality of life among this population.
The correlation between dental age, bone age, and chronological age is crucial for understanding the growth and development of children. This relationship is particularly important in the diagnosis and management of growth disorders. In children with isolated growth hormone deficiency (GHD), these correlations may provide insights into the extent and consistency of developmental delay and the effectiveness of therapeutic interventions. The aim of this study was to assess how dental and skeletal maturation correspond to chronological age. Among the 93 patients recruited, 48 with GHD (30 males and 18 females), aged 10.57 ± 2.24 years, met the inclusion criteria. The control group consisted of 48 healthy children. Clinical and biochemical assessments were performed. Dental age was assessed through clinical examination, whereas skeletal maturation was evaluated using hand-wrist radiographs. Analyses were conducted for the entire GHD group and for subgroups during and after treatment. The correlations between dental, skeletal, and chronological age were strong and statistically significant (p < 0.05). No significant correlation was found between the extent of dental age delay and bone age delay. Dental age delay was significantly greater in patients with GHD before treatment than in healthy children (-0.31 vs 0.41, p = 0.024). Bone age delay in children with GHD was more pronounced than dental age delay; it was 1.99 years before treatment and 1.32 years during treatment. Our results revealed significant differences between bone age and chronological age, as well as between bone age and dental age, in children with GHD, and these differences were reduced during treatment. Significant correlations between bone, dental, and chronological ages indicate that as chronological age increases, dental age and bone age also increase in a predictable manner. Dental and skeletal age delays in patients with GHD are not synchronized, and clinicians should therefore be aware of these discrepancies, particularly when planning dental interventions.
HPV vaccine hesitancy is prevalent among female college students in China, yet how trust interacts with cost concerns remains unclear. This study, grounded in the 3C model, examined whether trust in healthcare professionals buffers price-related barriers and identified high-risk subgroups. A cross-sectional survey recruited 4,326 female college students from 12 Chinese provinces. Trust, price perception, and vaccination intention were measured. Interaction effects were tested using the Breslow-Day test; a decision tree model (CART) identified high-risk profiles. Trust in healthcare professionals showed the strongest positive correlation with vaccination intention (r s = 0.610, p < 0.001), with a clear dose-response pattern. A significant trust-by-price interaction emerged (p = 0.008): among low-trust respondents, high price was associated with substantially higher hesitancy (78.5% vs. 54.3%, p < 0.001); among high-trust respondents, the price effect was negligible (35.6% vs. 30.1%, p = 0.12). The most frequently cited reasons for hesitancy were high cost (53.5%), fear of side effects (52.7%), and limited vaccine knowledge (46.3%). Decision tree analysis identified "low trust and high price" as the dominant high-risk profile, accounting for 32.4% of all hesitant individuals. Trust can buffer price-related barriers to HPV vaccination. Stratified interventions should prioritize the "low trust and high price" group through combined trust-building and financial support.
Chloroplast development and photosynthetic pigment synthesis in leaves are governed by a highly conserved Golden2-like (GLK) transcription factor network. However, the mechanisms sustaining green pigmentation in non-foliar organs such as flowers remain unclear. Here, we show that floral pigmentation is controlled by a GLK-independent pathway, identifying the AT-hook protein CmAHL8L as a central regulator of green coloration in chrysanthemum. Silencing CmAHL8L reduced green pigmentation in ray florets, accompanied by decreased chlorophyll and carotenoid levels. CmAHL8L promotes chlorophyll accumulation by repressing the transcriptional repressor CmAHL23, thereby derepressing GLUTAMYL-tRNA REDUCTASE 1 (CmHEMA1), while concurrently preventing carotenoid degradation through direct inhibition of CAROTENOID CLEAVAGE DIOXYGENASE (CmCCD4a). Mechanistically, CmAHL8L recruits the histone deacetylase CmHDT1 to remove H3K27ac marks at the CmAHL23 and CmCCD4a promoters, suppressing their transcription. We further demonstrate that this AHL8L-HDT1 complex is conserved across diverse species. Collectively, our work defines a predominant regulatory mechanism in photosynthetic pigments of the flower, distinct from leaf mechanisms, providing key genetic insights into the regulation and evolution of flower coloration.