Stroke is a neurological disease that leads to severe morbidity and mortality globally. Family caregivers are directly impacted by patients who have a stroke, especially regarding financial burdens. To describe and examine factors predicting family caregivers' financial burden, using the bidirectional relationship concept developed by Isik and colleagues (2019) as a guiding model to build a new framework for Thai family caregivers. A cross-sectional study with a predictive-correlational design was employed. Using a purposive sampling technique, 124 eligible family caregivers of dependent stroke survivors were recruited from two governmental tertiary care hospitals (Thailand). However, only 120 family caregivers were included after 4 extreme outliers were removed. The questionnaires comprised demographic information, illness perceptions, social support, financial management, non-medical costs, and family caregivers' financial burden. Descriptive and correlational and multiple regression (MR) analyses were used to analyse data. The MR analysis revealed the model's overall fit: F(7,112) = 27.185, p < 0.01. Age, educational level, family caregivers' income, social support, and family caregivers' financial management could help predict the financial burden for family caregivers of dependent stroke survivors, explaining 60.6% of the variance. Financial management was the most robust predictor of financial burden for family caregivers (β = 0.449; p < .01). Family caregivers' financial burden in dependent stroke survivors is an important focus. The findings suggested that hospital administrators and healthcare providers should prepare and tailor financial programs and support systems. Policymakers should also consider these factors when developing social welfare policies to mitigate the long-term financial burden on family caregivers. Nurses in Thailand still remain a valuable source of social support for family caregivers, helping them manage health concerns and reduce financial burdens.
This study aims to explore the impact of fertility stress on depressive symptoms, with a focus on analyzing the potential mediating effects of infertility stigma and family function in this process. A cross-sectional design was employed in which 1294 female partners of infertile couples were recruited from two tertiary-grade A hospitals in Hainan Province, China. Fertility stress, depressive symptoms, infertility stigma, and family function were assessed with validated self-report questionnaires. Structural equation modeling (SEM) was used to estimate the direct effect of fertility stress and the parallel mediating effects of infertility stigma and family function. The prevalence rate of depressive symptoms was 26.35%. The direct effect model indicated a significant positive association between fertility stress and depressive symptoms (β = 0.260, p < 0.001). The parallel mediation model revealed that infertility stigma (β = 0.176, p < 0.001) and family function (β = 0.052, p < 0.001) exerted full mediating effects. Specifically, fertility stress indirectly increased depressive symptoms by exacerbating infertility stigma; concurrently, low levels of family function exacerbated the negative impact of fertility stress on mental health. Fertility stress not only directly affects depressive symptoms, but also indirectly exacerbates depressive symptoms by intensifying infertility stigma and impairing family function. This study provides a new perspective for understanding the mental health mechanism in female partners of infertile couples, emphasizing that psychological interventions need to simultaneously focus on reducing infertility stigma and improving family function, which may offer a basis for informing relevant clinical practices and public health policies.
Abscisic acid (ABA) plays a central role in regulating plant growth and development and in mediating responses to both biotic and abiotic stresses. PYL proteins serve as the core receptors in the ABA signaling pathway. The characteristics of the PYL gene family and its response to abiotic stresses in mung bean (Vigna radiata L.) have not been clarified. In this study, we performed genome-wide screening of mung bean and identified nine PYL genes unevenly distributed across six chromosomes. Bioinformatic predictions revealed that all encoded VrPYL proteins are predicted to be hydrophilic and primarily localized to chloroplasts and the cytoplasm. Segmental duplication was the primary driver of the expansion of this gene family, with duplicated gene pairs having undergone purifying selection during evolution. Phylogenetic analysis showed that VrPYL proteins were divided into three groups, and members within each group exhibited conserved exon-intron structures and motif composition. Homology and synteny analyses indicated that the PYL gene family has remained relatively conserved among mung bean and other plant species. A protein domain analysis demonstrated that all VrPYL proteins contained the "helix-clamp" domain typical of the PYL gene family. Notably, the third and fourth amino acid residues within the CL2 region exhibited marked polymorphism: the valine-valine (VV) motif was the predominant combination, while the valine-threonine (VT) variant displayed mung bean-specific characteristics. Cis-element analysis of the VrPYL gene promoters revealed diverse hormone-responsive and stress-responsive elements. Furthermore, qRT-PCR assays showed that most VrPYL genes responded to ABA, PEG and salt stress treatments, with VrPYL3 and VrPYL4 emerging as promising candidate genes in response to drought and salt stress. Overall, this study lays a foundation for investigating the functions of VrPYL genes in abiotic stress responses and provides valuable genetic resources for molecular breeding.
BackgroundMost adolescent and young married women (AYMW) in Pakistan face challenges with access to contraceptives and associated services despite their high demand.ObjectiveThis research aimed to investigate the determinants of unmet needs for family planning (UMNFP) among AYMW in Pakistan.DesignWe have utilized the cross-sectional data of the 740 AYMW. The data was obtained from the Pakistan Demographic and Health Survey (PDHS) 2017-18.MethodsDescriptive and multivariable logistic regression analyses were performed using SPSS version 24.ResultsThe prevalence of UMNFP among AYMW was 58.9%. The result also showed that UMNFP was significantly higher among AYMW with secondary school education as compared with no education (AOR = 1.278, 95% CI = 1.045, 2.751), belonged to poorer wealth quintiles as compared to those poorest wealth quintiles (AOR = 1.256, 95% CI = 1.044, 2.775), those who faced opposition to using contraceptives from their husband (AOR = 1.433, 95% CI = 1.007, 3.348), who had a fear of contraceptive's side effects (AOR = 1.728, 95% CI = 1.127, 4.335), lack of access to family planning services (AOR = 3.596, 95% CI = 1.528, 5.543), and high cost of contraceptive (AOR = 3.093, 95% CI = 1.813, 4.719).ConclusionWe conclude that fear of side effects for using contraceptives, lack of access to contraceptive services, and the high cost of contraceptive methods are the primary factors of high UMNFP among AYMW in Pakistan. Measures are required to empower women's socio-economic profile, and they need to implement strategies to improve the educational status and instill behavior change regarding contraceptive acceptance and safety in females and men. Based on the empirical evidence, this research proposes a comprehensive policy strategy to meet the objectives of Sustainable Development Goal (SDG) 3, specifically target 3.7.1, that directly addresses the unmet need for family planning.
Engaging people with lived experience (PWLE) and family members (/F) in mental health and/or substance use health research is an increasingly common practice and has many benefits. However, challenges are also encountered; these challenges include the experience of unequal power dynamics on research teams. This pragmatic qualitative descriptive study aimed to understand the experience of power dynamics in mental health/substance use health research engagement contexts, using an engagement framework. Four focus group discussions were conducted with 18 PWLE/F aged 19-79 who had experience engaging in mental health and/or substance use research. A co-designed semi-structured interview guide was used. Discussions were audio recorded, transcribed, analysed using codebook thematic analysis and discussed with a Lived Experience Working Group. Three primary themes were generated from the data: (1) Leadership, knowledge and expertise generate power. (2) Power dynamics should be acknowledged and balanced to improve research quality. (3) Power can be shared through authentic engagement practices. While knowledge and expertise generate power, researchers are not the only ones to hold knowledge and expertise, which necessitates the sharing of power. The mitigating strategies to help research teams address power are consistent with recommendations for conducting authentic engagement as a whole. Following best practices for PWLE engagement can help balance power dynamics on engaged research teams. All aspects of this study were guided by a Lived Experience Working Group, from the identification of the research question to the interpretation and reporting of the results. People with lived experience and family members are co-authors on this manuscript.
SUMMARYThe mycobacterial cell envelope, one of the most complex membranes found in bacteria, plays a major role in bacterial pathogenesis, virulence, and antimicrobial resistance. Biogenesis and modeling of this cell envelope are heavily influenced by the mycobacterial membrane protein large (MmpL) family of transporters due to their ability to export fatty acids and lipid components. Select MmpL transporters can also function as siderophore exporters to help regulate the acquisition of iron, which is critical for mycobacterial survival. Additionally, certain MmpLs can participate in active efflux of antimycobacterial drugs, directly contributing to antimicrobial resistance. Given the physiological significance of these MmpL membrane proteins and their potential to serve as important antimycobacterial targets, questions regarding their functional roles, cellular assemblies, interactions, and regulation need to be fully addressed. In this review, we summarize our current knowledge on the structures and functions of these MmpL transporters. It is our hope that researchers in the field will continue to build upon these efforts and apply various structural, biophysical, and biochemical methodologies to fully elucidate how MmpL transporters coordinate to participate in cell envelope biogenesis, cell elongation and division, and antimicrobial resistance.
BackgroundPeritoneal fibrosis (PF) limits the long-term use of peritoneal dialysis (PD), with effective therapies lacking. Ferroptosis, an iron-dependent cell death process, has been implicated in organ fibrosis, but its role in PD-related PF remains unexplored. Quercetin, a natural flavonoid, possesses potential anti-fibrotic and anti-ferroptotic properties.MethodsPD effluent cells from patients with different dialysis durations were analyzed for the expression of fibrosis markers (α-smooth muscle actin and collagen I) and ferroptosis-related markers (glutathione peroxidase 4 (GPX4) and solute carrier family 7 member 11 (SLC7A11)). In vitro, human peritoneal mesothelial cells (MeT-5A) exposed to high glucose were treated with quercetin to examine its effects on mitochondrial ultrastructure and marker expression. A rat model of PF was established through daily intraperitoneal injection of high-glucose dialysate, with or without quercetin administration, to evaluate histological and molecular changes in the parietal peritoneum.ResultsProlonged dialysis duration was associated with upregulated fibrotic markers and downregulated ferroptosis-related genes in patient samples. In vitro, high glucose induced mitochondrial damage and a profibrotic phenotype in MeT-5A cells, which were significantly attenuated by quercetin. Quercetin restored the expression of GPX4 and SLC7A11, comparable to the effects of the ferroptosis inhibitor ferrostatin-1. In vivo, quercetin treatment markedly alleviated high-glucose-induced peritoneal thickening and fibrosis while enhancing the expression of ferroptosis suppressors.ConclusionOur findings demonstrate that ferroptosis contributes to the pathogenesis of PD-associated PF. Quercetin mitigates fibrotic progression by modulating ferroptosis, highlighting its promise as a novel therapeutic agent for preventing or treating this complication.
Burn injuries in elderly patients often present complex clinical and psychological challenges, especially when compounded by functional decline, emotional vulnerability, and spiritual distress. This case series illustrated a holistic psychotherapeutic approach implemented in a consultation-liaison psychiatry (CLP) setting for three elderly burn patients, each with unique psychological and spiritual needs. Interventions included supportive psychotherapy to address anxiety and mood disturbances, involvement of family members to enhance emotional security and reduce treatment resistance, spiritual facilitation aligned with patients' religious values, and cognitive reorientation techniques to manage episodes of acute confusion and delirium. These tailored approaches proved effective in improving patients' emotional adjustment, cooperation with care, and treatment adherence. The integration of psychotherapeutic, familial, and spiritual interventions underscores the importance of culturally sensitive and individualized CLP strategies for elderly burn survivors. However, the findings are limited by the small sample size and the qualitative nature of the data, which may restrict generalizability. Nevertheless, these observations highlight the value of interdisciplinary collaboration in optimizing recovery and psychological well-being among older adults in burn units. Les brûlés âgés posent souvent des problèmes cliniques et psychologiques complexes, particulièrement quand ils s’intègrent dans un contexte de déclin cognitif, fragilité émotionnelle et détresse spirituelle. Nous rapportons les cas de 3 patients âgés brûlés ayant chacun des besoins psychologiques et spirituels spécifiques, pris en charge de manière globale via une consultation de psychiatrie de liaison. Les interventions associaient support psychothérapeutique devant l’anxiété et les troubles de l’humeur, l’implication de la famille pour optimiser la sécurité émotionnelle et améliorer l’observance thérapeutique, l’intervention d’aumôniers selon les convictions religieuses et techniques de réorientation cognitive en cas de confusion ou de délire. Elles se sont révélées efficaces en améliorant l’état émotionnel, la participation aux soins et l’adhésion au traitement. Cette intégration des participants souligne l’importance des stratégies intégratives individualisées dans la prise en charge des patients brûlés âgés par les équipes de psychiatrie de liaison. Cependant, la généralisation des résultats de cette courte série est aléatoire. Toutefois, ceci met en avant la nécessité d’une approche pluridisciplinaire du traitement et du bien-être psychologique des patients âgés hospitalisés en CTB.
Asylum-seeking populations face a disproportionate burden of adverse mental health outcomes, yet empirical evidence on the factors that promote resilience and empowerment within these communities remain limited. This exploratory qualitative study examined the lived experiences of asylum-seeking parents through the lens of the family resilience model. Semistructured, in-depth interviews were conducted with 13 low-income Eritrean asylum-seeking parents in Israel, aged 25-40, most of whom resided in two-parent households. Data were analyzed, and themes were derived inductively using constructivist grounded theory principles, with the family resilience model serving as an orienting framework rather than a deductive coding scheme. Findings indicate that disruptions in the normal life continuum across three domains-legal rights, identity perception, and the intergenerational family continuum-generate a cumulative cycle of risk and vulnerability that challenges mental health and overall family functioning. Concurrently, protective and adaptive processes operating within the nuclear family, as well as the personal and community levels, form a multilayered support system that fosters resilience and empowerment. This study contributes to existing literature on strength-based approaches and offers policy and practice recommendations aimed at supporting asylum-seeking families. (PsycInfo Database Record (c) 2026 APA, all rights reserved).
Family Nurse Practitioner (FNP) programs often lack structured preclinical competency verification, which delays identification of learning needs and creates patient safety risks. Although registered nurses demonstrate sophisticated clinical judgment within team-based practice, FNP practice demands autonomous diagnostic reasoning, generating differential diagnoses and formulating management plans. This shift requires intentional educational support through formative assessment. At one Western United States public university FNP program, students entered practicum without standardized preclinical evaluation. Faculty observed wide variation in preparedness, from overconfidence to hesitation. This single-cohort, mixed methods pilot educational program evaluation implemented a formative preclinical Objective Structured Clinical Examination for 12 FNP students to evaluate confidence in primary care assessment and diagnostic reasoning while exploring curriculum integration feasibility. Students rated confidence using the Simulation Effectiveness Tool-Modified; faculty used the Lasater Clinical Judgment Rubric. Structured debriefings and surveys captured qualitative data. Two 30-minute standardized patient encounters, an adult and pediatric wellness visits incorporating anemia recognition, followed International Nursing Association for Clinical Simulation and Learning standards. Prebriefing, encounters, documentation, and debriefing integrated Kolb's experiential learning and Tanner's clinical judgment frameworks. Students reported moderate confidence in primary care assessment (M = 2.32) and diagnostic reasoning (M = 2.26), with lower confidence in clinical decision making (M = 1.70). Faculty ratings paralleled student self-assessments: highest in noticing (M = 2.7), lowest in reflecting (M = 2.0). Students (M = 3.90) and faculty (M = 4.89) rated the Objective Structured Clinical Examination as educationally valuable and appropriate; however, faculty expressed sustainability concerns (M = 2.44). The preclinical Objective Structured Clinical Examination provided structured opportunity for diagnostic reasoning practice and identification of learning needs before practicum entry, demonstrating feasibility within competency-based FNP education.
Background: This study investigated influenza vaccination coverage and its predictors among medical staff in multiple Chinese regions to develop targeted vaccination promotion measures.Methods: A cross-sectional questionnaire survey was conducted on medical workers from Beijing, Hebei, Hunan, Shaanxi, Yunnan and other provinces. Questionnaires collected demographic information, influenza/vaccine knowledge, personal and family vaccination history, and vaccine-related health beliefs. We calculated intra-class Correlation Coefficient (ICC) to evaluate hospital clustering due to nested data, adopted binary logistic regression as primary analysis, and applied two-level multilevel logistic regression to correct biased standard errors for robustness.Results: 476 valid questionnaires were retrieved from 483 distributed ones (98.6%). ICC = 0.021 suggested negligible hospital clustering, and the overall vaccination rate was only 16.4% (78/476). Multivariate analysis identified three positive predictors: vaccine training (OR = 2.503, 95% CI 1.337-4.686), family influenza infection (OR = 2.606, 95% CI 1.338-5.076) and family vaccination (OR = 8.266, 95% CI 4.100-16.663). Perceived barriers negatively predicted uptake (OR = 0.589, 95% CI 0.452-0.767). Staff in primary hospitals had higher coverage than those in tertiary hospitals (OR = 3.640, 95% CI 1.420-9.333).Conclusion: The overall influenza vaccination rate among medical staff remains relatively low. To increase the vaccination rate, in addition to strengthening professional training on influenza vaccine-related knowledge, it is also essential to optimize vaccination accessibility and foster a positive social and occupational vaccination atmosphere. Meanwhile, based on the health belief model of influenza vaccination, targeted health education should be carried out by focusing on reducing perceived barriers and improving health beliefs, so as to effectively enhance the influenza vaccination status of medical staff.
Multiple morphological abnormalities of the sperm flagella (MMAF), uncommonly causing primary infertility, are typical features of aberrant spermatozoa flagellum morphologies, which manifest as shortness, absence, bending, coiling, and irregularity of flagella. CFAP44, an important component of flagella assembly, has attracted significant interest due to its critical role in MMAF pathogenesis. Understanding the variants associated with CFAP44 can provide insights into the molecular mechanisms underlying MMAF. A comprehensive clinical evaluation was conducted on an infertile Chinese male patient from a nonconsanguineous family with sever asthenozoospermia (no progressive sperm). By performing whole-exome sequencing (WES), a novel variant of CFAP44 was identified. Sanger sequencing was performed to confirm the variant. To better investigate its pathogenicity, In silico variant analyses, minigene splicing assays and RT-PCR in vivo were performed. As a result, a CFAP44 homozygous deep-intronic variant (NM_001164496.1:c.1890+5G>C) was detected in the proband by WES. Sanger sequencing confirmed this variant in this family. Splice site prediction suggested that this variant may be a disease-causing variant. Then, exon 15 skipping was identified through minigene assays and RT-PCR in vivo, resulting in a 111-bp deletion within the mutated sequence, thereby indicating a disruption in the normal splicing of the CFAP44 transcript. This is the first study to detect a homozygous variant (c.1890+5G>C) within the CFAP44 gene causing MMAF in a Chinese family. Our results confirmed the pathogenicity of this deep-intronic variant and expanded the mutational spectrum of the CFAP44 gene. Consequently, this study may help elucidate the effect of CFAP44 on MMAF and provide a theoretical basis for MMAF.
Adipose tissue-derived stem cells (AdSCs) are widely used for regenerative medicine purposes. There is always a need to accelerate cell proliferation and protect the cells from apoptosis when cell transplantation, especially AdSCs, is targeted. Therefore, this study evaluated the effect of lithium chloride on the proliferation and growth kinetic of AdSCs. The study was undertaken in the Stem Cell Technology Research Center, Shiraz University of Medical Sciences, Shiraz, Iran, in 2020. Adipose tissue specimens were provided from the abdominal region of a 35-year-old woman. In an in vitro study, human AdSCs were characterized morphologically, by osteo- and adipogenic differentiation properties, and by flow cytometry. They were later treated with lithium chloride to evaluate its effect on cell proliferation and the growth kinetics of AdSCs. 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay investigated lithium chloride effect on the proliferation rate and apoptosis of AdSCs. Quantitative Real Time Polymerase Chain Reaction (qPCR) was carried out to determine the expression of apoptosis genes of Apoptosis Regulator BCL2 Associated X (BAX) and B-cell lymphoma 2 (Bcl-2) protein family. AdSCs showed mesenchymal characteristics, and lithium chloride at a dose of 6 µM had an increasing impact on cell proliferation and protected the cells from apoptosis. A non-significant increase in expression of the Bcl-2 gene (P=0.057) and a significant decrease in BAX gene (P=0.034) expression were visible. Our findings indicate that the addition of lithium chloride to the culture medium enhanced the proliferation of AdSCs and protected them against apoptosis.
Medicinal plants serve as invaluable sources of bioactive compounds, yet the molecular basis of their secondary metabolite biosynthesis remains largely unexplored. Piper chaba Hunter, an important but understudied member of the Piperaceae family, is known for its pharmacologically active alkaloids, particularly piperine. To our knowledge, this is the first de novo transcriptomic profiling of spike, leaf, and root tissues of P. chaba to uncover the genetic pathways regulating its metabolite production. Piperine, a major bioactive compound, was quantified using UPLC. The highest concentration was observed in the spike (331.3 mg/g), followed by the root (10.3 mg/g) and leaves (2.82 mg/g). High-quality RNA sequencing of leaves, roots, and spikes using next-generation sequencing (NGS) generated 228,481 transcripts, and 184,574 unigenes were identified after redundancy removal. Coding sequences (CDSs) derived from these unigenes were annotated using BLASTX and KEGG databases, which highlighted significant metabolic pathways, including those related to piperine biosynthesis. Thirteen candidate genes potentially associated with the piperine biosynthetic pathway were identified based on transcriptome annotation and pathway analysis. Validation of nine selected genes, including farnesyl pyrophosphate synthase and piperic acid synthase, was performed through qRT-PCR using the 2-ΔΔCt method, supporting their expression patterns potentially associated with piperine and related metabolite biosynthesis. Functional annotation categorized the CDS into Gene Ontology domains, with transcription factors such as bHLH and NAC families playing prominent roles in metabolic regulation. Additionally, 5050 SSRs were identified, offering potential markers for genetic studies. This pioneering study establishes a molecular framework for understanding the biosynthetic pathways of P. chaba, providing valuable insights for its application in sustainable medicine and agriculture.
Glypican-3 (GPC3) belongs to the glypican family of heparan sulfate proteoglycans and is frequently overexpressed in hepatocellular carcinoma (HCC). The overexpression of GPC3 is associated with the poor clinical outcomes, suggesting its potential as a clinically relevant biomarker and therapeutic target. Therefore, anti-GPC3 monoclonal antibodies (mAbs) have been developed in various modalities for tumor diagnosis and therapy. In this study, 88 clones of novel anti-GPC3 mAbs were established using a flow cytometry-based high-throughput screening, the Cell-Based Immunization and Screening (CBIS) method. Among them, a clone G3Mab-25 (IgG1, κ) recognized GPC3-overexpressed Chinese hamster ovary-K1 (CHO/GPC3) but not parental CHO-K1 in flow cytometry. Furthermore, G3Mab-25 recognizes endogenous GPC3 in GPC3-expressing HCC cell lines, including HepG2, HuH-7, and JHH-5. G3Mab-25 specifically recognized only CHO/GPC3, but not other GPC family-overexpressed CHO-K1. The dissociation constant values of G3Mab-25 for CHO/GPC3, HepG2, HuH-7, and JHH-5 were determined to be 1.8 × 10-8 M, 7.3 × 10-9 M, 3.9 × 10-9 M, and 1.4 × 10-9 M, respectively. Moreover, G3Mab-25 detects the N-terminal fragment of GPC3 in western blotting. In immunohistochemistry, G3Mab-25 showed a diverse staining pattern for GPC3 in HCC tissues. G3Mab-25, established by the CBIS method, is a versatile mAb for basic research and is expected to contribute to tumor diagnosis and therapy.
Ultra-processed foods (UPFs) are industrial formulations characterized by high energy density, low nutritional quality, and the extensive use of additives, and their consumption has increased markedly worldwide. In many high-income countries, children and adolescents now derive up to 50-60% of their total daily energy intake from UPFs, raising major public health concerns. This narrative review synthesizes current evidence on UPF consumption across critical life stages, with a particular focus on pregnancy, childhood, and adolescence, and examines its potential implications for short- and long-term health outcomes. Available evidence consistently links high UPF intake in pediatric populations to excess weight gain, metabolic syndrome, and early cardiovascular risk. Additional adverse outcomes include dental caries and a higher prevalence of allergic diseases, such as atopic dermatitis and asthma. Several biological mechanisms may mediate these associations, including impaired satiety regulation, excessive intake of free sugars and saturated fats, disruption of the food matrix, and alterations in gut microbiota composition, immune function, and inflammatory pathways. Emerging research also indicates that exposure to UPFs may begin before birth, as maternal consumption during pregnancy and lactation has been associated with unfavorable offspring outcomes, including altered neurodevelopment, increased adiposity, and immune-related conditions. Familial, socioeconomic, and behavioral factors strongly influence early exposure to UPFs. Modifiable determinants such as breastfeeding duration, parental nutrition literacy, shared family meals, and screen time represent key targets for preventive interventions. Overall, the evidence highlights the urgent need for life-course-oriented nutritional strategies that promote unprocessed and minimally processed foods, reinforce family-based nutrition education, and support healthy dietary patterns from pregnancy through childhood and adolescence to reduce the long-term burden of non-communicable diseases.
THAP1-associated dystonia (DYT-THAP1) is classically described as an early-onset disorder with craniocervical involvement and potential for generalization. However, increasing reports suggest a broader phenotypic spectrum, including adult-onset presentations. We aimed to characterize the clinical phenotype of genetically confirmed DYT-THAP1 with age at onset ≥ 40 years, and to highlight an illustrative case. A scoping review was conducted following Joanna Briggs Institute methodology. Comprehensive searches of PubMed, MDSGene, Google Scholar, and regional databases identified studies reporting patient-level clinical data in individuals with genetically confirmed THAP1 mutations and late-onset disease. Data on age of onset, site of onset, distribution, sex, family history, mutation geste antagoniste were extracted and synthesized descriptively. Twenty-two studies comprising 50 patients met the set inclusion criteria. Cranial dystonia was the most common site of onset (n = 22), followed by cervical (n = 13), while limb onset was uncommon. Most patients presented with segmental distribution (n = 27), followed by focal (n = 20), and only 3 cases demonstrated generalized involvement. The majority of cases were sporadic (37/50). Associated clinical features and geste antagoniste were infrequently and inconsistently reported across studies. We additionally present a Filipina with late-onset focal lower limb dystonia, further highlighting an atypical pattern of limb onset. Collectively, these findings suggest that late-onset THAP1-associated dystonia may exhibit a phenotype distinct from classical early-onset presentations characterized by cranial and cervical predominance, segmental distribution, and frequent sporadic occurrence. Recognition of this broader phenotypic spectrum may facilitate consideration of genetic etiologies in adult-onset dystonia, even in the absence of a family history.
To develop a Retrieval-Augmented Generation (RAG) question-answering system for stroke patients and family caregivers, and evaluate its performance and usability. We constructed a localized knowledge base using clinical practice guidelines, consensus, expert opinion, textbooks, systematic review, evidence summary, and peer-reviewed literature. Three LLMs (GPT-4o, Claude3.7, and Qwen3) were first evaluated for accuracy using 184 exam questions under zero-shot and RAG configurations. Thirty open-ended stroke-related questions were assessed by three experienced clinicians across four dimensions. Usability testing was conducted with 20 stroke survivors and family caregivers using the best-performing model, measuring System Usability Scale (SUS) and Net Promoter Score (NPS). RAG integration improved accuracy, relevance, and completeness across all three LLMs, with GPT-4o under RAG configuration achieving the highest overall mean score. However, the addition of RAG slightly reduced understandability for Claude3.7 and Qwen3. Usability testing yielded high acceptance. RAG can enhance the reliability of LLM-generated responses in stroke-related questions, offering trusted, guideline-based information. The high usability ratings suggest early feasibility for real-world deployment, while future research should assess its linguistic accessibility and long-term clinical benefits in real-world caregiving contexts.
Glucose-regulated Protein 78 (GRP78, also known as BiP/HSPA5) is a central member of the Hsp70 family. As a key molecular chaperone in the endoplasmic reticulum (ER), it plays an important role in cell survival and biological function by maintaining protein folding homeostasis and regulating endoplasmic reticulum stress (ERS) and the unfolded protein response (UPR). Its function is precisely regulated by various post-translational modifications (PTMs), including phosphorylation and acetylation. In addition, GRP78 can translocate to subcellular locations such as the cell membrane and nucleus, where it performs non-classical functions under stress conditions. Under pathological states, the aberrant expression and function of GRP78 are extensively involved in the onset and progression of diverse human diseases, including cancer, neurodegenerative diseases, infectious diseases, cardiovascular diseases, inflammatory diseases and metabolic diseases, and often exhibit a dual role dependent on tissue specificity and disease stage. To date, a variety of intervention strategies have been developed, such as small-molecule modulators, antibodies and genetic intervention approaches. These strategies have demonstrated promising potential in preclinical studies, yet are confronted with challenges including insufficient specificity and delayed clinical translation. This paper systematically elucidates the structure, PTMs, biological functions and disease regulatory mechanisms of GRP78, summarizes the existing intervention strategies, and discusses the unresolved issues and future research directions in this field. Future research should focus on developing highly specific regulatory tools and integrating precision medicine strategies to advance the clinical translation and application of GRP78 as a therapeutic target.
Extracellular vesicles and EV-enriched extracellular particles are increasingly recognized as potential mediators of intercellular communication. In coral reef ecosystems, dinoflagellate symbionts of the family Symbiodiniaceae play central roles in host metabolism, environmental acclimation, and stress responses; however, the molecular composition of extracellular particles released by cultured Symbiodiniaceae remains poorly understood. In this study, a host-isolated Symbiodiniaceae culture derived from the sea anemone Exaiptasia diaphana was established under host-free laboratory conditions for EV-enriched particle isolation and characterization. Physicochemical analysis of the recovered extracellular particle fraction showed an average diameter of 534.1 ± 63.9 nm, a polydispersity index of 0.733 ± 0.08, and an average zeta potential of - 14.57 ± 1.55 mV, indicating a heterogeneous and negatively charged extracellular particle suspension. Small RNA analysis showed that the EV-associated RNA fraction contained multiple RNA biotypes, with rRNA- and tRNA-derived reads representing the dominant annotated components, whereas miRNA-like sequences accounted for only a minor fraction of the annotated small RNA pool. Comparison against an antisense Exaiptasia diaphana CDS dataset further identified retained EV-associated small RNAs showing sequence complementarity to host coding transcripts, including cytohesin-1 and EPG5. These matches are interpreted as candidate sequence-level observations rather than evidence of functional host regulation. In parallel, miRNA-oriented analysis identified candidate miRNA-like sequences after downstream filtering. Proteomic profiling by LC-MS/MS generated 4,086 accession-level matches. After removal of uninformative entries and consolidation of duplicate protein names, 834 non-redundant named proteins were retained and classified into nine functional groups, including proteins involved in metabolism and energy production, transport and membrane trafficking, photosynthesis and chloroplast function, and signal transduction and regulation. Representative annotations included 14-3-3-related proteins, Rab/ARF family proteins, Hsp70, Hsp90, and oxygen-evolving enhancer protein. These results provide an initial qualitative molecular characterization of EV-associated molecules released by a host-isolated Symbiodiniaceae culture and serve as a baseline for future studies of algal extracellular communication and cnidarian-dinoflagellate symbiosis.