Inflammation is a defining feature of the tumor microenvironment (TME) and a key driver of cancer progression. Among inflammatory mediators, the interleukin-1 (IL-1) family of cytokines serves as a central mediator linking tissue damage, metabolic stress and microbial cues to innate immune activation. Myeloid cells are major components of this network, with macrophages and neutrophils acting both as highly responsive targets of IL-1 family signaling and as important sources of IL-1 family cytokines, thereby establishing self-reinforcing inflammatory loops within tumors. Recent advances in single-cell and spatial analyses have revealed the remarkable heterogeneity of tumor-associated macrophages (TAMs) and tumor-associated neutrophils (TANs), highlighting how IL-1 family cytokines shape their recruitment, differentiation, and functional reprogramming in cancer. In turn, myeloid-derived IL-1 family cytokines contribute to inflammatory networks that influence tumor growth, immune suppression, and stromal remodeling. Here, we review the reciprocal interactions between IL-1 family cytokines/receptors and myeloid cells in cancer, focusing on how IL-1 family members instruct macrophage and neutrophil responses and how these cells shape IL-1 family-driven inflammatory circuits in the TME.
To clarify the clinical characteristics of type 2 diabetes in adolescents and young adults (T2DMY) patients, and their treatment strategies involving Traditional Chinese Medicine (TCM) and Western Medicine. This study was conducted at Dongfang Hospital of Beijing University of TCM. Clinical data of outpatients and inpatients from 2011 to 2023 were retrieved from the electronic medical record database with type 2 diabetes mellitus (T2DM) as the first diagnosis. A total of 405 outpatients and 570 inpatients with T2DMY were included in the analysis. Compared with middle aged and elderly T2DM patients (T2DME), T2DMY patients have a higher proportion of diabetes family history and higher body mass index, poorer control of blood glucose, blood lipid, liver and kidney function, and a higher incidence of non-alcoholic fatty liver disease and gout. In terms of anti-diabetes treatment, T2DMY patients are more likely to receive metformin and insulin drugs. In terms of TCM diagnosis and treatment, compared with T2DME patients, T2DMY patients are more frequently diagnosed with the syndrome of phlegm damp trapped spleen, and more herbs such as Fuling (Poria) and Chenpi (Pericarpium Citri Reticulatae) are more frequently used to invigorate the spleen and dispel dampness. Compared with T2DME patients, T2DMY patients have worse metabolism. In the treatment of TCM, more attention can be paid to the function of the spleen, and the herbal medicine can be used to enhance the function of the spleen and dispell dampness when it is compatible with Qitonifying drugs.
Grief is typically conceptualized as an individual process, yet it unfolds within families and is shaped by its dynamics. We conducted a systematic review to synthesize evidence examining how family dynamics influence grief responses. A pre-registered review (PROSPERO registration: CRD420251061451) was conducted in accordance with PRISMA guidelines. Four databases (CINAHL, Scopus, PsycINFO, Medline) and gray literature were searched to identify studies that reported original data, involved two or more members of multiple families, and focused on post-death grief, with the last search in June 2025, yielding 7,806 records. Twenty-nine studies met inclusion criteria and methodological quality was assessed. Findings were narratively synthesized into four themes: communication and cohesion, caregiver influence on child adjustment, roles and reorganization, and cultural and societal influence. Evidence was limited by self-report measures, retrospective data, and cross-sectional designs. Findings suggest that addressing family dynamics in clinical practice, community programs, and policy may promote healthier adaptation following bereavement.
To investigate the effects of moxibustion at Zusanli (ST36) on ferroptosis-related proteins in synovial inflammation of rats with rheumatoid arthritis (RA) and verify the mechanism by cell experiments. A RA rat model was established using a "disease-syndrome integration" modeling method. The rats were randomly divided into a blank control group (Control group) and a model replication group. Rats with successfully replicated RA models were further divided into a model control group (RA group) and a moxibustion treatment group (RA + Mox group). After intervention, the rats' ankle swelling degree and small animal ultrasound examination were conducted and synovial tissue was examined for pathology, lipid reactive oxygen species (ROS) detection, ferrous ion Fe2+ double staining, and immunohistochemistry analysis. Serum from three groups of rats were extracted and used for cellular assays, cell counting kit-8 and Western blot validation. (a) Compared to Control group rats, RA rats showed significantly increased footpad swelling (P < 0.01) and joint inflammation levels (P < 0.001); compared to RA group, the RA + Mox rats showed significantly decreased footpad swelling (P < 0.05) and joint inflammation levels (P < 0.01). (b) There was no difference in lipid ROS levels in the synovial tissue of RA rats compared to Control group rats (P > 0.05), but the lipid ROS levels in the synovial tissue of RA + Mox rats were significantly increased (P < 0.01). Compared to Control group rats, RA rats had significantly lower Fe2+ levels (P < 0.05); compared to RA rats, the Fe2+ levels in RA+Mox rats were significantly increased (P < 0.01). There was no significant difference in beclin 1(BECN1) expression in the synovial tissue of RA rats compared to Control group rats (P >0.05), but BECN1 expression in the synovial tissue of RA + Mox rats was significantly increased (P < 0.01) compared to RA rats. Compared to Control group rats, RA rats had significantly higher Solute Carrier Family 7 Member 11 Gene (SLC7A11) levels in synovial tissue (P < 0.05); compared to RA rats, the SLC7A11 levels in RA + Mox rats were significantly decreased (P < 0.05). (c) In the lipopolysaccharides (10 ng/mL) model, 50% concentration of RA rats serum promoted human RA fibroblast-like synovial cell line (MH7A) proliferation (48 h) (P < 0.05) and 50% concentration of RA + Mox rat serum inhibited MH7A proliferation (48, 72 h) (P < 0.001). Both 25% and 50% concentrations of RA + Mox rat serum upregulated BECN1 and downregulated SLC7A11 expression in MH7A. Moxibustion at Zusanli (ST36) suggests a potential to relieve footpad swelling and synovial inflammation in RA rats, alleviate synovial tissue hyperplasia and thickening. It may induce lipid ROS accumulation in synovial tissue, upregulating Fe2+ levels, upregulating BECN1 expression, and downregulating SLC7A11 expression in RA rats. Moreover, 50% concentration of rat serum after moxibustion inhibited the proliferation of synovial fibroblasts and regulated the expression of ferroptosis-related proteins.
Against the backdrop of China's aging society and under the macro policy of building a Healthy China proposed at the Fifth Plenary Session of the 18th Central Committee of the Communist Party of China, the dissemination of Traditional Chinese Medicine (TCM) health knowledge has emerged as particularly crucial and imperative. This paper systematically examines the current status of TCM health knowledge dissemination in China. It identifies multiple challenges in the dissemination process, including multidimensional constraints related to content dissemination, media channels, and audience characteristics. Drawing on these findings, this paper proposes a strategic framework centered on high-quality content, with standardized media platforms as key hubs and audience empowerment as the ultimate goal.
WD40-repeat (WDR) proteins constitute one of the largest and most functionally diverse scaffold families in eukaryotes. By folding tandem WD repeats into β-propeller domains, they provide modular interaction surfaces that assemble multi-protein complexes governing transcription and epigenetic control, ubiquitin-dependent proteostasis, RNA metabolism, and cell-cycle progression. Despite their pervasive involvement in oncogenic signaling and hallmark cancer phenotypes, the cancer field still lacks an integrated framework that connects WDR structural logic to context-dependent mechanisms and, critically, to actionable biomarkers and therapeutic strategies; existing evidence remains dispersed across tumor types and molecular pathways. This review synthesizes current knowledge to address that gap. We first summarize core structural principles of WD40 β-propellers and explain how multivalent binding and partner selection enable WDR proteins to function as assembly platforms in oncogenic networks. We then consolidate mechanistic evidence showing how representative WDR proteins shape malignant state transitions, including sustained proliferation, survival under stress, epigenetic plasticity, invasion and metastasis, and therapy resistance, by rewiring chromatin programs, ubiquitination circuits, and RNA and translation outputs across cancers. Finally, we highlight translational progress and opportunities. Overall, this review integrates the fragmented WDR research into a clinically oriented framework that clarifies their potential as biomarkers for early detection, stratified diagnosis, and treatment-response prediction, and delineates druggable entry points and rational combination strategies, thereby providing a translational roadmap to enable more precise cancer diagnosis and more effective targeted therapies in the future.
Advances in neonatal and pediatric critical care have expanded the focus from short‑term survival to include greater attention to long‑term neurodevelopmental health and family well‑being. This narrative review synthesizes the evolution of neurodevelopmental and neuroprotective care across neonatal (NICU), pediatric (PICU), and cardiovascular (CVICU/PCICU) intensive care settings. Developmental care emerged in the NICU through individualized, cue‑based approaches such as the Newborn Individualized Developmental Care and Assessment Program (NIDCAP), emphasizing stress reduction, protection of sleep, optimized sensory environments, and parent-infant coregulation. As survivorship after critical illness improved, parallel concerns about post‑intensive care morbidities, including cognitive, behavioral, and functional impairments, catalyzed adoption of family‑centered and brain‑focused practices in the PICU, supported by contemporary guidelines integrating pain and sedation optimization, delirium prevention, environmental stewardship, and early mobility. More recently, dedicated cardiac neurodevelopmental programs have adapted NICU principles to the high‑acuity CVICU/PCICU population, pairing hemodynamic vigilance with developmental goals through structured interdisciplinary models (e.g., developmental rounds, holding protocols, early therapy, feeding support, and caregiver mental health resources). Across settings, common implementation domains include family partnership, cue‑based care, protected sleep and circadian support, sensory modulation, humane pain and sedation strategies, early rehabilitation, and coordinated follow‑up after discharge.  While the strength of evidence varies by unit type and outcome, available data support feasibility and potential benefits for delirium reduction, functional recovery, feeding, parent experience, and early developmental trajectories. Continued multicenter research and implementation science are needed to define optimal bundles, equity‑informed delivery, and durable long‑term outcomes. • Neurodevelopmental care is well established in NICUs, emphasizing cue-based care, pain reduction, environmental protection, and family partnership. • Survivors of pediatric and cardiac critical illness remain at risk for cognitive, behavioral, emotional, and functional impairments. • This review extends neurodevelopmental care beyond the NICU to PICU and CVICU settings. • It proposes a unified multidisciplinary framework for brain-focused critical care across pediatric ICU environments.
Family caregivers play a vital role in supporting dependent older adults, particularly during hospital-to-home transitions. Yet their contribution often remains insufficiently documented in nursing records, which may limit the visibility of caregiver-related information across care settings. To examine the visibility of the nursing focus "Caregiver Role" in electronic nursing records of hospitalized older adults and its incorporation into discharge documentation. A retrospective cross-sectional study was conducted using electronic nursing records of 577 patients aged ≥65 years with documented self-care dependence, admitted to an internal medicine department in a European country (January-March 2023). Data were retrieved from the national electronic health record (SClínico®), which uses the International Classification for Nursing Practice (ICNP) to structure nursing diagnoses and interventions. Descriptive statistics were applied. Although caregivers were routinely identified at admission, only 76 patients (13.2%) had at least one documented caregiver-related nursing focus. Among these, 124 caregiver-related diagnosis entries were recorded, most frequently "Committed caregiver role." Interventions were primarily classified under generic categories (e.g., assess, guide). Fewer than 10% of discharge documentation included caregiver-related content. These findings indicate a discrepancy between the identification of family caregivers and their formal integration into nursing care plans and discharge documentation. Improving the systematic documentation of caregiver-related information may enhance the continuity and visibility of caregiver involvement across care transitions.
Adverse experiences during childhood such as family violence, neglect, poverty, poor parental mental or physical health have negative immediate and lifelong impacts on children's health and development. Although many families experience adversities, families experience barriers to seeking support, and many professionals lack confidence to have sensitive conversations with these families. Aiming to inform the development of resources to guide professionals, we undertook a scoping review to (1) identify and describe communication frameworks for professionals and (2) describe if/how they were evaluated. Searches were conducted in Medline, Emcare, PsycInfo, Cumulative Index in Nursing and Allied Health Literature and Scopus from inception to January 2025. Following the Preferred Reporting Items for Systematic reviews and Meta-Analyses extension for Scoping Reviews (PRISMA-ScR), we located 15 communication frameworks contained within 33 manuscripts. Key characteristics of the communication frameworks are presented, such as practice setting and intended users, which adversities were addressed and how they were evaluated. There were two broad types of communication framework, those which required professionals to actively screen and respond to family adversities, and those which provided opportunistic guidance and response without explicit screening. Most communication frameworks were in the global north, and many were not evaluated beyond their initial context. We could not locate any communication frameworks embedded within non-health-related settings, and none comprehensively addressed all adverse experiences known to impact children. Nonetheless, this review identified available evidence that can help inform tailoring and development of communication frameworks to build professionals' capacity for early intervention for family adversities.
Missed nursing care is a common and critical issue in emergency departments, where high patient acuity, time pressure, and frequent interruptions compromise patient safety and care quality, yet no validated emergency-specific missed nursing care scale currently exists in domestic emergency care settings. The aim of this study was to develop a valid and reliable emergency department-specific scale, based on universal and existing specialized scales, to assess missed nursing care in emergency settings. A modified Delphi method was used. A total of 21 experts were invited. The process consisted of two rounds. Preliminary scale items were developed through a literature review, qualitative interviews, and research team discussion based on the missed nursing care theoretical model and Maslow's hierarchy of needs theory. From November 2025 to January 2026, 21 experts in emergency medicine, nursing, and nursing management from various healthcare institutions were invited to participate in two rounds of online Delphi studies. The first round involved rating the initial items' importance, proposing viewpoints and suggestions for improvement and identifying of redundant and/or missing items. The second round re-evaluated and provided feedback on the revised items from the first round. Two Delphi rounds were completed: 21 of 24 invited experts responded in Round 1, and 17 of 21 responded in Round 2. Among 91 statements evaluated in Round 2, 88 (96.7%) achieved consensus (importance score ≥ 4 and CV ≤ 0.25). The ultimately formed Emergency Department Missed Nursing Care Assessment Scale comprises three sections: The Emergency Missed Nursing Care Items include five dimensions: Safety-Related Care, Physiological Needs-Related Care, Affection-Related Care, Respect-Related Care, and Cognitive Needs-Related Care, totaling 43 items. The Emergency Missed Nursing Care Causes dimension comprises seven categories: human resource factors, material resource factors, communication factors, nursing team factors, patient family factors, organizational management factors, and work environment factors, totaling 30 items; The Emergency Missed Nursing Care Outcomes dimension encompasses three categories: patient level, nurse level, and hospital level, totaling 15 items, The overall content validity index (S-CVI) of the scale is 0.87. The Missed Nursing Care Scale, developed using the Delphi method, demonstrates strong content validity, which provides a solid foundation for its scientific rigor. Its reliability is intended to be further verified through large-scale surveys, thereby offering a targeted evaluation tool for investigating missed nursing care in emergency departments. Patient participation is a crucial component in the initial development of this scale. We conducted semi-structured interviews with five patients who had received treatment in the emergency department. These interviews aimed to explore their experiences of missed nursing care during their emergency visits, understand the impacts of such shortcomings, and solicit their suggestions for improving care services. Their insights directly influenced the content and relevance of the preliminary scale items. Additionally, this study included perspectives from healthcare professionals by conducting semi-structured interviews with fourteen emergency department nurses. These interviews examined the issue of missed nursing care from a frontline clinical perspective, focusing on its occurrence in daily practice, influencing factors, and perceived consequences. The feedback from nurses played a crucial role in forming the initial item pool, ensuring the scale's contextual appropriateness and its clinical practicality.
Early life adversity is associated with increased cardiometabolic risk across the life course, potentially via epigenetic mechanisms. However, few studies have prospectively examined how distinct domains of early life adversity influence molecular profiles and cardiometabolic health. In the CHAMACOS cohort, a longitudinal study of rural Latino youth, we measured adversity prospectively from pregnancy through age 7 across six domains: Learning Environment, Parent-Child Interaction, Maternal Adversity, Family Dysfunction, Economic Adversity, and Stressful Life Events. Leukocyte DNA methylation (DNAm) was measured at four timepoints between ages 7 and 18, gene expression (RNA transcripts) at age 14, and body mass index (BMI) and insulin resistance (HOMA-IR) at age 18. Early life adversity was associated with differential DNAm at ages 7, 14, and 18, with 14 Bonferroni- and 101 FDR-significant differentially methylated probes (DMPs) across all timepoints. Economic adversity was the domain most strongly associated with DMPs (4 Bonferroni- and 38 FDR-significant). Methylation changes at several DMPs were significantly associated with BMI and HOMA-IR at age 18. These findings provide longitudinal evidence that early life adversity, particularly economic adversity, becomes biologically embedded via DNAm, with functional and cardiometabolic consequences, highlighting potential targets for early interventions to reduce lifelong disease risk. Difficult experiences in early childhood may raise the risk of heart and metabolic disease later in life, possibly by changing how genes are switched on or off. This study followed a group of Latino children in rural California from before birth through age 18, measuring six types of hardship experienced between the prenatal period and age 7: home learning environment, parent-child relationship quality, mother’s own stress, family dysfunction, economic hardship, and stressful life events.Chemical tags on DNA (called DNA methylation) that control gene activity were measured at four time points between ages 7 and 18, along with gene activity at age 14, and body mass index and insulin resistance at age 18.Children who experienced more early hardship showed measurable differences in DNA methylation at ages 7, 14, and 18. Economic hardship had the strongest influence on these molecular changes. Several of those changes were linked to higher body mass index and worse insulin regulation at age 18.The study suggests that childhood hardship — especially financial hardship — becomes physically embedded in the body at a molecular level, in ways that affect metabolic health into young adulthood. This points to early childhood as a key window for interventions that could reduce metabolic disease risk across a person’s lifetime.
Philadelphia-negative myeloproliferative neoplasms (MPNs) carry a disproportionate thrombotic burden that cannot be explained by conventional cardiovascular risk factors or blood count parameters alone. This review synthesizes emerging evidence positioning MPN-associated thrombosis as a distinct pathobiologic entity, clonal thrombo-inflammation, driven by the convergence of somatic mutations and innate immune activation. We examine the continuum from clonal hematopoiesis of indeterminate potential (CHIP) to overt MPN, highlighting how Janus kinase 2 (JAK2)V617F and other driver mutations reprogram myeloid cells toward hyperinflammatory phenotypes. A recurring mechanistic theme is NOD-like receptor family pyrin domain containing 3 (NLRP3) inflammasome activation and interleukin-1 family signaling, which may create a feed-forward loop in which mutant clones amplify inflammatory circuits that, in turn, may enhance clonal fitness and contribute to thrombogenicity across multiple cellular compartments. We propose the 'thrombotic niche' as a conceptual, multi-compartment model encompassing mutant hematopoietic stem cells, hyperinflammatory myeloid effectors, hyperreactive platelets, platelet-leukocyte aggregates, and activated endothelium, but it remains a hypothesis-generating framework that lacks direct prospective clinical validation. Current cytoreductive strategies inadequately address this underlying biology, leaving substantial residual vascular risk. Emerging anti-inflammatory and anti-clonal strategies targeting interleukin-1 beta (IL-1β) (canakinumab), mutant-selective JAK2 inhibition, NLRP3 inflammasome blockade, and P-selectin-mediated adhesion are biologically plausible, but their ability to reduce thrombotic events in MPN remains unproven and should be viewed as hypothesis-generating rather than established clinical benefit. We conclude by outlining a translational research agenda integrating inflammation-aware risk stratification, niche-directed imaging, and spatial multi-omics to guide precision anti-inflammatory interventions in MPN.
Healthcare professionals other than dietitians are widely perceived as credible sources of nutrition information by patients, despite many of these professionals having received limited nutrition training. Little is known about where healthcare professionals obtain nutrition information and how reliance on various sources of nutrition information relates to their self-perceived nutrition competence. This study aimed to investigate the association between the frequency of accessing nutrition information from evidence-based and non-evidence-based sources and healthcare professionals' self-perceived nutrition competence. A cross-sectional online survey was conducted using a questionnaire adapted from the NUTrition COMPetence (NUTCOMP) tool. Independent variables included self-reported frequencies of accessing various nutrition information sources in the preceding 30 days, measured by Likert-scale questions. The primary outcome was self-perceived nutrition competence assessed by NUTCOMP scores. A robust linear regression model was created to evaluate associations between NUTCOMP scores and frequencies of accessing different nutrition information sources, adjusting for age, sex, profession, education level, workplace, and previous nutrition education. The statistical significance level was set at 0.05. A total of 450 healthcare professionals working in healthcare facilities across China were enrolled, including 302 (67.11%) nurses and 124 (27.56%) doctors. The median NUTCOMP score was 120 (interquartile range 102-141). The most popular information sources were colleagues (n = 293), social media (n = 222), and professional websites (n = 121). More frequent access to nutrition information from colleagues (β = 3.75, p < 0.001), friends or family members (β = 2.71, p = 0.02), and academic webinars or continuing education (β = 3.92, p = 0.002) were significantly associated with higher NUTCOMP scores. Healthcare professionals in China frequently accessed nutrition information from both evidence-based and non-evidence-based sources. Frequencies of accessing nutrition information from colleagues, friends or family members, and academic webinars or continuing education were positively associated with self-perceived nutrition competence. The association observed with non-evidence-based sources highlights the need to better understand how information-seeking behaviors influence professional confidence and clinical practice. Future research is needed to develop strategies to strengthen evidence-based nutrition information sharing that may enhance nutrition competence.
In Japan, solitary deaths have become a social issue, with an increasing number of cases in which the body is discovered long after death. This study aimed to clarify the factors underlying such delays. Cases of death at home were extracted from forensic autopsies. In each case, we collected information about the deceased and their living conditions. The postmortem interval until finding (PMI-f) was calculated by measuring the time between death and discovery. We classified the cases into long PMI-f (LPMI-f; having PMI-f of ≥3 days) and short PMI-f (SPMI-f; having PMI-f of <3 days), and examined the factors that lead to LPMI-f. The characteristics of the group living alone with a PMI-f of <24 h and living with family or acquaintances with an LPMI-f were also analyzed. Among the 420 cases included, 244 (58.1%) were in the LPMI-f group. The LPMI-f group had higher number of males; older individuals; those living alone; those found inside their homes; single, retired, or non-employed individuals; those without long-term care certification; and those with drinking habits. Forty-seven individuals lived alone and had PMI-f of <24 h. Regular visits from relatives living separately led to early detection after death. In the LPMI-f group, 56 individuals lived with family or acquaintances. The absence of regular visits can result in delayed discovery after death; however, the time between death and discovery could be shortened by implementing systems such as allowing neighbors to check the person's safety by noticing uncollected mail.
Substance Use Disorder represents a complex global public health challenge, yet the effectiveness of treatment centers remains debated due to lack of consensus on standardized international indicators and heterogeneity of treatment modalities. This systematic review aimed to identify and synthesize key international indicators for measuring treatment success, compare effectiveness of different modalities, and assess impact on social reintegration. Following Preferred Reporting Items for Systematic Reviews and Meta-Analyses 2020 and Population, Intervention, Comparison, Outcome frameworks, we conducted systematic searches of PubMed, Scopus, Web of Science, and Cochrane Library. Two reviewers independently screened 4,234 records, extracted data from 28 included studies, and assessed quality using Cochrane Risk of Bias 2 and Newcastle-Ottawa Scale. Heterogeneity was quantified using I-squared and tau-squared statistics. Core indicators emerged in three domains: physiological (abstinence, daily functioning), psychological (reduced anxiety/depression, craving reduction), and social (employment, family relations). Medication-Assisted Treatment with methadone and buprenorphine demonstrated consistent effectiveness in reducing substance use and preventing relapse. Psychosocial interventions, particularly Cognitive Behavioral Therapy and Mindfulness-Based Relapse Prevention, significantly enhanced quality of life. Integrated models combining pharmacological and psychosocial approaches outperformed single-modality treatments. However, 78.6% of studies originated from four high-income countries, and only 17.9% reported outcomes beyond 12 months. Effective Substance Use Disorder treatment requires integrated models with standardized, multidimensional outcome indicators. Future research must prioritize long-term outcomes and address the substantial evidence gap in low- and middle-income countries. Not applicable.
Endocrine therapies targeting estrogen receptor alpha (ERα), expressed in ~70% of breast cancers, remain the standard of care for ER+ disease. However, 30-40% of patients experience recurrence and metastasis, with 5-year survival rates of only 31.9%. Using the Carle Foundation Hospital cohort and liver metastatic patient-derived xenograft models, we identified upregulated lipid metabolism and acetyl-CoA production as metabolic vulnerabilities. We demonstrate that combining Fulvestrant (Fulv) with an inhibitor of Acyl-CoA Synthetase Short Chain Family Member 2 (ACSS2) synergistically reduces metastatic breast cancer cell viability. Through isotope tracing, CUT&RUN sequencing, immunofluorescence, western blot, and RNA sequencing, we show that Fulv increases ACSS2 expression and acetate utilization, redirecting acetate flux from the TCA cycle toward fatty acid synthesis. Nuclear ACSS2 chromatin occupancy increases with Fulv treatment, expanding ERα/ACSS2/H3K27ac co-occupancy at tumor progression genes, an effect abolished by ACSS2 inhibition. RNA sequencing revealed that ACSS2 inhibition suppresses Fulv-induced metabolic and oncogenic transcriptional programs. In a therapy-resistant xenograft model, combination treatment reduced Fulv-dependent metastatic burden. These findings establish ACSS2 as a driver of endocrine resistance through nuclear acetyl-CoA provision for epigenetic reprogramming, representing a novel therapeutic target in metastatic breast cancer.
Spiritual counseling has expanded rapidly in Turkiye over the past two decades. Hospitals, prisons, family guidance offices, eldercare facilities, disaster-response systems, and addiction recovery programs now host spiritual counselors as part of routine care. The methodological foundation of these services, however, remains underdeveloped. Using a conceptual review and theoretical integration approach, this article proposes-but does not empirically test-a framework that links spiritual counseling practice in Turkiye to the Intention Code Model (NIKOM), a recently formulated cognitive model that conceptualizes mental life through if-then schemas (codes), their activation, and their alignment with bodily systems. The article reviews the institutional landscape of spiritual counseling in Turkiye, situates NIKOM among adjacent cognitive models, and shows how core Islamic concepts-tawakkul, ṣabr, shukr, tawba, and dhikr-can be interpreted as functions relevant to counseling practice. A standardized five-stage intervention template is proposed and applied to six service domains. The article closes by offering five testable propositions, considering ethical limits, and articulating concrete referral criteria. The proposed framework is theoretically grounded and empirically testable; clinical efficacy is not claimed.
Atherosclerosis (AS) is an aging-related chronic inflammatory disease. Histone lysine crotonylation (Kcr) is a posttranslational modification, which is widespread as acetylation; however, its roles are largely unknown in senescent macrophage of atherosclerosis. In this study, we report that histone Kcr of macrophages is abnormally elevated in atherosclerosis. Here, we show that ACSS2 (acyl-CoA synthetase short chain family member 2) is identified to increase the histone 3 lysine 9 crotonylation (H3K9cr) level in macrophages. Mechanistically, under pathological stimuli, the elevated ACSS2 increases H3K9cr expression, which enriches at the promoter of senescence-associated secretory phenotype genes, driving senescence and atherosclerosis. Functional analysis demonstrates that ACSS2 knockdown inhibits atherosclerosis in male mice by decreasing H3K9cr expression. We also verify the ACSS2 specific inhibitor, VY-3-135, as a potentially promising therapeutic agent for alleviating atherosclerosis. Furthermore, increased ACSS2 and H3K9cr correlate with senescence in human atherosclerotic lesions. Collectively, our work lays foundation for understanding the macrophage senescence mediated by Kcr and provides a potential therapeutic target for AS.
Mental health practitioners assess and treat trauma and dissociation by considering the biopsychosocial factors influencing the symptomatology of clients. In this process, clinicians often default to a prescriptive model that inherently assigns generalized cultural values to certain marginalized groups. Particularly for Latines, clinicians may overaccentuate the cultural value of familismo, the centering of family, for all Latine clients. These cultural values often translate into clinicians' expectations that their Latine clients will cherish their familial relationships in ways that make familismo an asset in treatment. However, for multiply marginalized Latines who endure intersectionality, familismo may not only be a detriment to trauma treatment, but the source of psychological distress itself. In this theoretical article, we center sexual and gender minoritized (SGM) Latines as we reconceptualize familismo as a potentially oppressive cultural value that may additionally be a contributing structural factor to both betrayal trauma exposure and dissociation by way of double-consciousness (du Bois, 1903). We define and briefly review the literature on familismo, intersectionality, and secondary marginalization. We also describe how intersectionality may contribute to dissociation and resistance through the framework of double-consciousness. We use a hypothetical case example to demonstrate the role of double-consciousness in dissociative responses to betrayal and discuss the implications for clinical practice and research.
Non-allergic rhinitis syndrome (NAR) is a chronic rhinitis characterized by the significant absence of an allergy history, negative skin prick test results, and normal serum IgE levels. Nasal cytology is a valuable diagnostic method that enables qualitative and quantitative assessment of inflammatory cells - including eosinophils, neutrophils, mast cells, and lymphocytes - in the nasal mucosa. This study aimed to evaluate the levels of nasal eosinophilia in a pediatric NAR population and to evaluate the correlation of this local inflammatory biomarker with clinical severity scales such as ARIA and PRQLQ. This prospective, cross-sectional study included 103 children aged 5-18 years: 53 with NAR and 50 healthy controls. Symptom duration and severity were classified according to ARIA 2019 criteria. The Paediatric Rhinitis Quality of Life Questionnaire (PRQLQ) was used for quality of life assessment. Nasal cytology specimens were collected by nasal swab from the middle meatus and the eosinophil percentage was calculated by counting a total of 100 cells in the area of highest cell density. A total of 103 children were enrolled: 53 NAR patients and 50 healthy controls. Median age was 10 (8-13) years in the study group and 11 (8-14) years in the control group. Family history of allergy was significantly higher in the study group (30.2%) compared to controls (12.0%) (p = 0.024). Median nasal eosinophil level was 7.0 (3.5-15.5) in the study group and 0 (0-3.0) in controls; the difference was statistically significant (p < 0.001). The nasal eosinophil cut-off value was determined as 3.5%. No significant difference was found between nasal eosinophil groups (< 3.5% and ≥ 3.5%) and any PRQLQ subscale or total score (p > 0.05). Nasal cytology may serve as a simple, non-invasive diagnostic tool to identify NAR subtypes and to determine clinical severity in pediatric patients.