As the primary living environment for disabled older adults, families play a crucial role in disease prevention and maintaining their health. However, research has found that both disabled older adults and their family members experience numerous physiological, psychological, and social adaptation problems when adjusting to the changes brought by disability, severely impacting the overall health status of the family. Therefore, guided by the ERG (Existence-Relatedness-Growth) theory, this study aims to understand the family health needs of families with disabled older adults in the community, providing a basis for improving the health level of these families and developing targeted intervention programs. From December 2024 to February 2025, this study employed purposive and snowball sampling to select 12 pairs of disabled older adults and their primary caregivers from communities under the jurisdiction of Zhengzhou City, Henan Province for semi-structured interviews. Thematic analysis was applied to organize and analyze the interview data. Deductive analysis indicated that the famliy health needs of families with disabled older adults in the community can be summarized into the following three themes: existence needs (daily living needs, economic support needs, environmental modification needs), relatedness needs (family communication needs, social resource connection needs, social participation needs), and growth needs (autonomy and dignity maintenance needs, family development needs, demand for technology-enabled solutions). The results show that the family health needs of families with disabled older adults in the community are unique and diverse. Community health workers and social workers can develop and implement effective strategies based on the different levels of family needs to promote the health level of families with disabled older adults and improve the overall quality of life of these families.
Home environments shape children's dietary habits, but which factors are most influential is unclear. The study purpose was to identify factors in the home environment associated with child intake of fruit and vegetables (FV) and sugar-sweetened beverages (SSBs) using a national dataset collected in 2013-2015 in the U.S. Data from 5,138 school-aged children (4-15 years old) from 130 U.S. communities were collected in 2013-2015. Parents and/or children completed a dietary screener and additional survey questions to assess household socioeconomic status (SES), grocery shopping sources, home food availability, social support for healthy eating, eating out frequency, and other home eating and related behaviors. Other child characteristics included breastfeeding history, intake of school foods, and participation in other nutrition programs. Community variables included predominant race/ethnicity and SES. Classification and regression trees (CART) identified key predictors of intake. The FV and SSB CARTS had 14 and 12 terminal groups, respectively. Children with the highest FV intake (0.54 SD from mean cups/day; 13% of sample) had fruit more often available at home, dark green vegetables more often available at home, ate dinner with family more often, had SSBs less often available at home, and were breastfed longer. Conversely, children in the two groups with the lowest FV intake either had fruit less often available at home, and family never complimented their eating (-0.86; 2%), or they had family that rarely or sometimes complimented their eating, and perceived school lunches as unhealthy (-0.87; 1%). For SSB intake, the lowest consumers (-0.63 SD from mean tsp/day sugar; 17%) never or rarely had SSBs available at home, and lived in higher SES communities. Children in the two groups with the highest SSB intakes had SSBs available at home more often, and lived in a SNAP-participating household and either ate out less often, used a phone/computer for social networking, and had SSBs available at home very often (1.3; 1%), or they ate out more often, and were breastfed for a shorter duration (1.1; 5%). Home availability of FV and SSBs were the most salient predictors of intake of both FV and SSBs, while other predictors differed between FV and SSB intake. Study findings highlight several actionable home-environment strategies to test in future studies to improve school-aged children's diets.
Choline is an essential nutrient required for the synthesis of key molecules, such as phosphatidylcholine, sphingomyelin, acetylcholine, and S-adenosylmethionine. Choline metabolism encompasses two phases, namely the postprandial and postabsorptive states. The former enables the digestion, absorption, distribution, and storage of choline derivatives after a meal, while the latter allows the cellular utilization of choline and the mobilization of stored choline-containing molecules during fasting. Understanding choline metabolism is fundamental to the study of lipid disorders such as steatohepatitis or atherosclerosis, as well as neurodegenerative diseases, including Alzheimer's disease, and inflammatory signaling pathways. Members of the alkaline phosphatase (AP) superfamily are prominent contributors to extracellular choline metabolism. Within this family, several APs and ectonucleotide pyrophosphatases/phosphodiesterases (ENPP) members are required for physiological choline metabolism. While intestinal alkaline phosphatase (IAP) and alkaline sphingomyelinase/ENPP7 both participate in the digestion of choline-containing derivatives in the gut during the postprandial phase, circulating ENPP2, ENPP6, and tissue-nonspecific alkaline phosphatase (TNAP) act during the postabsorptive phase to generate choline. In this review we first provide a comprehensive overview of choline metabolism and then describe how APs and ENPPs have functionally and structurally co-evolved to catalyze sequential reactions within this metabolic pathway.
Cornelia de Lange syndrome is a rare congenital disorder marked by considerable clinical variability, including intellectual disability, growth retardation, distinctive facial features, limb abnormalities, and multisystem involvement. The condition is primarily linked to mutations in genes encoding components of the cohesin complex that are essential for chromosomal stability and gene regulation. We report a case of a mild type of Cornelia de Lange syndrome caused by a de novo mutation in an Iranian family. We investigated a 19-year-old Iranian male individual presenting with developmental delay, borderline intellectual disability, dysmorphic facial features, and multisystem involvement. Whole-exome sequencing was performed to identify causative variants. A de novo heterozygous variant affecting the start codon of NIPBL (NM_133433.4:c.2T>A; NP_597677.2:p.Met1Lys) was identified. This variant was absent from population databases and predicted to disrupt normal translation initiation. Sanger sequencing and co-segregation analysis confirmed the genetic findings. In silico tools and population databases were utilized to assess variant pathogenicity. Clinically, the patient exhibited classical Cornelia de Lange syndrome features with relatively mild intellectual impairment compared with typical loss-of-function cases, consistent with the hypothesis of potential use of alternative start sites. This case shows a known NIPBL start-loss variant's correlation with a relatively mild clinical presentation and offers more genotype-phenotype evidence for it. This finding suggests a possible role for downstream translation initiation as a modifier of disease severity, although further functional validation is required. Comprehensive genetic analysis remains essential for accurate diagnosis, prognosis, and counseling in patients with Cornelia de Lange syndrome.
GATA transcription factors play important roles in plant development as well as light and hormone responses. Carrot is a kind of valuable root vegetable. The above-ground part of the carrot is affected by light during growth, which in turn affects the growth status of taproots. The functions of GATA factors have been characterized in several plant species. Little is known about the GATA factors in carrot biological process. In this study, 30 GATA family members were first identified in the carrot genome and classified into four subfamilies, named A-GATA, B-GATA, C-GATA, and D-GATA. C-GATA and D-GATA have specific functional motifs suggesting evolutionary conservation among plants. Predicted cis-elements of GATA factors revealed their potential hormone-responsive and light-responsive functions. Among them, B-GATA has been studied extensively and is represented by the GNC and GNL genes. There were three GNC/GNL homologs in carrot: DcGATA18, DcGATA20, and DcGATA22. Functional analysis revealed that the GNC homolog gene DcGATA20 was mainly expressed in carrot leaves, followed by petioles, and was barely detectable in taproots. Overexpression of DcGATA20 exhibited promotion of chlorophyll accumulation and increased the expression levels of DcGUN4 and DcCHLI1, along with a significant increase in expression of the transcription factor, DcGLK1, which is important for chlorophyll synthesis. In addition, the expression of the chlorophyll degradation gene DcSGR1 (STAY GREEN 1) was decreased. These results indicated that GNC genes exhibit functional conservation in carrot and may be helpful for understanding other GATA members' functions.
Metaphyseal anadysplasia 1, which includes Spondyloepimetaphyseal dysplasia Missouri type, is a rare autosomal dominant skeletal dysplasia characterized by short stature, mild limb deformities, and transient metaphyseal irregularities that typically resolve with age. The condition is caused by heterozygous missense variants in the MMP13 gene, encoding matrix metalloproteinase 13, a key enzyme in endochondral ossification and extracellular matrix remodeling. Pathogenic variants in MMP13 are exceedingly rare, with only a few families reported. We report two siblings, aged 3 and 1 years, in Sweden, presenting with clinical and radiological features consistent with Metaphyseal anadysplasia 1. Their father, of Syrian origin, exhibited short stature and mild femoral bowing. Genetic analysis revealed a novel heterozygous missense variant c.217T>C, p.(Ser73Pro) in MMP13, inherited from the affected father, and located within the same MMP13 domain as previously reported patients. The family pedigree demonstrates multiple affected individuals with short stature and bowed femurs, consistent with autosomal dominant inheritance. Radiographic imaging of father confirmed persistent but mild skeletal abnormalities. This report expands the genotypic spectrum of Metaphyseal anadysplasia 1 and suggests a putative mutational hotspot in exon 2. It further emphasizes the importance of thorough clinical, radiological, and genetic evaluation in families with short stature and metaphyseal irregularities and a clinical long-term follow-up is proposed with regular radiographic monitoring.
School belonging is a key protective factor for socioemotional functioning during the preschool period. Counsellors working in preschool institutions play an important role in developing sense of school belonging by meeting their emotional and social needs and fostering a positive school environment. This study examined the views of school counsellors working in preschool education institutions in Türkiye regarding sense of school belonging and, to support these views and to reveal their reflection at the level of institutional practice, analysed routine guidance and counselling documents to identify how belonging-supportive practices are formally planned, implemented, and recorded over the school year. A phenomenological qualitative design was employed. Data were collected through structured interviews with school counsellors and complemented by document analysis of counselling artefacts to examine how belonging practices are formally planned, implemented, and documented across the school year. The document corpus comprised 186 written artefacts from 10 kindergartens. Data were analysed using computer-aided content analysis, and a hierarchical code-subcode model was utilised in MAXQDA 2020. Findings indicated that counsellors conceptualised school belonging as children's feelings of acceptance and security within the school community and described belonging-related differences in children's emotions, participation, and peer interactions. Counsellors also highlighted multi-level strategies targeting emotional safety, peer relationships, teacher practices, and family involvement. Complementing these findings, the document analysis yielded five practice-oriented domains through which counselling services may support school belonging: (1) emotional safety and adjustment to school routines, (2) support for peer relationships and social problem-solving, (3) cultivation of a positive classroom/school climate through teacher collaboration, (4) systematic family involvement and parent education, and (5) developmental monitoring and evaluation. Document analysis corroborated counsellors' reported perspectives by providing practice-level evidence of how belonging-supportive strategies were formally embedded in institutional plans and documented in artefacts. Preschool children's school belonging is supported through a year-long programme of practice spanning children, teachers, and families. Strengthening preventive counselling services that promote emotional safety, peer-inclusion, and family-school collaboration may improve school belonging in early childhood, as this phenomenon has far-reaching implications for children's educational trajectories, working lives, and broader societal and democratic engagement.
The P-Rex family proteins P-Rex1 and P-Rex2 are Dbl-type guanine-nucleotide exchange factors (GEFs) that activate Rac small GTPases upon synergistic stimulation by PIP3 and Gβγ, acting as coincidence detectors for PI3K and GPCR signalling. P-Rex Rac-GEFs control physiological responses ranging from inflammation, innate and adaptive immunity to GPCR trafficking, glucose homeostasis, and the function of the vascular endothelium, nervous system, and adipose tissue. P-Rex2 also increases PI3K-signalling through its catalysis-independent inhibition of the tumour suppressor PTEN. Deregulated levels of P-Rex1 are linked to fibrotic diseases, asthma, and autism spectrum disorders, and both P-Rex1 and P-Rex2 are deregulated in metabolic diseases. Upregulation of P-Rex1 and P-Rex2 as well as activating P-Rex2 mutations also occur in many types of cancer, including breast, prostate, lung, liver and colorectal cancer, as well as in melanoma and glioma. and contribute to tumour growth or metastasis depending on the P-Rex protein and cancer type. Deregulation of P-Rex1 in cancer typically promotes tumour growth or metastasis, whereas upregulation or mutation of P-Rex2 in cancer is mostly associated with tumour growth. Recently, structural data have increased our understanding of P-Rex regulation, the first P-Rex inhibitors have been developed, and GEF-activity independent functions of P-Rex proteins in GPCR trafficking, neutrophil-responses, innate immunity, and glucose homeostasis have been described. This review summarises the P-Rex literature from the discovery of the P-Rex protein family in 2002 to the present, with a focus on recent advances.
Drought threatens apple (Malus domestica) growth and productivity, often leading to irreversible economic losses. C1-papain family cysteine proteases are key enzymes in plant responses to abiotic stress, yet their specific roles under drought conditions remain largely uncharacterized in apple. Sequence analysis identified MdCP37 as a member of the C1-papain family. Here, we demonstrate that overexpression of MdCP37 (OE) in transgenic apple increases drought sensitivity, while RNAi-mediated silencing of MdCP37 enhances drought tolerance. Under drought stress, MdCP37-OE lines displayed reduced antioxidant enzyme activity and suppressed expression of drought-responsive genes, whereas RNAi lines exhibited opposite trends. Moreover, MdCP37 accelerated chlorophyll and ribulose-1,5-bisphosphate carboxylase/oxygenase (Rubisco) degradation and promoted leaf senescence under drought conditions. Collectively, our findings establish MdCP37 as a negative regulator of drought tolerance in apple and offer theoretical support for improving drought resilience in apple breeding programs, particularly in arid regions.
Children with autism spectrum disorder (ASD) frequently exhibit selective eating behaviors characterized by food refusal and limited dietary variety, which can lead to nutritional deficiencies and impaired family functioning. This study evaluated the effectiveness of the Schmetterling Nutritional Behavior Intervention (NBI) Program, a creative behavioral intervention integrating established behavioral strategies with innovative components, including imitation chaining, shaping, and therapist-guided exoskeleton modeling. Three children (YW, RA, and JK) diagnosed with autism spectrum disorder (ASD) participated in a single-case experimental design. The study employed the Childhood Autism Rating Scale, 2nd Edition (CARS-2) assessing autism symptom severity, while the Child Eating Behavior Questionnaire (CEBQ) measured changes in eating behavior. Substantial increases in food acceptance were observed across all participants, with the highest improvements in food responsiveness, enjoyment of food, and food fussiness. Tau-U analysis revealed large and significant intervention effects for both therapist-implemented and parent-implemented sessions. Although CARS-2 scores remained within the 'severe' classification range, notable percentage reductions suggested clinically relevant improvements in core autism symptoms. These findings support the Schmetterling NBI Program as an individualized, evidence-based approach to enhancing dietary diversity and reducing maladaptive feeding behaviors in children with ASD. Children with autism spectrum disorder (ASD) commonly demonstrate selective eating patterns, including food refusal and restricted dietary repertoire, which may contribute to nutritional deficits and compromised family dynamics. This investigation examined the efficacy of the Schmetterling Nutritional Behavior Intervention (NBI) Program, a novel behavioral intervention that synthesizes established behavioral methodologies with innovative components such as imitation, shaping procedures, and therapist-guided training. Utilizing a single-case experimental design, three children diagnosed with ASD (YW, RA, and JK) were assessed with the Childhood Autism Rating Scale, Second Edition (CARS-2) to evaluate autism symptom severity, and the Child Eating Behavior Questionnaire (CEBQ) to measure alterations in feeding behavior. Results indicated substantial improvements in food acceptance across all participants, with pronounced enhancements in food responsiveness, enjoyment of food, and reductions in food fussiness. Tau-U statistical analysis demonstrated large and significant intervention effects for both therapist-administered and parent-implemented sessions. Although CARS-2 scores remained within the severe classification range, notable percentage reductions indicated clinically meaningful improvements in core autism symptomatology. These findings support the Schmetterling NBI Program as an individualized, evidence-based intervention for promoting dietary diversity and reducing maladaptive feeding behavior among children with ASD. Replicating our preliminary findings in a larger sample and finding evidence-based tailored interventions for children with ASD pose important challenges for future research.
Aging and increased life expectancy generate growing challenges for end-of-life care in old age, particularly in rural contexts marked by territorial and health inequalities. From the perspective of gerontological geography and the notions of autonomy and agency of older adults, this study aims to generate an understanding of end-of-life as a lived experience from the subjective worlds of and with the people involved. To this end, a qualitative study, with an ethnographic approach and case study strategy, was conducted in the Los Lagos Region of Chile between 2022 and 2023. This included semi-structured interviews and ethnographic observation of rural older adults in the end-of-life stages, their caregivers, and rural health teams. The results show that remaining at home is a central desire and organizes care, sustained primarily by feminized family networks and rural primary care. The home becomes a space of care, and health teams play a key role in providing clinical and relational support at the end-of-life. It is concluded that end-of-life care in rural areas requires territorial approaches that recognize autonomy in old age and the structural inequalities of these processes. El envejecimiento y aumento de la esperanza de vida generan desafíos crecientes para los cuidados de fin de vida en la vejez, particularmente en contextos rurales marcados por desigualdades territoriales y sanitarias. Desde la geografía gerontológica, y las nociones de autonomía y agencia de las personas mayores, este estudio se propone generar una comprensión del fin de vida como experiencia vital desde los mundos subjetivos de y con las personas implicadas. Para ello, se realizó un estudio cualitativo, de enfoque etnográfico y estrategia de estudio de caso, en la Región de Los Lagos, Chile, entre 2022 y 2023, que incluyó entrevistas semiestructuradas y observación etnográfica a personas mayores rurales en etapas de fin de vida, las personas cuidadoras y los equipos de salud rural. Los resultados muestran que la permanencia en el hogar constituye un deseo central y organiza los cuidados, sostenidos principalmente por redes familiares feminizadas y por la atención primaria rural. El hogar se transforma en un espacio de cuidado y los equipos de salud cumplen un rol clave en acompañamiento clínico y relacional del fin de vida. Se concluye que los cuidados de fin de vida en la ruralidad requieren enfoques territoriales que reconozcan autonomía en la vejez y las desigualdades estructurales de estos procesos.
To understand circumstances surrounding transitions between initial drug use, non-prescribed opioid use, and injection drug use (IDU) among people who use non-prescribed opioids in the rural U.S. We interviewed adults who use non-prescribed opioids in 10 states. We coded transcript data regarding age, drug, modality, circumstances for each "first use" event and transitions to illicit opioid use/IDU. Transition-related themes were categorized using the Social Ecological Model (SEM) through iterative qualitative memoing. We calculated frequencies and measures of central tendency. Participants (n = 304, mean age [MA] = 36 years, 56% male) reported marijuana or opioid pills as first drug used (60%, reported MA = 13, and 16%, MA = 19, respectively). First opioid use (MA = 20) was typically pills (74%); 43% were initially prescribed opioids for pain. Of participants reporting IDU (92%, MA = 24), first drugs injected were methamphetamine (26%), opioid pills (22%), and heroin (22%). Reasons for first injection of these three substances were recreational (65%, 84%, 66%, respectively) followed by mental health coping (35%, 16%, 33%). Interviews revealed factors influencing transition to illicit opioid use/IDU at environmental, interpersonal, and intrapersonal levels of the SEM, including early household exposure to drugs, and family/peer encouragement to use opioids for coping. Participants described initial use of prescribed opioids following surgery or workplace injury, followed by illicit use of opioids and later IDU for recreational as well as practical goals. IDU was facilitated by intimate partners and friends in the context of diminished local access to illicit opioid pills. Among people who use opioids and inject drugs in the rural U.S., drug use typically started in pre-adolescence, first opioid use in early adulthood, and IDU a few years later, highlighting the need for early intervention. Methamphetamine comprised a substantial proportion of initial IDU raising concerns for polysubstance use. Drug use for coping highlights the need for increased mental health resources in rural areas.
Understanding how women navigate induced abortion care pathways is critical to ensuring person-centred, quality reproductive health services. Evidence indicates that persistent abortion stigma, the lack of choices of abortion methods and respectful care during abortion remain a global challenge to reproductive healthcare. Yet there is minimal evidence regarding abortion care pathways. This study explored induced abortion care pathways in Addis Ababa healthcare facilities. We used a descriptive qualitative approach, adopting purposive sampling techniques to recruit women who sought induced abortion care from seven facilities. The data were collected from May to July 2024. In-depth semi-structured interviews with sixteen women were digitally recorded and transcribed into the local language before being translated into English. Data were coded, organised, and analysed using inductive thematic analysis. Five main themes and their corresponding subthemes were developed through data analysis. Themes were: (i) social and emotional support, (ii) moral and social meanings shaping abortion care, (iii) accessibility and service delivery, (iv) perceived competency of abortion providers, and (v) physical and emotional effects of abortion. Many women attended the clinic alone, without their families, and received no support. Women often sought care at clinics away from their community due to concerns related to fear of stigma and social pressure. This study found long waiting times to receive abortion care, a lack of medicine and ultrasound at some facilities and limited availability of second-trimester abortions. Women reported that many providers were welcoming and competent, while others reported poor communication, the use of medical jargon, and stigmatising behaviours. Participant reported pressure to accept methods they did not want during contraceptive counselling and fear of breaches in privacy and confidentiality. Participants also described physical symptoms such as bleeding and pain, and felt ashamed and upset after the abortion, which could be associated with negative experiences. Inadequate social support, abortion stigma, and barriers to accessing abortion services, such as long waiting times and insufficient resources, were identified as significant gaps. These findings emphasised the need to strengthen person-centred abortion care and address systemic and socio-cultural barriers that undermine the quality of care. Abortion care should be easy to access, fair for everyone, and respectful of women’s needs. Kind communication and emotional support during abortion enhance the quality of care. This study explored abortion care experiences in healthcare facilities in Addis Ababa.We spoke with women who came for abortion care. We conducted face-to-face interviews employing open-ended questions. We analysed the data by thoroughly reading and checking the information to identify common patterns in women’s experiences.Women had varied experiences of support. Some received strong support from family or friends, which made them feel less worried and more confident. Some went through the abortion procedure alone as they feared pressure or shame. Many women felt abortion was a “sin” or morally wrong, while others felt confident that they had made the best decision for their lives. Women reported waiting times and service availability as challenges to accessing quality care. In addition, negative experiences such as feeling judged and ignored, as well as poor communication from providers, are reported. Women explained physical symptoms such as bleeding, fatigue and emotional outcomes including anxiety, guilt and self-blame after abortion. At the same time, some felt relieved after the abortion and satisfied with the care received.This study found that women faced challenges such as stigma and judgment, long waiting times, and limited availability of abortion services in some places. Improving the quality of abortion care can help women feel supported, reduce emotional distress, and protect their health and dignity.
Lipid phosphate phosphatases (LPPs) dephosphorylate lipid phosphates to regulate signaling and metabolism. Among the three mammalian isoforms, LPP1, LPP2, and LPP3, LPP2 has been strongly associated with cancer, making it a potential therapeutic target. However, the molecular mechanisms underlying its structural organization, substrate recognition, and catalysis remain elusive. Here, we report the cryo-EM structure of human LPP2 (hLPP2). hLPP2 assembles as a homo-tetramer, with phosphatidylcholine bound in the substrate pocket. The tetrameric arrangement provides a structural basis for LPP oligomerization. The wide, open-ended substrate pocket explains the enzyme's broad substrate specificity. Structural comparison with PAP2 family members, including hG6PC1 and ecPgpB, suggests a conserved catalytic mechanism and highlights the regulatory role of residue E159 in stabilizing the catalytic center and phosphate release. Collectively, these findings advance our understanding of the structural basis and enzymatic mechanism of LPPs and may provide insights for the development of novel cancer therapies.
Executive function is an essential cognitive domain for typical human behavior which is disrupted in neurodevelopmental and neurodegenerative disorders, but little is known about its underlying molecular basis. To address this, we perform genome-wide association studies (GWAS) using three different measures of executive function in UK Biobank (N = 84,238) and NIHR BioResource's Genes and Cognition (N = 9932) study participants, followed by a meta-analysis. The trail-making alphanumeric (TMA) measure is the most heritable phenotype (h²=7-26%), associated with 18 independent loci that exhibit a similar direction of effect in both cohorts. Across these loci, in-silico follow-up implicates 178 genes, of which NT5DC2 and RP11-579E24.2 are independently replicated prior to meta-analysis. TMA is linked to pan-cerebral differences in brain structure, with brain-enriched genes showing a biphasic expression profile from early development through to later life. Our data implicate specific cell types, histone modifications and butyrophilin immunoglobulin family proteins as potential targets for promoting cognitive resilience.
Periodontitis, a chronic inflammatory disease, is increasingly prevalent among young people and impairs their quality of life. Adverse childhood experiences (ACE), depressive symptoms, and suboptimal health status (SHS) are linked to health risks and chronic diseases, but their interrelationships with periodontitis in Chinese young adults remain unclear. This study aimed to explore associations among these factors. From December 2024 to May 2025, 2,888 participants (aged 18-35) from Tongji Hospital completed surveys on demographics, ACE, depressive symptoms, and SHS. Periodontitis was diagnosed according to the 2018 criteria. Simple, parallel, and chain mediation models were used, controlling for age, sex, marital status, and smoking. Periodontitis prevalence was 25.00% and higher in married individuals (P < 0.001) and smokers (P = 0.004). ACE correlated positively with depressive symptoms (r = 0.28, P < 0.001), SHS (r = 0.19, P < 0.001), and periodontitis (r = 0.16, P < 0.001). Mediation analyses showed: Simple model: Depressive symptoms and SHS partially mediated the effect of ACE on periodontitis (indirect effect = 0.011 for both). Parallel model: Only SHS significantly mediated the effect (indirect effect = 0.011). Chain model: ACE was related to periodontitis via "depressive symptoms → SHS" (indirect effect = 0.010), with significant direct and indirect effects. ACE associated with higher periodontitis risk in young people. This association included both a direct link between ACE and periodontitis, and an indirect link through the chain pathway of "depressive symptoms → SHS"; among these pathways, SHS was a key mediator. The study was registered in the Chinese Clinical Trial Registry (ChiCTR) with the registration number ChiCTR2500103464. Childhood trauma can exert long‐term impacts on health, including oral health. This study involving 2,888 Chinese young adults aged 18‐35 found that 25% of the participants had periodontitis. Those who experienced childhood abuse, neglect, or family issues showed a higher association with the disease. The research revealed two pathways linking early trauma to periodontitis: a direct association and an indirect chain of “depressive symptoms → suboptimal health status (e.g., persistent fatigue).” While depressive symptoms played a role, suboptimal health status was the critical mediator. Higher periodontitis rates in married individuals and smokers may relate to stress or lifestyle factors. The findings suggested that early identification of childhood trauma, combined with interventions targeting mental health or overall well‐being (e.g., counseling, health management), could be more effective than oral care alone in prevention. This underscored the association between early‐life experiences and long‐term health and the need for integrated interventions.
To assess the foveal microvasculature in adult offspring of patients with neovascular age-related macular degeneration (nAMD) who exhibit no clinical or imaging signs of AMD, and to compare these parameters with those of healthy controls without a family history of AMD. This cross-sectional study included 82 adult offspring of patients with nAMD and 85 age- and sex-matched controls. Optical coherence tomography angiography (OCTA) was used to evaluate vessel densities of the superficial and deep capillary plexuses (SCP and DCP), the foveal avascular zone (FAZ), outer retinal flow, and choriocapillaris (CCP) flow area. There were no significant differences in demographic or visual parameters between groups, nor in FAZ area, perimeter, or acircularity index. However, vessel densities in all SCP and DCP zones, as well as outer retinal and CCP flow areas, were significantly reduced in the nAMD offspring group (all p < 0.05). Subclinical microvascular alterations in SCP, DCP, and CCP were identified in clinically unaffected adult offspring of patients with nAMD. These findings suggest a potential heritable vascular component in early AMD pathogenesis and support the use of OCTA as a tool for risk stratification.
In this review we comprehensively discuss organic cation transporter novel 1 (OCTN1), encoded by the SLC22A4 gene as a member in the solute carrier 22 (SLC22) family, which facilitates the cellular transport of diverse cationic and zwitterionic substrates. OCTN1 is highly expressed in many vital organs in humans, where it facilitates absorption and distribution of both endogenous compounds and therapeutic drugs. Among its substrates, ergothioneine (EGT) serves as the primary antioxidant and anti-inflammatory molecule, underscoring the essential role of OCTN1 in cellular defense and inflammation control. Genetic polymorphisms in SLC22A4 significantly alter OCTN1 expression, substrate affinity, and drug pharmacokinetics, with strong associations to susceptibility and treatment outcomes in human diseases. Insights from knockout models revealed that OCTN1 deficiency leads to reduced EGT availability, heightened oxidative stress, and aggravated inflammation, particularly in the tissues such as intestine, liver and lung. Moreover, OCTN1 activity is dynamically regulated by epigenetic modifications, cytokines, and hormones, linking it to immune modulation and disease progression. Put together, OCTN1 plays a defined role via high-affinity EGT transport, while its broader transport capacity and pharmacological relevance remain under investigation, with possible - though not yet established - implications for inflammation-associated biomarker development.
Reptiles often inhabit environments that are in close proximity to humans and livestock, creating opportunities for parasite transmission. They are common in areas where they find shelter, food and warmth. The Bengal monitor lizard (Varanus bengalensis), a member of the family Varanidae, represents one of the largest groups of extant poikilothermic predators. Monitor lizards are known to harbor several tick species that serve as vectors for a variety of pathogens. No prior information is available in the literature regarding ticks infesting V. bengalensis in Pakistan as well as regarding the occurrence of Toxoplasma gondii in these ticks. Therefore, we aimed to determine the molecular prevalence of T. gondii in Amblyomma gervaisi ticks (n = 93) collected from 24 V. bengalensis in Buner District, Khyber Pakhtunkhwa Province, Pakistan, between May and September 2023. Polymerase chain reaction (PCR) amplified a 300 bp fragment specific for the ITS-1 region of T. gondii in 10 of the 93 (11%) A. gervaisi ticks. DNA sequencing and BLAST analysis confirmed the presence of T. gondii. Phylogenetic analysis showed that these sequences clustered with the ITS-1 sequences of T. gondii detected in reptiles and mammals from Pakistan, Brazil, China, Tunisia and Portugal. The prevalence of T. gondii in A. gervaisi was not limited to a specific tick sex, feeding stage or month of sampling. However, among the tick developmental stages, nymphs had the highest rate of T. gondii infection. In conclusion, for the very first time from Pakistan, we are reporting the presence of T. gondii in A. gervaisi that were infesting monitor lizards. We recommend that similar and large scale studies should be conducted in all those areas of Pakistan that are unexplored for the presence of T. gondii in A. gervaisi ticks. Prevalence of this parasite should also be screened in all the animals harboring these as well as other tick species. This will help in better understanding of T. gondii transmission to new hosts that will lead toward its effective control.
Osteoporosis (OP) is a systemic metabolic bone disorder. The excessive activation of osteoclasts (OCs) leads to a decrease in bone mass and damage to the bone microstructure, which plays a crucial role in OP. β-Hydroxybutyrate (BHB), the main component of ketone bodies, not only serves as an ancillary fuel substituting for glucose but also induces anti-oxidative, anti-inflammatory, and cardioprotective features via binding to several target proteins, including histone β-hydroxybutyrylation (Kbhb). Recent research has found that BHB has a positive therapeutic effect on OP, but the underlying molecular mechanism remains unclear. In this study, we established osteoporosis (OP) animal models induced by estrogen deficiency and type 2 diabetes using ovariectomized (OVX) and db/db mice, respectively, and administered BHB to OP mice via free drinking in vivo. Our results indicated that BHB increased bone mineral density (BMD), improved bone microstructure, and inhibited the OC formation. Additionally, BHB upregulated the levels of PanKbhb, H3K9bhb, and H3K27bhb modifications in the bone tissue of OP mice. In vitro, we found that BHB or β-hydroxybutyryl-CoA (BHB-CoA) could inhibit RANKL-induced OC differentiation and bone resorption, and upregulate histone Kbhb levels in a concentration-dependent manner. Furthermore, the effects of BHB or BHB-CoA-induced histone Kbhb were reversed by inhibiting the activity of Acyl-CoA synthetase short-chain family member 2 (ACSS2) or histone acyltransferase P300. In summary, our data reveal that BHB may alleviate bone loss caused by estrogen deficiency and type 2 diabetes through ACSS2/P300-induced histone Kbhb.