Silicosis is an irreversible, progressive occupational lung disease caused by chronic inhalation of crystalline silica (SiO₂), with no approved disease-modifying therapies currently available. Its pathological hallmark is a hostile fibrotic microenvironment driven by excessive reactive oxygen species (ROS), chronic inflammation, and mitochondrial dysfunction in alveolar epithelial type 2 (AEC2) cells; this microenvironment is the primary bottleneck for stem cell-based silicosis therapy, as it severely impairs the engraftment of exogenous AEC2 cells. Metformin (Met) exerts mitochondria-protective effects to preserve AEC2 function, but its clinical translation for silicosis is limited by low oral bioavailability and non-specific systemic distribution. Here, we developed a ROS-responsive biomimetic liposome (TK-PSBs@Met, also termed TPM NPs) for targeted Met delivery to AEC2s in fibrotic lungs, via a design combining pulmonary surfactant (PS)-mediated AEC2 targeting and thioketal (TK)-based ROS-triggered on-demand drug release. In vitro, TPM NPs reversed SiO₂-induced epithelial-mesenchymal transition (EMT), suppressed fibrotic and inflammatory responses, and restored mitochondrial function in A549 cells, a well-established AEC2 cell model. In vivo, TPM NPs significantly boosted the functional engraftment of TdTomato⁺ AEC2 stem cells, promoted alveolar regeneration, and attenuated collagen deposition and inflammation in SiO₂-induced silicosis mice. Mechanistically, TPM NPs mitigated silicotic fibrosis via a dual synergistic mechanism: remodeling the hostile fibrotic microenvironment and activating the AMPK/PGC-1α/NRF1/TFAM signaling axis to restore AEC2 mitochondrial biogenesis. Collectively, this TPM NP-AEC2 combinatorial therapy offers a translatable precision strategy for silicosis treatment and establishes a new paradigm for nanomedicine-augmented stem cell therapy in refractory fibrotic lung diseases.

Neonatal hypoxic-ischemic encephalopathy (NHIE) is a leading cause of morbidity and mortality in term infants. The anesthetic dexmedetomidine (Dex) has been shown to reduce brain damage. In this study, hypoxia-ischemia (HI) in neonatal rats caused significant cerebral infarction, neurological deficits, learning and cognitive impairments, inflammatory responses, and microglia polarization. Dex treatment mitigated HI-induced brain injury in rats. Lipopolysaccharide (LPS) increased inflammation in BV2 cells, elevated M1 polarization markers, and raised the proportion of M1 cells. Dex reduced inflammation and M1 polarization in BV2 cells. Rbm47 was identified as a target of Dex, being downregulated in NHIE rat brain tissues and upregulated by Dex. Rbm47 co-localized with microglia and was decreased as the microglia marker Iba-1 increased. Adenovirus-mediated overexpression of Rbm47 alleviated brain injury in NHIE rats and reduced microglial inflammation and M1 activation, both in vitro and in vivo. Conversely, knockdown of Rbm47 hindered the protective effects of Dex against BV2 cell inflammation and M1 polarization. This study indicates that Rbm47 mediates the protective effects of Dex against NHIE brain injury.

Cardiovascular diseases (CVD) stand as the primary cause of mortality and form the most prevalent disease category. Numerous studies have demonstrated that aging serves as a crucial pathogenic factor in the progression of CVD. Nevertheless, the molecular mechanisms underlying cardiovascular aging have not been fully elucidated. Research in various aging models has consistently shown that aging is attributed to the dysfunction of a complex transcriptional regulatory network that maintains the body's health, tissue homeostasis, and stress resistance. Transcription factors and chromatin regulatory factors are involved in almost all cellular activities, and an increasing amount of evidence indicates that as key regulatory elements, transcription factors and chromatin regulators control cellular senescence by regulating the transcription of related genes. Therefore, the aim of this review is to summarize the specific role of transcriptional regulation in the mechanism of cardiovascular aging, providing new strategies for the treatment of CVD.

Psychological interventions are recommended for people under Crisis Resolution Home Treatment Teams (CRHTTs). Non-registered psychology roles (Assistant Psychologists (APs) and Trainee Associate Psychological Practitioners (TAPPs)) are potentially both cost and clinically effective for delivering brief interventions in CRHTTs. This study aimed to quantitatively examine routine outcome change associated with two brief, skills-based interventions (the Crisis Toolbox (CTB) and the Emotion Coping Skills (ECS)) delivered by APs and TAPPs in one CRHTT. A retrospective service evaluation of 490 service users who accessed either the CTB or ECS between June 2020 and February 2025 was employed. The Clinical Outcomes in Routine Evaluation - 10 (Core-10) and Mental Health Confidence Scale (MHCS) measures were completed pre- and post- intervention. Paired samples t-tests were conducted and demographics (age, gender, and ethnicity) collected. There was a statistically significant effect in improving scores on both measures at the post-intervention timepoint (CORE-10: 8.636, 95% CI [7.810 to 9.461], t(297) = 20.586, p < .001; MHCS: -13.537, 95% CI [-14.827 to -12.237], t{293) = -20.568, p < .001). This significant effect remained when looking at males and females separately. Asian and Black ethnic groups were underrepresented in the sample compared to local demographics, whilst other ethnic groups showed similar representation. Findings suggest that CTB and ECS may be clinically effective in reducing distress and increasing confidence in coping with mental health challenges for service users. Additionally, this evaluation has highlighted the need for better understanding UK ethnic minority representation in CRHTTs and consideration of possible barriers to access.

Neurological disorders represent a leading cause of global mortality and disability, yet treatment options remain limited due to the challenges of targeting pathogenic proteins, particularly those considered "undruggable" by conventional small molecules. Targeted protein degradation (TPD) has expanded the druggable proteome by harnessing proteasomal and lysosomal pathway to eliminate these targets, offering the advantages of lower toxicity and reduced resistance compared to traditional modulation. This review systematically delineates TPD mechanisms according to their degradation pathways, including proteasomal, endosomal-lysosomal, and autophagy-lysosomal systems, and highlights their unique applications in brain diseases. However, the translation of TPD to neurological disease is limited by physicochemical liabilities, cell-type dependence, risks associated with whole-protein ablation, the blood-brain barrier (BBB) and poor brain bioavailability. To address these translational barriers, we emphasize the integration of TPD with drug delivery systems (DDS) as a pivotal strategy. By optimizing pharmacokinetics, stability, and BBB penetration, nano-DDS significantly enhances brain targeting and therapeutic precision. Finally, we evaluate recent progress in nano-TPD systems and offer critical insights into their future trajectory in treating complex brain disorders.

The study aimed to systematically interpret and synthesize data obtained from qualitative research on the life experiences of individuals with fecal incontinence.

A comprehensive literature search covering the years 2010 to 2023 was conducted on December 1, 2023, using the CINAHL, MEDLINE, PubMed, Web of Science, OpenAIRE, and OVID electronic databases. The search process followed PRISMA guidelines. The study was registered in PROSPERO (CRD42024507571).

Qualitative studies focusing on the life experiences of individuals with fecal incontinence were included. A total of 16 studies met the inclusion criteria and were incorporated into the meta-synthesis.

Relevant data from the included studies were systematically extracted, focusing on participants' experiences, perceptions, and coping mechanisms related to fecal incontinence.

Data were analyzed using thematic synthesis. Five analytical themes were identified: (1) the meaning of fecal incontinence for the individual, (2) perceived barriers to the management of fecal incontinence, (3) negative effects of fecal incontinence on life, (4) developing individual coping strategies, and (5) expectations.

Fecal incontinence was found to be more than a physical condition, significantly affecting individuals' mental health as well as their sexual and social lives. Social stigma, taboos, and limited awareness among health care professionals hinder patients from expressing their symptoms and seeking help, often leading to concealment of the condition. These findings highlight the need for educational interventions and awareness campaigns to reduce stigma and address the psychosocial dimensions of fecal incontinence.

When outbreaks of emerging and reemerging zoonotic diseases are discussed, little attention is paid to differential gender impacts, or to gender involvement and roles in different settings during the outbreak. Gender roles shape how individuals' interactions with animals, wildlife, other people and the environment, which influences exposure to zoonotic pathogens. For example, in some rural communities, men may face risks of exposure to emerging pathogens during hunting whilst women who primarily take care of domestic animals may face prolonged exposure to other zoonotic diseases. In some settings, women (and men) lack access to health protection, education or communication with health officials (medical doctors or veterinarians). In some cultures, women are not allowed to speak directly with male service providers, further limiting their access to critical information and services. One Health is a holistic, inclusive approach which should be incorporating a gender lens when considering zoonoses. This includes thinking about the need to create appropriate gender sensitive policies that address disparities in surveillance, response, prevention, detection, and control of the disease (or health issue) being addressed. In this paper, we highlight these issues through several case studies that demonstrate the importance of including gender in zoonotic disease response and, ideally, when implementing prevention measures.

Pharmaceutical Care (PC) has emerged as a vital component of the healthcare system, involving the provision of medication therapy to achieve specific outcomes that enhance a patient's quality of life. Therefore, this study aims to evaluate PharmD interns' self-reported attitudes, perceptions of the skills required to provide PC using multiple domains (technical, psychosocial, communication, and administrative aspects) and perceived barriers to implementing PC, and recommendations. A cross-sectional study was conducted between May and December 2023, utilizing pretested questionnaires with PharmD interns at Saudi universities in Riyadh, Saudi Arabia. The questionnaire included sociodemographic information, attitudes (13 items), perceptions (24 items), importance (19 items), barriers (17 items) toward PC, and recommendations (4 items). To find out the association between variables chi-square, Analysis of Variance, and Spearman correlation were used to examine differences in perceptions and correlations between attitude and perception scores, with a P value < .05 considered statistically significant. A total of 216 PharmD interns participated, with 59.7% being male, 94.9% Saudi nationals, and a mean age of 24.08 ± 0.98 years. The majority (72.7%) were 24 years old. Participants were from public (57.9%) and private (42.1%) universities in Riyadh. The mean attitude score towards PC was 51.25 ± 9.38, and the mean perception score was 106.67 ± 16.01. Attitude scores were significantly associated with gender and university type (P < .001), while perception scores showed significant associations with gender, age, and university type (P < .01). The results of the Spearman correlation analysis indicated a moderate, statistically significant positive correlation between mean attitude and mean perception scores (R = 0.345, P < .01). Most interns agreed that pharmacists should prevent and solve medication-related problems (86.6%) and provide PC (85.7%). However, 43.5% believed that PC is not worth the additional workload. The most frequently reported barriers were lack of financial compensation (65.8%), inadequate staffing (62.5%), limited private counseling areas (60.7%). Most of the PharmD interns have a positive attitude towards PC but face structural and educational barriers to PC implementation. Future research should focus on overcoming these barriers and promoting Interprofessional healthcare courses to enhance patient outcomes.

Depression and anxiety are among the most common comorbidities in individuals with Parkinson's disease (PD). Yet their prevalence and contributing factors in Saudi Arabia are poorly examined. This study aimed to estimate the prevalence of depression and anxiety among patients with PD in Saudi Arabia, along with contributors, demographics, and clinical correlates. A cross-sectional study was conducted in Riyadh, Saudi Arabia, in which 130 patients diagnosed with PD completed the validated Arabic versions of the Patient Health Questionnaire-9 (PHQ-9) and Generalized Anxiety Disorder-7 (GAD-7) to ascertain the presence of depression and anxiety, respectively. Sociodemographic, patient-related factors, and clinical data were also collected and analyzed in conjunction with the aforementioned scales using univariate and multivariable logistic regression. Depression and anxiety were present in 67.7% and 62.3% of participants, respectively. Compared with the age group 41-50 years, the 51-60 and 61-70 groups were less likely to be depressed or anxious (P = .013 and P = .008). Lower education (high school or less) was associated with both depression and anxiety (P = .021 and P = .017). Anxiety (GAD-7) was associated with a history of major depressive disorder (P = .003). Longer PD duration was associated with higher odds of both anxiety and depression (P ≤ .001). Our study shows a high prevalence of anxiety and depression in patients with PD, particularly among those with longer disease duration and lower educational attainment. Routine neuropsychological screening and early multidisciplinary care are warranted.

Early detection of cognitive dysfunction through reliable biomarkers remains a critical challenge in geriatric medicine. While conventional peripheral blood parameters offer convenient and cost-effective biomarker potential, previous studies have been limited by their focus on isolated cell populations. This study investigates both individual blood cell parameters and their derived ratios to comprehensively evaluate their relationship with cognitive function. In this cross-sectional conducted from 2022 to 2024, we enrolled 109 participants (51 with cognitive impairment and 58 controls) from the Haikou City Community Health Service Center. Cognitive function was assessed using the Montreal Cognitive Assessment (MoCA). We analyzed 26 blood parameters, including traditional metrics and calculated indices such as lymphocyte-to-monocyte ratio, platelet-to-lymphocyte ratio, and systemic immune-inflammation index (SII). The relationship between these parameters and cognitive domains was evaluated using comprehensive statistical analyses. Fifteen parameters showed significant differences between groups. Binary logistic regression identified SII as a risk factor (OR: 1.008, 95% CI: 1.003-1.012, P = .002). The receiver operating characteristic curve analysis indicated that the diagnostic accuracy of SII (AUC = 0.911, 95% CI: 0.856-0.966) was significantly superior to that of the sole parameter, the number of lymphocyte count (AUC = 0.702, 95% CI: 0.604-0.801). Our findings suggest that lower lymphocyte counts and elevated SII levels are associated with increased risk of cognitive impairment. These results provide new insights into the relationship between systemic inflammation and cognitive decline, with potential implications for clinical practice.