AlSedairy SA et al. · Jul 1, 2026
Adipocyte hypertrophy is an obesity-related metabolic dysfunction, which is frequently associated with decreased mitochondrial activity during adipocyte development. The current study aimed to assess the potential of epoxy clerodane diterpene (ECD) (IUPAC: 5R, 10R)-4R, 8R-dihydroxy-2S, 3R:15, 16-diepoxycleroda-13(16), 17, 12S:18,1S-dilactone) extracted from Cassia tora on adipocyte differentiation, lipid accumulation, mitochondrial function, and inflammation. Human bone marrow mesenchymal stem cells (hMSCs) were stimulated into adipocytes using the standard differentiation medium. The methodological design included the evaluation of ECD cytotoxicity, lipid accumulation, mitochondrial membrane potential, qRT-PCR, and ELISA. ECD didn't significantly reduce the cellular viability; however, it decreased lipid accumulation by 65%, 87%, and 87.5% at doses of 2, 4, and 8 μM, respectively. Also, at 4 µM of ECD, it decreased adipocyte hypertrophy, increased mitochondrial membrane potential, raised the expression of thermogenesis-related genes (UCP-1, PPARγC1α, SREBP1c), decreased the expression of adipogenic proteins (C/EBPα, PPARγ), increased adiponectin levels, and reduced inflammatory markers (IL-4, TNF-α) compared to untreated controls. Thus, ECD may hold tremendous promise as a natural agent for controlling adipogenesis, and its impacts on lipid metabolism, mitochondrial function, and inflammatory responses demonstrate its potential for therapeutic use in the treatment of obesity and associated metabolic diseases.
Agricultural and Biological Sciences
Uddin S et al. · Jul 1, 2026
Mutagenesis combined with ionomic profiling offers a powerful approach to explore the genetic basis of essential and toxic element accumulation in rice grain and to generate materials for marker-assisted breeding. However, large-scale ionomic screening has not previously been conducted in Bangladeshi rice germplasm. To isolate mutants with altered grain concentrations of iron, zinc (Zn), arsenic (As), and cadmium (Cd), we mutagenized BRRI dhan84 using ethyl methanesulfonate (EMS; 0.5% and 1%) and gamma rays (250, 300, 350, and 400 Gy). A total of 8503 M 2 plants were screened for brown rice ionome using inductively coupled plasma mass spectrometry (ICP-MS). Candidate mutants were selected based on robust Z-scores (|Z-scores| > 2) of the elements for individual plants, resulting in the isolation of 38 mutants. To validate the screening process, two mutants were characterized in detail: high grain As (osabcc1-3) and low grain Zn and Cd (oshma2-4). Whole genome sequencing of the mutants and the correlation between phenotype and genotype in the F 2 population indicated that OsABCC1 and OsHMA2 are likely the causal genes. The osabcc1-3 mutant carries a splice-site mutation at the exon-intron junction of OsABCC1, whereas oshma2-4 harbors a 3.3 kb insertion in OsHMA2. Notably, oshma2-4 exhibited similar growth and yield to BRRI dhan84 in a paddy field, suggesting its potential for breeding low-Cd rice. Together, these results demonstrate the effectiveness of ionomic screening in Bangladeshi rice for uncovering allelic variation controlling metal homeostasis and provide valuable genetic resources and physiological insights relevant to rice improvement.
Agricultural and Biological Sciences
Goble SR et al. · Jul 1, 2026
An ICD-10 code specific for hepatic encephalopathy (HE), K76.82, was introduced in October of 2022. We aimed to assess changes in HE documentation following the introduction of this code. Using the National Inpatient Sample, we compared utilization of ICD-10 codes historically used to identify HE before and after K76.82. From 2016 to 2021, 20.0% of cirrhosis hospitalizations included a non-specific HE code, decreasing to 4.7% in 2023. K76.82 was used in 20.3% of hospitalizations in 2023. The introduction of K76.82 has dramatically changed the documentation of HE, and future studies assessing HE trends and outcomes need to account for these changes.
Medicine
Pellowe M et al. · Jul 1, 2026
This study describes the implementation of a mechanistic subcutaneous (SC) injection model for the Open Systems Pharmacology platform. As the SC route of administration is gaining increased popularity, there is a growing need for tools to predict, analyze, and understand the SC absorption process and the mechanisms involved. The interplay between molecular, formulation, administration, and physiological properties influences both the rate and extent of drug appearance in circulation. The primary objective of this study was to provide a structural modeling basis for mechanistic simulations of drug absorption after SC administration, considering fundamental molecular properties and systemic disposition characteristics. A key aspect of the model design was the intention to support generalizability and translational application across drug characteristics and species, providing a consistent structure for both small molecules and biologics. The SC model was implemented leveraging the structure and parameterization of PK-Sim to allow unified integration to the whole-body physiologically based pharmacokinetic model. An input-response analysis and a set of case examples were conducted to visualize model responsiveness and illustrate potential application in drug development. The generic framework may also serve as the backbone for further implementations to describe complex injection and formulation dependencies. Collectively, this framework establishes a mechanistic foundation for the simulation of SC drug absorption of both small molecules and biologics, providing a basis for further development and informed evaluation across preclinical and clinical stages within the Open Systems Pharmacology platform.
Pharmacology, Toxicology and Pharmaceutics
Zhong D et al. · Jul 1, 2026
Renal aging shortens healthspan and propagates organ dysfunction beyond the kidney, yet its molecular drivers remain incompletely defined. Here we identify microsomal prostaglandin E synthase-2 (mPGES-2) as a critical regulator of renal aging and its skeletal consequence. Genetic ablation of Ptges2 improved health indices in aged mice, prolonged median survival, and markedly alleviated glomerulosclerosis, podocyte injury, and renal senescence. Single-cell transcriptomic analysis, together with podocyte- and tubule-specific knockout models, showed that podocyte mPGES-2, rather than tubular mPGES-2, is the dominant intrarenal driver of aging-related kidney injury. Mechanistically, mPGES-2 promoted podocyte senescence through a PGE 2 /EP1 signaling axis. Podocyte-specific Ptges2 deletion also mitigated age-related osteoporosis and restored renal calcitriol and α-klotho, supporting a kidney-bone mechanism secondary to impaired renal endocrine function. Consistent with the genetic models, pharmacological inhibition of mPGES-2 with SZ0232 attenuated renal aging and improved bone microarchitecture in aged mice. Both genetic deficiency and pharmacological inhibition of mPGES-2 were well tolerated, with no overt adverse effects on major organs. These findings identify podocyte mPGES-2 as a druggable determinant of renal aging and a potential therapeutic target for aging-associated osteoporosis.
Medicine
Li PWC et al. · Jul 1, 2026
Background ICU survivors frequently develop post-intensive care syndrome (PICS), a cluster of persistent physical, cognitive and psychological impairments that substantially impair recovery and quality of life. Existing rehabilitation approaches are predominantly monomodal and exercise-focused, yielding inconsistent outcomes and failing to address the multidimensional burden of PICS adequately. Aim To evaluate the feasibility and preliminary efficacy of COMBAT-ICU, a home-based Combined Activity and Cognitive Intervention for ICU survivors at risk of PICS. Study design A parallel, three-arm, assessor-blinded pilot randomised controlled trial randomised 36 ICU survivors (1:1:1) to COMBAT-ICU-an 8-week blended program of progressive physical exercise and computerised cognitive training delivered via supervised home visits and online sessions-an exercise-only group or an attention control group. The primary outcomes were feasibility (recruitment, retention and intervention adherence) and safety; secondary exploratory outcomes encompassed PICS severity, physical capacity, cognition, mental health and health-related quality of life (HRQoL). Results COMBAT-ICU was feasible and safe (36 ICU survivors randomised), with no serious adverse events recorded, retention exceeding 82% at follow-up and session adherence exceeding 90%. COMBAT-ICU produced significantly greater reductions in PICS severity versus attention control at post-intervention (p = 0.014, d = -0.50) and follow-up (p = 0.043, d = -0.45). It also yielded clinically meaningful moderate-to-large effect sizes for walking endurance, global cognition, short-term memory and HRQoL index scores compared with attention control and consistently outperformed exercise-only across cognitive and HRQoL domains. Between-group differences in anxiety and depressive symptoms were small across all active groups. Conclusions COMBAT-ICU is feasible and shows promising preliminary efficacy in mitigating PICS. Integrating cognitive and physical training within a home-based blended delivery model may confer synergistic benefits beyond exercise alone, providing domain-specific effect size estimates and a compelling rationale for definitive multicentre trials. Relevance to clinical practice Multidomain home-based rehabilitation is a viable post-discharge strategy for ICU survivors. COMBAT-ICU offers an evidence-informed, scalable framework to enhance survivorship care, pending confirmation in larger, fully powered trials. Trial registration The trial was registered at ClinicalTrials.gov (NCT06117761).
Medicine
Hong J et al. · Jul 1, 2026
Accelerating global climate risks increasingly threaten renewable energy infrastructure (REI). However, little evidence on heterogeneous impacts of climate risks on REI across countries, the moderating role of REI resilience, and post-disaster recovery patterns is available, despite their critical importance for guiding resilient energy transitions and informing disaster risk governance. To address these issues, we employed dynamic panel models in 215 countries and regions from 2004 to 2022. We find that (1) climate risk significantly damages global REI, with disaster frequency and institutional resilience having mitigation effects. (2) The damage follows an inverted U-shape with increasing disaster frequency and an "N" shape with increasing disaster duration. As renewable energy generation share increases, the damage intensifies and progresses through four increasingly severe stages. (3) Economic resilience exhibits a "Creative destruction" effect in developed nations and a "Build back better" recovery in poor countries. (4) Although social resilience worsens climate disaster damage globally, high disaster frequency and institutional resilience can facilitate a "Recovery to trend" in socially advanced nations. (5) REI in South America is the most affected, followed by Asia and Africa, whereas Europe is the least impacted. Wind energy is the most vulnerable, followed by bioenergy, solar, and hydropower.
Engineering
Jang HY et al. · Jul 1, 2026
Amyloid beta (Aβ), a key component of drusen in age-related macular degeneration (AMD), induces oxidative stress, mitochondrial dysfunction, and degeneration in the retinal pigment epithelium (RPE), contributing to progressive vision loss in the elderly. We investigated the protective role of Humanin (HN), a mitochondria-derived peptide with known neuroprotective effects in Aβ-related neurodegenerative diseases, in retinal pathology induced by subretinal injection of FITC-labeled Aβ. HN enhanced the clearance of Aβ-accumulated mitochondria in the RPE while preserving retinal function and RPE barrier integrity. In ARPE-19 cells, HN activated AMP-activated protein kinase (AMPK), leading to phosphorylation of ULK1 and Beclin1, which promoted the interaction between Beclin1 and Parkin and their translocation to mitochondria. This process facilitated the removal of Aβ-accumulated mitochondria in the RPE. Our results demonstrate that targeting mitophagy in the RPE with HN may offer a promising therapeutic strategy for AMD.
Medicine
Tejakum W et al. · Jul 1, 2026
Background Raising adolescents with intellectual disabilities in Thailand is challenging. Whilst some mothers show resilience, limited understanding exists of the factors within these cultural contexts that contribute to resilience. This qualitative study explores experiences of mothers caring for adolescent children with intellectual disabilities in Thailand. Methods Semi-structured interviews were conducted with 12 Thai mothers of adolescents with intellectual disabilities at the Rajanukul Institute in Thailand. Interview transcripts were analysed using thematic analysis, guided by Braun and Clarke (2006). Results Six themes were developed, detailing mothers' resilience journeys: becoming a mother of a child with intellectual disabilities, finding my way, navigating challenges, support systems, holding on to faith, and forward-thinking strategies. Conclusion This study reveals that resilience amongst mothers is a dynamic process shaped by personal attributes, coping strategies, social support, and cultural and spiritual beliefs. These findings highlight the need for culturally sensitive interventions to strengthen parental resilience.
Psychology
Silva BBRD et al. · Jul 1, 2026
The study was conducted in Brazil and aimed to systematically review empirical research examining the association between maternal indicators of anxiety, stress, and depression and the developmental outcomes of preterm children. A literature search was conducted across PubMed, Web of Science, PsycINFO, EMBASE, Scopus, LILACS, and SciELO. Sixteen studies were analyzed. The systematic review revealed a significant association between maternal anxiety, depression, and stress indicators and poorer developmental outcomes for children born prematurely. This association was observed whether it was considered a single indicator of maternal mental health or a combination of two or more indicators. The systematic review affirms the impact of maternal mental health on the development of preterm children in early childhood.
Medicine