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464 papers

Clinicopathological and molecular characterization of HPV-associated cervical poorly cohesive carcinoma: a rare aggressive entity.

Liu W et al. · Jul 1, 2026

Primary signet-ring cell carcinoma and poorly differentiated adenocarcinoma with poorly cohesive morphology in the cervix are rare conditions, and their clinicopathological features remain poorly described. This study defines primary cervical poorly differentiated adenocarcinomas meeting the diagnostic criteria for poorly cohesive carcinoma as outlined in the 2019 WHO Classification of Digestive System Tumors as 'HPV-associated cervical poorly cohesive carcinomas' (HPV-associated CPCC) and describe their clinicopathological and molecular features. Sixteen HPV-associated CPCC cases were analyzed and classified into three histological subtypes: signet-ring cell carcinoma (n = 4), not otherwise specified (n = 6), and mixed types (n = 6). All patients were Chinese (median age: 46 years; range: 30-66). Vaginal bleeding was the primary presenting symptom (100.0%). High-risk human papillomavirus (HPV) was identified in all tumors, with HPV-18 as the predominant genotype (n = 13), HPV-16 in two cases, and a single case exhibiting concurrent infection with HPV-16, -18, and -58. Overall, 56.3% presented with advanced-stage disease (International Federation of Gynecology and Obstetrics [FIGO] IIIB-IVB), frequently involving regional lymph nodes (56.3%) and distant sites (18.8%). Histopathological examination revealed diffuse stromal infiltration (100%), lymphovascular invasion (75.0%), necrosis (75.0%), and desmoplasia. Immunohistochemically, all cases showed p16 block positivity. Variable expression of antibody-drug conjugate targets was observed, with HER2-low expression (33.3%), and positive staining for Trop-2 (85.7%), nectin-4 (42.9%), and tissue factor (92.3%). During follow-up, disease-specific mortality was 50.0%. The 3-year overall survival rate was 56.3%, which was significantly lower in advanced-stage disease (45.0%) than in early-stage disease (75.0%). Whole-exome sequencing revealed low tumor mutational burden (median 1.28 Muts/Mb), recurrent mutations in AK1, ARHGAP39, KRT24, MICAL3, SLC6A9 (27.3%), KRAS, and KMT2C (18.2%), alongside MUC2 copy gain (63.6%) and bidirectional Y_RNA alterations (gain 54.5%/loss 45.5%). Collectively, HPV-associated CPCC represents a distinct and aggressive subtype characterized by distinctive histopathological features, a predominant association with HPV18, frequent presentation at advanced stages, and marked molecular and biomarker heterogeneity.

Medicine

Podocyte mPGES-2 Determines Renal Aging and Contributes to Senile Osteoporosis.

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

Home-Based Combined Activity and Cognitive Intervention for Post-Intensive Care Syndrome: A Pilot Randomised Controlled Trial.

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

Global Renewable Energy Infrastructure Resilience Under Climate Risks.

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

Humanin Mitigates Aβ-Induced Retinal Pigment Epithelium Injury via AMPK-Beclin1-Dependent Mitophagy.

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

Exploring Resilience in Mothers of Adolescents With Intellectual Disabilities in Thailand: A Qualitative Study.

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

How important are quantum mechanical effects in controlling biological functions: Enzymes, electron transfer and bird navigation.

Zhang A et al. · Jul 1, 2026

In light of the centennial of the Schrödinger equation, this article addresses the popular idea that quantum mechanical effects play an important role in biological systems. We start by defining what is qualified as a quantum effect. We then clarify the idea that quantum mechanical tunneling is a crucial factor in enzyme catalysis. Here we show that quantum tunneling is in fact anticatalytic and that there is no consistent theoretical and experimental evidence that the tunneling effects are enhanced significantly by enzymes relative to the corresponding reference solution reactions. We next turn to electron transfer reactions, arguing that in most cases the efficiency of the reaction is controlled by classical effects. We also consider the low barrier hydrogen bond idea and clarify its anticatalytic nature. In addition, we present a specific case study of electron transfer in a protein system potentially responsible for bird navigation, providing a concrete example for evaluating the role of quantum and classical effects under biologically relevant conditions. We argue that for the electron transfer step in this system, the most important control is associated with the classical control of the relevant potential surfaces and the fluctuations of the key energy gaps.

Chemistry

Characterization of the Ligamentum Mucosum in the Feline and Canine Stifle.

Ko NT et al. · Jul 1, 2026

In humans, the ligamentum mucosum (LM) is described as a ligamentous structure originating from the femoral intercondylar notch and inserting into the infrapatellar fat pad. Proposed clinical implications include knee stabilization, contribution to post-operative revascularization of adjacent structures, and causation of anterior knee pain if inflamed. Published reports of the LM are rare in dogs and, to our knowledge, none exist for cats. Because common veterinary gross anatomy texts omit the LM from their descriptive anatomy of the stifle, students sometimes mistake the LM for the cranial cruciate ligament. Therefore, a description of the LM in the feline and canine stifle would serve as an important veterinary anatomy learning resource. The aim of this project was to characterize the LM in the cat and dog. Stifles were dissected from 62 cat hindlimbs (n = 24 preserved, n = 38 fresh) and 47 dog hindlimbs (n = 9 preserved, n = 38 fresh). The presence or absence of the LM was determined and described. Representative samples were processed for haematoxylin and eosin staining. Grossly, the LM was found bilaterally in 95.2% of cats and in 83.0% of canine limbs, appearing as an elastic, friable band of white-to-pink tissue tethering the infrapatellar fat pad to the femoral intercondylar notch. Histological samples revealed collagen fibrils, vascular structures and neural tissue. These data provide evidence of the LM in the cat and dog, and bolster currently available anatomic educational resources. The presence of the LM in the canine and feline stifle merits further investigation into its function in health and disease states.

Veterinary

Renal expression of Bach1 and oxidative stress in chronic kidney disease: evidence from a preclinical model.

Cruz BOD et al. · Jul 1, 2026

Introduction The transcription factor BTB and CNC homology 1 (Bach1) represses the nuclear factor erythroid 2-related factor 2 (Nrf2), which controls antioxidant gene expression, and its role in chronic kidney disease (CKD) remains unclear. Methods CKD was induced by 5/6 nephrectomy in rats. Kidney fibrosis and oxidative stress markers were measured. The gene expression of Nrf2, Bach1, and nuclear factor kappa B (NF-κB) was assessed. Results CKD increased oxidative stress markers in plasma, kidney, and heart, as well as promoted kidney fibrosis. Moreover, CKD reduced cardiac Nrf2 expression. However, Bach1, Nrf2, and NF-κB remained unchanged in the kidney. Conclusion CKD did not modulate Bach1 mRNA levels in the kidneys of 5/6 nephrectomized rats.

Biochemistry, Genetics and Molecular Biology

Formulation of Peptide-Based Nanoparticles Using a Microfluidic Device.

Hammoum T et al. · Jul 1, 2026

Peptide-based nanoparticles (PBN) have emerged as a promising alternative to lipid nanoparticles (LNP) for nucleic acid delivery and efficient cellular uptake. In this study, we evaluated the formulation of WRAP5 (W- and R-rich amphipathic peptide 5)-based PBN using a microfluidic device and assessed the impact of key process parameters, flow rate ratio (FRR), total flow rate (TFR), and mixing channel design, on nanoparticle characteristics. Across 72 formulations encapsulating small interfering RNA (siRNA) or plasmid DNA (pDNA), dynamic light scattering revealed consistent mean sizes ranging from 50 to 70 nm, with a low polydispersity index (PdI < 0.22), independent of FRR, TFR, or mixer type. Stability studies demonstrated that siRNA-loaded PBN exhibited moderate size increases during storage at 4°C, whereas pDNA-loaded PBN remained highly stable for up to 70 days. Biological assays confirmed robust activity: WRAP5:siRNA PBN achieved approximately 50% CDK4 silencing in GIST-T1 cells, and WRAP5:pDNA PBN mediated efficient mCHERRY expression in HeLa cells, regardless of formulation method or storage duration. These findings highlight the robustness and scalability of WRAP5-based PBN, contrasting with LNP systems that require stringent control of FRR and TFR, and partially underscore their potential for nucleic acid delivery applications.

Biochemistry, Genetics and Molecular Biology