Wang S et al. · Jul 1, 2026
Oxidative stress drives tumor microenvironment (TME) remodeling by inducing metabolic reprogramming and cellular senescence. Glutamine, a key substrate supporting oxidative stress defense, has been implicated in TME remodeling and metastasis, yet its specific role in initiating tumor invasion remains unclear. Here, oxidative stress induced the generation of senescent macrophages in the TME, and clinical samples showed that their accumulation positively correlates with malignancy. We established cisplatin- and radiation-induced senescent macrophage models that exhibited distinct senescence-associated secretory phenotypes (SASP) and enhanced squamous cell carcinoma (SCC) migration and invasion. Integrated metabolomic and transcriptomic analyses revealed the glutamine-glutamate pathway as a central metabolic hub, with glutaminase 2 upregulated to drive glutaminolysis and strongly associated with IL-1β expression. Mechanistically, IL-1β secreted by senescent macrophages promoted tumor invasion by downregulating IL-1R2 and activating NF-κB signaling in SCC cells. Targeting the glutamine metabolism-regulated IL-1β/IL-1R2 axis effectively suppressed SCC invasion. These findings uncover a novel metabolic mechanism linking glutamine metabolism to SASP regulation and suggest a therapeutic strategy to limit SCC invasion.
Biochemistry, Genetics and Molecular Biology
Huang H et al. · Jul 1, 2026
Elastin-collagen nanoparticles (ECnPs) have been shown in our previous studies to self-assemble into different morphologies, including nanoplates and nanovesicles, by manipulating the sequence length of the elastin-like peptide (ELPs) and collagen-like peptide (CLPs) of a given conjugate. In this work, we demonstrate that the morphologies of ECnPs can also be modulated, for a given ECnP sequence, with variations in solution pH and/or the amount of encapsulated drug. Specifically, the peptide (VPGYG) 6 -(GPO) 8 preferentially formed nanovesicles under basic conditions but assembled into nanoplates under acidic conditions. Another sequence, (VPGWG) 2 (VPGFG) 2 -(GPO) 8 , produced nanovesicles when loaded with a high concentration of dexamethasone-carboxyfluorescein (Dex-CF), but transitioned to nanoplates at lower drug loading. Furthermore, in addition to the different morphologies observed for a given set of initial solution conditions, our studies also illustrate the possibility of triggering vesicle-to-plate transformations for a given ECnP with release of Dex-CF over time. These results highlight multiple avenues for controlling ECnP morphology, expanding their applicability as a flexible and efficient drug delivery platform.
Biochemistry, Genetics and Molecular Biology
Fortis HO et al. · Jul 1, 2026
Endurance competition preparation involves complex psychological, logistical, and sociocultural factors. This study investigated the pre-race nutrition practices of female endurance athletes, by applying a newly developed extended Theory of Planned Behaviour, including behavioural execution to the framework to capture real-world influences (ETPB-X). Using a convergent mixed-methods design, 27 female triathletes competing at the 2024 IRONMAN World Championships completed questionnaires, 48-h food diaries, and semi-structured interviews before and after the race. Quantitative data (n = 23) were analysed for energy and macronutrient intake, whereas qualitative data were thematically coded using the conceptual ETPB-X framework, incorporating attitudes, subjective norms, perceived behavioural control (PBC), utilitarian drivers, and behavioural execution. Only 26% (6/23) of athletes achieved carbohydrate loading guidelines (8-12 g·kg -1 body mass (BM)·day -1 ), with an overall mean intake of 6.4 ± 2.1 g·kg -1 BM. Higher carbohydrate intake correlated with faster finish times (r = -0.50, p = 0.035), whereas fibre intake was positively associated with gastrointestinal (GI) symptom severity (r = 0.85, p < 0.001). Qualitative findings revealed that adherence to diet plans was influenced by PBC, travel logistics, emotional regulation, and athlete identity. This study provides a novel application of the ETPB-X framework to pre-race nutrition in female endurance athletes. Athletes often under-achieve carbohydrate loading targets despite awareness, with success determined as much by psychosocial and contextual factors as by knowledge. Practically, enhancing PBC, improving planning/preparation, and delivering clear goal-aligned education may bridge the intention-behaviour gap. Integrating behavioural frameworks into performance nutrition offers a pathway towards more effective athlete-centred interventions.
Biochemistry, Genetics and Molecular Biology
Bhuiyan MSA et al. · Jul 1, 2026
Background Inclusion body hepatitis (IBH), caused by fowl adenoviruses (FAdVs), is an emerging disease of commercial broilers associated with significant economic losses. In Malaysia, molecular epidemiological data on circulating FAdV serotypes have largely been restricted to Peninsular regions, with limited information available from East Malaysia (Sabah), despite its rapidly expanding poultry industry and distinct production systems. This regional knowledge gap limits comprehensive understanding of FAdV transmission dynamics at the national level. Objectives This study aimed to detect FAdV infection in broiler flocks with IBH-compatible lesions in Sabah, Malaysia, and to characterize circulating serotypes and their phylogenetic relationships. Methods Thirty pooled tissue samples (liver and gizzard) and 60 serum samples were collected from three broiler farms (YAN, KON, and NIS). FAdV detection was performed using polymerase chain reaction (PCR) targeting the hexon gene. Serological responses were assessed using enzyme-linked immunosorbent assay (ELISA). Positive PCR products were sequenced, and phylogenetic analysis was conducted to determine serotype distribution and genetic relatedness. Results FAdV DNA was detected in 33.3% (10/30; 95% CI: 17.3-52.8) of pooled tissue samples, with detection rates of 70% (95% CI: 44.4-97.5), 20% (95% CI: 2.5-55.6) and 10% (95% CI: 0.3-44.5) in the YAN, KON and NIS farms, respectively. Although descriptive differences were observed among farms, these variations were not statistically significant (p > 0.05). All positive samples yielded the expected 897 bp hexon gene amplicon. ELISA revealed high seropositivity in unvaccinated flocks, with the highest mean antibody titre observed in the YAN farm (24,716.5 ± 4516.1). Molecular characterization identified FAdV-8b (species E) and FAdV-11 (species D), indicating co-circulation. Phylogenetic analysis showed close relatedness to strains from Korea, Belgium, China and Australia. Conclusions The co-circulation of FAdV-8b and FAdV-11 in Sabah broiler farms underscores the need for continuous molecular surveillance, enhanced biosecurity and breeder-level vaccination strategies using locally circulating FAdV strains to control IBH in Malaysia.
Biochemistry, Genetics and Molecular Biology
Zhang Y et al. · Jul 1, 2026
Aging is characterized by progressive physiological decline and age-related pathologies, yet the molecular determinants underlying lineage- and species-specific aging traits remain poorly understood. Although protein-coding regulators have dominated aging research, the contribution of long non-coding RNAs (lncRNAs), particularly primate-specific lncRNAs, has not been systematically explored. Here, through evolutionary screening and cross-species aging-associated analyses, we identified a set of primate-specific lncRNAs (including LINC01021, CTC-575 l10.1, CTA-150C2.13, and RP11-305F18.1, etc.) associated with human aging, and we functionally characterized LINC01021 as a representative candidate to assess their causal involvement. In human cells, LINC01021 promotes cellular senescence, whereas its silencing attenuates senescence-associated phenotypes. Mechanistically, LINC01021 is predominantly located in the nucleus, where it facilitates DAZAP1-dependent destabilization of RBMX mRNA, leading to activation of the P53 pathway and induction of canonical senescence features. At the organismal level, ectopic expression of human LINC01021 in mice contributes to aging-like phenotypes, including increased frailty and impaired motor coordination. Together, these findings implicate primate-specific lncRNAs in lineage-restricted aging and highlight an evolutionarily recent regulatory layer that may modulate aging trajectories.
Biochemistry, Genetics and Molecular Biology
Paiva BR et al. · Jul 1, 2026
Introduction Exogenous lifestyle factors, such as different cultures, diets, and geo-graphic location, can alter the microbiota in patients with chronic kidney disease (CKD), which is closely related to inflammation. However, few studies have examined how these factors influence the composition of the microbiota. Thus, the objective of this study was to characterize and compare the intestinal microbiota profile and inflammation in CKD patients undergoing hemodialysis (HD) in the Southern and Southeastern regions of Brazil. Methods Blood and stool samples were obtained from two groups of HD patients: one from the city of Blumenau (Southern region) and the other from the city of Rio de Janeiro (Southeastern region). Fecal DNA was extracted, and the V4 region of the bacterial 16S ribosomal RNA gene was sequenced. The fecal microbiome was analyzed using bioinformatic tools. Plasma concentrations of IL-6 and TNF-α were evaluated by ELISA. Results Thirty patients were included in the study, with 14 individuals residing in the Southern region (group S) [50% male, 58 (13.5) years of age] and 16 individuals residing in the Southeastern region (group SE) [47.1% male, 57 (19) years of age]. The α- and β-diversity indices of the intestinal microbiota did not differ significantly between the groups. However, patients from the Southern region had higher plasma TNF-α (p = 0.008) and IL-6 (p = 0.003) levels than those from the Southeastern region. Conclusion Although HD patients with CKD residing in the Southern and Southeastern regions present similar intestinal microbial patterns, patients from the Southern region had higher concentrations of inflammatory markers.
Biochemistry, Genetics and Molecular Biology
Shahparvari MR et al. · Jul 1, 2026
Background Pancreatic steatosis (PS) is a metabolic condition associated with obesity, insulin resistance, and fatty liver disease. Advanced Glycation End Products (AGEs), abundant in processed and high-temperature-cooked foods, have been linked to several metabolic disorders; however, their relationship with PS has not been previously examined. Methods In this case-control study, 278 individuals with gallstones, aged 55.7 ± 15.1 years, were classified as cases (with PS, n = 89) or controls (without PS, n = 189). PS was defined based on increased echogenicity of the pancreatic parenchyma relative to surrounding structures. Dietary intake was assessed using a food frequency questionnaire. Logistic regression models were used to estimate odds ratios (ORs) and 95% confidence intervals (CIs) for PS across quartiles of dietary AGE intake. The fully adjusted model included age, sex, total energy intake, body mass index, smoking status, and alcohol consumption. Results Higher dietary AGE intake was significantly associated with an increased likelihood of PS. In the crude model, odds of PS did not differ significantly across quartiles of dietary AGE intake compared with the lowest quartile. After adjustment for age and sex, individuals in the highest quartile had higher odds of PS (OR = 3.56; CI: 1.1-11.6; p = 0.040). In the fully adjusted model, significant associations were observed for the third (OR = 2.76; CI: 1.69-11.1) and fourth (OR = 3.3; CI: 1.79-13.7) quartiles of dietary AGE intake compared with the lowest quartile. A significant positive trend in the odds of PS was observed across increasing quartiles of dietary AGE intake (p for trend = 0.024). Conclusion Our findings suggest a potential role of dietary AGEs in pancreatic fat accumulation; however, causality cannot be inferred. Larger prospective and interventional studies are needed to confirm these associations and to determine whether reducing dietary AGE exposure can beneficially influence pancreatic fat.
Biochemistry, Genetics and Molecular Biology
Munro ML et al. · Jul 1, 2026
Aim The ryanodine receptor (RyR2) is an intracellular Ca 2+ release channel which mediates numerous cellular functions across different tissues. Dysregulation of RyR2 channel activity leads to pathological Ca 2+ release, which often underlies disrupted cellular signaling in disease states. In the heart, RyR2 channels forms discrete clusters and calcium release units (CRUs) which control channel activity. These structures demonstrate nanoscale remodeling in disease states associated with pathological Ca 2+ release activity in the heart. Hence, these nanoscale structures are critical in regulating Ca 2+ release in health and disease. RyR2 is also expressed in brain; however, whether analogous clusters and CRUs form in neurons remains unexplored. Methods Using super-resolution imaging, we assessed RyR2 organization in CA1 pyramidal neurons of wild-type mice. Furthermore, we used the APP/PS1 mouse model of Alzheimer's disease (AD) to assess whether there is nanoscale remodeling of RyR2 in a setting associated with pathological Ca 2+ release in neurons. Results Here, we provide the first identification and detailed characterization of RyR2 clusters in central nervous system neurons, which are comparable to those reported in the heart. Moreover, we observed a decrease in RyR2 cluster size and reduced CRU organization in AD mice at an age associated with high plaque burden and cognitive deficits. This remodeling is analogous to that reported in pathological states in the heart. Conclusion Together, these findings implicate the nanoscale remodeling of RyR2 clusters and CRUs as a novel mechanism underlying Ca 2+ channel dysregulation and neuronal dysfunction in AD.
Biochemistry, Genetics and Molecular Biology