Tang YJ et al. · Jul 1, 2026
Background Sepsis-induced acute kidney injury (S-AKI) is a major global public health concern, yet effective therapeutic strategies remain limited. Mitochondrial dysfunction in renal tissues is a key pathogenic mechanism underlying S-AKI. GTS-21, a selective α7 nicotinic acetylcholine receptor (α7nAChR) agonist, exhibits anti-inflammatory and renoprotective effects in S-AKI. Methods We investigated the role of α7nAChR in S-AKI using both in vitro (lipopolysaccharide (LPS)-induced renal tubular cell injury) and in vivo (caecal ligation and puncture (CLP)-induced septic mice) models, with GTS-21 treatment. Results GTS-21 significantly attenuated mitochondrial dysfunction, suppressed apoptosis, and alleviated inflammation, thereby protecting renal tubular cells and renal tissues against LPS- and CLP-induced injury. Mechanistically, GTS-21 activated α7nAChR and upregulated myocyte enhancer factor 2 (MEF2), peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC-1α), and heme oxygenase-1 (HO-1), which collectively mediate its anti-oxidative, anti-apoptotic and anti-inflammatory effects. Conclusion These findings suggest that GTS-21 may represent a potential therapeutic strategy for sepsis-induced kidney injury.
Neuroscience
Özbek R et al. · Jul 1, 2026
Background and aim Orf virus (ORFV) is the etiologic agent of infectious ecthyma, a common worldwide disease that occasionally causes zoonotic infections. In this study, we aimed to detect and molecularly characterise circulating ORFV strains in goats from different provinces in eastern Türkiye. Materials and methods Skin lesion samples collected during ORFV outbreaks between 2022 and 2024 were analysed. Following DNA extraction, positive samples identified by real-time PCR were analysed using a multi-locus phylogenetic approach targeting the structural F1L, the major envelope protein B2L, and the virulence-related VIR gene regions. Sequencing was performed using the Sanger method, followed by phylogenetic analysis using the Maximum Likelihood method in MEGA X. Results Phylogenetic analysis revealed high genetic similarity (95.63% to 99.48%) between the Turkish strains and global isolates from countries such as China, India, Iran, and Malaysia. Notably, while most isolates shared 100% similarity, the isolate from one specific province (Tunceli) exhibited significant nucleotide substitutions and a separate clustering pattern, particularly in the VIR gene. Conclusion The results demonstrate that ORFV strains circulating in Türkiye display close phylogenetic clustering with Asian strains. The study highlights that multi-locus analyses, especially utilising the highly variable VIR gene, are essential for identifying regional genetic heterogeneity and monitoring microbial evolution. These findings provide a pilot reference for future epidemiological surveillance and vaccine development strategies in the region.
Immunology and Microbiology
Bauler S et al. · Jul 1, 2026
Iron-deficiency anemia is the most common micronutrient deficiency and a leading cause of disability-adjusted life years among adolescent girls and young women (AGYW) globally. Although multiple micronutrient supplementation (MMS) provides a broader range of micronutrients than iron-folic acid supplementation (IFAS) prior to conception, the acceptability of MMS and home-based supplementation strategies remains underexplored. We assessed the acceptability of MMS, IFAS, and a contextualized nutrition curriculum delivered via school clubs in a two-arm cluster-randomized trial across three rural secondary schools in Monapo District, Mozambique. Fourteen teachers (clusters) were randomized to deliver either weekly school-based IFAS or daily home-based MMS. A total of 492 AGYW aged 13-20 years were enrolled (240 IFAS; 252 MMS); both arms received the same nutrition curriculum. Participants in both arms reported increased energy, improved appetite, and relief from menstrual symptoms. IFAS was significantly more acceptable than MMS for smell, and some participants perceived the once-weekly IFAS regimen as less burdensome than daily MMS. Some AGYW also reported that male peers perceived MMS as birth control, or assumed the girls were pregnant, due to the image of a pregnant woman on the pill bottle. Ratings of the nutrition curriculum and teachers' facilitation were positive in both arms. Participants generally preferred the regimen they were assigned, and family support facilitated adherence. These findings suggest home-based supplementation may be a feasible and acceptable strategy for reaching in-school and out-of-school AGYW in Mozambique. Including boys in future interventions and redesigning the MMS label could help reduce misconceptions and enhance acceptability.
Medicine
Poudel P et al. · Jul 1, 2026
The creatine transporter (CRT/SLC6A8) plays a key role in cellular energy homeostasis, yet the molecular mechanism underlying creatine transport remains poorly understood. Here, we reconstruct the complete transport cycle of human CRT using a hybrid simulation strategy that combines constant-force steered molecular dynamics (cf-sMD) with targeted molecular dynamics (tMD). This approach captures continuous progression through the outward-open, outward-occluded, inward-occluded, and inward-open states and reveals a water-assisted, sequential intracellular release of Na2, creatine, and Na1. Hydration analysis shows that progressive water penetration into the binding pocket weakens protein-substrate and protein-ion interactions and destabilizes the bound state before release. Residue-level contact analysis identifies residues that interact with creatine along the transport pathway, while dynamic network analysis reveals a TM1-TM6 communication backbone that mediates long-range coupling during transport. Together, these results provide a molecular framework for creatine transport and establish an approach for investigating transport mechanisms across the broader solute carrier family.
Biochemistry, Genetics and Molecular Biology
Markova G et al. · Jul 1, 2026
In this study, we applied machine learning tools to automatically track the positions of preschool children in a natural free play setting and derived spatial and temporal features from these data to identify social interactions between them. We observed a sample of 20 preschool children (10 female, 10 male; M ± SD = 3.95 ± 0.82 years) in groups of three children each. Friendship among children was assessed, and friend dyads were paired either with a mutual friend (n = 12 groups) or with a mutually disliked peer (n = 11 groups). We used a ceiling-mounted camera to record 10-min free play sessions of the 23 groups and used an automated keypoint tracking software to extract children's locations over time from the videos. From this data, we derived the following measures for each dyad within the group: distance, social orientation, and paired correlations of children's position and speed. Additionally, a human rater coded all occurrences of social interactions in the videos. Automated measures reliably predicted the occurrence of children's social interactions, validating our choice of spatial and temporal features. Friend dyads were closer, oriented more toward each other, and showed higher position and speed correlations than non-friends. Social orientation and speed correlation varied over time, and speed correlation increased in mixed-group contexts, especially among friends. These findings highlight the value of tracking-based approaches for detecting both fine-grained interactive behavior and affiliative ties, offering key insights into the spatial dynamics of young children's peer interactions.
Psychology
Jeandel M et al. · Jul 1, 2026
Transmethylation reactions, which are crucial for regulating gene expression, require S-adenosyl-L-methionine (SAM) as methyl donor. The substrate for SAM synthesis is methionine, which can be produced by methionine synthase (MS) whose dysfunctions are associated with SAM synthesis alterations despite the presence of methionine in the milieu, suggesting a preferential use of the methionine produced de novo. This highlights the crucial role of MS activity and would imply nuclear import of SAM or MS nuclear localization, allowing protein-protein interactions with the methionine adenosyl-transferases (MAT) responsible for SAM production. Using subcellular fractions of human cells, biochemical and cellular approaches, including incorporation of 14 C-methyltetrahydrofolate, here we provide the experimental evidence of MS localization and activity in the nucleus where it interacts with MATα2, the catalytic subunit of MATII, and the methyltransferase DNMT3b. These results support the idea that spatial compartmentalization of one-carbon metabolism could play a major role in regulating the epigenome.
Medicine
Tomberli L et al. · Jul 1, 2026
Background A strong sense of school belonging (SoSB) supports students' emotional well-being, engagement, and adjustment. For students hospitalized because of chronic or complex conditions, maintaining SoSB is challenging yet essential for successful school reintegration. Methods Using a Grounded Theory approach, this study combined interviews with 16 parents, 32 mainstream teachers, 31 hospital teachers, and one association, alongside drawings from 14 hospitalized students. Data were collected pre- and post-COVID-19. Drawings were analyzed through a meaning-making approach, and all materials underwent iterative coding and constant comparison. Results Students reported strong emotional bonds with hospital teachers but felt forgotten by their mainstream schools. Peer contact was limited, and teachers felt unprepared to manage absences and reintegration. Structural gaps and weak communication between schools hindered continuity. Both formal (e.g., remote lessons) and informal (e.g., messages, drawings) exchanges, along with psychologists and associations, emerged as protective factors. Implications for school health policy, practice, and equity Findings highlight the need for integrated school-health policies, teacher training, and structured collaboration to ensure equitable relational continuity. Conclusions Promoting SoSB during hospitalization is crucial for recovery, resilience, and educational equity.
Medicine
Sodré V et al. · Jul 1, 2026
Pyridines are found in many pharmaceuticals and agrochemicals, but are synthesised from fossil fuel conversion. 2,4- and 2,5-pyridinedicarboxylic acids have been reported as products from bioconversion of renewable lignin feedstocks using engineered strains of Rhodococcus jostii RHA1 (Z. Mycroft et al. , Green Chem. , 2015, 17 , 4974-4979), but previously it has been uncertain whether the formation of the pyridine ring was assisted by enzyme catalysis. The 4,5-extradiol ring fission product of protocatechuic acid, 4-carboxy-2-hydroxymuconate 6-semialdehyde (CHMS) shows structural similarity to α-ketoglutaric acid, the substrate for reductive amination by glutamate dehydrogenase (GDH). Testing of five glutamate dehydrogenase (GDH) isozymes from R. jostii RHA1 revealed that GDH5 catalyses NADH-dependent reductive amination of CHMS, and its cyclisation to form a dihydropyridine product. The dihydropyridine can be oxidised to 2,4-pyridinedicarboxylic acid using recombinant P. fluorescens dye-decolorizing peroxidase DyP1B, providing a route to substituted pyridines from a renewable feedstock.
Engineering
Lin Y et al. · Jul 1, 2026
Homooligomerisation is a prevalent and important process that many proteins undergo to form the quaternary structures required for biological function. However, determining oligomeric states and structures experimentally remains technically challenging and time-consuming for many proteins. Here, we show that the protein structure prediction tools AlphaFold2-Multimer and AlphaFold3 can be used to quickly and accurately predict oligomeric states and structures for a range of soluble and membrane proteins. Across over 4700 proteins, AlphaFold2-Multimer provides reliable oligomeric state predictions in the majority of cases, however accuracy is more limited for proteins lacking close structural representatives in the AlphaFold training set, highlighting the dependence of these methods on robust training data. Together, our results suggest both the utility and current limitations of AlphaFold-based oligomeric state prediction, highlight cases where multiple physiologically relevant assemblies may be plausible, and provide practical guidance for minimizing computational cost, identifying challenging cases, and applying these methods to proteins lacking experimental structural data.
Biochemistry, Genetics and Molecular Biology
Martin LN et al. · Jul 1, 2026
This study explored how a history of childhood maltreatment shapes the transition to parenthood, with a focus on how partners jointly negotiate this adjustment within the couple relationship. Using Interpretative Phenomenological Analysis (IPA), in-depth semi-structured interviews were conducted with 11 heterosexual couples (22 individuals) living in the United States, in which at least one partner reported a history of childhood maltreatment. Interviews were analyzed for emergent themes related to adjustment to parenthood, relational functioning, and dyadic support processes. Four overarching dyadic themes emerged: (1) relational meaning-making of childhood maltreatment, (2) relational challenges activated by maltreatment history, (3) dyadic support as co-regulation for maltreatment-related vulnerability, and (4) couples' resilient and intentional orientation toward family life. Findings suggest that supportive romantic partnerships may function as a relational context through which parenting-related self-doubt is negotiated, emotional safety is fostered, and caregiving approaches distinct from participants' own childhood experiences are collaboratively constructed. These insights have implications for dyadic interventions during the transition to parenthood that aim to support reflective parenting and relational resilience.
Psychology