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461 papers

Personalized eye protection for head CT organ-based tube current modulation: A deep learning approach to derive 3D eyeball models from a single-view topogram.

Meng X et al. · Jul 1, 2026

Background The lens of the eye is highly radiosensitive, yet personalized shielding during head CT remains challenging due to the lack of a rapid, pre-scan localization method. Purpose To develop and validate a deep learning solution that enables automated, patient-specific eye protection by generating a precise 3D eyeball model directly from a single-view topogram. Methods Our two-stage approach combines an advanced data simulation pipeline-which generates realistic training topograms from digitally reconstructed radiographs (DRRs) using a table-movement-aware model and CycleGAN-based stylization-with a dedicated generative network (EyeGen-Net). The model was trained on 400 synthetic and validated on 100 real clinical samples. Results EyeGen-Net achieved a Dice Similarity Coefficient of 0.79 ± 0.08, a Hausdorff Distance of 5.40 ± 1.57 mm, and an Average Surface Distance of 1.84 ± 0.65 mm against expert segmentations. Crucially, phantom validation demonstrated that the derived 3D model facilitates organ-based tube current modulation (OBTCM), yielding an approximate 30% reduction in lens dose across different scanning modes without compromising diagnostic image quality. Conclusions This work provides a practical, automated pathway for implementing personalized radioprotection in routine head CT, aligning with the ALARA (As Low As Reasonably Achievable) principle.

Medicine

Radiation dose optimization in coronary CT angiography clinical application of absolute phase gating in patients with atrial fibrillation.

Li Y. · Jul 1, 2026

Background Atrial fibrillation (AF) poses significant challenges for coronary CT angiography (CCTA) due to R-R interval variability, often necessitating high radiation dose protocols. Absolute phase gating, which uses fixed millisecond delays rather than percentage-based cardiac cycle timing, may optimize image quality while reducing radiation exposure. Purpose To evaluate whether absolute phase gating reduces radiation dose while maintaining diagnostic accuracy and image quality compared to conventional relative phase gating in patients with AF undergoing CCTA. Methods This retrospective matched cohort study included 280 consecutive patients with AF (140 per group) who underwent CCTA between January 2021 and December 2023. Patients were matched by heart rate, BMI, and calcium score. The absolute phase gating group used fixed 300-millisecond post-R-wave triggering; the relative phase gating group used conventional 75% R-R interval triggering. Primary endpoints were diagnostic accuracy (sensitivity, specificity) for ≥50% stenosis and assessable segment ratio. Secondary endpoints included radiation dose parameters and image quality scores. Invasive coronary angiography served as reference standard in 118 patients (42.14%). Results Radiation dose was 64.28% lower with absolute phase gating (median DLP: 187.50 vs. 524.80 mGy·cm, p Conclusions In patients with AF undergoing CCTA, absolute phase gating can potentially reduce radiation dose while maintaining or improving diagnostic performance relative to the conventional relative phase gating protocol used at our institution. Because the magnitude of any dose reduction depends in part on the acquisition window and dose-modulation settings of the compared protocols, the benefit should be interpreted in the context of the specific comparator. These findings are consistent with the Image Wisely initiative for responsible patient radiation dose management.

Medicine

Engineering Extracellular Vesicles for Anti-Aging Therapy: Mechanisms, Applications, and Perspectives.

Huang X et al. · Jul 1, 2026

Aging is a multifactorial process driven by interconnected hallmarks, including chronic inflammation, mitochondrial dysfunction, genomic and epigenetic alterations, and dysregulated intercellular communication. Extracellular vesicles (EVs), naturally derived nanoscale membrane vesicles capable of transporting diverse bioactive cargoes across tissues and biological barriers, have emerged as a highly promising platform for regenerative and anti-aging therapeutics. In this review, we systematically summarize the multifaceted anti-aging mechanisms of EVs, including suppression of the senescence-associated secretory phenotype (SASP), remodeling of the immune microenvironment, mitochondrial restoration and metabolic reprogramming, DNA damage repair, epigenetic modulation, recovery of proteostasis, activation of regenerative signaling pathways, and cross-organ communication-mediated rejuvenation. Beyond mechanistic insights, we integrate the targeting biology and cellular entry properties of EVs, encompassing natural tropism determinants, engineered targeting strategies, biodistribution profiles, receptor-ligand interactions, intracellular trafficking, and subcellular cargo release. Unlike previous reviews focusing on a single EV source or isolated pathways, we establish a comprehensive framework connecting molecular mechanisms with delivery engineering, tissue targeting, biosafety assessment, scalable manufacturing, and clinical translation. We address major technical bottlenecks limiting EV therapeutics-including EV heterogeneity, suboptimal delivery efficiency, endosomal degradation, and the lack of standardized quality-control frameworks-while highlighting emerging solutions such as bioengineered EVs, hybrid vesicle platforms, biomaterial-assisted delivery systems, and ultrasound-enhanced targeting technologies. By bridging fundamental biology, nanomedicine engineering, and clinical translation, this review provides a strategic roadmap for the development of next-generation precision anti-aging nanotherapeutics with systemic regulatory capacity, translational feasibility, and broad clinical potential.

Biochemistry, Genetics and Molecular Biology

Molecular Interplay of PARN and Telomerase: Tail Modifiers and Disease Implications.

Felicitus S et al. · Jul 1, 2026

Poly(A)-specific ribonuclease (PARN) and telomerase are two indispensable tail-modifying enzymes that are required in two critical cellular processes: the control of the rate of RNA stability and maintenance of telomere integrity, respectively. Pathogenic variations in genes that code for PARN and telomerase complex enzymes have been implicated in several rare genetic diseases, including bone marrow failure syndromes, telomere biology-related disorders, and neoplastic ailments. This is further exemplified by defects in p53 signaling, which not only exacerbate the effects of telomere shortening but also negatively regulate PARN activity, thereby promoting cancer development and accelerated aging. This review examines the molecular interactions between PARN and telomerase, as well as their implications in disease development, with a focus on emerging therapeutic strategies that target the pathways regulated by these two enzymes.

Medicine

Aging and Western Diet Synergistically Impair Hepatic Thyroid Hormone Signaling to Promote Metabolic Dysfunction-Associated Steatotic Liver Disease (MASLD) in Mice.

Zhang X et al. · Jul 1, 2026

Metabolic dysfunction-associated steatotic liver disease (MASLD) is primarily driven by a Western-style diet and exacerbated with aging, yet underlying mechanisms remain unclear. Given the essential role of thyroid hormone (TH) in MASLD progression, we hypothesized that impaired intrahepatic TH action during aging promotes MASLD progression and severity of MASH with fibrosis. We evaluated hepatic TH metabolism in young (18-24 weeks) and old (108-120 weeks) C57BL/6J mice fed either a normal chow diet (NCD) or a Western diet with fructose (WDF) for 8 weeks. Liver histology, metabolic parameters, inflammatory and fibrotic markers, intrahepatic thyroxine (T4) and triiodothyronine (T3) concentrations, and activities of deiodinase enzymes (Dio1 and Dio3) were measured. Additionally, an in vitro hepatocyte senescence model using AML12 cells was employed to assess age-related alterations in deiodinase expression and the therapeutic efficacy of resmetirom (an FDA-approved thyromimetic). Aging and WDF synergistically exacerbated hepatic inflammation and fibrosis, accompanied by significant reductions in intrahepatic T4 and T3. Aging markedly decreased Dio1 activity, which converts T4 to active T3, whereas WDF partially restored Dio1 in old mice. Conversely, Dio3 activity, responsible for TH inactivation, increased with age but exhibited age-dependent differential responses to WDF, findings mirrored in senescent hepatocytes. Notably, resmetirom significantly reduced senescence markers, inhibited senescence-associated secretory phenotype (SASP) genes, inflammasome activation, endoplasmic reticulum (ER) stress, and activated autophagy. Collectively, our findings demonstrate that aging and stress by a Western-style diet synergistically impair hepatic TH signaling, accelerating MASLD progression. Furthermore, resmetirom improved hepatic senescence, highlighting its potential therapeutic repurposing for aging-associated hepatic pathologies, including MASLD.

Medicine

Cellular Heterogeneity During Arterial Aging.

Xu H et al. · Jul 1, 2026

Arterial aging is a major risk factor for cardiovascular disease and is associated with progressive changes in vascular structure and function, including arterial stiffening, reduced elasticity, extracellular matrix remodeling, chronic low-grade inflammation, and accumulation of senescence-associated cell states. Recent advances in single-cell RNA sequencing (scRNA-seq) have provided new opportunities to resolve the cellular heterogeneity underlying these age-related alterations in the arterial wall. In this review, we summarize current single-cell studies of arterial aging by focusing first on key phenotypic programs, including cellular senescence, extracellular matrix remodeling, inflammaging, and altered intercellular communication, and then discuss how these programs are reflected in endothelial cells, smooth muscle cells, fibroblasts, and immune cells. Across studies, aging is recurrently associated with endothelial dysfunction, smooth muscle cell phenotypic modulation, fibroblast-related matrix remodeling, and immune activation, although the degree of conservation varies depending on species, vascular bed, sex, and disease context. We further discuss emerging evidence that vascular aging involves not only cell-intrinsic transcriptional changes but also alterations in communication networks across the arterial wall. Although current single-cell studies have substantially improved our understanding of arterial aging, important limitations remain, including inconsistent cell-state annotation across studies, incomplete functional validation, and limited spatial and epigenetic resolution. Future integration of cross-species analyses with spatial transcriptomics, single-cell epigenomic approaches, and functional studies will help refine the cellular framework of arterial aging and improve its translational relevance.

Biochemistry, Genetics and Molecular Biology

α7nAChR agonist GTS-21 ameliorates sepsis-induced acute kidney injury via MEF2/PGC-1α/HO-1 axis in mice.

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

Molecular Characterisation of Orf Virus in Goats From Eastern Türkiye.

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

Adolescent Acceptability of School and Home Micronutrient Supplementation and Nutrition Curriculum in Mozambique.

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

From extracellular entry to intracellular release: A water-assisted transport cycle for creatine in SLC6A8.

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