Cytokinesis requires tightly coordinated membrane trafficking and cytoskeletal remodelling to ensure accurate physical separation of daughter cells. Rab11a, a recycling endosome-associated small GTPase, and KIF13A, a kinesin-3 family microtubule motor protein, have each been implicated in late mitotic events. However, the mechanistic relationship between Rab11a-mediated endosomal trafficking and KIF13A-driven transport during abscission remains insufficiently defined. This study aimed to elucidate the spatial and functional interplay between Rab11a and KIF13A during cytokinesis and to determine the consequences of disrupting this axis on mitotic progression and genomic stability. Rab11a and KIF13A were depleted in HeLa cells using shRNA-and siRNA-mediated knockdown strategies. Subcellular localisation and colocalisation at the intercellular bridge were examined by immunofluorescence microscopy and quantified using Pearson's correlation coefficient. Functional outcomes were assessed through multinucleation, micronuclei formation, telophase accumulation, and LAP2-positive chromatin bridge assays. Mitotic timing from nuclear envelope breakdown to abscission was quantified by live-cell spinning-disk confocal microscopy. Rab11a and KIF13A exhibited pronounced colocalisation at the ICB during cytokinesis. Depletion of either protein reduced its spatial association with the other. It resulted in marked cytokinetic defects, including increased multinucleation, micronuclei formation, telophase delay, and elevated chromatin bridge frequency. Live-cell imaging demonstrated a significant prolongation of the cytokinesis-to-abscission interval, accompanied by an extended overall mitotic M-phase. Mechanistically, loss of Rab11a or KIF13A impaired CHMP4B recruitment to the ICB, reduced PI3P accumulation, and enhanced Aurora B signalling, consistent with activation of the abscission checkpoint. These findings establish the Rab11a-KIF13A axis as a critical regulator of late mitosis, integrating endosomal trafficking with ESCRT-III-dependent abscission. Disruption of this pathway compromises abscission accuracy and promotes genomic instability, highlighting its essential role in maintaining mitotic integrity and its potential relevance in tumorigenesis. Continued exploration of the KIF13A-Rab11 interaction will yield a deeper understanding of mitotic progression and cellular organisation.
The ongoing military conflict involving the United States, Israel, and Iran has transformed long-theorized nuclear emergency scenarios into credible near-term threats. Iran's Bushehr Nuclear Power Plant, located on the Persian Gulf coastline just 17 km from the city of Bushehr, lies closer to several Gulf Cooperation Council capitals than to Tehran. At the same time, Qatar, the United Arab Emirates, Kuwait, Bahrain, and Saudi Arabia depend on seawater desalination for 60-90 % of their freshwater supply, with strategic reserves typically lasting between 36 hours and seven days. This convergence of nuclear proximity and water dependency creates a compound public health risk insufficiently addressed in the current literature. This review aimed to characterize plausible nuclear and radiation threat scenarios in the Middle East, map the spectrum of public health consequences from immediate blast and thermal injuries to long-term genetic damage, examine the risk of radiation contamination of the Persian Gulf leading to regional water supply collapse, and propose an evidence-based preparedness framework. A narrative review of peer-reviewed studies, international agency reports, and governmental guidance was conducted using MEDLINE/PubMed, Web of Science, Scopus, and grey literature from major global health and nuclear safety organizations. A single nuclear detonation in a major Gulf city could result in hundreds of thousands of immediate casualties while rendering seawater unusable for desalination over a prolonged period. Freshwater reserves would be rapidly depleted, leading to the simultaneous collapse of healthcare services, food systems, and sanitation infrastructure. Children and fetuses represent the most vulnerable groups, with increased risks of thyroid cancer, neurodevelopmental damage, and heritable mutations following radiation exposure. Key preparedness strategies include potassium iodide prophylaxis, shelter-in-place protocols, expansion of water reserves to at least 90 days, and strengthened regional civil defense coordination. Preparing for low-probability, high-impact events is far less costly than the consequences of inaction. See also the graphical abstract(Fig. 1).
Scrub typhus is a re-emerging but often underdiagnosed tropical zoonosis in India. Its clinical heterogeneity, serological overlap with other endemic infections, and frequent absence of pathognomonic signs contribute to delayed diagnosis and high complication rates. Central nervous system, pulmonary, and renal involvement signify severe disease and are associated with considerable morbidity and mortality. We describe three cases of previously healthy young adult males (ages 24-32) who presented with severe, organ-threatening complications of scrub typhus: acute encephalitis syndrome (AES), acute respiratory distress syndrome (ARDS), and acute kidney injury (AKI). All patients had evidence of systemic inflammation, thrombocytopenia, and multiorgan dysfunction. Eschars-although present in all cases-were initially missed or overlooked, delaying causal diagnosis. Serologic cross-reactivity with dengue, chikungunya, and leptospira further complicated early recognition. Despite early initiation of doxycycline upon clinical suspicion, one patient with ARDS succumbed to progressive hypoxemia and multiorgan failure. These cases underscore the protean and fulminant nature of scrub typhus and highlight the diagnostic importance of thorough skin examination in febrile patients with unexplained CNS, pulmonary, or renal involvement. In endemic settings, empiric doxycycline should be considered early, even in the absence of classical signs. Early recognition and treatment remain the most critical determinants of survival. Our experience reinforces that scrub typhus, though elusive, is a potentially treatable cause of severe febrile illness when promptly identified.
Chronic low-grade inflammation (LGI) is increasingly recognized as a biologically meaningful contributor to heterogeneity in major psychiatric disorders. The tryptophan (Trp)-kynurenine (KYN) metabolic pathway is a leading candidate mechanism because immune and stress-related signals can redirect Trp metabolism toward bioactive KYNs that influence glutamatergic signaling, redox balance, energetics, and immune feedback. In treatment-resistant depression and schizophrenia spectrum psychosis, this pathway is especially relevant because inflammatory burden often coexists with anhedonia, fatigue, cognitive dysfunction, and negative symptoms. Yet the literature remains difficult to integrate. Studies often rely on shallow biomarker panels, inconsistent inflammatory phenotyping, mixed matrices, and incomplete handling of major confounders, including smoking, adiposity, sleep disruption, infection timing, and medication exposure. Interpretation is further complicated by the kynurenic acid (KYNA) paradox and by central-peripheral discrepancies, as KYNA-related findings are strongly shaped by biological context and compartment, with blood measures often diverging from cerebrospinal fluid profiles and therefore not reliably reflecting central branch balance. This review therefore aimed to identify the Trp-KYN nodes most relevant to chronic LGI in psychiatry, synthesize clinical and preclinical evidence by disorder and symptom module, and define realistic near- and long-term research priorities. Here we highlight that Trp-KYN findings become more coherent when interpreted as context-dependent branch-balance signatures rather than standalone biomarkers. This framework can improve comparability, sharpen stratification, and support biomarker-enriched translational psychiatry. More broadly, it offers a practical model for linking immune biology to symptom dimensions across heterogeneous brain disorders. See also the graphical abstract(Fig. 1).
Cognitive decline and dementia represent major and growing global health challenges, driven largely by population aging and increased longevity. Currently, more than 55 million people worldwide live with dementia, a figure projected to rise to approximately 153 million by 2050. Alzheimer's disease accounts for the majority of cases, and despite extensive research, effective disease-modifying therapies remain limited. Consequently, increasing attention has shifted toward prevention strategies targeting modifiable risk factors. Accumulating evidence indicates that dementia is not an inevitable consequence of aging and that up to 45 % of cases may be attributable to potentially modifiable lifestyle and environmental factors operating across the life course. Lifestyle behaviors-including diet, physical activity, smoking, alcohol consumption, sleep, and social and cognitive engagement-have emerged as key targets for intervention. In particular, adherence to healthy dietary patterns such as the Mediterranean, DASH, and MIND diets has been associated with better cognitive outcomes, while unhealthy dietary patterns may increase risk. However, findings across studies remain heterogeneous, and uncertainties persist regarding causality, optimal exposure timing, and specific lifestyle components. Recent large prospective cohorts, meta-analyses, umbrella reviews, and multidomain intervention trials have advanced understanding of these associations but have also highlighted important gaps, including limited randomized evidence and underrepresentation of diverse populations. This narrative review critically synthesizes current evidence on lifestyle factors and dietary patterns associated with cognitive decline and dementia risk, focusing on recent high-quality studies. By integrating findings across domains, it aims to clarify areas of consensus and uncertainty, inform prevention strategies, and identify priorities for future research and public health action. See also the graphical abstract(Fig. 1).
Whether the Malnutrition-Sarcopenia Syndrome (MSS) represents a distinct clinical entity or simply describes severe malnutrition with prominent muscle wasting remains debated. Nevertheless, the coexistence of inadequate nutritional status and severe loss of skeletal muscle mass, strength, and function creates clinically significant challenges that warrant focused attention. The causes of MSS involve a vicious cycle driven by insufficient dietary intake, inflammation, hormone deficiency as well as physical inactivity. In a bidirectional relationship, malnutrition accelerates muscle protein breakdown and impairs synthesis, while sarcopenia reduces functional capacity and potentially leads to decreased physical activity and loss of independence. The consequences are substantial and include accelerated functional decline and delayed convalescence, reflected by prolonged hospital length of stay and higher rates of increased mortality compared to single conditions. Effective countermeasures require integrated interventions addressing both components simultaneously: adequate protein and energy intake, and vitamin D, combined with progressive resistance training, treatment of underlying diseases, and medication optimization. This multidisciplinary approach demonstrates synergistic benefits that exceed addressing either condition alone. Regardless of whether MSS constitutes a unique syndrome, recognizing this clinical pattern serves the pragmatic purpose of identifying vulnerable older adults who require comprehensive, simultaneous nutritional and functional interventions to break the vicious cycle and improve outcomes. See also the graphical abstract(Fig. 1).
Metabolic dysfunction-associated steatotic liver disease (MASLD) and type 2 diabetes mellitus (T2DM) are two common, interconnected conditions that pose a major global health challenge. The worldwide prevalence of MASLD among individuals with T2DM exceeds 60 %, with a substantial proportion of cases having metabolic dysfunction-associated steatohepatitis (MASH) and an increased risk of liver-related complications, such as cirrhosis, liver failure, or hepatocellular carcinoma. The coexistence of MASLD and T2DM is also associated with poorer glycemic control and a higher risk of cardiovascular events, chronic kidney disease, and mortality. Notably, MASLD increases the risk of developing T2DM, with risk rising stepwise with liver disease severity, especially liver fibrosis. The close bidirectional relationship between MASLD and T2DM creates a vicious cycle that drives liver disease progression, worsens insulin resistance, and impairs glucose metabolism. This likely reflects shared underlying mechanisms, including insulin resistance, low-grade inflammation, lipotoxicity, adipose tissue dysfunction, and an altered gut-liver axis. Screening strategies are crucial for MASLD and T2DM, with current guidelines recommending assessment of liver fibrosis in all individuals with T2DM and regular screening for dysglycemia in those with MASLD. Pharmacological treatments, especially incretin-based therapies, sodium-glucose cotransporter 2 inhibitors, and resmetirom, show significant benefits across metabolic, hepatic, and extrahepatic outcomes. Overall, recognizing and addressing the bidirectional relationship between MASLD and T2DM is essential for better risk stratification, earlier intervention, and reduced long-term hepatic and extrahepatic complications. This narrative review summarizes current evidence on the bidirectional relationship between MASLD and T2DM, discussing epidemiological data, pathophysiological mechanisms, clinical implications, and therapeutic options. See also the graphical abstract(Fig. 1).
Hypertension remains one of the most prevalent and consequential cardiovascular risk factors worldwide and is a leading cause of heart disease. Hypertensive heart disease may manifest in alterations in left ventricular (LV) geometry, including concentric remodeling, concentric hypertrophy, and eccentric hypertrophy, representing adaptive responses to chronic pressure or volume overload that may progress to maladaptive remodeling and heart failure. LV geometric patterns, defined by LV mass and relative wall thickness, carry important diagnostic and prognostic implications independent of blood pressure levels. This review provides a comprehensive and contemporary overview of the relationship between hypertension and LV geometry. We summarize key determinants of hypertensive LV remodeling, including cumulative blood pressure exposure, sex differences, metabolic comorbidities, obesity, pericardial adiposity, and obstructive sleep apnea. We discuss current approaches to screening and diagnosis, highlighting the strengths and limitations of electrocardiography, echocardiography, and cardiac magnetic resonance imaging. We review emerging applications of artificial intelligence in electrocardiographic and echocardiographic assessment, with particular attention to their potential to improve detection, phenotypic differentiation, and prognostication. We further examine the prognostic significance of LV remodeling in hypertension and review evidence supporting regression of LV hypertrophy through intensive blood pressure control, management of comorbidities, and lifestyle interventions. Early identification and reversal of hypertensive LV remodeling may offer a critical opportunity to prevent progression to heart failure and reduce long-term cardiovascular morbidity and mortality. See also the graphical abstract(Fig. 1).
Arthritis is one of the most prevalent chronic musculoskeletal disorders worldwide, affecting more than 300 million individuals and representing a leading cause of pain, disability, and reduced quality of life. The global burden of osteoarthritis and rheumatoid arthritis continues to rise due to population aging, sedentary lifestyles, and increasing metabolic comorbidities. Liposomal drug carriers hold great promise in maximizing dexamethasone's therapeutic utility while minimizing its first-pass effect and systemic toxicity. Due to their biocompatibility, slow-release capability, and potential for target-specific delivery, liposomes enable localized drug sequestration within inflamed joints through both passive and active targeting mechanisms. This review aims to analyze the pharmacological action of dexamethasone in arthritis in conjunction with the advantages inherent to liposomal formulations, as well as recent advancements in liposome design, such as stimuli-responsive and theranostic liposomes. Despite their great promise, limitations, including drug leakage, immunogenicity, and regulatory hurdles, remain major impediments to their clinical use. Future directions indicate promise for personalized, image-directed liposomal therapies in a paradigm shift for arthritis treatment. Overall, liposomal dexamethasone represents a major breakthrough in the safe design of target-specific, effective anti-inflammatory therapies for arthritis. See also the graphical abstract(Fig. 1).
The 'New York City Marathon' is one of the world's largest and most influential mass-participation marathons. Although numerous studies have examined performance trends, participation patterns, pacing behavior, environmental influences, and physiological aspects of runners in this event, no review has synthesized the evidence specific to this race. This study aimed to systematically summarize the scientific literature on the 'New York City Marathon'. A systematic search of Scopus, PubMed, Web of Science, Embase, and Cochrane was conducted using terms related to the 'New York City Marathon' to identify studies published up to February 2026. Eligible studies included runners of all ages, sexes, and performance levels, with no restrictions on publication date, topic, or study design. Extracted data included: (1) authors; (2) publication year; (3) study design; (4) sample characteristics; (5) variables assessed; and (6) main findings. Results were synthesized narratively by domain. Seventy-six publications met the inclusion criteria. Participation increased markedly over time, driven primarily by growth among women and age-group runners. While elite and competitive age-group performances improved in recent decades, mean finish times across the entire field increased by ~40 min since the 1970s, reflecting the democratization of marathon running. Ethiopian runners were the youngest and fastest. Peak performance occurred at 29.7 years in women and 34.8 years in men (1-year age intervals), and in the 30-34 and 35-39 age groups, respectively (5-year intervals). Approximately 10 % of runners experienced major injuries during training or the race that prevented starting or finishing. Higher training volumes increased injury risk, with foot, knee, and hip injuries most common, whereas adequate preparation reduced risk. Environmental conditions-particularly temperature-had a stronger influence on race times than course metrics. Performance declined with increasing temperature, especially among slower runners and among men aged 30-64 and women aged 40-64. Runners generally adopted a positive pacing strategy with a final spurt in the last segment (40-42.2 km). The fastest split occurred between 5-10 km and the slowest between 35-40 km, coinciding with the undulating terrain entering Central Park. Older athletes paced more evenly than younger athletes. Men showed a larger decrease in running speed from the fastest to the slowest splits than women (21.1 % vs. 16.7 %). Slower runners exhibited greater early-race deceleration but larger late-race speed increases, whereas faster runners maintained the most even pacing. Participation in the 'New York City Marathon' has grown substantially, driven by increased involvement of women and age-group runners. Although elite performance has improved, overall mean finish times have slowed due to broader participation. Ethiopian runners were the youngest and fastest, with peak performance occurring in the early to mid-30s. Injury prevalence was considerable, particularly with higher training volumes, though adequate preparation mitigated risk. Higher temperatures slowed performance, especially among slower runners. Pacing was predominantly positive, with older athletes pacing more evenly and faster runners showing the smallest performance decline. Future research should explore cardiovascular monitoring technologies-including real-time ECG streaming during the race-and assess the impact of innovations such as carbon-plated "supershoes" on performance and pacing. See also the graphical abstract(Fig. 1).
Topical drug delivery routes have long served as a primary therapeutic approach for treating various skin disorders. However, conventional formulations, like creams, ointments, and gels, have a number of drawbacks, such as systemic toxicity, short duration of action, low skin permeability, and drug instability. Through the advancement of innovative delivery carriers such solid lipid nanoparticles, nanostructured lipid carrier system, nanoemulsions, & transdermal patches, recent developments in nanotechnology have completely changed topical delivery. These technologies improve skin penetration, provide regulated release, and increase medication absorption. Furthermore, because of their excellent therapeutic results, tailored particle size, and high entrapment effectiveness, formulations such as cubosomes, nanogels, and microsponges are being investigated. The significant expansion of topical delivery platforms, particularly hydrogel-based and nanoemulgel formulations, is highlighted by biostatistics from 2023-2024. Novel delivery systems have shown considerable effectiveness in treating dermatological disorders such atopic dermatitis, psoriasis, and eczema in clinical trials. Concurrently, the anti-inflammatory, antioxidant, and antibacterial qualities of botanical substances such as curcumin, bolstered by improved delivery through liposomal and nanocurcumin formulations, have demonstrated encouraging outcomes. This review explored the advancement of nanotechnology-enabled topical and transdermal delivery platforms, their clinical use, technical developments, and the growing use of natural bioactives like curcumin in dermatological treatment are all thoroughly covered in this study. The combined results highlight how crucial novel formulations and delivery methods are to resolving issues with the skin barrier and enhancing patient outcomes. See also the graphical abstract(Fig. 1).
The ubiquitous soil bacterium Bacillus cereus is one of the major pathogens causing toxin-based foodborne diseases, manifesting as diarrhoeal or emetic syndrome. Main symptoms of the former are diarrhoea and abdominal pain, caused by the proteinaceous enterotoxins haemolysin BL (Hbl), non-haemolytic enterotoxin (Nhe) and cytotoxin K (CytK). Responsible for the latter is the cyclic dodecadepsipeptide cereulide, leading to nausea and vomiting, and, in severe and rare cases, also to organ failure and death. This review first addresses the complex taxonomy of the B. cereus group as well as the distribution of toxin genes within this group. Further, recent developments in studying the multifaceted intrinsic and extrinsic factors regulating enterotoxin and ces gene expression and toxin secretion are summarised. Special emphasis is placed on the latest findings regarding the mode of action of the pore-forming toxins, as well as on specific target structures and receptors, and the activation of cellular signalling pathways and inflammatory/apoptotic responses upon toxin exposure. Production and toxicity of the relatively new discovered cereulide isoforms are also discussed. A profound understanding of the fundamental processes of toxin formation and action is essential for accurate risk assessment of B. cereus isolates and for improving diagnostic procedures to increase food safety. See also the graphical abstract(Fig. 1).
Insufficient early vascularization remains a major limitation for the successful integration of implanted dermal substitutes. To overcome this challenge, nanofat has recently been introduced as a promising fat derivative for implant seeding. The present study investigated whether short-term ex vivo pretreatment with the hypoxia-mimetic agent deferoxamine (DFO) can further enhance the in vivo vascularization capacity of nanofat. Nanofat from green fluorescent protein (GFP)+ donor mice was pretreated for 1 h with DFO (1 mM) or vehicle and subsequently seeded onto collagen-glycosaminoglycan-based dermal substitutes, which were implanted into dorsal skinfold chambers of syngeneic GFP- recipient mice. Implant vascularization, microhemodynamics, tissue integration and inflammatory response were assessed over a 14-day period using intravital fluorescence microscopy, histology and immunohistochemistry. Dermal substitutes seeded with DFO-pretreated nanofat exhibited a faster and more extensive vascularization, as evidenced by a significantly higher functional microvessel density in both implant border and center zones when compared to controls. Most blood-perfused microvessels originated from the GFP+ DFO-pretreated nanofat. The improved vascularization was associated with reduced leukocyte-endothelial cell interactions in peri-implant venules as well as a decreased implant infiltration by macrophages and neutrophils, indicating an attenuation of the early innate inflammatory response. Moreover, DFO pretreatment promoted the tissue integration of the implants and regenerative extracellular matrix remodeling, as evidenced by increased collagen III deposition. These findings demonstrate that short-term ex vivo DFO pretreatment effectively primes nanofat to enhance microvascular network formation and suppress inflammation, resulting in an accelerated and improved engraftment of nanofat-seeded dermal substitutes. See also the graphical abstract(Fig. 1).
