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Abstract Aging is a complex biological process characterized by the gradual decline of cellular functions, increased susceptibility to diseases, and impaired stress responses. Hypoxia, defined as reduced oxygen availability, is a critical factor that influences aging through molecular pathways involving hypoxia‐inducible factors (HIFs), oxidative stress, inflammation, and epigenetic modifications. This review explores the interconnected roles of hypoxia in aging, highlighting how hypoxic conditions exacerbate cellular damage, promote senescence, and contribute to age‐related pathologies, including cardiovascular diseases, neurodegenerative disorders, cancer, metabolic dysfunctions, and pulmonary conditions. By examining the molecular mechanisms linking hypoxia to aging, we identify key pathways that serve as potential therapeutic targets. Emerging interventions such as HIF modulators, antioxidants, senolytics, and lifestyle modifications hold promise in mitigating the adverse effects of hypoxia on aging tissues. However, challenges such as the heterogeneity of aging, lack of reliable biomarkers, and safety concerns regarding hypoxia‐targeted therapies remain. This review emphasizes the need for personalized approaches and advanced technologies to develop effective antiaging interventions. By integrating current knowledge, this review provides a comprehensive framework that underscores the importance of targeting hypoxia‐induced pathways to enhance healthy aging and reduce the burden of age‐related diseases.

IntroductionThe coronavirus disease 2019 (COVID-19) pandemic, caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has posed extraordinary challenges to global health systems and economies. The virus’s rapid evolution has resulted in several variants of concern (VOCs), including the highly transmissible Omicron variant, characterized by extensive mutations. In this study, we investigated the genetic diversity, population differentiation, and evolutionary dynamics of the Omicron VOC during the fifth wave of COVID-19 in Pakistan.MethodsA total of 954 Omicron genomes sequenced during the fifth wave of COVID-19 in Pakistan were analyzed. A Bayesian framework was employed for phylogenetic reconstructions, molecular dating, and population dynamics analysis.ResultsUsing a population genomics approach, we analyzed Pakistani Omicron samples, revealing low within-population genetic diversity and significant structural variation in the spike (S) protein. Phylogenetic analysis showed that the Omicron variant in Pakistan originated from two distinct lineages, BA.1 and BA.2, which were introduced from South Africa, Thailand, Spain, and Belgium. Omicron-specific mutations, including those in the receptor-binding domain, were identified. The estimated molecular evolutionary rate was 2.562E-3 mutations per site per year (95% HPD interval: 8.8067E-4 to 4.1462E-3). Bayesian skyline plot analysis indicated a significant population expansion at the end of 2021, coinciding with the global Omicron outbreak. Comparative analysis with other VOCs showed Omicron as a highly divergent, monophyletic group, suggesting a unique evolutionary pathway.ConclusionsThis study provides a comprehensive overview of Omicron’s genetic diversity, genomic epidemiology, and evolutionary dynamics in Pakistan, emphasizing the need for global collaboration in monitoring variants and enhancing pandemic preparedness.

Extracellular vesicles (EVs) have emerged as key intercellular communication and pathogenesis mediators. Parasitic organisms’ helminths, cause widespread infections with significant health impacts worldwide. Recent research has shed light on the role of EVs in the lifecycle, immune evasion, and disease progression of these parasitic organisms. These tiny membrane-bound organelles including microvesicles and exosomes, facilitate the transfer of proteins, lipids, mRNAs, and microRNAs between cells. EVs have been isolated from various bodily fluids, offering a potential diagnostic and therapeutic avenue for combating infectious agents. According to recent research, EVs from helminths hold great promise in the diagnosis of parasitic infections due to their specificity, early detection capabilities, accessibility, and the potential for staging and monitoring infections, promote intercellular communication, and are a viable therapeutic tool for the treatment of infectious agents. Exploring host-parasite interactions has identified promising new targets for diagnostic, therapy, and vaccine development against helminths. This literature review delves into EVS’s origin, nature, biogenesis, and composition in these parasitic organisms. It also highlights the proteins and miRNAs involved in EV release, providing a comprehensive summary of the latest findings on the significance of EVs in the biology of helminths, promising targets for therapeutic and diagnostic biomarkers.

Japanese encephalitis virus (JEV) causes acute viral encephalitis in humans and reproductive disorders in pigs. JEV emerged during the 1870s in Japan, and since that time, JEV has been transmitted exclusively throughout Asia, according to known reporting and sequencing records. A recent JEV outbreak occurred in Australia, affecting commercial piggeries across different temperate southern Australian states, and causing confirmed infections in humans. A total of 47 human cases and 7 deaths were reported. The recent evolving situation of JEV needs to be reported due to its continuous circulation in endemic regions and spread to non-endemics areas. Here, we reconstructed the phylogeny and population dynamics of JEV using recent JEV isolates for the future perception of disease spread. Phylogenetic analysis shows the most recent common ancestor occurred about 2993 years ago (YA) (95% Highest posterior density (HPD), 2433 to 3569). Our results of the Bayesian skyline plot (BSP) demonstrates that JEV demography lacks fluctuations for the last two decades, but it shows that JEV genetic diversity has increased during the last ten years. This indicates the potential JEV replication in the reservoir host, which is helping it to maintain its genetic diversity and to continue its dispersal into non-endemic areas. The continuous spread in Asia and recent detection from Australia further support these findings. Therefore, an enhanced surveillance system is needed along with precautionary measures such as regular vaccination and mosquito control to avoid future JEV outbreaks.

Abstract Haemonchus contortus is a hematophagous endoparasite of small ruminants, which is responsible for huge economic losses in livestock sector. Hyaluronidase produced by infective larvae of H. contortus can degrade hyaluronic acid present in the host’s abomasal tissue. Thus, it facilitates larval tissue invasion and early establishment. We herein explored this ability of hyaluronidase in H. contortus, and tested whether hyaluronidase is utilized as a virulence factor by H. contortus while establishing the infection. We first successfully blocked the hyaluronidase gene in L3 larvae by RNA interference (RNAi), which was subsequently confirmed by qPCR, enzymatic activity, and immunohistochemistry assays. Using these larvae we then conducted in vivo and in vitro assays on sheep to assess the effects of hyaluronidase suppression on larval invasion and establishment of infection. The in vivo assay showed a significant drop in worm burden in siRNA treated group in comparison to control group. During in vitro assay we applied an ovine ex vivo model where siRNA treated group of larvae showed significantly reduced invasion of the abomasal tissue explants as compared to control group. These findings indicate that hyaluronidase plays a key role in host’s tissue invasion and larval establishment, and it is used as a virulence factor by H. contortus while establishing the infection. As an invasive virulence molecule, its functional research is thus conducive to the prevention of haemonchosis.

Zymomonas mobilis, a promising candidate for industrial biofuel production, is capable of nitrogen fixation naturally without hindering ethanol production. However, little is known about the regulation of nitrogen fixation in Z. mobilis. We herein conducted a high throughput analysis of proteome and protein acetylation in Z. mobilis under N2-fixing conditions and established its first acetylome. The upregulated proteins mainly belong to processes of nitrogen fixation, motility, chemotaxis, flagellar assembly, energy production, transportation, and oxidation–reduction. Whereas, downregulated proteins are mainly related to energy-consuming and biosynthetic processes. Our acetylome analyses revealed 197 uniquely acetylated proteins, belonging to major pathways such as nitrogen fixation, central carbon metabolism, ammonia assimilation pathway, protein biosynthesis, and amino acid metabolism. Further, we observed acetylation in glycolytic enzymes of central carbon metabolism, the nitrogenase complex, the master regulator NifA, and the enzyme in GS/GOGAT cycle. These findings suggest that protein acetylation may play an important role in regulating various aspects of N2-metabolism in Z. mobilis. This study provides new knowledge of specific proteins and their associated cellular processes and pathways that may be regulated by protein acetylation in Z. mobilis.

Metagenomic analysis of mosquito-borne and mosquito-specific viruses is useful to understand the viral diversity and for the surveillance of pathogens of medical and veterinary importance. Yunnan province is located at the southwest of China and has rich abundance of mosquitoes. Arbovirus surveillance is not conducted regularly in this province particularly at animal farms, which have public health as well as veterinary importance. Here, we have analyzed 10 pools of mosquitoes belonging to Culex tritaeniorhyncus, Aedes aegypti, Anopheles sinensis, and Armigeres subalbatus species, collected from different animal farms located at Yunnan province of China by using metagenomic next-generation sequencing technique. The generated viral metagenomic data reveal that the viral community matched by the reads was highly diverse and varied in abundance among animal farms, which contained more than 19 viral taxonomic families, specific to vertebrates, invertebrates, fungi, plants, protozoa, and bacteria. Additionally, a large number of viral reads were related to viruses that are non-classified. The viral reads related to animal viruses included parvoviruses, anelloviruses, circoviruses, flaviviruses, rhabdoviruses, and seadornaviruses, which might be taken by mosquitoes from viremic animal hosts during blood feeding. Notably, the presence of viral reads matched with Japanese encephalitis virus, Getah virus, and porcine parvoviruses in mosquitoes collected from different geographic sites suggested a potential circulation of these viruses in their vertebrate hosts. Overall, this study provides a comprehensive knowledge of diverse viral populations present at animal farms of Yunnan province of China, which might be a potential source of diseases for humans and domestic animals.

Japanese encephalitis (JE) is a vaccine-preventable disease caused by the Japanese encephalitis virus (JEV), which is primarily prevalent in Asia. JEV is a Flavivirus, classified into a single serotype with five genetically distinct genotypes (I, II, III, IV, and V). JEV genotype III (GIII) had been the most dominant strain and caused numerous outbreaks in the JEV endemic countries until 1990. However, recent data shows the emergence of JEV genotype I (GI) as a dominant genotype and it is gradually displacing GIII. The exact mechanism of this genotype displacement is still unclear. The virus can replicate in mosquito vectors and vertebrate hosts to maintain its zoonotic life cycle; pigs and aquatic wading birds act as an amplifying/reservoir hosts, and the humans and equines are dead-end hosts. The important role of pigs as an amplifying host for the JEV is well known. However, the influence of other domestic animals, especially birds, that live in high abundance and close proximity to the human is not well studied. Here, we strive to briefly highlight the role of birds in the JEV zoonotic transmission, discovery of birds as a natural reservoirs and amplifying host for JEV, species of birds susceptible to the JEV infection, and the proposed effect of JEV on the poultry industry in the future, a perspective that has been neglected for a long time. We also discuss the recent in vitro and in vivo studies that show that the newly emerged GI viruses replicated more efficiently in bird-derived cells and ducklings/chicks than GIII, and an important role of birds in the JEV genotype shift from GIII to GI.

Abstract Background The limited availability of complex coronary intervention facilities and qualified operators, due to the high cost associated with chronic total occlusion (CTO) percutaneous intervention (PCI) equipment and a shortage of necessary skills, has led to a scarcity of capable medical centers in Pakistan. This study seeks to examine the outcomes and potential complications associated with CTO PCI procedures conducted at the Cardiac Catheterization Laboratories of a prominent national institute in Pakistan, which handles a large volume of cases. Results Three hundred and six patients were included in the study in the study period of six months. The mean age was 59.49 (± 9.16) years: 256 (83.66%) were male and 50 (16.34%) were female. CTO was successfully re-vascularized in 237 (77.5%) with a complication rate of 13.7%. Two hundred and ninety-eight (97.39%) patients underwent an antegrade approach, while RCA was the most common target vessel (47.71%). Diabetes was the only significant associated risk factor with CTO PCI failure (30.43% vs. 30.43%, P-value = 0.015). Conclusion We achieved an excellent procedural success rate with a low complication rate. CTO procedural failure is associated with a higher complication rate, and diabetes is among the risk factors that lead to higher procedural failure.