Bacterial antimicrobial resistance (AMR) poses a significant global public health challenge. The escalation of AMR is primarily attributed to the horizontal gene transfer (HGT) of antibiotic resistance genes (ARGs), often facilitated by plasmids. This underscores the critical need for a comprehensive understanding of the resistance mechanisms and transmission dynamics of these plasmids. In this study, we utilized in vitro drug sensitivity testing, conjugation transfer assays, and whole-genome sequencing to investigate the resistance mechanism of an extensively drug-resistant (XDR) Pseudomonas aeruginosa clinical isolate, MAS152. We specifically focused on analyzing the drug-resistant plasmid pMAS152 it harbors and its potential for widespread dissemination. Bioinformatics analysis revealed that MAS152 carries a distinct IncpP-2A plasmid, pMAS152, characterized by a 44.8 kb multidrug resistance (MDR) region. This region houses a 16S rRNA methyltransferase (16S-RMTase) gene, rmtB, conferring high-level resistance to aminoglycoside antibiotics. Notably, this region also contains an extended-spectrum β-Lactamase (ESBL) gene, bla_PER-1, and an efflux pump operon, tmexCD-oprJ, which mediate resistance to β-Lactams and quinolone antibiotics, respectively. Such a combination of ARGs, unprecedented in reported plasmids, could significantly undermine the effectiveness of first-line antibiotics in treating P. aeruginosa infections. Investigation into the genetic environment of the MDR region suggests that Tn2 and IS91 elements may be instrumental in the horizontal transfer of rmtB. Additionally, a complex Class I integron with an ISCR1 structure, along with TnAs1, seems to facilitate the horizontal transfer of bla_PER-1. The conjugation transfer assay, coupled with the annotation of conjugation-related genes and phylogenetic analysis, indicates that the plasmid pMAS152 functions as a conjugative plasmid, with other genus Pseudomonas species as potential hosts. Our findings provide vital insights into the resistance mechanisms and transmission potential of the XDR P. aeruginosa isolate MAS152, underlining the urgent need for novel strategies to combat the spread of AMR. This study highlights the complex interplay of genetic elements contributing to antibiotic resistance and underscores the importance of continuous surveillance of emerging ARGs in clinical isolates.

Phospholipase C (PLC) enzymes are vital for various body functions as they facilitate key signaling pathways that regulate numerous physiological processes. PLC in eukaryotic cells converts phosphatidylinositol 4,5-bisphosphate (PIP ₂ ) into inositol 1,4,5-triphosphate (IP ₃ ), and diacylglycerol, a pivotal pathway modulating intracellular calcium levels. The systematic review investigates the structural characteristics and metabolic pathways of PLC, PIP ₂ , and IP ₃ within human systems, examining isoform functions of PLC and potential therapeutic applications. Specifically, different PLC subfamilies and isozymes across cells and tissues can alter the effect of the pathway through distinct PIP ₂ binding affinities, enzyme expressions, activation modes, and activity rates. PIP ₂ , an inner membrane component, participates in multiple signaling pathways—PLC, PI3K/AKT/mTOR, and phosphatidylinositol 5 phosphate—modulating diverse cellular functions. The secondary messenger IP ₃ predominantly regulates intracellular Ca ²⁺ levels via IP ₃ receptor-associated calcium ion channels. Alterations in this pathway, from PLC mutations to receptor variations and antagonist presence, can impact human cellular functions with diverse clinical implications. Therapeutic potential exists to modulate specific functions through the PLC-PIP ₂ -IP ₃ pathway, though certain PLC targets are challenging for drug development due to their critical roles and complex networks. Further research is necessary to comprehensively grasp the clinical implications and potential of targeting specific pathway components.

Scientific questions Diarrhea susceptibility varies with age, and its epidemiology evolves with period and cohort changes. Therefore, understanding age, period, and cohort effects on diarrhea incidence and death is crucial. Evidence before this study Although the latest data from the Global Burden of Disease Study (GBD) 2021 showed that the number of deaths related to diarrhea worldwide decreased by 60.3% between 1990 and 2021, the problem of health inequality remains serious. The mortality rate of children with diarrhea in sub-Saharan Africa was more than 150 times that of high-income regions in 2021. Previous studies focused on trends or descriptions, lacking age-period-cohort analysis or burden driver decomposition. New findings The epidemiology of diarrhea demonstrates distinct patterns across age groups, with incidence risk declining until the age of 20 before increasing again after 60. Similarly, the risk of death was highest in young children aged 0-4 and saw a resurgence in individuals over 60 years of age. Over time, population growth has been identified as the primary driver of changes in the overall disease burden. Despite this, the burden of diarrhea is forecast to continue its downward trend. A significant disparity remains, as countries with a lower sociodemographic Index (SDI) continue to bear a disproportionately high burden; however, it is noted that these inequality gaps have narrowed over time. Significance of the study This study not only informs the development and allocation of health resources for diarrhea prevention, complementing previous GBD research, but also demonstrates the need for targeted public health strategies to address inequalities via improved healthcare, protection for vulnerable populations, and increased coverage and development of vaccines.

Southeast Asian countries are at the forefront of public health pressures due to a confluence of factors such as population growth, urbanization, environmental pollution, and infectious diseases (re)emergence. Therefore, the ability to be able to conduct research addressing local and regional needs is of paramount importance. As such, biobanking activities, the standardized collection of biological samples, and associated data, developed over the past few decades supporting ongoing biomedical and clinical research, as well as surveillance are of critical importance. However, the regulatory landscape of biobanking is not widely understood and reported, which this narrative review aims to address for the ASEAN member states. It is evident that there are specific regulatory arrangements within each ASEAN member state, which though may be sufficient for the current level of operations, are unlikely to support a regional sharing of biological samples, data, and eventually benefits from the conducted research. Additionally, legacy and often-overlapping regulatory frameworks exist, which raise the need of an eventual consolidation under a single framework. Thus, this field requires further study as well as the creation of viable, practical proposals that would allow for biobanking harmonization and thus the exchange of biological samples and data to be achieved regionally, if not further afield.