Browse Articles

Plasma lipopolysaccharide levels predict mortality in acutely ill children in Low- and Middle-Income Countries

Abstract Childhood mortality remains high in low-resource settings, where environmental enteric dysfunction (EED) is prevalent. Peripheral blood bacterial lipopolysaccharides (LPS) are potential biomarkers of intestinal microbial translocation and inflammation; however, the effects of LPS translocation on mortality in this context remains unexplored. We investigate the association between plasma LPS and mortality among 638 acutely ill hospitalised children and compare them to 251 well community peers in a nested case-cohort (NCC) conducted between November 2016 and January 2019 across 9 sites in 6 countries in sub-Saharan Africa and South Asia. Higher levels of plasma LPS and inflammatory biomarkers (fecal calprotectin, plasma myeloperoxidase, and CD14) are associated with elevated 90-day mortality, and those associations are independent of wasting status. Non-survivors with high plasma LPS exhibit elevated gram-negative enteric microbiota, increased fecal biomarkers of EED, systemic inflammatory proteins, and differentially expressed proteins linked to the Insulin-like growth factor (IGF) nutritional axis, Interleukin-1 and collagen regeneration. Cellular interaction network models deconvoluted from a single-cell transcriptomic dataset enable an exploratory investigation of systemic immune responses and epithelial-immune cells crosstalk active in pathways leading to mortality. This knowledge can guide the identification of potential therapeutic signaling pathways in settings with high EED and malnutrition.

Thymol-rich essential oil from Oliveria decumbens Vent. exhibits antibacterial activity

Targeting tumor metabolic flexibility enhances radiotherapeutic efficacy via mitochondrial complex I Inhibition in an intracranial S180 sarcoma mouse model

Programmable targeted RNA degradation via dCas13d-directed chaperone-mediated autophagy (dCasCMA)

Hybrid quantum-classical stochastic programming for co-planning 5G base stations and photovoltaic power stations in urban communities

Genotype × environment interaction studies in monoecious and gynoecious bitter gourd (Momordica charantia L.) genotypes for stability using multi-model based approach

Genome graphs reveal the importance of structural variation in Mycobacterium tuberculosis evolution and drug resistance

Abstract Structural variants (SVs) are increasingly recognized as key drivers of bacterial evolution, yet their role has not been explored thoroughly. This is due to limitations in traditional short-read sequencing and linear reference-based analyses, which can miss complex structural changes. Tuberculosis (TB), a disease caused by Mycobacterium tuberculosis ( Mtb ), remains a major global health concern. In this study, we harness long-read sequencing technologies and genome graph tools to construct a Mtb pangenome reference graph (PRG) from 859 high-quality, diverse, long-read assemblies. To enable accurate genotyping of SVs leveraging the PRG, we developed miniwalk, a tool that outperforms a traditional linear genome-based approach in precision for SV detection. We characterize patterns of structural variation genome-wide, revealing a virulence-associated ESX-5 deletion to be recurrent across the phylogeny, and fixed in a sub-lineage of L4. Systematic screens for additional genes that are recurrently affected by SVs implicated those related to metal homeostasis, including a copper exporter fixed in the widely distributed L1.2.1 sub-lineage. Lastly, we genotyped 41,134 isolates and found SVs putatively associated with resistance to various first and second-line drugs. These findings underscore the broader role of SVs in shaping Mtb diversity, highlighting their importance in both understanding evolution and designing strategies to combat drug-resistant TB.

Fear of missing out predicts loneliness through psychological and social pathways among doctoral students

Study of severe early childhood caries in children under general anesthesia from a single hospital

Pyridinium ylides as photocatalytic atom transfer reagents

Socio-demographic and occupational factors influencing expatriate construction workers’ musculoskeletal pain

Incidence and determinants for non-suicidal self-injury in an Italian prison in Milan (Feb–Oct 2023): a retrospective cohort analysis

An apical ring protein essential for conoid complex assembly and daughter cell formation in Toxoplasma gondii

Abstract In Toxoplasma gondii , the conoid complex consists of intraconoidal microtubules (ICMTs), preconoidal rings (PCRs), apical polar ring (APR), and the conoid. This organelle plays an important role for initiation of gliding motility, required for host cell invasion and egress. The molecular mechanisms governing stepwise assembly of the conoid complex remain poorly understood. We previously identified CGP, an essential protein required for motility initiation. Here, we demonstrate that CGP is crucial for anchoring FRM1 and other PCR components to mature PCRs, while the initial assembly in daughter cells is unaffected. Cryo-electron tomography of CGP-depleted parasites reveals the absence of the PCRs in the mature parasites, demonstrating that CGP is essential for stabilising the PCRs after replication. Using CGP as bait, we identify a protein required for the early assembly of the nascent conoid complex. The APR scaffold assembly factor (ASAF1) defines the position of the conoid complex before tubulin polymerisation. Depletion of ASAF1 results in failure of conoid complex assembly, disorganised microtubules, and lack of daughter cell formation. Collectively, our findings reveal two essential proteins that play critical roles in the early and late stages of conoid complex formation, providing insight into the mechanisms of conoid complex assembly.

Blinder–Oaxaca decomposition analysis of the urban-rural gap in child nutrition in Bangladesh

Evaluation of the administrative chief duty system in a tertiary reproductive hospital through personnel analysis

Structural insights into mechanisms of zinc scavenging by the Candida albicans zincophore Pra1

Abstract Candida albicans causes over 400,000 life-threatening, and an additional half a billion of mucosal infections annually. In response to infection, the host limits essential micronutrient availability, including zinc, to restrict growth of the invading pathogen. As assimilation of zinc is essential for C. albicans pathogenicity, limitation induces secretion of the zincophore protein Pra1 to scavenge zinc from the host. Pra1 also plays a number of important roles in host-pathogen interactions and is conserved in most fungi. However, the structure of fungal zincophores is unknown. Here, we present cryo-EM structures of C. albicans Pra1 in apo- and zinc-bound states, at 2.8 and 2.5 Å resolution respectively. Our work reveals a hexameric ring with multiple zinc binding sites. Through genetic studies, we show that these sites are essential for C. albicans growth under zinc restriction but do not affect the inflammatory properties of Pra1. These data create a foundation for future work to explore the structural basis of Pra1-mediated host-pathogen interactions, C. albicans zinc uptake, as well as therapeutics development.

Dynamics of postnatal upper airway bacteria colonization in preterm infants <1000g and bronchopulmonary dysplasia

Abstract Aberrant microbial colonization of premature infants is increasingly recognized as a risk factor for severe acute morbidities. The aim of this study was to evaluate the correlation of bacterial upper airway colonization within the first 6 weeks of life in preterm infants <1000g and risk of moderate/severe bronchopulmonary dysplasia (BPD). In this retrospective two-center cohort study postnatal upper airway bacterial colonization of premature infants with a birth weight <1000g was analyzed. Bacteria were categorized into facultative- and highly pathogenic. Within 242 infants, a birth weight cutoff of 800g prevailed as the most relevant discriminator for risk of BPD. Furthermore, center, male sex, duration of antibiotic therapy, and delayed detection of facultative pathogenic bacteria after week 4 was associated with the development of BPD. Using classification tree analyses for the binary outcome, antibiotic therapy was more importance in infants <800g, whereas in those with a birth weight ≥800g, delayed colonization with facultative pathogenic bacteria was more relevant than antibiotic exposure. We add delayed colonization of the upper airway with facultative pathogenic bacteria to the risks for BPD. The variations of microbial colonization should be considered in future studies on the pathogenesis of BPD and new treatment modalities.

Mapping key mitochondrial genes in Alzheimer’s disease through human tissue and iPSC derived neurons

Discovery of a bifunctional PKMYT1-targeting PROTAC empowered by AI-generation

Degradation of textile dyes using Biancaea sappan extract coated zinc nanoparticle

Abstract This study presents a green and efficient method for synthesizing zinc oxide (ZnO) nanoparticles using Biancaea sappan leaf extract, marking the first report of this plant’s application in nanoparticle fabrication. The extract coated ZnO nanoparticles (BSE-ZnONPs) displayed enhanced multifunctional bioactivity, showing strong antibacterial inhibition against Staphylococcus sp. (45 mm), high anti-inflammatory activity (95.57%), and notable antioxidant potential (78.65% inhibition at 500 µg/mL). Under optimized conditions (200 mg/L, pH 1, 7.5 min ultrasonication), the nanocomposite achieved 98.88% dye degradation efficiency, surpassing similar green-synthesized ZnO systems reported previously (< 95%). The BSE-ZnONPs maintained over 84% efficiency for two reuse cycles and retained moderate activity (42.7%) in the third cycle, confirming good recyclability. Cytotoxicity studies revealed high cell viability in L929 cells (IC₅₀ = 151.48 µg/mL), and in vivo assays using Oreochromis niloticus demonstrated significant mitigation of dye-induced histopathological damage. These results highlight the superior catalytic and biocompatible performance of BSE-ZnONPs and their potential as a sustainable nanotechnological solution for textile wastewater treatment and aquatic ecosystem protection.