Xylooligosaccharide recovery from sugarcane bagasse using β-xylosidase-less xylanase, BsXln1, produced by Bacillus stercoris DWS1: Characterization, antioxidant potential and influence on probiotics growth under anaerobic conditions.

Xylooligosaccharides (XOS) are excellent prebiotic which improve health through selective modulation of beneficial gut microbiome. Its production from agroresidues using microbial xylanase is considered as sustainable and economic approach. In this study a xylanase producing bacterium isolated from decaying wood soil was phylogenetically identified and designated as Bacillus stercoris DWS1.

Structural and hemodynamic analysis of Weaire-Phelan scaffolds made of Ti-alloy as bone replacement component: A preclinical investigation.

In recent years, additively manufactured metallic scaffolds have generated significant interest among researchers working in the field of bone tissue engineering and orthopaedic implants. Although such intricate, porous architectures are promising as bone substitutes, they need to be thoroughly tested for structural robustness as well as their capacity for bony integration. In this present work, we introduced and preclinically evaluated the biomechanical viability of Weaire-Phelan (WP) Ti-alloy scaffolds as bone replacement components.

Zinc Oxide Nanoparticles Incorporated in Poly-Hydroxyethyl Methacrylate/Acrylamide Membrane Trigger the Key Events of Full-Thickness Wound Healing in a Rabbit Model.

Zinc oxide nanoparticles are known to possess anti-inflammatory, antibacterial, and antiseptic properties and find wide application in the preparation of topical ointments. Wound dressings in the form of hydrogels can replenish the wound microenvironment to aid the healing process in a multidimensional way. We have fabricated a composite hydrogel using 1-3 wt.

The Discovery and Preclinical Profile of ALG-000184, a Prodrug of the Potent Hepatitis B Virus Capsid Assembly Modulator ALG-001075.

Chronic hepatitis B (CHB) represents a significant unmet medical need with few options beyond lifelong treatment with nucleoside analogues, which rarely leads to a functional cure. Novel agents that reduce levels of HBV DNA, RNA and other viral antigens could lead to better treatment outcomes. The capsid assembly modulator (CAM) class of compounds represents an important modality for chronic suppression and to improve functional cure rates, either alone or in combination.

A Retrospective Analysis of Lessons Learned and Perspectives on Expansion of Verbal Autopsy Implementation in Zambia, 2023.

Accurate cause-of-death statistics are vital for public health policy, but less than one-third of deaths globally are assigned a cause. Verbal autopsy (VA) methods are crucial in low- and middle-income countries lacking complete civil registration and vital statistics (CRVS) systems. We explored VA implementation in Zambia by using a previously developed framework.

Benchmark computations of nearly degenerate singlet and triplet states of N-heterocyclic chromophores. I. Wavefunction-based methods.

In this paper, we investigate the role of electron correlation in predicting the S1-S0 and T1-S0 excitation energies and, hence, the singlet-triplet gap (ΔEST) in a set of cyclazines, which act as templates for potential candidates for fifth generation organic light emitting diode materials. This issue has recently garnered much interest with the focus being on the inversion of the ΔEST, although experiments have indicated near degenerate levels with both positive and negative being within the experimental error bar [J. Am.

Live imaging of airway epithelium reveals that mucociliary clearance modulates SARS-CoV-2 spread.

SARS-CoV-2 initiates infection in the conducting airways, where mucociliary clearance inhibits pathogen penetration. However, it is unclear how mucociliary clearance impacts SARS-CoV-2 spread after infection is established. To investigate viral spread at this site, we perform live imaging of SARS-CoV-2 infected differentiated primary human bronchial epithelium cultures for up to 12 days.

Using the theoretical domains framework to identify the sociocultural barriers and enablers to access and use of primary and maternal healthcare services by rural Bangladeshi women: a qualitative study.

In Bangladesh, increasing the use of primary healthcare (PHC) and maternal healthcare (MHC) services is the main focus of achieving the United Nations Sustainable Development Goal-3, ensuring healthy lives and wellbeing for all. However, little is known about the sociocultural barriers and enablers to accessing and using PHC and MHC services among rural Bangladeshi women. This qualitative study aimed to identify sociocultural barriers and enablers to accessing and using PHC and MHC services among Bangladeshi rural women by using the Theoretical Domains Framework (TDF).

An assessment of excess mortality during the COVID-19 pandemic, a retrospective post-mortem surveillance in 12 districts - Zambia, 2020-2022.

Background: The number of COVID-19 deaths reported in Zambia (N = 4069) is most likely an underestimate due to limited testing, incomplete death registration and inability to account for indirect deaths due to socioeconomic disruption during the pandemic. We sought to assess excess mortality during the COVID-19 pandemic in Zambia.

Methods: We conducted a retrospective analysis of monthly-death-counts (2017-2022) and individual-daily-deaths (2020-2022) of all reported health facility and community deaths at district referral health facility mortuaries in 12 districts in Zambia.

Discovery and Preclinical Profile of ALG-055009, a Potent and Selective Thyroid Hormone Receptor Beta (THR-β) Agonist for the Treatment of MASH.

Agonists of thyroid hormone receptor β (THR-β) decreased LDL cholesterol (LDL-C) and triglyceride (TG) levels in human clinical trials for patients with dyslipidemia. The authors present the highly potent and selective compound ALG-055009 () as a potential best in class THR-β agonist. The high metabolic stability and good permeability translated well in vivo to afford a long in vivo half-life pharmacokinetic profile with limited liability for DDI, and it overcomes certain drawbacks seen in recent clinical candidates.

Pandemic burden in low-income settings and impact of limited and delayed interventions: A granular modelling analysis of COVID-19 in Kabwe, Zambia.

Objectives: Pandemic response in low-income countries (LICs) or settings often suffers from scarce epidemic surveillance and constrained mitigation capacity. The drivers of pandemic burden in such settings, and the impact of limited and delayed interventions remain poorly understood.

Methods: We analysed COVID-19 seroprevalence and all-cause excess deaths data from the peri-urban district of Kabwe, Zambia between March 2020 and September 2021 with a novel mathematical model.

Global siRNA Screen Reveals Critical Human Host Factors of SARS-CoV-2 Multicycle Replication.

Defining the subset of cellular factors governing SARS-CoV-2 replication can provide critical insights into viral pathogenesis and identify targets for host-directed antiviral therapies. While a number of genetic screens have previously reported SARS-CoV-2 host dependency factors, these approaches relied on utilizing pooled genome-scale CRISPR libraries, which are biased towards the discovery of host proteins impacting early stages of viral replication. To identify host factors involved throughout the SARS-CoV-2 infectious cycle, we conducted an arrayed genome-scale siRNA screen.

Gephyrin promotes autonomous assembly and synaptic localization of GABAergic postsynaptic components without presynaptic GABA release.

Synapses containing γ-aminobutyric acid (GABA) constitute the primary centers for inhibitory neurotransmission in our nervous system. It is unclear how these synaptic structures form and align their postsynaptic machineries with presynaptic terminals. Here, we monitored the cellular distribution of several GABAergic postsynaptic proteins in a purely glutamatergic neuronal culture derived from human stem cells, which virtually lacks any vesicular GABA release.

Effect of social and behavioral change interventions on minimum dietary diversity among pregnant women and associated socio-economic inequality in Rajasthan, India.

Background: Maternal dietary diversity is a key to improving the birth and child health outcomes. Besides socio-economic factors, the nutrition specific program- Social and Behavioural Change Communication (SBCC) interventions aimed to improve maternal dietary diversity has varied levels of impact on the socio-economic groups in poor resource setups.

Objective: To measure the factors associated with the minimum dietary diversity (MDD) among pregnant women in selected districts of Rajasthan with special emphasis on the SBCC components.

COVID-19 mortality sentinel surveillance at a tertiary referral hospital in Lusaka, Zambia, 2020-2021.

Deaths from COVID-19 likely exceeded official statistics in Zambia because of limited testing and incomplete death registration. We describe a sentinel COVID-19 mortality surveillance system in Lusaka, Zambia. We analyzed surveillance data on deceased persons of all ages undergoing verbal autopsy (VA) and COVID-19 testing at the University Teaching Hospital (UTH) mortuary in Lusaka, Zambia, from April 2020 through August 2021.

Drug target prediction through deep learning functional representation of gene signatures.

Many machine learning applications in bioinformatics currently rely on matching gene identities when analyzing input gene signatures and fail to take advantage of preexisting knowledge about gene functions. To further enable comparative analysis of OMICS datasets, including target deconvolution and mechanism of action studies, we develop an approach that represents gene signatures projected onto their biological functions, instead of their identities, similar to how the word2vec technique works in natural language processing. We develop the Functional Representation of Gene Signatures (FRoGS) approach by training a deep learning model and demonstrate that its application to the Broad Institute's L1000 datasets results in more effective compound-target predictions than models based on gene identities alone.

An in vivo duck hepatitis B virus model recapitulates key aspects of nucleic acid polymer treatment outcomes in chronic hepatitis B patients.

Nucleic acid polymers (NAPs) are an attractive treatment modality for chronic hepatitis B (CHB), with REP2139 and REP2165 having shown efficacy in CHB patients. A subset of patients achieve functional cure, whereas the others exhibit a moderate response or are non-responders. NAP efficacy has been difficult to recapitulate in animal models, with the duck hepatitis B virus (DHBV) model showing some promise but remaining underexplored for NAP efficacy testing.

Gene Editing and Small Molecule Inhibitors of the RNA Binding Protein IGF2BP2/IMP2 Show its Potential as an Anti-Cancer Drug Target.

Background: The RNA-binding protein IGF2BP2/IMP2/VICKZ2/p62 is an oncofetal protein that is overexpressed in several cancer entities. Employing IMP2 knockout colorectal cancer cells, we could show the important role of IMP2 in several hallmarks of cancer. This study aimed to functionally characterize IMP2 in lung (A549, LLC1) and hepatocellular carcinoma (HepG2, Huh7) cell lines to assess its role as a potential target for these cancer entities.

In Vitro Evaluation of Drug-Drug Interaction Potential of Epetraborole, a Novel Bacterial Leucyl-tRNA Synthetase Inhibitor.

Epetraborole (EBO) is a boron-containing inhibitor of bacterial leucyl-tRNA synthetase, with potent activity against nontuberculous mycobacteria (NTM) and Gram-negative bacteria, including . EBO is being developed for the treatment of NTM lung disease and melioidosis, administered in combination with other therapeutic agents in both diseases. Therefore, EBO and its major circulating metabolite M3 were evaluated in comprehensive drug-drug interaction (DDI) in vitro studies.