The Asian Pacific association for the study of the liver clinical practice guidelines for the diagnosis and management of metabolic dysfunction-associated fatty liver disease.

Metabolic dysfunction-associated fatty liver disease (MAFLD) affects over one-fourth of the global adult population and is the leading cause of liver disease worldwide. To address this, the Asian Pacific Association for the Study of the Liver (APASL) has created clinical practice guidelines focused on MAFLD. The guidelines cover various aspects of the disease, such as its epidemiology, diagnosis, screening, assessment, and treatment.

Evaluation of a hydrogel platform for encapsulated multivalent Vibrio antigen delivery to enhance immune responses and disease protection against vibriosis in Asian seabass (Lates calcarifer).

This study reports the development and evaluation of a novel multivalent oral hydrogel vaccine designed to protect Asian seabass (Lates calcarifer) against vibriosis caused by multiple Vibrio species. The hydrogel formulation, composed of alginate and bentonite, was engineered to encapsulate three Vibrio pathogens (V. harveyi, V.

Bridging the gap between research and decision making: A European survey to enhance cooperation in wastewater-based epidemiology (WBE) for illicit drugs.

Objectives: Illicit drug use presents a significant challenge to global health and public safety, requiring innovative and effective monitoring strategies. This study aimed to evaluate the current landscape of wastewater-based epidemiology (WBE) for monitoring illicit drugs in Europe, focusing on collaboration, current practices, and barriers, while identifying opportunities for improvement.

Study Design: Cross-sectional survey-based study.

Tumor Microenvironment pH-Sensitive Peptidomimetics for Targeted Anticancer Drug Delivery.

Cell-penetrating peptides (CPPs) are known for their effective intracellular transport of bioactives such as therapeutic proteins, peptides, nucleic acid, and small molecule drugs. However, the excessive cationic charges that promote their membrane permeability result in nonselective delivery and cellular toxicity. In this study, we report a decamer cell-penetrating peptidomimetic, , designed to selectively deliver anticancer drugs into tumor cells in response to the acidic microenvironment.

Identification of a Series Containing a Pentafluorophenyl Moiety That Targets Pks13 to Inhibit Growth of .

Although not currently in the infectious disease spotlight, there is still a pressing need for new agents to treat tuberculosis caused by . As there is an ever-increasing amount of clinical resistance to the current drugs, ideally new drugs would be found against novel targets to circumvent pre-existing resistance. A phenotypic growth screen identified a novel singleton, , as an inhibitor of growth.

activities of lipopeptides against fluconazole-resistant .

has increasingly become a global threat due to its wide range of antifungal resistances as well as its ability to sustain outbreaks in clinical settings. Two lipopeptides, C14-NleRR-NH (Nel) and C14-WRR-NH (WR), were evaluated against six fluconazole-resistant isolates. Both molecules showed good antimicrobial activity as demonstrated by MIC determination, time-kill, and microscopy experiments.

Targeted Degradation of ZBP1 with Covalent PROTACs for Anti-Inflammatory Treatment of Infections.

Z-DNA binding protein 1 (ZBP1) has emerged as a critical pathogen-sensing protein that upon activation, triggers necroptotic signaling cascades, leading to a potent inflammatory response and potentially causing significant tissue damage. However, available drugs specifically developed for the effective inhibition or degradation of ZBP1 is still lacking so far. In this study, we developed a potent covalent recognition-based PROTAC (C-PROTAC) molecule for the degradation of ZBP1.

Blend Uniformity and Content Uniformity in Oral Solid Dosage Manufacturing: an IQ Consortium Industry Position Paper.

The IQ Consortium Uniformity Testing Working Group reviewed the current BU and CU testing practices among ten member companies. All ten companies presented their current approach to BU and CU testing at the three stages of Product Lifecycle Management: the Process Design Stage, the Process Qualification Stage, and the Continuous Verification Stage. With this information on hand, the Uniformity Testing Working Group members developed a risk-based approach to BU and CU testing, and proposed innovative methods to reduce or eliminate blend sampling based on risk to Uniformity of Dosage Unit (UDU) testing.

Modulating Coordination Environment of Single Nickel Atom in Covalent Organic Framework to Enhance Photocatalytic Hydrogen Evolution Reaction.

Covalent organic frameworks (COFs) have emerged as fascinating platforms for photocatalytic hydrogen evolution reactions in recent years. However, the relationship between the coordination environment of metals in a covalent organic framework and catalytic properties is still rarely studied. In this study, a covalent organic framework (COF-BP), containing a benzothiazole unit with typical electron-withdrawing properties, was successfully synthesized from 4,4'-(benzo-2,1,3-thiadiazole-4,7-diyl)dianiline and 3,3',5,5'-tetraformyl-4,4'-biphenyldiol.

Presentation of a new multifunctional oral cavity simulator: the "MOCS".

This article describes a new multifunctional oral cavity simulator (MOCS) that allows, with little technical support and easy handling, the laboratory development of dental hard tissue lesions under clinically similar conditions. The MOCS consists of a heating unit containing three independent cylindrical chambers with three specimen holders inside. Liquids flow through the surfaces of specimens by inlets on the lid of the chamber, which is connected to a medium/artificial saliva source through a computer-controlled peristaltic pump.

Plasma Proteomic Assessment of Calcific Aortic Valve Disease in Older Adults.

Background: Calcific aortic valve disease (CAVD), and ensuing severe aortic stenosis (AS), is the foremost valvular disorder of aging, yet preventive therapies are lacking. A better understanding of the molecular underpinnings of aortic valve calcification (AVC) is necessary to develop pharmacologic interventions.

Methods And Results: We undertook large-scale plasma proteomics in a cohort study of adults ≥65 years old, the CHS (Cardiovascular Health Study), to identify individual proteins associated with echocardiographic AVC and incident moderate/severe AS.

Formation and Stability of the Propionitrile:Acetylene Co-Crystal Under Titan-Relevant Conditions.

Propionitrile (also known as ethyl cyanide, CHCHCN) and acetylene (CH) are two organic molecules that have been detected in Titan's atmosphere. Over time, they may interact with each other as they are transported to Titan's surface. We sought to determine if any reactions or associations such as co-crystal formation might occur between the two molecules.

Novel Tissue-Specific Multifunctionalized Nanotechnological Platform Encapsulating Riluzole Against Motor Neuron Diseases.

Background: Motor neuron diseases are neurological disorders characterized by progressive degeneration of upper and/or lower motor neurons. Amyotrophic Lateral Sclerosis (ALS) is the most common form of motor neuron diseases, where patients suffer progressive paralysis, muscle atrophy and finally death. Despite ALS severity, no treatment is safe and fully effective.

The airborne herbivore-induced plant volatile indole is converted to benzoxazinoid defense compounds in maize plants.

Herbivore-induced plant volatiles act as danger signals to prime defense responses in neighboring plants, yet in many cases the mechanism behind this priming is not known. Volatile signals may be recognized directly by receptors and/or converted into other active compounds. Here we investigate the metabolic fate of volatile indole, a known priming signal in maize (Zea mays), to determine if its conversion to other compounds could play a role in its priming of defenses.

Molecular Epidemiology Clinical Manifestations, Decolonization Strategies, and Treatment Options of Methicillin-Resistant Infection in Neonates.

Preterm and low-birth-weight neonates are particularly susceptible to methicillin-resistant (MRSA) colonization, whereas MRSA infection is associated with significant neonatal morbidity and mortality globally. The objective of our study was to examine the current body of knowledge about molecular traits, epidemiology, risk factors, clinical presentation, decolonization techniques, and available treatments for MRSA infection in neonates. MRSA strains that predominate in neonatal units, namely healthcare-associated (HA)-MRSA, differ from community-acquired (CA)-MRSA strains in molecular characteristics, toxin synthesis, including Panton-Valentine leukocidin, and resistance to antibiotics.

Exploring miR-21 Knock-Out Using CRISPR/Cas as a Treatment for Lung Cancer.

Background: Lung cancer is a leading cause of cancer-related deaths worldwide. Its high incidence and poor prognosis demonstrate the need to investigate new therapies. The PI3K/AKT pathway is activated in carcinogenic processes such as invasion, proliferation, and drug resistance.

Improved Inhibitors Targeting the Thymidylate Kinase of Multidrug-Resistant with Favorable Pharmacokinetics.

This study aims to design improved inhibitors targeting the thymidylate kinase (TMK) of (), the causative agent of infectious disease tuberculosis that is associated with high morbidity and mortality in developing countries. TMK is an essential enzyme for the synthesis of bacterial DNA. We have performed computer-aided molecular design of TMK inhibitors by modification of the reference crystal structures of the lead micromolar inhibitor TKI1 bound to TMK of strain H37Rv (PDB entries: 5NRN and 5NR7) using the computational approach MM-PBSA.

Elevated Serum Levels of Acid Sphingomyelinase in Female Patients with Episodic and Chronic Migraine.

Migraine is one of the most common neurological disorders and the second most disabling human condition. The molecular mechanisms of migraine have been linked to neuropeptide release, endothelial dysfunction, oxidative stress and inflammatory processes. Acid sphingomyelinase (aSMase) is a secreted enzyme that leads to sphingomyelin degradation to produce ceramide.

Early Detection of the Pathogenetic Variants of Homologous Recombination Repair Genes in Prostate Cancer: Critical Analysis and Experimental Design.

It has been shown that the pathogenic variants (PVs) of the DNA Damage Response (DDR) genes, whether of a germinal or somatic nature, represent a predictive biomarker of high sensitivity to treatment with inhibitors of the enzyme poly-ADP-ribose polymerase (PARP) in patients with hormone-resistant metastatic prostate cancer (HRPCa). Moreover, the detection of PVs of the Homologous Recombination Repair (HRR) genes in PCa patients can help to define the patient's prognosis and the choice of the therapeutic procedure. Among men with metastatic PCa, the frequency of PVs in HRR genes ranges from 11% to 33%, which is a significantly higher rate compared to non-metastatic PCa, where the incidence is between 5% and 10%.

Mechanisms of Resistance to Anti-PD-1 Immunotherapy in Melanoma and Strategies to Overcome It.

Resistance to anti-PD-1 therapy in melanoma remains a major obstacle in achieving effective and durable treatment outcomes, highlighting the need to understand and address the underlying mechanisms. The first key factor is innate anti-PD-1 resistance signature (IPRES), an expression of a group of genes associated with tumor plasticity and immune evasion. IPRES promotes epithelial-to-mesenchymal transition (EMT), increasing melanoma cells' invasiveness and survival.

Imaging and outcome correlates of ctDNA methylation markers in prostate cancer: a comparative, cross-sectional [⁶⁸Ga]Ga-PSMA-11 PET/CT study.

Background: To validate the clinical utility of a previously identified circulating tumor DNA methylation marker (meth-ctDNA) panel for disease detection and survival outcomes, meth-ctDNA markers were compared to PSA levels and PSMA PET/CT findings in men with different stages of prostate cancer (PCa).

Methods: 122 PCa patients who underwent [⁶⁸Ga]Ga-PSMA-11 PET/CT and plasma sampling (03/2019-08/2021) were analyzed. cfDNA was extracted, and a panel of 8 individual meth-ctDNA markers was queried.

Photophysical and structural aspects of poly-L-tryptophan: π-π stacking interaction with an excited state intermolecular proton transfer probe 3-Hydroxynaphthoic acid revealed by experiments and molecular simulation.

In biophysical studies involving proteins, the involvement of the intrinsic fluorophore Tryptophan and its energy transfer/binding interactions are already well-investigated areas. Theoretical studies have also been well corroborated with experimental findings. However, in polymeric Tryptophans (specifically homopolymers), several queries still need to be addressed - their structure, the environment of each Tryptophan and the binding preferences of the latter.

Plasma proteomics for cognitive decline and dementia-A Southeast Asian cohort study.

Introduction: The prognostic utility of plasma proteomics for cognitive decline and dementia in a Southeast Asian population characterized by high cerebrovascular disease (CeVD) burden is underexplored.

Methods: We examined this in a Singaporean memory clinic cohort of 528 subjects (n = 300, CeVD; n = 167, incident cognitive decline) followed-up for 4 years.

Results: Of 1441 plasma proteins surveyed, a 12-protein signature significantly predicted cognitive decline (q-value < .

Chemical and electrochemical lithiation of van der Waals oxytelluride VTeO.

Reversible lithium intercalation into the van der Waals phase VTeO, forming new phases LiVTeO with approaching 2, is reported using both chemical and electrochemical methods. The progress of each reaction was followed using powder X-ray diffraction and the crystal structure of the intercalated phase with = 1, LiVTeO, was refined using powder neutron diffraction. The intercalated Li ions occupy vacant pseudo-octahedral sites and the unit cell expands on reduction with no change in symmetry.