Comparison of Measured Glomerular Filtration Rate Versus Estimated Glomerular Filtration Rate in Indian Cirrhotic Patients: Report of a Pilot Study.

Background: Renal impairment significantly affects morbidity and mortality rates of cirrhosis patients. Studies on glomerular filtration rate (eGFR) estimation did not include cirrhosis patients. These equations are erroneous and unreliable in cirrhosis due to sarcopenia.

Structural Conversion of Serotonin into Amyloid-like Nanoassemblies Conceptualizes an Unexplored Neurotoxicity Risk.

The neuromodulator 5-hydroxytryptamine, known as serotonin, plays a key regulatory role in the central nervous system and peripheral organs; however, several research revelations have indicated a direct link between the oxidation of serotonin and a plethora of detrimental consequences. Hence, the question of how several neuronal and non-neuronal complications originate via serotonin oxidation remains an important area of investigation. Here, we show the autoxidation-driven structural conversion of serotonin into hemolytic and cytotoxic amyloid-like nanoassemblies under physiological conditions.

Catalytic Cycloisomerization-Oxidative Cyclization Reaction Sequence of Enyne Diesters Derived from 2-Propargyloxyarylaldehydes.

Enyne diesters derived from 2-propargyloxyarylaldehydes are converted into 2-oxopyranochromenes via In(OTf)-catalyzed cycloisomerization and 2,3-dichloro-5,6-dicyano-1,4-benzoquinone (DDQ)-mediated oxidative cyclization reaction sequence in one pot. The process possesses broad substrate scope and good functional group compatibility and generates various 4-(hetero)aryl-substituted 2-oxopyranochromenes in 32-79% yields (over two steps). 2-Oxopyranochromenes undergo selective decarboxylation under Krapcho conditions.

Rapid Coaggregation of Proteins Without Sequence Similarity: Possible Role of Conformational Complementarity.

Despite extensive research on the sequence-determined self-assembly of both pathogenic and nonpathogenic proteins, the question of how the sequence identity would influence the coassembly or cross-seeding of diverse proteins without distinct sequence similarity remains largely unanswered. Here, we demonstrate that the rapid coaggregation of proteins with negligible sequence similarity is fundamentally governed by preferred heteromeric interactions between their partially unfolded states via the gain of additional charge complementarity and hydrophobic interactions. The partial loss of intramolecular interactions and concurrent gain of non-native intrinsically disordered regions with sticky groups become crucial for both aggressive heteromeric primary nucleation and secondary nucleation events.

Occurrence of biofilm forming Escherichia coli in drinking water supply system in Kathmandu.

Biofilm development in gram negative bacterial contaminants in water supply systems is linked to persistence as well as antibiotic resistance, which threatens water quality and hence the public health. This study aimed to investigate phenotypic and genetic capacity of biofilm formation by Escherichia coli isolated from supply water with their antibiotic susceptibility pattern. Altogether fifty water samples collected from a city supply water distribution scheme in Kathmandu were analyzed to assess the physicochemical and microbiological quality.

Multidisciplinary advances in kombucha fermentation, health efficacy, and market evolution.

Kombucha, a fermented tea beverage, has seen a significant rise in global popularity. This increase is attributed to its reported health benefits and extensive cultural heritage. The comprehensive review examines kombucha through microbiology, biochemistry, and health sciences, highlighting its therapeutic potential and commercial viability.

Tailoring the Molecular Structure of 6-Gingerol for Targeting the Phase Separation in Human Lysozyme.

Human lysozyme undergoes a phase-separation process to form insoluble amyloid-architects that cause several pathologies including systemic amyloidosis. Here we have tailored 6-gingerol by extending its molecular framework with active functional groups to specifically target lysozyme phase-transition events. Aggregation assay revealed that tailored 6-gingerol with 4-aromatic moieties (MTV4) substantially suppressed the conversion of the lysozyme low-density liquid phase (LDLP) to solid-phase structured amyloids.

Cu(II) Specifically Disassembles Insulin Amyloid Nanostructures via Direct Interaction with Cross-β Fibrils.

In this work, we demonstrate direct evidence of the antiamyloid potential of Cu(II) ions against amyloid formation of insulin. The Cu(II) ions were found to efficiently disassemble the preformed amyloid nanostructures into soluble species and suppress monomer fibrillation under aggregation-prone conditions. The direct interaction of Cu(II) ions with the cross-β structure of amyloid fibrils causes substantial disruption of both the interchain and intrachain interactions, predominantly the H-bonds and hydrophobic contacts.

Multiomics unveils extracellular vesicle-driven mechanisms of endothelial communication in human carotid atherosclerosis.

Carotid atherosclerosis is orchestrated by cell-cell communication that drives progression along a clinical continuum (asymptomatic to symptomatic). Extracellular vesicles (EVs) are cell-derived nanoparticles representing a new paradigm in cellular communication. Little is known about their biological cargo, cellular origin/destination, and functional roles in human atherosclerotic plaque.

Molecular insights into the phase transition of lysozyme into amyloid nanostructures: Implications of therapeutic strategies in diverse pathological conditions.

Lysozyme, a well-known bacteriolytic enzyme, exhibits a fascinating yet complex behavior when it comes to protein aggregation. Under certain conditions, this enzyme undergoes flexible transformation, transitioning from partially unfolded intermediate units of native conformers into complex cross-β-rich nano fibrillar amyloid architectures. Formation of such lysozyme amyloids has been implicated in a multitude of pathological and medical severities, like hepatic dysfunction, hepatomegaly, splenic rupture as well as spleen dysfunction, nephropathy, sicca syndrome, renal dysfunction, renal amyloidosis, and systemic amyloidosis.

Rising Trends in Metabolically Healthy Obesity in Cancer Patients and Its Impact on Cardiovascular Events: Insights from a Contemporary Nationwide Analysis in the USA (2016-2020).

Obesity or overweight raises the risk of developing 13 types of cancer, representing 40% of all cancers diagnosed in the United States annually. Given the ongoing debate surrounding the impact of metabolically healthy obesity (MHO) on cardiovascular outcomes, it is crucial to comprehend the incidence of Major Adverse Cardiovascular and Cerebrovascular Events (MACCEs) and the influence of MHO on these outcomes in cancer patients. Data of hospitalized cancer patients with and without obesity were analyzed from the National Inpatient Sample 2016-2020.

GENESIS-Guidance, Education, Networking, and Empowerment-based Smart Initiative for Students research in health care: A research modeling experience from a newly established medical college.

The importance of undergraduate medical research has been undermined in Indian medical education. Various studies show there is a drastic difference between the research output of Indian medical graduates in comparison to Western counterparts. With all the challenges identified, a student-oriented research committee was formed -Guidance, Education, Networking, and Empowerment-based Smart Initiative for Students (GENESIS) research in health care - A research modeling experience from a newly established medical college.

Pleiotropic Nanostructures Built from l-Histidine Show Biologically Relevant Multicatalytic Activities.

The essential amino acid histidine plays a central role in the manifestation of several metabolic processes, including protein synthesis, enzyme-catalysis, and key biomolecular interactions. However, excess accumulation of histidine causes histidinemia, which shows brain-related medical complications, and the molecular mechanism of such histidine-linked complications is largely unknown. Here, we show that histidine undergoes a self-assembly process, leading to the formation of amyloid-like cytotoxic and catalytically active nanofibers.

Bacteria-mediated green synthesis of silver nanoparticles and their antifungal potentials against Aspergillus flavus.

The best biocontroller Bacillus subtilis produced silver nanoparticles (AgNPs) with a spherical form and a 62 nm size through green synthesis. Using UV-vis spectroscopy, PSA, and zeta potential analysis, scanning electron microscopy, and Fourier transform infrared spectroscopy, the properties of synthesized silver nanoparticles were determined. Silver nanoparticles were tested for their antifungicidal efficacy against the most virulent isolate of the Aspergillus flavus fungus, JAM-JKB-BHA-GG20, and among the 10 different treatments, the treatment T6 [PDA + 1 ml of NP (19: 1)] + Pathogen was shown to be extremely significant (82.

Nurturing Empathy through Arts, Literature, and Role Play for Postgraduate Trainees of Ophthalmology.

Background And Purpose: Empathy is essential in patient-centered compassionate health care. Lack of formal training, workload, patient factors, and digitalization have been attributed to its regression. Empathy can be nurtured by educational interventions.

The FLRT3-UNC5B checkpoint pathway inhibits T cell-based cancer immunotherapies.

Cancers exploit coinhibitory receptors on T cells to escape tumor immunity, and targeting such mechanisms has shown remarkable clinical benefit, but in a limited subset of patients. We hypothesized that cancer cells mimic noncanonical mechanisms of early development such as axon guidance pathways to evade T cell immunity. Using gain-of-function genetic screens, we profiled axon guidance proteins on human T cells and their cognate ligands and identified fibronectin leucine-rich transmembrane protein 3 (FLRT3) as a ligand that inhibits T cell activity.

Kurarinone targets JAK2-STAT3 signaling in colon cancer-stem-like cells.

Natural compounds are known to regulate stemness/self-renewal properties in colon cancer cells at molecular level. In the present study, we first time studied the colon cancer stem-like cells targeting potential of Kurarinone (KU) and explored the underlying mechanism. Cytotoxic potential of KU was checked in colon cancer cells.

Prevalence of human papillomavirus infection and associated factors among women attending cervical cancer screening in setting of Addis Ababa, Ethiopia.

Human papillomaviruses (HPVs) are circular, nonenveloped small double-stranded DNA viruses that infect stratified epithelium and can cause a number of life-threatening diseases. HPV is the central risk factor for developing cervical cancer and is estimated that approximately 98% of this disease is associated with oncogenic types of HPV. HPV infection leads to an estimated 266,000 cervical cancer deaths annually.

Discovery of anticancer compound possessing potential to bind γ-secretase catalytic subunit and inhibit notch promoter activity.

Gamma secretase (GS) is an important therapeutic target in anticancer drug discovery. Increased GS activity activates notch signaling pathway which is associated with cancer stemness and drug resistance in cancer cells. A total of 69,075 natural and their derivative compounds were screened to identify the lead compound on the basis of GS catalytic domain binding potential and selective anticancer efficacy.

Directional Endothelial Communication by Polarized Extracellular Vesicle Release.

Background: Extracellular vesicles (EVs) contain bioactive cargo including miRNAs and proteins that are released by cells during cell-cell communication. Endothelial cells (ECs) form the innermost lining of all blood vessels, interfacing with cells in the circulation and vascular wall. It is unknown whether ECs release EVs capable of governing recipient cells within these 2 separate compartments.

Natural bioactive compounds and FOXO3a in cancer therapeutics: An update.

Forkhead box protein 3a (FOXO3a) is a transcription factor that regulates various downstream targets upon its activation, leading to the upregulation of tumor suppressor and apoptotic pathways. Hence, targeting FOXO3a is an emerging strategy for cancer prevention and treatment. Recently, Natural Bioactive Compounds (NBCs) have been used in drug discovery for treating various disorders including cancer.

Leveraging plasmonic hot electrons to quench defect emission in metal-semiconductor nanostructured hybrids.

Modeling light-matter interactions in hybrid plasmonic materials is vital to their widening relevance from optoelectronics to photocatalysis. Here, we explore photoluminescence (PL) from ZnO nanorods (ZNRs) embedded with gold nanoparticles (Au NPs). A progressive increase in Au NP concentration introduces significant structural disorder and defects in ZNRs, which paradoxically quenches defect related visible PL while intensifying the near band edge (NBE) emission.

Synthesis of Azonia Aromatic Heterocycles Bearing 6-6-6-5-6 Pentacyclic Core via Intramolecular [4 + 2]-Cycloaddition and Oxidative Aromatization Reaction Sequence in One Pot.

Cationic aza-heterocycle-fused compounds have gained wide applications in materials science, biological applications, and synthetic organic chemistry. In this report, synthesis of benzothiazolochromenopyridinium tetrafluoroborates, a novel molecular scaffold, bearing 6-6-6-5-6 pentacyclic core is described that proceeds via (i) piperidine-catalyzed Knoevenagel condensation between 2-propargyloxyarylaldehydes bearing internal alkynes and 2-benzothiazoleacetonitrile, (ii) intramolecular formal [4 + 2]-cycloaddition, and (iii) crucial molecular oxygen-mediated oxidative aromatization reaction sequence in one pot. These quaternary pyridinium salts are obtained at ambient temperature in good to high yields.

Initiation of Brain Extract Fibrillation and Effective Cellular Internalization of Tryptophan Fibrils Unveils Its Neurotoxicity Risk.

Recent discoveries on the self-assembly of aromatic amino acids into amyloid-like neurotoxic nanostructures have initiated a quest to decode the molecular mechanisms for the initiation of neurodegeneration. Moreover, the multicomponent nature of the amyloid deposits still questions the existing and well-defined amyloid cascade hypothesis. Hence, deciphering the neurotoxicity of amyloid-like nanostructures of aromatic amino acids becomes crucial for understanding the etiology of amyloidogenesis.

NKG2D receptor signaling shapes T cell thymic education.

The role of natural killer group 2D (NKG2D) in peripheral T cells as a costimulatory receptor is well established. However, its contribution to T cell thymic education and functional imprint is unknown. Here, we report significant changes in development, receptor signaling, transcriptional program, and function in T cells from mice lacking NKG2D signaling.