Transcriptional state dynamics lead to heterogeneity and adaptive tumor evolution in urothelial bladder carcinoma.

Intra-tumor heterogeneity contributes to treatment failure and poor survival in urothelial bladder carcinoma (UBC). Analyzing transcriptome from a UBC cohort, we report that intra-tumor transcriptomic heterogeneity indicates co-existence of tumor cells in epithelial and mesenchymal-like transcriptional states and bi-directional transition between them occurs within and between tumor subclones. We model spontaneous and reversible transition between these partially heritable states in cell lines and characterize their population dynamics.

Concurrent determination of anti-microbial and anti-inflammatory drugs in lachrymal fluid and tissue by LC-MS/MS: A potential treatment for microbial keratitis and its PK-PD evaluation.

Unforeseen surfacing of microbial keratitis (MKT) over the years has led to a requisite for promising treatment strategy involving combination of antifungal and antibacterial agents. Subsequently, symptoms associated with MKT including inflammation and watery eyes require treatment with anti-inflammatory agents. Thus, a requirement of functional clinical treatment strategy involving combination of anti-inflammatory corticosteroids (Betamethasone) with antifungal polyene (Amphotericin B, AmB) and antibacterials macrolide (Azithromycin, AZT) and aminoglycoside (Neomycin, NEO).

Revolutionizing Biological Science: The Synergy of Genomics in Health, Bioinformatics, Agriculture, and Artificial Intelligence.

With climate emergency, COVID-19, and the rise of planetary health scholarship, the binary of human and ecosystem health has been deeply challenged. The interdependence of human and nonhuman animal health is increasingly acknowledged and paving the way for new frontiers in integrative biology. The convergence of genomics in health, bioinformatics, agriculture, and artificial intelligence (AI) has ushered in a new era of possibilities and applications.

Energy transfer from phycobilisomes to photosystem I at 77 K.

Phycobilisomes serve as a light-harvesting antenna of both photosystem I (PSI) and II (PSII) in cyanobacteria, yet direct energy transfer from phycobilisomes to PSI is not well documented. Here we recorded picosecond time-resolved fluorescence at wavelengths of 605-760 nm in isolated photosystem I (PSI), phycobilisomes and intact cells of a PSII-deficient mutant of sp. PCC 6803 at 77 K to study excitation energy transfer and trapping.

Elucidating the molecular determinants for binding modes of a third-generation HIV-1 integrase strand transfer inhibitor: Importance of side chain and solvent reorganization.

The first and second-generation clinically used HIV-1 integrase (IN) strand transfer inhibitors (INSTIs) are key components of antiretroviral therapy (ART), which work by blocking the integration step in the HIV-1 replication cycle that is catalyzed by a nucleoprotein assembly called an intasome. However, resistance to even the latest clinically used INSTIs is beginning to emerge. Developmental third-generation INSTIs, based on naphthyridine scaffold, are promising candidates to combat drug-resistant viral variants.

A framework for generalizable neural networks for robust estimation of eyelids and pupils.

Deep neural networks (DNNs) have enabled recent advances in the accuracy and robustness of video-oculography. However, to make robust predictions, most DNN models require extensive and diverse training data, which is costly to collect and label. In this work, we seek to improve the codevelop pylids, a pupil- and eyelid-estimation DNN model based on DeepLabCut.

Assessment of microbial population in integrated CW-MFC system and investigation of organics and fecal coliform removal pathway.

The current study is focused on understanding the operational mechanism of an integrated constructed wetland-microbial fuel cell (CW-MFC) reactor emphasizing fecal coliform (FC) removal. Few studies are available in the literature investigating the inherent mechanisms of pathogen inactivation in a CW-MFC system. Raw domestic wastewater was treated in three vertical reactors, one planted constructed wetland (R1), one planted CW-MFC (R2), and one unplanted CW-MFC (R3).

The Genetic Drivers of Juvenile, Young, and Early-Onset Parkinson's Disease in India.

Background: Recent studies have advanced our understanding of the genetic drivers of Parkinson's disease (PD). Rare variants in more than 20 genes are considered causal for PD, and the latest PD genome-wide association study (GWAS) identified 90 independent risk loci. However, there remains a gap in our understanding of PD genetics outside of the European populations in which the vast majority of these studies were focused.

Os odontoideum and craniovertebral junction instability secondary to dystonia: case series and review of the literature.

Introduction: Os odontoideum refers to a rounded ossicle detached from a hypoplastic odontoid process at the body of the axis. The aetiology has been debated and believed to be either congenital or acquired (resulting from trauma). Os odontoideum results in incompetence of the transverse ligament and thus predisposes to atlantoaxial instability and spinal cord injury.

The pectinolytic activity of Burkholderia cepacia and its application in the bioscouring of cotton knit fabric.

Background: Enzymatic catalysis in different industrial applications is often preferred over chemical methods due to various advantages, such as higher specificity, greater efficiency, and less environmental footprint. Pectinases are a group of enzymes that catalyze the degradation of pectic compounds, the key components of plant middle lamella and the primary cell wall. Pectinases have found applications in multiple industrial processes, including cotton bioscouring, fruit juice extraction and its clarification, plant fiber degumming, paper making, plant biomass liquefaction, and saccharification, among others.

Lattice models for ballistic aggregation: Cluster-shape-dependent exponents.

We study ballistic aggregation on a two-dimensional square lattice, where particles move ballistically in between momentum and mass conserving coalescing collisions. Three models are studied based on the shapes of the aggregates: In the first the aggregates remain point particles, in the second they retain the fractal shape at the time of collision, and in the third they assume a spherical shape. The exponents describing the power-law temporal decay of number of particles and energy as well as dependence of velocity correlations on mass are determined using large-scale Monte Carlo simulations.

Introducing -Sulfinylamines into Visible-Light-Induced Carbene Chemistry for the Synthesis of Diverse Amides and α-Iminoesters.

A rare example of visible-light-mediated diverse reactivity of -sulfinylamines with different types of carbene precursors has been disclosed. Acylsilanes and aryldiazoacetates have been utilized as nucleophilic and electrophilic carbene precursors into the N═S═O linchpin, to achieve valuable amides and α-iminoesters, respectively. Interestingly, diazocarbonyls can also participate in the amidation reaction with -sulfinylamines via generated ketenes.

A chemodosimetric approach for the visual detection of nerve agent simulant diethyl chlorophosphate (DCP) in liquid and vapour phase.

In this work, a novel fluorescent ratiometric switch, 8-((6-(1-benzo[]imidazol-2-yl)pyridin-2-yl)methoxy)quinoline (BIPQ), has been introduced for sensing an organophosphorus (OP) chemical vapor threat, diethyl chlorophosphate (DCP), the low-toxic mimic of the real nerve agent sarin (GB). BIPQ is efficient at detecting DCP in both solution and gaseous phase and has potential practical application with high sensitivity and selectivity. The probe shows significant ratiometric emission in the presence of DCP along with a distinct color change from blue to cyan under UV light.

Genomic Exploration of Distinct Molecular Phenotypes Steering Temozolomide Resistance Development in Patient-Derived Glioblastoma Cells.

Chemotherapy using temozolomide is the standard treatment for patients with glioblastoma. Despite treatment, prognosis is still poor largely due to the emergence of temozolomide resistance. This resistance is closely linked to the widely recognized inter- and intra-tumoral heterogeneity in glioblastoma, although the underlying mechanisms are not yet fully understood.

All about being old and shooting hairs: clade age and urticating hair explain the patterns of diversification in tarantulas.

The extreme asymmetry of species richness distribution across the tree of life has always intrigued evolutionary biologists. Two competing explanations have been proposed to explain this pattern-the clade age hypothesis and diversification rate variation. While these two scenarios may not be mutually exclusive, to what extent time and diversification rates interact to explain species richness patterns remains understudied.

Production performance, haematological parameters, serum biochemistry, and expression of HSP-70 in broiler chickens fed dietary ascorbic acid during heat stress.

An experiment was carried out to assess the efficacy of supplemental ascorbic acid (AA) on broiler chicken production performance, blood haematological profile, biochemical profile, and carcass traits under heat stress conditions. A total of 192-day-old broiler chicks were divided into four groups, each with six replicates of eight each (4 × 6 × 8). Four corn-based dietary treatments were formulated: T (control diet), T (T + AA at 200 mg/kg), T (T + AA at 400 mg/kg), and T (T + AA at 600 mg/kg) for a period of 42 days.

Trends in Formulation Approaches for Sustained Drug Delivery to the Posterior Segment of the Eye.

The eye, an intricate organ comprising physical and physiological barriers, poses a significant challenge for ophthalmic physicians seeking to treat serious ocular diseases affecting the posterior segment, such as age-related macular degeneration (AMD) and diabetic retinopathy (DR). Despite extensive efforts, the delivery of therapeutic drugs to the rear part of the eye remains an unresolved issue. This comprehensive review delves into conventional and innovative formulation strategies for drug delivery to the posterior segment of the eye.

Electrochemical generation of high-valent oxo-manganese complexes featuring an anionic N5 ligand and their role in O-O bond formation.

Generation of high-valent oxomanganese complexes through controlled removal of protons and electrons from low-valent congeners is a crucial step toward the synthesis of functional analogues of the native oxygen evolving complex (OEC). In-depth studies of the water oxidation activity of such biomimetic compounds help in understanding the mechanism of O-O bond formation presumably occurring in the last step of the photosynthetic cycle. Scarce reports of reactive high-valent oxomanganese complexes underscore the impetus for the present work, wherein we report the electrochemical generation of the non-heme oxomanganese(IV) species [(dpaq)Mn(O)] (2) through a proton-coupled electron transfer (PCET) process from the hydroxomanganese complex [(dpaq)Mn(OH)]ClO (1).

Mechanistic Insight into the Abiotic Interactions of Selenate and Selenite with Natural Organic Matter.

Natural organic matter (NOM) decreases the selenium (Se) mobility in soil and sediment. Biotic dissimilatory reduction of selenate and selenite and assimilation of the reduced Se species into biomolecules are thought to be primarily responsible for this decreased Se mobility. However, the possibility of Se immobilization due to the abiotic interaction of Se species with NOM is still poorly understood.