"The COVID-19 pandemic in BRICS: Milestones, interventions, and molecular epidemiology".

Brazil, Russia, India, China, and South Africa (BRICS) are a group of developing countries with shared economic, healthcare, and scientific interests. These countries navigate multiple syndemics, and the COVID-19 pandemic placed severe strain on already burdened BRICS' healthcare systems, hampering effective pandemic interventions. Genomic surveillance and molecular epidemiology remain indispensable tools for facilitating informed pandemic intervention.

AlphaMut: A Deep Reinforcement Learning Model to Suggest Helix-Disrupting Mutations.

Helices are important secondary structural motifs within proteins and are pivotal in numerous physiological processes. While amino acids (AA) such as alanine and leucine are known to promote helix formation, proline and glycine disfavor it. Helical structure formation, however, also depends on its environment, and hence, prior prediction of a mutational effect on a helical structure is difficult.

Interfacial Assembly of Peptide Carbon Dot Hybrids Enables Photoinduced Electron Transfer with Improved Photoresponse.

Assemblies at the interface represent a powerful tool for integrating organic and inorganic components into hybrid nanostructures. Carbon dots are both excellent electron donors and acceptors, offering opportunities for their potential uses in light-harvesting applications. To further improve their functions, integration of acceptor carbon dots into donor organic nanostructures is of great interest for improving photophysical properties useful for photoinduced electron transfer.

Calcineurin inhibition enhances lifespan by defecation defects-mediated calorie restriction and nuclear hormone signaling.

Calcineurin is a highly conserved calcium/calmodulin-dependent serine/threonine protein phosphatase with diverse functions. Inhibition of calcineurin is known to enhance the lifespan of through multiple signaling pathways. Aiming to study the role of calcineurin in regulating innate immunity, we discover that calcineurin is required for the rhythmic defecation motor program (DMP) in .

Anomalous lattice contraction and emerging topological phases in Bi-substituted SmIrO.

We demonstrate that substituting Bi for Sm in the pyrochlore Sm$_2$Ir$_2$O$_7$ induces an anomalous lattice contraction, with $\Delta a \sim -0.012$~\AA~observed at 10\% Bi substitution, where 'a' denotes the lattice constant. Beyond 10\% Bi substitution, the lattice expands according to Vegard's law.

Biotin-Pt(IV)-Ru(II)-Boron-Dipyrromethene Prodrug as "Platin Bullet" for Targeted Chemo- and Photodynamic Therapy.

Using the principle of "Magic Bullet", a cisplatin-derived platinum(IV) prodrug heterobimetallic complex, -[Pt(NH)Cl{Ru(tpy-BODIPY)(tpy-COO)}(biotin)]Cl (, ), having two axial ligands, namely, biotin as water-soluble B-vitamin for enhanced cellular uptake and a BODIPY-ruthenium(II) (, ) photosensitizer having ,,-donor tpy (4'-phenyl-2,2':6',2″-terpyridine) bonded to boron-dipyrromethene (BODIPY), is developed as a "Platin Bullet" for targeted photodynamic therapy (PDT). exhibited intense absorption near 500 nm and emission near 513 nm (λ = 488 nm) in a 10% dimethyl sulfoxide-Dulbecco's phosphate-buffered saline medium (pH 7.2).

Senescent cells inhibit mouse myoblast differentiation via the SASP-lipid 15d-PGJ mediated modification and control of HRas.

Senescent cells are characterized by multiple features such as increased expression of senescence-associated β-galactosidase activity (SA β-gal) and cell cycle inhibitors such as p21 or p16. They accumulate with tissue damage and dysregulate tissue homeostasis. In the context of skeletal muscle, it is known that agents used for chemotherapy such as Doxorubicin (Doxo) cause buildup of senescent cells, leading to the inhibition of tissue regeneration.

Development of Natural-Product-Inspired ABCB1 Inhibitors Through Regioselective Tryptophan C3-Benzylation.

The emergence of drug resistance in cancer cells eventually causing relapse is a serious threat that demands new advances. Upregulation of the ATP-dependent binding cassette (ABC) transporters, such as ABCB1, significantly contributes to the emergence of drug resistance in cancer. Despite more than 30 years of therapeutic discovery, and several generations of inhibitors against P-gp, the search for effective agents that minimize toxicity to human cells, while maintaining efflux pump inhibition is still underway.

Concise Total Synthesis of (-)-Codeine.

Codeine and morphine are among the few natural products that are used directly as drugs for medical treatment. However, the availability of these is widely dependent on natural resources. Herein, we report an efficient enantioselective seven-step synthesis of (-)-codeine starting from simpler starting materials.

Order/Disorder Transitions Upon Protein Binding: A Unifying Perspective.

When two proteins bind to each other, this process is often accompanied by a change in their structural states (from disordered to ordered or vice versa). As it turns out, there are 10 distinct possibilities for such binding-related order/disorder transitions. Out of this number, seven scenarios have been experimentally observed, while another three remain hitherto unreported.

Hydrogen Bonding-Driven Self-Coacervation of Nonionic Homopolymers for Stimuli-Triggered Therapeutic Release.

Inspired by the unique functionalities of biomolecular membraneless organelles (MLOs) formed via liquid-liquid phase separation (LLPS) of intrinsically disordered proteins (IDPs) and nucleic acids, a great deal of effort has been devoted to devising phase-separated artificial subcellular dynamic compartments. These endeavors aim to unravel the molecular mechanism underlying the formation and intracellular delivery of susceptible macromolecular therapeutics. We report herein pyroglutamic acid (PGA)-based well-defined homopolymers featuring stimuli-tunable reversible self-coacervation ability.

Enzymatic Functionalization of RNA Oligonucleotides by Terminal Uridylyl Transferase Using Fluorescent and Clickable Nucleotide Analogs.

We report a systematic study on controlling the enzyme activity of a terminal uridylyl transferase (TUTase) called SpCID1, which provides methods to effect site-specific incorporation of a single modified nucleotide analog at the 3'-end of an RNA oligonucleotide (ON). Responsive heterocycle-modified fluorescent UTP probes that are useful in analyzing non-canonical nucleic acid structures and azide- and alkyne-modified UTP analogs that are compatible for chemoenzymatic functionalization were used as study systems. In the first strategy, we balanced the concentration of essential metal ion cofactors (Mg and Mn ions) to restrict the processivity of the enzyme, which gave a very good control on the incorporation of clickable nucleotide analogs.

A hydrogel based on Fe(II)-GMP demonstrates tunable emission, self-healing mechanical strength and Fenton chemistry-mediated notable antibacterial properties.

Supramolecular hydrogels serve as an excellent platform to enable reactive oxygen species (ROS) generation while maintaining controlled localized conditions, thereby mitigating cytotoxicity. Herein, we demonstrate hydrogel formation using guanosine-5'-monophosphate (GMP) with tetra(4-carboxylphenyl) ethylene (1) to exhibit aggregation-induced emission (AIE) and tunable mechanical strength in the presence of divalent metal ions such as Ca, Mg, and Fe. The addition of divalent metal ions leads to structural transformation in the metallogels (M-1GMP).

Comparison of the transcriptome, lipidome, and c-di-GMP production between BCGΔBCG1419c and BCG, with Mincle- and Myd88-dependent induction of proinflammatory cytokines in murine macrophages.

We have previously reported the transcriptomic and lipidomic profile of the first-generation, hygromycin-resistant (Hyg) version of the BCGΔBCG1419c vaccine candidate, under biofilm conditions. We recently constructed and characterized the efficacy, safety, whole genome sequence, and proteomic profile of a second-generation version of BCGΔBCG1419c, a strain lacking the BCG1419c gene and devoid of antibiotic markers. Here, we compared the antibiotic-less BCGΔBCG1419c with BCG.

An exchange of single amino acid between the phosphohydrolase modules of Escherichia coli MutT and Mycobacterium smegmatis MutT1 switches their cleavage specificities.

MutT proteins belong to the Nudix hydrolase superfamily that includes a diverse group of Mg requiring enzymes. These proteins use a generalized substrate, nucleoside diphosphate linked to a chemical group X (NDP-X), to produce nucleoside monophosphate (NMP) and the moiety X linked with phosphate (XP). E.

Prevalence and patterns of vitamin D deficiency and its role in cognitive functioning in a cohort from South India.

Vitamin D (VitD) is a naturally occurring, fat-soluble vitamin which regulates calcium and phosphate homeostasis in the human body and is also known to have a neuroprotective role. VitD deficiency has often been associated with impaired cognition and a higher risk of dementia. In this study, we aimed to explore the relationship between levels of VitD and cognitive functioning in adult individuals.

Effective Alkoxide Trapping by TMSX in the Presence of TPP Catalyst in Glycidol Acetal Rearrangements.

This study demonstrates a nucleophile-catalyzed, trimethylsilyl halide-promoted rearrangement reaction of glycidol acetals to form halogenated cyclic acetals. The acetal group has been activated selectively in the presence of trimethylsilyl cation, which is used as -generated alkoxide trapping reagent. Nucleophilic chloride and bromide ions participate in addition reactions with epoxides predominantly via S1-type epoxide opening, while non-nucleophilic iodide and triflate ions induce a positive charge at the epoxide carbon.

Heterologous expression, biochemical characterization and prospects for insecticide biosensing potential of carboxylesterase Ha006a from Helicoverpa armigera.

Enzymes have attracted considerable scientific attention for their crucial role in detoxifying a wide range of harmful compounds. In today's global context, the extensive use of insecticides has emerged as a significant threat to the environment, sparking substantial concern. Insects, including economically important pests like Helicoverpa armigera, have developed resistance to conventional pest control methods through enzymes like carboxyl/cholinesterases.

Photodynamic Therapy with Targeted Release of Boron-Dipyrromethene Dye from Cobalt(III) Prodrugs in Red Light.

Boron-dipyrromethene (BODIPY) dyes are promising photosensitizers for cellular imaging and photodynamic therapy (PDT) owing to their excellent photophysical properties and the synthetically tunable core. Metalation provides a convenient way to overcome the drawbacks arising from their low aqueous solubility. New photo-/redox-responsive Co(III) prodrug chaperones are developed as anticancer PDT agents for efficient cellular delivery of red-light-active BODIPY dyes.

Exploring the potential of pheophorbide A, a chlorophyll-derived compound in modulating GLUT for maintaining glucose homeostasis.

Introduction: Pheophorbide A, a chlorophyll-breakdown product, is primarily investigated for its anti-oxidant and anti-inflammatory activity. Recent reports on pheophorbide A have shown its potential in lowering blood glucose levels, thus leading to the exploration of its use in diabetes management. Literature has also shown its effect on enhanced insulin secretion, whereas its mechanism on glucose stimulated insulin secretion (GSIS) in pancreatic β cells remains unexplored.

Strategic design of a rare trigonal symmetric luminescent covalent organic framework by linker modification.

We designed a trigonal symmetric imine-linked covalent organic framework (COF), TFPC-DAB, with control over the angularity of the building units, where a bent C2-symmetric diamine, such as 1,3-diaminobenzene (1,3-DAB or DAB), with an exo-angle of 120° was used instead of those with an exo-angle of 180°, in combination with a C3-symmetric trialdehyde, such as tri(4-formylphenoxy)cyanurate (TFPC). Its synthesis was accomplished by reacting the building units in a mixture of mesitylene/dioxane/6 M acetic acid under solvothermal conditions. The phase purity, thermal stability, and porosity of TFPC-DAB were established by various analytical techniques.

Nitro Indole Derivatives as Novel Dual-Polarity Matrices for MALDI Mass Spectrometry and Imaging with Broad Applications.

A new matrix framework is presented in this study for the improved ionization efficiency of complex mixtures by matrix-assisted laser desorption ionization (MALDI) mass spectrometry/imaging. Five nitro indole (NI) derivatives [3-methyl-4-nitro-1H-indole (3,4-MNI), 3-methyl-6-nitro-1H-indole (3,6-MNI), 2,3-dimethyl-4-nitro-1H-indole (2,3,4-DMNI), 2,3-dimethyl-6-nitro-1H-indole (2,3,6-DMNI), and 4-nitro-1H-indole (4-NI)] were synthesized and shown to produce both positive and negative ions with a broad class of analytes as MALDI matrices. NI matrices were compared to several common matrices, such as 2,5-dihydroxybenzoic acid (DHB), alpha-cyano-4-hydroxylcinnamic acid (CHCA), sinapinic acid (SA), 1,5-diaminonaphthelene (1,5-DAN), and 9-aminoacridine (9-AA), for the analysis of lipid, peptide, protein, glycan, and perfluorooctanesulfonic acid (PFOS) compounds.

Zwitterionic Polysulfobetaine Inhibits Cancer Cell Migration Owing to Actin Cytoskeleton Dynamics.

Cell migration is an essential dynamic process for most living cells, mainly driven by the reorganization of actin cytoskeleton. To control actin dynamics, a molecular architecture that can serve as a nucleator has been designed by polymerizing sulfobetaine methacrylate. The synthesized zwitterionic polymer, poly(sulfobetaine methacrylate) (), effectively nucleates the polymerization process of G-actin and substantially accelerates the rate of polymerization.