An implantable system for opioid safety.

Naloxone can effectively rescue victims from opioid overdose, but less than 5% survive due to delayed or absent first responder intervention. Current overdose reversal systems face key limitations, including low user adherence, false positive detection, and slow antidote delivery. Here, we describe a subcutaneously implanted robotic first responder to overcome these challenges.

Deciphering the Seed Size-Dependent Cellular Internalization Mechanism for α-Synuclein Fibrils.

Aggregation of α-synuclein (α-Syn) and Lewy body (LB) formation are the key pathological events implicated in Parkinson's disease (PD) that spread in a prion-like manner. However, biophysical and structural characteristics of toxic α-Syn species and molecular events that drive early events in the propagation of α-Syn amyloids in a prion-like manner remain elusive. We used a neuronal cell model to demonstrate the size-dependent native biological activities of α-Syn fibril seeds.

Nucleo-cytoplasmic environment modulates spatiotemporal p53 phase separation.

Liquid-liquid phase separation of various transcription factors into biomolecular condensates plays an essential role in gene regulation. Here, using cellular models and in vitro studies, we show the spatiotemporal formation and material properties of p53 condensates that might dictate its function. In particular, p53 forms liquid-like condensates in the nucleus of cells, which can bind to DNA and perform transcriptional activity.

A BOIMPY Dye Enables Multi-Photoinduced Electron Transfer Catalysis: Reaching Super-Reducing Properties.

An established concept to create radical intermediates is photoexcitation of a catalyst to a higher energy intermediate, subsequently leading to a photoinduced electron transfer (PET) with a reaction partner. The known concept of consecutive photoinduced electron transfer (con-PET) leads to catalytically active species even higher in energy by the uptake of two photons. Generally speaking, increased photon uptake leads to a more potent reductant.

Design, Synthesis, Magnetic Properties, and Hydrogen Evolution Reaction of a Butterfly-like Heterometallic Trinuclear [CuMn] Cluster.

A novel heterometallic trinuclear cluster [CuMn(cpdp)(NO)(Cl)] () has been designed and synthesized by employing a molecular library approach that uses CuCl·2HO and Mn(NO)·4HO as inorganic metal salts and Hcpdp as a multifunctional organic scaffold (Hcpdp = ,'-bis[2-carboxybenzomethyl]-,'-bis[2-pyridylmethyl]-1,3-diaminopropan-2-ol). This heterometallic cluster has emerged as an unusual ferromagnetic material and promising electrocatalyst for hydrogen evolution reaction (HER) in the domain of inorganic and materials chemistry. Crystal structure analysis establishes the structural arrangement of , revealing a butterfly-like topology with an unusual seven-coordinated Mn(II) center.

Early augmentation therapy with dextromethorphan in mild to moderate major depressive disorder: A group sequential, response adaptive randomized controlled trial.

Aim: Therapeutic latency, lack of response, and adverse drug reactions are major challenges in current treatment approaches for major depressive disorder (MDD). Following the success of ketamine, more clinical research on NMDA antagonists is needed for a safe and long-term therapy in MDD. Hence, this study was conducted to evaluate the efficacy and safety of adjunct dextromethorphan to SSRIs in MDD.

A Cross-sectional Study on Internet Gaming Disorder and Its Association with Personality Traits in Engineering Students.

Background: In the field of psychiatry and mental health, Internet gaming disorder (IGD) is a relatively new concept. In the past few decades, as online gaming and internet usage became increasingly prevalent, this became a topic of concern and research. Therefore, this study aims to estimate the prevalence of IGD and its association with personality traits among students.

One-Pot Green Synthesis and Biological Evaluation of Dimedone-Coupled 2,3-Dihydrofuran Derivatives to Divulge Their Inhibition Potential against Staphylococcal Thioredoxin Reductase Enzyme.

New therapeutic leads are in global demand against multiple drug-resistant , as presently there is no drug of choice left to treat this pathogen. In the present work, we have designed, synthesized, and in vitro validated dimedone-coupled 2,3-dihydrofuran (DDHF)-based inhibitor scaffolds against Staphylococcal thioredoxin reductase (SaTR), a pivotal drug target enzyme of Gram-positive pathogens. Accordingly, a green multicomponent method that is both efficient and one pot has been optimized to synthesize DDHF derivatives.

Independent LUMO Reactivity in Mesoionic N-Heterocyclic Thiones: Synthesis of a Stable Radical Anion.

Mesoionic compounds, with positive and negative charges, are expected to have dual-site highest occupied molecular orbital (HOMO, donor) and lowest unoccupied molecular orbital (LUMO, acceptor) reactivity. Herein, we report a novel class of air-stable mesoionic N-heterocyclic thiones (mNHTs) synthesized from abnormal N-heterocyclic carbenes (aNHCs). DFT studies revealed a highly polarized exocyclic thione moiety and computed Fukui function analysis suggests the dual-site HOMO/LUMO reactivity of mNHTs predicting donor property at the negatively charged 'S' center while acceptor property at the cationic imidazole ring.

Leishmania major-induced alteration of host cellular and systemic copper homeostasis drives the fate of infection.

Copper plays a key role in host-pathogen interaction. We find that during Leishmania major infection, the parasite-harboring macrophage regulates its copper homeostasis pathway in a way to facilitate copper-mediated neutralization of the pathogen. Copper-ATPase ATP7A transports copper to amastigote-harboring phagolysosomes to induce stress on parasites.

Ultrasound-generated bubbles enhance osteogenic differentiation of mesenchymal stromal cells in composite collagen hydrogels.

Hydrogels can improve the delivery of mesenchymal stromal cells (MSCs) by providing crucial biophysical cues that mimic the extracellular matrix. The differentiation of MSCs is dependent on biophysical cues like stiffness and viscoelasticity, yet conventional hydrogels cannot be dynamically altered after fabrication and implantation to actively direct differentiation. We developed a composite hydrogel, consisting of type I collagen and phase-shift emulsion, where osteogenic differentiation of MSCs can be non-invasively modulated using ultrasound.

Metal-free Borylation of α-Naphthamides and Phenylacetic Acid Drug.

Site-selective C-H borylation is an important strategy for constructing molecular diversity in arenes and heteroarenes. Although transition-metal-catalyzed borylation is well explored, developing metal-free strategies remains scarce. Herein, we developed a straightforward approach for BBr-mediated selective C-H borylation of naphthamide and phenyl acetamide derivatives under metal-free conditions.

AcrIF11 is a potent CRISPR-specific ADP-ribosyltransferase encoded by phage and plasmid.

Phage-encoded anti-CRISPR (Acr) proteins inhibit CRISPR-Cas systems to allow phage replication and lysogeny maintenance. Most of the Acrs characterized to date are stable stoichiometric inhibitors, and while enzymatic Acrs have been characterized biochemically, little is known about their potency, specificity, and reversibility. Here, we examine AcrIF11, a widespread phage and plasmid-encoded ADP-ribosyltransferase (ART) that inhibits the Type I-F CRISPR-Cas system.

Corannulene Amino Acid-Derived Water-Soluble Amphiphilic Buckybowls as Broad-Spectrum Membrane Targeting Antibacterial Agents.

To date, the use of corannulene has been restricted in the area of material science, but its application in biomedical research has yet to be established due to its nonsolubility in an aqueous environment and synthetic infeasibility. Herein, we detail the development of a new family of highly curved π-conjugated corannulene-containing unnatural α-amino acid (CAA) derivatives to overcome this challenge. These CAAs have been extended as novel constituents for the synthesis of corannulene-containing water-soluble cationic peptides (CCPs), which display inhibitory activity against broad-spectrum pathogenic bacteria along with drug-resistant bacteria via a membrane-damaging mechanism.

Palladium-Catalyzed Remote C-H Functionalization: Non-Covalent Interactions and Reversibly Bound Templates.

Pd-catalysis has stood as a pivotal force in synthetic transformations for decades, maintaining its status as a paramount tool in the realm of C-H bond activation. While functionalization at proximal positions has become commonplace, achieving selective and sustainable access to distal positions continues to captivate scientific endeavors. Recently, a noteworthy trend has emerged, focusing on the utilization of non-covalent interactions to address the challenges associated with remote functionalization.

KDM6A regulates immune response genes in multiple myeloma.

The histone H3 at lysine 27 (H3K27) demethylase lysine demethylase 6A (KDM6A) is a tumor suppressor in multiple cancers, including multiple myeloma (MM). We created isogenic MM cells disrupted for KDM6A and tagged the endogenous protein to facilitate genome-wide studies. KDM6A binds genes associated with immune recognition and cytokine signaling.

Molecular landscape of prostate cancer bone metastasis.

Prostate cancer (PC) has a high propensity to develop bone metastases, causing severe pain and pathological fractures that profoundly impact a patients' normal functions. Current clinical intervention is mainly palliative focused on pain management, and tumor progression is refractory to standard therapeutic regimens. This limited treatment efficacy is at least partially due to a lack of comprehensive understanding of the molecular landscape of the disease pathology, along with the intensive overlapping of physiological and pathological molecular signaling.

Engineered Chlorella vulgaris improves bioethanol production and promises prebiotic application.

Microalgal biomass for biofuel production, integration into functional food, and feed supplementation has generated substantial interest worldwide due to its high growth rate, non-competitiveness for agronomic land, ease of cultivation in containments, and presence of several bioactive molecules. In this study, genetic engineering tools were employed to develop transgenic lines of freshwater microalga Chlorella vulgaris with a higher starch content, by up-regulating ADP-glucose pyrophosphorylase (AGPase), which is a rate-limiting enzyme in starch biosynthesis. Expression of the Escherichia coli glgC (AGPase homolog) gene in C.

A prospective observational study to assess the epidemiological profile of multiple primary cancers in Eastern India.

Background: Multiple primary cancers once thought to be rare have become increasingly common as the lifespan of cancer survivors has increased with availability of better and more effective cancer treatment. However, their exact incidence is not known and data on their epidemiological characteristics are not available.

Aim: The aim of this study is to study the epidemiologic characteristics of multiple primary cancers in the eastern region of India.

A critical appraisal on the involvement of plant-based extracts as neuroprotective agents (2012-2022): an effort to ease out decision-making process for researchers.

The purpose of this review study is to provide a condensed compilation of 164 medicinal plants that have been investigated for their neuroprotective aspects by researchers between the years 2012 and 2022 which also includes a recent update of 2023-2024. After using certain keywords to retrieve the data from SCOPUS, it was manually sorted to eliminate any instances of duplication. The article is streamlined into three major segments.

Solid-state NMR assignment of α-synuclein polymorph prepared from helical intermediate.

Synucleinopathies are neurodegenerative diseases characterized by the accumulation of α-synuclein protein aggregates in the neurons and glial cells. Both ex vivo and in vitro α-synuclein fibrils tend to show polymorphism. Polymorphism results in structure variations among fibrils originating from a single polypeptide/protein.

Perception and Acceptance of the Newly Introduced COVID-19 Precaution (THIRD) Vaccination Dose among Health Workers at an Indian Medical College.

Introduction: India has run a nationwide vaccination campaign against COVID-19, which has recently introduced a precaution (third) dose for health workers. This study assessed the perception and attitude of health workers toward the Indian vaccination campaign against COVID-19, with an emphasis on this major change.

Materials And Methods: A printed questionnaire was distributed among health-care workers at the Medical College of West Bengal.