Large enhancement of ferroelectric properties of perovskite oxides via nitrogen incorporation.

Perovskite oxides have a wide variety of physical properties that make them promising candidates for versatile technological applications including nonvolatile memory and logic devices. Chemical tuning of those properties has been achieved, to the greatest extent, by cation-site substitution, while anion substitution is much less explored due to the difficulty in synthesizing high-quality, mixed-anion compounds. Here, nitrogen-incorporated BaTiO thin films have been synthesized by reactive pulsed-laser deposition in a nitrogen growth atmosphere.

Targeted NIR Fluorescent Mechanically Interlocked Molecules-Peptide Bioconjugate for Live Cancer Cells Submitochondrial Stimulated Emission Depletion Super-Resolution Microscopy.

Herein, a water-soluble, ultrabright, near-infrared (NIR) fluorescent, mechanically interlocked molecules (MIMs)-peptide bioconjugate is designed with dual targeting capabilities. Cancer cell surface overexpressed αβ integrin targeting two RGDS tetrapeptide residues is tethered at the macrocycle of MIMs-peptide bioconjugate via Cu(I)-catalyzed click chemistry on the Wang resin, and mitochondria targeting lipophilic cationic TPP functionality is conjugated at the axle dye. Living carcinoma cell selective active targeting, subsequently cell penetration, mitochondrial imaging, including the ultrastructure of cristae, and real-time tracking of malignant mitochondria by MIMs-peptide bioconjugate (RGDS)-Mito-MIMs-TPP are established by stimulated emission depletion (STED) super-resolved fluorescence microscopy.

Comparative efficacy and safety of co-amoxiclav, cefpodoxime proxetil, and levofloxacin in patients with acute uncomplicated bacterial tonsillitis: A prospective, open-label, parallel group study.

Background: No clinical trials have compared the efficacy and safety of beta-lactam antibiotics and fluoroquinolones in acute uncomplicated bacterial tonsillitis. This study aimed to compare the efficacy and safety of co-amoxiclav (amoxicillin/clavulanic acid), cefpodoxime proxetil, and levofloxacin monotherapy in patients with acute uncomplicated bacterial tonsillitis.

Methods: This was a prospective, open-label, parallel-group study where 90 patients with acute uncomplicated bacterial tonsillitis were equally divided into three groups to receive either tablet co-amoxiclav 625 mg thrice daily, tablet cefpodoxime proxetil 200 mg twice daily, or tablet levofloxacin 500 mg once daily for five days.

How the development of chronic morbidity and multimorbidity depends on natural age of menopause: Results from nationally representative cross-sectional Indian study.

Background: Multimorbidity development is linked with the age at menopause. Fewer studies are available to support the findings. This study was conducted to find, how multimorbidity is associated with the natural age of menopause.

A Novel Approach to Assessing the Potential of Electronic Decision Support Systems to Improve the Quality of Antenatal Care in Nepal.

Introduction: Electronic decision-support systems (EDSSs) aim to improve the quality of antenatal care (ANC) through adherence to evidence-based guidelines. We assessed the potential of the mHealth integrated model of hypertension, diabetes, and ANC EDSS and the World Health Organization EDSS to improve the quality of ANC in primary-level health care facilities in Nepal.

Methods: From December 2021 to January 2023, we conducted a mixed-methods evaluation in 19 primary-level ANC facilities in Bagmati Province, Nepal.

Raman signatures of inversion symmetry breaking structural transition in quasi-1D compound, (TaSe4)3I.

The breaking of inversion symmetry combined with spin-orbit coupling, can give rise to intrigu- ing quantum phases and collective excitations. Here, we report systematic temperature dependent Raman scattering and theoretical calculations of phonon modes across the inversion symmetry- breaking structural transitions in a quasi-one-dimensional compound (TaSe4)3I. Our investigation revealed the emergence of three additional Raman-active modes in Raman spectra of the low- temperature (LT) non-centrosymmetric (NC) structure of the material.

A new pipeline SPICE identifies novel JUN-IKZF1 composite elements.

Transcription factor partners can cooperatively bind to DNA composite elements to augment gene transcription. Here, we report a novel protein-DNA binding screening pipeline, termed Spacing Preference Identification of Composite Elements (SPICE), that can systematically predict protein binding partners and DNA motif spacing preferences. Using SPICE, we successfully identified known composite elements, such as AP1-IRF composite elements (AICEs) and STAT5 tetramers, and also uncovered several novel binding partners, including JUN-IKZF1 composite elements.

E-cigarettes increase the risk of adenoma formation in murine colorectal cancer model.

E-cigarettes (E.cigs) cause inflammation and damage to human organs, including the lungs and heart. In the gut, E.

Presence of Fragmented Intratumoral Thrombosed Microvasculature in the Necrotic and Peri-Necrotic Regions on SWI Differentiates IDH Wild-Type Glioblastoma From IDH Mutant Grade 4 Astrocytoma.

Background: Isocitrate dehydrogenase (IDH) wild-type (IDH) glioblastomas (GB) are more aggressive and have a poorer prognosis than IDH mutant (IDH) tumors, emphasizing the need for accurate preoperative differentiation. However, a distinct imaging biomarker for differentiation mostly lacking. Intratumoral thrombosis has been reported as a histopathological biomarker for GB.

Association of Anaesthetists guidelines: the use of blood components and their alternatives 2024.

Background: The administration of blood components and their alternatives can be lifesaving. Anaemia, bleeding and transfusion are all associated with poor peri-operative outcomes. Considerable changes in the approaches to optimal use of blood components and their alternatives, driven by the findings of large randomised controlled trials and improved haemovigilance, have become apparent over the past decade.

Enhancing photocatalytic hydrogen peroxide generation by tuning hydrazone linkage density in covalent organic frameworks.

The conversion of solar energy into chemical energy or high-value chemicals has attracted considerable research interest in the context of the global energy crisis. Hydrogen peroxide (HO) is a versatile and powerful oxidizing agent widely used in chemical synthesis and medical disinfection. HO also serves as a clean energy source in fuel cells, generating electricity with zero-carbon emissions.

Nanoscale thickness Octave-spanning coherent supercontinuum light generation.

Coherent broadband light generation has attracted massive attention due to its numerous applications ranging from metrology, sensing, and imaging to communication. In general, spectral broadening is realized via third-order and higher-order nonlinear optical processes (e.g.

TransConv: convolution-infused transformer for protein secondary structure prediction.

Context: Protein secondary structure prediction is essential for understanding protein function and characteristics and can also facilitate drug discovery. Traditional methods for experimentally determining protein structures are both time-consuming and costly. Computational biology offers a viable alternative by predicting protein structures from their sequences.

Xalnesiran with or without an Immunomodulator in Chronic Hepatitis B.

Background: Xalnesiran, a small interfering RNA molecule that targets a conserved region of the hepatitis B virus (HBV) genome and silences multiple HBV transcripts, may have efficacy, with or without an immunomodulator, in patients with chronic HBV infection.

Methods: We conducted a phase 2, multicenter, randomized, controlled, adaptive, open-label platform trial that included the evaluation of 48 weeks of treatment with xalnesiran at a dose of 100 mg (group 1), xalnesiran at a dose of 200 mg (group 2), xalnesiran at a dose of 200 mg plus 150 mg of ruzotolimod (group 3), xalnesiran at a dose of 200 mg plus 180 μg of pegylated interferon alfa-2a (group 4), or a nucleoside or nucleotide analogue (NA) alone (group 5) in participants with chronic HBV infection who had virologic suppression with NA therapy. The primary efficacy end point was hepatitis B surface antigen (HBsAg) loss (HBsAg level, <0.

Hidden domain boundary dynamics toward crystalline perfection.

A central paradigm of nonequilibrium physics concerns the dynamics of heterogeneity and disorder, impacting processes ranging from the behavior of glasses to the emergent functionality of active matter. Understanding these complex mesoscopic systems requires probing the microscopic trajectories associated with irreversible processes, the role of fluctuations and entropy growth, and the timescales on which nonequilibrium responses are ultimately maintained. Approaches that illuminate these processes in model systems may enable a more general understanding of other heterogeneous nonequilibrium phenomena, and potentially define ultimate speed and energy cost limits for information processing technologies.

Semisynthesis of Alkaloid Derivatives: Pyranoacridone-Hydroxamic Acid Cytotoxic Conjugates with HDAC and Topoisomerase II α Dual Inhibitory Activity.

Inspired by our previous efforts in the semisynthetic modification of naturally occurring pyranoacridones, we report the targeted design and semisynthesis of dual inhibitors of HDAC and topoisomerase II α (Topo II α) derived from des--methylacronycine () and noracronycine () pyranoacridone alkaloids. Designed from the clinically approved SAHA, the cytotoxic pyranoacridone nuclei from the alkaloids served as the capping group, while a hydroxamic acid moiety functioned as the zinc-binding group. Out of 16 compounds evaluated in an cytotoxicity assay, KT32 () with noracronycine () as the capping group and five-carbon linker hydroxamic acid side chains showed good cytotoxic activity with IC values of 1.

2-Cyanopyrimidine-Containing Molecules for N-Terminal Selective Cyclization of Phage-Displayed Peptides.

Current methods for the macrocyclization of phage-displayed peptides often rely on small molecule linkers that nonspecifically react with targeted amino acid residues. To expand tool kits for more regioselective macrocyclization of phage-displayed peptides, this study explores the unique condensation reaction between an N-terminal cysteine and nitrile along with the reactivity of an internal cysteine. Five 2-cyanopyrimidine derivatives were synthesized for this purpose and evaluated for their selective macrocyclization of a protein-fused model peptide.

Clozapine and Pneumonia: Synthesizing the Link by Reviewing Existing Reports-A Systematic Review and Meta-Analysis.

Clozapine is a highly effective antipsychotic used for treating treatment-refractory psychotic and mood disorders. However, clozapine also has a serious risk of side effects leading to mortality, particularly its potentiated risk of leading to pneumonia. This review aims to overview the demographic and health-related risk factors leading to pneumonia to better inform risk assessment for clozapine users and to summarise current theories on the mechanisms for clozapine-associated pneumonia.

A new pipeline SPICE identifies novel JUN-IKZF1 composite elements.

Transcription factor partners can cooperatively bind to DNA composite elements to augment gene transcription. Here, we report a novel protein-DNA binding screening pipeline, termed Spacing Preference Identification of Composite Elements (SPICE), that can systematically predict protein binding partners and DNA motif spacing preferences. Using SPICE, we successfully identified known composite elements, such as AP1-IRF composite elements (AICEs) and STAT5 tetramers, and also uncovered several novel binding partners, including JUN-IKZF1 composite elements.

Enhanced identification of small molecules binding to hnRNPA1 via cryptic pockets mapping coupled with X-Ray fragment screening.

The human heterogeneous nuclear ribonucleoprotein (hnRNP) A1 is a prototypical RNA-binding protein essential in regulating a wide range of post-transcriptional events in cells. As a multifunctional protein with a key role in RNA metabolism, deregulation of its functions has been linked to neurodegenerative diseases, tumour aggressiveness and chemoresistance, which has fuelled efforts to develop novel therapeutics that modulates its RNA binding activities. Here, using a combination of Molecular Dynamics (MD) simulations and graph neural network pockets predictions, we showed that hnRNPA1 N-terminal RNA binding domain (UP1) contains several cryptic pockets capable of binding small molecules.

Two-Layer Retrieval-Augmented Generation Framework for Low-Resource Medical Question Answering Using Reddit Data: Proof-of-Concept Study.

Background: The increasing use of social media to share lived and living experiences of substance use presents a unique opportunity to obtain information on side effects, use patterns, and opinions on novel psychoactive substances. However, due to the large volume of data, obtaining useful insights through natural language processing technologies such as large language models is challenging.

Objective: This paper aims to develop a retrieval-augmented generation (RAG) architecture for medical question answering pertaining to clinicians' queries on emerging issues associated with health-related topics, using user-generated medical information on social media.

Interaction of a Novel Dihydroxy Dibenzoazacrown with Different Surfactants: A Physicochemical and Spectroscopic Investigation.

Interaction of a novel dihydroxy dibenzoazacrown (HDTC) with various surfactants of different charges, for example, anionic (sodium dodecylsulfate, SDS), cationic (dodecyl trimethylammonium bromide, DTAB), cationic gemini (butanediyl-1,4-bis(dimethylcetylammonium bromide), 16-4-16), ionic liquid (1-hexadecyl-3-methylimidazolium chloride, CMImCl), and nonionic (polyoxyethylene sorbitan monostearate, Tween-60), has been investigated at a widespread range of surfactant concentrations (including premicellar, micellar, and postmicellar regime) in 15% (v/v) EtOH medium at room temperature. Several experimental techniques, viz., tensiometry, UV-vis spectroscopy, and steady-state fluorimetry, are implemented to explicate these interactions.

Designing of an mRNA vaccine against high-risk human papillomavirus targeting the E6 and E7 oncoproteins exploiting immunoinformatics and dynamic simulation.

Human papillomavirus 16 and human papillomavirus 18 have been associated with different life-threatening cancers, including cervical, lung, penal, vulval, vaginal, anal, and oropharyngeal cancers, while cervical cancer is the most prominent one. Several research studies have suggested that the oncoproteins E6 and E7 are the leading cause of cancers associated with the human papillomavirus infection. Therefore, we developed two mRNA vaccines (V1 and V2) targeting these oncoproteins.