Design, Synthesis, and Antibacterial Activities of Multi-Functional C-Functionalized 1,4-Naphthoquinonyl Organoseleniums.

A practical and efficient reaction for C-selenylation of 1,4-naphthoquinones has been explored. This coupling reaction of two redox structural motifs, such as 2-bromo-1,4-naphthoquinone with diaryldiselenide/ebselen has been achieved by using sodium borohydride reducing agent at room temperature. Using this approach, several 2-selenylated-1,4-naphthoquinones were obtained in moderate to good yields and thoroughly characterized by multinuclear (H, C, and Se) NMR, cyclic voltammetry, and mass spectrometry.

Toward a resource-optimized dynamic quantum algorithm via non-iterative auxiliary subspace corrections.

Recent quantum algorithms pertaining to electronic structure theory primarily focus on the threshold-based dynamic construction of ansatz by selectively including important many-body operators. These methods can be made systematically more accurate by tuning the threshold to include a greater number of operators into the ansatz. However, such improvements come at the cost of rapid proliferation of the circuit depth, especially for highly correlated molecular systems.

3,5-disubstituted pyridines with potent activity against drug-resistant clinical isolates.

We designed and synthesized a series of compounds with a 3,5-disubstituted pyridine moiety and evaluated them against (Mtb) and drug-resistant Mtb clinical isolates. A library of 3,5-disubstituted pyridine was synthesized. The compounds were screened for activity against H37Rv.

Development of naphthalimide hydrazide derivatives as potent antibacterial agents against carbapenem-resistant .

In this work, a novel series of naphthalimide hydrazide derivatives were designed, synthesized and evaluated against a bacterial pathogen panel. Most of the compounds were found to exhibit potent antibacterial activity against carbapenem-resistant BAA 1605, with MIC ranging from 0.5 to 16 μg mL.

Novel Peripherally Selective Cannabinoid Receptor 1 Neutral Antagonist Improves Metabolic Dysfunction-Associated Steatotic Liver Disease in Mice.

The prevalence of metabolic dysfunction-associated steatotic liver disease (MASLD) is increasing globally. MASLD is characterized by clinically significant liver steatosis, and a subset of patients progress to more severe metabolic-disorder-associated steatohepatitis (MASH) with liver inflammation and fibrosis. Cannabinoid receptor 1 (CB1) antagonism is a proven therapeutic strategy for the treatment of the phenotypes that underlie MASLD, though work on early centrally penetrant compounds largely ceased following adverse psychiatric indications in humans.

Isolation, characterization and antimicrobial activity study of Thymus vulgaris.

Herbal medicines are important for ensuring sustainable development goals (SDGs) in healthcare, particularly in developing countries with high rates of antimicrobial resistance (AMR) and little access to medical facilities. Thymus vulgaris is a widely used herbal medicinal plant known for its secondary metabolites and antimicrobial properties. The present study involved a comprehensive examination of the isolation, characterization, and antibacterial activity of Thymus vulgaris obtained from Ethiopia.

Accurate determination of excitation energy: An equation-of-motion approach over a bi-exponential coupled cluster theory.

The calculation of molecular excited states is critically important to decipher a plethora of molecular properties. In this paper, we develop an equation of motion formalism on top of a bi-exponentially parameterized ground state wavefunction toward the determination of excited states. While the ground state bi-exponential parameterization ensures an accurate description of the wavefunction through the inclusion of high-rank correlation effects, the excited state is parameterized by a novel linear response operator with an effective excitation rank beyond two.

Brolucizumab versus aflibercept for recalcitrant diabetic macular edema in Indian real-world scenario - The BRADIR study.

Purpose: To compare the safety and efficacy of aflibercept with brolucizumab for recalcitrant diabetic macular edema (DME).

Observations: At week 52, no significant visual improvement was noted in the eyes treated with either brolucizumab ( = 0.527) or aflibercept ( = 0.

Quantitative matching of forensic evidence fragments using fracture surface topography and statistical learning.

The complex jagged trajectory of fractured surfaces of two pieces of forensic evidence is used to recognize a "match" by using comparative microscopy and tactile pattern analysis. The material intrinsic properties and microstructures, as well as the exposure history of external forces on a fragment of forensic evidence have the premise of uniqueness at a relevant microscopic length scale (about 2-3 grains for cleavage fracture), wherein the statistics of the fracture surface become non-self-affine. We utilize these unique features to quantitatively describe the microscopic aspects of fracture surfaces for forensic comparisons, employing spectral analysis of the topography mapped by three-dimensional microscopy.

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.

Facile one-pot synthesis of N-pyridinylaminonaphthol derivatives and their antibacterial evaluation against multidrug-resistant Staphylococcus aureus.

The escalating severity of the menace posed by bacterial resistance has rendered the existing antibiotics less effective, thus necessitating the discovery of new antibacterial agents. The current study reports the exploration of substituted N-pyridinylaminonaphthols produced by a straightforward, one-pot multicomponent reaction process as antibacterial agents. The synthesized derivatives were assessed in vitro for their antibacterial properties against a panel of bacterial pathogens.

A phase I safety and efficacy clinical trial of plocabulin and gemcitabine in patients with advanced solid tumors.

Plocabulin (Plo) induces depolymerization of tubulin fibers with disorganization and fragmentation of the microtubule network leading to mitosis. Plo combined with gemcitabine (Gem) showed synergistic anti-tumor activity in preclinical studies. This phase I trial evaluated the safety, pharmacokinetics (PK) and efficacy of Plo 10-min infusion plus Gem on Day 1 and 8 every 3-week in patients with advanced solid tumors.

Erlotinib Treatment in Colorectal Cancer Suppresses Autophagy Based on Mutation.

The gene is mutated in approximately 45% of colorectal cancer patients. There are currently very few targeted treatments or therapies equipped to directly inhibit due to its unusual structural intricacies. Erlotinib, an EGFR inhibitor, has previously been demonstrated to reduce cell viability by inducing autophagy in lung cancer cell lines with varying EGFR mutations.

Transitioning from Aflibercept to Biosimilar Ranibizumab in Neovascular AMD (The TRANSFORM Trial): A Multicenter Observational Study.

Purpose: This study investigates the efficacy of transitioning patients with neovascular age-related macular degeneration (nAMD) from aflibercept (T1) to biosimilar ranibizumab (T2), an approach not previously documented in literature.

Methods: In this multicenter observational study, patients over 50 years of age with nAMD were shifted from intravitreal aflibercept (IVI AFL) to biosimilar ranibizumab (B-RBZ) due to financial constraints. This study employed standardized ophthalmological methods to assess visual acuity (VA), central macular thickness (CMT), and subretinal and intraretinal fluid.

Projective quantum eigensolver via adiabatically decoupled subsystem evolution: A resource efficient approach to molecular energetics in noisy quantum computers.

Quantum computers hold immense potential in the field of chemistry, ushering new frontiers to solve complex many-body problems that are beyond the reach of classical computers. However, noise in the current quantum hardware limits their applicability to large chemical systems. This work encompasses the development of a projective formalism that aims to compute ground-state energies of molecular systems accurately using noisy intermediate scale quantum (NISQ) hardware in a resource-efficient manner.

Understanding the mechanisms underlying cognitive control in psychosis.

Background: Cognitive control (CC) involves a top-down mechanism to flexibly respond to complex stimuli and is impaired in schizophrenia.

Methods: This study investigated the impact of increasing complexity of CC processing in 140 subjects with psychosis and 39 healthy adults, with assessments of behavioral performance, neural regions of interest and symptom severity.

Results: The lowest level of CC (Stroop task) was impaired in all patients; the intermediate level of CC (Faces task) with explicit emotional information was most impaired in patients with first episode psychosis.

Synthesis and biological evaluation of new naphthalimide-thiourea derivatives as potent antimicrobial agents active against multidrug-resistant and .

The emergence of antibiotic resistance to and , particularly MRSA, VRSA, and drug-resistant tuberculosis, poses a serious threat to human health. Towards discovering new antibacterial agents, we designed and synthesized a series of new naphthalimide-thiourea derivatives and evaluated them against a panel of bacterial strains consisting of , , , , and various mycobacterial pathogens. Compounds 4a, 4l, 4m, 4n, 4q, 9f, 9l, 13a, 13d, 13e, 17a, 17b, 17c, 17d, and 17e demonstrated potent antibacterial activity against with MIC 0.

Noise-independent route toward the genesis of a COMPACT ansatz for molecular energetics: A dynamic approach.

Recent advances in quantum information and quantum science have inspired the development of various compact, dynamically structured ansätze that are expected to be realizable in Noisy Intermediate-Scale Quantum (NISQ) devices. However, such ansätze construction strategies hitherto developed involve considerable measurements, and thus, they deviate significantly in the NISQ platform from their ideal structures. Therefore, it is imperative that the usage of quantum resources be minimized while retaining the expressivity and dynamical structure of the ansatz that can adapt itself depending on the degree of correlation.

Impact of carbamazepine on SMARCA4 (BRG1) expression in colorectal cancer: modulation by KRAS mutation status.

SMARCA4 is a gene traditionally considered a tumor suppressor. Recent research has however found that SMARCA4 likely promotes cancer growth and is a good target for cancer treatment. The drug carbamazepine, an autophagy inducer, was used on colorectal cancer cell lines, HCT1116 and Hke3 (KRAS mutant and wildtype).

Machine learning assisted construction of a shallow depth dynamic ansatz for noisy quantum hardware.

The development of various dynamic ansatz-constructing techniques has ushered in a new era, making the practical exploitation of Noisy Intermediate-Scale Quantum (NISQ) hardware for molecular simulations increasingly viable. However, such ansatz construction protocols incur substantial measurement costs during their execution. This work involves the development of a novel protocol that capitalizes on regenerative machine learning methodologies and many-body perturbation theoretical measures to construct a highly expressive and shallow ansatz within the variational quantum eigensolver (VQE) framework with limited measurement costs.

Antimicrobial peptide mimetic minimalistic approach leads to very short peptide amphiphiles-gold nanostructures for potent antibacterial activity.

Strategically controlling concentrations of lipid-conjugated L-tryptophan (vsPA) guides the self-assembly of nanostructures, transitioning from nanorods to fibres and culminating in spherical shapes. The resulting Peptide-Au hybrids, exhibiting size-controlled 1D, 2D, and 3D nanostructures, show potential in antibacterial applications. Their high biocompatibility, favourable surface area-to-volume ratio, and plasmonic properties contribute to their effectiveness against clinically relevant bacteria.

Noncoding RNA Profile in Reovirus Treated -Mutated Colorectal Cancer Patients.

Purpose: To investigate the alterations in the expression of noncoding, micro, and small RNA expression during treatment with oncolytic reovirus in -mutated colorectal cancer.

Methods: Oncolytic reovirus treatment was administered in phase 1 clinical trial (NCT01274624) for 5 days every 28 days, and blood samples were collected before the administration of the reovirus and 48 h, 8 days, and 15 days after its administration on day 1. Data from the blood samples were sorted using Transcriptome Analysis Software (TAC) 4.

One-pot synthesis of thioethers from indoles and -quinone methides using thiourea as a sulfur source.

Thiourea is an inexpensive and user friendly sulfur reagent that acts as a sulfur source. A simple and efficient protocol has been developed to access thioethers by reacting indoles with -quinone methides using thiourea as the sulfur source. In our experiments, the reaction apparently proceeded through an -(3-indolyl)isothiuronium iodide intermediate and subsequent generation of indolethiol that attacked the 1,6 position of -quinone methides to give desired thioethers in good to excellent yields.