Machine learning-assisted SERS sensor for fast and ultrasensitive analysis of multiplex hazardous dyes in natural products.

The adulteration of natural products with multiple azo dyes has become a serious public health concern. Thus, on-site trace additive detection is demanded. Herein, we developed a gold-nanorod-based surface-enhanced Raman scattering (SERS) sensor to detect trace amounts of azo dyes, including lemon yellow, sunset yellow, golden orange II, acid red 73, coccine, and azorubine.

ClickGen: Directed exploration of synthesizable chemical space via modular reactions and reinforcement learning.

Despite the significant potential of generative models, low synthesizability of many generated molecules limits their real-world applications. In response to this issue, we develop ClickGen, a deep learning model that utilizes modular reactions like click chemistry to assemble molecules and incorporates reinforcement learning along with inpainting technique to ensure that the proposed molecules display high diversity, novelty and strong binding tendency. ClickGen demonstrates superior performance over the other reaction-based generative models in terms of novelty, synthesizability, and docking conformation similarity for existing binders targeting the three proteins.

Metallodrugs: Synthesis, mechanism of action and nanoencapsulation for targeted chemotherapy.

As a multifactorial and heterogeneous disease, cancer has a high mortality rate, and the search for more effective treatments is an enormous challenge. Metal coordination compounds open a range of possibilities that conventional organic and biological molecules can no longer fulfil due to increasing drug resistance. Metallodrugs still have tremendous potential to help overcome drug resistance and find new cures in medicine, considering that at least 25 metallic elements participate in healthy functioning of the human body.

Global Trends of Mechanical Thrombectomy in Acute Ischemic Stroke Over the Past Decade: A Scientometric Analysis Based on WOSCC and GBD Database.

Objective: To present a global overview of the current research landscape and emerging trends in mechanical thrombectomy for acute ischemic stroke (AIS) over the past decade.

Methods: A thorough search was conducted on the Web of Science on May 20, 2024, focusing on original articles and reviews in English. Bibliometric tools were employed to make a network analysis and visual representation.

Isorhapontigenin alleviates acetaminophen-induced liver injury by promoting fatty acid oxidation.

Acetaminophen (APAP) is a widely used analgesic and antipyretic medicine. It is frequently employed to alleviate pain and mitigate fever-related symptoms, but it can cause liver injury or even liver failure when overdosed. Isorhapontigenin, a compound derived from Chinese herbs and grapes, has been demonstrated to exhibit antioxidant and anti-inflammatory effects.

The Synthesis of Benzazepines via Sequential [3 + 2]-Annulation and [3,3]-Sigmatropic Rearrangement.

A novel annulation reaction of prop-2-ynylsulfonium salts with sulfur ylides and nitrosobenzenes has been developed, affording various benzazepines in moderate to good yields. Prop-2-ynylsulfonium salts act as C synthons in the reactions, providing a promising benzazepine skeleton in a one-pot operation with readily accessible starting materials.

Remolding the tumor microenvironment by bacteria augments adoptive T cell therapy in advanced-stage solid tumors.

The intricate tumor microenvironment presents formidable obstacles to the efficacy of adoptive T cell therapy in the management of solid tumors by limiting the infiltration and inducing exhaustion of the transferred T cells. Here, we developed a bacterial-based adjuvant approach that augments the efficacy of adoptive T-cell therapy for solid tumor treatment. Our study reveals that intratumor injection of E.

Nucleic Acid Covalent Tags.

The selective and site-specific chemical labeling of proteins has emerged as a pivotal research area in chemical biology and cell biology. An effective protein labeling typically meets several criteria, including high specificity, rapid and robust conjugation under physiological conditions, operation at low concentrations with biocompatibility, and minimal perturbation of the protein function and activity. The conjugation of nucleic acids with proteins has garnered significant attention recently due to the rapid advancements in nucleic acid probe technologies, leveraging the programmable nature of nucleic acids alongside the multifaceted functionalities of proteins.

Insights into direct KRAS inhibition strategies for cancer treatment.

KRAS is the most commonly mutated isoform in RAS-driven cancers. In the early stage, KRAS was deemed as an "undruggable" cancer target due to the lack of suitable binding pockets. With the development of KRAS inhibitors in recent years, strategies that directly suppress oncogenic KRAS have achieved significant breakthroughs.

Photoactivated hydride therapy under hypoxia beyond ROS.

As compared to oxidative phototherapy, studies on reactive reductive species-participating photodynamic therapy (PDT) are rare. Porphyrins are typical photosensitizers restricted by the oxygen level, but efficacy and selectivity are always incompatible in PDT. Herein, we report that phlorins are ideal hydride (H) donors and explore a water-soluble triphenylphosphonium-modified zinc-coordinated porphyrin (ZnPor) for photogeneration of zinc-cored phlorin (ZnPhl).

FragGen: towards 3D geometry reliable fragment-based molecular generation.

3D structure-based molecular generation is a successful application of generative AI in drug discovery. Most earlier models follow an atom-wise paradigm, generating molecules with good docking scores but poor molecular properties (like synthesizability and drugability). In contrast, fragment-wise generation offers a promising alternative by assembling chemically viable fragments.

An Oral PROTAC Targeting HPK1 Degradation Potentiates Anti-Solid Tumor Immunity.

Hematopoietic progenitor pinase1 (HPK1) knockout has been identified as an efficient route to enhance anti-tumor immune response. Here, this work develops an oral proteolysis targeting chimera (PROTAC) targeting HPK1 to efficiently and selectively degrade HPK1 to augment immunotherapeutic outcomes. In a postoperative tumor model of human cervical cancer in NSG mice, the orally-administrated PROTAC can reach tumors, down-regulate HPK1 levels in locally-administrated CAR-T cells, and promote their efficiency in inhibiting solid tumor recurrence, achieving 50% partial response (PR) and 50% complete response (CR).

Exploring the Efficacy of pH-Responsive Vancomycin/Ag/ZIF-8 Nanoparticles Modified with Hyaluronic Acid for Enhanced Antibacterial Therapy and Wound Healing.

This study introduces a novel type of metal-organic framework material, specifically zeolitic imidazolate framework-8 (ZIF-8), that is integrated with silver nanoparticles and further enhanced by incorporating vancomycin (Van) to create a composite named as Van/Ag/ZIF-8. This composite demonstrates a potent and smart antimicrobial effect due to its ability for releasing silver ions and Van in a controlled manner, especially in the microacidic conditions surrounding bacterial cells. Furthermore, we used hyaluronic acid to modify Van/Ag/ZIF-8, resulting in a composite denoted as Van/Ag/ZIF-8@HA.

Improving the Dehydroepiandrosterone Induced PCOS Rat Model: Interplay of Age, High Fat Diet, and Treatment Regimen on Reproductive and Metabolic Phenotypes.

Polycystic ovary syndrome (PCOS) is a ubiquitous reproductive condition with triggering hallmarks such as glucose intolerance, hyperandrogenism, and dyslipidemia. Despite the existence of various PCOS animal models, an ideal model which could encompass all PCOS-specific phenotype is of dire need. Dehydroepiandrosterone (DHEA) induced PCOS rats are frequently employed; though, determining the superior model among pubertal and prepubertal rats, incorporation of high fat diet (HFD), and their sustainability remains uncertain.

Development of PROTACs using computational approaches.

Proteolysis-targeting chimeras (PROTACs) are drugs designed to degrade target proteins via the ubiquitin-proteasome system. With the application of computational biology/chemistry technique in drug design, numerous computer-aided drug design and artificial intelligence (AI)-driven drug design (CADD/AIDD) methods have recently emerged to facilitate the development of PROTAC drugs. We systematically review the role of in silico tools in PROTAC drug design, emphasizing how computational software can model PROTAC action and structure, predict activity, and assist in molecule design.

Microwave-assisted, sulfhydryl-modified β-cyclodextrin-silymarin inclusion complex: A diverse approach to improve oral drug bioavailability via enhanced mucoadhesion and permeation.

The current study aimed to generate a sulfhydryl-modified β-cyclodextrin-silymarin complex (sulfhydryl-modified β-CD-SMN complex) and to evaluate the enchantment in solubility, permeability, and bioavailability of a model BCS Class IV drug silymarin (SMN). For this purpose, sulfhydryl-modified β-CD was synthesized by replacing all primary and secondary -OH groups at the β-CD backbone with sulfhydryl groups via a novel microwave-assisted technique. Afterward, sulfhydryl-modified β-CD was complexed with silymarin and characterized by FTIR and H NMR spectroscopy.

Comparison of Phosphate and Bicarbonate Buffer Solutions as Dissolution Test Media for Predicting Bioequivalence of Febuxostat Formulation.

The purpose of the present study was to compare phosphate buffer (PPB) and bicarbonate buffer (BCB) solutions as dissolution test media for predicting the bioequivalence (BE) of an immediate-release (IR) formulation. Febuxostat was used as a model of free acid drugs. One reference formulation (RF) and three test formulations (TF) were employed in this study.

Dopamine agonist Rotigotine mitigates lipopolysaccharide-induced neuroinflammation and memory impairment in mice.

Background: Dopaminergic signaling in the Central Nervous System (CNS) has been observed in the pathophysiology of memory deficits. Rotigotine belongs to a non-ergot-based dopamine receptor agonist possessing anti-inflammatory properties. However, it is uncertain if it has a role in ameliorating cognitive decline.

New chemometrics-assisted spectrophotometric methods for simultaneous determination of co-formulated drugs montelukast, rupatadine, and desloratadine in their different dosage combinations.

Two accurate, precise and robust multivariate chemometric methods were developed for the simultaneous determination of montelukast sodium (MON), rupatadine fumarate (RUP) and desloratadine (DES). These methods provide a cost-effective alternative to chromatographic techniques by utilizing spectrophotometry in pharmaceutical quality control. The proposed approaches, partial least squares-1 (PLS-1) and artificial neural network (ANN), were optimized using genetic algorithm (GA) to select the most influential wavelengths, enhancing model performance.

Efficacy of probiotics as adjuvant therapy in bronchial asthma: a systematic review and meta-analysis.

Background: Asthma is a chronic, heterogeneous disease characterized by airway inflammation. Asthma exacerbations significantly increase the disease burden, necessitating new therapeutic approaches. Emerging evidence suggests probiotics, through the gut-lung axis, may benefit asthma management by modulating immune responses and reducing inflammation.

Unraveling the Mysteries of Alzheimer's Disease Using Artificial Intelligence.

Alzheimer's disease (AD) is a multidimensional, complex condition that affects individuals all over the world. Despite decades of experimental and clinical research that has revealed various processes, many concerns concerning the origin of Alzheimer's disease remain unresolved. Despite the notion that there isn't a complete set of jigsaw pieces, the growing number of public data-sharing initiatives that collect biological, clinical, and lifestyle data from those suffering from Alzheimer's disease has resulted in virtually endless volumes of knowledge about the disorder, far beyond what humans can comprehend.

A comprehensive review on the green synthesis of silver nanoparticles from marine sources.

The primary purpose of this review is to explore the green synthesis of silver nanoparticle (AgNP) using natural biomolecules derived from marine sources. This review aims to evaluate the effectiveness of environmentally friendly approaches for synthesizing AgNPs and to examine their potential applications across various fields such as medicine, biotechnology, and environmental remediation. The key research question focuses on understanding how marine biomolecules, including polysaccharides, proteins, enzymes, amino acids, alkaloids, and vitamins, contribute to the formation of AgNPs and how these green-synthesized nanoparticles retain their functional properties.