ADSL promotes autophagy and tumor growth through fumarate-mediated Beclin1 dimethylation.

As an enzyme with a critical role in de novo purine synthesis, adenylosuccinate lyase (ADSL) expression is upregulated in various malignancies. However, whether ADSL possesses noncanonical functions that contribute to cancer progression remains poorly understood. Here, we demonstrate that protein kinase R-like endoplasmic reticulum kinase (PERK) activated by lipid deprivation or ER stress phosphorylates ADSL at S140, leading to an enhanced association between ADSL and Beclin1.

Antimicrobial Susceptibility of Clinical Isolates of Stenotrophomonas maltophilia Isolates from Europe, Asia, and Latin America (2018-2023).

Background: The occurrence of Stenotrophomonas maltophilia infections, especially pneumonia, has increased consistently in the last years. We evaluated the antimicrobial susceptibility of a large collection of S. maltophilia collected in Europe, Asia, and Latin America.

Chalcogen dihydrobenzofuran compounds as potential neuroprotective agents: an in vitro and in silico biological investigation.

Oxidative stress arises from an imbalance between reactive species (RS) production and the antioxidant defense, increasing the brain susceptibility to neurodegenerative and psychiatric diseases. Besides, changes in the expression or activity of neurotransmitter metabolism enzymes, such as monoamine oxidases (MAO), are also associated with mental disorders, including depression. Considering this, antioxidant and MAO-A activity inhibitory potential of six 2,3-chalcogenodihydrobenzofurans (2,3-DHBF) was investigated through in vitro and in silico tests.

The role of carbon and nitrogen ratio on sewage sludge microbiota for producing polyhydroxyalkanoates.

The products of an advanced sewage sludge fermentation process can be used to generate polyhydroxyalkanoates (PHAs), precursors of bioplastics considered excellent candidates for replacing petroleum-derived plastics. The aerobic feast-anoxic famine cycling strategy has proven to be an efficient method for enriching sewage sludge microbiota with PHA-producing microorganisms. This work evaluated the effect of different carbon to nitrogen ratios (C/N) of 3.

Computer-aided design of novel anthranilic diamides containing fluorinated alkoxy groups as potential ryanodine receptor insecticides.

Background: Increasing the diversity of lead compounds has been shown to enhance the efficacy of diamide insecticides. Fifty novel compounds were precisely designed and synthesized utilizing fragment-based assembly and virtual screening coupling.

Results: The median lethal concentration (LC) values of compounds X-30 and X-40 against Mythimna separata were 0.

Ecdysteroids in Native Trees and Callus Cultures of the Genus Vitex L. of the Flora of Russia and Vietnam.

Introduction: Vitex L. is a large genus of tropical and subtropical trees used in medicine of many nations. Some species are used in gynecology due to flavonoids, iridoids, and diterpenes.

Proteo-Transcriptomic Analysis Reveals the Mechanisms Underlying Escherichia coli Phenotypic Shifts Under Blue Light.

Bacteria can adapt their lifestyles, including microbial growth, metabolism, and biofilm formation, in response to light signaling. However, the molecular pathways through which blue light affects the lifestyle of Escherichia coli (E. coli) remain incomplete and poorly understood.

Ginsenoside Rd protects against acute liver injury by regulating the autophagy NLRP3 inflammasome pathway.

Ginsenoside Rd (Rd) is a bioactive compound predominantly found in Panax ginseng C.A. Meyer and Panax notoginseng (Burkill) F.

Impacts of climate change on the suitable habitat of Angelica sinensis and analysis of its drivers in China.

Climate change is shifting optimal habitats for medicinal plants, potentially compromising the efficacy and therapeutic value of herbal remedies. Global warming and increased extreme weather events threaten the sustainability and pharmaceutical integrity of Angelica sinensis (Oliv.) Diels (A.

Metallofullerenol Gd@C(OH) preserves human erythrocyte plasma membrane integrity from AAPH-induced oxidative stress: molecular mechanisms and antioxidant activity.

Metallofullerenols and fullerenols have attracted attention due to their remarkable ability to interact with various biologically relevant molecules, paving the way for biomedical applications, ranging from medical imaging techniques to drug carriers, acting with increased efficiency and reduced side effects. In this work, we investigated the effects of two fullerene derivatives, Gd@C(OH) and C(OH), on erythrocyte membrane components under oxidative stress conditions induced by 2,2'-azobis(2-amidinopropane) dihydrochloride (AAPH) as a source of peroxyl radicals. The results demonstrated that gadolinium encapsulation within the fullerene cage enhanced the electron affinity of Gd@C(OH), resulting in stronger antioxidant activity.

Implications of frequent hitter E3 ligases in targeted protein degradation screens.

Targeted protein degradation (TPD) offers a promising approach for chemical probe and drug discovery that uses small molecules or biologics to direct proteins to the cellular machinery for destruction. Among the >600 human E3 ligases, CRBN and VHL have served as workhorses for ubiquitin-proteasome system-dependent TPD. Identification of additional E3 ligases capable of supporting TPD would unlock the full potential of this mechanism for both research and pharmaceutical applications.

Utilizing TP53 hotspot mutations as effective predictors of gemcitabine treatment outcome in non-small-cell lung cancer.

TP53 mutations are recognized to correlate with a worse prognosis in individuals with non-small cell lung cancer (NSCLC). There exists an immediate necessity to pinpoint selective treatment for patients carrying TP53 mutations. Potential drugs were identified by comparing drug sensitivity differences, represented by the half-maximal inhibitory concentration (IC50), between TP53 mutant and wild-type NSCLC cell lines using database analysis.

From past to present: tracing the trends of diabetes drug trials in mainland China.

Background: This study aimed to analyze the changing trend of diabetes drugs clinical trials in China during 2013-2023, and provided a reference for the research and development of diabetes drugs.

Methods: Diabetes drug clinical trial data were obtained from the registration and information disclosure platform of the National Medical Products Administration (NMPA) between January 1, 2013, and December 31, 2023. Trends of clinical trials on diabetes drugs were systematically analyzed in terms of characteristics, trial design, time trends, drug type, and indications.

A Pair of Fluorescent Probes Enabling Precise Diagnosis of Liver Cancer by Complementary Imaging.

Hepatocellular carcinoma (HCC) is by far the predominant malignant liver cancer, with both high morbidity and mortality. Early diagnosis and surgical resections are imperative for improving the survival of HCC patients. However, limited by clinical diagnosis methods, it is difficult to accurately distinguish tumor tissue and its boundaries in the early stages of cancer.

Antiseizure Medications: Advancements, Challenges, and Prospects in Drug Development.

Epilepsy is a neurological disorder affecting millions of people worldwide. Antiseizure medications (ASM) remain a critical therapeutic intervention for treating epilepsy, notwithstanding the rapid development of other therapies. There have been substantial advances in epilepsy medications over the past three decades, with over 20 ASMs now available commercially.

Co-Delivery of Glycyrrhizin and Paclitaxel via Gelatin-Based Core-Shell Nanoparticles Ameliorates 1,2-Dimethylhydrazine-Induced Precancerous Lesions in Colon.

Colorectal cancer is a lethal malignancy that begins from acquired/inherent premalignant lesions. Thus, targeting these lesions at an early stage of the disease could impede the oncogenesis and maximize the efficacy. The present work underscores a combinatorial therapy of paclitaxel (PTX) and glycyrrhizin (GL) delivered via gelatin-derived core-shell nanoparticles [AC-PCL(GL + PTX)-GNPs] for effective management of precancerous lesions.

FDA-approved drugs featuring macrocycles or medium-sized rings.

Macrocycles or medium-sized rings offer diverse functionality and stereochemical complexity in a well-organized ring structure, allowing them to fulfill various biochemical functions, resulting in high affinity and selectivity for protein targets, while preserving sufficient bioavailability to reach intracellular compartments. These features have made macrocycles attractive candidates in organic synthesis and drug discovery. Since the 20th century, more than three-score macrocyclic drugs, including radiopharmaceuticals, have been approved by the US Food and Drug Administration (FDA) for treating bacterial and viral infections, cancer, obesity, immunosuppression, inflammatory, and neurological disorders, managing cardiovascular diseases, diabetes, and more.

Regional environmental impacts on growth traits and phytochemical profiles of Glycyrrhiza glabra L. for enhanced medicinal and industrial use.

Identifying the optimal cultivation regions and evaluating the impact of environmental factors are crucial for selecting the best conditions for the commercial production of important medicinal and industrial plants. This study examined the effects of different cultivation areas-Rayen, Eghlid, Kalat, and Zanjan-on the agro-morphological and phytochemical traits of Glycyrrhiza glabra. The findings revealed that the location where the plants were grown significantly influenced their physical and chemical characteristics.

Supramolecular discrimination and diagnosis-guided treatment of intracellular bacteria.

Pathogenic intracellular bacteria pose a significant threat to global public health due to the barriers presented by host cells hindering the timely detection of hidden bacteria and the effective delivery of therapeutic agents. To address these challenges, we propose a tandem diagnosis-guided treatment paradigm. A supramolecular sensor array is developed for simple, rapid, accurate, and high-throughput identification of intracellular bacteria.

Phenolic Compounds and Pharmacological Potential of Extracts for the Treatment of Neurodegenerative Diseases.

The search for neuroprotective compounds in lavender is driven by its traditional use for brain health, with antioxidant activity serving as a key mechanism in reducing oxidative stress and supporting cognitive function. Lavender's potential to protect neurons is based on its calming, anti-stress properties, which increase the brain's resistance to neurodegeneration. Although lavender is not a traditional medicinal plant in Ukraine, it is increasingly recognised for its medicinal properties and is widely cultivated in the country.

High-Yield Production of Polyhydroxybutyrate and Poly(3-hydroxybutyrate--3-hydroxyhexanoate) from Crude Glycerol by a Newly Isolated Species Oh_219.

Crude glycerol (CG), a major biodiesel production by-product, is the focus of ongoing research to convert it into polyhydroxyalkanoate (PHA). However, few bacterial strains are capable of efficiently achieving this conversion. Here, 10 PHA-producing strains were isolated from various media.

2-Aminothiophene Derivatives-New Drug Candidates Against Leishmaniasis: Drug Design, Synthesis, Pharmacomodulation, and Antileishmanial Activity.

: Leishmaniasis is one of the 20 Neglected Tropical Diseases according to the WHO, affecting approximately 12 million people in four continents, generating serious public health problems. The lack of therapeutic options, associated with toxicity and the emergence of resistance to the few available drugs, makes it urgent to develop new drug options. In this context, the aims of this work are to expand the knowledge about the pharmacophore group responsible for the antileishmanial potential of 2-aminothiophene derivatives.

Fabrication and In Vivo Evaluation of In Situ pH-Sensitive Hydrogel of Sonidegib-Invasomes via Intratumoral Delivery for Basal Cell Skin Cancer Management.

Background/objectives: Basal cell skin cancer (BCSC) develops when skin cells proliferate uncontrollably. Sonidegib (SDB) is a therapeutic option for the treatment of BCSC by inhibiting hedgehog signaling. The problems with SDB's low solubility, poor bioavailability, resistance, poor targeting, and first-pass action make it less effective when taken orally.

The Facile Solid-Phase Synthesis of Thiazolo-Pyrimidinone Derivatives.

A thiazolo-pyrimidinone derivative library was developed through a facile solid-phase synthesis method. For the reaction, the thiazolo[4,5-]pyrimidin-7(6)-one structure was synthesized through efficient Thorpe-Ziegler and cyclization reactions. The thiazolo[4,5-]pyrimidin-7(6)-one derivative library with a diversity of three had a total of four synthesis steps and 57 compounds.

Characteristics of Hydrogels as a Coating for Microneedle Transdermal Delivery Systems with Agomelatine.

Agomelatine (AGM) is an effective antidepressant with low oral bioavailability due to intensive hepatic metabolism. Transdermal administration of agomelatine may increase its bioavailability and reduce the doses necessary for therapeutic effects. However, transdermal delivery requires crossing the barrier.