Nanomedicine breakthroughs overcoming pancreatic cancer drug resistance through precision nano-interventions.

Pancreatic ductal adenocarcinoma (PDAC) is one of the most lethal malignancies, primarily due to its rapid acquisition of drug resistance and the complex tumor microenvironment. Conventional cancer therapies, including chemotherapy and radiotherapy, often fail to elicit durable responses because PDAC cells exhibit both intrinsic and extrinsic resistance, in which the intrinsic resistance is driven by genetic mutations, epigenetic alterations, overexpression of efflux transporters, and the presence of cancer stem cells while the extrinsic resistance is mediated by a dense desmoplastic stroma, hypovascularity, and immunosuppressive cellular components. This review comprehensively analyzes these multifactorial resistance mechanisms and examines cutting-edge nanotechnology-based strategies designed to circumvent them.

Discovery of potent and selective PKMYT1 inhibitors for the treatment of CCNE1-amplified cancer.

PKMYT1 has recently emerged as a promising synthetic lethal target, having attracted considerable research interest over the past two years. To date, most reported inhibitors are structural analogs of RP-6306. In this study, we employed molecular dynamics (MD) simulation-guided strategies to design a novel series of selective and potent PKMYT1 inhibitors.

miR-150-5p Regulates Merkel Cell Carcinoma Progression by Targeting FTO That Stabilizes CTNNB1 via mA Modification.

MicroRNAs (miRNAs) are small regulatory molecules playing important roles in different physiological and pathological processes, but only several miRNAs were functionally characterized in Merkel cell carcinoma (MCC). We previously identified miR-150-5p as one of the differentially expressed miRNAs between MCC metastases and primary tumors. In the present study, we further investigated the functional role of miR-150-5p in MCC progression.

Design, synthesis, and biological evaluation of 5-chlorine-2-amino-pyrimidine derivatives as potent PLK4 inhibitors.

Serine/threonine kinase PLK4, a critical regulator of centrosome duplication, is closely associated with tumorigenesis due to its role in centrosome amplification. PLK4 is overexpressed in multiple cancers and has recently emerged as a promising therapeutic target for TRIM37-amplified breast cancer. Developing safe and effective PLK4 inhibitors holds significant therapeutic potential.

Application of Nanotechnology in TACE Treatment of Liver Cancer.

Liver cancer, particularly hepatocellular carcinoma (HCC), remains a global health challenge with limited therapeutic options for advanced stages. Transarterial chemoembolization (TACE), the first-line treatment for intermediate and advanced-stage HCC, faces limitations such as incomplete tumor embolization and systemic toxicity. This review synthesizes recent advancements in nanotechnology to address these challenges, focusing on nanoparticles (NPs) as embolic agents, drug carriers, and imaging contrast agents.

An efficient approach for the extraction of glycoproteins from American ginseng by natural deep eutectic solvent.

Glycoproteins have not been reported in the previous studies of American ginseng. This study focuses on developing an efficient method for the extraction of glycoproteins from American ginseng (GAG). Three choline chloride (ChCl)-based natural deep eutectic solvents (NADES) and three extraction techniques including microwave-, ultrasound-, and heating and stirring-assisted extraction were evaluated in the study.

Biosafety considerations triggered by genome-editing technologies.

Since the discovery of the double helix structure of deoxyribonucleic acid (DNA), significant progress has been made in engineering technologies such as gene analysis and editing, greatly promoting the development of biomedical research and clinical applications. In recent years, the rapid development of genome-editing technologies, especially the clustered regularly interspaced short palindromic repeats-associated protein 9 (CRISPR-Cas9) system, have brought unprecedented opportunities for biomedical research and clinical applications. However, with the widespread application of genome-editing technologies, biosafety issues have gradually attracted the attention of the scientific community and the public.

Highly efficient and selective Sr capture using robust two-dimensional MOF nanosheets decorated with cage-like cavities.

The urgent need for efficient extraction of radio-strontium (Sr) from complex aquatic environments arises from its extreme radiotoxicity to both ecosystems and human health, which remains a significant challenge. In this study, we developed an ultrathin 2D Cu-MOF-COOH nanosheet with cage-like cavities for strontium separation. Incorporating the permanent cavity structures on the MOF nanosheet can fully utilize its structural characteristics of a largely exposed surface area and accessible adsorption sites in pollutant removal, and the comprehensive interactions between pollutants with the active sites and cavities on the exposed surfaces can achieve highly selective and efficient capture.

Low-dimensional compact states in 3D moiré lattices.

Moiré lattices formed by superimposing rotated two-dimensional (2D) periodic sublattices, such as twisted bilayer graphene, can exhibit fascinating properties not observed in their individual constituent layers. Despite extensive research on 2D moiré lattices, the physics of three-dimensional (3D) moiré lattices-formed by superimposing rotated 3D periodic sub-lattices with crystallographic symmetries, which exhibit unique 3D potentials determined by twisting angles-remains largely unexplored. In this work, we demonstrate that depending on the choice of rotation angles, moiré potentials composed of two cubic sub-lattices can exhibit three different phases: they can be fully 3D incommensurate, incommensurate in only one spatial direction (while remaining periodic in the orthogonal plane), or fully periodic.

Clinical outcomes after HBsAg clearance in chronic hepatitis B patients treated with Peg-IFN α: A study with an 11- to 173-month follow-up.

To investigate the risk and influencing factors of long-term liver adverse events in chronic hepatitis B patients achieving hepatitis B surface antigen (HBsAg) clearance after pegylated interferon α (Peg-IFN α) treatment, a retrospective analysis was conducted on 456 patients at Beijing Ditan Hospital from 2008 to 2023 who achieved HBsAg clearance and discontinued Peg-IFN α treatment. The baseline was defined as the time of HBsAg clearance and treatment cessation. The endpoint was the first occurrence of liver adverse events (hepatocellular carcinoma or ascites) or last follow-up.

Asymmetric C-C Coupling to Drive CO Conversion to Acetate.

Electrochemical reduction of carbon monoxide (CORR) provides pathways for decarbonizing chemical manufacturing by producing high-value multicarbon (C) products, though achieving high activity and selectivity toward a single principal C product remains challenging. Acetate, a critical liquid product, can be metabolized by bacteria to synthesize long-chain carbon compounds. Here, we design a core-shell CuO/Cu-2-methylimidazole (CuIM) catalyst with dual Cu sites (Cu and Cu) during the CORR, which shifts the reaction pathway from symmetric *CO-*CO coupling to asymmetric *CH-*CO coupling, thereby enhancing acetate formation.

Efficacy and safety of extract in the treatment of acute high altitude disease, based on studies involving populations in China: A systematic review and meta-analysis.

Introduction: To evaluate the efficacy and safety of extract (RCE) for the treatment of patients with acute high altitude disease (AHAD).

Methods: This study systematically retrieved randomized controlled trials (RCTs) published prior to September 2024 from eight distinct databases. It included AHAD patients, with the control group receiving either conventional western medicine (WM) or placebo, and the experimental group receiving RCE alone or in conjunction with WM.

Rational design of CZL-S092: A novel indazole-based PLK4 inhibitor targeting neuroblastoma through virtual screening and fragment-based drug design strategies.

Polo like kinase 4 (PLK4) is a critical member of the polo-like kinase family that works as a master regulator of centriole duplication and mitotic progression. Overexpression of PLK4 has been documented in various cancers and PLK4 inhibitors are regarded as a potential strategy for cancer treatment. In this study, we identified indazole derivative 8 as a hit compound through a virtual screening approach.

Design, synthesis, and biological evaluation of novel -(1-indazol-6-yl)benzenesulfonamide derivatives as potent PLK4 inhibitors.

PLK4 is a serine/threonine protein kinase situated at the centrosome, acting as a crucial regulatory element in the regulation of cell mitosis and significantly contributing to the preservation of genomic integrity. The overexpression of PLK4 is intricately linked to the onset and progression of several cancers, influencing a range of actions in tumor cells, such as proliferation, differentiation, migration, and invasion. PLK4 has been identified as a target for the therapy of several malignancies, especially breast cancer characterized by elevated levels.

IRF8 facilitates bovine ephemeral fever virus replication by downregulating IRF9.

Interferon regulatory factor 8 (IRF8), an essential member of the IRFs protein family, serves as a critical transcriptional regulator in cytokine signaling, gene transcription, and the differentiation and proliferation of immune cells. However, its function on the bovine ephemeral fever virus (BEFV) infection has not been described. In this study, we demonstrate that BEFV infection upregulates the expression of IRF8, and IRF8 promotes the replication of BEFV.

Diosgenin promoted OPCs differentiation via blocking GLUR2/GAPDH interaction in a pilocarpine rat model of epilepsy.

Background: Central nervous system (CNS) demyelination is associated with the occurrence of epileptic seizure, highlighting the imperative need for myelin repair strategy. Inefficient differentiation of naïve oligodendrocyte precursor cells (OPCs) into myelin-producing oligodendrocytes (OLs) is an essential pathological obstacle and a therapeutic target of myelin sheath repair.

Purpose: Our work discovers that diosgenin, a natural steroid sapogenin, distinct from its classic cardioprotective effects, directly stimulates OPCs maturation predominantly in the corpus callosum, assuring CNS myelin recovery.

Discovery of a potent, broad-spectrum and in vivo effective deuterated tetrazole CYP51 inhibitor.

Invasive fungal infections (IFIs) are a serious infectious disease worldwide, characterized by high mortality and morbidity. Azole drugs are the most commonly used drugs for the treatment of invasive fungal infections. However, because azole drugs can easily interact with human CYPs metabolic enzymes, the risk of drug-to-drug interaction is high when multiple drugs are used together with azole drugs in clinic.

Design, Synthesis, and Biological Activity Evaluation of Deuterated Diphenyl Azole Alcohol-Based CYP51 Inhibitors.

In recent years, the incidence of invasive fungal infections (IFIs) has risen significantly, leading to increased clinical use of azole antifungals. However, their therapeutic utility remains limited by emerging drug resistance, inadequate oral bioavailability, and adverse effects. This study focused on optimizing pharmacokinetic properties through a molecular hybridization strategy, integrating structural features of and .

Surface display of CadR protein on Rhodopseudomonas palustris CGA009 for enhanced heavy metal bioremediation.

Heavy metal pollution poses significant ecological and public health risks, and surface display engineering shows promise for bioremediation in this area. Although anoxygenic photosynthetic purple nonsulfur bacteria (PNSB) have been effectively applied to degrade pollutants due to their metabolic versatility, the use of surface display technology in PNSB remains very limited. In this study, we constructed a surface display system using Rhodopseudomonas palustris CGA009 as the host.

Functional expression of proton pumps in Rhodobacter sphaeroides enhanced energy supply and photo-fermentative hydrogen production.

Photo-fermentative hydrogen production by Rhodobacter sphaeroides (R. sphaeroides) is an energy-consuming process. In this study, a proton-pumping channel (Proteorhodopsin (PR) or Gloeobacter rhodopsin (GR)) was introduced into R.

Exploring the severity and risk factors of non-alcoholic fatty liver disease using the SAF scoring system.

Objective: The steatosis, activity, and fibrosis (SAF) score is a histological scoring system developed by the European Association for the Study of the Liver to evaluate liver biopsy samples in cases of non-alcoholic fatty liver disease (NAFLD). Based on histopathological results and SAF scores, NAFLD patients were categorized into mild, moderate, and severe groups. We compared the differences between these groups and identified the risk factors influencing lesion severity.

Effects of water aerobics on body composition in obesity and overweight people: a systematic review and meta-analysis.

Objectives: Obesity and overweight significantly impact public health. The benefits of water aerobics (WAs) have been shown in obesity and overweight people, but the effects of WAs on body composition improvement are still unclear.

Design: Systematic review and meta-analysis.

Progress in the Application of Novel Nanomaterials in Targeted Therapy for Liver Cancer.

In recent years, nanobiotechnology, widely used in hepatoma, holds great promise for improving targeted hepatocarcinoma therapy. On account of the unique properties of low toxicity, good tolerance, biocompatibility, and biodegradability of new nanomaterials, a targeted drug delivery system (TDDS) has been constructed, which can boost the therapeutic effect of hepatoma-targeted drugs, reduce drug toxicity, and minimize off target reactions by enhancing permeability retention effect (EPR) and active targeting, thus improving existing liver cancer targeted therapy strategies. Different nanoparticles have their own advantages and disadvantages.

Nanoparticle-based drug delivery systems: opportunities and challenges in the treatment of esophageal squamous cell carcinoma (ESCC).

Esophageal squamous cell carcinoma (ESCC) is an aggressive malignancy characterized by limited treatment options and poor prognosis. Nanoparticle-based drug delivery systems have emerged as a promising strategy to enhance cancer therapy efficacy by improving drug targeting, reducing toxicity, and enabling multifunctional applications. This review highlights some key types of nanoparticles, including liposomes, polymeric nanoparticles, metallic nanoparticles, dendrimers, and quantum dots, which could effectively improve the delivery of various drugs used in chemotherapy, radiotherapy, and immunotherapy, offering more precise and effective treatment options.

The metacaspase TaMCA1-mediated crosstalk between autophagy and PCD contributes to the defense response of wheat seedlings against powdery mildew.

Powdery mildew (PM), is a significant fungal disease that poses a considerable threat to global agricultural productivity. Autophagy and programmed cell death (PCD) are crucial plant defense responses against PM. However, the role of metacaspases (MCAs) in mediating the interplay between autophagy and PCD in wheat's resistance to PM remains unknown.