EASyMap-Guided Stepwise One-Pot Multienzyme (StOPMe) Synthesis and Multiplex Assays Identify Functional Tetraose-Core-Human Milk Oligosaccharides.

Carbohydrates are biologically and medicinally important molecules that are attracting growing attention to their synthesis and applications. Unlike the biosynthetic processes for nucleic acids and proteins, carbohydrate biosynthesis is not template-driven, more challenging, and often leads to product variations. In lieu of templates for carbohydrate biosynthesis, we describe herein a new concept of designing enzyme assembly synthetic maps (EASyMaps) as blueprints to guide glycosyltransferase-dependent stepwise one-pot multienzyme (StOPMe) synthesis to systematically access structurally diverse carbohydrates in a target-oriented manner.

Discovery of potent, highly selective, and orally bioavailable factor XIa inhibitors for anticoagulant therapy.

Factor XIa (FXIa) has emerged as a promising target for novel anticoagulant development since inhibiting it can reduce thrombosis without significant bleeding risks. Despite a few FXIa inhibitors entering clinical trials, none have been approved for the market yet. Here, we present highly selective and orally bioavailable FXIa inhibitors derived from compound 1, 4-(5-chloro-2-(1H-tetrazol-1-yl)phenyl)-5-methoxypyridin-2(1H)-one.

A novel nomogram for predicting postoperative pneumonia risk in patients with localized bronchiectasis.

Background: Pneumonia is one of the most common complications after lung resection. However, there are currently no reports of postoperative pneumonia in patients with bronchiectasis.

Objectives: Our study aims to construct a new nomogram to predict the risk of postoperative pneumonia in patients with localized bronchiectasis.

DNA methylation and immune evasion in triple-negative breast cancer: challenges and therapeutic opportunities.

Triple-negative breast cancer (TNBC) is an aggressive subtype of breast cancer characterized by the lack of estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor 2 (HER2). Chemotherapy remains the primary treatment option, yet TNBC frequently develops resistance, leading to relapse and metastasis. Emerging evidence highlights the potential of combining DNA methylation inhibitors with immune checkpoint inhibitors (ICIs).

Lycopene inhibits doxorubicin-induced heart failure by inhibiting ferroptosis through the Nrf2 signaling pathway.

Aims: Lycopene (LYC) is a dietary nutrient that plays a protective role in various cardiovascular diseases. Doxorubicin (DOX)-induced cardiotoxicity is an important cause of poor prognosis in many cancer patients treated with anthracyclines. This study aims to investigate the protective effects of LYC against DOX-induced heart failure (HF) and specific underlying mechanisms.

Carbon monoxide potentiates the effect of corticosteroids in suppressing inflammatory responses in cell culture.

Inflammation is a pathology implicated in a wide range of human diseases. Recent years have seen tremendous progress in developing new types of anti-inflammatory agents for the treatment of inflammation of various origins. However, each has its own strengths and weaknesses.

Exploring the role of metabolic pathways in TNBC immunotherapy: insights from single-cell and spatial transcriptomics.

The article provides an overview of the current understanding of the interplay between metabolic pathways and immune function in the context of triple-negative breast cancer (TNBC). It highlights recent advancements in single-cell and spatial transcriptomics technologies, which have revolutionized the analysis of tumor heterogeneity and the immune microenvironment in TNBC. The review emphasizes the crucial role of metabolic reprogramming in modulating immune cell function, discussing how specific metabolic pathways, such as glycolysis, lipid metabolism, and amino acid metabolism, can directly impact the activity and phenotypes of various immune cell populations within the TNBC tumor microenvironment.

Validation of the efficacy of the porous medium model in hemodynamic analysis of iliac vein compression syndrome.

Iliac Vein Compression Syndrome (IVCS) is a common risk factor for deep vein thrombosis in the lower extremities. The objective of this study was to investigate whether employing a porous medium model to simulate the compressed region of an iliac vein could improve the reliability and accuracy of Computational Fluid Dynamics (CFD) analysis outcomes of IVCS. Pre-operative Computed Tomography (CT) scan images of patients with IVCS were utilized to reconstruct models illustrating both the compression and collateral circulation of the iliac vein.

15-Deoxy-Δ-12,14-Prostaglandin J2 Represses Immune Escape of Lung Adenocarcinoma by Polarizing Macrophages Through Epidermal Growth Factor Receptor/Ras/Raf Pathway.

Lung adenocarcinoma (LUAD) is a widespread and deadly form of cancer. Prostaglandin 15-deoxy-Δ-12,14-prostaglandin J2 (15d-PGJ2) possesses antioxidant, anti-inflammatory, and anticancer properties. However, it is unclear whether this effect on LUAD progression stems from its ability to influence macrophage polarization.

Colchicine reduces neointima formation and VSMC phenotype transition by modulating SRF-MYOCD activation and autophagy.

Vascular smooth muscle cell (VSMC) phenotype transformation significantly contributes to vascular intimal hyperplasia. However, effective preventive and therapeutic measures are lacking. Colchicine, a binary alkaloid derived from Colchicum autumnale, is traditionally used for treating inflammatory diseases.

Multicomponent Heterogeneous Semiconductor Photocatalytic Sulfinylsulfonylation of Alkenes with Alkyl Iodides and SO.

A multicomponent heterogeneous semiconductor photocatalytic sulfinylsulfonylation of alkenes with alkyl iodides and SO was displayed under mild metal-free conditions by using boron carbonitride (BCN) as the alternative photocatalyst. This approach has resulted in the production of a wide range of structurally diverse sultine products in moderate to high yields, using readily available starting materials including alkyl iodides and olefins with broad functional group tolerance. The method is also suitable for the late-stage functionalization of complex bioactive molecules.

Low Expression of Mitochondrial Ribosomal Protein S5 is Associated With Poor Prognosis in Patients With Clear Cell Renal Cell Carcinoma.

Mitochondrial ribosomal protein S5 (MRPS5) is abnormally expressed in various tumor tissues and may be a key molecule for the regulation of tumors. Our aim is to investigate the relationship between the expression of MRPS5 in clear cell renal cell carcinoma (ccRCC) and the prognosis of patients. MRPS5 expression in fresh tumoral tissues and peritumoral tissues of patients with ccRCC was examined by quantitative reverse transcription polymerase chain reaction, western blotting, and immunohistochemical staining, respectively.

A Tale of Two Cities in Fluorescent Sensing of Carbon Monoxide: Probes That Detect CO and Those That Detect Only Chemically Reactive CO Donors (CORMs), but Not CO.

Carbon monoxide (CO) is endogenously produced with a range of pharmacological activities. Sensitive and selective detection of CO is critical to studying its biology. Since the first report of a CO fluorescent probe in 2012, more than 100 papers on this topic have appeared.

Chitosan nanoparticles alleviate chromium toxicity by modulating metabolic homeostasis and promoting chromium sequestration in Zea mays L.

Chitosan nanoparticles (CSNPs) have been proposed as a potential alternative in alleviating chromium (Cr) toxicity. However, the mechanisms underlying remains poorly understood. This study investigates the effects of CSNPs on carbon/nitrogen metabolism, cell wall Cr binding capacity, and antioxidant activity in Zea mays L.

Nuclear translocation of SIRT4 mediates deacetylation of U2AF2 to modulate renal fibrosis through alternative splicing-mediated upregulation of CCN2.

TGF-β stimulates CCN2 expression which in turn amplifies TGF-β signaling. This process promotes extracellular matrix production and accelerates the pathological progression of fibrotic diseases. Alternative splicing plays an important role in multiple disease development, while U2 small nuclear RNA auxiliary factor 2 (U2AF2) is an essential factor in the early steps of pre-mRNA splicing.

Metal-Free CO Prodrugs Activated by Molecular Oxygen Protect against Doxorubicin-Induced Cardiomyopathy in Mice.

Carbon monoxide has been extensively studied for its various therapeutic activities in cell cultures and animal models. Great efforts have been made to develop noninhalational approaches for easy and controlled CO delivery. Herein, we introduce a novel metal-free CO prodrug approach that releases CO under near-physiological conditions.

Dronedarone hydrochloride inhibits gastric cancer proliferation in vitro and in vivo by targeting SRC.

Background: Gastric cancer (GC) is a significant global concern, ranking as the fifth most prevalent cancer. Unfortunately, the five-year survival rate is less than 30 %. Additionally, approximately 50 % of patients experience a recurrence or metastasis.

protein targeted activation of -mediated PANoptosis promotes sepsis-induced acute kidney injury.

Background: Acute kidney injury (AKI) frequently occurs as a complication of sepsis. PANoptosis refers to a type of inflammatory programmed cell death that exhibits key characteristics of apoptosis, necroptosis, and pyroptosis. Here, we evaluated the role of absent in melanoma 2 (AIM2) and eukaryotic translation initiation factor 2 alpha kinase 2 (EIF2AK2) in septic AKI.