Screening and Preparation of Nanobodies for SIGLEC-15 Detection.

As an important member of the Siglec family, SIGLEC-15 plays an important role in osteoclast differentiation, bone remodeling, and tumor immune evasion. In the tumor microenvironment, SIGLEC-15 functions independently of the B7-H1/PD-1 pathway. In this study, the SIGLEC-15 fusion protein (SIGLEC-15-Fc) was successfully expressed and purified using a eukaryotic expression system.

Enhanced bile acid detection and analysis in liver fibrosis with pseudo-targeted metabolomics.

Bile acids (BAs) are essential signaling molecules that engage in host and gut microbial metabolism, playing a crucial role in maintaining organismal stability. Liquid chromatography-mass spectrometry (LC-MS) is a widely employed technique for metabolite analysis in biological samples due to its high sensitivity, excellent specificity, and low detection limits. This method has emerged as the mainstream approach for the detection and analysis of BAs.

Online extraction-LC-MS/MS is an alternative imaging tool for spatial-resolved metabolomics: Mint leaf as a pilot study.

An attempt was made here to a complemental analytical tool for classical MSI approach. OLE-LC-MS/MS imaging was proposed to plot the spatial-resolved metabolome through deploying mint leaf as a proof-of-concept. A dried leaf underwent chemical composition characterization using OLE-LC-Qtof-MS.

A comprehensive review of current insights into the virulence factors of SARS-CoV-2.

The evolution of SARS-CoV-2 pathogenicity has been a major focus of attention. However, the determinants of pathogenicity are still unclear. Various hypotheses have attempted to elucidate the mechanisms underlying the evolution of viral pathogenicity, but a definitive conclusion has yet to be reached.

Utilizing physiologies, transcriptomics, and metabolomics to unravel key genes and metabolites of Bge. seedlings in response to drought stress.

Drought stress inhibits Bunge () seedling growth and yield. Here, we studied the effects of drought stress on the different parts of seedlings through physiological, transcriptomic, and metabolomics analyses, and identified key genes and metabolites related to drought tolerance. Physiological analysis showed that drought stress increased the accumulation of hydrogen peroxide (HO), enhanced the activity of peroxidase (POD), decreased the activity of catalase (CAT) and the contents of chlorophyll b and total chlorophyll, reduced the degree of photosynthesis, enhanced oxidative damage in seedlings, and inhibited the growth of plants.

A comprehensive review of the impact of anthocyanins from purple/black Rice on starch and protein digestibility, gut microbiota modulation, and their applications in food products.

This review explores the impact of anthocyanins derived from purple and black rice on starch and protein digestibility, gut microbiota modulation, and their applications in food production. Anthocyanins are shown to reduce starch digestibility by forming complexes with starch, thereby inhibiting key digestive enzymes. Additionally, they can influence protein digestion by inducing structural changes that enhance resistance to digestive processes.

Design, Synthesis, and biological evaluation of 7H-Pyrrolo[2,3-d]pyrimidines as potent HPK1 kinase inhibitors.

Hematopoietic progenitor kinase 1 (HPK1) has emerged as a promising target for cancer immunotherapy due to its critical role as a negative regulator of T cell receptor (TCR) signaling. Despite this potential, no HPK1 inhibitors have been approved for cancer treatment, underscoring the need for structurally novel inhibitors. Herein, we describe the design, synthesis and biological evaluation of a series of potent HPK1 inhibitors based on our previously identified hit 9.

Design, synthesis and structure-activity relationship of novel 1,2,4-triazolopyrimidin-5-one derivatives targeting GABA and Na1.2 with antiepileptic activity.

A novel class of 7-phenyl-[1,2,4]triazol-5(4H)-one derivatives was designed and synthesized, and their in vivo anticonvulsant activities were evaluated using subcutaneous pentylenetetrazole (Sc-PTZ) and maximal electroshock (MES) tests. Compounds 3u, 4f and 4k exhibited significant anticonvulsant activities in the Sc-PTZ model with ED values of 23.7, 17.

Apolipoprotein A-IV and its derived peptide, T55-121, improve glycemic control and increase energy expenditure.

It is crucial to understand the glucose control within our bodies. Bariatric/metabolic surgeries, including laparoscopic sleeve gastrectomy (LSG) and Roux-en-Y gastric bypass (RYGB), provide an avenue for exploring the potential key factors involved in maintaining glucose homeostasis since these surgeries have shown promising results in improving glycemic control among patients with severe type 2 diabetes (T2D). For the first time, a markedly altered population of serum proteins in patients after LSG was discovered and analyzed through proteomics.

Potential therapeutic strategies for MASH: from preclinical to clinical development.

Current treatment paradigms for metabolic dysfunction-associated steatohepatitis (MASH) are based primarily on dietary restrictions and the use of existing drugs, including anti-diabetic and anti-obesity medications. Given the limited number of approved drugs specifically for MASH, recent efforts have focused on promising strategies that specifically target hepatic lipid metabolism, inflammation, fibrosis, or a combination of these processes. In this review, we examined the pathophysiology underlying the development of MASH in relation to recent advances in effective MASH therapy.

Draft Genome of Naganishia uzbekistanensis from a Clinical Pulmonary Infection.

This study presents the first high-quality assembled genome of Naganishia uzbekistanensis, derived from a clinical isolate CY11558 obtained from a patient with a postoperative pulmonary infection. This work provides an improved reference assembly for downstream research and diagnosis of infections caused by this species.

Stromal architecture and fibroblast subpopulations with opposing effects on outcomes in hepatocellular carcinoma.

Dissecting the spatial heterogeneity of cancer-associated fibroblasts (CAFs) is vital for understanding tumor biology and therapeutic design. By combining pathological image analysis with spatial proteomics, we revealed two stromal archetypes in hepatocellular carcinoma (HCC) with different biological functions and extracellular matrix compositions. Using paired single-cell RNA and epigenomic sequencing with Stereo-seq, we revealed two fibroblast subsets CAF-FAP and CAF-C7, whose spatial enrichment strongly correlated with the two stromal archetypes and opposing patient prognosis.

The History of Studies on Oxetane Ring Formation in Paclitaxel Biosynthesis.

There is no doubt that breakthroughs in the enzyme-mediated formation of the oxetane ring in paclitaxel biosynthesis constitute significant milestones in the biosynthesis of complex natural products. In this review, we summarize the understanding of the biosynthesis of the oxetane ring of paclitaxel from different viewpoints. Generally, it covers five aspects, (1) a different understanding of the mechanistic formation of the oxetane ring on the basis of sound chemical reasoning, (2) a reasonable speculation of the biosynthetic pathways and suitable surrogate substrates for oxetane ring formation based on the natural and chemical logical analysis, (3) Taxus genome-enabled enzymes identification, (4) the discovery of different enzymes that mediate oxetane ring formation, and (5) a mechanistic investigation involving the use of isotopic labelling experiments and quantum chemical calculations.

The Anti-Neuroinflammatory Effects of Cepharanthine in Uric Acid-Induced Neuroinflammation.

Ethnopharmacological Relevance: Cepharanthine (CEP) is an alkaloid extracted from Stephania cephalantha Hayata, a traditional Chinese medicine (TCM) renowned for its heatclearing and dehumidifying properties. For centuries, Stephania cephalantha Hayata has been employed in the treatment of a wide range of diseases, including pain, edema, inflammation, and fever.

Aim Of The Study: Our research aims to investigate the role and mechanism of Cepharanthine in ameliorating uric acid (UA) induced neuroinflammatory responses.

Discovery of Metabolic Reprogramming 2-Quinolones as Effective Antimicrobials for MRSA-Infected Wound Therapy.

To date, the abuse of antibiotics and a gradual decline in novel antibiotic discovery enlarge the threat of drug-resistant bacterial infections, especially methicillin-resistant (MRSA). Herein, inspired by the unique structures and antibacterial activities of 2-quinolones, a class of novel 2-quinolones with substituted pyridines was synthesized. Notably, compound , the derivative with a methylpyridine fragment, showed potent antibacterial and antibiofilm activities, especially for MRSA strains (MIC = 0.

Intraspecific identification and genetic diversity analysis of Paeonia lactiflora based on chloroplast genes rpoB and psbK-psbI.

Background: Paeonia lactiflora Pall., a member of Paeoniaceae family, is a medicinal herb widely used in traditional Chinese medicine. Chloroplasts are multifunctional organelles containing distinct genetic material.

Design of ROS-Triggered Sesquiterpene Lactone SC Prodrugs as TrxR1 Covalent Inhibitors for the Treatment of Non-Small Cell Lung Cancer.

Thioredoxin reductase 1 (TrxR1) is an important therapeutic target for nonsmall cell lung cancer (NSCLC) treatment due to its overexpression in NSCLC cells. In this work, to address the deficiency that sesquiterpene lactone containing α-methylene-γ-lactone moiety was rapidly metabolized by endogenous nucleophiles, series of novel thioether derivatives were designed and synthesized based on a reactive oxygen species (ROS)-triggered prodrug strategy. Among them, prodrug exhibited potent cytotoxicity against NSCLC cells and better release rates in response to ROS.

Mitochondrial genome of : features, RNA editing, and insights into male sterility.

Introduction: Mitochondria are essential organelles that provide energy for plants. They are semi-autonomous, maternally inherited, and closely linked to cytoplasmic male sterility (CMS) in plants. , a widely used medicinal plant from the Caprifoliaceae family, is rich in chlorogenic acid (CGA) and its analogues, which are known for their antiviral and anticancer properties.

Ailanthone induces triple-negative breast cancer cells death involving the inhibition of OTUB1-mediated ERRα deubiquitylation.

Introduction: Triple-negative breast cancer (TNBC) remains the most aggressive subtype of breast cancer, and effective therapeutic strategies are needed. Estrogen-related receptor alpha (ERRα) is considered a promising target for managing TNBC.

Objectives: Here, we aimed to screen natural products to find downregulator of ERRα and elucidate its mechanism of action.

20-Deoxyingenol ester and ether derivatives: Synthesis, properties and cytotoxicity.

The C-3 and C-5 substituted 20-deoxyingenol monoesters are important active components in Euphorbiaceae plants. Nonetheless, their similar physical properties make them difficult to distinguish. The present study developed fast and efficient rules for identifying the esterification sites of 20-deoxyingenol based on a series of chemical syntheses of monoesters and literature research, utilizing NMR spectroscopy, optical rotation analysis, and chromatographic retention behavior.

Rationally designed highly amphipathic antimicrobial peptides demonstrating superior bacterial selectivity relative to the corresponding α-helix peptide.

De novo design of antimicrobial peptides is a pivotal strategy for developing new antibacterial agents, leveraging its rapid and efficient nature. (XXYY), where X represents cationic residues, Y denotes hydrophobic residues, and n varies from 2 to 4, is a classical α-helix template. Based on which, numerous antimicrobial peptides have been synthesized.

Investigating the Effect and Potential Mechanism of Rhamnetin 3--α-Rhamnoside on Acute Liver Injury In Vivo and In Vitro.

: Rhamnetin 3--α-rhamnoside (ARR) is a major flavonoid of the herb Franch. & Sav., which has been used for treating liver diseases in China.

Silybin Cocrystals with Improved Solubility and Bioavailability.

Silymarin, an extract from milk thistle, is widely recognized for its therapeutic potential in treating liver disorders. However, its clinical utility is limited by the poor solubility and low bioavailability of its key active ingredient, Silybin. In this study, we sought to address this issue through the development of a novel cocrystal of Silyin.

Pharmacodynamic Mechanisms of Cicadae Periostracum in Parkinson's Disease: A Metabolomics-Based Study.

Cicadae Periostracum (CP) is a traditional Chinese animal-derived medicine with the potential to treat Parkinson's disease (PD). This study aims to explore the pharmacodynamic mechanisms of CP against PD-based on metabolomics technology and provide a theoretical basis for developing new anti-PD medicine. First, MPP-induced SH-SY5Y cells were used to evaluate the anti-PD activity of CP.