Uncovering the naturally occurring covalent inhibitors of SARS-CoV-2 M from the Chinese medicine sappanwood and deciphering their synergistic anti-M effects.

Ethnopharmacological Relevance: The Chinese medicine sappanwood is primarily sourced from the dried heartwood of the medicinal plant Caesalpinia sappan Linn., which has been found with a variety of valuable properties including anti-inflammatory, anti-oxidant, and anti-viral effects. Preliminary investigations have demonstrated that sappanwood showed strong anti-SARS-CoV-2 M effects, but the key constituents responsible for SARS-CoV-2 M inhibition and their anti-M mechanisms have not been uncovered.

Biochemical, structural, and cellular characterization of S-but-3-yn-2-ylglycine as a mechanism-based covalent inactivator of the flavoenzyme proline dehydrogenase.

The mitochondrial flavoenzymes proline dehydrogenase (PRODH) and hydroxyproline dehydrogenase (PRODH2) catalyze the first steps of proline and hydroxyproline catabolism, respectively. The enzymes are targets for chemical probe development because of their roles in cancer cell metabolism (PRODH) and primary hyperoxaluria (PRODH2). Mechanism-based inactivators of PRODH target the FAD by covalently modifying the N5 atom, with N-propargylglycine (NPPG) being the current best-in-class of this type of probe.

Symbiosis vs Pathogenesis in Plants: Reflections and Perspectives.

Plant-microbe partnerships constitute a complex and intricately woven network of connections that have evolved over countless centuries, involving both cooperation and antagonism. In various contexts, plants and microorganisms engage in mutually beneficial partnerships that enhance crop health and maintain balance in ecosystems. However, these associations also render plants susceptible to a range of pathogens.

NKAP: a new m6A RNA binding protein predicts prognosis and immunotherapy response in head and neck squamous cell carcinoma.

Objective: This study aimed to investigate whether NKAP (nuclear factor κB activating protein) serves as a prognostic marker and predictive biomarker for immunotherapy response in head and neck squamous cell carcinoma (HNSCC).

Methods: A retrospective cohort study combined with in vitro analyses was conducted. NKAP mRNA expression levels were assessed in 520 HNSCC tumor tissues and 44 normal tissues from the TCGA dataset and validated in a clinical cohort (n=32).

Bioimpedance Measurements of Fibrotic and Acutely Injured Lung Tissues.

In injured and diseased tissues, changes in molecular and cellular compositions, as well as tissue architecture, lead to alterations in both physiological and physical characteristics. Notably, the electrical properties of tissues, which can be characterized as bioelectrical impedance (bioimpedance), are closely linked to the health and pathological conditions of the tissues. This highlights the significant role of quantitatively characterizing these electrical properties in improving the accuracy and speed of diagnosis and prognosis.

Exploring the role of transcription factor TWIST1 in bladder cancer progression.

The transcription factor TWIST1 is a major regulator of Epithelial-Mesenchymal Transition, enhancing cancer cell mobility and invasive potential. Overexpression of TWIST1 is associated with tumor progression and poor prognosis. In our study, we explored the role of TWIST1 as both a prognostic biomarker and a therapeutic target in bladder cancer (BC), as well as the relationship between its promoter methylation and mRNA expression in bladder cancer patients.

Silibinin, a PLC-β3 inhibitor, inhibits mast cell activation and alleviates OVA-induced asthma.

The immunoglobulin E (IgE) receptor FcεRI (Fc epsilon RI) plays a crucial role in allergic reactions. Recent studies have indicated that the interaction between FcεRIβ and the downstream protein phospholipase C beta 3 (PLCβ3) leads to the production of inflammatory cytokines. The aim of this study was to develop small molecules that inhibit the protein-protein interactions between FcεRIβ and PLCβ3 to treat allergic inflammation.

Gold(I)-Catalyzed 2-Deoxy-β-glycosylation via 1,2-Alkyl/Arylthio Migration: Synthesis of Velutinoside A Pentasaccharide.

2-Deoxy-β-glycosides are essential components of natural products and pharmaceuticals; however, the corresponding 2-deoxy-β-glycosidic bonds are challenging to chemically construct. Herein, we describe an efficient catalytic protocol for synthesizing 2-deoxy-β-glycosides via either IPrAuNTf-catalyzed activation of a unique 1,2--positioned C2--propargyl xanthate (OSPX) leaving group or (PhO)PAuNTf-catalyzed activation of a 1,2--C2--alkynylbenzoate (OABz) substituent of the corresponding thioglycosides. These activation processes trigger 1,2-alkyl/arylthio-migration glycosylation, enabling the synthesis of structurally diverse 2-deoxy-β-glycosides under mild reaction conditions.

PgpP is a broadly conserved phosphatase required for phosphatidylglycerol lipid synthesis.

The cytoplasmic membrane of bacteria is composed of a phospholipid bilayer made up of a diverse set of lipids. Phosphatidylglycerol (PG) is one of the principal constituents and its production is essential for growth in many bacteria. All the enzymes required for PG biogenesis in have been identified and characterized decades ago.

Emergence and evolution of heterocyte glycolipid biosynthesis enabled specialized nitrogen fixation in cyanobacteria.

Heterocytes, specialized cells for nitrogen fixation in cyanobacteria, are surrounded by heterocyte glycolipids (HGs), which contribute to protection of the nitrogenase enzyme from oxygen. Diverse HGs preserve in the sediment and have been widely used as evidence of past nitrogen fixation, and structural variation has been suggested to preserve taxonomic information and reflect paleoenvironmental conditions. Here, by comprehensive HG identification and screening of HG biosynthetic gene clusters throughout cyanobacteria, we reconstruct the convergent evolutionary history of HG structure, in which different clades produce the same HGs.

A single-cell atlas of the Culex tarsalis midgut during West Nile virus infection.

The mosquito midgut functions as a key interface between pathogen and vector. However, studies of midgut physiology and virus infection dynamics are scarce, and in Culex tarsalis-an extremely efficient vector of West Nile virus (WNV)-nonexistent. We performed single-cell RNA sequencing on Cx.

Minimization of the Bacillus subtilis divisome suggests FtsZ and SepF can form an active Z-ring, and reveals the amino acid transporter BraB as a new cell division influencing factor.

Bacterial cytokinesis begins with polymerization of the tubulin homologue FtsZ into a ring-like structure at midcell, the Z-ring, which recruits the late cell division proteins that synthesize the division septum. Assembly of FtsZ is carefully regulated and supported by a dozen conserved cell division proteins. Generally, these proteins are not essential, but removing more than one is in many cases lethal.

Chemigenetic Ca2+ indicators report elevated Ca2+ levels in endothelial Weibel-Palade bodies.

Weibel-Palade bodies (WPB) are secretory organelles exclusively found in endothelial cells and among other cargo proteins, contain the hemostatic von-Willebrand factor (VWF). Stimulation of endothelial cells results in exocytosis of WPB and release of their cargo into the vascular lumen, where VWF unfurls into long strings of up to 1000 µm and recruits platelets to sites of vascular injury, thereby mediating a crucial step in the hemostatic response. The function of VWF is strongly correlated to its structure; in order to fulfill its task in the vascular lumen, VWF has to undergo a complex packing/processing after translation into the ER.

Site-selective photo-crosslinking for the characterisation of transient ubiquitin-like protein-protein interactions.

Non-covalent protein-protein interactions are one of the most fundamental building blocks in cellular signalling pathways. Despite this, they have been historically hard to identify using conventional methods due to their often weak and transient nature. Using genetic code expansion and incorporation of commercially available unnatural amino acids, we have developed a highly accessible method whereby interactions between biotinylated ubiquitin-like protein (UBL) probes and their binding partners can be stabilised using ultraviolet (UV) light-induced crosslinks.

Enhanced silk production and pupal weight in Bombyx mori through CRISPR/Cas9-mediated circadian Clock gene disruption.

The domesticated silkworm, Bombyx mori, is crucial for global silk production, which is a significant economic activity supporting millions of livelihoods worldwide. Beyond traditional silk production, the growing demand for insect larvae in cosmetics, biomedical products, and animal feed underscores the need to enhance B. mori productivity.

Anti-inflammatory effects of palm11-PrRP31 in a rat model of lipopolysaccharide-induced acute inflammation.

Lipopolysaccharides (LPS) are major components of Gram-negative bacteria. LPS not only induce endotoxemia and inflammation, but also contribute to various diseases. In experimental settings, LPS administration serves as a model for acute inflammatory responses.

Folding and Functionalizing DNA Origami: A Versatile Approach Using a Reactive Polyamine.

DNA nanotechnology is a powerful synthetic approach to crafting diverse nanostructures through self-assembly. Chemical decoration of such nanostructures is often required to tailor their properties for specific applications. In this Letter, we introduce a pioneering method to direct the assembly and enable the functionalization of DNA nanostructures using an azide-bearing functional polyamine.

Evaluation of nationwide analysis surveillance for methicillin-resistant within Genomic Medicine Sweden.

National epidemiological investigations of microbial infections greatly benefit from the increased information gained by whole-genome sequencing (WGS) in combination with standardized approaches for data sharing and analysis. To evaluate the quality and accuracy of WGS data generated by different laboratories but analysed by joint pipelines to reach a national surveillance approach. A national methicillin-resistant (MRSA) collection of 20 strains was distributed to nine participating laboratories that performed in-house procedures for WGS.

The Arabidopsis Basic-Helix-Loop-Helix Transcription Factor LRL1 Activates Cell Wall-Related Genes during Root Hair Development.

Lotus japonicus-ROOT HAIR LESS1-LIKE1 (LRL1) of Arabidopsis thaliana encodes a basic helix-loop-helix (bHLH) transcription factor (TF) involved in root hair development. Root hair development is regulated by an elaborate transcriptional network, in which GLABRA2 (GL2), a key negative regulator, directly represses bHLH TF genes, including LRL1 and ROOT HAIR DEFECTIVE6 (RHD6). Although RHD6 and its paralogous TFs have been shown to connect downstream to genes involved in cell morphological events such as endomembrane and cell wall modification, the network downstream of LRL1 remains elusive.

New insights in the systematics of the Hemiuroidea (Digenea: Hemiurata) based on the integrative taxonomy approach.

Opistholecithum sandugaense n. g. n.

100 years Cell and Tissue Research: the founders and their successors.

One hundred years ago, Cell and Tissue Research was founded under the title "Zeitschrift für Zellen- und Gewebelehre," later "Zeitschrift für Zellforschung und mikroskopische Anatomie." The founders were four eminent German and Swiss cell biologists and zoologists, R. Goldschmidt, W.

Emerging Frontiers in Colorectal Cancer Therapy: From Targeted Molecules to Immunomodulatory Breakthroughs and Cell-Based Approaches.

Colorectal cancer (CRC) is ranked as the second leading cause of cancer-related deaths globally, necessitating urgent advancements in therapeutic approaches. The emergence of groundbreaking therapies, including chimeric antigen receptor-T (CAR-T) cell therapies, oncolytic viruses, and immune checkpoint inhibitors, marks a transformative era in oncology. These innovative modalities, tailored to individual genetic and molecular profiles, hold the promise of significantly enhancing patient outcomes.

Engineered Immunomodulatory Extracellular Vesicles from Epithelial Cells with the Capacity for Stimulation of Innate and Adaptive Immunity in Cancer and Autoimmunity.

Extracellular vesicles (EVs) are generated in all cells. Systemic administration of allogenic EVs derived from epithelial and mesenchymal cells has been shown to be safe, despite carrying an array of functional molecules, including thousands of proteins. To address whether epithelial cell-derived EVs can be modified to acquire the capacity to induce an immune response, we engineered 293T EVs to harbor the immunomodulatory molecules CD80, OX40L, and PD-L1.

Is there still a place for lymph node dissection for stage III melanoma since the approval of adjuvant therapy.

Purpose Of Review: This review aims to explore the evolving management strategies for stage III melanoma, focusing on the comparative effectiveness of traditional surgical approaches like complete lymph node dissection (CLND) versus modern adjuvant therapies. It also examines the latest evidence on the efficacy, risks, and complications of these strategies, emphasizing the role of shared decision-making between patients and clinicians.

Recent Findings: Recent clinical trials and meta-analyses, including the MSLT-II and DeCOG-SLT studies, have demonstrated that CLND may not significantly improve survival outcomes in melanoma patients with sentinel lymph node biopsy (SLNB)-positive status.

Strength of Genetic Associations with Thyrotropin Values Differs Between Populations with Similarity to African and European Reference Populations.

Epidemiological data suggest the population distribution of thyrotropin (TSH) values is shifted toward lower values in self-identified Black non-Hispanic individuals compared with self-identified White non-Hispanic individuals. It is unknown whether genetic differences between individuals with genetic similarities to African reference populations (GSA) and those with similarities to European reference populations (GSE) contribute to these observed differences. We aimed to compare genome-wide associations with TSH and putative causal TSH-associated variants between GSA and GSE groups.