Cd99l2 regulates excitatory synapse development and restrains immediate-early gene activation.

Cd99 molecule-like 2 (Cd99l2) is a type I transmembrane protein that plays a role in the transmigration of leukocytes across vascular endothelial cells. Despite its high expression in the brain, the role of Cd99l2 remains elusive. We find that Cd99l2 is expressed primarily in neurons and positively regulates neurite outgrowth and the development of excitatory synapses.

LIN28B-mediated PI3K/AKT pathway activation promotes metastasis in colorectal cancer models.

Colorectal cancer (CRC) remains a leading cause of cancer death due to metastatic spread. LIN28B is overexpressed in 30% of CRCs and promotes metastasis, yet its mechanisms remain unclear. In this study, we genetically modified CRC cell lines to overexpress LIN28B, resulting in enhanced PI3K/AKT pathway activation and liver metastasis in mice.

Analogue-Sensitive Inhibition of Histone Demethylases Uncovers Member-Specific Function in Ribosomal Protein Synthesis.

Lysine demethylases (KDMs) catalyze the oxidative removal of the methyl group from histones using earth-abundant iron and the metabolite 2-oxoglutarate (2OG). KDMs have emerged as master regulators of eukaryotic gene expression and are novel drug targets; small-molecule inhibitors of KDMs are in the clinical pipeline for the treatment of human cancer. Yet, mechanistic insights into the functional heterogeneity of human KDMs are limited, necessitating the development of chemical probes for precision targeting.

PYGO2 promotes resistance to chemotherapy via reducing apoptosis and G2/M cell cycle arrest in esophageal carcinoma cells.

5-FU is a widely used chemotherapy drug for esophageal carcinomas, but therapy failure has been observed in 5-FU-resistant patients. Overcoming this resistance is a significant challenge in cancer treatment, requiring identifying and targeting important resistance mechanisms. PYGO2 expression is crucial in developing resistance to various chemotherapy drugs.

Standard: Human gastric organoids.

Organoid technology provides a transformative approach to understand human physiology and pathology, offering valuable insights for scientific research and therapeutic development. Human gastric organoids, in particular, have gained significant interest for applications in disease modeling, drug discovery, and studies of tissue regeneration and homeostasis. However, the lack of standardized quality control has limited their extensive clinical applications.

CD9/SOX2-positive cells in the intermediate lobe of the rat pituitary gland exhibit mesenchymal stem cell characteristics.

Adult tissue stem cells of the anterior pituitary gland, CD9/SOX2-positive cells, are believed to exist in the marginal cell layer (MCL) bordering the residual lumen of the Rathke's pouch. These cells migrate from the intermediate lobe side of the MCL (IL-MCL) to the anterior lobe side of the MCL and may be involved in supplying hormone-producing cells. Previous studies reported that some SOX2-positive cells of the anterior lobe differentiate into skeletal muscle cells.

Epigenetics in the modern era of crop improvements.

Epigenetic mechanisms are integral to plant growth, development, and adaptation to environmental stimuli. Over the past two decades, our comprehension of these complex regulatory processes has expanded remarkably, producing a substantial body of knowledge on both locus-specific mechanisms and genome-wide regulatory patterns. Studies initially grounded in the model plant Arabidopsis have been broadened to encompass a diverse array of crop species, revealing the multifaceted roles of epigenetics in physiological and agronomic traits.

Triple Threat: How Global Fungal Rice and Wheat Pathogens Utilize Comparable Pathogenicity Mechanisms to Drive Host Colonization.

Plant pathogens pose significant threats to global cereal crop production, particularly for essential crops like rice and wheat, which are fundamental to global food security and provide nearly 40% of the global caloric intake. As the global population continues to rise, increasing agricultural production to meet food demands becomes even more critical. However, the production of these vital crops is constantly threatened by phytopathological diseases, especially those caused by fungal pathogens such as , the causative agent of rice blast disease, , responsible for head blight (FHB) in wheat, and , the source of Septoria tritici blotch (STB).

Predictive modelling of acute Promyelocytic leukaemia resistance to retinoic acid therapy.

Acute Promyelocytic Leukaemia (APL) arises from an aberrant chromosomal translocation involving the Retinoic Acid Receptor Alpha (RARA) gene, predominantly with the Promyelocytic Leukaemia (PML) or Promyelocytic Leukaemia Zinc Finger (PLZF) genes. The resulting oncoproteins block the haematopoietic differentiation program promoting aberrant proliferative promyelocytes. Retinoic Acid (RA) therapy is successful in most of the PML::RARA patients, while PLZF::RARA patients frequently become resistant and relapse.

A Bifunctional Peptide with Penetration Ability for Treating Retinal Angiogenesis via Eye Drops.

Numerous diseases, such as diabetic retinopathy and age-related macular degeneration, can lead to retinal neovascularization, which can seriously impair the visual function and potentially result in blindness. The presence of the blood-retina barrier makes it challenging for ocularly administered drugs to penetrate physiological barriers and reach the ocular posterior segments, including the retina and choroid. Herein, we developed an innovative bifunctional peptide, Tat-C-RP7, which exhibits excellent penetration capabilities and antiangiogenic properties aimed at treating retinal neovascularization diseases.

Translational nanorobotics breaking through biological membranes.

In the dynamic realm of translational nanorobotics, the endeavor to develop nanorobots carrying therapeutics in rational applications necessitates a profound understanding of the biological landscape of the human body and its complexity. Within this landscape, biological membranes stand as critical barriers to the successful delivery of therapeutic cargo to the target site. Their crossing is not only a challenge for nanorobotics but also a pivotal criterion for the clinical success of therapeutic-carrying nanorobots.

HIF1α Plays a Crucial Role in the Development of TFE3-Rearranged Renal Cell Carcinoma by Orchestrating a Metabolic Shift Toward Fatty Acid Synthesis.

Tumor development often requires cellular adaptation to a unique, high metabolic state; however, the molecular mechanisms that drive such metabolic changes in TFE3-rearranged renal cell carcinoma (TFE3-RCC) remain poorly understood. TFE3-RCC, a rare subtype of RCC, is defined by the formation of chimeric proteins involving the transcription factor TFE3. In this study, we analyzed cell lines and genetically engineered mice, demonstrating that the expression of the chimeric protein PRCC-TFE3 induced a hypoxia-related signature by transcriptionally upregulating HIF1α and HIF2α.

The aerial epidermis is a major site of quinolizidine alkaloid biosynthesis in narrow-leafed lupin.

Lupins are promising protein crops that accumulate toxic quinolizidine alkaloids (QAs) in the seeds, complicating their end-use. QAs are synthesized in green organs (leaves, stems, and pods) and a subset of them is transported to the seeds during fruit development. The exact sites of biosynthesis and accumulation remain unknown; however, mesophyll cells have been proposed as sources, and epidermal cells as sinks.

Investigating combined hypoxia and stemness indices for prognostic transcripts in gastric cancer: Machine learning and network analysis approaches.

Introduction: Gastric cancer (GC) is among the deadliest malignancies globally, characterized by hypoxia-driven pathways that promote cancer progression, including stemness mechanisms facilitating invasion and metastasis. This study aimed to develop a prognostic decision tree using genes implicated in hypoxia and stemness pathways to predict outcomes in GC patients.

Materials And Methods: GC RNA-seq data from The Cancer Genome Atlas (TCGA) were analyzed to compute hypoxia and stemness scores using Gene Set Variation Analysis (GSVA) and the mRNA expression-based stemness index (mRNAsi).

DNMT3A loss drives a HIF-1-dependent synthetic lethality to HDAC6 inhibition in non-small cell lung cancer.

encodes a DNA methyltransferase involved in development, cell differentiation, and gene transcription, which is mutated and aberrant-expressed in cancers. Here, we revealed that loss of promotes malignant phenotypes in lung cancer. Based on the epigenetic inhibitor library synthetic lethal screening, we found that small-molecule HDAC6 inhibitors selectively killed -defective NSCLC cells.

Virseqimprover: an integrated pipeline for viral contig error correction, extension, and annotation.

Despite the recent surge of viral metagenomic studies, it remains a significant challenge to recover complete virus genomes from metagenomic data. The majority of viral contigs generated from de novo assembly programs are highly fragmented, presenting significant challenges to downstream analysis and inference. To address this issue, we have developed Virseqimprover, a computational pipeline that can extend assembled contigs to complete or nearly complete genomes while maintaining extension quality.

Critical Steps in Shotgun Metagenomics-Based Diagnosis of Bloodstream Infections Using Nanopore Sequencing.

Shotgun metagenomics offers a broad detection of pathogens for rapid blood stream infection of pathogens but struggles with often low numbers of pathogens combined with high levels of human background DNA in clinical samples. This study aimed to develop a shotgun metagenomics protocol using blood spiked with various bacteria and to assess bacterial DNA extraction efficiency with human DNA depletion. The Blood Pathogen Kit (Molzym) was used to extract DNA from EDTA-whole blood (WB) and plasma samples, using contrived blood specimens spiked with bacteria for shotgun metagenomics diagnostics via Oxford Nanopore sequencing and PCR-based library preparation.

Mannose Promotes β-Amyloid Pathology by Regulating BACE1 Glycosylation in Alzheimer's Disease.

Hyperglycemia accelerates Alzheimer's disease (AD) progression, yet the role of monosaccharides remains unclear. Here, it is demonstrated that mannose, a hexose, closely correlates with the pathological characteristics of AD, as confirmed by measuring mannose levels in the brains and serum of AD mice, as well as in the serum of AD patients. AD mice are given mannose by intra-cerebroventricular injection (ICV) or in drinking water to investigate the effects of mannose on cognition and AD pathological progression.

Royal Jelly's Strong Selective Cytotoxicity Against Lung Malignant Cells and Macromolecular Alterations in Cells Observed by FTIR Spectroscopy.

Introduction/objective: Several nutraceuticals, food, and cosmetic products can be developed using royal jelly. It is known for its potential health benefits, including its ability to boost the immune system and reduce inflammation. It is rich in vitamins, minerals, and antioxidants, which can improve general health.

Root Development of Tomato Plants Infected by the Cacao Pathogen Moniliophthora perniciosa Is Affected by Limited Sugar Availability.

Moniliophthora perniciosa is the causal agent of the witches' broom disease of cacao (Theobroma cacao), and it can infect the tomato (Solanum lycopersicum) 'Micro-Tom' (MT) cultivar. Typical symptoms of infection are stem swelling and axillary shoot outgrowth, whereas reduction in root biomass is another side effect. Using infected MT, we investigated whether impaired root growth derives from hormonal imbalance or sink competition.

Early Initiation of Bundle Sheath Cells During Leaf Development as Visualised by SCARECROW Expression in Dicotyledonous C Plants.

The C type of dicotyledonous plants exhibit a higher density of reticulate veins than the C type, with a nearly 1:1 ratio of mesophyll cells (MCs) to bundle sheath cells (BSCs). To understand how this C-type cell pattern is formed, we identified two SCARECROW (SCR) genes in C Flaveria bidentis, FbSCR1 and FbSCR2, that fully or partially complement the endodermal cell layer-defective phenotype of Arabidopsis scr mutant. We then created FbSCRs promoter β-glucuronidase reporter (GUS) lines of F.

Tumor Vaccine Exploiting Membranes with Influenza Virus-Induced Immunogenic Cell Death to Decorate Polylactic Coglycolic Acid Nanoparticles.

Immunogenic cell death (ICD) of tumor cells, which is characterized by releasing immunostimulatory "find me" and "eat me" signals, expressing proinflammatory cytokines and providing personalized and broad-spectrum tumor antigens draws increasing attention in developing a tumor vaccine. In this study, we aimed to investigate whether the influenza virus (IAV) is efficient enough to induce ICD in tumor cells and an extra modification of IAV components such as hemeagglutinin (HA) will be helpful for the ICD-induced cells to elicit robust antitumor effects; in addition, to evaluate whether the membrane-engineering polylactic coglycolic acid nanoparticles (PLGA NPs) simulating ICD immune stimulation mechanisms hold the potential to be a promising vaccine candidate, a mouse melanoma cell line (B16-F10 cell) was infected with IAV rescued by the reverse genetic system, and the prepared cells and membrane-modified PLGA NPs were used separately to immunize the melanoma-bearing mice. IAV-infected tumor cells exhibit dying status, releasing high mobility group box-1 (HMGB1) and adenosine triphosphate (ATP), and exposing calreticulin (CRT), IAV hemeagglutinin (HA), and tumor antigens like tyrosinase-related protein 2 (TRP2).

Prophage-DB: a comprehensive database to explore diversity, distribution, and ecology of prophages.

Background: Viruses that infect prokaryotes (phages) constitute the most abundant group of biological agents, playing pivotal roles in microbial systems. They are known to impact microbial community dynamics, microbial ecology, and evolution. Efforts to document the diversity, host range, infection dynamics, and effects of bacteriophage infection on host cell metabolism are extremely underexplored.

Identification and validation of the important role of KIF11 in the development and progression of endometrial cancer.

Background: Human kinesin family member 11 (KIF11) plays a vital role in regulating the cell cycle and is implicated in the tumorigenesis and progression of various cancers, but its role in endometrial cancer (EC) is still unclear. Our current research explored the prognostic value, biological function and targeting strategy of KIF11 in EC through approaches including bioinformatics, machine learning and experimental studies.

Methods: The GSE17025 dataset from the GEO database was analyzed via the limma package to identify differentially expressed genes (DEGs) in EC.

Pathogen delivery route impacts disease severity in experimental Mycoplasma ovipneumoniae infection of domestic lambs.

M. ovipneumoniae is a respiratory pathogen that can cause mild to moderate pneumonia and reduced productivity in domestic lambs. However, studies on both natural and experimental M.