Orchestrated desaturation reprogramming from stearoyl-CoA desaturase to fatty acid desaturase 2 in cancer epithelial-mesenchymal transition and metastasis.

Background: Adaptative desaturation in fatty acid (FA) is an emerging hallmark of cancer metabolic plasticity. Desaturases such as stearoyl-CoA desaturase (SCD) and fatty acid desaturase 2 (FADS2) have been implicated in multiple cancers, and their dominant and compensatory effects have recently been highlighted. However, how tumors initiate and sustain their self-sufficient FA desaturation to maintain phenotypic transition remains elusive.

Unbiased Drug Target Prediction Reveals Sensitivity to Ferroptosis Inducers, HDAC and RTK Inhibitors in Melanoma Subtypes.

Background: The utilization of PD1 and CTLA4 inhibitors has revolutionized the treatment of malignant melanoma (MM). However, resistance to targeted and immune-checkpoint-based therapies still poses a significant problem.

Objective: Here, we mine large-scale MM proteogenomic data to identify druggable targets and forecast treatment efficacy and resistance.

A comprehensive review on microbial hyaluronan-degrading enzymes: from virulence factors to biotechnological tools.

Hyaluronan (HA), a natural high molecular weight polysaccharide, has extensive applications in cosmetology and medical treatment. Hyaluronan-degrading enzymes (Hyals) act as molecular scissors that cleave HA by breaking the glucosidic linkage. Hyals are present in diverse organisms, including vertebrates, invertebrates and microorganisms, and play momentous roles in biological processes.

Construction of a random survival forest model based on a machine learning algorithm to predict early recurrence after hepatectomy for adult hepatocellular carcinoma.

Background And Aims: Hepatocellular carcinoma (HCC) exhibits a propensity for early recurrence following liver resection, resulting in a bleak prognosis. At present, majority of the predictive models for the early postoperative recurrence of HCC rely on the linear assumption of the Cox Proportional Hazard (CPH) model. However, the predictive efficacy of this model is constrained by the intricate nature of clinical data.

Life cycle and morphogenetic differentiation in heteromorphic cell types of a cosmopolitan marine microalga.

Gephyrocapsa huxleyi is a prevalent, bloom-forming phytoplankton species in the oceans. It exhibits a complex haplodiplontic life cycle, featuring a diploid-calcified phase, a haploid phase and a third 'decoupled' phase produced during viral infection. Decoupled cells display a haploid-like phenotype, but are diploid.

New benzimidazole-indole-amide derivatives as potent α-glucosidase and acetylcholinesterase inhibitors.

New derivatives 6a-m with benzimidazole-indole-amide scaffold were developed, synthesized, and assessed for potential inhibitory effects on α-glucosidase and acetylcholinesterase (AChE). These compounds were synthesized by various amine derivatives. With the exception of two compounds, the α-glucosidase inhibitory activities of the title derivatives were more than that of the positive control acarbose.

Molecular phenotypes of critical illness confer prognostic and biological enrichment in sub-Saharan Africa: a prospective cohort study from Uganda.

The generalisability of critical illness molecular phenotypes to low- and middle-income countries (LMICs) is unknown. We show that molecular phenotypes derived in high-income countries (hyperinflammatory and hypoinflammatory, reactive and uninflamed) stratify sepsis patients in Uganda by physiological severity, mortality risk and dysregulation of key pathobiological domains. A classifier model including data available at the LMIC bedside modestly discriminated phenotype assignment (area under the receiver operating characteristic curve (AUROC) 0.

Structures of Polyacetoxybriaranes Extracted from the Sea Whip Octocoral Junceella fragilis.

In the present study, an algae-containing octocoral, Junceella fragilis, was subjected to chemical screening. The analysis resulted in the extraction of six polyacetoxybriaranes: a new compound, identified as fragilide Z (1), alongside previously identified analogs, which included 12-epi-fragilide G (2), fragilide P (3), junceellolide D (4), junceellonoid A (5), and juncin ZI (6). The structures of compounds 2-6 were investigated through single-crystal X-ray diffraction analysis, whereas that of 1 was examined through two-dimensional nuclear magnetic resonance analysis.

Molecular architectures of centrosomes in C. elegans embryos visualized by cryo-electron tomography.

Centrosomes organize microtubules that are essential for mitotic divisions in animal cells. They consist of centrioles surrounded by pericentriolar material (PCM). Questions related to mechanisms of centriole assembly, PCM organization, and spindle microtubule formation remain unanswered, partly due to limited availability of molecular-resolution structural data inside cells.

Tuft cells transdifferentiate to neural-like progenitor cells in the progression of pancreatic cancer.

Pancreatic ductal adenocarcinoma (PDA) is partly initiated through the transdifferentiation of acinar cells to metaplasia, which progresses to neoplasia and cancer. Tuft cells (TCs) are chemosensory cells not found in the normal pancreas but arise in cancer precursor lesions and diminish during progression to carcinoma. These metaplastic TCs (mTCs) suppress tumor progression through communication with the tumor microenvironment, but their fate during progression is unknown.

Iron(ing) out parkinsonisms: The interplay of proteinopathy and ferroptosis in Parkinson's disease and tau-related parkinsonisms.

Parkinsonian syndromes are characterised by similar motor-related symptomology resulting from dopaminergic neuron damage. While Parkinson's disease (PD) is the most prevalent parkinsonism, we also focus on two other variants, Progressive supranuclear palsy (PSP) and Corticobasal degeneration (CBD). Due to the clinical similarities of these parkinsonisms, and since definite diagnoses are only possible post-mortem, effective therapies and novel biomarkers of disease are scarce.

A new oligothiophene-derivatized fluorescent sensor for detecting and imaging of Hg in water/soil/urine/tea/seafood samples and living plants.

Considering the high toxicity of Hg to living organisms, accurately and sensitively detecting Hg in environments, biology and food systems is of the utmost importance. Herein, we present a new fast-responsive oligothiophene-derivatized fluorescent sensor TTB for Hg detection in real water/soil/urine/food samples. Sensor TTB shows a quick response, ultrahigh specificity, strong anti-disturbance, high-sensitivity with a satisfactory detection limit of 0.

Chemical characterization and antioxidant potential of Arthrospira sp., Thalassiosira sp., and Raphidonema sp.

Microalgae are emerging as valuable sources of bioactive compounds. This study evaluates hexane extracts from Thalassiosira sp. and Raphidonema sp.

Dipropyl phthalate induces craniofacial chondrogenic defects in zebrafish embryos.

Dipropyl phthalate (DPRP), a plasticizer commonly utilized in the plastics industry, has been identified in food and the environment and has the potential to present a hazard to human health and the environment. In this study, the first comprehensive evaluation of DPRP-induced craniofacial chondrogenic defects was conducted using a zebrafish model. Zebrafish embryos were exposed to 1, 2, and 4 mg/L DPRP from 6 to 96 h post-fertilization.

SDF-1/CXCR4 axis maintains porcine prospermatogonia undifferentiated state through regulation of transcription suppressor PLZF.

Prospermatogonia (ProSGs), the progenitors of spermatogonial stem cells in neonatal testes, undergo critical migration to the testicular microenvironment-a fundamental process for testicular development and subsequent spermatogenic capacity. The SDF-1/CXCR4 chemokine axis serves as an essential molecular guidance mechanism, directing ProSGs toward the basal membrane of seminiferous tubules. Nevertheless, the precise molecular mechanisms governing this axis remain incompletely understood.

Transcription factor-mediated reprogramming to antigen-presenting cells.

Antigen-presenting cells (APCs) are a heterogenous group of immune cells composed by dendritic cells (DCs) and macrophages (Mϕ), which are critical for orchestrating immunity against cancer or infections. Several strategies have been explored to generate APC subsets, including enrichment from peripheral blood and differentiation from pluripotent or multipotent cells. During development, the generation of APC subsets is instructed by transcription factors (TFs).

Cryo-EM structure of the human Pannexin-3 channel.

Pannexin-3 (PANX3) is a member of the pannexin family of large-pore, ATP-permeable channels conserved across vertebrates. PANX3 contributes to various developmental and pathophysiological processes by permeating ATP and Ca ions; however, the structural basis of PANX3 channel function remains unclear. Here, we present the cryo-EM structure of human PANX3 at 2.

Discovery and optimization of 1,2,4-triazole derivatives as novel ferroptosis inhibitors.

Ferroptosis is a novel form of regulated cell death characterized by iron-dependent lipid ROS accumulation, which is associated with various diseases, including acute organ injury, neurodegenerative disorders, and cancer. Pharmacological inhibition of ferroptosis has great potential for the treatment of these diseases. However, the clinical translation of many ferroptosis inhibitors is hindered by their inadequate activity or suboptimal pharmacokinetic profiles.

Functional genomics of primary congenital glaucoma by pathway analysis and functional characterization of CYP1B1 mutations.

CYP1B1 is the most common gene implicated in primary congenital glaucoma (PCG) - the most common form of childhood glaucoma. How CYP1B1 mutations cause PCG is not known. Understanding the mechanism of PCG caused by CYP1B1 mutations is crucial for disease management, therapeutics development, and potential prevention.

Patent landscape of small molecule inhibitors of METTL3 (2020-present).

Introduction: Methyltransferase-like protein 3 (METTL3), in complex with METTL14, is the key 'writer' protein for RNA mA methylation, accounting for almost all mRNA mA modifications. Recent studies reveal that METTL3 is implicated in the development and progression of various types of cancers. Targeting METTL3 with small molecule inhibitors represents a promising therapeutic strategy for cancer.

Self-maintenance of zonal hepatocytes during adult homeostasis and their complex plasticity upon distinct liver injuries.

Hepatocytes are organized into distinct zonal subsets across the liver lobule, yet their contributions to liver homeostasis and regeneration remain controversial. Here, we developed multiple genetic lineage-tracing mouse models to systematically address this. We found that the liver lobule can be divided into two major zonal and molecular hepatocyte populations marked by Cyp2e1 or Gls2.

Multiplex Trifluoromethyl and Hydroxyl Radical Chemistry Enables High-Resolution Protein Footprinting.

Hydroxyl radical-based protein footprinting (HRPF) coupled with mass spectrometry is a valuable medium-resolution technique in structural biology, facilitating the assessment of protein structure and molecular-level interactions in solution conditions. In HRPF with X-rays (XFP), hydroxyl radicals generated by water radiolysis covalently label multiple amino acid (AA) side chains. However, HRPF technologies face challenges in achieving their full potential due to the broad (>10) dynamic range of AA reactivity with OH and difficulty in detecting slightly modified residues, most notably in peptides with highly reactive residues like methionine, or where all residues have low OH reactivities.

NanoCMSer: a consensus molecular subtype stratification tool for fresh-frozen and paraffin-embedded colorectal cancer samples.

Colorectal cancer (CRC) is a significant contributor to cancer-related mortality, emphasizing the need for advanced biomarkers to guide treatment. As part of an international consortium, we previously categorized CRCs into four consensus molecular subtypes (CMS1-CMS4), showing promise for outcome prediction. To facilitate clinical integration of CMS classification in settings where formalin-fixed paraffin-embedded (FFPE) samples are routinely used, we developed NanoCMSer, a NanoString-based CMS classifier using 55 genes.

Emergence of Omicron FN.1 a descendent of BQ.1.1 in Botswana.

Botswana, like the rest of the world, has been significantly impacted by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). In December 2022, we detected a monophyletic cluster of genomes comprising a sublineage of the Omicron variant of concern (VOC) designated as B.1.

Liquid-liquid separation in gut immunity.

Gut immunity is essential for maintaining intestinal health. Recent studies have identified that intracellular liquid-liquid phase separation (LLPS) may play a significant role in regulating gut immunity, however, the underlying mechanisms remain unclear. LLPS refers to droplet condensates formed through intracellular molecular interactions, which are crucial for the formation of membraneless organelles and biomolecules.