PD-L1 (22C3) expression and prognostic implications in esophageal squamous cell carcinoma.

Programmed cell death-ligand 1 (PD-L1) clone 22C3 is the only Food and Drug Administration-approved companion diagnostic test for pembrolizumab for the treatment of esophageal squamous cell carcinoma (ESCC). However, prior studies conducted in Asia and Europe have used various PD-L1 antibody clones other than 22C3. We aimed to study the expression profile of PD-L1, specifically of clone 22C3, in ESCC and its significance with regards to histological features, clinical parameters, and overall survival in a case series from two large US hospital systems.

Impact of glucagon-Like peptide-1 agonists in optimizing abdominal wall Reconstruction patients.

Purpose: Pre-optimization of obese patients prior to abdominal wall reconstruction (AWR) is essential in mitigating their increased preoperative risks. Traditionally diet, exercising, bariatric surgery are the tools typically prescribed for weight loss. The advent of glucagon-like peptide-1 agonists (GLP-1A) which stimulate insulin secretion and inhibit gastric emptying have improved the weight loss armamentarium.

The role of patient-specific variables in protein corona formation and therapeutic efficacy in nanomedicine.

Despite their potential, the adoption of nanotechnology in therapeutics remains limited, with only around eighty nanomedicines approved in the past 30 years. This disparity is partly due to the "one-size-fits-all" approach in medical design, which often overlooks patient-specific variables such as biological sex, genetic ancestry, disease state, environment, and age that influence nanoparticle behavior. Nanoparticles (NPs) must be transported through systemic, microenvironmental, and cellular barriers that vary across heterogeneous patient populations.

Differentiation signals induce APOBEC3A expression via GRHL3 in squamous epithelia and squamous cell carcinoma.

Two APOBEC DNA cytosine deaminase enzymes, APOBEC3A and APOBEC3B, generate somatic mutations in cancer, thereby driving tumour development and drug resistance. Here, we used single-cell RNA sequencing to study APOBEC3A and APOBEC3B expression in healthy and malignant mucosal epithelia, validating key observations with immunohistochemistry, spatial transcriptomics and functional experiments. Whereas APOBEC3B is expressed in keratinocytes entering mitosis, we show that APOBEC3A expression is confined largely to terminally differentiating cells and requires grainyhead-like transcription factor 3 (GRHL3).

Colibactin Exerts Androgen-dependent and -independent Effects on Prostate Cancer.

Background And Objective: The etiology of prostate cancer (PC) is multifactorial and poorly understood. It has been suggested that colibactin-producing Escherichia coli positive for the pathogenicity island pks (pks) initiate cancers via induction of genomic instability. In PC, androgens promote oncogenic translocations.

Tools, techniques, and challenges in preparing cytology specimens for ancillary studies: results of the ASC Optimizing Cytology and Small Biopsy Specimen Processing for Ancillary Studies task force survey.

Introduction: Ancillary testing on cytopathology and other small biopsy specimens is crucial for diagnosis and provides critical information to clinicians. Testing is dependent on preanalytic factors and would benefit from standardization of specimen collection protocols across laboratories. To assess institutional practices and areas of need for evidence-based standards, we surveyed current practices across cytopathology laboratories.

Light-Driven Installation of Aminooxyhomolysine on Histones and Its Application for Synthesizing Stable and Site-Specific 3'-DNA-Histone Cross-Links.

Histones react with various aldehyde-containing DNA modifications to form reversible but long-lived DNA-histone cross-links. The investigation of their biochemical effects and repair mechanisms has been impeded due to their reversibility and the lack of methods for synthesizing stable and structure-defined DNA-histone cross-links. Herein, we present a visible-light-driven strategy to install an aminooxyhomolysine on a histone at a defined position.

Combining vitamin E metabolite 13'-carboxychromanol and a lactic acid bacterium synergistically mitigates colitis and colitis-associated dysbiosis in mice.

Synbiotics may be useful to mitigate intestinal diseases such as ulcerative colitis. Here we show that combining 13'-carboxychromanol (δT3-13'), a metabolite of vitamin E δ-tocotrienol (δT3) via omega-oxidation, and Lactococcus lactis subsp. cremori (L.

The molecular chaperone ALYREF promotes R-loop resolution and maintains genome stability.

Unscheduled R-loops usually cause DNA damage and replication stress, and are therefore a major threat to genome stability. Several RNA processing factors, including the conserved THO complex and its associated RNA and DNA-RNA helicase UAP56, prevent R-loop accumulation in cells. Here, we investigate the function of ALYREF, an RNA export adapter associated with UAP56 and the THO complex, in R-loop regulation.

Self-catalytic enhancement of Cu-EDTA decomplexation and simultaneous Cu recovery via a dual-cathode electrochemical process.

Heavy metals that are readily chelated with coexisting organic ligands in industrial wastewaters impose threats to environment and human health but are also valuable metal resources. Traditional treatment methods generally require additional chemicals and generate secondary contaminants. Here, a reagent-free dual-cathode electrochemical system was proposed for the efficient destruction of Cu-organic complexes and synchronous cathodic recovery of Cu, whereby in situ production of HO at carbon aerogel (CA) cathode was coupled with the reduction of Cu(II) to Cu(I) and finally to Cu(0) at Ti cathode.

Designing proteins: Mimicking natural protein sequence heterogeneity.

This study presents an enhanced protein design algorithm that aims to emulate natural heterogeneity of protein sequences. Initial analysis revealed that natural proteins exhibit a permutation composition lower than the theoretical maximum, suggesting a selective utilization of the 20-letter amino acid alphabet. By not constraining the amino acid composition of the protein sequence but instead allowing random reshuffling of the composition, the resulting design algorithm generates sequences that maintain lower permutation compositions in equilibrium, aligning closely with natural proteins.

Discovery, Biosynthesis, Total Synthesis, and Biological Activities of Solanapyrones: [4 + 2] Cycloaddition-Derived Polyketides of Fungal Origin.

Solanapyrones are metabolites bearing a 3,4-dehydrodecalin moiety isolated from cultures of different fungi that are associated with plant diseases. Research on solanapyrones resulted in the first report of a Diels-Alderase enzyme implicated in natural product biosynthesis related to the formation of the 3,4-dehydrodecalin core. In addition, several total syntheses of solanapyrones have been reported, which are also connected with the formation of the characteristic cycloaddition-derived 3,4-dehydrodecalin moiety.

Intra-lymph node crosslinking of antigen-bearing polymers enhances humoral immunity and dendritic cell activation.

Lymph node (LN)-resident dendritic cells (DCs) are a promising target for vaccination given their professional antigen-presenting capabilities and proximity to a high concentration of immune cells. Direct intra-LN injection has been shown to greatly enhance the immune response to vaccine antigens compared to traditional intramuscular injection, but it is infeasible to implement clinically in a vaccination campaign context. Employing the passive lymphatic flow of antigens to target LNs has been shown to increase total antigen uptake by DCs more than inflammatory adjuvants, which recruit peripheral DCs.

Addressing statistical challenges in the analysis of proteomics data with extremely small sample size: a simulation study.

Background: One of the most promising approaches for early and more precise disease prediction and diagnosis is through the inclusion of proteomics data augmented with clinical data. Clinical proteomics data is often characterized by its high dimensionality and extremely limited sample size, posing a significant challenge when employing machine learning techniques for extracting only the most relevant information. Although there is a wide array of statistical techniques and numerous analysis pipelines employed in proteomics data analysis, it is unclear which of these methods produce the most efficient, reproducible, and clinically meaningful results.

Virion morphology and on-virus spike protein structures of diverse SARS-CoV-2 variants.

The evolution of SARS-CoV-2 variants with increased fitness has been accompanied by structural changes in the spike (S) proteins, which are the major target for the adaptive immune response. Single-particle cryo-EM analysis of soluble S protein from SARS-CoV-2 variants has revealed this structural adaptation at high resolution. The analysis of S trimers in situ on intact virions has the potential to provide more functionally relevant insights into S structure and virion morphology.

Missing microbial eukaryotes and misleading meta-omic conclusions.

Meta-omics is commonly used for large-scale analyses of microbial eukaryotes, including species or taxonomic group distribution mapping, gene catalog construction, and inference on the functional roles and activities of microbial eukaryotes in situ. Here, we explore the potential pitfalls of common approaches to taxonomic annotation of protistan meta-omic datasets. We re-analyze three environmental datasets at three levels of taxonomic hierarchy in order to illustrate the crucial importance of database completeness and curation in enabling accurate environmental interpretation.

Biochemical and steady-state kinetic analyses of arsenate reductases from an arsenic-tolerant strain of Citrobacter youngae IITK SM2.

Arsenic (As) poisoning in aquifers is a serious problem worldwide, especially in the middle-Gangetic Plain (MGP) of India. Microbially-mediated As speciation in such aquifers is governed by the arsenate-reductase enzyme, ArsC, encoded by the arsC gene of As-metabolizing bacteria. In this study, ArsC1 (119 aa) and ArsC2 (141 aa) of a highly resistant strain to arsenic, Citrobacter youngae IITK SM2 (CyIITKSM2), isolated from a mixed-oxic MGP groundwater were biochemically characterized.

Generation of BT-Amide, a Bone-Targeted Pyk2 Inhibitor, Effective Oral Administration, for the Prevention of Glucocorticoid-Induced Bone Loss.

Glucocorticoid-induced osteoporosis (GIOP) is the leading cause of iatrogenic osteoporosis due to the widespread clinical use of glucocorticoids (GC) as immunosuppressants. Previous research identified the proline-rich tyrosine kinase 2, Pyk2, as a critical mediator of GC-induced bone loss, and that blocking Pyk2 could protect the skeleton from adverse GC actions. However, systemic administration of current Pyk2 inhibitors causes harmful side effects, such as skin lesions.

The Pfam protein families database: embracing AI/ML.

The Pfam protein families database is a comprehensive collection of protein domains and families used for genome annotation and protein structure and function analysis (https://www.ebi.ac.

Electrochemical Nanosensor-Based Emerging Point-Of-Care Tools: Progress and Prospects.

Early detection of disease remains a crucial challenge in medicine. Delayed diagnosis often leads to limited treatment options, increased disease progression, and unfortunately, even death in some cases. To address this, the need for rapid, cost-effective, and noninvasive diagnostic tools is paramount.

SEI Formation and Lithium-Ion Electrodeposition Dynamics in Lithium Metal Batteries via First-Principles Kinetic Monte Carlo Modeling.

The stabilization and enhanced performance of lithium metal batteries (LMBs) depend on the formation and evolution of the Solid Electrolyte Interphase (SEI) layer as a critical component for regulating the Li metal electrodeposition processes. This study employs a first-principles kinetic Monte Carlo (kMC) model to simulate the SEI formation and Li electrodeposition processes on a lithium metal anode, integrating both the electrochemical electrolyte reduction reactions and the diffusion events giving place to the SEI aggregation processes during battery charge and discharge processes. The model replicates the competitive interactions between organic and inorganic SEI components, emphasizing the influence of the cycling regime.

Insights into the efficiencies of different biological treatment systems for pharmaceuticals removal: A review.

This review presents a comprehensive analysis of current research on biological treatment processes for removing pharmaceutical compounds (PhCs) from wastewater. Unlike previous studies on this topic, our study specifically delves into the effectiveness and drawbacks of various treatment approaches such as traditional wastewater treatment facilities (WWTP), membrane bioreactors (MBRs), constructed wetlands (CW), and moving bed biofilm reactors (MBBR). Through the examination and synthesis of information gathered from more than 200 research studies, we have created a comprehensive database that delves into the effectiveness of eliminating 19 particular PhCs, including commonly studied compounds such as acetaminophen, ibuprofen, diclofenac, naproxen, ketoprofen, indomethacin, salicylic acid, codeine, and fenoprofen, amoxicillin, azithromycin, ciprofloxacin, ofloxacin, tetracycline, atenolol, propranolol, and metoprolol.