Pan-Cancer Insights: A Study of Microbial Metabolite Receptors in Malignancy Dynamics.

Background/objectives: The role of the gut microbiome in cancer biology has become an increasingly prominent area of research, particularly regarding the role of microbial metabolites and their receptors (MMRs). These metabolites, through the various gut-organ axes, have been proven to influence several pathogenetic mechanisms. This study conducted a comprehensive pan-cancer analysis of MMR transcriptomic profiles across twenty-three cancer types, exploring the mechanisms through which they can influence cancer development and progression.

Mutant huntingtin protein decreases with CAG repeat expansion: implications for therapeutics and bioassays.

Huntington's disease is an inherited neurodegenerative disorder caused by a CAG repeat expansion that encodes a polyglutamine tract in the huntingtin (HTT) protein. The mutant CAG repeat is unstable and expands in specific brain cells and peripheral tissues throughout life. Genes involved in the DNA mismatch repair pathways, known to act on expansion, have been identified as genetic modifiers; therefore, it is the rate of somatic CAG repeat expansion that drives the age of onset and rate of disease progression.

PDA Stenting for Ductal-Dependent Cyanotic Congenital Heart Disease: History and View from 10,000 Feet.

This article provides a historical review and a current perspective on the procedures used to palliate cyanosis in ductal-dependent infants. Eighty years ago, Helen Taussig, Alfred Blalock, and Vivien Thomas developed the first effective treatment. The Blalock-Taussig-Thomas (BTT) shunt is the historical predecessor of both the contemporary-modified BTT shunt and interventional stenting of the Patent Ductus Arteriosus (PDA).

PDA Stenting for Ductal-Dependent Cyanotic Congenital Heart Disease: History and View From 10,000 Feet.

This article provides a historical review and a current perspective on the procedures used to palliate cyanosis in ductal-dependent infants. Eighty years ago, Helen Taussig, Alfred Blalock and Vivien Thomas developed the first effective treatment. The Blalock-Taussig-Thomas (BTT) shunt is the historical predecessor of both the contemporary modified BTT shunt and interventional stenting of the Patent Ductus Arteriosus (PDA).

Temperature field analysis and compensation improvement of load cell.

During the operation of load cell, heat is generated by the strain gauge and the electronics on the PCB board, which leads to temperature gradients within the sensor itself. These temperature gradients are unstable at different ambient temperatures. Compensation inaccuracies can also occur when compensating for sensor measurements at different temperatures This paper proposes a method to change the position of temperature compensation resistors to address errors caused by the temperature field effect of the strain gauge sensor itself.

Unpacking unstructured data: A pilot study on extracting insights from neuropathological reports of Parkinson's Disease patients using large language models.

The aim of this study was to make unstructured neuropathological data, located in the NeuroBioBank (NBB), follow Findability, Accessibility, Interoperability, and Reusability principles and investigate the potential of large language models (LLMs) in wrangling unstructured neuropathological reports. By making the currently inconsistent and disparate data findable, our overarching goal was to enhance research output and speed. The NBB catalog currently includes information from medical records, interview results, and neuropathological reports.

Identification of SLC35A1 as an essential host factor for the transduction of multi-serotype recombinant adeno-associated virus (AAV) vectors.

We conducted a genome-wide CRISPR/Cas9 screen in suspension 293-F cells transduced with rAAV5. The highly selected genes revealed after two rounds of screens included the previously reported , , and , along with a cluster of genes involved in glycan biogenesis, Golgi apparatus localization and endoplasmic reticulum penetration. In this report, we focused on solute carrier family 35 member A1 (), a Golgi apparatus-localized cytidine 5'-monophosphate-sialic acid (CMP-SIA) transporter.

The Generation of ROS by Exposure to Trihalomethanes Promotes the IκBα/NF-κB/p65 Complex Dissociation in Human Lung Fibroblast.

Disinfection by-products used to obtain drinking water, including halomethanes (HMs) such as CHCl, CHCl, and BrCHCl, induce cytotoxicity and hyperproliferation in human lung fibroblasts (MRC-5). Enzymes such as superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GPx) modulate these damages through their biotransformation processes, potentially generating toxic metabolites. However, the role of the oxidative stress response in cellular hyperproliferation, modulated by nuclear factor-kappa B (NF-κB), remains unclear.

Landscape of Interactions between Stromal and Myeloid Cells in Ileal Crohn's Disease; Indications of an Important Role for Fibroblast-Derived CCL-2.

Background And Aims: Monocyte recruitment in the lamina propria and inflammatory phenotype driven by the mucosal microenvironment is critical for the pathogenesis of inflammatory bowel disease. However, the stimuli responsible remain largely unknown. Recent works have focused on stromal cells, the main steady-state cellular component in tissue, as they produce pro-inflammatory chemokines that contribute to the treatment-resistant nature of IBD.

INT-1B3, an LNP formulated miR-193a-3p mimic, promotes anti-tumor immunity by enhancing T cell mediated immune responses via modulation of the tumor microenvironment and induction of immunogenic cell death.

microRNAs (miRNAs) are small, non-coding RNAs that regulate expression of multiple genes. MiR-193a-3p functions as a tumor suppressor in many cancer types, but its effect on inducing specific anti-tumor immune responses is unclear. Therefore, we examined the effect of our lipid nanoparticle (LNP) formulated, chemically modified, synthetic miR-193a-3p mimic (INT-1B3) on anti-tumor immunity.

The Effect of Open and Closed Oocyte Vitrification Systems on Embryo Development: A Systematic Review and Network Meta-Analysis.

: Open and closed vitrification systems are commonly employed in oocyte cryopreservation; however, there is limited evidence regarding a comparison of their separate impact on oocyte competence. This study uniquely brings to the literature, data on the effect of open versus closed vitrification systems on laboratory and clinical outcomes, and the effect of cooling and warming rates. : A systematic search of the literature was performed using the databases PubMed/MEDLINE and the Cochrane Central Library, limited to articles published in English up to January 2023.

SRX3177, a CDK4/6-PI3K-BET inhibitor, in combination with an RdRp inhibitor, Molnupiravir, or an entry inhibitor MU-UNMC-2, has potent antiviral activity against the Omicron variant of SARS-CoV-2.

Despite considerable progress in developing vaccines and antivirals to combat COVID-19, the rapid mutations of the SARS-CoV-2 genome have limited the durability and efficacy of the current vaccines and therapeutic interventions. Hence, it necessitates the development of novel therapeutic approaches or repurposing existing drugs that target either viral life cycle, host factors, or both. Here, we report that SRX3177, a potent triple-activity CDK4/6-PI3K-BET inhibitor, blocks replication of the SARS-CoV-2 Omicron variant with IC values at sub-micromolar concentrations without any impact on the cell proliferation of Calu-3 cells at and below its IC concentration.

Exploring Microbial Metabolite Receptors in Inflammatory Bowel Disease: An In Silico Analysis of Their Potential Role in Inflammation and Fibrosis.

Metabolites produced by dysbiotic intestinal microbiota can influence disease pathophysiology by participating in ligand-receptor interactions. Our aim was to investigate the differential expression of metabolite receptor (MR) genes between inflammatory bowel disease (IBD), healthy individuals (HIs), and disease controls in order to identify possible interactions with inflammatory and fibrotic pathways in the intestine. RNA-sequencing datasets containing 643 Crohn's disease (CD) patients, 467 ulcerative colitis (UC) patients and 295 HIs, and 4 -infected individuals were retrieved from the Sequence Read Archive, and differential expression was performed using the RaNA-seq online platform.

HIV envelope trimers and gp120 as immunogens to induce broadly neutralizing antibodies in cows.

The study of immunogens capable of eliciting broadly neutralizing antibodies (bnAbs) is crucial for the development of an HIV vaccine. To date, only cows, making use of their ultralong CDRH3 loops, have reliably elicited bnAbs following immunization with HIV Envelope trimers. Antibody responses to the CD4 binding site have been readily elicited by immunization of cows with a stabilized Env trimer of the BG505 strain and, with more difficulty, to the V2-apex region of Env with a cocktail of trimers.

Metabolomics and Lipidomics Analyses Aid Model Classification of Type 2 Diabetes in Non-Human Primates.

Type 2 diabetes (T2D) is a global public health issue characterized by excess weight, abdominal obesity, dyslipidemia, hyperglycemia, and a progressive increase in insulin resistance. Human population studies of T2D development and its effects on systemic metabolism are confounded by many factors that cannot be controlled, complicating the interpretation of results and the identification of early biomarkers. Aged, sedentary, and overweight/obese non-human primates (NHPs) are one of the best animal models to mimic spontaneous T2D development in humans.

A CAG repeat threshold for therapeutics targeting somatic instability in Huntington's disease.

The Huntington's disease mutation is a CAG repeat expansion in the huntingtin gene that results in an expanded polyglutamine tract in the huntingtin protein. The CAG repeat is unstable and expansions of hundreds of CAGs have been detected in Huntington's disease post-mortem brains. The age of disease onset can be predicted partially from the length of the CAG repeat as measured in blood.

Potent inhibitors targeting cyclin-dependent kinase 9 discovered virtual high-throughput screening and absolute binding free energy calculations.

Due to the crucial regulatory mechanism of cyclin-dependent kinase 9 (CDK9) in mRNA transcription, the development of kinase inhibitors targeting CDK9 holds promise as a potential treatment strategy for cancer. A structure-based virtual screening approach has been employed for the discovery of potential novel CDK9 inhibitors. First, compounds with kinase inhibitor characteristics were identified from the ZINC15 database virtual high-throughput screening.

Improving CNV Detection Performance in Microarray Data Using a Machine Learning-Based Approach.

Copy number variation (CNV) is a primary source of structural variation in the human genome, leading to several disorders. Therefore, analyzing neonatal CNVs is crucial for managing CNV-related chromosomal disabilities. However, genomic waves can hinder accurate CNV analysis.

Quick model-based viscoelastic clot strength predictions from blood protein concentrations for cybermedical coagulation control.

Cybermedical systems that regulate patient clotting in real time with personalized blood product delivery will improve treatment outcomes. These systems will harness popular viscoelastic assays of clot strength such as thromboelastography (TEG), which help evaluate coagulation status in numerous conditions: major surgery (e.g.

BETA prime: a first-in-man phase 1 study of AdAPT-001, an armed oncolytic adenovirus for solid tumors.

AdAPT-001 is an oncolytic adenovirus (OAV) with a transforming growth factor beta (TGF-ß) trap, which neutralizes the immunosuppressive and profibrotic cytokine, TGF-ß. The aim or purpose of this phase 1 study was to assess the safety and tolerability and, secondarily, the efficacy of AdAPT-001 after single intratumoral injection (IT) (Part 1) and multidose IT injection (Part 2) in patients with superficially accessible, advanced refractory solid tumors. Part 1 enrolled 9 patients with a 3 + 3 single dose-escalation safety run-in involving 2.

Analysis of Return-to-Zero Error after the First Load of Load Cell.

The return-to-zero error of the resistance strain load cell is most obvious in the first zero-return process during loading and unloading. To improve the accuracy of the load cell, it is necessary to figure out the cause of the error. The influence of the temperature, material, and weld cup were analyzed in this paper.

Protein-Based Anchoring Methods for Nucleic Acid Detection in Lateral Flow Format Assays.

The use of lateral flow assays to detect nucleic acid targets has many applications including point-of-care diagnostics, environmental monitoring, and food safety. A sandwich format, similar to that in protein immunoassays, is often used to capture the target nucleic acid sequence with an immobilized complementary strand anchored to a substrate, and then to visualize this event using a complementary label nucleic acid bound to a nanoparticle label. A critical component of high-sensitivity nucleic acid detection is to utilize high-density capture surfaces for the effective capture of target nucleic acid.

Thermal Image Processing for Respiratory Estimation from Cubical Data with Expandable Depth.

As healthcare costs continue to rise, finding affordable and non-invasive ways to monitor vital signs is increasingly important. One of the key metrics for assessing overall health and identifying potential issues early on is respiratory rate (RR). Most of the existing methods require multiple steps that consist of image and signal processing.

A defined roadmap of radial glia and astrocyte differentiation from human pluripotent stem cells.

Human gliogenesis remains poorly understood, and derivation of astrocytes from human pluripotent stem cells (hPSCs) is inefficient and cumbersome. Here, we report controlled glial differentiation from hPSCs that bypasses neurogenesis, which otherwise precedes astrogliogenesis during brain development and in vitro differentiation. hPSCs were first differentiated into radial glial cells (RGCs) resembling resident RGCs of the fetal telencephalon, and modulation of specific cell signaling pathways resulted in direct and stepwise induction of key astroglial markers (NFIA, NFIB, SOX9, CD44, S100B, glial fibrillary acidic protein [GFAP]).

Association between Cerebrospinal Fluid and Serum Biomarker Levels and Diagnosis, Injury Severity, and Short-Term Outcomes in Patients with Acute Traumatic Spinal Cord Injury.

Acute traumatic spinal cord injury (SCI) is recognized as a global problem that can lead to a range of acute and secondary complications impacting morbidity and mortality. There is still a lack of reliable diagnostic and prognostic biomarkers in patients with SCI that could help guide clinical care and identify novel therapeutic targets for future drug discovery. The aim of this prospective controlled study was to determine the cerebral spinal fluid (CSF) and serum profiles of 10 biomarkers as indicators of SCI diagnosis, severity, and prognosis to aid in assessing appropriate treatment modalities.