Continuous Blood Gas Control Based on Active Disturbance Rejection Control During Ex Vivo Porcine Liver Perfusion.

Background: Membrane oxygenators facilitate extracorporeal gas exchange, necessitating the monitoring of blood gas. Recent advances in normothermic machine perfusion (NMP) for ex vivo liver offer solutions to the shortage of donor liver. However, maintaining physiological blood gas levels during prolonged NMP is complex and costly.

Structure-Guided Optimization and Preclinical Evaluation of 6--Benzylguanine-Based Pin1 Inhibitor for Hepatocellular Carcinoma Treatment.

Hepatocellular carcinoma (HCC) is a major cause of cancer-related deaths globally, and the need for effective systemic therapies for HCC is urgent. Our previous work reveals that Pin1 is a potential anti-HCC target, which regulates miRNA biogenesis and identifies as a novel Pin1 inhibitor to suppresses HCC. However, a great demand in HCC therapy as well as the limited chemical stability and pharmacokinetic feature of motivated us to find improved Pin1 inhibitors.

Verticillin A-Loaded Surgical Buttresses Prevent Local Pancreatic Cancer Recurrence in a Murine Model.

The fungal metabolite verticillin A is a potent and selective histone methyltransferase inhibitor. It regulates apoptosis, the cell cycle, and stress response, and displays potent activity in the suppression of tumor cell growth in several different in vivo models. Verticillin A sensitizes pancreatic cancer cells to anti-PD-1 immunotherapy by regulating PD-L1 expression.

A molecular module improves rice grain quality and yield at high temperatures.

Excessive temperatures during grain filling can compromise endosperm starch biosynthesis and decrease grain quality and yield in rice. However, the molecular mechanisms underlying these remain unclear. Here, we show that heat shock protein OsHsp40-1 interacts with and elevates the ATPase activity of OsHsp70-2 in rice.

FOXP2-immunoreactive corticothalamic neurons in neocortical layers 6a and 6b are tightly regulated by neuromodulatory systems.

The / gene, linked to fine motor control in vertebrates, is a potential candidate gene thought to play a prominent role in human language production. It is expressed specifically in a subset of corticothalamic (CT) pyramidal cells (PCs) in layer 6 (L6) of the neocortex. These L6 FOXP2+ PCs project exclusively to the thalamus, with L6a PCs targeting first-order or both first- and higher-order thalamic nuclei, whereas L6b PCs connect only to higher-order nuclei.

Abundant repressor binding sites in human enhancers are associated with the fine-tuning of gene regulation.

The regulation of gene expression relies on the coordinated action of transcription factors (TFs) at enhancers, including both activator and repressor TFs. We employed deep learning (DL) to dissect HepG2 enhancers into positive (PAR), negative (NAR), and neutral activity regions. Sharpr-MPRA and STARR-seq highlight the dichotomy impact of NARs and PARs on modulating and catalyzing the activity of enhancers, respectively.

Mechanism of hsa_circ_0069443 promoting early pregnancy loss through ALKBH5/FN1 axis in trophoblast cells.

Studies have shown that circRNAs play an important regulatory role in trophoblast function and embryonic development. Based on sequencing and functional experiments, we found that hsa_circ_0069443 can regulate the function of trophoblast cells, and its presence is found in the exosomes secreted by trophoblast cells. It is known that exosomes mediate the interaction between the uterus and embryo, which is crucial for successful pregnancy.

Deep learning uncovers histological patterns of YAP1/TEAD activity related to disease aggressiveness in cancer patients.

Over the last decade, Hippo signaling has emerged as a major tumor-suppressing pathway. Its dysregulation is associated with abnormal expression of and -family genes. Recent works have highlighted the role of YAP1/TEAD activity in several cancers and its potential therapeutic implications.

Primitive to visceral endoderm maturation is essential for mouse epiblast survival beyond implantation.

The implantation of the mouse blastocyst initiates a complex sequence of tissue remodeling and cell differentiation events required for morphogenesis, during which the extraembryonic primitive endoderm transitions into the visceral endoderm. Through single-cell RNA sequencing of embryos at embryonic day 5.0, shortly after implantation, we reveal that this transition is driven by dynamic signaling activities, notably the upregulation of BMP signaling and a transient increase in Sox7 expression.

Infiltrating lipid-rich macrophage subpopulations identified as a regulator of increasing prostate size in human benign prostatic hyperplasia.

Introduction: Macrophages exhibit marked phenotypic heterogeneity within and across disease states, with lipid metabolic reprogramming contributing to macrophage activation and heterogeneity. Chronic inflammation has been observed in human benign prostatic hyperplasia (BPH) tissues, however macrophage activation states and their contributions to this hyperplastic disease have not been defined. We postulated that a shift in macrophage phenotypes with increasing prostate size could involve metabolic alterations resulting in prostatic epithelial or stromal hyperplasia.

Targeted barcoding of variable antibody domains and individual transcriptomes of the human B-cell repertoire using Link-Seq.

Here, we present Link-Seq, a highly efficient droplet microfluidic method for combined sequencing of antibody-encoding genes and the transcriptome of individual B cells at large scale. The method is based on 3' barcoding of the transcriptome and subsequent single-molecule PCR in droplets, which freely shift the barcode along specific gene regions, such as the antibody heavy- and light-chain genes. Using the immune repertoire of COVID-19 patients and healthy donors as a model system, we obtain up to 91.

A genetically encoded fluorescent biosensor for sensitive detection of cellular c-di-GMP levels in .

Cyclic di-guanosine monophosphate (c-di-GMP) acts as a second messenger regulating bacterial behaviors including cell cycling, biofilm formation, adhesion, and virulence. Monitoring c-di-GMP levels is crucial for understanding these processes and designing inhibitors to combat biofilm-related antibiotic resistance. Here, we developed a genetically encoded biosensor, cdiGEBS, based on the transcriptional activity of the c-di-GMP-responsive transcription factor MrkH.

Depression-related innate immune genes and pan-cancer gene analysis and validation.

Background: Depression, a prevalent chronic mental disorder, presents complexities and treatment challenges that drive researchers to seek new, precise therapeutic targets. Additionally, the potential connection between depression and cancer has garnered significant attention.

Methods: This study analyzed depression-related gene expression data from the GEO database.

Imputation for Lipidomics and Metabolomics (ImpLiMet): a web-based application for optimization and method selection for missing data imputation.

Motivation: Missing values are prevalent in high-throughput measurements due to various experimental or analytical reasons. Imputation, the process of replacing missing values in a dataset with estimated values, plays an important role in multivariate and machine learning analyses. The three missingness patterns, including missing completely at random, missing at random, and missing not at random, describe unique dependencies between the missing and observed data.

Correction: Novel pyrimidine linked acyl thiourea derivatives as potent α-amylase and proteinase K inhibitors: design, synthesis, molecular docking and ADME studies.

[This corrects the article DOI: 10.1039/D4RA05799F.].

iRGD-Targeted Biosynthetic Nanobubbles for Ultrasound Molecular Imaging of Osteosarcoma.

Purpose: Osteosarcoma is the most common primary malignant tumor of the bone. However, there is a lack of effective means for early diagnosis due to the heterogeneity of tumors and the complexity of tumor microenvironment. αvβ3 integrin, a crucial role in the growth and spread of tumors, is not only an effective biomarker for cancer angiogenesis, but also highly expressed in many tumor cells.

Rapid introgression of the clubroot resistance gene into cabbage skeleton inbred lines through marker assisted selection.

Unlabelled: Clubroot, caused by , is a globally pervasive soil-borne disease that poses a significant challenge primarily in cruciferous crops. However, the scarcity of resistant materials and the intricate genetic mechanisms within cabbage present major obstacles to clubroot resistance (CR) breeding. In our previous research, we developed an Ogura CMS cabbage variety, "17CR3", which harbors the gene, crucial for CR.

Molecular dynamics of chemotactic signalling orchestrates dental pulp stem cell fibrosis during aging.

Aging often triggers dental pulp fibrosis, resulting in clinical repercussions such as increased susceptibility to dental infections, compromised tooth vitality, and reduced responsiveness to dental interventions. Despite its prevalence, the precise molecular mechanisms underlying this condition remains unclear. Leveraging single-cell transcriptome analysis from both our own and publicly available datasets, we identified Ccrl2 macrophages as particularly vulnerable during the early stages of aging.

Rab10-associated tubulation as an early marker for biogenesis of the assembly compartment in cytomegalovirus-infected cells.

Introduction: Cytomegalovirus (CMV) infection reorganizes early endosomes (EE), recycling endosome (RE), and trans-Golgi network (TGN) and expands their intermediates into a large perinuclear structure that forms the inner part of the cytoplasmic assembly complex (AC). The reorganization begins and results with the basic configuration (known as pre-AC) in the early (E) phase of infection, but the sequence of developmental steps is not yet well understood. One of the first signs of the establishment of the inner pre-AC, which can be observed by immunofluorescence, is the accumulation of Rab10.

Computationally Assisted Noncanonical Amino Acid Incorporation.

Genetic encoding of noncanonical amino acids (ncAAs) with desired functionalities is an invaluable tool for the study of biological processes and the development of therapeutic drugs. However, existing ncAA incorporation strategies are rather time-consuming and have relatively low success rates. Here, we develop a virtual ncAA screener based on the analysis and modeling of the chemical properties of all reported ncAA substrates to virtually determine the recognition potential of candidate ncAAs.

Transient Expression of Zika NS2B Protein Antigen in and Use for Arboviruses Diagnosis.

Zika (ZIKV) and Dengue (DENV) viruses are clinically significant due to their severe neurological and hemorrhagic complications. Rapid diagnostics often rely on nonstructural proteins to generate specific antibodies. This study aimed to produce IgG antibodies from the recombinant ZIKV protein and plant-expressed NS2B protein for arbovirus detection in serum and urine samples.

Protective effects of resveratrol on the expression of , and genes in the ovary and their activity in the serum of rats exposed to lead acetate: An experimental study.

Background: Lead (Pb) could be toxic to the female reproductive system, and resveratrol (Res) may overcome this toxicity.

Objective: To investigate the Res impact on the catalase (), glutathione peroxidase (), and superoxide dismutase () gene expression in the ovary and on the Cat and Gpx enzyme activity in the serum of rats exposed to lead acetate.

Materials And Methods: In this experimental study, 33 female Wistar rats (8-10 wk, 180-200 gr) were divided into 6 groups: a control group (normal saline), a Res group (40 mg/kg), and a Pb group (lead acetate 30 mg/kg).

Molecular docking and molecular dynamics simulation studies of inhibitor candidates against 3-hydroxykynurenine transaminase and implications on vector control.

Isoxazole and oxadiazole derivatives inhibiting 3-hydroxykynurenine transaminase (3HKT) are potential larvicidal candidates. This study aims to identify more suited potential inhibitors of 3HKT (3HKT) through molecular docking and molecular dynamics simulation. A total of 958 compounds were docked against 3HKT (PDB ID: 2CH2) using Autodock vina and Autodock4.

Molecular and cellular regulators of embryo implantation and their application in improving the implantation potential of IVF-derived blastocysts.

Background: In vitro fertilization (IVF) and embryo transfer (ET) are widely used in reproductive biology. Despite the transfer of high-quality blastocysts, the implantation rate of IVF-derived blastocysts remains low after ET.

Methods: This article provides a comprehensive review of current research on embryo implantation regulators and their application to improve the implantation potential of IVF-derived blastocysts.

Evaluation of a surrogate virus neutralization assay for detecting neutralizing antibodies against SARS-CoV-2 in an African population.

The global resurgence of coronaviruses and the move to incorporate COVID-19 vaccines into the expanded program for immunization have warranted for a high-throughput and low-cost assay to measure and quantify mounted neutralizing antibodies as an indicator for protection against SARS-CoV-2. Hence, we evaluated the surrogate-virus-neutralization-assay (sVNT) as an alternative assay to the pseudo-virus neutralization assay (pVNT). The sVNT was used to measure neutralizing antibodies among 119 infected and/or vaccinated blood samples, against wild-type SARS-CoV-2 (WT) and the Omicron-variant with reference to the pVNT.