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.

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.].

Advancements in drug discovery: integrating CADD tools and drug repurposing for PD-1/PD-L1 axis inhibition.

Despite significant strides in improving cancer survival rates, the global cancer burden remains substantial, with an anticipated rise in new cases. Immune checkpoints, key regulators of immune responses, play a crucial role in cancer evasion mechanisms. The discovery of immune checkpoint inhibitors (ICIs) targeting PD-1/PD-L1 has revolutionized cancer treatment, with monoclonal antibodies (mAbs) becoming widely prescribed.

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.

Biomaterial Cues for Regulation of Osteoclast Differentiation and Function in Bone Regeneration.

Tissue regeneration involves dynamic dialogue between and among different cells and their surrounding matrices. Bone regeneration is specifically governed by reciprocity between osteoblasts and osteoclasts within the bone microenvironment. Osteoclast-directed resorption and osteoblast-directed formation of bone are essential to bone remodeling, and the crosstalk between these cells is vital to curating a sequence of events that culminate in the creation of bone tissue.

A vacuolar invertase gene modulates sugar metabolism and postharvest fruit quality and stress resistance in tomato.

Sugars act as signaling molecules to modulate various growth processes and enhance plant tolerance to various abiotic and biotic stresses. Moreover, sugars contribute to the postharvest flavor in fleshy fruit crops. To date, the regulation of sugar metabolism and its effect in plant growth, fruit ripening, postharvest quality, and stress resistance remains not fully understood.

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.

Stem cell-derived exosome delivery systems for treating atherosclerosis: The new frontier of stem cell therapy.

Cardiovascular diseases (CVDs) are a leading cause of mortality worldwide. As a chronic inflammatory disease with a complicated pathophysiology marked by abnormal lipid metabolism and arterial plaque formation, atherosclerosis is a major contributor to CVDs and can induce abrupt cardiac events. The discovery of exosomes' role in intercellular communication has sparked a great deal of interest in them recently.

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.

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.

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.

FOXR2 in cancer development: emerging player and therapeutic opportunities.

Cancer, a leading cause of global mortality, remains a significant challenge to increasing life expectancy worldwide. Forkhead Box R2 (FOXR2), identified as an oncogene within the FOX gene family, plays a crucial role in developing various endoderm-derived organs. Recent studies have elucidated FOXR2-related pathways and their involvement in both tumor and non-tumor diseases.

Melanoma-derived extracellular vesicles transfer proangiogenic factors.

Angiogenesis, the expansion of pre-existing vascular networks, is crucial for normal organ growth and tissue repair, but is also involved in various pathologies, including inflammation, ischemia, diabetes, and cancer. In solid tumors, angiogenesis supports growth, nutrient delivery, waste removal, and metastasis. Tumors can induce angiogenesis through proangiogenic factors including VEGF, FGF-2, PDGF, angiopoietins, HGF, TNF, IL-6, SCF, tryptase, and chymase.

Copper-Induced Transgenerational Plasticity in Plant Defence Boosts Aphid Fitness.

Transgenerational plasticity in plants is an increasingly recognized phenomenon, yet it is mostly unclear whether transgenerational plasticity is relevant to both the fitness of the plant and its interacting species. Using monoclonal strains of the giant duckweed (Spirodela polyrhiza) and its native herbivore, the waterlily aphid (Rhopalosiphum nymphaeae), we assessed whether pre-treating plants with copper excess, both indoors and outdoors, induces transgenerational plasticity in plant defences that alter plant and herbivore fitness. Outdoors, copper pre-treatment tended to increase plant growth rates under recurring copper excess.

The Proximal Protonation Source in Cu-NHx-C Single Atom Catalysts Selectively Boosts CO2 to Methane Electroreduction.

Regulating the coordination environment of active sites has proved powerful for tapping into their catalytic activity and selectivity in homogeneous catalysis, yet the heterogeneous nature of copper single-atom catalysts (SACs) makes it challenging. This work reports a bottom-up approach to construct a SAC (rGO@Cu-N(Hx)-C) by inlaying preformed amine coordinated Cu2+ units into reduced graphene oxide (rGO), permitting molecular level revelation on how the proximal N-site functional groups (N-H or N-CH3) impact on the carbon dioxide reduction reaction (CO2RR). It is demonstrated that the N-H moiety of rGO@Cu-NHx-C can serve as an in-situ protonation agent to accelerate the CO2-to-methane reduction kinetics, delivering a methane current density (163 mA/cm2) 2.

PerC B-Cells Activation via Thermogenetics-Based CXCL12 Generator for Intraperitoneal Immunity Against Metastatic Disseminated Tumor Cells.

During cancer peritoneal metastasis (PM), conventional antigen-presenting cells (dendritic cells, macrophages) promote tumorigenesis and immunosuppression in peritoneal cavity. While intraperitoneal immunotherapy (IPIT) has been used in clinical investigations to relieve PM, the limited knowledge of peritoneal immunocytes has hindered the development of therapeutic IPIT. Here, a dendritic cell-independent, next-generation IPIT is described that activates peritoneal cavity B (PerC B) cell subsets for intraperitoneal anti-tumor immunity via exogenous antigen presentation.

Multiomic analyses direct hypotheses for Creutzfeldt-Jakob disease risk genes.

Prions are assemblies of misfolded prion protein that cause several fatal and transmissible neurodegenerative diseases, with the most common phenotype in humans being sporadic Creutzfeldt-Jakob disease (sCJD). Aside from variation of the prion protein itself, molecular risk factors are not well understood. Prion and prion-like mechanisms are thought to underpin common neurodegenerative disorders meaning that the elucidation of mechanisms could have broad relevance.

Refinement of Atomic Polarizabilities for a Polarizable Gaussian Multipole Force Field with Simultaneous Considerations of Both Molecular Polarizability Tensors and In-Solution Electrostatic Potentials.

Atomic polarizabilities are considered to be fundamental parameters in polarizable molecular mechanical force fields that play pivotal roles in determining model transferability across different electrostatic environments. In an earlier work, the atomic polarizabilities were obtained by fitting them to the B3LYP/aug-cc-pvtz molecular polarizability tensors of mainly small molecules. Taking advantage of the recent PCMRESPPOL method, we refine the atomic polarizabilities for condensed-phase simulations using a polarizable Gaussian Multipole (pGM) force field.

Deep Learning Predicts Non-Normal Transmission Distributions in High-Field Asymmetric Waveform Ion Mobility (FAIMS) Directly from Peptide Sequence.

Peptide ion mobility adds an extra dimension of separation to mass spectrometry-based proteomics. The ability to accurately predict peptide ion mobility would be useful to expedite assay development and to discriminate true answers in a database search. There are methods to accurately predict peptide ion mobility through drift tube devices, but methods to predict mobility through high-field asymmetric waveform ion mobility (FAIMS) are underexplored.

Foliar spray double-stranded RNA targeting HvIAP1 induces high larval and adult mortality in Henosepilachna vigintioctopunctata.

Background: Exogenous double-stranded RNA (dsRNA) has the potential to serve as an effective alternative to conventional chemical pesticides for the control of insect pests, because it can specifically inhibit essential gene expression in these organisms. However, identifying suitable gene targets remains a crucial step in the development of RNA interference (RNAi)-based pest control strategies.

Results: In this study, three apoptosis-related genes were selected to evaluate their potential for RNAi-induced lethality in Henosepilachna vigintioctopunctata via foliar spray dsRNAs.