An Rcs Stress-Based High-Throughput Screen Reveals Novel Gyrase Inhibitors as Indirect Inducers of Cell Envelope Stress in Gram-Negative Bacteria.

The highly impermeable cell envelope of Gram-negative bacteria is an important hurdle to the development of novel antibacterials. However, compounds that disrupt the integrity of the cell envelope can act as potent antibiotics by directly inhibiting cell growth and viability or by enhancing the penetration of other, larger antibiotics otherwise unable to pass this barrier. To identify such novel compounds, we used the European Lead Factory compound libraries to screen >500,000 small molecules for inducing the Rcs cell envelope stress response in .

Targeting the KLF5/PI3K/AKT axis as a therapeutic strategy to overcome neoadjuvant chemoresistance in colorectal cancer.

Background: Oxaliplatin-based neoadjuvant chemotherapy (NAC) is the standard treatment for advanced colorectal cancer (CRC), yet resistance to NAC poses a significant clinical challenge.

Methods: To investigate the mechanisms of chemoresistance, we analyzed single-cell RNA sequencing (scRNA-seq) data from CRC patients undergoing NAC. Comprehensive analyses, including InferCNV, differentially expressed genes analysis, pathway enrichment, cell communication, and SCENIC were performed.

MITF promotes MFN2-dependent mitochondrial fusion to protect retinal pigment epithelial cells from mitochondrial damage.

There is growing indication that protecting the retinal pigment epithelium (RPE) against mitochondrial damage is crucial for preventing RPE cell dysfunction and retinal degeneration. However, the molecular mechanisms remain largely unknown. Here, we show that microphthalmia-associated transcription factor (MITF), a potent antioxidant inducer in RPE, promotes mitochondrial fusion in RPE cells and protects them from mitochondrial uncoupler carbonyl cyanide 3-chlorophenylhydrazone (CCCP)-induced mitochondrial damage in ARPE-19 or mouse primary RPE cells ex vivo and Mitf heterozygous mice (Mitf-/+), Mitf-overexpressing transgenic mice (Dct-Mitf) or AAV mediated MITF overexpression mice in vivo.

Impacts of human activities on vegetation dynamics amid climate change: A case study of the Hanjiang River Basin (China).

Investigating the interplay between vegetation, climate change, and anthropogenic activities is essential for advancing global environmental research. The Hanjiang River Basin exhibits heightened susceptibility to anthropogenic influences that markedly alter its ecological dynamics. This study utilized MODIS NDVI data (2002-2022) alongside precipitation and temperature data to evaluate the distinct impacts of climatic factors and anthropogenic activities on NDVI variability by applying Pearson correlation and residual analysis.

Design, Synthesis, and Antibacterial Evaluation of Rifampicin-Siderophore Conjugates.

The growing concern over antibiotic resistance has sparked increased attention toward developing alternative antibiotic strategies. One promising approach, known as the "Trojan horse" strategy, involves the use of siderophores to hijack bacteria's iron transport systems as a way of delivering antibiotics inside the bacterial cell. This method is particularly promising in tackling Gram-negative bacteria, which have an outer membrane that many antibiotics cannot penetrate.

Investigating the Impact of the Gut Microbiota on Nasal Polyp Development: Insights from Mendelian Randomization.

Introduction: Chronic rhinosinusitis with nasal polyps has a high post-surgery recurrence, suggesting complex pathology. However, research into underlying mechanisms and contributing factors, such as gut microbiota, is lacking. This study aimed to investigate the causal relationship between nasal polyps and gut microbiota, and to identify and quantify the potential mediating roles of metabolic pathways.

Genotype-dependent induction of embryogenic callus and programmed cell death in Korean pine.

Background: The strong genotype dependence of embryogenic callus (EC) induction limits the high-frequency regeneration of Korean pine (Pinus koraiensis) via somatic embryogenesis (SE).

Methods: We examined the morphological and histocytological features of various callus types using external morphology, microstructure, and ultrastructure analyses. To assess their embryogenic potential, we conducted somatic embryogenesis (SE) experiments.

Tyrosine kinase inhibitors induce cardiotoxicity by causing Ca overload through the inhibition of phosphoinositide 3-kinase activity.

Background: Tyrosine kinase inhibitors (TKIs) are commonly used in cancer treatment, but their off-target effects can lead to serious cardiotoxicity. Our previous studies have revealed that upregulation of phosphoinositide 3-kinase (PI3K) confers considerable protection against calcium (Ca) disorders and cardiac dysfunction induced by sunitinib. However, the involvement of PI3K inhibition in the prevention of cardiomyocyte contraction induced by other TKIs remains unclear.

A large-scale retrospective study in metastatic breast cancer patients using circulating tumour DNA and machine learning to predict treatment outcome and progression-free survival.

Monitoring levels of circulating tumour-derived DNA (ctDNA) provides both a noninvasive snapshot of tumour burden and also potentially clonal evolution. Here, we describe how applying a novel statistical model to serial ctDNA measurements from shallow whole genome sequencing (sWGS) in metastatic breast cancer patients produces a rapid and inexpensive predictive assessment of treatment response and progression-free survival. A cohort of 149 patients had DNA extracted from serial plasma samples (total 1013, mean samples per patient = 6.

Uncovering the genetic mechanism of rind color trait in watermelon using fine mapping and comparative transcriptomic analysis.

The rind color of watermelon fruit is a significant trait that directly affects consumer acceptability. However, the genetic regulatory mechanisms underlying rind color remain poorly understood. In this study, we crossed two differentiated watermelon lines (K2Q "female parent line with a light green rind" and K2S "male parent line with a dark green rind") and developed segregated F mapping populations.

Integration and functionality of human iPSC-derived microglia in a chimeric mouse retinal model.

Introduction: Microglia, the resident immune cells of the central nervous system, play a pivotal role in maintaining homeostasis, responding to injury, and modulating neuroinflammation. However, the limitations of rodent models in accurately representing human microglia have posed significant challenges in the study of retinal diseases.

Methods: PLX5622 was used to eliminate endogenous microglia in mice through oral and intraperitoneal administration, followed by transplantation of human induced pluripotent stem cell-derived microglia (hiPSC-microglia, iMG) into retinal explants to create a novel ex vivo chimeric model containing xenotransplanted microglia (xMG).

Catheter Ablation of Idiopathic Left Anterior Fascicular Ventricular Arrhythmias: Predicting Origin Sites via Mapping and Electrocardiography.

Background: Idiopathic ventricular arrhythmias (VAs) arising from the left anterior fascicle (LAF) are uncommonly seen, and their characteristics still need to be sufficiently investigated. This study aimed to conclude these VAs' characteristics and explore efficient ablation strategies.

Methods: Data were analyzed from 118 patients undergoing successful catheter ablation for LAF VAs.

Safety and efficacy of inclisiran in treating hypercholesterolemia: A systemic review and meta-analysis.

Aims: To evaluate the efficacy and safety of inclisiran in the treatment of hypercholesterolemia.

Date Synthesis: Randomized controlled trials comparing inclisiran with a placebo were searched until April 2024. Overall, 8 studies involving 4947 patients were included.

Knowledge, attitudes, and practice of physicians and pharmacists regarding the prevention and treatment of cardiovascular toxicity associated with cancer treatment.

This study aimed to explore physicians' and pharmacists' knowledge, attitudes, and practice (KAP) regarding the prevention and treatment of cardiovascular toxicity associated with cancer treatment. A multicenter cross-sectional study included physicians and pharmacists between April 2023 and June 2023. The study included 918 participants (514 physicians and 404 pharmacists).

Synthesis and Evaluation of Carbapenem/Metallo-β-Lactamase Inhibitor Conjugates.

Antibiotics, particularly the β-lactams, are a cornerstone of modern medicine. However, the rise of bacterial resistance to these agents, particularly through the actions of β-lactamases, poses a significant threat to our continued ability to effectively treat infections. Metallo-β-lactamases (MBLs) are of particular concern due to their ability to hydrolyze a wide range of β-lactam antibiotics including carbapenems.

Preparing Retinal Organoid Samples for Transmission Electron Microscopy.

Retinal organoids (ROs) are a three-dimensional culture system mimicking human retinal features that have differentiated from induced pluripotent stem cells (iPSCs) under specific conditions. Synapse development and maturation in ROs have been studied immunocytochemically and functionally. However, the direct evidence of the synaptic contact ultrastructure is limited, containing both special ribbon synapses and conventional chemical synapses.

Development of a multiple cross displacement amplification combined with nanoparticles-based biosensor assay for rapid and sensitive detection of Streptococcus pyogenes.

Background: S. pyogenes, is a primary pathogen that leads to pharyngitis and can also trigger severe conditions like necrotizing fasciitis and streptococcal toxic shock syndrome (STSS), often resulting in high mortality rates. Therefore, prompt identification and appropriate treatment of S.

Texture characterization and classification of polarized images based on multi-angle orthogonal difference.

The Local Binary Pattern (LBP) and its variants are capable of extracting image texture and have been successfully applied to classification. However, LBP has not been used to extract and describe the texture of polarized images, and simple LBP cannot characterize the polarized texture information from different polarizations of angles. In order to solve these problems, we propose a new multi-angle orthogonal difference polarization image texture descriptor (MODP_ITD) by analyzing the relationship between the difference of orthogonal difference polarization images from different angles and the pixel intensity distribution in the local neighborhood of images from different angles.

Illuminated fulvic acid stimulates denitrification and As(III) immobilization in flooded paddy soils via an enhanced biophotoelectrochemical pathway.

Fulvic acid (FA) is a representative photosensitive dissolved organic matter (DOM) compound that occurs naturally in paddy soils. In this study, the effect of a FA + nitrate treatment (0, 4 and 8 mg/L FA + 20 mmol/L nitrate) on denitrification and As(III) immobilization in flooded paddy soils was assessed under dark and intermittently illuminated conditions (12 h light+12 h dark). The FA input stimulated denitrification in illuminated soils (~100 % of nitrate removal within 6 days) compared to dark conditions (~92 % nitrate removal after 6 days).

Novel Endophytic sp. GSE25 Strain Significantly Controls and Reduces Deoxynivalenol in Wheat.

Fusarium heading blight (FHB) is a devastating disease in wheat, primarily caused by field invasion of . Due to the scarcity of resistant wheat varieties, the agricultural sector resorts to chemical fungicides to control FHB incidence. On the other hand, biocontrol represents a promising, eco-friendly approach aligned with sustainable and green agriculture concepts.

Phylogenetic Variation of Gene and Development of PCR-RFLP Analysis for the Identification of NX Genotypes in Species Complex.

NX toxins have been described as a novel group of type A trichothecenes produced by members of the species complex (FGSC). Differences in structure between NX toxins and the common type B trichothecenes arise from functional variation in the trichothecene biosynthetic enzyme Tri1 in the FGSC. The identified highly conserved changes in the gene can be used to develop specific PCR-based assays to identify the NX-producing strains.

DNA damage induced by CDK4 and CDK6 blockade triggers anti-tumor immune responses through cGAS-STING pathway.

CDK4/6 are important regulators of cell cycle and their inhibitors have been approved as anti-cancer drugs. Here, we report a STING-dependent anti-tumor immune mechanism responsible for tumor suppression by CDK4/6 blockade. Clinical datasets show that in human tissues, CDK4 and CDK6 are over-expressed and their expressions are negatively correlated with patients' overall survival and T cell infiltration.