AXL inhibition prevents RPA2/CHK1-mediated homologous recombination to increase PARP inhibitor sensitivity in hepatocellular carcinoma.

Homologous recombination defects (HRD) render cells fail to repair DNA double-strand break (DSB), which causes synthetic lethality in these cells with punch by poly (ADP-ribose) polymerase (PARP) inhibitors (PARPi). Here, we reveal a receptor tyrosine kinase, AXL, whose inhibition leads to HRD in hepatocellular carcinoma (HCC) cells. AXL is upregulated in HCC tumors, which is positively correlated with low survival rates.

Evaluating somatosensory evoked potentials in predicting treatment outcomes for thoracolumbar spinal compression fractures using closed reduction and over-extension techniques.

Objective: To evaluate the predictive value of somatosensory evoked potentials (SEPs) for the efficacy of closed reduction combined with over-extension reduction technique (PVP) in managing thoracolumbar spinal compression fractures.

Methods: Data were collected from 125 patients who underwent closed reduction with PVP and SEP monitoring from February 2021 to July 2023. We evaluated surgery success rates, incidence of bone cement leakage, and patient recovery outcomes including vertebral anterior height, Oswestry Disability Index (ODI), and Cobb angle restoration.

Impact of High-Temperature Feeds on Gut Microbiota and MAFLD.

The purpose of this study is to investigate the effects of non-obese MAFLD on the gut microbiota and metabolic pathways caused by high-temperature processed meals. It was decided to divide the eighteen male Sprague-Dawley rats into three groups: the control group, the dry-fried soybeans (DFS) group, and the high-fat diet (HFD) group. Following the passage of twelve weeks, a series of physical, biochemical, histological, and microbiological examinations were carried out.

Effects of Medik polysaccharide derived from different regions on the intestinal immune functions of lambs.

Plant polysaccharide are widely studied as potential prebiotics because of their potential to protect and enhance the immunity of lambs. In this study, the polysaccharide content of Medik from Aksu (AK) and Shanshan (SS) at different cutting periods was determined, and the functions of Medik polysaccharide were investigated to useas an immunomodulator. Our results indicated that the content of Medik polysaccharide is the highest at the maturity stage, and the polysaccharide content of Medik produced in Shanshan area is higher as compared to the Aksu area.

miR-520e and its promoter region DNA methylation as potential biomarkers in atherosclerosis.

In atherosclerosis, DNA methylation plays a key regulatory role in the expression of related genes. However, the molecular mechanisms of these processes in human umbilical vein endothelial cells (HUVECs) are unclear. Here, using high-throughput sequencing from the Infinium HumanMethylation450 assay, we manifested that the cg19564375 methylation of miR-520e promoter region in the peripheral blood of acute coronary syndrome (ACS) patients was higher than that of healthy controls.

Light-induced β-hydroxy sulfone synthesis in DNA-encoded libraries.

We here describe a visible-light photooxidation of sulfinate salts with common alkenes to yield β-hydroxy sulfones on DNA. This process demonstrates a broad substrate compatibility and achieves conversion rates ranging from moderate to excellent. Most importantly, it presents a straightforward, efficient, and metal-free approach for synthesizing Csp-rich DNA-encoded libraries.

PTOV1-AS1 desensitizes colorectal cancer cells to 5-FU through depressing miR-149-5p to activate the positive feedback loop with Wnt/β-catenin pathway.

5-Fluorouracil is a commonly used chemotherapy drug for colorectal cancer. Resistance to 5-Fluorouracil remains a challenge. This research aimed to explore the mechanism of 5-Fluorouracil resistance in colorectal cancer.

Constructive on-DNA Thiol Aerial Oxidization for DNA-Encoded Library Synthesis.

A novel on-DNA oxidative disulfide formation method has been developed. Under ambient conditions, the methodology showcased wide applicability and swift implementation in routine DNA-encoded library synthesis to access pharmaceutically relevant motifs.

On-DNA Morita-Baylis-Hillman Reaction: Accessing Targeted Covalent Inhibitor Motifs in DNA-Encoded Libraries.

We herein present the first application of the on-DNA Morita-Baylis-Hillman (MBH) reaction for the creation of pharmaceutically relevant targeted covalent inhibitors (TCIs) with an α-hydroxyl Michael acceptor motif. Adapting a DNA-compatible organocatalytic process, this MBH reaction for covalent selection-capable DNA encoded library (DEL) synthesis grants access to densely functionalized and versatile precursors to explore novel chemical space for molecule recognition in drug discovery. Most importantly, this methodology sheds light on potentially unexpected reaction outcomes of the MBH reaction.

Development of On-DNA Cyclic Imide Synthesis for DNA Encoded Library Construction.

Here, we describe a novel method for the on-DNA synthesis of cyclic imides, an important class of molecules that includes several well-known medications. Significantly, the new method enabled on-DNA synthesis under mild conditions with high conversions and a broad functional group tolerance, utilizing ubiquitous bifunctional amines and bis-carboxylic acid, or alkyl halides, and therefore served as the linchpin for DNA encoded library (DEL) synthesis. The mechanism study of off-DNA and on-DNA chemical transformations revealed unique insights in contrast to conventional chemical transformation.

Optimizing the fuel economy of hydrostatic power-split system in continuously variable tractor transmission.

The aim of this study is to enhance the fuel economy of a continuously variable tractor transmission by analyzing its energy and fuel consumption. First, we present the principle of a self-developed tractor transmission based on power splitting and examine its parasitic power characteristics. Next, we construct a mathematical model of the hydraulic system, mechanical system, and entire transmission, calibrating the model to ensure the accuracy of subsequent results.

Bovine pulmonary surfactant alleviates inflammation and epithelial cell apoptosis in the early phase of lipopolysaccharide-induced acute lung injury in rats.

We investigate the impact of bovine pulmonary surfactant (PS) on LPS-induced ALI in vitro and in vivo to improve recognition and prevent mortality in sepsis-induced ALI. Primary alveolar type II (AT2) cells were treated with LPS alone or in combination with PS. Cell morphology observation, CCK-8 proliferation assay, flow cytometry apoptosis assay, and ELISA for inflammatory cytokine levels were performed at different time points after treatment.

Spermine synthase () serves as a prognostic biomarker in head and neck squamous cell carcinoma: a bioinformatics analysis.

Background: Head and neck squamous cell carcinoma (HNSC) is an aggressive type of cancer that lacks early detection, and therefore, has a low 5-year survival rate. The spermine synthase () gene has been shown to be associated with Snyder-Robinson syndrome and poor prognosis of multiple cancers; however, its regulatory role in HNSC has never been investigated. Therefore, we explored the potential predictive value of in HNSC.

Short-Term Exposure of PM and Epigenetic Aging: A Quasi-Experimental Study.

Epigenetic age (EA) is an emerging DNA methylation-based biomarker of biological aging, but whether EA is causally associated with short-term PM exposure remains unknown. We conducted a quasi-experimental study of 26 healthy adults to test whether short-term PM exposure accelerates seven EAs with three health examinations performed before, during, and after multiple PM pollution waves. Seven EAs were derived from the DNA methylation profiles of the Illumina HumanMethylationEPIC BeadChip from CD4+ T-helper cells.

N-Alkyl Linkers for DNA-Encoded Chemical Libraries.

A series of novel N-alkyl linkers that connect small-molecule library members with their encoding DNA oligonucleotides has been developed. In comparison with the standard amide linker (usually constructed with oligo-AOP-NH ), the N-alkyl linker is not only more chemically stable, but also provides better structural diversity at the linkage point. Chemical variety in the vicinity of the polyglycol terminus, in particular, could affect binding interactions with the target protein.

PHF5A promotes colorectal cancerprogression by alternative splicing of TEAD2.

Dysregulated alternative splicing (AS) plays critical roles in driving cancer progression, and the underlying mechanisms remain largely unknown. Here, we demonstrated that PHF5A, a component of U2 small nuclear ribonucleoproteins, was frequently upregulated in colorectal cancer (CRC) samples and associated with poor prognosis. PHF5A promoted proliferation and metastasis of CRC cells and .

Submucosal hematoma with a wide range of lesions, severe condition and atypical clinical symptoms: A case report.

Background: Submucosal hematoma (SH) is one of the rare causes of upper gastrointestinal bleeding. As a rare and critical disease in clinical practice, it should be paid more attention to by clinicians to avoid missed diagnosis and misdiagnosis. Most of the esophageal submucosal hematomas have clear causes, including retrosternal pain, dysphagia, Here, we report a rare case of SH extending from the hypopharynx to the lower esophagus caused by oral administration of hirudin and panax notoginseng powder, with atypical clinical manifestation.

Cardiorespiratory responses in healthy young adults with exposure to indoor airborne PAEs: A randomized, crossover trial of air purification.

Background: Phthalic acid esters (PAEs) are widely used as plasticizers in industrial process and consumer products. Nowadays, PAEs are ubiquitous in the environment and are reported to be associated with cardiorespiratory diseases. However, studies about the association between indoor airborne PAEs exposure and cardiorespiratory health were limited, and the potential biological mechanism remains under-recognized.

Urinary metabolites of polycyclic aromatic hydrocarbons after short-term fine particulate matter exposure: A randomized crossover trial of air filtration.

Research on the relationship between short-term exposure to fine particulate matter (PM) and urinary metabolites of polycyclic aromatic hydrocarbons (PAHs) is sparse in the nonoccupationally exposed populations. A quasi-experimental observation of haze events nested within a randomized crossover trial of alternative 1-week real or sham indoor air filtration was conducted to evaluate the associations of urinary monohydroxy-PAHs (OH-PAHs) with short-term exposure to PM and PM-bound PAHs. The study was conducted among 57 healthy college students in Beijing, China.

Effects of air purification of indoor PM on the cardiorespiratory biomarkers in young healthy adults.

Ambient fine particulate matter (PM ), as one of the predominant air pollutants, has achieved effective control in recent years in China. Whether the use of indoor air purifiers is still necessary needs further exploration. A randomized crossover trial was conducted in 54 healthy students in Beijing, China.

Micromechanical model for the ferromagnetic shape memory alloy-epoxy resin composite considering variant reorientation and magneto-mechanical coupling.

The mechanical and magnetic properties of Ferromagnetic Shape Memory Alloy-Epoxy Resin (FSMA-ER) composite which is a new kind of functional composite material are investigated in this work. Based on the Mori-Tanaka method and equivalent inclusion theory of the micromechanics, a micromechanical constitutive model in the form of tensor for this new composite is established, which considers the interaction between different variants in FSMA, as well as the interaction between FSMA and epoxy resin. The mechanical and magnetic behavior of the FSMA-ER composite under complex loads can be well described by this model.

FAP-Targeted Photodynamic Therapy Mediated by Ferritin Nanoparticles Elicits an Immune Response against Cancer Cells and Cancer Associated Fibroblasts.

Cancer-associated fibroblasts (CAFs) are present in many types of tumors and play a pivotal role in tumor progression and immunosuppression. Fibroblast-activation protein (FAP), which is overexpressed on CAFs, has been indicated as a universal tumor target. However, FAP expression is not restricted to tumors, and systemic treatment against FAP often causes severe side effects.

Untargeted metabolomics characteristics of nonobese nonalcoholic fatty liver disease induced by high-temperature-processed feed in Sprague-Dawley rats.

Background: Nonalcoholic fatty liver disease (NAFLD) has become one of the most common chronic liver diseases in the world. In our early clinical data and questionnaire analysis of NAFLD, it was found that the body mass index of some patients did not meet the diagnostic criteria for overweight or obesity. The consumption of high-temperature-processed foods such as fried food, hot pot and barbecue is closely related to the occurrence of nonobese NAFLD.