Glabridin restore the sensitivity of colistin against mcr-1-positive Escherichia coli by polypharmacology mechanism.

The clinical effectiveness of colistin against multidrug-resistant Gram-negative pathogen infections has been threatened by the emergence of the plasmid-mediated colistin-resistant gene mcr-1. This development underscores the urgent need for innovative therapeutic strategies that target resistance mechanisms. In this study, we demonstrated that glabridin can restore the sensitivity of colistin to mcr-1-positive Escherichia coli (E.

When multiple instance learning meets foundation models: Advancing histological whole slide image analysis.

Deep multiple instance learning (MIL) pipelines are the mainstream weakly supervised learning methodologies for whole slide image (WSI) classification. However, it remains unclear how these widely used approaches compare to each other, given the recent proliferation of foundation models (FMs) for patch-level embedding and the diversity of slide-level aggregations. This paper implemented and systematically compared six FMs and six recent MIL methods by organizing different feature extractions and aggregations across seven clinically relevant end-to-end prediction tasks using WSIs from 4044 patients with four different cancer types.

Single-cell RNA sequencing reveals the role of immune-related autophagy in aseptic loosening of biomaterials bone-implant.

This study employed single-cell RNA sequencing (scRNA-seq) to investigate the role of immune-related autophagy in the mechanism of aseptic loosening (AL) of biomaterial bone-implant. Through single-cell analysis of AL tissues, we mapped the cellular landscape, revealing various cell types and their characteristics within the context of AL. Our study specifically targeted immune cell subpopulations, including macrophages and neutrophils.

Targeted therapy for glioblastoma utilizing hyaluronic acid-engineered liposomes for adriamycin delivery.

Glioblastoma (GBM) is a malignant tumor with highly heterogeneous and invasive characteristics leading to a poor prognosis. The CD44 molecule, which is highly expressed in GBM, has emerged as a highly sought-after biological marker. Therapeutic strategies targeting the cell membrane protein CD44 have emerged, demonstrating novel therapeutic potential.

PTPN23-dependent activation of PI3KC2α is a therapeutic vulnerability of BRAF-mutant cancers.

BRAF mutations drive initiation and progression of various tumors. While BRAF inhibitors are effective in BRAF-mutant melanoma patients, intrinsic or acquired resistance to these therapies is common. Here, we identify non-receptor-type protein tyrosine phosphatase 23 (PTPN23) as an alternative effective target in BRAF-mutant cancer cells.

RYR3 Variants Are Potentially Associated With Idiopathic (Non-Lesional) Partial Epilepsy/Susceptibility of Seizures, Toward Understanding the Gene-Disease Association by Genetic Dependent Nature.

The RYR3 gene encodes a brain-type ryanodine receptor that functions to release calcium from intracellular storage and plays an essential role in calcium signaling. The associations between RYR3 variants and brain disorders remain unknown. We performed whole-exome sequencing in patients with idiopathic (non-lesional) partial epilepsy of unknown etiology.

Bacterial extracellular vesicles in the initiation, progression and treatment of atherosclerosis.

Atherosclerosis is the primary cause of cardiovascular and cerebrovascular diseases. However, current anti-atherosclerosis drugs have shown conflicting therapeutic outcomes, thereby spurring the search for novel and effective treatments. Recent research indicates the crucial involvement of oral and gastrointestinal microbiota in atherosclerosis.

Bioprinted Fibroblast Mediated Heterogeneous Tumor Microenvironment for Studying Tumor-Stroma Interaction and Drug Screening.

Cancer-associated fibroblasts (CAFs) are crucial stromal cells in the tumor microenvironment, affecting cancer growth, angiogenesis, and matrix remodeling. Developing an effective in vitro tumor model that accurately recapitulates the dynamic interplay between tumor and stromal cells remains a challenge. In this study, a 3D bioprinted fibroblast - mediated heterogeneous breast tumor model was created, with tumor cells and fibroblasts in a bionic matrix.

Ischemic Area-Targeting and Self-Monitoring Nanoprobes Ameliorate Myocardial Ischemia/Reperfusion Injury by Scavenging ROS and Counteracting Cardiac Inflammation.

Precise and effective management of myocardial ischemia/reperfusion injury (MIRI) is still a formidable challenge in clinical practice. Additionally, real-time monitoring of drug aggregation in the MIRI region remains an open question. Herein, a drug delivery system, hesperadin and ICG assembled in PLGA-Se-Se-PEG-IMTP (HI@PSeP-IMTP), is designed to deliver hesperadin and ICG to the MIRI region for in vivo optical imaging tracking and to ameliorate MIRI.

A Highly Bioactive Organic-Inorganic Nanoparticle for Activating Wnt10b Mediated Osteogenesis by Specifically Anchor CCN3 Protein.

The rapid and efficient bone regeneration is still in unsatisfactory outcomes, demonstrating alternative strategy and molecular mechanism is necessary. Nanoscale biomaterials have shown some promising results in enhancing bone regeneration, however, the detailed interaction mechanism between nanomaterial and cells/tissue formation is not clear. Herein, a molecular-based inorganic-organic nanomaterial poly(citrate-siloxane) (PCS) is reported which can rapidly enhance osteogenic differentiation and bone formation through a special interaction with the cellular surface communication network factor 3 (CCN3), further activating the Wnt10b/β-catenin signaling pathway.

Platelet membrane biomimetic nanomedicine induces dual glutathione consumption for enhancing cancer radioimmunotherapy.

Radiotherapy (RT) is one of the most common treatments for cancer. However, intracellular glutathione (GSH) plays a key role in protecting cancer from radiation damage. Herein, we have developed a platelet membrane biomimetic nanomedicine (PMD) that induces double GSH consumption to enhance tumor radioimmunotherapy.

An oral microbiota-based deep neural network model for risk stratification and prognosis prediction in gastric cancer.

Background: This study aims to develop an oral microbiota-based model for gastric cancer (GC) risk stratification and prognosis prediction.

Methods: Oral microbial markers for GC prognosis and risk stratification were identified from 99 GC patients, and their predictive potential was validated on an external dataset of 111 GC patients. The identified bacterial markers were used to construct a Deep Neural Network (DNN) model, a Random Forest (RF) model, and a Support Vector Machine (SVM) model for predicting GC prognosis.

Biomimetic bioreactor for potentiated uricase replacement therapy in hyperuricemia and gout.

Introduction: Uricase replacement therapy is a promising approach for managing hyperuricemia and gout but is hindered by challenges such as short blood circulation time, reduced catalytic activity, and excessive hydrogen peroxide (HO) production. These limitations necessitate innovative strategies to enhance therapeutic efficacy and safety.

Methods: We designed and synthesized RBC@SeMSN@Uri, a red blood cell-coated biomimetic self-cascade bioreactor, which encapsulates uricase (Uri) and a selenium-based nano-scavenger (SeMSN) within RBC membranes.

Ponatinib alleviates non-alcoholic steatohepatitis through TFEB-mediated autophagy.

Objective: Non-alcoholic steatohepatitis (NASH) is a progressive liver disease with lipid accumulation, inflammation, and liver fibrosis. Ponatinib, a third-generation tyrosine kinase inhibitors for the treatment of chronic myeloid leukemia, was found to improve metabolic disorders in mice. However, the role of ponatinib in liver inflammation and fibrosis remains to be elucidated.

Application of MRI image segmentation algorithm for brain tumors based on improved YOLO.

Objective: To assist in the rapid clinical identification of brain tumor types while achieving segmentation detection, this study investigates the feasibility of applying the deep learning YOLOv5s algorithm model to the segmentation of brain tumor magnetic resonance images and optimizes and upgrades it on this basis.

Methods: The research institute utilized two public datasets of meningioma and glioma magnetic resonance imaging from Kaggle. Dataset 1 contains a total of 3,223 images, and Dataset 2 contains 216 images.

The Superior Glenoid Humeral Ligament's Role in Superior Labrum Anterior-Posterior Lesions and Subtype Classification Based on Arthroscopic Views: A Multicenter, Retrospective Study.

Background: Superior labrum anterior-posterior (SLAP) lesions are common shoulder injuries. The 10-type classification system has been widely used to diagnose SLAP lesions since it was proposed. However, growing evidence from arthroscopic studies indicates the existence of many SLAP lesions, especially those associated with superior glenoid humeral ligament (SGHL) injuries, that were not included in the initial classification.

Poorly controlled type II diabetes mellitus significantly enhances postoperative chemoresistance in patients with stage III colon cancer.

Background: Type II diabetes mellitus (T2DM) has been associated with increased risk of colon cancer (CC) and worse prognosis in patients with metastases. The effects of T2DM on postoperative chemoresistance rate (CRR) and long-term disease-free survival (DFS) and overall survival (OS) in patients with stage III CC who receive curative resection remain controversial.

Aim: To investigate whether T2DM or glycemic control is associated with worse postoperative survival outcomes in stage III CC.

Involvement of the posterior limb of the internal capsule independently predicts the prognosis of patients with basal ganglia and thalamic hemorrhage.

Background: Intracerebral hemorrhage (ICH) is the most lethal and devastating subtype of stroke. Basal ganglia hemorrhage and thalamic hemorrhage are the most common types of ICH, accounting for 50-70% of all ICH cases, leading to disability and death, and it involves the posterior limb of the internal capsule to varying degrees. In this study, we investigated the impact of varying degrees of the involvement of the posterior limb of the internal capsule on the prognosis of patients with basal ganglia and thalamic ICH and assessed whether it improves the predictive accuracy of the max-ICH score, an existing scale for ICH functional outcome.

Development of a droplet digital PCR method for the detection of .

Background: Human infection with is mainly manifested as non-gonococcal urethritis, where it can lead to cervicitis, premature rupture of membranes and abortion in women, as well as infertility in males, which becomes a major problem in clinical diagnosis and treatment. At present, real-time fluorescence quantitative PCR and culture are the two main methods for detecting UU. The real-time fluorescence quantitative PCR method is cumbersome and cannot accomplish absolute quantification on nucleic acids, while the cultivation method has limitations such as low sensitivity and being time-consuming.

Exploring the Anti-PANoptosis Mechanism of Dachaihu Decoction Against Sepsis-Induced Acute Lung Injury: Network Pharmacology, Bioinformatics, and Experimental Validation.

Background: Dachaihu decoction (DCHD) is a common Chinese medicine formula against sepsis-induced acute lung injury (SALI). PANoptosis is a novel type of programmed cell death. Nevertheless, The mechanisms of DCHD against SALI via anti-PANoptosis remains unknown.

Analysis and Validation of Autophagy-Related Gene Biomarkers and Immune Cell Infiltration Characteristic in Bronchopulmonary Dysplasia by Integrating Bioinformatics and Machine Learning.

Background: Autophagy and immunity play important regulatory roles in lung developmental disorders. However, there is currently a lack of bioinformatics analysis on autophagy-related genes (ARGs) and immune infiltration in bronchopulmonary dysplasia (BPD). We aim to screen and validate the signature genes of BPD by bioinformatics and in vivo experiment.

An automatic and real-time echocardiography quality scoring system based on deep learning to improve reproducible assessment of left ventricular ejection fraction.

Background: Echocardiography can conveniently, rapidly, and economically evaluate the structure and function of the heart, and has important value in the diagnosis and evaluation of cardiovascular diseases (CVDs). However, echocardiography still exhibits significant variability in image acquisition and diagnosis, with a heavy dependency on the operator's experience. Image quality affects disease diagnosis in the later stage, and even image quality assessment still has variability in human evaluation.

Assessment of intratumor heterogeneity for preoperatively predicting the invasiveness of pulmonary adenocarcinomas manifesting as pure ground-glass nodules.

Background: The increased use of low-dose computed tomography (CT) for lung cancer screening has improved the detection of ground-glass nodules. However, as the clinical utility of CT findings to predict the invasiveness of pure ground-glass nodules (pGGNs) is currently limited, differentiating pGGNs that indicate invasive adenocarcinoma (IAC) from those that represent other histological entities is challenging. We aimed to quantify intratumor heterogeneity of lung adenocarcinomas characterized by pGGNs on CT to assess its efficacy in predicting IACs before surgery.

Correlations of anterior and posterior corneal parameters in Chinese myopic patients: a retrospective multicenter study.

Background: Whether the correlations between anterior and posterior corneal parameters vary according to different conditions is unknown. We aimed to investigate the anterior-to-posterior correlations of corneal parameters according to different refractive status and anterior segment dimension.

Methods: A total of 8,365 myopic eyes undergoing refractive surgery between 2017 and 2019 from multiple ophthalmic centers were consecutively included in the study.

F-FAPI-42 PET/CT for preoperatively identifying intrahepatic cholangiocarcinoma and hepatocellular carcinoma.

Background: Accurately differentiating hepatocellular carcinoma (HCC) from intrahepatic cholangiocarcinoma (ICC) is essential for therapeutic decision-making. This study aimed to explore the value of Fluor 18 (F)-conjugated fibroblast-activation protein inhibitor (FAPI-42) positron emission tomography-computed tomography (PET/CT) in distinguishing HCC from ICC preoperatively.

Methods: Patients with suspected intrahepatic lesions who underwent F-FAPI-42 PET/CT were retrospectively assessed and placed into an HCC group and an ICC group based on postoperative pathology.