Discovery of Phosphorylated Peptidomimetics Targeting Cbl-b SH2 Domain as Orthosteric Cbl-b Inhibitors by an Optimized Fluorescence Polarization Competition Assay.

Casitas B-lineage lymphoma-b (Cbl-b), a pivotal negative regulator of TCR signaling, is highly expressed in immune cells. Its inhibition potentiates immune-mediated antitumor effects. Herein, we constructed a potent fluorescent tracer, , based on the Cbl-b peptide inhibitor Utilizing this tracer, we established a fluorescence polarization (FP) assay with enhanced sensitivity, discriminative capacity, and precision for the activity evaluation and high-throughput screening of orthosteric Cbl-b Src homology 2 (SH2) domain inhibitors.

TSA-SAB co-loaded liposome self-dissolving microneedle synergistic delivery system: a breakthrough dual-drug loading strategy for multi-target therapy of hypertrophic scars.

The treatment of hypertrophic scars is constrained by inefficient transdermal delivery and challenges in co-delivery of multiple drugs. Although tanshinone IIA and salvianolic acid B exhibit multi-target antifibrotic potential, their divergent physicochemical properties limit combined application. This study proposes a novel transdermal system integrating co-loaded liposomes with dissolving microneedles (DMNs).

Radiomics analysis for the early diagnosis of common sexually transmitted infections and skin lesions.

Early identification of sexually transmitted infection (STI) symptoms can prevent subsequent complications and improve STI control. We analysed 597 images from STIAtlas and categorised the images into four typical STIs and two skin lesions by the anatomical sites of infections. We first applied nine image filters and 11 machine-learning image classifiers to the images.

Hospital type and clinical outcomes in peritoneal dialysis: Findings from the PDTAP study.

BackgroundThere are inequalities in resource allocation and services across peritoneal dialysis (PD) centers in China. This study aimed to explore the association between hospital type (university-affiliated vs. non-university-affiliated hospitals) and clinical outcomes in PD patients.

Association of air pollutants exposure and increased risk of peritoneal dialysis-related peritonitis: An observational study from PDTAP cohort.

IntroductionAlthough the impact of air pollutants on infectious diseases is well-known, there is limited evidence regarding its effects on peritoneal dialysis (PD) patients. This study aimed to investigate the association between air pollutants and PD-related peritonitis.MethodsThis is an observational study affiliated to the PD Telemedicine-assisted Platform Cohort Study (PDTAP study), which is a national-level cohort study in China.

ERK1-mediated GLYCTK2 phosphorylation promotes fructolysis to sustain glioblastoma survival under glucose deprivation.

Metabolic plasticity sustains glioblastoma (GBM) survival under nutrient stress, yet how fructolytic adaptation compensates for glucose deprivation remains unclear. Here, we identify glycerate kinase 2 (GLYCTK2) as a glucose-sensing metabolic checkpoint that maintains GBM cell viability through ERK1-mediated phosphorylation. Mechanistically, glucose deprivation-activated ERK1 phosphorylates GLYCTK2 at serine 220 directly, which prevents STUB1 (ubiquitin E3 ligase) binding, thereby abrogating the ubiquitination and degradation of GLYCTK2.

Asymmetric interfacial Ru single-atom sites and nanoparticles for promoting the hydrogen evolution reaction in a wide pH range.

Herein, the achieved asymmetric interfacial Ru single-atom sites and nanoparticles in Ru/NPC through the coordination-pyrolysis strategy exhibit remarkable HER activities with small overpotential and low Tafel slope in a wide pH range.

Bioactive natural alkaloid 6-Methoxydihydrosanguinarine exerts anti-tumor effects in hepatocellular carcinoma cells via ferroptosis.

Introduction: Ferroptosis is a form of regulated cell death driven by the accumulation of iron-dependent lipid peroxides, and ferroptosis-mediated cancer therapy has gained considerable attention. Despite emerging evidence that ferroptosis induction effectively suppresses hepatocellular carcinoma (HCC) progression and enhances chemosensitivity, the development of resistance to ferroptosis-targeting therapies remains a critical challenge. Natural active compounds have great potential in cancer treatment.

Associations between iron markers with hemoglobin and outcomes in peritoneal dialysis patients: results from the PDTAP study.

Background And Hypothesis: Iron metabolism markers, such as transferrin saturation (TSAT) and ferritin, are crucial in anemia management in patients with CKD and those undergoing dialysis, yet optimal levels remain unelucidated.

Methods: We conducted a prospective multicenter cohort study using data from the nationwide Peritoneal Dialysis Telemedicine-based Management Platform (PDTAP) to analyze TSAT, ferritin, and hemoglobin (Hb) levels, and their associations with mortality in the peritoneal dialysis (PD) population.

Results: Our study included 4429 PD patients, analyzing data through restricted cubic splines and Cox regression models, adjusted for multiple confounders.

Discovery of Novel Tofacitinib-ADTOH Molecular Hybridization Derivatives for the Treatment of Ulcerative Colitis.

The treatment of ulcerative colitis (UC) has been a major medical challenge due to the lack of safe and effective drugs. Molecular hybridization is a promising strategy for the development of drugs with pleiotropic activity, which has been demonstrated in a wide range of diseases. Tofacitinib has exhibited significant effects on the remission of UC, but a series of adverse effects have occurred during its clinical application.

Exploring artificial intelligence for differentiating early syphilis from other skin lesions: a pilot study.

Background: Early diagnosis of syphilis is vital for its effective control. This study aimed to develop an Artificial Intelligence (AI) diagnostic model based on radiomics technology to distinguish early syphilis from other clinical skin lesions.

Methods: The study collected 260 images of skin lesions caused by various skin infections, including 115 syphilis and 145 other infection types.

Iberverin Downregulates GPX4 and SLC7A11 to Induce Ferroptotic Cell Death in Hepatocellular Carcinoma Cells.

Ferroptosis, a recently elucidated style of regulated cell death, has emerged as a significant area of investigation in cancer biology. Natural active compounds that have anti-cancer effects are promising candidates for cancer prevention. Iberverin, a natural compound derived from var.

MDH2 Promotes Hepatocellular Carcinoma Growth Through Ferroptosis Evasion via Stabilizing GPX4.

The crosstalk between tumor progression and ferroptosis is largely unknown. Here, we identify malate dehydrogenase 2 (MDH2) as a key regulator of ferroptosis. MDH2 deficiency inhibits the growth of hepatocellular carcinoma (HCC) cells and enhances their sensitivity to ferroptosis induced by RAS-selective lethal 3 (RSL3), a compound known to cause ferroptosis.

Natural Product Auraptene Targets SLC7A11 for Degradation and Induces Hepatocellular Carcinoma Ferroptosis.

The natural product auraptene can influence tumor cell proliferation and invasion, but its effect on hepatocellular carcinoma (HCC) cells is unknown. Here, we report that auraptene can exert anti-tumor effects in HCC cells via inhibition of cell proliferation and ferroptosis induction. Auraptene treatment induces total ROS and lipid ROS production in HCC cells to initiate ferroptosis.

Corrosion and Interfacial Contact Resistance of NiTi Alloy as a Promising Bipolar Plate for PEMFC.

Titanium (Ti) is generally considered as an ideal bipolar plate (BPP) material because of its excellent corrosion resistance, good machinability and lightweight nature. However, the easy-passivation property, which leads to increased interfacial contact resistance (ICR) and subsequently decreased cell performance, limits its large-scale commercial application in proton exchange membrane fuel cells (PEMFCs). In this paper, we proposed a NiTi alloy prepared by suction casting as a promising bipolar plate for PEMFCs.

Modified nano zero-valent iron coupling microorganisms to degrade BDE-209: Degradation pathways and microbial responses.

Polybrominated diphenyl ethers (PBDEs) in soil and groundwater have garnered considerable attention owing to the significant bioaccumulation potential and toxicity. Currently, the coupling treatment method of nano zero-valent iron (nZVI) with dehalogenation microorganisms is a research hotspot in the field of PBDE degradation. In this study, various systems were established within anaerobic environments, including the nZVI-only system, microorganism-only system, and the nZVI + microorganisms system.

Cut-off values of haemoglobin and clinical outcomes in incident peritoneal dialysis: the PDTAP study.

Background: To explore the cut-off values of haemoglobin (Hb) on adverse clinical outcomes in incident peritoneal dialysis (PD) patients based on a national-level database.

Methods: The observational cohort study was from the Peritoneal Dialysis Telemedicine-assisted Platform (PDTAP) dataset. The primary outcomes were all-cause mortality, major adverse cardiovascular events (MACE) and modified MACE (MACE+).

Sensitive NIR Fluorescence Identification of Bacteria in Whole Blood with Bioorthogonal Nanoprobes for Early Sepsis Diagnosis.

Sepsis is one of the leading causes of death worldwide. The disease progression of sepsis is very fast, and there is a 7-9% increase in mortality every hour. Therefore, rapid and sensitive detection of pathogenic bacteria is crucial for the timely treatment of sepsis as well as the reduction of mortality.

Structural insights into partner selection for MYB and bHLH transcription factor complexes.

MYB and basic helix-loop-helix (bHLH) transcription factors form complexes to regulate diverse metabolic and developmental processes in plants. However, the molecular mechanisms responsible for MYB-bHLH interaction and partner selection remain unclear. Here, we report the crystal structures of three MYB-bHLH complexes (WER-EGL3, CPC-EGL3 and MYB29-MYC3), uncovering two MYB-bHLH interaction modes.

Telemedicine and Clinical Outcomes in Peritoneal Dialysis: A Propensity-Matched Study.

Introduction: Telemedicine (TM) has shown to provide potential benefits on clinical outcomes in patients with chronic kidney disease but limited evidences published in the peritoneal dialysis (PD) population. This study aimed to explore the long-term effects of TM on the mortality and technique failure.

Methods: The Peritoneal Dialysis Telemedicine-assisted Platform Cohort Study (PDTAP Study) was conducted prospectively in 27 hospitals in China since 2016.