Novel insights from spatial transcriptome analysis in solid tumors.

Since its first application in 2016, spatial transcriptomics has become a rapidly evolving technology in recent years. Spatial transcriptomics enables transcriptomic data to be acquired from intact tissue sections and provides spatial distribution information and remedies the disadvantage of single-cell RNA sequencing (scRNA-seq), whose data lack spatially resolved information. Presently, spatial transcriptomics has been widely applied to various tissue types, especially for the study of tumor heterogeneity. In this review, we provide a summary of the research progress in utilizing spatial transcriptomics to investigate tumor heterogeneity and the microenvironment with a focus on solid tumors. We summarize the research breakthroughs in various fields and perspectives due to the application of spatial transcriptomics, including cell clustering and interaction, cellular metabolism, gene expression, immune cell programs and combination with other techniques. As a combination of multiple transcriptomics, single-cell multiomics shows its superiority and validity in single-cell analysis. We also discuss the application prospect of single-cell multiomics, and we believe that with the progress of data integration from various transcriptomics, a multilayered subcellular landscape will be revealed.

High-Energy Phosphates and Ischemic Heart Disease: From Bench to Bedside.

The purpose of this review is to bridge the gap between clinical and basic research through providing a comprehensive and concise description of the cellular and molecular aspects of cardioprotective mechanisms and a critical evaluation of the clinical evidence of high-energy phosphates (HEPs) in ischemic heart disease (IHD). According to the well-documented physiological, pathophysiological and pharmacological properties of HEPs, exogenous creatine phosphate (CrP) may be considered as an ideal metabolic regulator. It plays cardioprotection roles from upstream to downstream of myocardial ischemia through multiple complex mechanisms, including but not limited to replenishment of cellular energy. Although exogenous CrP administration has not been shown to improve long-term survival, the beneficial effects on multiple secondary but important outcomes and short-term survival are concordant with its pathophysiological and pharmacological effects. There is urgent need for high-quality multicentre RCTs to confirm long-term survival improvement in the future.

The effect of exogenous creatine phosphate on myocardial injury after percutaneous coronary intervention.

OBJECTIVE: To evaluate the effect of exogenous creatine phosphate (CP) on myocardial injury after percutaneous coronary intervention (PCI). METHOD: Four hundred patients were divided to receive conventional therapy (control group) or 3-day intravenous infusion of CP after PCI (CP group). Levels of creatine kinase MB (CK-MB) and troponin I (TnI) were measured before and on postprocedural day 3. RESULTS: Postprocedural CK-MB and TnI in the CP group were significantly increased compared to the control group. In the CP group, 8.0% and 5.0% of patients had an increase in CK-MB 1 to 3 times and >3 times, respectively, which were significantly lower than that of the control group (19.0% and 9.0%, respectively); 12.0% and 10.0% of patients had an increase in TnI 1 to 3 times and >3 times, respectively, which were significantly lower than that of the control group (21.0% and 18.0%, respectively). CONCLUSION: Exogenous CP was helpful to reduce myocardial injury after PCI.

Impact of preprocedural high-sensitivity C-reactive protein on contrast-induced nephropathy in patients undergoing primary percutaneous coronary intervention.

We assessed the impact of preprocedural high-sensitivity C-reactive protein (hsCRP) on the incidence of contrast-induced nephropathy (CIN) in patients with ST-segment elevation myocardial infarction (STEMI) undergoing primary percutaneous coronary intervention (p-PCI). We retrospectively studied 1452 patients with STEMI undergoing p-PCI. Baseline clinical characteristics, CIN incidence, and other inhospital clinical outcomes were compared among hsCRP quartiles; 212 (14.6%) patients developed CIN. The overall inhospital mortality rate was 4.5% (65 patients). Univariate analysis revealed CIN incidence was significantly associated with hsCRP, with 7.44% for quartile Q1 (<3.00 mg/L), 12.6% for Q2 (3.00-5.90 mg/L), 16.9% for Q3 (5.91-11.4 mg/L), and 21.49% for Q4 (>11.4 mg/L; P < .001). Patients with a higher hsCRP experienced a higher rate of inhospital complications. After adjusting for potential confounders, hsCRP >6.50 mg/L was significantly associated with the occurrence of CIN. Preprocedural hsCRP levels are significantly related to the incidence of CIN in patients with STEMI undergoing p-PCI.

Chronic kidney disease and the risk of stent thrombosis after percutaneous coronary intervention with drug-eluting stents.

BACKGROUND: Chronic kidney disease (CKD) has been demonstrated to be associated with adverse clinical outcomes for patients with coronary artery disease (CAD). However, data on relation of CKD and stent thrombosis (ST) after drug-eluting stent (DES) implantation are limited. OBJECTIVES: This study was designed to examine whether CKD is associated with higher incidence of ST after elective coronary DES implantation compared with patients with normal renal function. METHODS: We consecutively enrolled 2,862 patients undergoing elective percutaneous coronary intervention (PCI) with DES. Demographic and clinical data were collected preoperatively. CKD was defined as estimated glomerular filtration rate (eGFR) < 60 ml/min, calculated using the modified MDRD equation. The primary outcome was 1-year definite or probable ST. RESULTS: Four hundred and forty-five participants (15.5%) had CKD before procedure. The incidence of 1-year definite or probable ST was significantly higher in CKD patients compared with patients with normal renal function (1.8% vs. 0.6%, P = 0.014). After adjustment for multiple clinical and biochemical covariates, CKD was an independent predictor of 1-year definite or probable ST (hazard rate [HR] 0.396, 95% CI 0.165-0.951, P = 0.038). CONCLUSION: CKD is significantly associated with increased incidence of 1-year definite or probable ST in patients undergoing PCI with DES.

The Drosophila RCC1 homolog, Bj1, regulates nucleocytoplasmic transport and neural differentiation during Drosophila development.

The Bj1 gene encodes the Drosophila homolog of RCC1, the guanine-nucleotide exchange factor for RanGTPase. Here, we provide the first phenotypic characterization of a RCC1 homolog in a developmental model system. We identified Bj1 (dRCC1) in a genetic screen to identify mutations that alter central nervous system development. We find that zygotic dRCC1 mutant embryos exhibit specific defects in the development and differentiation of lateral CNS neurons although cell division and the cell cycle appear grossly normal. dRCC1 mutant nerve cords contain abnormally large cells with compartmentalized nuclei and exhibit increased transcription in the lateral CNS. As RCC1 is an important component of the nucleocytoplasmic transport machinery, we find that dRCC1 function is required for nuclear import of nuclear localization signal sequence (NLS)-carrying cargo molecules. Finally, we show that dRCC1 is required for cell proliferation and/or survival during germline, eye and wing development and that dRCC1 appears to facilitate apoptosis.