Endocardial cells form the coronary arteries by angiogenesis through myocardial-endocardial VEGF signaling.

The origins and developmental mechanisms of coronary arteries are incompletely understood. We show here by fate mapping, clonal analysis, and immunohistochemistry that endocardial cells generate the endothelium of coronary arteries. Dye tracking, live imaging, and tissue transplantation also revealed that ventricular endocardial cells are not terminally differentiated; instead, they are angiogenic and form coronary endothelial networks. Myocardial Vegf-a or endocardial Vegfr-2 deletion inhibited coronary angiogenesis and arterial formation by ventricular endocardial cells. In contrast, lineage and knockout studies showed that endocardial cells make a small contribution to the coronary veins, the formation of which is independent of myocardial-to-endocardial Vegf signaling. Thus, contrary to the current view of a common source for the coronary vessels, our findings indicate that the coronary arteries and veins have distinct origins and are formed by different mechanisms. This information may help develop better cell therapies for coronary artery disease.

Integrated transcriptomics and epigenomics reveal chamber-specific and species-specific characteristics of human and mouse hearts.

DNA methylation, chromatin accessibility, and gene expression represent different levels information in biological process, but a comprehensive multiomics analysis of the mammalian heart is lacking. Here, we applied nucleosome occupancy and methylome sequencing, which detected DNA methylation and chromatin accessibility simultaneously, as well as RNA-seq, for multiomics analysis of the 4 chambers of adult and fetal human hearts, and adult mouse hearts. Our results showed conserved region-specific patterns in the mammalian heart at transcriptome and DNA methylation level. Adult and fetal human hearts showed distinct features in DNA methylome, chromatin accessibility, and transcriptome. Novel long noncoding RNAs were identified in the human heart, and the gene expression profiles of major cardiovascular diseases associated genes were displayed. Furthermore, cross-species comparisons revealed human-specific and mouse-specific differentially expressed genes between the atria and ventricles. We also reported the relationship among multiomics and found there was a bell-shaped relationship between gene-body methylation and expression in the human heart. In general, our study provided comprehensive spatiotemporal and evolutionary insights into the regulation of gene expression in the heart.

Machine learning in risk prediction of continuous renal replacement therapy after coronary artery bypass grafting surgery in patients.

OBJECTIVES: This study aimed to develop machine learning models for risk prediction of continuous renal replacement therapy (CRRT) following coronary artery bypass grafting (CABG) surgery in intensive care unit (ICU) patients. METHODS: We extracted CABG patients from the electronic medical record system of the hospital. The endpoint of this study was the requirement for CRRT after CABG surgery. The Boruta method was used for feature selection. Seven machine learning algorithms were developed to train models and validated using 10 fold cross-validation (CV). Model discrimination and calibration were estimated using the area under the receiver operating characteristic curve (AUC) and calibration plot, respectively. We used the SHapley Additive exPlanations (SHAP) method to illustrate the effects of the features attributed to the model and analyze the effects of individual features on the output of the mode. RESULTS: In this study, 72 (37.89%) patients underwent CRRT, with a higher mortality compared to those patients without CRRT. The Gaussian Naïve Bayes (GNB) model with the highest AUC were considered as the final predictive model and performed best in predicting postoperative CRRT. The analysis of importance revealed that cardiac troponin T, creatine kinase isoenzyme, albumin, low-density lipoprotein cholesterol, NYHA, serum creatinine, and age were the top seven features of the GNB model. The SHAP force analysis illustrated how created model visualized individualized prediction of CRRT. CONCLUSIONS: Machine learning models were developed to predict CRRT. This contributes to the identification of risk variables for CRRT following CABG surgery in ICU patients and enables the optimization of perioperative managements for patients.

Gut microbiota profiling in obese children from Southeastern China.

Childhood obesity not only has a negative impact on a child's health but is also a significant risk factor for adult obesity and related metabolic disorders, making it a major global public health concern. Recent studies have revealed the crucial role of gut microbiota in the occurrence and development of obesity, in addition to genetic and lifestyle factors. In this study, we recruited 19 normal-weight children and 47 children with varying degrees of obesity. A questionnaire survey was conducted to inquire about the family background, lifestyle habits and dietary composition of the 66 children. Findings indicate that fathers of obese children tend to be obese themselves, while children with highly educated mothers are more likely to maintain a normal weight. Furthermore, overweight children tend to spend more time on electronic devices and less time on physical activities compared to their normal-weight counterparts. Obese children exhibit significant differences in breakfast and dinner dietary composition when compared to children with normal weight. Additionally, the gut microbiota of these 66 children was analyzed using 16S rRNA sequencing. Analysis of gut microbiota composition showed similar compositions among children with varying degrees of obesity, but significant differences were observed in comparison to normal-weight children. Obese children exhibited a reduced proportion of Bacteroidota and an increased proportion of Firmicutes, resulting in an elevated Firmicutes/Bacteroidota ratio. Moreover, Actinobacteriota were found to be increased in the gut microbiota of children with varying degrees of obesity. PICRUSt analysis indicated significant metabolic differences in the microbiota functions between obese and normal-weight children, suggesting the composition of gut microbiota could be a crucial factor contributing to obesity. These findings provide valuable insights for the treatment of childhood obesity.

High-fat diet causes mitochondrial damage and downregulation of mitofusin-2 and optic atrophy-1 in multiple organs.

High-fat consumption promotes the development of obesity, which is associated with various chronic illnesses. Mitochondria are the energy factories of eukaryotic cells, maintaining self-stability through a fine-tuned quality-control network. In the present study, we evaluated high-fat diet (HFD)-induced changes in mitochondrial ultrastructure and dynamics protein expression in multiple organs. C57BL/6J male mice were fed HFD or normal diet (ND) for 24 weeks. Compared with ND-fed mice, HFD-fed mice exhibited increased body weight, cardiomyocyte enlargement, pulmonary fibrosis, hepatic steatosis, renal and splenic structural abnormalities. The cellular apoptosis of the heart, liver, and kidney increased. Cellular lipid droplet deposition and mitochondrial deformations were observed. The proteins related to mitochondrial biogenesis (TFAM), fission (DRP1), autophagy (LC3 and LC3-II: LC3-I ratio), and mitophagy (PINK1) presented different changes in different organs. The mitochondrial fusion regulators mitofusin-2 (MFN2) and optic atrophy-1 (OPA1) were consistently downregulated in multiple organs, even the spleen. TOMM20 and ATP5A protein were enhanced in the heart, skeletal muscle, and spleen, and attenuated in the kidney. These results indicated that high-fat feeding caused pathological changes in multiple organs, accompanied by mitochondrial ultrastructural damage, and MFN2 and OPA1 downregulation. The mitochondrial fusion proteins may become promising targets and/or markers for treating metabolic disease.

The Safety and Efficacy Evaluation of Dexmedetomidine for Procedural Sedation and Postoperative Behaviors in Pediatric Populations: A Systematic Review and Meta-analysis.

BACKGROUND: This study systematically evaluated the safety and efficacy of dexmedetomidine for procedural sedation and postoperative behaviors in a pediatric population as well as whether the results met the information required to draw conclusions. OBJECTIVE: To evaluate the safety and efficacy evaluation of dexmedetomidine for procedural sedation and postoperative behaviors in a pediatric population. METHODS: PubMed, Cochrane library, Web of Science and Ovid MEDLINE were searched to obtain randomized controlled trials (RCTs) comparing dexmedetomidine with control medicine and comparing different doses of dexmedetomidine. RESULTS: There were a total of 16 RCTs for a total of 3240 patients. Dexmedetomidine slowed down the heart rate (HR; mean difference: -13.27; 95% CI: -16.41 to 10.14; P < 0.001) and reduced postoperative delirium (risk ratio [RR]: 0.31; 95% CI: 0.20-0.50; P < 0.001), the number of pain patients (RR: 0.48; 95% CI: 0.30-0.75; P = 0.002), and desaturation (RR: 0.34; 95% CI: 0.13-0.89; P = 0.03) compared with the control group. The limitation was that it was difficult to determine the range of low- and high-dose dexmedetomidine. CONCLUSION AND RELEVANCE: Dexmedetomidine slowed down intraoperative HR within the normal range, which might reduce myocardial oxygen consumption. It reduced postoperative pain and postoperative complications: delirium and desaturation. Dexmedetomidine showed no dose-dependent increase in the procedural sedation time of pediatric patients. Clinically, dexmedetomidine can improve pediatric procedural sedation and postoperative behavior, and it can be considered as a related medicine for safety in pediatric surgery.

Atorvastatin reverses high cholesterol-induced cardiac remodelling and regulates mitochondrial quality-control in a cholesterol-independent manner: An experimental study.

Mitochondria are key regulators of cell fate, maintaining self-stability by a fine-tuned quality-control network including mitophagy, biogenesis, fission and fusion processes. Myocardial mitochondria can be impaired by hypercholesterolemia. Statins, such as atorvastatin, are considered the cornerstone in the management of hypercholesterolaemia primarily due to their marked cholesterol-lowering ability. The direct effect of atorvastatin on myocardial mitochondria remains unclear. We aimed to explore whether atorvastatin could attenuate myocardial mitochondrial defects induced by high cholesterol, and whether cycloastragenol, a potent telomerase activator, could be used as a potential complementary bioactive compound for obesity and hypercholesterolaemia treatment. We found that atorvastatin at a low dose (3 mg/kg) did not reduce elevated serum cholesterol, but reversed cardiac remodelling and dysfunction in C57BL/6J mice fed with high-fat diet (HFD). Atorvastatin reversed the upregulated mitophagy, mitochondrial fission and fusion, accompanied by mitochondrial biogenesis activation in HFD-fed mice hearts. Mitochondrial structural impairments were attenuated by atorvastatin in HFD-fed mice and oxidized low-density lipoprotein (ox-LDL) exposed HL-1 cardiomyocytes. The depolarized mitochondrial membrane potential and increased mitochondrial oxygen consumption rates in ox-LDL exposed HL-1 cells were recovered by atorvastatin. Furthermore, atorvastatin co-treated with cycloastragenol had better effects on reducing body weight, improving cardiac remodelling and dysfunction, and protecting mitochondria in high cholesterol. Conclusively, low-dose atorvastatin exhibited a cholesterol-independent cardioprotective effect through improving the mitochondrial quality-control network and repairing mitochondrial ultrastructure in high cholesterol. Atorvastatin plus cycloastragenol supplement therapy has a better effect on treating obesity and hypercholesterolaemia.

Plasmon Near-Field Coupling of Bimetallic Nanostars and a Hierarchical Bimetallic SERS "Hot Field": Toward Ultrasensitive Simultaneous Detection of Multiple Cardiorenal Syndrome Biomarkers.

Cardiorenal syndrome (CRS) has posed tremendous challenges in patient management, and the detection of serum biomarkers may provide opportunities for early diagnosis and effective treatment. Herein, we introduce a novel surface-enhanced Raman scattering (SERS)-based sandwich immunoassay platform to simultaneously detect cardiac troponin I (cTnI), N-terminal prohormone of brain natriuretic peptide (NT-ProBNP), and neutrophil gelatinase-associated lipocalin (NGAL) for the early diagnosis of CRS by using Raman reporter-molecule-labeled Ag-Au nanostars (Ag-Au NSs) as nanotags and a three-dimensional ordered macroporous (3DOM) Au-Ag-Au plasmonic array as substrate. The Ag-Au NSs prepared by galvanic replacement feature bimetallic composition and a multibranched structure so that high SERS stability and enhancement are exhibited. Meanwhile, a 3DOM Au-Ag-Au plasmonic array was fabricated through Au-assisted electrodeposition and was further covered by a protective Au layer; it is characterized by a large specific surface area and high homogeneity, serving as a "hot field". When the nanotags and substrate were combined, "hot spots" were generated from the plasmon near-field coupling, which greatly increased the SERS enhancement. The limits of detection (LODs) were 0.76, 0.53, and 0.41 fg mL-1 for cTnI, NT-ProBNP, and NGAL, respectively, and the Raman images indicated the approximate concentration ranges of the detected proteins for visual analysis. Taking advantage of the ultrasensitivity and multiplexing capability of this approach, we further analyzed clinical blood samples with high integrality, efficiency, and accuracy. Therefore, the presented SERS immunoassay platform holds promise as an ideal test method for point-of-care detection and a powerful tool for investigations into the complex CRS-related biological process.

Emerging role of Hippo signalling pathway in bladder cancer.

Bladder cancer (BC) is one of the most common cancers worldwide with a high progression rate and poor prognosis. The Hippo signalling pathway is a conserved pathway that plays a crucial role in cellular proliferation, differentiation and apoptosis. Furthermore, dysregulation and/or malfunction of the Hippo pathway is common in various human tumours, including BC. In this review, an overview of the Hippo pathway in BC and other cancers is presented. We focus on recent data regarding the Hippo pathway, its network and the regulation of the downstream co-effectors YAP1/TAZ. The core components of the Hippo pathway, which induce BC stemness acquisition, metastasis and chemoresistance, will be emphasized. Additional research on the Hippo pathway will advance our understanding of the mechanism of BC as well as the development and progression of other cancers and may be exploited therapeutically.

Urethral prolapse in prepubertal females: Report of seven cases.

Urethral prolapse is a rare lesion in female children, with a suggested incidence of one in 5000 in China. Most of the cases reported in children have been in girls of African descent. In this report, we present seven cases of Chinese pediatric patients with urethral prolapse. Patient ages ranged from 2 to 8 years. They all presented with a protruding mass in the vaginal opening and bleeding. Diagnosis was confirmed with the combination of clinical manifestation and supplementary examinations. The patients were treated with either conservative therapy (two of the seven patients) or surgical intervention (five of the seven patients). During a 2-week to 6-year follow-up, no case recurred. The literature on urethral prolapse is reviewed.

Astragaloside IV Prevents Cardiac Remodeling in the Apolipoprotein E-Deficient Mice by Regulating Cardiac Homeostasis and Oxidative Stress.

BACKGROUND: Hypercholesterolemia is a risk factor for the development of cardiac hypertrophy. Astragaloside IV (AST-IV) possesses cardiovascular protective properties. We hypothesize that AST-IV prevents cardiac remodeling with hypercholesterolemia via modulating tissue homeostasis and alleviating oxidative stress. METHODS: The ApoE-/- mice were treated with AST-IV at 1 or 10 mg/kg for 8 weeks. The blood lipids tests, echocardiography, and TUNEL were performed. The mRNA expression profile was detected by real-time PCR. The myocytes size and number, and the expressions of proliferation (ki67), senescence (p16INK4a), oxidant (NADPH oxidase 4, NOX4) and antioxidant (superoxide dismutase, SOD) were observed by immunofluorescence staining. RESULTS: Neither 1 mg/kg nor 10 mg/kg AST-IV treatment could decrease blood lipids in ApoE-/- mice. However, the decreased left ventricular ejection fraction (LVEF) and fractional shortening (FS) in ApoE-/- mice were significantly improved after AST-IV treatment. The cardiac collagen volume fraction declined nearly in half after AST-IV treatment. The enlarged myocyte size was suppressed, and myocyte number was recovered, and the alterations of genes expressions linked to cell cycle, proliferation, senescence, p53-apoptosis pathway and oxidant-antioxidants in the hearts of ApoE-/- mice were reversed after AST-IV treatment. The decreased ki67 and increased p16INK4a in the hearts of ApoE-/- mice were recovered after AST-IV treatment. The percentages of apoptotic myocytes and NOX4-positive cells in AST-IV treated mice were decreased, which were consistent with the gene expressions. CONCLUSION: AST-IV treatment could prevent cardiac remodeling and recover the impaired ventricular function induced by hypercholesterolemia. The beneficial effect of AST-IV might partly be through regulating cardiac homeostasis and anti-oxidative stress.

Discovery and evaluation of piperid-4-one-containing mono-carbonyl analogs of curcumin as anti-inflammatory agents.

We previously reported the design and discovery of three series of 5-carbon linker-containing mono-carbonyl analogs of curcumin (MCACs) as excellent anti-inflammatory agents. In continuation of our ongoing research, we designed and synthesized the fourth series of MCACs, whose central linker is a piperid-4-one. Their inhibitory effects against IL-6 production were evaluated in lipopolysaccharide (LPS)-stimulated macrophages. Among them, compounds F8, F29, F33, F35, and F36 exhibited the IC50 values under 5 µM. The structure-activity relationship was discussed. Mechanistically, F35 and F36 dose-dependently prevented LPS-induced NF-κB and ERK activation. Finally, pretreatment with F35 and F36 significantly protected the C57B/L6 mice from LPS-induced septic death. Together, these data present a series of new analogs of curcumin as promising anti-inflammatory agents.

Characterization of Two AGAMOUS-like Genes and Their Promoters from the Cymbidium faberi (Orchidaceae).

Arabidopsis AGAMOUS (AG) play roles in determining stamens' and carpels' identities, floral meristem determinacy, and repression of the A-function. Gynostemium fused by stamens and carpels is a characteristic reproductive structure in orchid flowers, which shows a considerable difference from the reproductive organs of eudicots and other monocot species. The molecular basis of orchid gynostemium development remains largely unknown. Here, we report the identification and functional characterization of two AG-like genes, CyfaAG1 and CyfaAG2, and their promoters from C. faberi. Both CyfaAG1 and CyfaAG2 are highly expressed in the anther cap, gynostemium, and ovary. Ectopic expression of CyfaAG1 and CyfaAG2 promotes early flowering of wild-type Arabidopsis. Moreover, ectopic expression of CyfaAG1 completely rescues floral defects in the Arabidopsis ag-1 mutant, while ectopic expression of CyfaAG2 only completes filament and carpel development. Our findings suggest that CyfaAG1 acts as an evolutionarily conserved C-function gene in determining reproductive organ identity and mediating floral meristem determinacy. CyfaAG2 redundantly mediates the C-function in floral meristem determinacy and gynostemium development. Our results provided more details to understand how the C-class function has been partitioned in orchids, and the roles of two AG orthologs in regulating gynostemium development in C. faberi.

Atorvastatin ameliorates lipid overload-induced mitochondrial dysfunction and myocardial hypertrophy by decreasing fatty acid oxidation through inactivation of the p-STAT3/CPT1 pathway.

Although statins are shown to have cardiac pleiotropic effects independent of lowering cholesterol, the underlying mechanism remains unclear. Mitochondrial dysfunction induced by increased fatty acid oxidation (FAO) is the culprit in the development of cardiac hypertrophy and dysfunction. This study was to explore whether the cardiac pleiotropic effects of atorvastatin were associated with FAO regulation, with a specific focus on carnitine palmitoyltransferase 1 (CPT1). High-fat diet (HFD)-fed mice and palmitic acid (PA)-stimulated neonatal rat primary cardiomyocytes (NRCMs) were treated with atorvastatin, with or without FAO modulators, signal transducer and activator of transcription 3 (STAT3) agonist, and inhibitor. Atorvastatin (3 mg/kg) did not reduce serum cholesterol levels in HFD-fed mice but ameliorated mitochondrial dysfunction and cardiac hypertrophy. In vitro, atorvastatin and the FAO inhibitor alleviated PA-induced mitochondrial dysfunction and cardiomyocyte hypertrophy. However, the FAO enhancer eliminated atorvastatin's protective effects. Furthermore, atorvastatin decreased CPT1 and FAO levels and prevented STAT3 phosphorylation and nuclear translocation. STAT3 inhibitor had the same inhibitory effects as atorvastatin on CPT1, FAO levels, and cardiomyocyte hypertrophy, whereas STAT3 agonist disrupted these effects of atorvastatin. Our results demonstrate that atorvastatin decreases myocardial FAO by inactivating the p-STAT3/CPT1 signaling pathway, which improves lipid overload-induced mitochondrial dysfunction and cardiac hypertrophy in a cholesterol-independent manner. This is the first study to explore the cardiac pleiotropic effects of atorvastatin with respect to FAO. However, whether atorvastatin regulates FAO in the cardiac hypertrophy model induced by other variables has not been investigated in this work, and this is expected to be performed in the future.

Low-dose atorvastatin protects skeletal muscle mitochondria in high-fat diet-fed mice with mitochondrial autophagy inhibition and fusion enhancement.

Despite the great clinical benefits of statins in cardiovascular diseases, their widespread use may lead to adverse muscle reactions associated with mitochondrial dysfunction. Some studies have demonstrated that statins provide substantial improvement to skeletal muscle health in mice. Our previous study found that oral treatment with atorvastatin (Ator, 3 mg/kg) protected myocardial mitochondria in high-fat diet (HFD)-fed mice. Therefore, this study aimed to explore the influence of low-dose Ator (3 mg/kg) on mitochondria in skeletal muscle under cholesterol overload. Male C57BL/6J mice were fed a HFD for 18 weeks and orally administered Ator (3 mg/kg) during the last 12 weeks. Ator treatment had no effects on elevated serum cholesterol and glucose levels in HFD-fed mice. Serum creatine kinase levels and the cross-sectional area of muscle cells were not affected by HFD feeding or Ator treatment. Increased expression of PINK1-LC3 II (activated mitophagy), MFN2 (fusion), and PGC-1α (biogenesis) proteins was induced in the skeletal muscles of HFD-fed mice. Treatment with Ator inhibited PINK1 and LC3 II protein expression, but further promoted MFN1, MFN2, and OPA1 expression. The impairments in mitochondrial quality and morphology in HFD-fed mice were attenuated by treatment with Ator. Furthermore, Ator treatment enhanced glucose oxidation capacity and restored ATP production in the skeletal muscles of HFD-fed mice. The study reveals that low-dose Ator has a protective effect on muscle mitochondria in mice, likely through inhibiting mitophagy and enhancing mitochondrial fusion. This suggests that skeletal muscle mitochondria may be one of low-dose Ator-mediated protective targets.

Identification of three metabolic subtypes in gastric cancer and the construction of a metabolic pathway-based risk model that predicts the overall survival of GC patients.

Gastric cancer (GC) is highly heterogeneous and GC patients have low overall survival rates. It is also challenging to predict the prognosis of GC patients. This is partly because little is known about the prognosis-related metabolic pathways in this disease. Hence, our objective was to identify GC subtypes and genes related to prognosis, based on changes in the activity of core metabolic pathways in GC tumor samples. Differences in the activity of metabolic pathways in GC patients were analyzed using Gene Set Variation Analysis (GSVA), leading to the identification of three clinical subtypes by non-negative matrix factorization (NMF). Based on our analysis, subtype 1 showed the best prognosis while subtype 3 exhibited the worst prognosis. Interestingly, we observed marked differences in gene expression between the three subtypes, through which we identified a new evolutionary driver gene, CNBD1. Furthermore, we used 11 metabolism-associated genes identified by LASSO and random forest algorithms to construct a prognostic model and verified our results using qRT-PCR (five matched clinical tissues of GC patients). This model was found to be both effective and robust in the GSE84437 and GSE26253 cohorts, and the results from multivariate Cox regression analyses confirmed that the 11-gene signature was an independent prognostic predictor (p < 0.0001, HR = 2.8, 95% CI 2.1-3.7). The signature was found to be relevant to the infiltration of tumor-associated immune cells. In conclusion, our work identified significant GC prognosis-related metabolic pathways in different GC subtypes and provided new insights into GC-subtype prognostic assessment.

Astragaloside IV alleviates hypoxia/reoxygenation-induced neonatal rat cardiomyocyte injury via the protein kinase a pathway.

BACKGROUND: Astragaloside IV (As-IV) exerts beneficial effects on hypoxia/reoxygenation (H/R)-induced cardiomyocyte injury, possibly through normalization of sarcoplasmic reticulum Ca(2+) ATPase (SERCA2a) function. The exact mechanisms remain unknown. This study was designed to investigate the role of protein kinase A (PKA) in the protective effect of As-IV on SERCA2a function. METHODS: Cultured cardiomyocytes from neonatal rats were exposed to 6 h of hypoxia followed by 3 h of reoxygenation (H/R) with or without As-IV treatment. Myocyte injury was determined by the creatine kinase (CK)-MB fraction in supernatant. Myocardial SERCA2a activity and PKA kinase activity were assessed. PKA subunit mRNA expression and Ser(16) phosphorylated phospholamban (Ser(16)-PLN) protein expression were detected by real-time PCR and Western blot, respectively. RESULTS: The administration of As-IV significantly decreased CK-MB release and restored SERCA2a activity in H/R cardiomyocytes. The mRNAs of PKA subunits, PKA-RIα, PKA-RIIα, PKA-RIIß, PKA-Cα and PKA-Cß, were downregulated in H/R cardiomyocytes. However, PKA-Cα mRNA expression was significantly increased after As-IV treatment. Meanwhile, there was a tendency to recovery of the H/R-induced PKA kinase activity decrease after As-IV treatment. The expression of Ser(16)-PLN protein, which is specifically phosphorylated by PKA, was upregulated in As-IV-treated H/R cardiomyocytes. CONCLUSIONS: These results suggest that the cardioprotection of As-IV may be through the upregulation of PKA and Ser(16)-PLN, thereby restoring SERCA2a function in H/R injury.

Oncolytic virus: A catalyst for the treatment of gastric cancer.

Gastric cancer (GC) is a leading contributor to global cancer incidence and mortality. According to the GLOBOCAN 2020 estimates of incidence and mortality for 36 cancers in 185 countries produced by the International Agency for Research on Cancer (IARC), GC ranks fifth and fourth, respectively, and seriously threatens the survival and health of people all over the world. Therefore, how to effectively treat GC has become an urgent problem for medical personnel and scientific workers at this stage. Due to the unobvious early symptoms and the influence of some adverse factors such as tumor heterogeneity and low immunogenicity, patients with advanced gastric cancer (AGC) cannot benefit significantly from treatments such as radical surgical resection, radiotherapy, chemotherapy, and targeted therapy. As an emerging cancer immunotherapy, oncolytic virotherapies (OVTs) can not only selectively lyse cancer cells, but also induce a systemic antitumor immune response. This unique ability to turn unresponsive 'cold' tumors into responsive 'hot' tumors gives them great potential in GC therapy. This review integrates most experimental studies and clinical trials of various oncolytic viruses (OVs) in the diagnosis and treatment of GC. It also exhaustively introduces the concrete mechanism of invading GC cells and the viral genome composition of adenovirus and herpes simplex virus type 1 (HSV-1). At the end of the article, some prospects are put forward to determine the developmental directions of OVTs for GC in the future.

Adenosine signaling: Optimal target for gastric cancer immunotherapy.

Gastric cancer (GC) is one of the most common malignancy and leading cause of cancer-related deaths worldwide. Due to asymptomatic or only nonspecific early symptoms, GC patients are usually in the advanced stage at first diagnosis and miss the best opportunity of treatment. Immunotherapies, especially immune checkpoint inhibitors (ICIs), have dramatically changed the landscape of available treatment options for advanced-stage cancer patients. However, with regards to existing ICIs, the clinical benefit of monotherapy for advanced gastric cancer (AGC) is quite limited. Therefore, it is urgent to explore an optimal target for the treatment of GC. In this review, we summarize the expression profiles and prognostic value of 20 common immune checkpoint-related genes in GC from Gene Expression Profiling Interactive Analysis (GEPIA) database, and then find that the adenosinergic pathway plays an indispensable role in the occurrence and development of GC. Moreover, we discuss the pathophysiological function of adenosinergic pathway in cancers. The accumulation of extracellular adenosine inhibits the normal function of immune effector cells and facilitate the effect of immunosuppressive cells to foster GC cells proliferation and migration. Finally, we provide insights into potential clinical application of adenosinergic-targeting therapies for GC patients.

Characterization of PISTILLATA-like Genes and Their Promoters from the Distyly Fagopyrum esculentum.

Arabidopsis PISTILLATA (PI) encodes B-class MADS-box transcription factor (TF), and works together with APETALA3 (AP3) to specify petal and stamen identity. However, a small-scale gene duplication event of PI ortholog was observed in common buckwheat and resulted in FaesPI_1 and FaesPI_2. FaesPI_1 and FaesPI_2 were expressed only in the stamen of dimorphic flower (thrum and pin) of Fagopyrum esculentum. Moreover, intense beta-glucuronidase (GUS) staining was found in the entire stamen (filament and anther) in pFaesPI_1::GUS transgenic Arabidopsis, while GUS was expressed only in the filament of pFaesPI_2::GUS transgenic Arabidopsis. In addition, phenotype complementation analysis suggested that pFaesPI_1::FaesPI_1/pFaesPI_2::FaesPI_2 transgenic pi-1 Arabidopsis showed similar a flower structure with stamen-like organs or filament-like organs in the third whorl. This suggested that FaesPI_2 only specified filament development, but FaesPI_1 specified stamen development. Meanwhile, FaesPI_1 and FaesPI_2 were shown to function redundantly in regulating filament development, and both genes work together to require a proper stamen identity. The data also provide a clue to understanding the roles of PI-like genes involved in floral organ development during the early evolution of core eudicots and also suggested that FaesPI_1 and FaesPI_2 hold the potential application in bioengineering to develop a common buckwheat male sterile line.