YBX1 inhibits mitochondrial-mediated apoptosis in ischemic heart through the PI3K/AKT signaling pathway

Background:Myocardial infarction(MI)is associated with higher morbidity and mortality in the world,especially in cold weather.YBX1 is an RNA-binding protein that is required for pathological growth of cardiomyocyte by regulating cell growth and protein synthesis.But YBX1,as an individual RNA-binding protein,regulates cardiomyocytes through signaling cascades during myocardial infarction remain largely unexplored.Methods:In vivo,the mouse MI model was induced by ligating the left anterior descending coronary artery(LAD),and randomly divided into sham operation group,MI group,MI+YBX1 knockdown/overexpression group and MI+negative control(NC)group.The protective effect of YBX1 was verified by echocardiography and triphenyltetrazolium chloride staining.In vitro,mitochondrial-dependent apoptosis was investigated by using CCK8,TUNEL staining,reactive oxygen species(ROS)staining and JC-1 staining in hypoxic neonatal mouse cardiomyocytes(NMCMs).Results:YBX1 expression of cardiomyocytes was downregulated in a mouse model and a cellular model on the ischemic condition.Compared to mice induced by MI,YBX1 overexpression mediated by adeno-associated virus serotype 9(AAV9)vector reduced the infarcted size and improved cardiac function.Knockdown of endogenous YBX1 by shRNA partially aggravated ischemia-induced cardiac dysfunction.In hypoxic cardiomyocytes,YBX1 overexpression decreased lactic dehydrogenase(LDH)release,increased cell viability,and inhibited apoptosis by affecting the expression of apoptosis related proteins,while knockdown of endogenous YBX1 by siRNA had the opposite effect.Overexpression of YBX1 restored mitochondrial dysfunction in hypoxic NMCMs by increasing mitochondrial membrane potential and ATP content and decreasing ROS.In hypoxic NMCMs,YBX1 overexpression increased the expression of phosphorylated phosphatidylinositol 3 kinase(PI3K)/AKT,and the anti-apoptosis effect of YBX1 was eliminated t by LY294002,PI3K/AKT inhibitor.Conclusion:YBX1 protected the heart from ischemic damage by inhibiting the mitochondrial-dependent apoptosis through PI3K/AKT pathway.It is anticipated that YBX1 may serve as a novel therapeutic target for MI.

Pan-plastome approach empowers the assessment of genetic variation in cultivated Capsicum species

Pepper species(Capsicum spp.)are widely used as food,spice,decoration,and medicine.Despite the recent old-world culinary impact,more than 50 commercially recognized pod types have been recorded worldwide from three taxonomic complexes(A,B,and P).The current study aimed to apply a pan-plastome approach to resolve the plastomic boundaries among those complexes and identify effective loci for the taxonomical resolution and molecular identification of the studied species/varieties.High-resolution pan-plastomes of five species and two varieties were assembled and compared from 321 accessions.Phyloplastomic and network analyses clarified the taxonomic position of the studied species/varieties and revealed a pronounced number of accessions to be the rare and endemic species,C.galapagoense,that were mistakenly labeled as C.annuum var.glabriusculum among others.Similarly,some NCBIdeposited plastomes were clustered differently from their labels.The rpl23-trnI intergenic spacer contained a 44 bp tandem repeat that,in addition to other InDels,was capable of discriminating the investigated Capsicum species/varieties.The rps16-trnQ/rbcL-accD/ycf3-trnS gene set was determined to be sufficiently polymorphic to retrieve the complete phyloplastomic signal among the studied Capsicum spp.The pan-plastome approach was shown to be useful in resolving the taxonomical complexes,settling the incomplete lineage sorting conflict and developing a molecular marker set for Capsicum spp.identification.

Chinese Medical Association consensus for standardized diagnosis and treatment of pancreatic neuroendocrine neoplasms

Pancreatic neuroendocrine neoplasms(pNENs)are rare and highly heterogeneous tumors originating from pluripotent stem cells with neuroendocrine differentiation in the pancreas,constituting approximately 3%of all pancreatic tumors.^([1])The global incidence of pNENs has been increasing recently,and most cases are sporadic and more common in women.^([1,2])pNENs are clinically divided into functioning and nonfunctioning tumors depending on whether the tumors are accompanied by a clinical syndrome related to specific hormone overproduction.

Multispectral Drone Imagery and SRGAN for Rapid Phenotypic Mapping of Individual Chinese Cabbage Plants

The phenotypic parameters of crop plants can be evaluated accurately and quickly using an unmanned aerial vehicle(UAV)equipped with imaging equipment.In this study,hundreds of images of Chinese cabbage(Brassica rapa L.ssp.pekinensis)germplasm resources were collected with a low-cost UAV system and used to estimate cabbage width,length,and relative chlorophyll content(soil plant analysis development[SPAD]value).The super-resolution generative adversarial network(SRGAN)was used to improve the resolution of the original image,and the semantic segmentation network Unity Networking(UNet)was used to process images for the segmentation of each individual Chinese cabbage.Finally,the actual length and width were calculated on the basis of the pixel value of the individual cabbage and the ground sampling distance.The SPAD value of Chinese cabbage was also analyzed on the basis of an RGB image of a single cabbage after background removal.After comparison of various models,the model in which visible images were enhanced with SRGAN showed the best performance.With the validation set and the UNet model,the segmentation accuracy was 94.43%.For Chinese cabbage dimensions,the model was better at estimating length than width.The R2 of the visible-band model with images enhanced using SRGAN was greater than 0.84.For SPAD prediction,the R2 of the model with images enhanced with SRGAN was greater than 0.78.The root mean square errors of the 3 semantic segmentation network models were all less than 2.18.The results showed that the width,length,and SPAD value of Chinese cabbage predicted using UAV imaging were comparable to those obtained from manual measurements in the field.Overall,this research demonstrates not only that UAVs are useful for acquiring quantitative phenotypic data on Chinese cabbage but also that a regression model can provide reliable SPAD predictions.This approach offers a reliable and convenient phenotyping tool for the investigation of Chinese cabbage breeding traits.

Effect of kidney-reinforcing,blood-activating and stasis-removing recipes on adhesion molecule expression of bone marrow mesenchymal stem cells from chronic aplastic anemia patients

OBJECTIVE:To explore the effect of kidney-reinforcing,blood-activating and stasis-removing recipes on adhesion molecule expression of bone marrow mesenchymal stem cells(MSCs) from patients with chronic aplastic anemia(CAA).METHODS:We used threeTraditional Chinese Medicine recipes,namely a kidney-reinforcing recipe(KRR),blood-activating and stasis-removing recipe(BASRR),and kidney-reinforcing,blood-activating and stasis-removing recipe(KRBASRR),and a normal saline control to prepare herbal medicine serum in Sprague Dawley rats.Thirty CAA patients were enrolled in the experimental group,including 17 kidney-Yang deficient patients and 13 kidney-Yin deficient patients.Ten healthy individuals were included in the control group.MSCs were isolated from bone marrow samples,and the cell density was observed to measure their proliferation ability by microscopy on days 2,7,and 14 after isolation.In addition,the expression of adhesion molecules of bone marrow MSCs(CD106,CD49d,CD31 and CD44) were detected by flow cytometry after 48 h of treatment with the four different herbal medicine serums.RESULTS:The proliferation of MSCs from kidney-Yang deficient and kidney-Yin deficient patients was weaker than that of MSCs from the control group.The expression of all adhesion molecules of bone marrow MSCs from CAA patients was obviously lower than that in the control group(P< 0.01).The expression of CD49d and CD31 in MSCs from patients with a kidney-Yin deficiency was lower than in those with a kidney-yang deficiency(P< 0.05 and P<0.01,respectively).For kidney-Yang deficient patients,CD31 expression in the KRBASRR group was significantly higher than that in the BASRR group(P<0.01),while CD44 in the KRBASRR group was significantly higher than that in both KRR and BASRR groups(P<0.01).For kidney-Yin deficient patients,CD106 and CD49d expression in the KRBASRR group was obviously higher than that in the KRR group(P<0.05),while CD31 and CD44 expression in the KRBASRR group was significantly higher than that in both KRR and BASRR groups(P< 0.05 and P<0.01,respectively).CONCLUSION:The bone marrow microenvironment in CAA patients is abnormal.The effect of KRBASRR may be better than that of KRR and BASRR for kidney-Yang deficient and kidney-Yin deficient patients by improving the expression levels of MSC adhesion molecules.

Multispectral Drone Imagery and SRGAN for Rapid Phenotypic Mapping of Individual Chinese Cabbage Plants

The phenotypic parameters of crop plants can be evaluated accurately and quickly using an unmanned aerial vehicle(UAV)equipped with imaging equipment.In this study,hundreds of images of Chinese cabbage(Brassica rapa L.ssp.pekinensis)germplasm resources were collected with a low-cost UAV system and used to estimate cabbage width,length,and relative chlorophyll content(soil plant analysis development[SPAD]value).The super-resolution generative adversarial network(SRGAN)was used to improve the resolution of the original image,and the semantic segmentation network Unity Networking(UNet)was used to process images for the segmentation of each individual Chinese cabbage.

Efficacy and safety of S-1 based adjuvant chemoradiotherapy for resected pancreatic ductal adenocarcinoma with high-risk pathological feature: a prospective, single-arm, interventional study

Objective: It remains unclear whether adjuvant chemoradiotherapy (CRT) improves survival outcome of pancreatic ductal adenocarcinoma (PDAC) patients after surgery. This study aimed to investigate the efficacy and safety of tegafur/gimeracil/oteracil (S-1)-based adjuvant concurrent chemoradiotherapy in resected PDAC patients with defined high-risk pathological features.Methods: We conducted a single-arm, prospective, and interventional study at Zhongshan Hospital Fudan University from December 2012 to December 2019 and the last follow-up was conducted in December 2021. This study was approved by the Ethics Committee of Zhongshan Hospital Fudan University on December 27, 2012 (approval No. B2012-139). Resected PDAC patients with high-risk pathological features, including positive resection margin, pathological T3-4N1-2M0 disease, peripancreatic fat invasion, microvascular invasion, and perineural invasion, were recruited. Primary endpoint was overall survival and secondary endpoints were disease-free survival, treatment toxicity, and 2-, 5-year survival rates.Results: A total of 54 patients were recruited. Mean age was 63.6 years old (±7.2). The distribution of T and N stages were 24.1% for T1, 46.3% for T2, 27.8% for T3, 1.9% for T4, 33.3% for N1, and 11.1% for N2. Seven patients had R1 resection. The median overall survival and disease-free survival were 27.1 and 13.7 months, respectively, while no fatal adverse events were recorded. Subgroup analyses showed differences in survival outcomes among patients with microvascular invasion, different N stages, and preoperative CA 19-9 levels. Further, a Cox proportional hazard model demonstrated associations of lymph node metastases, CA 19-9 level, and microvascular invasion with overall survival and disease-free survival.Conclusion: S-1 -based adjuvant CRT showed promising efficacy and manageable toxicity in resected PDAC patients with highrisk pathological features.

China enters CAR-T cell therapy era

The emerging individualized and living-cell-based genetic engineering chimeric antigen receptor T(CAR-T)therapy demonstrates great curative effects in some hematological tumor treatments,thus it is turning out to be a star immunotherapy method of the world.1 Recently,the China NationalMedical Products Administration(NMPA)approved launching applications of two CAR-T cell cancer products,Axicabtagene Ciloleucel(FKC876)and Relmacabtagene Autoleucel(Carteyva),which marked the beginning of the of CAR-T cell therapy era in China(Figure 1).

Clinical Diagnosis and Treatment Recommendations for Immune Checkpoint Inhibitor-Associated Myocarditis

Immune checkpoint inhibitors(ICIs)are often beneficial in the treatment of multiple types of malignant tumors.However,ICI-associated myocarditis has introduced new clinical challenges.This report highlights the key clinical issues of ICI-associated myocarditis,such as risk factors,diagnosis and differential diagnosis,clinical classification and treatment,monitoring of outcomes,and restart of treatment.Additionally,practical guidance and suggestions for the diagnosis and treatment of ICI-associated myocarditis are proposed with reference to the relevant consensuses or guidelines and newly published evidence-based studies in China and other countries in combination with clinical experience of physicians from Shanghai,China.