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Abstract In plantae, basic leucine zipper (bZIP) transcription factors (TFs) are widespread and regulate a variety of biological processes under abiotic stress. However, it has not been extensively studied in Rosaceae, and the functional effects of bZIP on Eriobotrya japonica under salt stress are still unknown. Therefore, in this study, the bZIP TF family of 12 species of Rosaceae was analyzed by bioinformatics method, and the expression profile and quantitative real‐time polymerase chain reaction of E. japonica under salt stress were analyzed. The results showed that a total of 869 bZIP TFs were identified in 12 species of Rosaceae and divided into nine subfamilies. Differences in promoter cis‐elements between subfamilies vary depending on their role. Species belonging to the same subfamily have a similar number of chromosomes and the number of genes contained on each chromosome. Gene duplication analysis has found segmental duplication to be a prime force in the evolution of Rosaceae species. In addition, nine EjbZIPs were significantly different, including seven up‐regulated and two down‐regulated in E. japonica under salt stress. Especially, EjbZIP13 was involved in the expression of SA‐responsive proteins by binding to the NPR1 gene. EjbZIP27, EjbZIP30, and EjbZIP38 were highly expressed in E. japonica under salt stress, thus improving the salt tolerance capacity of the plants. These results can provide a theoretical basis for exploring the characteristics and functions of the bZIP TF family in more species and breeding salt‐tolerant E. japonica varieties. It also provides a reference for resolving the response mechanism of bZIP TF in 12 Rosaceae species under salt stress.

Abstract Background Diabetic cardiomyopathy (DCM), a serious complication of diabetes, leads to structural and functional abnormalities of the heart and ultimately evolves to heart failure. IL-37 exerts a substantial influence on the regulation of inflammation and metabolism. Whether IL-37 is involved in DCM is unknown. Methods The plasma samples were collected from healthy controls, diabetic patients and DCM patients, and the level of IL-37 and its relationship with heart function were observed. The changes in cardiac function, myocardial fibrosis and mitochondrial injury in DCM mice with or without IL-37 intervention were investigated in vivo. By an in vitro co-culture approach involving HG challenge of cardiomyocytes and fibroblasts, the interaction carried out by cardiomyocytes on fibroblast profibrotic activation was studied. Finally, the possible interactive mediator between cardiomyocytes and fibroblasts was explored, and the intervention role of IL-37 and its relevant molecular mechanisms. Results We showed that the level of plasma IL-37 in DCM patients was upregulated compared to that in healthy controls and diabetic patients. Both recombinant IL-37 administration or inducing IL-37 expression alleviated cardiac dysfunction and myocardial fibrosis in DCM mice. Mechanically, hyperglycemia impaired mitochondria through SIRT1/AMPK/PGC1α signaling, resulting in significant cardiomyocyte apoptosis and the release of extracellular vesicles containing mtDNA. Fibroblasts then engulfed these mtDNA-enriched vesicles, thereby activating TLR9 signaling and the cGAS-STING pathway to initiate pro-fibrotic process and adverse remodeling. However, the presence of IL-37 ameliorated mitochondrial injury by preserving the activity of SIRT1-AMPK-PGC1α axis, resulting in a reduction in release of mtDNA-enriched vesicle and ultimately attenuating the progression of DCM. Conclusions Collectively, our study demonstrates a protective role of IL-37 in DCM, offering a promising therapeutic agent for this disease. Graphical abstract Hyperglycemia aggravates mitochondrial injury through SIRT1/AMPK/PGC1α signaling, resulting in significant cardiomyocyte apoptosis and the release of extracellular vesicles containing mtDNA in DCM mice. Fibroblasts then engulf these mtDNA-enriched vesicles, activating TLR9 signaling and the cGAS-STING pathway to initiate profibrotic process and adverse remodeling. However, both exogenous and endogenous IL-37 ameliorate mitochondrial injury by preserving the activity of SIRT1-AMPK-PGC1α axis, and reducing the release of mtDNA-enriched vesicles, which attenuates the progression of DCM

Abstract Background Plant-specific TIFY proteins are widely found in terrestrial plants and play important roles in plant adversity responses. Although the genome of loquat at the chromosome level has been published, studies on the TIFY family in loquat are lacking. Therefore, the EjTIFY gene family was bioinformatically analyzed by constructing a phylogenetic tree, chromosomal localization, gene structure, and adversity expression profiling in this study. Results Twenty-six EjTIFY genes were identified and categorized into four subfamilies (ZML, JAZ, PPD, and TIFY) based on their structural domains. Twenty-four EjTIFY genes were irregularly distributed on 11 of the 17 chromosomes, and the remaining two genes were distributed in fragments. We identified 15 covariate TIFY gene pairs in the loquat genome, 13 of which were involved in large-scale interchromosomal segmental duplication events, and two of which were involved in tandem duplication events. Many abiotic stress cis-elements were widely present in the promoter region. Analysis of the Ka/Ks ratio showed that the paralogous homologs of the EjTIFY family were mainly subjected to purifying selection. Analysis of the RNA-seq data revealed that a total of five differentially expressed genes (DEGs) were expressed in the shoots under gibberellin treatment, whereas only one gene was significantly differentially expressed in the leaves; under both low-temperature and high-temperature stresses, there were significantly differentially expressed genes, and the EjJAZ15 gene was significantly upregulated under both low- and high-temperature stress. RNA-seq and qRT-PCR expression analysis under salt stress conditions revealed that EjJAZ2, EjJAZ4, and EjJAZ9 responded to salt stress in loquat plants, which promoted resistance to salt stress through the JA pathway. The response model of the TIFY genes in the jasmonic acid pathway under salt stress in loquat was systematically summarized. Conclusions These results provide a theoretical basis for exploring the characteristics and functions of additional EjTIFY genes in the future. This study also provides a theoretical basis for further research on breeding for salt stress resistance in loquat. RT-qPCR analysis revealed that the expression of one of the three EjTIFY genes increased and the expression of two decreased under salt stress conditions, suggesting that EjTIFY exhibited different expression patterns under salt stress conditions.

Ephedra sinica (E. sinica) holds significant economic and medicinal importance and is predominantly found in arid areas. Due to the limitations of environmental variables, growth habits, and human activities, the production and suitability areas of E. sinica have significantly decreased, especially in the five northwestern provinces of China. In this study, 212 distribution points of E. sinica and 40 environmental variables were obtained to project the habitat suitability of E. sinica under different emission scenarios in the future. It identified precipitation in the wettest month, monthly mean of the diurnal temperature difference, and solar radiation intensity in April and July as the primary environmental factors affecting the suitability of E. sinica in the region. The areas of high, medium, and low suitability in the region cover 103,000 km2, 376,500 km2, and 486,800 km2. Under future scenarios, the suitability areas from 2021 to 2100 will decrease by 20%, with high suitability areas decreasing by 65% to 85% particularly. With comprehensive environmental variables, the suitability areas of E. sinica from 2021 to 2100 are projected, filling the gap in the projection of E. sinica suitability areas in the five northwestern provinces of China over long time period. The suitability areas show a significant decreasing trend. This research provides valuable insights into the suitability areas and crucial environmental factors, offering theoretical support for future protection and management efforts for E. sinica.

The increase in atmospheric CO2 leads to global warming and ecological environment deterioration. Carbon storage modeling and assessment can promote the sustainable development of the ecological environment. This paper took Xinjiang as the study area, analyzed the spatial and temporal evolution of land use in four periods from 1990 to 2020, explored the spatial relationship of carbon stocks using the InVEST model, and coupled the GMOP model with the PLUS model to carry out multiple scenarios for the future simulation of land use in the study area. We found (1) Over time, the types with an increasing area were mainly impervious and cropland, and the types with a decreasing area were grassland, snow/ice, and barren; spatially, the types were predominantly barren and grassland, with the conversion of grassland to cropland being more evident in the south of Northern Xinjiang and north of Southern Xinjiang. (2) The evolutionary pattern of terrestrial carbon stocks is increasing and then decreasing in time, and the carbon sink areas are concentrated in the Tarim River Basin and the vicinity of the Ili River; spatially, there are differences in the aggregation between the northern, southern, and eastern borders. By analyzing the transfer in and out of various categories in Xinjiang over the past 30 years, it was obtained that the transfer out of grassland reduced the carbon stock by 5757.84 × 104 t, and the transfer out of Barren increased the carbon stock by 8586.12 × 104 t. (3) The land use layout of the sustainable development scenario is optimal under the conditions of satisfying economic and ecological development. The reduction in terrestrial carbon stocks under the 2020–2030 sustainable development scenario is 209.79 × 104 t, which is smaller than the reduction of 830.79 × 104 t in 2010–2020. Land optimization resulted in a lower loss of carbon stocks and a more rational land-use layout. Future planning in Xinjiang should be based on sustainable development scenarios, integrating land resources, and achieving sustainable economic and ecological development.

The distribution of forest-dominant tree species is crucial for ecosystem assessment. Remote sensing monitoring requires annual ground sample data, but consistent field surveys are challenging. This study addresses this by combining sample migration learning and machine learning for multi-year tree species classification in the Three Gorges Reservoir area in China. Using the continuous change detection and classification (CCDC) algorithm, sample data from 2023 were successfully migrated to 2018–2022, achieving high migration accuracy (R2 = 0.8303, RMSE = 4.64). Based on migrated samples, random forest (RF), support vector machine (SVM), and extreme gradient boosting (XGB) algorithms classified forest tree species with overall accuracies above 70% and Kappa coefficients above 0.6. XGB. They outperformed other algorithms, with classification accuracy of over 80% and Kappa above 0.75 in almost all years. The final map indicates stable distribution from 2018 to 2023, with eucalyptus covering over 40% of the forest area, followed by horsetail pine, fir, cypress, and wetland pine.

Assessing the spatio-temporal variability and driving forces of soil erosion on the Loess Plateau is critical for ecological and environmental management. In this paper, the Revised Universal Soil Loss Equation (RUSLE) model, the patch-generating land use simulation, and the Geographical Detector are used to investigate the spatio-temporal variations of the Loess Plateau’s soil erosion from 2000 to 2050. The results showed that: (1) The primary categories of soil erosion from 2000 to 2020 were moderate, mild, and slight, and the average level of soil erosion exhibited a decreasing and then an increasing tendency during the last 20 years. (2) Soil erosion was directly impacted by changes in land use, with cropland and forest being the primary land use and land cover changes in the study region. Cropland and construction land being turned into woodland between 2000 and 2020 resulted in a significant decrease in the severity of soil erosion. Projected soil erosion is expected to increase significantly between 2020 and 2050 due to arable land being converted into construction land. (3) The key variables impacting the spatial distribution of soil erosion were LUCC (Land-Use and Land-Cover Change), NDVI (Normalized Difference Vegetation Index), and slope, and the interplay of these variables may increase their ability to explain soil erosion. Grasslands with an NDVI ranging from 0.9 to 1, rain ranging from 0.805 to 0.854 m, a slope above 35°, and a terrain elevation ranging from 1595 to 2559 m were identified as having a high risk of soil erosion. Soil erosion prevention and management efforts should focus on the ecological restoration of upland areas in the future.

Soil erosion is an important environmental problem in China. The hilly region of Jiangnan is characterized by severe soil erosion due to its unique climate and intensive human activities. Therefore, assessing soil erosion in this area is of great significance for achieving regional sustainable development. Based on the spatial zoning of natural resources and the spatial differences in precipitation, land cover, topographic features, and soil texture, we estimated soil erosion from 2000 to 2020 using the Revised Universal Soil Loss Equation (RUSLE) model. The study showed that micro-erosion dominates spatially in the subtropical forest subzone of the eastern hills, accounting for more than 60% of the total erosion area. Intense erosion was found in woodlands and grasslands and the erosion intensity tended to be lower in the plains. Erosion occurred mainly in areas with slopes >8°. The areas with significantly lower erosion were mainly distributed at the boundaries between forests, arable land, and artificial land surfaces. The areas where soil erosion significantly increased over the study period were mainly found in farmland areas (31.70%). Soil erosion occurred because of a combination of factors, among which vegetation cover played a prominent role. Elevation and slope were correlated with soil erosion intensity. Severe erosion in different parts of the study area showed two trends of spatial aggregation and discrete distribution. This analysis of soil erosion in the study area by the RUSLE model provides reference data for the eastern subtropical forest subregion including the Jiangnan Hills.

Manganese toxicity is a major obstacle to agriculture in acid soils. Dark pericarp disease (DPD) is a newly spread physiological disorder induced by excess Mn in litchi, leading to undesirable fruit appearance and substantial economic loss. In this work, broadcast of alkaline soil conditioner in winter, followed by foliar sprays of ascorbic acid and sulfur solution at fruit development, was adopted to examine the effect of these combinations on DPD alleviation in a litchi orchard, with DPD morbidities of 70~85% in recent ten years. The combination of soil conditioner broadcast and foliar water spray was used as the control. At harvest, DPD incidence was significantly decreased by sulfur spray (3.3 ± 1.0%) and slightly reduced by ascorbic acid spray (10.7 ± 8.0%) compared to the control (12.9 ± 7.6%). Soil pH and available Mn were significantly increased and reduced by the soil conditioner broadcast. Sulfur spray significantly inhibited Mn uptake but enhanced the accumulation of Mg, Ca, sugars and cyanidin-3-rutinoside in the pericarp, leading to improved fruit pigmentation. Antioxidase activities were regulated to resist Mn stress by sulfur spray. The spray of ascorbic acid could not mitigate DPD as expected, probably due to the dose used. Conclusively, this study provides a practicable approach to mitigate Mn phytoavailability in acid soils.

Abstract Natural killer (NK) cell therapies, primarily based on chimeric antigen receptor NK cells (CAR‐NK), have been developed and applied clinically for therapeutic treatment of patients with mid‐to‐late‐stage tumors. However, NK cell therapy has limited efficacy due to insufficient antigen expression on the tumor cell surface. Here, a universal “illuminate tumor homogenization antigen properties” (ITHAP) strategy to achieve stable and controlled antigen expression on the surface of tumor cells using nanomedicine, thus significantly enhancing the immune recognizability of tumor cells, is described. The ITHAP strategy is used to generate bio‐liposomes (Pt@PL‐IgG) composed of intermingled platelet membranes and liposomes with NK‐activatable target antigen (IgG antibodies) and cisplatin pre‐drug. It is demonstrated that Pt@PL‐IgG successfully targets tumor cells using the autonomous drive of platelet membranes and achieves IgG implantation on tumor cells by utilizing membrane fusion properties. Moreover, it is shown that the Pt‐DNA complex combined with NK cell‐induced pyroptosis causes substantial interferon (IFN) secretion, thus providing a synthase‐stimulator of interferon genes (STING)‐IFN‐mediated positive immune microenvironment to further potentiate NK therapy. These results show that anchoring cancer cells with NK‐activatable target antigens is a promising translational strategy for addressing therapeutic challenges in tumor heterogeneity.

Background: Cardiac involvement is commonly present in various neuromuscular diseases which may develop life-threatening consequences. The early manifestation is often asymptomatic which however has been insufficiently studied. Objectives: We aim to characterize electrocardiographic (ECG) changes in neuromuscular diseases without cardiac symptoms. Methods: Adults having genetically and/or pathologically confirmed type 1 myotonic dystrophy (DM1), Becker muscular dystrophy (BMD), limb girdle muscular dystrophies (LGMDs) and mitochondrial diseases (MtDs) but without history of heart diseases and cardiovascular symptoms were enrolled. The 12-lead ECG characteristics and other test results at diagnosis were retrieved and analyzed. Results: 196 patients with neuromuscular diseases (44 DM1, 25 BMD, 82 LGMDs, 45 MtDs) were consecutively enrolled. ECG abnormalities were identified in 107 (54.6%) patients with a prevalence of 59.1% in DM1, 76.0% in BMD, 40.2% in LGMDs and 64.4% in MtDs. Conduction block was more commonly present in DM1 than the other groups (P

The processability and ultimate quality of coffee (Coffea arabica) are determined by the composition of the matured fruits. The basis of genetic variation in coffee fruit quality could be explained by studying color formation during fruit maturation. Transcriptome profiling was conducted on matured fruits of four C. arabica varieties (orange colored fruits (ORF); purple colored fruits (PF); red colored fruits (RF) and yellow colored fruits (YF)) to identify key color-regulating genes, biosynthesis pathways and transcription factors implicated in fruit color formation. A total of 39,938 genes were identified in the transcriptomes of the four C. arabica varieties. In all, 2745, 781 and 1224 differentially expressed genes (DEGs) were detected in YF_vs_PF, YF_vs_RF and YF_vs_ORF, respectively, with 1732 DEGs conserved among the three pairwise groups. Functional annotation of the DEGs led to the detection of 28 and 82 key genes involved in the biosynthesis of carotenoids and anthocyanins, respectively. Key transcription factors bHLH, MYB, NAC, MADS, and WRKY implicated in fruit color regulation were detected. The high expression levels of gene-LOC113688784 (PSY), gene-LOC113730013 (β-CHY), gene-LOC113728842 (CCD7), gene-LOC113689681 (NCED) and gene-LOC113729473 (ABA2) in YF may have accounted for the yellow coloration. The differential expression of several anthocyanin and carotenoid-specific genes in the fruits substantially account for the purple (PF), red (RF), and orange (ORF) colorations. This study provides important insights into fruit color formation and variations in C. arabica and will help to develop coffee varieties with specific color and quality traits.

The Loess Plateau is one of the most fragile ecological regions in China due to its shortage of water resources and severe soil erosion. The rapid development of urbanization and the implementation of the project of returning farmland to forest (grass) have caused the ecological environment of the region to be strongly impacted by human activities. It is necessary to investigate the spatial and temporal evolution characteristics of ecosystem services and trade-off/synergy relationships on the Loess Plateau, to achieve scientific management of ecological services and sustainable development of the region. This study quantitatively assesses three ecosystem services of water yield (WY), carbon storage (CS), and soil conservation (SC) on the Loess Plateau under different scenarios from 2000 to 2030 by using the InVEST and PLUS models. Further, the trade-off and synergistic relationships among the ecosystem services have been investigated by Spearman correlation analysis. The results showed that the land-use differences are more obvious under different policy scenarios, with a sharp expansion of constructed land, a gradual increase of forest land, and a continuous decrease of arable land in the Loess Plateau from 2000 to 2020; the water yield and soil conservation increase from 2000 to 2020, and the carbon storage shows an opposite trend. The soil conservation and carbon storage scenarios are the best under the ecological conservation scenario in 2030, while the water yield service is the best under the economic development scenario. There is a synergistic relationship between CS and SC, while there is a trade-off relationship between CS and WY. In addition, there are significant trade-off effects between SC and WY. These results can support guiding land-use management and ecological restoration.

Abstract Background Inferior wall ST‐segment elevation myocardial infarction (STEMI) is mostly caused by acute occlusion of right coronary artery (RCA) and left circumflex artery (LCX). Several methods and algorithms using 12‐lead ECG were developed to localize the lesion in inferior wall STEMI. However, the diagnostic properties of these methods remain under‐recognized. Aims The aim of this meta‐analysis is to compare the diagnostic properties among the methods of identifying culprit artery in inferior wall STEMI using 12‐lead ECG. Methods We performed a meta‐analysis to calculate the pooled sensitive, specificity, area under the curve (AUC) and diagnostic odds ratio (DOR) of each method. Results Thirty‐three studies with 4414 participants were included in the analysis. Methods using double leads had better diagnostic properties, especially ST‐segment elevation (STE) in III > II [with pooled sensitivity 0.89 (0.84–0.93), specificity 0.68 (0.57–0.79), DOR 17 (9–32), AUC 0.88 (0.85–0.91)], ST‐segment depression (STD) in aVL > I [with pooled sensitivity 0.82 (0.72–0.90), specificity 0.69 (0.48–0.86), DOR 11 (4–29), AUC 0.85 (0.81–0.88)], and STD V3/STE III ≤1.2 [with pooled sensitivity 0.88 (0.78–0.95), specificity 0.59 (0.42–0.75), DOR 12 (5–27), AUC 0.82 (0.78–0.85)]. Diagnostic algorithms, including Jim score[pooled sensitivity 0.70 (0.55–0.85), specificity 0.88 (0.75–0.96)], Fiol's algorithm [pooled sensitivity 0.54 (0.44–0.62), specificity 0.92 (0.88–0.96)] and Tierala's algorithm [pooled sensitivity 0.60 (0.49–0.71), specificity 0.91 (0.86–0.96)], were not superior to these simple methods. Conclusions Our meta‐analysis indicated that diagnostic methods using double leads had better properties. STE in III > II together with STD in aVL > I may be the most ideal method, for its accuracy and convenience.

Habitat quality has great significance in terms of regional ecological conservation and human welfare. In this study, we evaluated the spatial and temporal characteristics of land use and habitat quality in the temperate desert sub-region of the Ordos Plateau using patch-generating land use simulation (PLUS) and integrated valuation of ecosystem services and trade-offs (InVEST) models. From 2000 to 2020, the areas of grassland, cropland, and unused land in the study area increased significantly; the areas of water bodies and woodland increased slightly; and the area of wasteland decreased significantly. Moreover, the habitat quality in the temperate desert subzone of the Ordos Plateau showed a trend of initial increase and then decrease between 2000 and 2020. The areas of lower and low habitat quality first decreased and then increased, and the overall area decreased over time. Conversely, the areas of high and higher habitat quality initially increased and then decreased, and the overall area increased over time. The area of medium habitat quality first decreased and then increased, although the overall change was minimal. Based on the PLUS model, the predicted habitat quality of the study area in 2025 under the natural development scenario was compared to that predicted under the ecological conservation scenario. The comparison of results showed higher habitat quality and lower habitat degradation under the ecological conservation development scenario. These results can be used to provide a scientific basis and decision reference for the sustainable use of land resources and encouragement of high-quality socio-economic development in the temperate desert sub-region of the Ordos Plateau.

The study area was the Hulunbuir Plateau in northeastern China, based on a natural resource element observation study. The assessment of the spatial and temporal variation of soil erosion is crucial for implementing environmental management in the fragile ecosystem of the Hulunbuir Plateau. The study provides an interesting basis for soil erosion control on the Hulunbuir Plateau and other areas with similar climatic conditions, with the aim of providing sound data to support environmental protection policies in the study area. In this study, the spatial and temporal variations in soil erosion in the region from 2000 to 2020 were quantitatively assessed using the Revised Universal Soil Loss Equation. Furthermore, the patch-generating land use simulation model predicted future soil erosion. Land use prediction data were examined using Kappa coefficients. The prediction of future land use types using CMIP6 data and natural social data in the PLUS model were used to predict soil erosion for different future scenarios. The results showed that the soil erosion rate on the Hulunbuir Plateau showed a significant increasing trend in time from 2000 to 2020. Spatially, soil erosion increases gradually from the west to the east. Soil erosion occurs mainly on grasslands, while cultivated lands show a significant increasing trend by 2020. Slope erosion occurs mainly in areas between 15° and 35°. From 2020 to 2050, soil erosion will increase significantly due to increased precipitation. The soil erosion in SSP2–4.5 is better than the other scenarios.

Background: Atrial fibrillation (AF) is related to a higher risk of thromboembolic events and mortality. Some studies have demonstrated that the inflammatory biomarker interleukin-6 (IL-6) is associated with a higher risk of higher thrombosis in AF patients, but the real effect of IL-6 remains a controversy. Methods: We conducted a systematic review and meta-analysis to investigate the association between IL-6 and thromboembolic events, as well as bleeding events, acute coronary syndrome (ACS) events and all-cause mortality in AF. Results: A total of five studies involving 22 928 patients met our inclusion criteria for the systematic review. The higher level of IL-6 in AF patients is related to long-term thromboembolic events including stroke (RR 1.44, CI 95% 1.09-1.90, p=0.01). IL-6 meant a higher risk of long-term bleeding risk (RR 1.36, CI 95% 1.06-1.74, p=0.02), ACS risk (RR 1.81, CI 95% 1.43-2.30, p

Abstract Beyond hemostasis, thrombosis and wound healing, it is becoming increasingly clear that platelets play an integral role in inflammatory response and immune regulation. Platelets recognize pathogenic microorganisms and secrete various immunoregulatory cytokines and chemokines, thus facilitating a variety of immune effects and regulatory functions. In this review, we discuss recent advances in signaling of platelet activation-related biomarkers in inflammatory settings and application prospects to apply for disease diagnosis and treatment.

Diabetes is well recognized to increase the risk of heart failure, which is associated with higher mortality and morbidity. It is important for the development of novel therapeutic methods targeting heart failure in diabetic patients. Ferroptosis, an iron-dependent regulated cell death, has been implicated in the progression of diabetes-induced heart failure (DIHF). This study was designed to investigate the contribution of Nr2f2 to the activation of ferroptosis and mitochondrial dysfunction in DIHF. We established a diabetic model by a high-fat feeding diet combined with an intraperitoneal injection of streptozotocin. After 16 weeks, Nr2f2 expression was increased in heart tissue of DIHF mice. In vivo, DIHF mice overexpressing Nr2f2 (AAV9-cTNT-Nr2f2) exhibited severe heart failure and enhanced cardiac ferroptosis compared with DIHF control mice (AAV9-cTNT-ctrl), accompanied by mitochondrial dysfunction and aggravated oxidative stress reaction. In vitro, Nr2f2 knockdown ameliorated ferroptosis and mitochondrial dysfunction by negatively regulating PGC-1α, a crucial metabolic regulator. PGC-1α knockdown counteracted the protective effect of Nr2f2 knockdown. These data suggest that Nr2f2 promotes heart failure and ferroptosis in DIHF by modulating the PGC-1α signaling. Our study provides a new idea for the treatment of diabetes-induced heart failure.

Platelet activation and thrombus formation is a delicate process involving a series of crosstalk between different pathways. P70 ribosomal S6 kinase1 (S6K1) is a member of serine/threonine kinases and can be phosphorylated by 3-phosphoinositide-dependent protein kinase 1 (PDK1). S6K1 is widely reported to play important roles in cancers and metabolic diseases, but the role of S6K1 and the importance of phosphorylation on Thr229 in platelet activation have not been defined. PF-4708671 is a recently synthesized highly specific inhibitor of S6K1. In this study, we tested PF-4708671 to assess the role of S6K1 in platelet. PF-4708671 facilitated mouse and human platelet aggregation and ATP secretion induced by collagen, thrombin, and adenosine diphosphate through enhanced Akt and Gsk3β phosphorylation. PF-4708671 also accelerated integrin αIIbβ3-mediated clot retraction and spreading. Intravenously given PF-4708671 shortened the occlusion time in arterial thrombosis model. Further results demonstrated that S6K1 was phosphorylated by PDK1 on Thr229 in the resting platelets and dephosphorylated in response to agonist stimulation. PDK1-deficient mice showed higher aggregation when PI3K–Akt–Gsk3β signaling was blocked by the Gsk3β-inhibitor SB216763. Thus, S6K1 Thr229 phosphorylation might function as a regulator that prevents platelets from activation. S6K1 inhibition may yield potential pro-thrombotic effects and should be used cautiously when considered as a therapy.

Objective To evaluate the protective effect of pravastatin on atherosclerotic development and inflammatory monocyte subset in atherosclerotic apolipoprotein E (ApoE) −/− mice after myocardial infarction (MI). Methods Male ApoE −/− mice (8 weeks old) were fed a high-fat diet for 14 weeks throughout the experiment. A MI model was produced using 18-week-old ApoE −/− mice. They were randomly divided into three groups: sham group, MI group, and MI+Pra group (40 mg/kg/day pravastatin). After 4 weeks (at the end of the study period), the mice were sacrificed and cardiac function was evaluated by echocardiography. Aortic lesion areas were evaluated using oil red O staining. Plaque macrophage in aortic sinus was analyzed by immunofluorescence staining. Flow cytometry was used to explore the proportions of monocyte subsets in the blood, spleen, and bone marrow． Results Pravastatin improved cardiac function and reduced lesion areas. It also attenuated the supply of monocytes in spleen, especially the inflammatory Ly6C high monocyte subset. Pravastatin also subsequently reduced macrophage accumulation in atherosclerotic lesions. Conclusions MI accelerated chronic atherosclerosis progress. Pravastatin suppressed atherosclerotic development and inhibited inflammatory monocytosis after MI in ApoE −/− mice.

Objective To determine the prevalence of percutaneous coronary intervention (PCI) related myocardial damage (injury or myocardial infarction), investigate several cardiac biomarkers, explore possible risk factors and assess survival in patients undergoing elective PCI. Methods Patients >18 years of age who had undergone an elective PCI at Huashan hospital in Shanghai, China from October 2016 to June 2017 and had baseline and post-PCI results available for four cardiac biomarkers (cTnT, CK-MB mass, hs-CRP and NT-ProBNP) were eligible. Patients were separated into two groups according to whether or not they had PCI related myocardial damage. Results Of the 143 patients who were eligible for the study, 75 (52%) were classified as ‘controls,’ and 68 (48%) had PCI related myocardial damage. Of the 68 patients, 64 (45%) had PCI related myocardial injury and 4 (3%) had PCI related myocardial infarction. Elderly Chinese patients, with high systolic blood pressure on admission and who required multiple coronary segments for PCI had a high risk of myocardial damage. Relative cTnT or relative CK-MB mass may be useful cardiac biomarkers for monitoring PCI related myocardial damage, especially at 24h post-PCI. There was no significant difference in survival rates between controls and those with myocardial complications. Conclusions PCI related myocardial damage is common but appears to have no impact on prognosis. Senior age, high systolic blood pressure and multiple coronary segments for PCI are risk factors.

Summary: Background: To assess the morbidity and risk factors of contrast induced nephropathy (CIN) in Chinese very elderly patients. Methods: The very elderly patients whose age ≥75 year-old, from North Huashan Hospital, South Renji Hospital and Tongren Hospital, underwent coronary angiography or percutaneous coronary intervention, were included in this study. All of these patients were treated by hydration, those who developed contrast-induced nephropathy were divided into CIN group and the others were divided into non-CIN group. The baseline information was evaluated and serum creatinine was measured prior to the coronary angiography and 24 h, 48 h after procedure. The data was analyzed by the software SPSS17.0. Results: 163 very elderly patients were included in this study. The occurrence of CIN in very elderly patients was approximately 8.6%. In CIN group, serum creatinine concentration was statistical significance between prior data and 24 h/48 h after procedure data, but there's no statistically significant differences between 24 h data and 48 data after procedure. Multivariable analysis showed that patient's age (p value 0.026, OR 1.171, 95% CI 1.019–1.347), and complicated lesion (p value 0.025, OR 3.91, 95% CI 1.185–12.896) were correlation with CIN. Conclusion: The incidence of CIN with hydration treatment is similar to that of average patients. Very elderly patient with older age, higher dosage of contrast media and complicated lesion is vulnerable to develop CIN. Keywords: Contrast induced nephropathy, hydration treatment, morbidity, risk factors, very elderly patient

Background The factors that influence cognitive function in patients with atrial fibrillation (AF) remain unclear. Methods This study involved an AF group and control group (normal sinus rhythm) of 150 patients each. Cognitive function was assessed with the adjusted Mini-Mental State Examination (MMSEadj) score and Memory and Executive Screening (MES) score. The relationship between cognitive function and the CHA 2 DS 2 VASc score was analyzed. Subgroup analysis was performed according to stroke history. Clinical factors affecting the MMSE score were screened by logistic regression analysis. Results Baseline data were similar between the two groups. The MMSEadj and MES scores were significantly lower in the AF than control group; the mean MMSEadj score in the AF non-stroke subgroup and control non-stroke subgroup was 26.2 ± 2.7 and 27.9 ± 2.0, respectively. In non-stroke patients with AF, the MMSEadj and MES scores were negatively correlated with the CHA 2 DS 2 VASc score. Factors significantly influencing the MMSE score in these patients were age, education, smoking history, NT-proB-type natriuretic peptide, hemoglobin, and anticoagulation. Conclusion AF is associated with cognitive dysfunction regardless of stroke history. High CHA 2 DS 2 VASc scores are associated with impaired cognitive function. Factors influencing cognitive function in non-stroke patients with AF are age, education, smoking history, NT-proB-type natriuretic peptide, hemoglobin, and anticoagulation.

Dynamic endocytic and exocytic trafficking of integrins is an important mechanism for cell migration, invasion, and cytokinesis. Endocytosis of integrin can be classified as clathrin dependent and clathrin independent manners. And rapid delivery of endocytic integrins back to the plasma membrane is key intracellular signals and is indispensable for cell movement. Integrin αIIbβ3 plays a critical role in thrombosis and hemostasis. Although previous studies have demonstrated that internalization of fibrinogen-bound αIIbβ3 may regulate platelet activation, the roles of endocytic and exocytic trafficking of integrin αIIbβ3 in platelet activation are unclear. In this study, we found that a selective inhibitor of clathrin-mediated endocytosis pitstop 2 inhibited human platelet spreading on immobilized fibrinogen (Fg). Mechanism studies revealed that pitstop 2 did not block the endocytosis of αIIbβ3 and Fg uptake, but inhibit the recycling of αIIbβ3 to plasma membrane during platelet or CHO cells bearing αIIbβ3 spreading on immobilized Fg. And pitstop 2 enhanced the association of αIIbβ3 with clathrin, and AP2 indicated that pitstop 2 inhibit platelet activation is probably due to disturbance of the dynamic dissociation of αIIbβ3 from clathrin and AP2. Further study demonstrated that Src/PLC/PKC was the key pathway to trigger the endocytosis of αIIbβ3 during platelet activation. Pitstop 2 also inhibited platelet aggregation and secretion. Our findings suggest integrin αIIbβ3 trafficking is clathrin dependent and plays a critical role in platelet spreading, and pitstop 2 may serve as an effective tool to address clathrin-mediated trafficking in platelets.

Abstract Background To compare the accuracy of different obesity indexes, including waist circumference (WC), weight-to-height ratio (WHtR), body mass index (BMI), and lipid accumulation product (LAP), in predicting metabolic syndrome (MetS) and to estimate the optimal cutoffs of these indexes in a rural Chinese adult population. Methods This prospective cohort involved 8468 participants who were followed up for 6 years. MetS was defined by the International Diabetes Federation, American Heart Association, and National Heart, Lung, and Blood Institute criteria. The power of the 4 indexes for predicting MetS was estimated by receiver operating characteristic (ROC) curve analysis and optimal cutoffs were determined by the maximum of Youden’s index. Results As compared with WHtR, BMI, and LAP, WC had the largest area under the ROC curve (AUC) for predicting MetS after adjusting for age, smoking, drinking, physical activity, and education level. The AUCs (95% CIs) for WC, WHtR, BMI, and LAP for men and women were 0.862 (0.851–0.873) and 0.806 (0.794–0.817), 0.832 (0.820–0.843) and 0.789 (0.777–0.801), 0.824 (0.812–0.835) and 0.790 (0.778–0.802), and 0.798 (0.785–0.810) and 0.771 (0.759–0.784), respectively. The optimal cutoffs of WC for men and women were 83.30 and 76.80 cm. Those of WHtR, BMI, and LAP were approximately 0.51 and 0.50, 23.90 and 23.00 kg/m2, and 19.23 and 20.48 cm.mmol/L, respectively. Conclusions WC as a preferred index over WHtR, BMI, and LAP for predicting MetS in rural Chinese adults of both genders; the optimal cutoffs for men and women were 83.30 and 76.80 cm.

Abstract Background Foam cells play a key role in the occurrence and pathogenesis of atherosclerosis. Its formation starts with the ingestion of oxidized low-density lipoprotein (oxLDL). The process is associated with Ras related protein in brain 5 (Rab5) which plays a critical role in regulating endocytosis and early endosomal trafficking. Base on this, we presumed that Rab5 might participate in the maturation of foam cell. The aim of this study is to investigate the effect of Rab5 on macrophage cholesterol during the evolvement of macrophage when induced by oxLDL to the formation of foam cell. Methods Immunohistochemistry was performed to analyze the distribution of macrophages and Rab5 in atherosclerotic plaque. RNA inteference study and transfection of inactive mutant (GFP-Rab5-S34N) and active mutant (GFP-Rab5-Q79L) in U937-derived macrophage were utilized to investigate the impact of Rab5 on the process of macrophage cholesterol, which could be detected by oil red O staining, determination of intracellular lipid content, filipin staining, nile red staining and the costaining of early endosome antigen-1 (EEA-1) and 1,1′-dioctadecyl-3,3,3′,3′-tetramethylin dicarbocyanine (Dil)-labelled oxLDL (Dil-oxLDL). Results Rab5 was found abundantly localized in macrophage rich areas of human atherosclerotic lesions. On the foam cell study, the expression of Rab5 was increased after the incubation of oxLDL. The inteference study indicated the depletion of Rab5 led to the decreases of oil red O staining areas, total cholesterol and cholesterol esters in U937-derived marophages. Moreover, the fluorescence intensity of filipin and nile red staining were lower in GFP-Rab5-S34N as compared with GFP-Rab5-Q79L. The confocal study demonstrated less Dil-oxLDL was internalized in GFP-Rab5-S34N as compared with GFP-Rab5-Q79L; the result showed also the decrease in colocalization of internalized Dil-oxLDL and EEA-1 for GFP-Rab5-S34N as compared with GFP-Rab5-Q79L. Conclusions Rab5 plays an important role in modulating the intracellular cholesterol of macrophages and consequently mediating the formation of foam cells.

Abstract Limited information is available on the effect of hypertriglyceridemia–waist (HTGW) combination and its dynamic status on the risk of type 2 diabetes mellitus (T2DM) in rural China. A cohort of 12,086 participants 18 to 92 years old was retained in this study. Kaplan-Meier analysis yielded the cumulative incidence of T2DM for each phenotype group (based on TG level and waist circumference [WC] at baseline). Cox regression yielded hazard ratios relating HTGW (based on TG level and WC at baseline and follow-up) to risk of developing T2DM. After a median follow-up of 6.0 years (71,432 person-years of follow-up), T2DM developed in 621 participants. For HTGW participants, the incidence of T2DM was 26.4/1000, 20.6/1000, and 21.9/1000 person-years for males, females, and overall, respectively. The adjusted HR for HTGW associated with T2DM was 7.63 (95% CI 4.32–13.49) for males and 7.75 (4.71–12.78) for females. Compared with consistent HTGW, with transformation from baseline HTGW to normal WC and normal triglycerides level at follow-up, the risk of developing T2DM was reduced by 75% and 78% for males and females. HTGW is a major risk factor for T2DM, but the risk could be reduced by improved triglycerides level and WC.

Background/Aims: Mitochondrial DNA (mtDNA), acting as a newly found ‘danger-associated molecular patterns’ (DAMPs), is released into circulation upon tissue injury and performs as a considerable activator of inflammation and immune response. However, the role of circulating mtDNA in experimental autoimmune myocarditis (EAM) as well as Toll like receptor4 (TLR4) mediated cardiac inflammation and injury remains unknown. Methods: A model of EAM was established in BALB/c mice by immunization with porcine cardiac myosin. Lipopolysaccharide (LPS) was used to stimulate TLR4 activation in EAM mice and H9C2 cells. Results: LPS stimulation significantly aggravated cardiac inflammation and tissue injury in EAM, as demonstrated by increased myocardium inflammatory cell infiltration, and up-regulated inflammatory cytokines and troponin I(TnI) level in serum. Circulating mtDNA level was increased in EAM and TLR4 activation led to a greater elevation, which may be related to Reactive oxygen species (ROS) stress involved mtDNA damage characterized by reduced mtDNA copy number in myocardium tissue. In addition, the expression of Toll like receptor9 (TLR9), a ligand of mtDNA, was significantly up-regulated in the myocardium of EAM and EAM LPS group; meanwhile, TLR9 inhibition by ODN 2088 caused an inhibited apoptosis in LPS treated H9C2 cells. Moreover, in EAM and EAM LPS group, simultaneously giving ODN 2088 treatment significantly ameliorated cardiac inflammation and tissue injury compared with untreated group. Conclusion: Increased circulating mtDNA combined with upregulated TLR9 expression may corporately play a role in EAM as well as TLR4 activation mediated cardiac inflammation and injury.

Objective This study was performed to investigate the relationship between the serum cystatin C (Cys C) level and acute coronary syndrome (ACS) in patients of advanced age. Methods The study included 184 patients with ACS and 46 healthy control subjects. Statistical analysis was performed using SPSS version 14.0 (SPSS Inc., Chicago, IL, USA). Results The serum Cys C level was significantly higher in patients with than without ACS (1.24 ± 0.30 vs. 1.42 ± 0.46 mg/L, respectively). Patients with more stenotic coronary arteries were significantly more likely to have higher median serum Cys C and creatinine levels and a lower estimated glomerular filtration rate. The multivariate logistic regression analysis demonstrated that the serum Cys C level was independently associated with the presence of ACS and the quantity of stenotic coronary arteries after adjustment for confounding factors. Additionally, the serum Cys C level was positively correlated with age, the creatinine level, and the N-terminal pro-B-type natriuretic peptide level in all patients but was negatively correlated with the estimated glomerular filtration rate. Conclusion A high serum Cys C level was independently associated with ACS and the quantity of stenotic coronary arteries in patients of advanced age regardless of renal function.

Collection, characterization and utilization of genetic resources are crucial for developing varieties to meet current and future needs. Although mango is an economically important fruit tree, its genetic resources are still undocumented and are threatened in their natural habits. In this study, the variability of 452 mango accessions from three regions in China (Nujiang, Lancang river and Honghe) was assessed using 41 descriptors including qualitative and quantitative traits, with the aim to identify mango accessions with excellent agronomic and quality traits. To this end, descriptive and multivariate analyses were performed. Based on Shannon−Weaver diversity index, qualitative traits including pericarp color, fruit aroma, flesh color, and fruit flavor recorded the highest variability in the germplasm. Fruit related traits including pulp weight, peel weight, and fruit weight were the most diverse traits in the germplasm with a high coefficient of variation (CV > 40%). Significant differences (MANOVA test, p < 0.000) were observed among the three regions for most of the quantitative traits. Biologically significant and positive correlations were found among agronomically important traits such as fruit weight and pulp weight, fruit weight and edible rate. The hierarchical cluster analysis revealed tree clusters, indicating a low diversity in the germplasm. The majority of the descriptors contributed to the differentiation of the accessions. Accessions with good fruits quality (high fruit weight, pulp weight, and edible rate) were found in Cluster 2. Accessions in this cluster could be used for fruit quality improvement in mango breeding programs. Our study sheds light on the diversity of a large collection of natural mango population in China and provides relevant information for efficient conservation and harnessing of mango genetic resources.

Stem rot caused by Sclerotinia sclerotiorum in many important dicotyledonous crops, including oilseed rape (Brassica napus), is one of the most devastating fungal diseases and imposes huge yield loss each year worldwide. Currently, breeding for Sclerotinia resistance in B. napus, as in other crops, can only rely on germplasms with quantitative resistance genes. Thus, the identification of quantitative trait locus (QTL) for S. sclerotiorum resistance/tolerance in this crop holds immediate promise for the genetic improvement of the disease resistance. In this study, ten QTLs for stem resistance (SR) at the mature plant stage and three QTLs for leaf resistance (LR) at the seedling stage in multiple environments were mapped on nine linkage groups (LGs) of a whole genome map for B. napus constructed with SSR markers. Two major QTLs, LRA9 on LG A9 and SRC6 on LG C6, were repeatedly detected across all environments and explained 8.54-15.86% and 29.01%-32.61% of the phenotypic variations, respectively. Genotypes containing resistant SRC6 or LRA9 allele showed a significant reduction in disease lesion after pathogen infection. Comparative mapping with Arabidopsis and data mining from previous gene profiling experiments identified that the Arabidopsis homologous gene of IGMT5 (At1g76790) was related to the SRC6 locus. Four copies of the IGMT5 gene in B. napus were isolated through homologous cloning, among which, only BnaC.IGMT5.a showed a polymorphism between parental lines and can be associated with the SRC6. Furthermore, two parental lines exhibited a differential expression pattern of the BnaC.IGMT5.a gene in responding to pathogen inoculation. Thus, our data suggested that BnaC.IGMT5.a was very likely a candidate gene of this major resistance QTL.

AIMS: We aimed to replicate the association of the rs290487 (IVS3C/T) and rs7903146 (IVS3C/T) polymorphisms of transcription factor 7-like 2 (TCF7L2) and type 2 diabetes mellitus (T2DM) in Han Chinese people in Henan province, China. METHODS: In all, 1,842 patients with T2DM and 7,777 normal glucose-tolerant controls underwent genotyping for the T2DM-associated variants rs7903146 (IVS3C/T) and rs290487 (IVS3C/T). W performed a meta-analysis of the association of the risk alleles of rs7903146 (IVS3C/T) and rs290487 (IVS3C/T) in TCF7L2 and T2DM in Han Chinese by combining previous studies with the present study. RESULTS: We found that T2DM was associated with the CC genotype (1.364, 1.137-1.636, p = 0.001), the recessive model (1.457, 1.156-1.838, p = 0.001) of rs290487 (IVS3C/T) and haplotype CC (1.116, 1.034-1.204, p = 0.004) in Han Chinese. Moreover, our meta-analyses supported the association of the T allele (IVS3C/T) of rs7903146 (1.36, 1.24-1.48; p = 6.404×10(-12)) and T2DM but not the C allele of rs290487 (IVS3C/T) (0.99, 0.85-1.15, p = 0.890) in Han Chinese. We found no interactions between behavioral risk factors (smoking, alcohol drinking, and physical activity) and rs7903146 (IVS3C/T) and rs290487 (IVS3C/T) polymorphisms. CONCLUSIONS: The CC genotype and the recessive model of the variant rs290487 (IVS3C/T) and CC haplotype of rs7903146 (IVS3C/T) and rs290487 (IVS3C/T) in TCF7L2 may be associated with T2DM in Han Chinese people in Henan province, China.

BackgroundLittle is known about the plasma levels of N-terminal pro-brain natriuretic peptide (NT-proBNP), and the relationship between the severity of coronary heart disease (CHD) with NT-proBNP and multiple biomarkers in diabetic and pre-diabetic patients, compared to individuals with normal glucose levels.MethodsFour hundred and fifteen consecutive Chinese patients of both sexes were assigned to three groups on the basis of the new hemoglobin (Hb) A1c (HbA1c) cut-off points for diagnosis of diabetes and pre-diabetes. The three groups were divided into tertiles according to NT-proBNP, hs-CRP, cystatin C, and troponin T levels. Gensini scores were compared among the three groups and biomarker tertiles. Receiver operating characteristic (ROC) curves were used to obtain the angiographic CHD cut-off points for each biomarker. Stepwise multivariate linear correlation analysis was applied to examine the association between the severity of CHD and biomarker levels.ResultsGensini scores increased with increasing biomarker tertile levels and HbA1c. Gensini scores were significantly different in the middle and upper NT-proBNP tertiles of the diabetic, pre-diabetic and control groups. NT-proBNP had the highest positive and negative predictive values and area under the curve for CHD. Only NT-proBNP was identified as an independent variable for Gensini score.ConclusionsPlasma NT-proBNP may be an important biomarker to evaluate the severity of CHD and screen for CHD in diabetic or pre-diabetic patients.