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Abstract EphrinB2 (erythropoietin-producing hepatoma interactor B2) is a key Eph/ephrin family member, promoting angiogenesis, vasculogenesis, and lymphangiogenesis during embryonic development. However, the role of EphrinB2 in cardiac lymphangiogenesis following myocardial infarction (MI) and the potential molecular mechanism remains to be demonstrated. This study revealed that EphrinB2 prevented ischemic heart post-MI from remodeling and dysfunction by activating the cardiac lymphangiogenesis signaling pathway. Deletion of EphrinB2 impaired cardiac lymphangiogenesis and aggravated adverse cardiac remodeling and ventricular dysfunction post-MI. At the same time, overexpression of EphrinB2 stimulated cardiac lymphangiogenesis which facilitated cardiac infiltrating macrophage drainage and reduced inflammation in the ischemic heart. The beneficial effects of EphrinB2 on improving clearance of inflammatory response and cardiac function were abolished in Lyve1 knockout mice. Mechanistically, EphrinB2 accelerated cell cycling and lymphatic endothelial cell proliferation and migration by activating CDK5 and CDK5-dependent ISL1 nuclear translocation. EphrinB2 enhanced the transcriptional activity of ISL1 at the VEGFR3 (FLT4) promoter, and VEGFR3 inhibitor MAZ51 significantly diminished the EphrinB2-mediated lymphangiogenesis and deteriorated the ischemic cardiac function. We uncovered a novel mechanism of EphrinB2-driven cardiac lymphangiogenesis in improving myocardial remodeling and function after MI.

Abstract Background Previous research has revealed the potential impact of circadian rhythms on pulmonary diseases; however, the connection between circadian rhythm-associated Thyrotroph Embryonic Factor (TEF) and Pulmonary Arterial Hypertension (PAH) remains unclear. We aim to assess the genetic causal relationship between TEF and PAH by utilizing two sets of genetic instrumental variables (IV) and publicly available Pulmonary Arterial Hypertension Genome-Wide Association Studies (GWAS). Methods Total of 23 independent TEF genetic IVs from recent MR reports and PAH GWAS including 162,962 European individuals were used to perform this two-sample MR study. Gain- and loss-of-function experiments were used to demonstrate the role of TEF in PAH. Results Our analysis revealed that as TEF levels increased genetically, there was a corresponding increase in the risk of PAH, as evidenced by IVW (OR = 1.233, 95% CI: 1.054–1.441; P = 0.00871) and weighted median (OR = 1.292, 95% CI for OR: 1.064–1.568; P = 0.00964) methods. Additionally, the up-regulation of TEF expression was associated with a significantly higher likelihood of abnormal circadian rhythm (IVW: P = 0.0024733, β = 0.05239). However, we did not observe a significant positive correlation between circadian rhythm and PAH (IVW: P = 0.3454942, β = 1.4980398). In addition, our in vitro experiments demonstrated that TEF is significantly overexpressed in pulmonary artery smooth muscle cells (PASMCs). And overexpression of TEF promotes PASMC viability and migratory capacity, as well as upregulates the levels of inflammatory cytokines. Conclusion Our analysis suggests a causal relationship between genetically increased TEF levels and an elevated risk of both PAH and abnormal circadian rhythm. Consequently, higher TEF levels may represent a risk factor for individuals with PAH.

With the in-depth development of globalization and informatization, digital trade, as an emerging form of trade, is gradually reshaping the global economic landscape and becoming a new engine for driving economic growth. Among them, the impact of digital trade on the export competitiveness of enterprises in developing countries has become a common concern in academia. To reveal the causal relationship between the development of digital trade and the enhancement of export competitiveness in developing countries, this paper first constructs a theoretical model based on product quality heterogeneity and analyzes the impact of digital trade on the export competitiveness of enterprises on the basis of achieving supply and demand equilibrium; then, this paper constructs a comprehensive index system for measuring digital trade and enterprise export competitiveness, and establishes an empirical analysis model; on this basis, this paper uses the data of listed companies in the A-share market in the Yangtze River Economic Belt area from 2011 to 2021 for empirical analysis. The results of the empirical analysis show that for every one-unit increase in the level of digital trade development in the region, there will be a positive impact of 0.9041 units on the export competitiveness of enterprises. After a series of robustness tests and endogeneity analyses, the above empirical results are confirmed to be robust and reliable. Furthermore, this paper conducts a heterogeneity analysis and finally puts forward corresponding policy recommendations based on the above theoretical and empirical research results.

Despite its ambitious “economic sustainability” objectives, the China-Pakistan Economic Corridor (CPEC) has been the subject of growing environmental anxiety. Considering the CPEC developments, it is clear that Pakistan is ready to fully embrace this new industrial chapter and take advantage of its major benefits to solve social, energy, infrastructure, and economic problems. However, it should also seriously commit to undertaking proper environmental impact assessments and upgrading system resilience. Data was collected from 400 respondents from Pakistan, and structural equation modeling was applied with the help of AMOS. Factor analysis and structural equation modeling techniques were used to estimate the results and test the study's hypothesis. The results indicate a strong socio-economic impact across perceived economic, infrastructure, social, and total impacts, but they identify a negative association between infrastructure innovation and environmental sustainability. Moreover, results revealed that infrastructure supports social and economic growth, but it might have a substantial negative impact on biodiversity. According to findings, Pakistan may be more vulnerable to climate change due to three potential environmental issues: coal-fired power plants, CO2 concentration along the CPEC route, and increased traffic on the Karakorum Highway. Furthermore, future international trade will be significantly impacted by the corridor. It may, however, also accelerate the destruction of the ecosystem over time due to the industrial revolution.

Objective To investigate the correlation between mildly elevated pulmonary artery systolic pressure (PASP) on echocardiography and mortality, as well as long-term changes in PASP.Design Retrospective cohort study.Setting Shanghai, China, a single centre.Participants A total of 910 patients were enrolled in this study. From January to June 2016, 1869 patients underwent echocardiography at the Zhongshan Hospital affiliated with Fudan University. Patients with malignant tumours, previous heart or other solid organ transplantation, previous or scheduled ventricular assist device implantation, severe kidney dysfunction (uraemia and patients on dialysis) and a life expectancy of less than 1 year for any medical condition were excluded.Interventions No interventions were done.Primary and secondary outcome measures The predictors of death in patients with mild echocardiographic pulmonary hypertension were analysed using univariate and multivariate Cox regression analyses. Paired t-tests were used to calculate changes in the PASP values at baseline and follow-up for different patient groups.Results The 5-year survival of patients was 93.2%. Patients were grouped according to whether they had combined organic heart disease (OHD). The PASP value was an independent predictor of all-cause mortality in patients with OHD, with each 1 mm Hg increase associated with an HR of 1.02 (95% CI: 1.01–1.03, p=0.038) but not in patients without OHD. Of the total, 46% (419/910) of the patients with 5–6 years of echocardiography were investigated for changes in the PASP value. We found significant PASP reduction in patients without OHD (42.8±2.4 mm Hg vs 39.3±8.2 mm Hg, p

Fertilization alters crop yield, soil aggregation, and carbon sequestration potential. However, the specific effects and interactive mechanisms of long-term fertilization on soil organic carbon (SOC), aggregate-associated organic carbon (OC), and yield in dryland wheat fields remain poorly understood. Therefore, a field experiment with local farmer fertilization (NP), measured and controlled fertilization (NPK), chemical fertilizer plus organic fertilizer (NPKM), chemical fertilizer plus bio-organic fertilizer (NPKB), and no fertilizer (CK) was conducted for 10 years in a semi-arid region of China. We examined the characteristics of crop yield, SOC stock, and soil aggregate under different fertilization methods to explore the carbon sequestration mechanisms associated with increased yield. The results revealed a significant positive linear correlation between carbon sequestration and carbon input, with a carbon sequestration efficiency of 27.4%. Different fertilization treatments increased the proportion of macroaggregates (>0.25 mm) and significantly improved the water stability of soil aggregates, with the combined application of organic–inorganic fertilizers (NPKM and NPKB treatments) showing the most pronounced effect. A redundancy analysis revealed that carbon input was the most important factor affecting aggregate stability. Partial least squares path modeling revealed that SOC content was enhanced primarily because of the increase in macroaggregate-associated OC and carbon input, which in turn led to higher wheat yields. Our findings indicate that macroaggregate-associated OC and carbon inputs have significant implications for SOC sequestration in dryland fields. Thus, we suggest the integrated application of organic fertilizers with balanced NPK fertilizers to promote SOC accumulation, improve aggregate stability, and enhance crop yield.

Background: Data regarding the prognosis of Eisenmenger syndrome (ES) and effect of targeted drugs are limited. This study aimed to analyze the prognosis and impact of targeted drug therapy on the survival rate of patients with ES in the Chinese population. Methods: The data of patients with ES referred to our hospital between January 2010 and December 2020 were retrospectively analyzed. Data included baseline demographics, echocardiographic parameters, and clinical diagnoses. All patients were followed up via telephone interviews in February 2022. The primary endpoint was mortality. Results: Overall, 1,021 patients with ES were included. The 1-, 3-, 5-, 7-, 10-, and 12-year survival rates were 91.6%, 84.2%, 80.7%, 73.8%, 71.4%, and 69.9%, respectively. Patients with atrial septal defects had the best prognosis than those with ventricular septal defects, patent ductus arteriosus, and complex congenital heart disease (CHD) (P

The use of fertilizers is mainly adopted in arid regions to improve the soil carbon (C) pool and crop productivity. However, the mechanisms underlying improvements in dryland wheat field soils related to microbial metabolic activity and community structure remain poorly understood. Therefore, a field experiment with four fertilization treatments and no fertilizer as the control (CK) was conducted for 10 years in a semi-arid region of China. The results revealed that the combined application of chemical and organic fertilizers (fermented chicken manure) clearly increased the levels of soil organic carbon (SOC), dissolved organic carbon (DOC), and light-fraction organic carbon (LFOC) by 13.54–16.72%, 6.96–9.01%, and 11.00–13.51%, respectively, compared to the sole use of chemical fertilizers (FP treatment). Moreover, the combined treatment not only enhanced the metabolic activity of microorganisms concerning carbon source utilization but also increased the diversity of the bacterial community. This caused noticeable changes in the composition of the bacterial community. A Mantel test analysis revealed that Bacteroidetes and Mortierellomycota significantly enhanced the metabolic activity associated with carbohydrate, amino acid, and carboxylic acid C sources. Actinobacteria, Bacteroidetes, and Mortierellomycota facilitated the accumulation of active C and particulate organic carbon (POC), whereas Mortierellomycota specifically promoted the accumulation of heavy-fraction organic carbon (HFOC), thereby collectively influencing the SOC content. The combined application of chemical and organic fertilizers increased the abundance of Bacteroidetes and Mortierellomycota. This enhancement improved the metabolic utilization of carbohydrates, amino acids, and carboxylic acids, resulting in alterations in the types and quantities of soil metabolites. Consequently, these alterations ultimately affect the composition and quantity of the SOC pool in arid agroecosystems. In conclusion, the combined application of balanced NPK fertilizers and organic fertilizers has a strong positive effect in improving soil microbial activity and the soil C pool.

The quality of primary products in a supply chain is determined by the agent and the principal. Simultaneously, there are quota production constraints on the principals. Our discourse centers on the design of incentive contracts for agents within these supply chains. We derived the parameters describing the contract, level of effort, profits for both sides, and the minimum requirements of the principal for the proportion of high-quality primary products. This study compares the decision-making paradigms of agents and principals in various contexts. The results show that decision-making mechanisms are strongly influenced by individual effort costs, various internal and external organizational variables, and the interplay of efforts on both sides. Using numerical experiments, we investigate the effects of different situations between clients and contractors on contracting and effort strategies. The results show that when the agent exerts unilateral effort, reasonable incentive contracts can spur the agent to increase effort and thus increase the proportion of high-quality primary products. In the case of bilateral efforts, a well-calibrated contract design benefits the agent (bearing less risk). For the principal, the expected profit increases in most cases. When considering the quota production, it is necessary to set an appropriate limit on the proportion of high-quality primary products.

The Loess Plateau in China has long grappled with issues such as chronic soil erosion, poor soil structure, and diminished organic matter. Soil organic carbon plays a crucial role in enhancing soil fertility, and fertilization is a key tool that influences it. In a comprehensive field experiment, we examined five fertilization methods: no fertilization (CK); traditional fertilization used by local farmers (FP); nutrient-balanced fertilization with nitrogen, phosphorus, and potassium (OF); chemical fertilizers used in conjunction with organic fertilizers (OFM); and chemical fertilizers paired with bio-organic fertilizers (OFB). Our findings revealed that the OFM and OFB treatments were the most effective, explaining 84.35% and 81.26% of the variation in soil carbon sequestration, respectively. Further, the OF, OFM, and OFB treatments demonstrated superior effectiveness compared with the FP treatment in enhancing the soil carbon fractions. However, these fertilization patterns did not significantly alter the active-to-inert carbon ratio of the soil. OF, OFM, and OFB treatments enhanced the stability of soil carbon pools more than FP treatment. In structural equation modeling, factors such as microbial biomass nitrogen and phosphorus, soil pH, and β-N-acetyl glucosidase indirectly exhibited a limiting effect on the carbon pool stability index (CPSI), while β-glucosidase displayed an indirect positive correlation with the carbon fractions. In contrast, dissolved organic carbon, low-molecular-weight organic carbon, high-molecular-weight organic carbon, and crop yield demonstrated direct positive correlations with the CPSI. Consequently, both a balanced application of chemical fertilizers and the combination of organic and chemical fertilizers were effective in enhancing and sustaining the soil’s organic carbon content, thereby contributing to soil fertility stability. To this end, this study can inform the efficient selection and use of fertilizers, improving crop yield and soil carbon content.

Perennial rice is a new type of rice that allows the harvest of rice for multiple years without growing new seedlings annually. This technology represents a green and sustainable agricultural production mode with many advantages for balancing agricultural ecology and food security. However, the differences in regeneration patterns between perennial and annual rice and the gene regulatory pathways of the apical dominance in axillary bud growth after harvest in perennial rice are still unclear. In this study, perennial rice (PR23) and annual rice (Chugeng28) were used to investigate axillary bud growth patterns before and after apical spike removal. After elimination of apical dominance at different development stages, perennial rice rhizome axillary buds at the compression nodes germinated more rapidly than others and developed into new seedlings. The axillary buds at the high-position nodes in annual rice grew faster than those at other nodes. Furthermore, the global gene expression patterns of PR23 rhizome buds at compression nodes grown for 1, 3, 4, and 5 days after apical spike removal were analyzed by transcriptome sequencing. Compared with the control buds without apical removal, 264, 3,484, 2,095, and 3,398 genes were up-regulated, and 674, 3,484, 1,594, and 1,824 genes were down-regulated in the buds grown for 1, 3, 4, and 5 days after apical spike removal, respectively. Trend analysis of the expressed genes at different time points was performed and co-expression network was constructed to identify key genes in rhizome axillary bud regrowth. The results showed that 85 hub genes involved in 12 co-regulatory networks were mainly enriched in the light system, photosynthesis-antenna protein, plant hormone signal transduction, ABC transporter and metabolic pathways, which suggested that hormone and photosynthetic signals might play important roles in the regulation of rhizome axillary bud regeneration in perennial rice. Overall, this study clarified the differences in the regeneration patterns of axillary buds between perennial and annual rice and provided insight into the complex regulatory networks during the regeneration of rhizome axillary buds in perennial rice.