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Background In recent years, several studies have demonstrated that stress hyperglycemia is significantly associated with poor prognosis in patients diagnosed with acute coronary syndrome (ACS). In the present study, we aimed to investigate the potential associations between various markers of stress hyperglycemia, such as admission blood glucose (ABG), fasting blood sugar (FBS), and stress hyperglycemia ratio (SHR) with different definitions, and the occurrence of adverse cardiovascular events in patients diagnosed with ST-elevation myocardial infarction (STEMI) who have undergone percutaneous coronary intervention (PCI). Methods Our study enrolled a total of 1099 patients diagnosed with STEMI who underwent PCI from 2016 to 2021. The primary outcomes of this study were in-hospital death and all-cause mortality. Results Stress hyperglycemia was associated with a higher incidence of in-hospital death (ABG OR: 1.27 95% CI 1.19–1.36; FBS OR: 1.25 95% CI 1.16–1.35; SHR1 OR: 1.61 95% CI 1.21–2.14; SHR2 OR: 1.57, 95%CI 1.22–2.01; SHR3 OR: 1.59, 95%CI 1.24–2.05) and all-cause mortality (ABG HR: 1.10, 95% CI 1.07–1.14; FBS HR: 1.12, 95 CI 1.07–1.17; SHR1 HR: 1.19 95% CI 1.03–1.39; SHR2 HR: 1.28, 95%CI 1.14–1.44; SHR3 HR: 1.29, 95%CI 1.14–1.45) after adjusting for ischemic time, age, gender, BMI, hypertension, hyperlipidemia, diabetes mellitus (DM), current smoking history, chronic kidney disease (CKD), previous history of coronary artery disease (CAD), atrial fibrillation (AF), heart failure (HF), stroke, cancer, culprit vessel, multi-vessel disease. These associations exhibited a non-linear, J-shaped pattern, wherein the risk significantly increased when the ABG and FBS levels exceeded 5mmol/L. Moreover, the inflection point for SHR was estimated to be 1.2. Conclusions Stress hyperglycemia was significantly associated with an increased risk of in-hospital death and all-cause mortality in STEMI patients treated with PCI. Stress hyperglycemia should be considered a high-risk prognostic marker in all STEMI patients, regardless of with or without diabetes.

Transportation-related risk factors are a major source of morbidity and mortality in China, where the expansion of road networks and surges in personal vehicle ownership are having profound effects on public health. Road traffic injuries and fatalities have increased alongside increased use of motorised transport in China, and accident injury risk is aggravated by inadequate emergency response systems and trauma care. National air quality standards and emission control technologies are having a positive effect on air quality, but persistent air pollution is increasingly attributable to a growing and outdated vehicle fleet and to famously congested roads. Urban design favours motorised transport, and physical activity and its associated health benefits are hindered by poor urban infrastructure. Transport emissions of greenhouse gases contribute substantially to regional and global climate change, which compound public health risks from multiple factors. Despite these complex challenges, technological advances and innovations in planning and policy stand to make China a leader in sustainable, healthy transportation.

Mutations in the protein tyrosine phosphatase SHP2 affect cells in the bone marrow environment, which leads to aberrant activation of resident haematopoietic stem cells and thereby contributes to the development of leukaemia. A mutated microenvironment in leukaemia Hereditary mutations in the tyrosine phosphatase SHP2 (encoded by PTPN11 ), part of the Ras signalling pathway, have been linked to a syndrome leading to an increased risk of developing leukaemia. Previous studies in mouse models have shown that the function of haematopoietic stem cells carrying these mutations is defective, which suggests a cell-autonomous effect. Cheng-Kui Qu and colleagues find that the mutations also affect cells in the bone marrow environment, blocking their normal control on haematopoietic stem cells and thereby promoting the development of leukaemia. Administration of CCL3 receptor antagonists effectively reversed oncogenesis driven by the Ptpn11 -mutated bone marrow microenvironment. Germline activating mutations of the protein tyrosine phosphatase SHP2 (encoded by PTPN11 ), a positive regulator of the RAS signalling pathway 1 , are found in 50% of patients with Noonan syndrome 2 . These patients have an increased risk of developing leukaemia 3 , especially juvenile myelomonocytic leukaemia (JMML), a childhood myeloproliferative neoplasm (MPN). Previous studies have demonstrated that mutations in Ptpn11 induce a JMML-like MPN through cell-autonomous mechanisms that are dependent on Shp2 catalytic activity 4 , 5 , 6 , 7 . However, the effect of these mutations in the bone marrow microenvironment remains unclear. Here we report that Ptpn11 activating mutations in the mouse bone marrow microenvironment promote the development and progression of MPN through profound detrimental effects on haematopoietic stem cells (HSCs). Ptpn11 mutations in mesenchymal stem/progenitor cells and osteoprogenitors, but not in differentiated osteoblasts or endothelial cells, cause excessive production of the CC chemokine CCL3 (also known as MIP-1α), which recruits monocytes to the area in which HSCs also reside. Consequently, HSCs are hyperactivated by interleukin-1β and possibly other proinflammatory cytokines produced by monocytes, leading to exacerbated MPN and to donor-cell-derived MPN following stem cell transplantation. Remarkably, administration of CCL3 receptor antagonists effectively reverses MPN development induced by the Ptpn11 -mutated bone marrow microenvironment. This study reveals the critical contribution of Ptpn11 mutations in the bone marrow microenvironment to leukaemogenesis and identifies CCL3 as a potential therapeutic target for controlling leukaemic progression in Noonan syndrome and for improving stem cell transplantation therapy in Noonan-syndrome-associated leukaemias.

Background Cancer-associated fibroblasts (CAFs) are the prominent cell type in the tumor microenvironment (TME), and CAF subsets have been identified in various tumors. However, how CAFs spatially coordinate other cell populations within the liver TME to promote cancer progression remains unclear. Methods We combined multi-region proteomics (6 patients, 24 samples), 10X Genomics Visium spatial transcriptomics (11 patients, 25 samples), and multiplexed imaging (92 patients, 264 samples) technologies to decipher the expression heterogeneity, functional diversity, spatial distribution, colocalization, and interaction of fibroblasts. The newly identified CAF subpopulation was validated by cells isolated from 5 liver cancer patients and in vitro functional assays. Results We identified a liver CAF subpopulation, marked by the expression of COL1A2, COL4A1, COL4A2, CTGF, and FSTL1, and named F5-CAF. F5-CAF is preferentially located within and around tumor nests and colocalizes with cancer cells with higher stemness in hepatocellular carcinoma (HCC). Multiplexed staining of 92 patients and the bulk transcriptome of 371 patients demonstrated that the abundance of F5-CAFs in HCC was associated with a worse prognosis. Further in vitro experiments showed that F5-CAFs isolated from liver cancer patients can promote the proliferation and stemness of HCC cells. Conclusions We identified a CAF subpopulation F5-CAF in liver cancer, which is associated with cancer stemness and unfavorable prognosis. Our results provide potential mechanisms by which the CAF subset in the TME promotes the development of liver cancer by supporting the survival of cancer stem cells.

The roles of moisture sources and transports in the interannual and interdecadal precipitation variabilities during boreal summer over three subregions of East China, namely, South China (SC), the middle and lower Yangtze River valley (YRV), and North China (NC), are complex and different. In this paper, ERA-Interim reanalysis data collected 4 times per day from 1979 to 2017 are used to analyze the roles of moisture sources in the interannual and interdecadal variabilities in summer precipitation over the three subregions of East China. Using the hybrid single-particle Lagrangian integrated trajectory model, six atmospheric moisture sources, land area source (LD source), East China source (EC source, except for the target region), Indian Ocean source (IO source), Pacific Ocean source (PO source), South China Sea source (SCS source), and regional evapotranspiration sources (SC source, YRV source, and NC source), are defined. The precipitation of the IO and SCS sources accounts for 43.73% and 23.45% of the SC summer precipitation, respectively, thus dominating the interannual and interdecadal variabilities in the SC summer precipitation. For the YRV, the summer precipitation is influenced by the EC source precipitation (22.41%), YRV source precipitation (23.97%), IO source moisture (27.78%) and SCS source moisture (14.40%). The interannual and interdecadal variabilities in precipitation are influenced by all moisture sources except the LD source and PO source moisture transports. The land evapotranspiration, which includes the EC source moisture (39.04%) and NC source moisture (22.04%), is the major source of moisture for summer precipitation over NC. In addition, the westward moisture transport from the PO source does not directly arrive in East China during El Niño events. Simultaneously, most of the northward moisture is released over the western YRV. Warming in the tropical Indian Ocean is responsible for decreases in precipitation from the IO source, PO source, and SCS source. In addition, the significant increase in the PO source precipitation over the eastern YRV and the significant decrease in the IO source precipitation over the western YRV were induced by the Pacific decadal oscillation phase transition from warm to cold in approximately 1999.

Severe fever with thrombocytopenia syndrome (SFTS) is a tick-borne emerging infectious disease with a reported mortality rate of up to 30% in hospitalized patients. The causative agent, SFTS virus (SFTSV) is maintained in nature through a transmission cycle involving animal hosts and ticks. Therefore, effective control of SFTS in nature environments necessitates a comprehensive understanding of the tick-host circulation patterns that sustain viral persistence. We developed and calibrated mathematical models using seroprevalence survey data collected across China to assess the relative contributions of diverse domestic and wildlife host species to transmission, their determinants, and the effectiveness of various interventions. Our analysis identified poultry, previously unrecognized, as the most important species across the majority of survey sites, followed by goat/sheep, cattle, and rodents. These rankings remained robust even when parameter values were perturbed or certain host species were omitted from the survey. Across all sites, increasing tick mortality rate μ T and reducing transovarial transmission efficiency ϕ consistently ranked among the top five interventions that led to the most significant reduction in the overall R 0 . Understanding the relative host contributions is crucial for developing interventions. Our simulation results indicated that halving the contact rate of the most important species with ticks could yield a 25-fold greater reduction in transmission intensity compared to halving that of the second most important species.

Non-communicable diseases have replaced infectious diseases as the leading cause of death among urban residents; the percentage of years of life lost because of such diseases as a fraction of all-cause years of life lost increased from 50·0% (95% CI 48·5–53·0) in 1990 to 77·3% (76·5–78·1) in 2015.4 Health inequality also increased in urban areas.5 China has acted to address urban health challenges by passing strict environmental regulations and investing heavily in urban infrastructure.In traditional chinese medicine, human health is seen as the consequence of harmonisation between human beings and their environments and between the various parts of the human body and the focus is on disease prevention rather than treatment.16 Concepts from traditional Chinese medicine, such as the maintenance of regular daily activities (rest, diet, and exercise) and avoidance of negative health effects from environmental factors (eg, Fengshui) have become essential parts of Chinese culture.In 2007 alone, particulate matter with a diameter of less than 2·5 μm (PM2·5) affected the productivity of about 72 million workers in 30 Chinese provinces, causing an estimated economic loss of ¥346·3 billion (US$44·4 billion, about 1·1% of the national gross domestic product [GDP]).19 Total economic losses attributed to the public health effects of pollution from particulate matter with a diameter of less than 10 μm (PM10) and sulphur dioxide (SO2) pollution in 74 cities were estimated to be as high as ¥439·8 billion ($70·9 billion, about 2·3% of these cities' GDP) in the first half of 2015.20 China will also have a massive future burden of non-communicable diseases—most of which will affect urban areas—that will strain future health systems and limit economic growth in the country.Total annual premature deaths from such diseases are expected to increase from 3·11 million in 2013 to 3·52 million in 2030.21 Between 2012 and 2030, economic losses attributable to five key non-communicable diseases–ischaemic heart disease, cerebrovascular disease, diabetes, breast cancer, and chronic obstructive pulmonary disease–will total $23·03 trillion USD,22 which is more than twice of China's total GDP in 2015 ($11·07 trillion).

Amino acid-mediated metabolism is one of the key catabolic and anabolic processes involved in diverse cellular functions. However, the role of the semi-essential amino acid arginine in normal and malignant hematopoietic cell development is poorly understood. Here we report that a continuous supply of exogenous arginine is required for the maintenance/function of normal hematopoietic stem cells (HSCs). Surprisingly, knockout of Slc7a3 (CAT3), a major L-arginine transporter, does not affect HSCs in steady-state or under stress. Although Slc7a3 is highly expressed in naïve and activated CD8 T cells, neither T cell development nor activation/proliferation is impacted by Slc7a3 depletion. Furthermore, the Slc7a3 deletion does not attenuate leukemia development driven by Pten loss or the oncogenic Ptpn11 E76K mutation. Arginine uptake assays reveal that L-arginine uptake is not disrupted in Slc7a3 knockout cells. These data suggest that extracellular arginine is critically important for HSCs, but CAT3 is dispensable for normal hematopoiesis and leukemogenesis.

Background During Fritillaria thunbergii planting, pests and diseases usually invade the plant, resulting in reduced yield and quality. Previous studies have demonstrated that using biocontrol agents can effectively control grubs and affect the steroid alkaloids content in F. thunbergii . However, the molecular regulatory mechanisms underlying the differences in the accumulation of steroid alkaloids in response to biocontrol agents remain unclear. Results Combined transcriptomic and metabolic analyses were performed by treating the bulbs of F. thunbergii treated with biocontrol agents during planting. Otherwise, 48 alkaloids including 32 steroid alkaloids, 6 indole alkaloids, 2 scopolamine-type alkaloids, 1 isoquinoline alkaloid, 1 furoquinoline alkaloid, and 6 other alkaloids were identified. The content of steroidal alkaloids particularly peimine, peiminine, and veratramine, increased significantly in the group treated with the biocontrol agents. Transcriptome sequencing identified 929 differential genes using biocontrol agents, including 589 upregulated and 340 downregulated genes. Putative biosynthesis networks of steroid alkaloids have been established and combined with differentially expressed structural unigenes, such as acetyl-CoA C-acetyl-transferase, acelyl-CoAC-acetyltransferase3-hydroxy-3-methylglutaryl-coenzyme A synthase, 1-deoxy-D-xylulose-5-phosphate reductor-isomerase, 2-C-methyl-D-erythritol-4-phosphate cytidylyltransferase and 4-hydroxy-3-methylbut-2-enyl diphosphate reductase. In addition, biological processes such as amino acid accumulation and oxidative phosphorylation were predicted to be related to the synthesis of steroid alkaloids. Cytochrome P450 enzymes also play crucial roles in the steroid alkaloid synthesis. The transcription factor families MYB and bHLH were significantly upregulated after using biocontrol agents. Conclusions Biocontrol agents increased the steroid alkaloids accumulation of steroid alkaloids by affecting key enzymes in the steroid alkaloid synthesis pathway, biological processes of oxidative phosphorylation and amino acid synthesis, cytochrome P450 enzymes, and transcription factors. This study revealed the mechanism underlying the difference in steroidal alkaloids in F. thunbergii after using biocontrol agents, laying the groundwork for future industrial production of steroid alkaloids and ecological planting of medicinal materials in the future.

While mitochondria in different tissues have distinct preferences for energy sources, they are flexible in utilizing competing substrates for metabolism according to physiological and nutritional circumstances. However, the regulatory mechanisms and significance of metabolic flexibility are not completely understood. Here, we report that the deletion of Ptpmt1 , a mitochondria-based phosphatase, critically alters mitochondrial fuel selection – the utilization of pyruvate, a key mitochondrial substrate derived from glucose (the major simple carbohydrate), is inhibited, whereas the fatty acid utilization is enhanced. Ptpmt1 knockout does not impact the development of the skeletal muscle or heart. However, the metabolic inflexibility ultimately leads to muscular atrophy, heart failure, and sudden death. Mechanistic analyses reveal that the prolonged substrate shift from carbohydrates to lipids causes oxidative stress and mitochondrial destruction, which in turn results in marked accumulation of lipids and profound damage in the knockout muscle cells and cardiomyocytes. Interestingly, Ptpmt1 deletion from the liver or adipose tissue does not generate any local or systemic defects. These findings suggest that Ptpmt1 plays an important role in maintaining mitochondrial flexibility and that their balanced utilization of carbohydrates and lipids is essential for both the skeletal muscle and the heart despite the two tissues having different preferred energy sources. Cells are powered by mitochondria, a group of organelles that produce chemical energy in the form of molecules called ATP. This energy is derived from the breakdown of carbohydrates, fats, and proteins. The number of mitochondria in a cell and the energy source they use to produce ATP varies depending on the type of cell. Mitochondria can also switch the molecules they use to produce energy when the cell is responding to stress or disease. The heart and the skeletal muscles – which allow movement – are two tissues that require large amounts of energy, but it remained unknown whether disrupting mitochondrial fuel selection affects how these tissues work. To answer these questions, Zheng, Li, Li et al. investigated the role of an enzyme found in mitochondria called Ptpmt1. Genetically deleting Ptpmt1 in the heart and skeletal muscle of mice showed that while the development of these organs was not affected, mitochondria in these cells switched from using carbohydrates to using fats as an energy source. Over time, this shift damaged both the mitochondria and the tissues, leading to muscle wasting, heart failure, and sudden death in the mice. This suggests that balanced use of carbohydrates and fats is essential for the muscles and heart. These findings imply that long-term use of medications that alter the fuel that mitochondria use may be detrimental to patients’ health and could cause heart dysfunction. This may be important for future drug development, as well as informing decisions about medication taken in the clinic.