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Abstract Recently, innate immunity and inflammation were recognized as the key factors for acute kidney injury (AKI) caused by sepsis, which is closely related to high mortality. Stimulator of interferon genes (STING) has emerged as a critical component of innate immune and inflammatory responses. However, the role of STING in the pathogenesis of septic AKI remains unclear. This study demonstrated that the STING was significantly activated in tubular cells induced by lipopolysaccharide (LPS) in vivo and in vitro. Tubule-specific STING knockout attenuated LPS-induced renal dysfunction and pathological changes. Mechanistically, the STING pathway promotes NOD-like receptor protein 3 (NLRP3) activation. STING triggers endoplasmic reticulum (ER) stress to induce mitochondrial reactive oxygen species (mtROS) overproduction, enhancing thioredoxin-interacting protein activation and association with NLRP3. Eventually, the NLRP3 inflammasome leads to tubular cell inflammation and pyroptosis. This study revealed the STING-regulated network and further identified the STING/ER stress/mtROS/NLRP3 inflammasome axis as an emerging pathway contributing to tubular damage in LPS-induced AKI. Hence, targeting STING may be a promising therapeutic strategy for preventing septic AKI.

Renal ischemia reperfusion injury (RIRI) is an inevitable complication during renal surgery. Histone deacetylase 6 (HDAC6), a key member of the histone deacetylase family, is associated with multiple pathologies, including renal diseases. However, whether HDAC6 could become a potential therapeutic target for clinical application of RIRI remained to be proven. Here, we found that HDAC6 expression was abnormally enhanced by the transcription factor OSR2 in RIRI. Moreover, we were the first to validate that a selective HDAC6 degrader, proteolysis-targeting chimeras (PROTAC) NP8, could significantly improve RIRI. Further in vivo and in vitro mechanism studies have found that the reduction of HDAC6 alleviated RIRI by inhibiting ROS mediated apoptosis. Remarkably, a renal protective protein, Klotho, has been proven to be a target of HDAC6, and the degradation of HDAC6 restored KL expression, thereby ameliorating ROS mediated apoptosis. Overall, our results illustrated that the degradation of HDAC6 restrained ROS mediated apoptosis by restoring Klotho expression during RIRI. PROTAC-NP8 might be a potential therapeutic strategy for clinical prevention of RIRI.

ABSTRACT Purpose: To investigate the role of cyanidin-3-O-glucoside (C3G) in renal ischemia/reperfusion (I/R) injury and the potential mechanisms. Methods: Mouse models were established by clamping the left renal vessels, and in vitro cellular models were established by hypoxic reoxygenation. Results: Renal dysfunction and tissue structural damage were significantly higher in the I/R group. After treatment with different concentrations of C3G, the levels of renal dysfunction and tissue structural damage decreased at different levels. And its protective effect was most pronounced at 200 mg/kg. The use of C3G reduced apoptosis as well as the expression of endoplasmic reticulum stress (ERS)-related proteins. Hypoxia/reoxygenation (H/R)-induced apoptosis and ERS are dependent on oxidative stress in vitro. In addition, both AG490 and C3G inhibited the activation of JAK/STAT pathway and attenuated oxidative stress, ischemia-induced apoptosis and ERS. Conclusions: The results demonstrated that C3G blocked renal apoptosis and ERS protein expression by preventing reactive oxygen species (ROS) production after I/R via the JAK/STAT pathway, suggesting that C3G may be a potential therapeutic agent for renal I/R injury.

Objective The objective of the study was to identify the risk factors correlated with spontaneous preterm birth (SPTB) and iatrogenic preterm birth (IPTB), as well as to compare the pregnancy outcomes between SPTB and IPTB.Materials and methods A total of 1676 (343 SPTB, 144 IPTB and 1189 full-term control group) cases were collected from the International Peace Maternity & Child Health Hospital of Shanghai between August 2018 and October 2020. A case-control study was conducted to explore the risk factors and pregnancy outcomes of SPTB and IPTB.Results The study identified a set of risk factors for SPTB and IPTB, as well as differences in pregnancy outcomes. Reproductive tract infections and myoma of the uterus were the risk factors for SPTB (p

This study investigates dynamic risk spillover effects between renewable energy markets and Chinese green financial markets from a time-frequency perspective by utilizing weekly data from two types of markets with a span from January 2010 to August 2022. The results show that the total spillover and net spillover effects vary widely across time. Short-run spillover is more dominant than long-run spillover. In most cases, green finance markets play the role of risk receivers in the system, while renewable energy markets are the main risk transmitters in the short run and the main risk spillover contributors in the long run. Finally, we determine that the hedging effect of green finance assets in the renewable energy market may decrease after the COVID-19 pandemic.

With the development and refinement of the carbon emissions trading market, the relationship between the carbon market and the stock market has grown increasingly intertwined. This has led to a surge in research investigating the interactions between the carbon market and related sectors. This study examines the intensity and direction of spillover effects among ten industries associated with carbon emissions, spanning traditional and emerging energy sectors. Through static analysis, we find that spillover effects between industries in the carbon and stock markets are bidirectional and asymmetric. Dynamic analysis reveals that the carbon market, acting as the primary recipient of spillover effects, is notably influenced by traditional energy industries such as coal and oil, followed by photovoltaics, new energy vehicles, and others. The magnitude of these spillover effects is subject to fluctuations influenced by energy crises and events like the COVID-19 pandemic, while policy interventions can alter the overall trends in net spillover effects across various industries.

Abstract Background Insulin has been reported to exhibit anti-inflammatory activities in the context of bowel inflammation. However, the role of the interaction between insulin and the microbiota in gut health is unclear. Our goal was to investigate the mechanism of action of insulin in bowel inflammation and the relationship between insulin and the gut microbiota. Methods We used acute and chronic murine models of inflammatory bowel disease (IBD) to evaluate whether insulin influences the progression of colitis. Colonic tissues, the host metabolome and the gut microbiome were analyzed to investigate the relationship among insulin treatment, the microbiome, and disease. Experiments involving antibiotic (Abx) treatment and fecal microbiota transplantation (FMT) confirmed the association among the gut microbiota, insulin and IBD. In a series of experiments, we further defined the mechanisms underlying the anti-inflammatory effects of insulin. Results We found that low-dose insulin treatment alleviated intestinal inflammation but did not cause death. These effects were dependent on the gut microbiota, as confirmed by experiments involving Abx treatment and FMT. Using untargeted metabolomic profiling and 16S rRNA sequencing, we discovered that the level of the secondary bile acid lithocholic acid (LCA) was notably increased and the LCA levels were significantly associated with the abundance of Blautia, Enterorhadus and Rumi-NK4A214_group. Furthermore, LCA exerted anti-inflammatory effects by activating a G-protein-coupled bile acid receptor (TGR5), which inhibited the polarization of classically activated (M1) macrophages. Conclusion Together, these data suggest that insulin alters the gut microbiota and affects LCA production, ultimately delaying the progression of IBD. Graphical Abstract

As an important measure to achieve high-quality economic development in China, the implementation of low-carbon city pilot policy (LCCP) will inevitably have an impact on enterprises’ environmental protection behavior, but the empirical evidence in this field is limited. Therefore, based on the data of Chinese A-share listed industrial enterprises in Shanghai and Shenzhen from 2008 to 2020, this paper empirically tests the impact of LCCP on corporate environmental performance (EP) and its mechanism of action by using the multiperiod difference-in-difference (DID) method. The results show that (1) the implementation of LCCP has significantly improved EP, and after a series of necessary tests such as parallel trend and placebo, the conclusion remains robust. (2) LCCP promotes enterprises to improve their EP mainly through the pressure of environmental supervision, financing constraints, and market competition. (3) The policy effect of LCCP varies with the nature of enterprise property rights, pollution attributes, and technical level. State-owned enterprises, heavily polluting enterprises, and high-tech enterprises respond more positively to LCCP, and the effect of EP improvement affected by the policy is more obvious. Further analysis shows that facing the pressure of environmental policy, state-owned enterprises mainly deal with it through two methods: increasing environmental protection investment and strengthening green innovation; heavy-polluting enterprises tend to increase investment in environmental protection; high-tech enterprises mainly benefit from the improvement of the green innovation level. Our findings have important policy implications for improving LCCP to achieve high-quality economic development based on the improvement of EP.

Growing studies have shown the preventive effects of isomalt against metabolic diseases, nevertheless, its efficacy and action mechanisms on nonalcoholic fatty liver disease (NAFLD) remain unknown. Herein, isomalt supplementation significantly attenuated the high-sucrose diet-induced hepatic steatosis. Mechanically, dietary isomalt restored hepatic de novo lipogenesis dysfunction and intestinal epithelial integrity. Moreover, isomalt consumption regulated gut microbiota composition, including improving abundance of probiotic Akkermansia, but suppressing pathogens Acinetobacter and Corynebacterium_1. Quantification analyses of short-chain fatty acids showed that isomalt reduced faecal acetate concentrations, whereas elevated propionate and butyrate in hepatic steatosis. Additionally, targeted metabolomics profiling of tryptophan metabolism showed that isomalt increased faecal levels of 5-hydroxytryptophan, indole-3-carboxaldehyde and kynurenic acid, but reduced concentrations of 5-hydroxyindoleacetic acid and xanthurenic acid in rats. Thereby, our data demonstrate that dietary isomalt attenuates hepatic steatosis possibly via modulation of gut microbiota and its metabolic function, which provides new insights into preventing and treating NAFLD in future.

Background: Evidence on the potential negative health effects of short working hours remains limited. This study aimed to investigate the association between short working hours and perceived stress in a population-based sample from China. Methods: This cross-sectional study included 4368 participants aged 18–65 years from the China Health and Nutrition Surveys (CHNS) 2015. Working hours were categorized into

Mycoplasma pneumoniae (MP) is one of the main pathogens causing community acquired pneumonia (CAP) in children and adults. Previous pharmacological and clinical studies have shown that Polydatin (PD) exerts anti-inflammatory action by conferring protective benefit in MP pneumonia. However, the mechanism underlying the of PD on MP infection remains unclear. It was found that PD alleviated MP-induced injury by inhibiting caspase-1/gasdermin D (GSDMD)-mediated epithelial pyroptosis. The results demonstrated that PD inhibited the transformation of GSDMD to N-terminal gasdermin-N (GSDMD-N) by decreasing caspase-1 activation, as well as suppressed the formation and secretion of interleukin-1β (IL-1β) and interleukin-18 (IL-18), reversed Na, K-ATPase reduction, and suppressed LDH release both in vitro and vivo. Taken together, epithelial pyroptosis in BEAS‐2B cells and lung injury in mice were prevented by PD. In conclusion, PD suppressed pulmonary injury triggered by MP infection, by inhibiting the caspase-1/GSDMD-mediated epithelial pyroptosis signaling pathway. Thus, PD may be regarded as a potential therapy for MP-induced inflammation.

Key points Quantification of BMAT valuable information for the clinical diagnosis and treatment of OP. DECT can accurately quantify the BMAT of vertebrae. DECT has the same applicability as MRI in the study of OP.

Abstract Mycoplasma pneumoniae (MP) infection is a common cause of community-acquired pneumonia in children. Furthermore, many children with Mycoplasma pneumoniae pneumonia (MPP) have recurrent wheezing and reduced small airway function after their clinical symptoms have resolved, eventually leading to asthma. MPP can trigger immune disorders and systemic inflammatory responses. Hence, the intestine is the largest immune organ of the body. Therefore, we sought to investigate whether the alteration of intestinal flora is correlated with the development of wheezing in children with MPP. We collected 30 healthy children as group A, 50 children with nonwheezing MPP as group B, and 50 children with wheezing MPP as group C. We found that the percentage of eosinophil cells (EC) was significantly higher in group C than that in group B for routine blood tests and serum inflammatory factors. The serum cytokines, including IL-4, IL-17, TNF-α, and TGF-β, were significantly higher in group C than in group B. In addition, the level of IL-10 was significantly lower in group C than in group B. The distribution characteristics of intestinal flora strains in children with MPP were detected by sequencing of 16S rRNA gene amplicon sequencing. There were differences in the abundance of intestinal flora between children with MPP and healthy children, with lower abundance of Ruminococcus flavefaciens, Clostridium butyricum, Lactobacillus, and Bifidobacterium in the intestine of children with MPP compared to healthy children. The abundance of Ruminococcus flavefaciens and Clostridium butyricum was significantly lower in the intestine of children with wheezing MPP compared to children without wheezing MPP. In the correlation analysis between children with MPP and inflammatory factors, Ruminococcus flavefaciens was found to be negatively correlated with IL-17. Clostridium butyricum was negatively correlated with L-4, IL-17, TNF-α, and TGF-β; however, it positively correlated with IL-10. Thus, it was concluded that alterations in intestinal flora play a crucial role in the immune response to MPP, where a significant decline in intestinal Ruminococcus flavefaciens and Clostridium butyricum leads to an exacerbation of the inflammatory responses, which may promote the development of children with wheezing MPP.

Abstract Aims We aimed to investigate whether sacubitril–valsartan could further improve the prognosis, cardiac function, and left ventricular (LV) remodelling in patients following acute myocardial infarction (AMI). Methods and results We searched the PubMed, Embase, Cochrane Library, and China National Knowledge Infrastructure (CNKI) from inception to 10 May 2021 to identify potential articles. Randomized controlled trials (RCTs) meeting the inclusion criteria were included and analysed. Thirteen RCTs, covering 1358 patients, were analysed. Compared with angiotensin‐converting enzyme inhibitors (ACEI)/angiotensin receptor blockers (ARB), sacubitril–valsartan did not significantly reduced the cardiovascular mortality [risk ratio (RR) 0.65, 95% confidence interval (CI) 0.22 to 1.93, P = 0.434] and the rate of myocardial reinfarction (RR 0.65, 95% CI 0.29 to 1.46, P = 0.295) of patients following AMI, but the rate of hospitalization for heart failure (HF) (RR 0.48, 95% CI 0.35 to 0.66, P

Abstract The link between crude oil price and stock returns of the Group of Seven (G7) countries (Canada, France, Germany, Italy, Japan, the United Kingdom, and the United States) was analyzed in this study using monthly data from January 1999 to March 2020. We adopt a similar approach to Kilian (Am Econ Rev 99(3):1053–1069, 2009) and construct a structural vector autoregression framework to decompose crude oil price shocks into oil supply shock, oil aggregate demand shock, and oil-specific demand shock. We then explore the distinct effects of different kinds of oil price shocks from various sources. Based on the decomposed oil price shocks, we apply the connectedness approach and QQ regression to find time-varying co-movements and tail dependence between oil price shocks and G7 stock returns. There is no general correlation between the decomposed oil prices and stock returns in these countries. The effects of oil price shocks on stock returns across different stock market conditions appear to be heterogeneous. Oil supply shock appears to be a net transmitter of spillover effects for all G7 countries within the sample period.

ABSTRACT Interleukin-17 (IL-17) is associated with nonalcoholic fatty liver disease (NAFLD) and gut microbiota, and how IL-17 mediates the NAFLD/nonalcoholic steatohepatitis (NASH) process depending on the gut microbiota is unclear. We found that T helper 17 (TH17) cells were decreased in the small intestine in a methionine choline-deficient (MCD) diet-induced NASH model. IL-17-deficient (Il17−/−) mice showed alterations in intestinal microbiota, including the inhibition of probiotic growth and the overgrowth of certain pathogenic bacteria, and were prone to higher endotoxemia levels and more severe gastrointestinal barrier defects than wild-type (WT) mice. Furthermore, TH17 cells were responsible for restoring the intestinal barrier after administration of recombinant IL-17 to Il17−/− mice or injection of CD4+ T cells into a Rag1−/− mouse model. Additionally, transplantation of the microbiota from WT mice to Il17−/− mice restored the intestinal barrier. Notably, microbiota-depleted Il17−/− mice were resistant to MCD diet-induced intestinal barrier impairment. Fecal microbiota transplantation from Il17−/− mice to microbiota-depleted mice aggravated intestinal barrier impairment and then promoted the development of NASH. Collectively, this study showed that host IL-17 could strengthen intestinal mucosal barrier integrity and reduce dysbiosis-induced intestinal injury and secondary extraintestinal organ injury induced by a special diet. IMPORTANCE The morbidity of NASH has increased, with limited effective treatment options. IL-17 plays a protective role in the gut mucosa in high-fat-diet (HFD)-related metabolic disorders, and HFD-related microbiota dysbiosis is responsible for a decreased number of T helper 17 (TH17) cells in the lamina propria. The mechanism by which IL-17 mediates the NAFLD/NASH process depending on the gut microbiota is unclear. In our study, IL-17 originating from TH17 cells maintained intestinal barrier integrity and determined the outcomes of diet-related disease, which may be a target strategy for NAFLD/NASH.

Abstract Background Osteoporosis (OP) is a systemic metabolic bone disorder identified as an essential health issue worldwide. Orthopedic imaging approaches were commonly used with some limitations. Thus, our study aimed to investigate the diagnostic value of magnetic resonance spectroscopy (1-H MRS) and m-Dixon-Quant in OP. Methods A total of 76 subjects were enrolled in the study and bone mineral density (BMD) was measured using quantitative computed tomography (QCT). Then, the subjects were divided into three groups according to BMD: normal control group, osteopenia group and OP group. The following parameters were recorded for each patient: gender, age, height, body weight, waist circumference, and hip circumference. Further, the fat fraction percentage (FF%) values were determined by 1-H MRS and m-Dixon-Quant methods. Results In both 1-H MRS and magnetic resonance Imaging (MRI) m-Dixon-Quant, the FF% exhibited a negative correlation with BMD (P 0.05). Conclusions MRI investigations especially FF% value in the m-Dixon-Quant imaging system is correlated with OP. Its diagnostic value remains to be demonstrated on a large prospective cohort of patients. Besides, parameters such as age, gender, and height are important factors for predicting and diagnosing OP.

Adrenal Vein Sampling (AVS) is the gold standard for categorizing primary aldosteronism (PA). However, catheterization of the right adrenal vein (RAV) is challenging due the small size and variable location. This study aims to explore the relationship between the RAV orifice and the right kidney contour (RKC) on fluoroscopy, thus evaluating the potential of use the RKC as an anatomic marker for localizing RAV. Imaging data of 107 PA patients with successful bilateral AVS were retrospectively analyzed. Based on the body mass index (BMI), all patients were divided into the Normal Group (BMI < 24 kg/m2), Overweight Group (24 kg/m2 ≤ BMI < 28 kg/m2) and Obese Group (BMI ≥ 28 kg/m2). At the anterior view, the height level of RAV orifice was determined relative to vertebral bodies and disks. The distance from the RAV orifice to the upper edge of RKC was measured manually. The RAV orifice height level was mainly distributed from vertebral T11 to T12 (90.6%), and tended to be higher in patients with a larger BMI. The mean distance from the RAV orifice to the upper edge of RKC was 13.9±7.8mm, and had no difference among Normal group (n = 53, 14.1±8.2mm), Overweight group (n = 39, 13.7±8.0mm), and Obese group (n = 15, 13.9±5.5mm) (p = 0.981). Based on these findings, the RKC might be used as a landmark for localizing RAV on fluoroscopy, which is conductive to narrow down the exploration range and increase the success rate of RAV catheterization.

This paper aims to study the impact of salesperson human capital investment on the export performance of heterogeneous enterprises in China. To distinguish the different effects on the staff level and the management level, we define the human capital investment for the overall salespersons as human capital investment I and the human capital investment for the sales managers as human capital investment II, respectively measured by the salary of the ordinary salespersons and the ratio of expenses to sales. We find that human capital investment I has a significant positive effect on export performance, while human capital investment II shows a “positive U-shaped” relationship with export performance. Considering the heterogeneity of enterprise, the positive effect of human capital investment I is more significant than that of human capital investment II in enterprises with high R&D intensity. Moreover, with the improvement of technology intensity, both the promotion of human capital investment I and human capital investment II would generate greater influence on export performance.