Research progress on the relationship between phenotype and signaling pathways of pulmonary macrophages and asthma.

Asthma is a heterogeneous chronic inflammatory lung disease Lung tissue macrophages are important immune cells in respiratory tract. Lung macrophages are also heterogenous in that there are separate subsets and, depending on the environment, different effector functions. They have different phenotypes and biological functions in different disease environments. At present, the study on the different phenotypes and function analysis of macrophages in lung tissue is not perfect. Pulmonary macrophages undergo phenotypic changes during asthma. This review summarizes current literature and provides a detailed introduction to the role of macrophages as key inflammatory mediators in the pathogenesis of asthma, as well as existing knowledge gaps. In addition, we propose that regulatory macrophages may prevent the development of asthma by producing IL-10, and regulating the polarization of pulmonary macrophages may be a new direction for asthma treatment.

Applying the six-sigma methodology to determine the limits of quality control (QC) tests for a specific linear accelerator.

PURPOSE: We aimed to show the framework of the six-sigma methodology (SSM) that can be used to determine the limits of QC tests for the linear accelerator (Linac). Limits for QC tests are individually determined using the SSM. METHODS AND MATERIALS: The SSM is based on the define-measure-analyze-improve-control (DMAIC) stages to improve the process. In the "define" stage, the limits of QC tests were determined. In the "measure" stage, a retrospective collection of daily QC data using a Machine Performance Check platform was performed from January 2020 to December 2022. In the "analyze" stage, the process of determining the limits was proposed using statistical analyses and process capability indices. In the "improve" stage, the capability index was used to calculate the action limits. The tolerance limit was established using the larger one of the control limits in the individual control chart (I-chart). In the "control" stage, daily QC data were collected prospectively from January 2023 to May 2023 to monitor the effect of action limits and tolerance limits. RESULTS: A total of 798 sets of QC data including beam, isocenter, collimation, couch, and gantry tests were collected and analyzed. The Collimation Rotation offset test had the min-Cp, min-Cpk, min-Pp, and min-Ppk at 2.53, 1.99, 1.59, and 1.25, respectively. The Couch Rtn test had the max-Cp, max-Cpk, max-Pp, and max-Ppk at 31.5, 29.9, 23.4, and 22.2, respectively. There are three QC tests with higher action limits than the original tolerance. Some data on the I-chart of the beam output change, isocenter KV offset, and jaw X1 exceeded the lower tolerance and action limit, which indicated that a system deviation occurred and reminded the physicist to take action to improve the process. CONCLUSIONS: The SSM is an excellent framework to use in determining the limits of QC tests. The process capability index is an important parameter that provides quantitative information on determining the limits of QC tests.

Unexpected response of terrestrial carbon sink to rural depopulation in China.

China is experiencing large-scale rural-urban migration and rapid urbanization, which have had significant impact on terrestrial carbon sink. However, the impact of rural-urban migration and its accompanying urban expansion on the carbon sink is unclear. Based on multisource remote sensing product data for 2000-2020, the soil microbial respiration equation, relative contribution rate, and threshold analysis, we explored the impact of rural depopulation on the carbon sink and its threshold. The results revealed that the proportion of the rural population in China decreased from 63.91 % in 2000 to 36.11 % in 2020. Human pressure decreased by 1.82% in rural depopulation areas, which promoted vegetation restoration in rural areas (+8.45 %) and increased the carbon sink capacity. The net primary productivity (NPP) and net ecosystem productivity (NEP) of the vegetation in the rural areas increased at rates of 2.95 g C m-2 yr-1 and 2.44 g C m-2 yr-1. Strong rural depopulation enhanced the carbon sequestration potential, and the NEP was 1.5 times higher in areas with sharp rural depopulation than in areas with mild rural depopulation. In addition, the rural depopulation was accompanied by urban expansion, and there was a positive correlation between the comprehensive urbanization level (CUL) and NEP in 75.29 % of urban areas. In the urban areas, the vegetation index increased by 88.42 %, and the urban green space partially compensated for the loss of carbon sink caused by urban expansion, with a growth rate of 4.96 g C m-2 yr-1. Changes in rural population have a nonlinear impact on the NEP. When the rural population exceeds 545.686 people/km2, an increase in the rural population will have a positive impact on the NEP. Our research shows that rural depopulation offers a potential opportunity to restore natural ecosystems and thus increase the carbon sequestration capacity.

LncRNAH19 acts as a ceRNA of let-7 g to facilitate endothelial-to-mesenchymal transition in hypoxic pulmonary hypertension via regulating TGF-ß signalling pathway.

BACKGROUND: Hypoxic pulmonary hypertension (HPH) is a challenging lung arterial disorder with remarkably high incidence and mortality rates, and the efficiency of current HPH treatment strategies is unsatisfactory. Endothelial-to-mesenchymal transition (EndMT) in the pulmonary artery plays a crucial role in HPH. Previous studies have shown that lncRNA-H19 (H19) is involved in many cardiovascular diseases by regulating cell proliferation and differentiation but the role of H19 in EndMT in HPH has not been defined. METHODS: In this research, the expression of H19 was investigated in PAH human patients and rat models. Then, we established a hypoxia-induced HPH rat model to evaluate H19 function in HPH by Echocardiography and hemodynamic measurements. Moreover, luciferase reporter gene detection, and western blotting were used to explore the mechanism of H19. RESULTS: Here, we first found that the expression of H19 was significantly increased in the endodermis of pulmonary arteries and that H19 deficiency obviously ameliorated pulmonary vascular remodelling and right heart failure in HPH rats, and these effects were associated with inhibition of EndMT. Moreover, an analysis of luciferase activity indicated that microRNA-let-7 g (let-7 g) was a direct target of H19. H19 deficiency or let-7 g overexpression can markedly downregulate the expression of TGFßR1, a novel target gene of let-7 g. Furthermore, inhibition of TGFßR1 induced similar effects to H19 deficiency. CONCLUSIONS: In summary, our findings demonstrate that the H19/let-7 g/TGFßR1 axis is crucial in the pathogenesis of HPH by stimulating EndMT. Our study may provide new ideas for further research on HPH therapy in the near future.

Association between blood urea nitrogen to serum albumin ratio and in-hospital mortality in critical patients with diabetic ketoacidosis: a retrospective analysis of the eICU database.

Background: This study aimed to investigate the association between blood urea nitrogen to serum albumin ratio (BAR) and the risk of in-hospital mortality in patients with diabetic ketoacidosis. Methods: A total of 3,962 diabetic ketoacidosis patients from the eICU Collaborative Research Database were included in this analysis. The primary outcome was in-hospital death. Results: Over a median length of hospital stay of 3.1 days, 86 in-hospital deaths were identified. One unit increase in LnBAR was positively associated with the risk of in-hospital death (hazard ratio [HR], 1.82 [95% CI, 1.42-2.34]). Furthermore, a nonlinear, consistently increasing correlation between elevated BAR and in-hospital mortality was observed (P for trend =0.005 after multiple-adjusted). When BAR was categorized into quartiles, the higher risk of in-hospital death (multiple-adjusted HR, 1.99 [95% CI, (1.1-3.6)]) was found in participants in quartiles 3 to 4 (BAR≥6.28) compared with those in quartiles 1 to 2 (BAR<6.28). In the subgroup analysis, the LnBAR-hospital death association was significantly stronger in participants without kidney insufficiency (yes versus no, P-interaction=0.023). Conclusion: There was a significant and positive association between BAR and the risk of in-hospital death in patients with diabetic ketoacidosis. Notably, the strength of this association was intensified among those without kidney insufficiency.

Environmental judicial reform and corporate investment behavior - Based on a quasi-natural experiment of environmental courts.

Ensuring the effectiveness of environmental legislation and regulations necessitates enhancing the professional caliber of the environmental judiciary. Utilizing a multi-period difference-in-differences model, we explore the impact of environmental judicial reforms, exemplified by the establishment of environmental courts, on corporate investment behavior. We find that firms in regions with established environmental courts significantly increase their environmental investments and productive investments, while financial investments remain unaffected. Mechanism testing reveals that the environmental court affects corporate investment by strengthening local government environmental enforcement and promoting public environmental participation. Furthermore, the marginal effect of environmental courts is more pronounced in regions with fewer environmental regulations and lower economic development levels, as well as in state-owned enterprises. Compared to collegiate benches, environmental resources judicial tribunals exert a greater influence on corporate investment behavior. This study adds to the micro-economic analysis of environmental judiciary by providing empirical evidence on how formal institutional frameworks impact corporate investment behavior.

Anti-atherosclerotic effect of tetrahydroxy stilbene glucoside via dual-targeting of hepatic lipid metabolisms and aortic M2 macrophage polarization in ApoE-/- mice.

Tetrahydroxy stilbene glucoside (TSG) is a water-soluble natural product that has shown potential in treating atherosclerosis (AS). However, its underlying mechanisms remain unclear. Here, we demonstrate that an 8-week TSG treatment (100 mg/kg/d) significantly reduces atherosclerotic lesions and alleviates dyslipidemia symptoms in ApoE-/- mice. 1H nuclear magnetic resonance metabolomic analysis reveals differences in both lipid components and water-soluble metabolites in the livers of AS mice compared to control groups, and TSG treatment shifts the metabolic profiles of AS mice towards a normal state. At the transcriptional level, TSG significantly restores the expression of fatty acid metabolism-related genes (Srepb-1c, Fasn, Scd1, Gpat1, Dgat1, Pparα and Cpt1α), and regulates the expression levels of disturbed cholesterol metabolism-related genes (Srebp2, Hmgcr, Ldlr, Acat1, Acat2 and Cyp7a1) associated with lipid metabolism. Furthermore, at the cellular level, TSG remarkably polarizes aortic macrophages to their M2 phenotype. Our data demonstrate that TSG alleviates arthrosclerosis by dual-targeting to hepatic lipid metabolism and aortic M2 macrophage polarization in ApoE-/- mice, with significant implications for translational medicine and the treatment of AS using natural products.

Identification of novel signal of proton pump inhibitor-associated drug reaction with eosinophilia and systemic symptoms: a disproportionality analysis.

BACKGROUND: Proton pump inhibitors (PPIs) are commonly prescribed for treating upper gastrointestinal hemorrhage, eradicating Helicobacter pylori, and stress ulcer prophylaxis, among other digestive system diseases. Recent case reports provided limited evidence of a correlation between PPIs and drug reactions with eosinophilia and systemic symptoms (DRESS). However, there is currently no established association between PPIs and DRESS. AIM: This research aimed to identify the associations between PPIs and DRESS using the US Food and Drug Administration Adverse Events Reporting System (FAERS) database. METHOD: A retrospective investigation of DRESS associated with six PPIs used FAERS data from Q1 2004 to Q3 2023. Data mining algorithms were used to identify adverse events in the FAERS database that met the following criteria: (1) proportional reporting ratio (PRR) ≥ 2; (2) reporting odds ratio (ROR) > 1; (3) 95% confidence interval (CI) of ROR > 1; (4) Chi-square (χ2) ≥ 4 and case count ≥ 3. RESULTS: There were 495 reports of PPI-related DRESS, including pantoprazole (174, 35.2%), omeprazole (103, 20.8%), lansoprazole (103, 20.8%), esomeprazole (101, 20.4%), rabeprazole (8, 1.6%), and dexlansoprazole (6, 1.2%). The results indicated a significant association of three PPIs (pantoprazole, omeprazole, and lansoprazole) with DRESS. The sensitivity analysis demonstrated that only pantoprazole remained significantly associated with DRESS after 10 concomitant drugs had been removed (ROR: 3.00, PRR: 2.99, and information component [IC]: 1.57). CONCLUSION: This study identified the signals suggesting a potential association between DRESS and six PPIs. However, more investigation of epidemiological data is required to validate of these conclusions.

Acute hepatotoxicity of intravenous amiodarone in a Becker muscular dystrophy patient with decompensated heart failing and ABCB4 gene mutation: as assessed for causality using the updated RUCAM.

BACKGROUND: Cardiac dysfunction, including arrhythmias, may be one of the main clinical manifestations of Becker muscular dystrophy (BMD). Amiodarone is widely used to treat arrhythmia. However, multi-systemic toxicity caused by amiodarone, especially hepatotoxicity, should not be neglected. Here, we introduce a novel case of multi-systemic amiodarone toxicity involving the liver, renal and coagulation in BDM patient with ABCB4 gene mutation. CASE PRESENTATION: We present a case of a 16-year-old boy admitted with heart failure and atrial fibrillation (AF). He was diagnosed with Becker muscular dystrophy (BMD) and gene testing showed comorbid mutations in gene DMD, ABCB4 and DSC2. Amiodarone was prescribed to control the paroxysmal atrial fibrillation intravenously. However, his liver enzyme levels were sharply elevated, along with cardiac shock, renal failure and coagulation disorders. After bedside continuous renal replacement therapy, the patient's liver function and clinical status rehabilitated. CONCLUSIONS: ABCB4 gene mutation might be involved in amiodarone-induced hepatotoxicity. Studies in a cohort might help to prove this hypothesis in the future.

Comprehensive analysis of the association between triglyceride-glucose index and coronary artery disease severity across different glucose metabolism states: a large-scale cross-sectional study from an Asian cohort.

BACKGROUND: The triglyceride-glucose (TyG) index is associated with the development and prognosis of coronary artery disease (CAD). However, the impact of the TyG index on CAD severity across different glucose metabolism states exhibits significant disparities in previous research. METHODS: This cross-sectional study comprised 10,433 participants from a prospective cohort. Participants were categorized into four groups based on glucose metabolism state: normal glucose regulation (NGR), prediabetes (pre-DM), diabetes mellitus (DM) without insulin prescribed (Rx), and DM with insulin Rx. The TyG index was determined by the following formula: Ln [TG (mg/dL) × FPG (mg/dL) / 2], where TG is triglycerides and FPG is fasting plasm glucose. Statistical methods such as binary logistic regression, interaction analysis, restricted cubic spline (RCS), and receiver operating characteristic (ROC) were employed to analyze the relationship between the TyG index and CAD severity across the entire population and glucose metabolism subgroups. Mediation analysis was conducted to examine the mediating effects of glycated hemoglobin (HbA1c) on these relationships. Sensitivity analysis was performed to ensure the robustness of the findings. RESULTS: Multivariable logistic regression analysis revealed a significant positive association between the TyG index and multi-vessel CAD in the entire population (OR: 1.34; 95% CI: 1.22-1.47 per 1-unit increment). Subgroup analysis demonstrated consistent positive associations in the NGR, pre-DM, and DM non-insulin Rx groups, with the highest OR observed in the NGR group (OR: 1.67; 95% CI: 1.3-2.14 per 1-unit increment). No correlation was found in the DM with insulin Rx subgroup. RCS analyses indicated the distinct dose-response relationships across different glucose metabolism subgroups. Including the TyG index in the established model slightly improved the predictive accuracy, particularly in the NGR group. Mediation analyses showed varying mediating effects of HbA1c among different glucose metabolism subgroups. Sensitivity analysis confirmed the robustness of the aforementioned relationships in the new-onset CAD population and in individuals not using antilipidemic medications. CONCLUSIONS: The TyG index positively associated with CAD severity across all glucose metabolism states, except for individuals receiving insulin treatment. Moreover, it might serve as a supplementary noninvasive predictor of CAD severity in addition to established factors, especially in NGR patients.

Bacterial Symbiont Mediates Aphid Antiviral Systems to Inhibit the Propagation of a New Pathogenic Densovirus in Chinese Wheat Aphid, Sitobion miscanthi.

Sitobion miscanthi L-type symbiont (SMLS) is a bacterial symbiont commonly found in the wheat aphid S. miscanthi. A new aphid densovirus, S. miscanthi densovirus (SmDV), was recently identified in S. miscanthi. In this study, the similar cellular tropism of SmDV and SMLS in aphid embryos was uncovered using in situ hybridization. SmDV infection significantly decreased the longevity and number of S. miscanthi offspring. However, the SmDV titers were significantly suppressed after SMLS transmission, thus reducing the negative effects of SmDV infection on S. miscanthi fitness. Moreover, an integrative analysis of RNA-seq datasets showed that SMLS inhibited the expression of genes related to the phosphatidylinositol 3-kinase (Pl3K)/Akt pathways and further induced the expression of antiviral factors associated with the apoptosis and FoxO signaling pathways. These results indicate that SMLS mediates host antiviral defenses to inhibit the propagation of SmDV, which was further verified by an RNA interference assay.

High-Temperature-Resistant Profile Control System Formed by Hydrolyzed Polyacrylamide and Water-Soluble Phenol-Formaldehyde Resin.

To realize the effective profile control of a heavy oil reservoir, hydrolyzed polyacrylamide (HPAM) and water-soluble phenol-formaldehyde resin (PR) were chosen to prepare the profile control system, which gelled at medium or low temperatures and existed stably at high temperatures in the meantime. The effects of phenolic ratios, PR concentration, and HPAM concentration on the formation and strength of the gels were systematically studied by the gel-strength code method and rheological measurements. And the microstructure of the gels was investigated by scanning electron microscope measurements. The results showed that the gelling time of the HPAM-PR system was 13 h at 70 °C. The formed gel could stay stable for 90 days at 140 °C. In addition, the gels showed viscoelastic properties, and the viscosity reached 18,000 mPa·s under a 1.5 s-1 shearing rate due to their three-dimensional cellular network structure. The formation of the gels was attributable to the hydroxyl groups of the PR crosslinking agent, which could undergo the dehydration condensation reaction with amide groups under non-acidic conditions and form intermolecular crosslinking with HPAM molecules. And the organic crosslinker gel system could maintain stability at higher temperatures because covalent bonds formed between molecules.

Brain abscess caused by Streptococcus anginosus group: Three case reports.

BACKGROUND: This case series investigated the clinical manifestations, diagnoses, and treatment of cerebral abscesses caused by Streptococcus anginosus. We retrospectively analyzed the clinical characteristics and outcomes of three cases of cerebral abscesses caused by Streptococcus anginosus and conducted a comprehensive review of relevant literature. CASE SUMMARY: Case 1 presented with a history of left otitis media and exhibited high fever, confusion, and vomiting as primary symptoms. Postoperative pus culture indicated a brain abscess caused by Streptococcus constellatus infection. Case 2 experienced dizziness for two days as the primary symptom. Postoperative pus culture suggested an intermediate streptococcal brain abscess. Case 3: Enhanced head magnetic resonance imaging (MRI) and diffusion-weighted imaging revealed occupancy of the left temporal lobe, initially suspected to be a metastatic tumor. However, a postoperative pus culture confirmed the presence of a brain abscess caused by Streptococcus anginosus infection. The three cases presented in this case series were all patients with community-acquired brain abscesses resulting from angina caused by Streptococcus group infection. All three patients demonstrated sensitivity to penicillin, ceftriaxone, vancomycin, linezolid, chloramphenicol, and levofloxacin. Successful treatment was achieved through stereotaxic puncture, drainage, and ceftriaxone administration with a six -week course of antibiotics. CONCLUSION: Preoperative enhanced head MRI plays a critical role in distinguishing brain tumors from abscesses. Selecting the correct early diagnostic methods for brain abscesses and providing timely intervention are very important. This case series was in accordance with the CARE guidelines.

Effect of Remimazolam on Induction and Maintenance of General Anesthesia in Kidney Transplant Patients.

Purpose: This study aims to evaluate the effect of remimazolam on induction and maintenance of general anesthesia in kidney transplant patients. Methods: 120 patients undergoing kidney transplant were divided into two groups: Propofol group (Group P) and Remimazolam group (Group R). Anesthesia induction: remimazolam had injected IV at a dose of 0.15-0.35 mg/kg in Group R, while propofol had injected IV at a dose of 2.0-2.5 mg/kg in Group P. Anesthesia maintenance: remimazolam was injected IV at a dose of 0.3-1.0 mg·kg-1·h-1 and propofol was injected IV at a dose of 1-12 mg·kg-1·h-1 in Group R, propofol was injected IV at a dose of 3-12 mg·kg-1·h-1 in Group P. All patients have the same remaining anesthesia durgs. Results: Compared with Group P, in Group R the time of disappearance of the eyelash reflex and the time to drop to 60 in BIS was longer (P < 0.05), the time of awakening was shorted (P < 0.05), the MAP of T6 was fluctuated less (P < 0.05), the incidence of hypotension and injection pain during induction was reduced (P < 0.001), the incidence of intraoperative bradycardia during operation was reduced (P < 0.05), the dosages of sedatives drug during maintenance was reduced (P < 0.05). There was no statistically significant difference in postoperative renal function between the two groups of patients (P > 0.05). Conclusion: Remimazolam can be safely and effectively used for the induction and maintenance of general anesthesia in kidney transplant patients.

Xinbao Pill ameliorates heart failure via regulating the SGLT1/AMPK/PPARα axis to improve myocardial fatty acid energy metabolism.

BACKGROUND: Heart failure (HF) is characterized by a disorder of cardiomyocyte energy metabolism. Xinbao Pill (XBW), a traditional Chinese medicine formulation integrating "Liushen Pill" and "Shenfu Decoction," has been approved by China Food and Drug Administration for the treatment of HF for many years. The present study reveals a novel mechanism of XBW in HF through modulation of cardiac energy metabolism. METHODS: In vivo, XBW (60, 90, 120 mg/kg/d) and fenofibrate (100 mg/kg/d) were treated for six weeks in Sprague-Dawley rats that were stimulated by isoproterenol to induce HF. Cardiac function parameters were measured by echocardiography, and cardiac pathological changes were assessed using H&E, Masson, and WGA staining. In vitro, primary cultured neonatal rat cardiomyocytes (NRCMs) were induced by isoproterenol to investigate the effects of XBW on myocardial cell damage, mitochondrial function and fatty acid energy metabolism. The involvement of the SGLT1/AMPK/PPARα signalling axis was investigated. RESULTS: In both in vitro and in vivo models of ISO-induced HF, XBW significantly ameliorated cardiac hypertrophy cardiac fibrosis, and improved cardiac function. Significantly, XBW improved cardiac fatty acid metabolism and mitigated mitochondrial damage. Mechanistically, XBW effectively suppressed the expression of SGLT1 protein while upregulating the phosphorylation level of AMPK, ultimately facilitating the nuclear translocation of PPARα and enhancing its transcriptional activity. Knockdown of SGLT1 further enhanced cardiac energy metabolism by XBW, while overexpression of SGLT1 reversed the cardio-protective effect of XBW, highlighting that SGLT1 is probably a critical target of XBW in the regulation of cardiac fatty acid metabolism. CONCLUSIONS: XBW improves cardiac fatty acid energy metabolism to alleviate HF via SGLT1/AMPK/PPARα signalling axis.

Revealing the role of Peg13: A promising therapeutic target for mitigating inflammation in sepsis.

To investigate the role of Peg13 in modulating the inflammatory response in sepsis, we established Lipopolysaccharide (LPS)-induced 293T cells and mouse models. Peg13 expression was assessed at various time points after infection using RT-qPCR. The levels of high mobility group box 1 (HMGB1) and interleukin-6 (IL-6) were quantified through ELISA. A total of 44 septic patients and 36 healthy participants were recruited to measure Peg13 and HMGB1 levels in the blood. Peg13 demonstrated significant down-regulation in the supernatant of LPS-induced 293T cells and in the blood of LPS-induced mice. Moreover, the levels of proinflammatory cytokines HMGB1 and IL-6 were elevated in both the supernatant of LPS-induced cell models and blood specimens from LPS-induced murine models, and this elevation could be notably reduced by Peg13 suppression. In a clinical context, Peg13 and HMGB1 levels were higher in septic patients compared to healthy subjects. Peg13 exhibited a negative correlation with HMGB1, C-reactive protein (CRP), and erythrocyte sedimentation rate (ESR) among septic patients. Peg13 mitigates the inflammatory response by reducing the release of proinflammatory cytokines HMGB1 and IL-6 in sepsis, presenting a potential therapeutic target for alleviating inflammation in sepsis treatment.

A promoter polymorphism defines distinct roles in anther development for Col-0 and Ler-0 alleles of Arabidopsis ACYL-COA BINDING PROTEIN3.

Acyl-CoA-Binding Proteins (ACBPs) bind acyl-CoA esters and function in lipid metabolism. Although acbp3-1, the ACBP3 mutant in Arabidopsis thaliana ecotype Col-0, displays normal floral development, the acbp3-2 mutant from ecotype Ler-0 characterized herein exhibits defective adaxial anther lobes and improper sporocyte formation. To understand these differences and identify the role of ERECTA in ACBP3 function, the acbp3 mutants and acbp3-erecta (er) lines were analyzed by microscopy for anther morphology and high-performance liquid chromatography for lipid composition. Defects in Landsberg anther development were related to the ERECTA-mediated pathway because the progenies of acbp3-2 × La-0 and acbp3-1 × er-1 in Col-0 showed normal anthers, contrasting to that of acbp3-2 in Ler-0. Polymorphism in the regulatory region of ACBP3 enabled its function in anther development in Ler-0 but not Col-0 which harbored an AT-repeat insertion. ACBP3 expression and anther development in acbp3-2 were restored using ACBP3pro (Ler)::ACBP3 not ACBP3pro (Col)::ACBP3. SPOROCYTELESS (SPL), a sporocyte formation regulator activated ACBP3 transcription in Ler-0 but not Col-0. For anther development, the ERECTA-related role of ACBP3 is required in Ler-0, but not Col-0. The disrupted promoter regulatory region for SPL binding in Col-0 eliminates the role of ACBP3 in anther development.

Polydatin attenuates diabetic renal inflammatory fibrosis via the inhibition of STING pathway.

Diabetic nephropathy (DN) is a complication of diabetes and is mainly characterized by renal fibrosis, which could be attributed to chronic kidney inflammation. Stimulator of interferon genes (STING), a linker between immunity and metabolism, could ameliorate various metabolic and inflammatory diseases. However, the regulatory role of STING in DN remains largely unexplored. In this study, knockdown of STING decreased extracellular matrix (ECM), pro-inflammatory, and fibrotic factors in high glucose (HG)-induced glomerular mesangial cells (GMCs), whereas overexpression of STING triggered the inflammatory fibrosis process, suggesting that STING was a potential target for DN. Polydatin (PD) is a glucoside of resveratrol and has been reported to ameliorate DN by inhibiting inflammatory responses. Nevertheless, whether PD improved DN via STING remains unclear. Here, transcriptomic profiling implied that the STING/NF-κB pathway might be an important target for PD. We further found that PD decreased the protein expression of STING, and subsequently suppressed the activation of downstream targets including TBK1 phosphorylation and NF-κB nuclear translocation, and eventually inhibited the production of ECM, pro-inflammatory and fibrotic factors in HG-induced GMCs. Notably, results of molecular docking, molecular dynamic simulations, surface plasmon resonance, cellular thermal shift assay and Co-immunoprecipitation assay indicated that PD directly bound to STING and restored the declined proteasome-mediated degradation of STING induced by HG. In diabetic mice, PD also inhibited the STING pathway and improved the pathological changes of renal inflammatory fibrosis. Our study elucidated the regulatory role of STING in DN, and the novel mechanism of PD treating DN via inhibiting STING expression.

Atractylenolide I ameliorates sepsis-induced cardiomyocyte injury by inhibiting macrophage polarization through the modulation of the PARP1/NLRP3 signaling pathway.

Sepsis-induced cardiomyopathy (SIC) leads to high mortality and has no effective treatment strategy. Atractylenolide Ⅰ (AT-I) is a sesquiterpene lactone compound and possesses various biological activities such as anti-inflammatory and organ protection. This study was designed to explore the role and the mechanism of AT-I in SIC. CCK-8 assay was used to assess the viability of AT-I-treated RAW 264.7 cells and immunofluorescence assay was used to detect M1 marker CD86. The expressions of M1 markers Cox2, iNOS and CD11b and PARP1/NLRP3 signaling pathway-related proteins were detected using western blot. The transfection efficiency of oe-PARP1 was examined with RT-qPCR and western blot. The ROS activity in H9c2 cells was detected using DCFH-DA assay and western blot was used to detect the expressions of inflammation- and oxidative stress-related proteins. The apoptosis of H9c2 cells was detected using flow cytometry and western blot. The present study found that AT-I inhibited LPS-induced M1 polarization in RAW 264.7 cells through the downregulation of PARP1/NLRP3 signaling pathway, thereby inhibiting the oxidative stress and apoptosis of H9c2 cells. In conclusion, AT-I might be a promising therapeutic agent for SIC by suppressing macrophage polarization through the modulation of PARP1/NLRP3 signaling pathway.

Association of the stress hyperglycemia ratio with coronary artery disease complexity as assessed by the SYNTAX score in patients with acute coronary syndrome.

BACKGROUND: Mounting evidence supports a significant correlation between the stress hyperglycemia ratio (SHR) and both short- and long-term prognoses in patients with acute coronary syndrome (ACS). Nevertheless, research examining the association between the SHR and the complexity of coronary artery disease (CAD) is scarce. Therefore, this study aimed to explore the association between the SHR and CAD complexity, as assessed by the SYNTAX score, in patients with ACS. METHODS: A total of 4715 patients diagnosed with ACS were enrolled and divided into five groups according to the quintiles of the SHR. CAD complexity was assessed using the SYNTAX score and categorized as low (≤ 22) or mid/high (> 22) levels. Logistic regression was utilized to examine the association between the SHR and CAD severity (mid-/high SYNTAX score). Restricted cubic spline (RCS) curves were generated to assess the association between the SHR and CAD severity. Subgroup analyses were conducted to stratify outcomes based on age, sex, diabetes mellitus (DM) status, and clinical presentation. RESULTS: Among the total ACS population, 503 (10.7%) patients had mid/high SYNTAX scores. Logistic regression analysis revealed that the SHR was an independent risk factor for mid/high SYNTAX scores in a U-shaped pattern. After adjusting for confounding variables, Q1 and Q5 demonstrated elevated odds ratios (ORs) relative to the reference category Q3, with ORs of 1.61 (95% CI: 1.19 ∼ 2.19) and 1.68 (95% CI: 1.24 ∼ 2.29), respectively. Moreover, the ORs for Q2 (1.02, 95% CI: 0.73 ∼ 1.42) and Q4 (1.18, 95% CI: 0.85 ∼ 1.63) resembled that of Q3. Compared with the merged Q2-4 group, the ORs were 1.52 (95% CI: 1.21 ∼ 1.92) for Q1 group and 1.58 (95% CI: 1.25 ∼ 2) for the Q5 group. Subgroup analysis revealed that the U-shaped association between the SHR and mid/high SYNTAX score was attenuated in DM patients (P for interaction = 0.045). CONCLUSIONS: There were U-shaped associations between the SHR and CAD complexity in ACS patients, with an SHR ranging from 0.68 to 0.875 indicating a relatively lower OR for mid/high SYNTAX scores. Further studies are necessary to both evaluate the predictive value of the SHR in ACS patients and explore the underlying mechanisms of the observed U-shaped associations.