Insight into the relationship between metabolic enzymes and oxadiazon degradation in Oryza sativa for reducing environmental risks.

Oxadiazon (ODZ) is extensively utilized in agricultural fields for weed control owing to its strong effectiveness. However, excessive loading of ODZ in water bodies and agricultural soils can lead to various environmental concerns. Therefore, it is crucial to understand the ODZ metabolic process and associated mechanisms in crops to assess the likelihood of ODZ contamination in the environment. This study aimed to assess the effects of ODZ on the growth and toxicological responses of rice (Oryza sativa). The growth of rice tissues was notably compromised with the increase in ODZ concentrations. RNA sequencing in combination with liquid chromatography-quadrupole-time-of-flight-high-resolution mass spectrometry/mass spectrometry (LC-Q-TOF-HRMS/MS) analysis allowed for the identification of numerous transcriptional components associated with ODZ metabolism. Four libraries comprising rice roots and shoots exposed to ODZ were RNA-sequenced in triplicate. The application of environmentally realistic ODZ concentrations upregulated the expression of 844 genes in shoots and 1476 genes in roots. Gene enrichment analysis revealed the presence of multiple enzymes involved in ODZ metabolism and detoxification. These enzymes play a critical role in mitigating environmental stress and facilitating xenobiotic metabolism. Notably, among differentially expressed genes, several key enzymes were identified, including cytochrome P450s, protein kinases, aminotransferases, and ATP-binding cassette transporters involved in the metabolic process. Using LC-Q-TOF-HRMS/MS, 3 metabolites and 13 conjugates were identified in multiple metabolic pathways involving oxidation, hydrolysis, glycosylation, acetylation, and methylation. This study successfully established a potential link between the specific metabolic products of ODZ and increased activities of their corresponding enzymes. Moreover, this study considerably elucidates the detailed pathways and mechanisms involved in ODZ metabolism. The study findings provide valuable insights into the development of genotypes for reducing ODZ residues in paddy fields and minimizing their accumulation in rice crops.

Three-Dimensional Reticulated, Spongelike, Resilient Aerogels Assembled by SiC/Si3N4 Nanowires.

For nanofibrous aerogels, a three-dimensional porous structure with interwoven nanofibers as a pore wall has become an urgent demand, and it remains to be a challenge to ensure the mechanical stability and thermal insulation. Other than the reported nanofiber as raw materials to generate three-dimensional cellular nanofibrous aerogels, an alternative low-cost and facile procedure has been proposed here via tactfully utilizing polymer sponge as a template attached with reactive particles, followed by a carbothermal reduction process to realize nanowire growth and their replacement of the original framework. The resulting spongy aerogels with numerous interlaced SiC/Si3N4 nanowires as a skeleton exhibit an ultrahigh porosity of 99.79%. Meanwhile, compressive elasticity after a compression at strain of 35% for 400 cycles, a low thermal conductivity of 23.19 mW/(m K), an excellent absorption capacity of 33.9-95.3 times for varied organic solvents removal, along with flexibility in shape design favored by the initial organic sponge make this nanofibrous aerogel an ideal material for heat shielding, absorption, or catalyst support.

Gender-Related Differences in Clinical Characteristics and Outcomes of Premature Coronary Artery Disease: Insight from the FOCUS Registry.

INTRODUCTION: Although coronary artery disease (CAD) presentations and clinical outcomes differ by sex, little is known about premature CAD (PCAD). The present analysis aimed to evaluate the gender-related differences of PCAD in an Asian population from the FOCUS registry. METHODS: A total of 1397 Asian young patients with angiographically confirmed CAD undergoing drug-eluting stent implantation were included in this analysis and divided into two groups according to the genders. Patients were followed up for three years and clinical outcomes were compared between groups. RESULTS: Young women were older and more likely to have hypertension and diabetes than men (all p<0.001). In contrast, males with PCAD had higher BMI and higher prevalence of current smoking as well as previous vessel revascularizations (all p<0.05). Men were more likely to be manifested as total occlusive lesions (p<0.001). Regardless of the clinical characteristics, the cumulative incidences of adverse events such as major adverse cardiovascular event (MACE), cardiovascular death, and all-cause death were not significantly different at one- or three-year follow-up (all p>0.05). CONCLUSION: Despite remarkable differences in clinical characteristics between Asian males and females with PCAD, the two groups did not differ significantly in clinical outcomes.

Biosynthesis of D-glucaric acid from sucrose with routed carbon distribution in metabolically engineered Escherichia coli.

D-glucaric acid is a promising platform compound used to synthesize many other value-added or commodity chemicals. The engineering of Escherichia coli for efficiently converting D-glucose to D-glucaric acid has been attempted for several years, with mixed sugar fermentation recently gaining growing interests due to the increased D-glucaric acid yield. Here, we co-expressed cscB, cscA, cscK, ino1, miox, udh, and suhB in E. coli BL21 (DE3), functionally constructing an unreported route from sucrose to D-glucaric acid. Further deletion of chromosomal zwf, pgi, ptsG, uxaC, gudD, over-expression of glk, and use of a D-fructose-dependent translation control system for pgi enabled the strain to use sucrose as the sole carbon source while achieving a high product titer and yield. The titer of D-glucaric acid in M9 medium containing 10 g/L sucrose reached ~1.42 g/L, with a yield of ~0.142 g/g on sucrose.

Uptake, translocation, accumulation, and metabolism of fluroxypyr-meptyl and oxidative stress induction in rice seedling.

Fluroxypyr-meptyl (FLUME) is heterocyclic herbicide with internal absorption and transmission characteristics. Owing to its low cost and rapid efficacy, it has been widely used to control broad-leaved weeds in wheat, corn, and rice fields. However, the uptake, translocation, accumulation, and metabolism of FLUME in rice seedlings and the extent of oxidative stress induced by it remain largely unknown, which consequently restricts the comprehensive risk assessment of FLUME residues in the environment during rice production. Hence, we systematically investigated the growth and physiological responses of rice to FLUME and analyzed its uptake, translocation, accumulation, and metabolism in rice seedlings. The results indicated that under 0-0.12 mg/L FLUME treatment, only a small proportion of FLUME was translocated upward and accumulated in rice shoots following absorption via roots, with all the translocation factor values being < 1. Moreover, the distribution and enrichment ability of FLUME in rice seedlings were greater in roots than in shoots. Furthermore, we revealed that FLUME accumulation in rice seedlings evidently inhibited their growth and activated the defense system against oxidative stress, with an increase in the activity of antioxidant and detoxifying enzymes. In addition, multiple metabolic reactions of FLUME were observed in rice seedlings, including dehalogenation, hydroxylation, glycosylation, acetylation, and malonylation. Our study provides systematic insights into the uptake, translocation, accumulation, and metabolism of FLUME in rice seedlings as well as the oxidative stress induced by FLUME accumulation, which can help improve FLUME applications and environmental risk assessments in crops.

CCL11 released by GSDMD-mediated macrophage pyroptosis regulates angiogenesis after hindlimb ischemia.

Peripheral vascular disease (PVD) is an emerging public health burden with a high rate of disability and mortality. Gasdermin D (GSDMD) has been reported to exert pyroptosis and play a critical role in the pathophysiology of many cardiovascular diseases. We ought to determine the role of GSDMD in the regulation of perfusion recovery after hindlimb ischemia (HLI). Our study revealed that GSDMD-mediated pyroptosis occurred in HLI. GSDMD deletion aggravated perfusion recovery and angiogenesis in vitro and in vivo. However, how GSDMD regulates angiogenesis after ischemic injury remains unclear. We then found that GSDMD-mediated pyroptosis exerted the angiogenic capacity in macrophages rather than endothelial cells after HLI. GSDMD deletion led to a lower level of CCL11 in mice serum. GSDMD knockdown in macrophages downregulated the expression and decreased the releasing level of CCL11. Furthermore, recombinant CCL11 improved endothelial functions and angiogenesis, which was attenuated by CCL11 antibody. Taken together, these results demonstrate that GSDMD promotes angiogenesis by releasing CCL11, thereby improving blood flow perfusion recovery after hindlimb ischemic injury. Therefore, CCL11 may be a novel target for prevention and treatment of vascular ischemic diseases.

m6A demethylase ALKBH5 attenuates doxorubicin-induced cardiotoxicity via posttranscriptional stabilization of Rasal3.

The clinical application of anthracyclines such as doxorubicin (DOX) is limited due to their cardiotoxicity. N6-methyladenosine (m6A) plays an essential role in numerous biological processes. However, the roles of m6A and m6A demethylase ALKBH5 in DOX-induced cardiotoxicity (DIC) remain unclear. In this research, DIC models were constructed using Alkbh5-knockout (KO), Alkbh5-knockin (KI), and Alkbh5-myocardial-specific knockout (ALKBH5flox/flox, αMyHC-Cre) mice. Cardiac function and DOX-mediated signal transduction were investigated. As a result, both Alkbh5 whole-body KO and myocardial-specific KO mice had increased mortality, decreased cardiac function, and aggravated DIC injury with severe myocardial mitochondrial damage. Conversely, ALKBH5 overexpression alleviated DOX-mediated mitochondrial injury, increased survival, and improved myocardial function. Mechanistically, ALKBH5 regulated the expression of Rasal3 in an m6A-dependent manner through posttranscriptional mRNA regulation and reduced Rasal3 mRNA stability, thus activating RAS3, inhibiting apoptosis through the RAS/RAF/ERK signaling pathway, and alleviating DIC injury. These findings indicate the potential therapeutic effect of ALKBH5 on DIC.

Gasdermin D mediates endoplasmic reticulum stress via FAM134B to regulate cardiomyocyte autophagy and apoptosis in doxorubicin-induced cardiotoxicity.

Cardiomyocyte pyroptosis and apoptosis play a vital role in the pathophysiology of several cardiovascular diseases. Our recent study revealed that gasdermin D (GSDMD) can promote myocardial I/R injury via the caspase-11/GSDMD pathway. We also found that GSDMD deletion attenuated myocardial I/R and MI injury by reducing cardiomyocyte apoptosis and pyroptosis. However, how GSDMD mediates cardiomyocyte apoptosis and protects myocardial function remains unclear. Here, we found that doxorubicin (DOX) treatment resulted in increased apoptosis and pyroptosis in cardiomyocytes and that caspase-11/GSDMD could mediate DOX-induced cardiotoxicity (DIC) injury. Interestingly, GSDMD overexpression promoted cardiomyocyte apoptosis, which was attenuated by GSDMD knockdown. Notably, GSDMD overexpression exacerbated DIC injury, impaired cardiac function in vitro and in vivo, and enhanced DOX-induced cardiomyocyte autophagy. Mechanistically, GSDMD regulated the activity of FAM134B, an endoplasmic reticulum autophagy receptor, by pore formation on the endoplasmic reticulum membrane via its N-terminus, thus activating endoplasmic reticulum stress. In turn, FAM134B interacted with autophagic protein LC3, thus inducing cardiac autophagy, promoting cardiomyocyte apoptosis, and aggravating DIC. These results suggest that GSDMD promotes autophagy and induces cardiomyocyte apoptosis by modulating the reaction of FAM134B and LC3, thereby promoting DIC injury. Targeted regulation of GSDMD may be a new target for the prevention and treatment of DIC.

Relationship between body mass index and outcomes of coronary artery disease in Asian population: Insight from the FOCUS registry.

BACKGROUND: Obesity is often considered as a risk factor of cardiovascular events, but recent researches showed conflicting results regarding to the effect of body weight on prognosis of coronary artery disease (CAD). This study aimed to evaluate the relationship between body mass index (BMI) and clinical outcomes of CAD in Asian population. METHODS: A total of 4315 patients from the FOCUS registry were enrolled into this analysis. Patients were divided into 4 groups according to BMI: lean group (BMI<18.5 kg/m2), normal group (BMI 18.5-24.9 kg/m2), overweight group (BMI 25-30 kg/m2) and obesity group (BMI>30 kg/m2). Follow-up was continued to 3 years to evaluate clinical outcomes, and the primary endpoint was a composite of all-cause death and myocardial infarction (MI). RESULTS: Patients with higher BMI were more likely to be associated with cardiovascular risk factors like hypertension, hypercholesterolemia and diabetes, but not smoking. At the end of the follow-up period, however, the incidence of a composite endpoint of all-cause death and MI was significantly lower in the higher BMI (overweight and obese) subsets, as compared with the lower BMI group (5.2% vs. 8.0%, p < 0.001). So did the cumulative rates of all-cause death (p < 0.001), cardiovascular death (p < 0.001), and a combined endpoint of cardiovascular death and MI (p = 0.001). CONCLUSIONS: In Asian patients with CAD, an inverse association between BMI and long-term prognosis was observed. Although overweight or obese patients were associated with more metabolism-associated comorbidities, they had significantly lower adverse events at 3-year follow up after percutaneous coronary intervention.

Optimal strategy of primary percutaneous coronary intervention for acute myocardial infarction due to unprotected left main coronary artery occlusion (OPTIMAL): study protocol for a randomised controlled trial.

BACKGROUND: Primary percutaneous coronary intervention (PCI) for patients presenting with acute myocardial infarction (AMI) caused by left main coronary artery occlusion is associated with significantly higher mortality and risks of major adverse cardiovascular events. Deferred stent implantation may improve prognosis of primary PCI by reducing distal embolization and no-reflow phenomenon. There is no randomized clinical trial focusing on the effect and outcome of deferred stent implantation on primary PCI for left main coronary artery occlusion in contrast with conventional strategy. METHODS: The Optimal Strategy of Primary Percutaneous Coronary Intervention for Acute Myocardial Infarction due to Unprotected Left Main Coronary Artery Occlusion (OPTIMAL) study (ClinicalTrials.gov Identifier: NCT03282773) is an open-label, randomized, multicenter clinical trial in which 480 patients presenting with AMI caused by left main coronary artery occlusion recruited from 30 hospitals in mainland China will be randomly assigned 1:1 to immediate stenting or deferred stenting (scheduled 4-10 days after primary angioplasty) groups. The primary endpoint is a composite of all-cause mortality or recurrent myocardial infarction at 30 days after randomization. The secondary outcomes include all-cause mortality, cardiac death, recurrent myocardial infarction, and unplanned target vessel revascularization at 30 days, 6 months, and 12 months. DISCUSSION: The OPTIMAL study is designed to compare the clinical performance of deferred stenting with that of immediate stenting for AMI caused by left main coronary artery occlusion. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT03282773 . Registered on 10 September 2017.

Clinical Characteristics and Outcomes in Asian Patients With Premature Coronary Artery Disease: Insight From the FOCUS Registry.

OBJECTIVES: Premature coronary artery disease (PCAD) is increasingly common in Asian countries; however, less is known regarding its characteristics and clinical outcomes. This study aims to describe clinical characteristics and investigate clinical outcomes in real-world Asian patients with PCAD. METHODS: A total of 4700 Asian patients undergoing drug-eluting stent implantation were included in our study and divided into PCAD group and mature CAD (MCAD) group according to their onset age. All patients were followed up for 3 years to observe their clinical outcomes. RESULTS: Patients with PCAD were more likely to be associated with acute coronary syndrome (ACS; P = .03) and acute occlusive lesion ( P < .001). Reference diameter ( P < .001) and lesion diameter stenosis ( P = .001) were significantly greater in PCAD group. Conversely, the MCAD group was more likely to be associated with left main disease, severe calcification lesion and small vessel involvement. The cumulative incidences of major adverse cardiovascular event (MACE; P = .007), cardiovascular death ( P < .001), and all cause death ( P < .001) were significantly lower in PCAD group than those in MCAD group. CONCLUSIONS: Although more often manifested as ACS, PCAD is associated with lower risks of MACE and cardiovascular death than MCAD in real-world Asian population.

Relationship of serum mannose-binding lectin levels with the development of sepsis: a meta-analysis.

Many studies have evaluated the association between serum levels of mannose-binding lectin (MBL) and sepsis; however, the findings are inconclusive and conflicting. For a better understanding of MBL in sepsis, we conducted a comprehensive meta-analysis. Potential relevant studies were identified covering Science Citation Index, the Cochrane Library, PubMed, Embase, CINAHL, and Current Contents Index databases. Two reviewers extracted data and assessed studies independently. Statistical analyses were conducted with the version 12.0 STATA statistical software. Ten papers were collected for meta-analysis. Results identified that sepsis patients had considerably lower MBL level than those in the controls (standardized mean difference (SMD) = 1.59, 95 % confidence interval (95%CI) = 0.86∼2.31, P < 0.001). Ethnicity-subgroup analysis showed that sepsis patients were associated with decreased serum MBL level in contrast to the healthy controls in Asians (SMD = 3.07, 95%CI = 1.27∼4.88, P = 0.001) and Caucasians (SMD = 1.00, 95%CI = 0.35∼1.65, P = 0.003). In the group-stratified subgroup analysis, subjects with lower serum MBL level did underpin susceptibility to sepsis in the infants subgroup (SMD = 2.57, 95%CI = 1.59∼3.55, P < 0.001); however, this was not the case in the adults subgroup (SMD = 0.13, 95%CI = -1.30∼1.55, P = 0.862). Our study suggests an important involvement of serum MBL level in sepsis patients considering their lower level compared to controls, especially among infants.