Development and Validation of Prognostic Models for Bleeding and Ischemia in Elderly Patients With Comorbid Acute Coronary Syndrome and Atrial Fibrillation.

BACKGROUND: Acute coronary syndrome and atrial fibrillation are common cardiovascular diseases in elderly individuals. Patients with comorbidities face increased risks of bleeding and ischemia; however, there is a lack of prognostic models for quantifying these risks in this special population. METHODS AND RESULTS: In this retrospective cohort study, 1851 patients (≥65 years old) with acute coronary syndrome and atrial fibrillation from 2 hospitals in China were included in the development cohort (1252 individuals) and 2 external validation cohorts (284 and 315 individuals). During 1-year follow-up, 96 Bleeding Academic Research Consortium type 3 or 5 bleeding events and 245 thromboembolic events were observed. In the development cohort, the concordance indexes for bleeding at 3, 6, and 12 mo ranged from 0.737 to 0.845 and for ischemia ranged from 0.723 to 0.777. The calibration curve and decision curve analysis indicated adequate calibration and clinical practicability. The concordance indexes varied from 0.679 to 0.809 in the validation cohorts. Subgroup analyses focusing on anticoagulant drugs and antithrombotic therapy were conducted, revealing similar discrimination and calibration. Kaplan-Meier curves demonstrated significant differences (log-rank P<0.001). Additionally, the models outperformed conventional models in concordance indexes, integrated discrimination improvement, and net reclassification improvement. CONCLUSIONS: Our study provides 2 robust prognostic models with easily available clinical factors for predicting bleeding and ischemia in elderly patients with acute coronary syndrome and atrial fibrillation. Furthermore, we provide online calculators to facilitate individualized risk evaluation and clinical decision-making. REGISTRATION: URL: www.chictr.org.cn/. Unique Identifier: ChiCTR2200067185.

Polyvinyl chloride and polybutylene adipate microplastics affect peanut and rhizobium symbiosis by interfering with multiple metabolic pathways.

Microplastics (MPs), widely presented in cultivated soil, have caused serious stresses on crop growth. However, the mechanism by which MPs affect legumes and rhizobia symbiosis is still unclear. Here, peanut seedlings were inoculated with Bradyrhizobium zhanjiangense CCBAU 51778 and were grown in vermiculite with 3 %/5 % (w/w) addition of PVC (polyvinyl chloride)-MPs/PBAT (polybutylene adipate)-MPs. PVC-MPs and PBAT-MPs separately decreased nodule number by 33-100 % and 2.62-80.91 %. Transcriptome analysis showed that PVC-MPs affected more DEGs (differentially expressed genes) than PBAT-MPs, indicating PVC-MPs were more devastating for the symbiosis than PBAT-MPs. Functional annotation revealed that PVC-MPs and PBAT-MPs enriched DEGs related to biosynthesis pathways such as flavonoid, isoflavonoid, and phenylpropanoid, in peanut. And when the dose increased from 3 % to 5 %, PVC-MPs mainly enriched the pathways of starch and sucrose metabolism, alanine, aspartate and glutamate metabolism, diterpenoid biosynthesis, etc.; PBAT-MPs enriched cysteine and methionine metabolism, photosynthesis, MAPK signaling, and other pathways. These significantly enriched pathways functioned in reducing nodule number and promoting peanut tolerance to MPs stresses. This study reveals the effect of PVC-MPs and PBAT-MPs on peanut and rhizobium symbiosis, and provides new perspectives for legume production and environmental safety.

Transcriptomic and Metabolomic Analyses Reveal the Roles of Flavonoids and Auxin on Peanut Nodulation.

Rhizobia form symbiotic relationships with legumes, fixing atmospheric nitrogen into a plant-accessible form within their root nodules. Nitrogen fixation is vital for sustainable soil improvements in agriculture. Peanut (Arachis hypogaea) is a leguminous crop whose nodulation mechanism requires further elucidation. In this study, comprehensive transcriptomic and metabolomic analyses were conducted to assess the differences between a non-nodulating peanut variety and a nodulating peanut variety. Total RNA was extracted from peanut roots, then first-strand and second-strand cDNA were synthesized and purified. After sequencing adaptors were added to the fragments, the cDNA libraries were sequenced. Our transcriptomic analysis identified 3362 differentially expressed genes (DEGs) between the two varieties. Gene ontology and Kyoto Encyclopedia of Genes and Genomes analyses revealed that the DEGs were mainly involved in metabolic pathways, hormone signal transduction, secondary metabolic biosynthesis, phenylpropanoid biosynthesis, or ABC transport. Further analyses indicated that the biosynthesis of flavonoids, such as isoflavones, flavonols, and flavonoids, was important for peanut nodulation. A lack of flavonoid transport into the rhizosphere (soil) could prevent rhizobial chemotaxis and the activation of their nodulation genes. The downregulation of AUXIN-RESPONSE FACTOR (ARF) genes and lower auxin content could reduce rhizobia's invasion of peanut roots, ultimately reducing nodule formation. Auxin is the major hormone that influences the cell-cycle initiation and progression required for nodule initiation and accumulates during different stages of nodule development. These findings lay the foundation for subsequent research into the nitrogen-fixation efficiency of peanut nodules.

Comparative analysis of the effects of conventional and biodegradable plastic mulching films on soil-peanut ecology and soil pollution.

In agricultural production, biodegradable plastic mulching film (Bio-PMF) has the potential to replace conventional plastic mulching film (CPMF) due to its degradability, but their impacts on soil-crop ecology are controversial. In this study, from 2019 to 2021, effects of CPMF and Bio-PMF on the soil-crop ecology and soil pollution were evaluated on a peanut farm. Compared to the Bio-PMF, an overall improvement in the soil-peanut ecology under the CPMF was observed, including an increase of 10.77 ± 4.8% in peanut yield, an amelioration of four soil physicochemical properties (total P and available P in the flowering stage, total P and temperature in the mature stage), an increase of rhizobacterial relative abundances in class level (Bacteroidia, Blastocatellia, Thermoleophilia and Vicinamibacteria in the flowering stage, Nitrospira and Bacilli in the mature stage) and genus level (RB41 and Bacillus in the flowering stage, Bacillus and Dongia in the mature stage), and an enhancement of soil nitrogen metabolism abilities (ureolysis, nitrification and aerobic ammonia in the flowering stage, nitrate reduction and nitrite ammonification in the mature stage). These preserved soil nutrients and temperature, reshaped rhizobacterial communities, and enhanced soil nitrogen metabolism abilities in the mature stage were obviously correlated with peanut yield under CPMF. However, such remarkable relations were not existed under Bio-PMF. In addition, compared with Bio-PMF, CPMF significantly increased the contents of dimethyl phthalate (DMP), diethyl phthalate (DEP), dibutyl phthalate (DBP) and microplastics (MPs) in soil by 79.93, 44.55, 138.72 and 14.1%, respectively. Thus, CPMF improved soil-peanut ecology and caused serious soil pollution, while Bio-PMF introduced little pollutants into the soil and had little impact on soil-peanut ecology. Based on these, the degradation ability of CPMF or the ecological improvement capacity of Bio-PMF should be improved to obtain the environmentally and soil-crop ecology friendly plastic film in the future.

Nitrogen fertilization rates mediate rhizosphere soil carbon emissions of continuous peanut monoculture by altering cellulose-specific microbess.

Introduction: Crops influence both soil microbial communities and soil organic carbon (SOC) cycling through rhizosphere processes, yet their responses to nitrogen (N) fertilization have not been well investigated under continuous monoculture. Methods: In this study, rhizosphere soil microbial communities from a 5-year continuous mono-cropped peanut land were examined using Illumina HighSeq sequencing, with an N fertilization gradient that included 0 (N0), 60 (N60), 120 (N120) and 180 (N180) kg hm-2. Soil respiration rate (R s) and its temperature sensitivity (Q 10) were determined, with soil carbon-acquiring enzyme activities assayed. Results and discussion: The obtained results showed that with N fertilization, soil mineral N (Nmin) was highly increased and the soil C/N ratio was decreased; yields were unchanged, but root biomass was stimulated only at N120. The activities of ß-1,4-glucosidase and polyphenol oxidase were reduced across application rates, but that of ß-1,4-cellobiohydrolase was increased only at N120. Bacterial alpha diversity was unchanged, but fungal richness and diversity were increased at N60 and N120. For bacterial groups, the relative abundance of Acidobacteria was reduced, while those of Alphaproteobacteria and Gammaproteobacteria were increased at N60 and N120. For fungal members, the pathogenic Sordariomycetes was inhibited, but the saprotrophic Agaricomycetes was promoted, regardless of N fertilization rates. RDA identified different factors driving the variations in bacterial (root biomass) and fungal (Nmin) community composition. N fertilization increased R s slightly at N60 and significantly at N120, mainly through the promotion of cellulose-related microbes, and decreased R s slightly at N180, likely due to carbon limitation. N fertilization reduced microbial biomass carbon (MBC) at N60, N120 and N180, decreased SOC at N120 and N180, and suppressed dissolved organic carbon (DOC) at N180. In addition, the unchanged Q 10 may be a joint result of several mechanisms that counteracted each other. These results are of critical importance for assessing the sustainability of continuously monocultured ecosystems, especially when confronting global climate change.

Cyclic-di-AMP Phosphodiesterase Elicits Protective Immune Responses Against Mycobacterium tuberculosis H37Ra Infection in Mice.

Many antigens from Mycobacterium tuberculosis (M. tuberculosis) have been demonstrated as strong immunogens and proved to have application potential as vaccine candidate antigens. Cyclic di-AMP (c-di-AMP) as a bacterial second messenger regulates various bacterial processes as well as the host immune responses. Rv2837c, the c-di-AMP phosphodiesterase (CnpB), was found to be relative to virulence of M. tuberculosis and interference with host innate immune response. In this study, recombinant CnpB was administered subcutaneously to mice. We found that CnpB had strong immunogenicity and induced high levels of humoral response and lung mucosal immunity after M. tuberculosis intranasally infection. CnpB immunization stimulated splenocyte proliferation and the increasing number of activated NK cells but had little effects on Th1/Th2 cellular immune responses in spleens. However, CnpB induced significant Th1/Th2 cellular immune responses with a decreased number of T and B cells in the lungs, and significantly recruits of CD4+ and CD8+ T cells after M. tuberculosis attenuated strain H37Ra infection. Besides, we first reported that CnpB could stimulate IFN-ß expression transitorily and inhibit the autophagy of macrophages in vitro. In mice intranasally infection model, CnpB immunization alleviated pathological changes and reduced M. tuberculosis H37Ra loads in the lungs. Thus, our results suggested that CnpB interferes with host innate and adaptive immune responses and confers protection against M. tuberculosis respiratory infection, which should be considered in vaccine development as well as a drug target.

Intracellular codelivery of anti-inflammatory drug and anti-miR 155 to treat inflammatory disease.

Atherosclerosis (AS) is a lipid-driven chronic inflammatory disease occurring at the arterial subendothelial space. Macrophages play a critical role in the initiation and development of AS. Herein, targeted codelivery of anti-miR 155 and anti-inflammatory baicalein is exploited to polarize macrophages toward M2 phenotype, inhibit inflammation and treat AS. The codelivery system consists of a carrier-free strategy (drug-delivering-drug, DDD), fabricated by loading anti-miR155 on baicalein nanocrystals, named as baicalein nanorods (BNRs), followed by sialic acid coating to target macrophages. The codelivery system, with a diameter of 150 nm, enables efficient intracellular delivery of anti-miR155 and polarizes M1 to M2, while markedly lowers the level of inflammatory factors in vitro and in vivo. In particular, intracellular fate assay reveals that the codelivery system allows for sustained drug release over time after internalization. Moreover, due to prolonged blood circulation and improved accumulation at the AS plaque, the codelivery system significantly alleviates AS in animal model by increasing the artery lumen diameter, reducing blood pressure, promoting M2 polarization, inhibiting secretion of inflammatory factors and decreasing blood lipids. Taken together, the codelivery could potentially be used to treat vascular inflammation.

Coptidis rhizoma and its main bioactive components: recent advances in chemical investigation, quality evaluation and pharmacological activity.

BACKGROUND: Coptidis rhizoma (CR) is the dried rhizome of Coptis chinensis Franch., C. deltoidea C. Y. Cheng et Hsiao or C. teeta Wall. (Ranunculaceae) and is commonly used in Traditional Chinese Medicine for the treatment of various diseases including bacillary dysentery, typhoid, tuberculosis, epidemic cerebrospinal meningitis, empyrosis, pertussis, and other illnesses. METHODS: A literature survey was conducted via SciFinder, ScieneDirect, PubMed, Springer, and Wiley databases. A total of 139 selected references were classified on the basis of their research scopes, including chemical investigation, quality evaluation and pharmacological studies. RESULTS: Many types of secondary metabolites including alkaloids, lignans, phenylpropanoids, flavonoids, phenolic compounds, saccharides, and steroids have been isolated from CR. Among them, protoberberine-type alkaloids, such as berberine, palmatine, coptisine, epiberberine, jatrorrhizine, columamine, are the main components of CR. Quantitative determination of these alkaloids is a very important aspect in the quality evaluation of CR. In recent years, with the advances in isolation and detection technologies, many new instruments and methods have been developed for the quantitative and qualitative analysis of the main alkaloids from CR. The quality control of CR has provided safety for pharmacological applications. These quality evaluation methods are also frequently employed to screen the active components from CR. Various investigations have shown that CR and its main alkaloids exhibited many powerful pharmacological effects including anti-inflammatory, anti-cancer, anti-diabetic, neuroprotective, cardioprotective, hypoglycemic, anti-Alzheimer and hepatoprotective activities. CONCLUSION: This review summarizes the recent phytochemical investigations, quality evaluation methods, the biological studies focusing on CR as well as its main alkaloids.

Triterpenoids from Cyclocarya paliurus and their inhibitory effect on the secretion of apoliprotein B48 in Caco-2 cells.

Five previously undescribed compounds including two triterpenoid aglycones, 3ß,23-dihydroxy-1,12-dioxo-olean-28-oic acid and 3ß,23,27-trihydroxy-1-oxo-olean-12-ene-28-oic acid, and three triterpenoid glucosides cyclocarioside L-N, along with 17 known compounds were isolated from a CH3Cl-soluble extract of the leaves of Cyclocarya paliurus. Two 27-nor-triterpenoid glycosides were isolated from the genus for the first time. Furthermore, the characterized compounds were tested for the inhibitory effects on apoliprotein B48 secretion in Caco-2 cells. Seven triterpenoid aglycones together with four triterpenoid saponins significantly decreased the apoliprotein B48 oversecretion induced by oleic acid in Caco-2 cells.

In Situ Growth of Clean Pd Nanoparticles on Polystyrene Microspheres Assisted by Functional Reduced Graphene Oxide and Their Excellent Catalytic Properties.

Herein an in situ growth of clean palladium nanoparticles (Pd NPs) on functional reduced graphene oxide (RGO)-coated polystyrene (PS) microspheres is achieved by a simple two-step process. On the basis of the hydrophobic interaction and π-electron interaction, the PS/RGO composite particles are first prepared by the reduction of graphene oxide in the presence of PS microspheres. Second, without using any additional reducing agent or stabilizer, the clean Pd NPs grow in situ on the surface of PS/RGO composite particles in water through a spontaneous redox reaction between Pd2+ and RGO. Significantly, owing to the stabilizer-free surface of Pd NPs and the synergistic effect of RGO and Pd NPs, the resultant PS/RGO@Pd composite particles feature pronounced catalytic activity toward the reduction of p-nitrophenol and Suzuki coupling reactions. Moreover, the catalyst particles can be easily recovered by centrifugation because of the large size of support microspheres and recycled consecutively.

Cytotoxic and apoptosis-inducing activity of C21 steroids from the roots of Cynanchum atratum.

Two new (1-2) and two known C21 steroids (3-4) were isolated from the roots of Cynanchum atratum. Their structures were elucidated by detailed 1D and 2D spectroscopic. The MTT assay showed that compounds 1-4 displayed obvious cytotoxic activities against HepG2 cells with IC50 values ranging from 10.19µM to 76.12µM. Compounds 1-3 also exhibited cytotoxic effects in A549 cells with IC50 values of 30.87-95.39µM. Compound 3 showed the antiproliferative activity via G0/G1 cell cycle arrest and proapoptosis in HepG2 cells by Flowcytometry analysis. Western blotting analysis revealed that compound 3 could induce HepG2 cell apoptosis via the mitochondrial pathway by downregulating Bcl-2 expression, upregulating Bax protein expression, and activating caspase-9 and caspase-3.

Antihyperlipidaemic effect of triterpenic acid-enriched fraction from Cyclocarya paliurus leaves in hyperlipidaemic rats.

CONTEXT: Cyclocarya paliurus (Batal) Iljinskaja (Juglandaceae) is an edible and medicinal plant; the leaves are used in Chinese folkloric medicine to treat dyslipidaemia and diabetes. OBJECTIVE: This study evaluates the antihyperlipidaemic potential of the triterpenic acid-enriched fraction (TAE) from C. paliurus and the underlying mechanism. MATERIALS AND METHODS: The hyperlipidaemic rats were induced by high fat diet for 6 weeks. After oral administration of TAE (200 and 400 mg/kg), the neutral fraction (150 and 300 mg/kg) and statin (4 mg/kg) to the hyperlipidaemic rats for 4 weeks, lipid profile and apolipoprotein (apoB48) level in plasma, and the expression levels of apoB48, microsomal triglyceride transfer protein (MTP), phosphorylation of mitogen-activated protein kinase (MAPK) and tumour necrosis factor α (TNF-α) in intestine were examined. The main constituents in the TAE were identified by HPLC-MS. RESULTS: TAE administration (400 mg/kg) decreased the levels of atherogenic lipids in serum and liver (p < 0.05) and increased serum high-density lipoprotein cholesterol by 19.7%. Furthermore, TAE treatment (200 and 400 mg/kg) decreased plasma apoB48 level by 15.3 and 19.5%, downregulated intestinal apoB48 and MTP expression levels (p < 0.05), and inhibited TNF-α expression by 36.2 and 56.2% and the phosphorylation level of MAPK by 8.8 and 13.2%, respectively. HPLC analysis revealed the presence of pentacyclic- and tetracyclic-triterpene acids in TAE. CONCLUSION AND DISCUSSION: These findings suggested that TAE possessed antihyperlipidaemic activity partially involved in the inhibitory effect on apoB48 overproduction, which may provide evidence about its potential role in ameliorating dyslipidaemia.

Contributions of rational soil tillage to compaction stress in main peanut producing areas of China.

Tillage intensities largely affect soil compaction dynamics in agro-ecosystems. However, the contribution of tillage intensities on compaction changes in underground peanut (Arachis hypogaea) fields has not been quantified. We thus aimed to better understand the role of soil tillage intensities in mitigation of compaction stress for peanuts. Using three field tillage experiments in major Chinese peanut producing areas, we quantified the effects of (1) no tillage, (2) shallow (20 cm) plowing, (3) deep (30 cm) plowing and (4) deep (30 cm) loosening on changes in soil bulk density at 0-10 cm, 10-20 cm and 20-30 cm depths, roots and pods growth, and nutrient accumulation. Results showed that tillage management effectively mitigated soil compaction stress for peanut growth and production. Greater beneficial improvement for the underground growth of roots and pods, and N accumulation ranked as deep plowing > shallow plowing and deep loosening. Respective increases of 7.5% and 4.6% in root biomass productions and peanut yields were obtained when soil bulk density was decreased by 0.1 g cm-3. Our results suggest that the mitigation of soil compaction stress by deep plowing could be a key tillage strategy for increasing peanut yields in the field.

The chloroform extract of Cyclocarya paliurus attenuates high-fat diet induced non-alcoholic hepatic steatosis in Sprague Dawley rats.

BACKGROUND: Hepatic steatosis (HS) is the early stage of nonalcoholic fatty liver disease which is caused by impaired hepatic lipid homeostasis. Cyclocarya paliurus, an herbal tea consumed in China, has been demonstrated to ameliorate abnormal lipid metabolism for the treatment of metabolic diseases. PURPOSE: We aimed to investigate the regulative effect of chloroform extract from Cyclocarya paliurus (ChE) on treatment of HS, as well as key factors involved in hepatic lipid metabolism. STUDY DESIGN: Sprague Dawley rats were fed with high-fat diet (HFD) for 6 weeks to induce HS and treated with or without ChE by gavage for 4 weeks. METHODS: The body weight, relative liver weight and liver fat content were measured. Serum and liver total cholesterol, triglyceride and non-esterified fatty acids, as well as hepatic malonaldehyde levels were accessed by biochemical methods. Serum and liver TNF-α levels were quantified by ELISA kit. Histologic analysis and 1H-MRS study were performed to evaluate HS level. RT-PCR and Western blot were also applied to observe the expression changes of key factors involved in hepatic lipid intake, synthesis, utilization and export. RESULTS: ChE significantly decreased the rats' body weight, serum lipid and TNF-α level. ChE also reduced their relative liver weight, liver fat content, hepatic oxidative products and TNF-α level. Hepatic steatosis in HFD-fed rats was effectively regressed after 2-weeks administration of ChE. Moreover, ChE treatment remarkably reduced HFD-induced high expression level of fatty acid synthesis genes (including sterol-regulatory element-binding protein 1, acetyl-CoA carboxylase 1 and fatty acid synthase). However, it had no effect on mRNA expression of some genes involved in lipid uptake, ß-oxidation and lipid outflow. CONCLUSION: ChE exerted a promising regression effect on HS due to a reduced level of serum non-esterified fatty acids which might lead to a decrease in the amount of lipid taken in by the liver, as well as owing to the inhibition of hepatic lipid de novo synthesis to reduce liver lipid production.

C21 steroidal glycosides from Cynanchum stauntonii induce apoptosis in HepG2 cells.

Two new (1-2) and three known (3-5) C21 steroidal glycosides were isolated from Cynanchum stauntonii. Their structures were elucidated on the basis of 1D and 2D-NMR spectroscopic data as well as HRTOFMS analysis. The cytotoxicity of the compounds against A549, HepG2, and 4T1 cell lines were evaluated by MTT assay. Compound 4 exhibited good inhibitory activities with the IC50 values 26.82, 12.24, and 44.12 µM, respectively. Furthermore, compound 4 could induce G1 phase arrest, upregulate the expression levels of caspases-3, -9, and Bax, and downregulate the expression level of Bcl-2. These results indicated that compound 4 might be valuable to anticancer drug candidates.

Cholesterol-lowering effects and potential mechanisms of different polar extracts from Cyclocarya paliurus leave in hyperlipidemic mice.

ETHNOPHARMACOLOGICAL RELEVANCE: Cyclocarya paliurus Batal., native only to China, is widely consumed as a Chinese traditional folk medicine for the prevention and treatment of hyperlipidemia, obesity, and diabetes. The aim of the study is to investigate the cholesterol-lowering effect and potential mechanisms of different polar extracts from Cyclocarya paliurus leaves in mice fed with high-fat-diet. MATERIALS AND METHODS: Cyclocarya paliurus leaves extracts were orally administered to diet-induced hyperlipidemic mice for 4 weeks. Simvastatin was used as a positive control. Body weight, food intake, histopathology of liver and adipose tissues, hepatic and renal function indices, lipid profiles in the serum and liver were evaluated. Total bile acid concentrations of the liver and feces were also measured. Furthermore, the activities and mRNA expression of cholesterol metabolism-related enzymes including 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase, cholesterol 7α-hydroxylase (CYP7A1) and acyl-CoA cholesterol acyltransferase 2 (ACAT2) in the livers of the mice were analyzed. LC-MS detection was performed to identify the components in the active fraction of Cyclocarya paliurus extracts. RESULTS: Different Cyclocarya paliurus polar extracts, especially ChE reduced the levels of serum total cholesterol (TC), triglycerides (TG), low-density lipoprotein cholesterol (LDL-C) and hepatic TC and TG, enhanced the level of serum high-density lipoprotein cholesterol (HDL-C), restored hepatic and renal function indices and histomorphology. HMG-CoA reductase activity and mRNA expression were decreased, while CYP7A1 activity and mRNA expression as well as the level of fecal and hepatic bile acid were increased by ChE. LC-MS analysis of ChE revealed the presence of six main triterpenoids, which might be responsible for its antihyperlipidemic bioactivity. CONCLUSIONS: Evidently ChE possesses the best antihyperlipidemic activity, and the cholesterol-lowering effect is at least partly attributed to its role in promoting the conversion of cholesterol into bile acids by upgrading the activity and mRNA expression of CYP7A1 and inhibiting those of HMG-CoA reductase to lower the cholesterol biosynthesis.