Bacillus suppresses nitrogen efficiency of soybean-rhizobium symbiosis through regulation of nitrogen-related transcriptional and microbial patterns.

The regulation of legume-rhizobia symbiosis by microorganisms has obtained considerable interest in recent research, particularly in the common rhizobacteria Bacillus. However, few studies have provided detailed explanations regarding the regulatory mechanisms involved. Here, we investigated the effects of Bacillus (Bac.B) on Bradyrhizobium-soybean (Glycine max) symbiosis and elucidated the underlying ecological mechanisms. We found that two Bradyrhizobium strains (i.e. Bra.Q2 and Bra.D) isolated from nodules significantly promoted nitrogen (N) efficiency of soybean via facilitating nodule formation, thereby enhanced plant growth and yield. However, the intrusion of Bac.B caused a reverse shift in the synergistic efficiency of N2 fixation in the soybean-Bradyrhizobium symbiosis. Biofilm formation and naringenin may be importantin suppression of Bra.Q2 growth regulated by Bac.B. In addition, transcriptome and microbiome analyses revealed that Bra.Q2 and Bac.B might interact to regulateN transport and assimilation, thus influence the bacterial composition related to plant N nutrition in nodules. Also, the metabolisms of secondary metabolites and hormones associated with plant-microbe interaction and growth regulation were modulated by Bra.Q2 and Bac.B coinoculation. Collectively, we demonstrate that Bacillus negatively affects Bradyrhizobium-soybean symbiosis and modulate microbial interactions in the nodule. Our findings highlight a novel Bacillus-based regulation to improve N efficiency and sustainable agricultural development.

AcEXPA1, an α-expansin gene, participates in the aluminum tolerance of carpetgrass (Axonopus compressus) through root growth regulation.

KEY MESSAGE: AcEXPA1, an aluminum (Al)-inducible expansin gene, is demonstrated to be involved in carpetgrass (Axonopus compressus) root elongation under Al toxicity through analyzing composite carpetgrass plants overexpressing AcEXPA1. Aluminum (Al) toxicity is a major mineral toxicity that limits plant productivity in acidic soils by inhibiting root growth. Carpetgrass (Axonopus compressus), a dominant warm-season turfgrass widely grown in acidic tropical soils, exhibits superior adaptability to Al toxicity. However, the mechanisms underlying its Al tolerance are largely unclear, and knowledge of the functional genes involved in Al detoxification in this turfgrass is limited. In this study, phenotypic variation in Al tolerance, as indicated by relative root elongation, was observed among seventeen carpetgrass genotypes. Al-responsive genes related to cell wall modification were identified in the roots of the Al-tolerant genotype 'A58' via transcriptome analysis. Among them, a gene encoding α-expansin was cloned and designated AcEXPA1 for functional characterization. Observed Al dose effects and temporal responses revealed that Al induced AcEXPA1 expression in carpetgrass roots. Subsequently, an efficient and convenient Agrobacterium rhizogenes-mediated transformation method was established to generate composite carpetgrass plants with transgenic hairy roots for investigating AcEXPA1 involvement in carpetgrass root growth under Al toxicity. AcEXPA1 was successfully overexpressed in the transgenic hairy roots, and AcEXPA1 overexpression enhanced Al tolerance in composite carpetgrass plants through a decrease in Al-induced root growth inhibition. Taken together, these findings suggest that AcEXPA1 contributes to Al tolerance in carpetgrass via root growth regulation.

Comparison of the efficacy of HoLEP and TURP in the treatment of elderly benign prostatic hyperplasia patients: a retrospective study.

OBJECTIVE: To prove that holmium laser prostatectomy (HoLEP) is safe and effective in the treatment of benign prostatic hyperplasia (BPH), and is superior to transurethral prostatectomy (TURP) for elderly patients. METHODS: We retrospectively studied 565 HoLEP patients and 76 TURP elderly patients. HoLEP patients were first divided into three groups according to their age(Under 65 years old group, 65-79 years old group and over 80 years old group), and their preoperative, intraoperative, and postoperative characteristics were then compared. Secondly, the same characteristics of HoLEP and TURP patients over 80 years were compared. Chi-square test, one-way ANOVA and Fisher's exact test were used in this study. RESULTS: Firstly, we compared HoLEP patients in different age groups and found that there was statistically significant difference in diabetes, CCVD and bladder stones, among the three groups (P<0.05).Secondlye, we compared HoLEP and TURP treatments in elderly patients (≥80 years old). The patients with HoLEP had a higher share of diabetes, CCVD and anticoagulation (P<0.05). Moreover, compared with TURP patients, HoLEP patients had shorter enucleation duration, more enucleate prostate weight, fewer hemoglobin diminutions, shorter bladder irrigation time, shorter catheter-indwelling period, and shorter hospital period (P<0.05). Although there was no difference in IPSS, Qmax and QOL between the two groups before operation (P>0.05), the difference was statistically significant, 6 months after the operation (P<0.05). CONCLUSION: HoLEP is safe and effective for BPH patients, and is superior to transurethral TURP for elderly patients.

The Silkworm Carboxypeptidase Inhibitor Prevents Gastric Cancer Cells' Proliferation through the EGF/EGFR Signaling Pathway.

Gastric cancer is a common malignant tumor originating from the gastric mucosa epithelium. Studies have shown that bioactive substances such as antimicrobial peptides and cantharidin contained in a variety of insects can exert anti-cancer functions; when compared with chemotherapy drugs, these bioactive substances have less toxicity and reduced side effects. Here, we report the first Bombyx mori carboxypeptidase inhibitor that is specifically and highly expressed in silk glands, which can significantly prevent the proliferation of gastric cancer cells by inhibiting the MAPK/ERK pathway initiated by EGF/EGFR through the promotion of expression of the proto-oncogene c-Myc, thereby affecting the expression of related cyclins. Through molecular docking and virtual screening of silkworm carboxypeptidase inhibitors and epidermal growth factor receptors, we identified a polypeptide that overlapped with existing small-molecule inhibitors of the receptor. In the present work, we explore the medicinal potential and application of silkworm carboxypeptidase inhibitors to promote the development of anti-tumor drugs from insect-derived substances.

A Berberine Bridge Enzyme-Like Protein, GmBBE-like43, Confers Soybean's Coordinated Adaptation to Aluminum Toxicity and Phosphorus Deficiency.

Phosphorus (P) deficiency and aluminum (Al) toxicity often coexist and are two major limiting factors for crop production in acid soils. The purpose of this study was to characterize the function of GmBBE-like43, a berberine bridge enzyme-like protein-encoding gene, in soybean (Glycine max) adaptation to Al and low P stresses. Present quantitative real-time PCR (qRT-PCR) assays confirmed the phosphate (Pi)-starvation enhanced and Al-stress up-regulated expression pattern of GmBBE-like43 in soybean roots. Meanwhile, the expression of a GmBBE-like43-GFP chimera in both common bean hairy roots and tobacco leaves demonstrated its cell wall localization. Moreover, both transgenic Arabidopsis and soybean hairy roots revealed the function of GmBBE-like43 in promoting root growth under both Al and low P stresses. GmBBE-like43-overexpression also resulted in more H2O2 production on transgenic soybean hairy root surface with oligogalacturonides (OGs) application and antagonized the effects of Al on the expression of two SAUR-like genes. Taken together, our results suggest that GmBBE-like43 might be involved in the soybean's coordinated adaptation to Al toxicity and Pi starvation through modulation of OGs-oxidation in the cell wall.

Rationale and design for comparison of non-compliant balloon with drug-coating balloon angioplasty for side branch after provisional stenting for patients with true coronary bifurcation lesions: a prospective, multicentre and randomised DCB-BIF trial.

INTRODUCTION: Provisional stenting using drug-eluting stent is effective for simple coronary bifurcation lesions. Kissing balloon inflation using conventional non-compliant balloon is the primary treatment of side branch (SB) after main vessel (MV) stenting. Drug-coating balloon (DCB) is reported to be associated with less frequent clinical events in in-stent restenosis and small vessel disease. The importance of DCB in bifurcation treatment is understudied. Accordingly, this trial is designed to investigate the superiority of DCB to non-compliant balloon angioplasty for SB after provisional stenting in patients with true coronary bifurcation lesions. METHODS AND ANALYSIS: The DCB-BIF trial is a prospective, multicentre, randomised, superiority trial including 784 patients with true coronary bifurcation lesions. Patients will be randomised in a 1:1 fashion to receive either DCB or non-compliant balloon angioplasty if SB diameter stenosis >70% after MV stenting. The primary endpoint is the composite of major adverse cardiac event at the 1-year follow-up, including cardiac death, myocardial infarction (MI) or clinically driven target lesion revascularisation. The major secondary endpoints include all-cause death, periprocedural MI, spontaneous MI, clinically driven target vessel revascularisation, in-stent restenosis, stroke and individual component of the primary endpoint. The safety endpoint is the risk of stent thrombosis. ETHICS AND DISSEMINATION: The study protocol and informed consent have been reviewed and approved by the Institutional Review Board of all participating centres. The written informed consent for participation in the trial will be obtained from all participants. The results of this study will be published in a peer-reviewed journal and disseminated at conferences. TRIAL REGISTRATION NUMBER: NCT04242134.

Characterization of Metal Tolerance Proteins and Functional Analysis of GmMTP8.1 Involved in Manganese Tolerance in Soybean.

Manganese is an essential micronutrient for plant growth but can be toxic to plants when it reaches excessive levels. Although metal tolerance proteins (MTPs), which belong to the cation diffusion facilitator (CDF) family, have been demonstrated to play critical roles in manganese (Mn) tolerance in plants, the characteristics and functions of GmMTP members in the response of soybean (Glycine max) to Mn toxicity have not been documented. In this study, growth inhibition was observed in soybean plants that were exposed to a toxic level of Mn in hydroponics, as reflected by the generation of brown spots, and decreased leaf chlorophyll concentration and plant fresh weight. Subsequent genome-wide analysis resulted in the identification of a total of 14 GmMTP genes in the soybean genome. Among these GmMTPs, 9 and 12 were found to be regulated by excess Mn in leaves and roots, respectively. Furthermore, the function of GmMTP8.1, a Mn-CDF homologue of ShMTP8 identified in the legume Stylosanthes hamata that is involved in Mn detoxification, was characterized. Subcellular localization analysis showed that GmMTP8.1 was localized to the endoplasmic reticulum (ER). Heterologous expression of GmMTP8.1 led to the restoration of growth of the Mn-hypersensitive yeast (Saccharomyces cerevisiae) mutant Δpmr1, which is made defective in Mn transport into the Golgi apparatus by P-type Ca/Mn-ATPase. Furthermore, GmMTP8.1 overexpression conferred tolerance to the toxic level of Mn in Arabidopsis (Arabidopsis thaliana). Under excess Mn conditions, concentrations of Mn in shoots but not roots were decreased in transgenic Arabidopsis, overexpressing GmMTP8.1 compared to the wild type. The overexpression of GmMTP8.1 also led to the upregulation of several transporter genes responsible for Mn efflux and sequestration in Arabidopsis, such as AtMTP8/11. Taken together, these results suggest that GmMTP8.1 is an ER-localized Mn transporter contributing to confer Mn tolerance by stimulating the export of Mn out of leaf cells and increasing the sequestration of Mn into intracellular compartments.

Novel ß-mannanase/GLP-1 fusion peptide high effectively ameliorates obesity in a mouse model by modifying balance of gut microbiota.

We constructed a novel ß-mannanase/GLP-1 fusion peptide, termed MGLP_1, and evaluated its ability to ameliorate obesity in a high-fat/high-sugar diet (HFSD)-induced mouse model. Eight-wk MGLP_1 treatment notably reduced obesity, as reflected by significant changes of body weight, serum triglyceride level, fatty liver and adipose tissue distribution. Amelioration of HFSD-induced gut dysbiosis by MGLP_1 was evidenced by reduced abundance ratio of bacterial phyla Firmicutes to Bacteroidetes, enhanced abundance of beneficial probiotic genera (Bifidobacterium, Lachnospiraceae, Ileibacterium), and reduced abundance of harmful genera (Clostridium, Romboutsia). Mechanisms of weight loss were investigated by comparing effects of treatment with MGLP_1 vs. prebiotics manno-oligosaccharides (MOS). MGLP_1 ameliorated gut microbiota imbalance by enhancing carbohydrate catabolism, whereas MOS promoted glycan synthesis and metabolism. Our findings, taken together, indicate that MGLP_1 fusion peptide has strong potential for amelioration of obesity by modifying relationships between gut microbiota and lipid and glucose metabolism.

Roles of ncRNAs as ceRNAs in Gastric Cancer.

Although ignored in the past, with the recent deepening of research, significant progress has been made in the field of non-coding RNAs (ncRNAs). Accumulating evidence has revealed that microRNA (miRNA) response elements regulate RNA. Long ncRNAs, circular RNAs, pseudogenes, miRNAs, and messenger RNAs (mRNAs) form a competitive endogenous RNA (ceRNA) network that plays an essential role in cancer and cardiovascular, neurodegenerative, and autoimmune diseases. Gastric cancer (GC) is one of the most common cancers, with a high degree of malignancy. Considerable progress has been made in understanding the molecular mechanism and treatment of GC, but GC's mortality rate is still high. Studies have shown a complex ceRNA crosstalk mechanism in GC. lncRNAs, circRNAs, and pseudogenes can interact with miRNAs to affect mRNA transcription. The study of the involvement of ceRNA in GC could improve our understanding of GC and lead to the identification of potential effective therapeutic targets. The research strategy for ceRNA is mainly to screen the different miRNAs, lncRNAs, circRNAs, pseudogenes, and mRNAs in each sample through microarray or sequencing technology, predict the ceRNA regulatory network, and, finally, conduct functional research on ceRNA. In this review, we briefly discuss the proposal and development of the ceRNA hypothesis and the biological function and principle of ceRNAs in GC, and briefly introduce the role of ncRNAs in the GC's ceRNA network.

Estimation of SPAD value in waterlogged winter wheat based on characteristic indices of hyperspectral and digital image.

To explore the optimal monitoring method for soil and plant analyzer development (SPAD) of winter wheat under waterlogging stress based on hyperspectral and digital image techno-logy, the correlations between SPAD of the waterlogged winter wheat and fifteen indices of hyperspectral characteristic and fourteen indices of digital image feature were analyzed under a micro-plot which could be irrigated and drainage separately. Then, the BP neural network models for SPAD estimation were constructed based on the optimal monitoring feature indices. Compared with the normal winter wheat, SPAD and the value of hyperspectral reflectance did not change under short-term waterlogging (less than 7 d), whereas the SPAD was significantly decreased after more than 12 d waterlogging treatment with the value being close to zero at the late stage of growth. The estimation accuracy based on the digital image characteristics of green minus red, excess red index, norma-lized redness index and excess green index showed similar results compared to that using the BP network model based on the characteristics of the corresponding hyperspectral band. The highest R2 between the measured value and the predicted value was 0.86, while the root mean square error (RMSE) was 3.98. Compared with the BP network models built with the digital image feathers, the accuracy of the models based on the four hyperspectral characteristic indices (carotenoid reflex index, yellow edge amplitude, normalized difference vegetation index and structure insensitive pigment index) for SPAD was significantly improved, with the highest R2 of 0.97 and the lowest RMSE of 1.95. Our results suggest that both hyperspectral and digital image technology could be used to estimate SPAD value of waterlogged winter wheat and that the BP network model based on hyperspectral characteristic indices performed better in the estimation accuracy.

Physiological and transcriptomic analyses reveal the roles of secondary metabolism in the adaptive responses of Stylosanthes to manganese toxicity.

BACKGROUND: As a heavy metal, manganese (Mn) can be toxic to plants. Stylo (Stylosanthes) is an important tropical legume that exhibits tolerance to high levels of Mn. However, little is known about the adaptive responses of stylo to Mn toxicity. Thus, this study integrated both physiological and transcriptomic analyses of stylo subjected to Mn toxicity. RESULTS: Results showed that excess Mn treatments increased malondialdehyde (MDA) levels in leaves of stylo, resulting in the reduction of leaf chlorophyll concentrations and plant dry weight. In contrast, the activities of enzymes, such as peroxidase (POD), phenylalanine ammonia-lyase (PAL) and polyphenol oxidase (PPO), were significantly increased in stylo leaves upon treatment with increasing Mn levels, particularly Mn levels greater than 400 µM. Transcriptome analysis revealed 2471 up-regulated and 1623 down-regulated genes in stylo leaves subjected to Mn toxicity. Among them, a set of excess Mn up-regulated genes, such as genes encoding PAL, cinnamyl-alcohol dehydrogenases (CADs), chalcone isomerase (CHI), chalcone synthase (CHS) and flavonol synthase (FLS), were enriched in secondary metabolic processes based on gene ontology (GO) analysis. Numerous genes associated with transcription factors (TFs), such as genes belonging to the C2H2 zinc finger transcription factor, WRKY and MYB families, were also regulated by Mn in stylo leaves. Furthermore, the C2H2 and MYB transcription factors were predicted to be involved in the transcriptional regulation of genes that participate in secondary metabolism in stylo during Mn exposure. Interestingly, the activation of secondary metabolism-related genes probably resulted in increased levels of secondary metabolites, including total phenols, flavonoids, tannins and anthocyanidins. CONCLUSIONS: Taken together, this study reveals the roles of secondary metabolism in the adaptive responses of stylo to Mn toxicity, which is probably regulated by specific transcription factors.

Plasma biomarkers and plaque strain predict long-term cardiovascular events in patients with acute coronary syndrome.

To test whether circulating and intracoronary biomarkers and coronary plaque strain have additive values to Global Registry of Acute Coronary Events (GRACE) score for predicting long-term cardiovascular events in ACS patients. One hundred ACS patients were enrolled and the GRACE score and plasma levels and intracoronary gradients of a number of biomarkers were measured. Coronary plaque burden and morphology in non-critical stenotic plaques were determined by intravascular ultrasound (IVUS) technique, and the maximal shear strain (SSmax) and maximal area strain (ASmax) were determined by intravascular ultrasound elastography (IVUSE) technique. Patients were followed for cardiovascular events and the predictive values of clinical characteristics, plasma biomarkers and plaque parameters were compared with GRACE score, and the incremental values of these measurements to the GRACE score were assessed. GRACE score, plasma biomarkers and plaque strain were independent predictors of cardiovascular events. Combination of GRACE score, plasma biomarkers and plaque strains significantly improved the predictive value of the GRACE score alone with the receiver-operating characteristic area increased from 0.457 to 0.667 (P=0.014). The combination of circulating and intracoronary biomarkers, plaque strain and GRACE score provides a better predictive tool than GRACE score alone in patients with ACS.

MYST1/KAT8 contributes to tumor progression by activating EGFR signaling in glioblastoma cells.

With short survival time, glioblastoma (GBM) is the most malignant tumor in the central nervous system. Recently, epigenetic enzymes play essential roles in the regulation of tumorigenesis and cancer development of GBM. However, little is known about MYST1/KAT8/MOF, a histone acetylation enzyme, in GBM. The present study shows that MYST1 promotes GBM progression through activating epidermal growth factor receptor (EGFR) signaling. MYST1 expression was increased in GBM and was negatively correlated with prognosis in patients with glioma and GBM. Knockdown of MYST1 reduced cell proliferation and BrdU incorporation in LN229, U87, and A172 GBM cells. Besides, MYST1 downregulation also induced cell cycle arrest at G2M phase, as well as the reduced expression of CDK1, Cyclin A, Cyclin B1, and increased expression of p21CIP1/Waf1 . Meanwhile, Self-renewal capability in vitro and tumorigenecity in vivo were also impaired after MYST1 knockdown. Importantly, MYST1 expression was lowly expressed in mesenchymal subtype of GBM and was positively correlated with EGFR expression in a cohort from The Cancer Genome Atlas. Western blot subsequently confirmed that phosphorylation and activation of p-Try1068 of EGFR, p-Ser473 of AKT and p-Thr202/Tyr204 of Erk1/2 were also decreased by MYST1 knockdown. Consistent with the results above, overexpression of MYST1 promoted GBM growth and activated EGFR signaling in vitro and in vivo. In addition, erlotinib, a US Food and Drug Administration approved cancer drug which targets EGFR, was able to rescue MYST1-promoted cell proliferation and EGFR signaling pathway. Furthermore, the transcription of EGF, an EFGR ligand, was shown to be positively regulated by MYST1 possibly via H4K16 acetylation. Our findings elucidate MYST1 as a tumor promoter in GBM and an EGFR activator, and may be a potential drug target for GBM treatment.

Discovery of Selective Butyrylcholinesterase (BChE) Inhibitors through a Combination of Computational Studies and Biological Evaluations.

As there are increased levels and activity of butyrylcholiesterase (BChE) in the late stage of Alzheimer's disease (AD), development of selective BChE inhibitors is of vital importance. In this study, a workflow combining computational technologies and biological assays were implemented to identify selective BChE inhibitors with new chemical scaffolds. In particular, a pharmacophore model served as a 3D search query to screen three compound collections containing 3.0 million compounds. Molecular docking and cluster analysis were performed to increase the efficiency and accuracy of virtual screening. Finally, 15 compounds were retained for biological investigation. Results revealed that compounds 8 and 18 could potently and highly selectively inhibit BChE activities (IC50 values < 10 µM on human BChE, selectivity index BChE > 30). These active compounds with novel scaffolds provided us with a good starting point to further design potent and selective BChE inhibitors, which may be beneficial for the treatment of AD.

Advances in the Mechanisms of Plant Tolerance to Manganese Toxicity.

Manganese (Mn) is an essential element for plant growth due to its participation in a series of physiological and metabolic processes. Mn is also considered a heavy metal that causes phytotoxicity when present in excess, disrupting photosynthesis and enzyme activity in plants. Thus, Mn toxicity is a major constraint limiting plant growth and production, especially in acid soils. To cope with Mn toxicity, plants have evolved a wide range of adaptive strategies to improve their growth under this stress. Mn tolerance mechanisms include activation of the antioxidant system, regulation of Mn uptake and homeostasis, and compartmentalization of Mn into subcellular compartments (e.g., vacuoles, endoplasmic reticulum, Golgi apparatus, and cell walls). In this regard, numerous genes are involved in specific pathways controlling Mn detoxification. Here, we summarize the recent advances in the mechanisms of Mn toxicity tolerance in plants and highlight the roles of genes responsible for Mn uptake, translocation, and distribution, contributing to Mn detoxification. We hope this review will provide a comprehensive understanding of the adaptive strategies of plants to Mn toxicity through gene regulation, which will aid in breeding crop varieties with Mn tolerance via genetic improvement approaches, enhancing the yield and quality of crops.

Down-Regulation of Phosphoribosyl Pyrophosphate Synthetase 1 Inhibits Neuroblastoma Cell Proliferation.

Phosphoribosyl pyrophosphate synthetase 1 (PRPS1) is a key enzyme in de novo nucleotide synthesis and nucleotide salvage synthesis pathways that are critical for purine and pyrimidine biosynthesis. Abnormally high expression of PRPS1 can cause many diseases, including hearing loss, hypotonia, and ataxia, in addition to being associated with neuroblastoma. However, the role of PRPS1 in neuroblastoma is still unclear. In this study, we found that PRPS1 was commonly expressed in neuroblastoma cells and was closely related to poor prognosis for cancer. Furthermore, down-regulation of PRPS1 inhibited neuroblastoma cell proliferation and tumor growth in vitro and in vivo via disturbing DNA synthesis. This study provides new insights into the treatment of neuroblastoma patients and new targets for drug development.

Physiological responses and proteomic changes reveal insights into Stylosanthes response to manganese toxicity.

BACKGROUND: Manganese (Mn), an essential element for plants, can be toxic when present in excess. Stylo (Stylosanthes) is a pioneer tropical legume with great potential for Mn tolerance, but its Mn tolerance mechanisms remain poorly understood. RESULTS: In this study, variations in Mn tolerance were observed among nine stylo genotypes. Stylo genotype 'RY5' exhibited the highest Mn tolerance compared to the other tested genotypes, whereas 'TF2001' was a Mn-sensitive genotype. The mechanisms underlying the response of stylo to Mn toxicity were further investigated using these two genotypes with contrasting Mn tolerance. Results showed that stylo genotype RY5 exhibited Mn tolerance superior to that of genotype TF2001, showing lower reductions in leaf chlorophyll concentration, chlorophyll fluorescence parameters, photosynthetic indexes and plant dry weight under Mn toxicity. A label-free quantitative proteomic analysis was conducted to investigate the protein profiles in the leaves and roots of RY5 in response to Mn toxicity. A total of 356 differentially expressed proteins (DEPs) were identified, including 206 proteins from leaves and 150 proteins from roots, which consisted of 71 upregulated, 62 downregulated, 127 strongly induced and 96 completely suppressed proteins. These DEPs were mainly involved in defense response, photosynthesis, carbon fixation, metabolism, cell wall modulation and signaling. The qRT-PCR analysis verified that 10 out of 12 corresponding gene transcription patterns correlated with their encoding proteins after Mn exposure. Finally, a schematic was constructed to reveal insights into the molecular processes in the leaves and roots of stylo in response to Mn toxicity. CONCLUSIONS: These findings suggest that stylo plants may cope with Mn toxicity by enhancing their defense response and phenylpropanoid pathways, adjusting photosynthesis and metabolic processes, and modulating protein synthesis and turnover. This study provides a platform for the future study of Mn tolerance mechanisms in stylo and may lead to a better understanding of the potential mechanisms underlying tropical legume adaptation to Mn toxicity.

Association of lymphocyte to monocyte ratio with severity of coronary artery disease.

The aim of this study was to investigate the relationship between lymphocyte to monocyte ratio (LMR) and the severity of coronary artery disease (CAD) by using Gensini score.A total of 199 patients, who had undergone coronary angiography, were included in the study and retrospectively analyzed. Among them, 49 patients who had normal coronary arteries were selected as the control group. Patients with CAD were divided into 2 groups, those with low Gensini score (≤40) and those with high Gensini score (≥40).Our results showed that LMR in the severe atherosclerosis group was significantly lower than those of the mild atherosclerosis group and the control group. There was a closely significant correlation between the Gensini score and LMR (r = -0.362, P < .001). Furthermore, multivariate logistic regression analysis demonstrated that LMR (odds ratio, 0.715; 95% confidence interval [CI], 0.551-0.927; P = .012) was independent predictors of severe atherosclerosis. Using an optimal LMR cut-off value of 5.06, LMR predicted severe atherosclerosis with a sensitivity of 57.1% and specificity of 69.7% (area under curve = 0.634; 95% CI, 0.545-0.724; P = .005). Then patients with CAD group was divided into 2 groups according to the LMR value of 5.06. Patients with LMR ≤ 5.06 had worse prognosis, with a higher rate of cardiovascular events during up to 1 year follow-up.Our study demonstrated that LMR was independently and positively associated with the severity of coronary atherosclerosis, providing a new insight in the application of inflammation index evaluating the severity of CAD. And LMR may be a useful predictor of future cardiovascular events in patients with CAD.

Effects of spironolactone in heart failure with preserved ejection fraction: A meta-analysis of randomized controlled trials.

BACKGROUND: Heart failure with preserved ejection fraction (HFpEF) is a common syndrome, accounting for more than one half of all heart failure patients, which is associated with high morbidity and mortality. But there is little evidence-based therapeutic strategies for the management of HFpEF. Previous studies reported the effects of spironolactone on HFpEF; however, the results were inconsistent. In this meta-analysis, we evaluated the effects of spironolactone on HFpEF. METHODS: Articles were searched on PubMed, EMBASE, and COCHRANE databases before May, 2017, and were supplemented by hand searches of reference lists of included studies and review articles. Eligible articles were restricted to randomized controlled trials (RCTs). The odds ratios (ORs) of the dichotomous data, mean difference (MD) of continuous data, and 95% confidence intervals (CIs) were calculated to assess the effects of spironolactone in patients with HFpEF. RESULTS: A total of 7 studies including 4147 participants were analyzed. There were significant improvements on the E/e' index (MD -1.38; 95% CI, -2.03 to -0.73; P < .0001) and E/A velocity ratio (MD -0.05; 95% CI, -0.10 to -0.00; P = .03) under spironolactone treatment compared with placebo, while there was no effect on the deceleration time (MD 1.04; 95% CI, -8.27 to 10.35; P = .83). Subgroup analyses on the E/A velocity ratio showed that there was obvious benefit from spironolactone therapy in patients with follow-up periods >6 months but not in those with follow-up periods ≤6 months. There was no reduction in all-cause mortality and hospitalization compared with placebo. And no improvement in 6-minute walk distance was seen compared with placebo. CONCLUSION: This meta-analysis demonstrates that the use of spironolactone improves left ventricular diastolic function in patients with HFpEF, whereas it has no effect on all-cause mortality and hospitalization, and the 6-minute walk distance. Further larger size, multicenter, RCTs are required to confirm the effects of spironolactone on patients with HFpEF.

Comparison of everolimus-eluting bioresorbable vascular scaffolds and metallic stents: three-year clinical outcomes from the ABSORB China randomised trial.

AIMS: Absorb bioresorbable vascular scaffolds (BVS) and XIENCE cobalt-chromium everolimus-eluting stents (CoCr-EES) had comparable angiographic and clinical outcomes up to one year in patients enrolled in the ABSORB China randomised trial. Whether these favourable results with BVS continue beyond one year up to three years is unknown. In this study we sought to analyse the outcomes from the trial up to three-year follow-up. METHODS AND RESULTS: ABSORB China was a prospective, open-label, multicentre trial in which 480 patients with one or two native coronary artery lesions were randomised 1:1 to BVS (N=241) vs. CoCr-EES (N=239). Clinical endpoints included target lesion failure (TLF; cardiac death, target vessel-related myocardial infarction or ischaemia-driven target lesion revascularisation), its components, and definite/probable stent/scaffold thrombosis (ST). There were no significant differences in clinical outcomes in patients treated with BVS and CoCr-EES up to three years, including TLF (5.5% vs. 4.7%, p=0.68) and definite/probable ST (0.9% vs. 0.0%, p=0.50). STs in the BVS arm consisted of one probable subacute event at 15 days and one definite very late event at 622 days. Among 32 BVS patients with a reference vessel diameter between 2.25 and 3.75 mm by quantitative coronary angiography and in whom post-dilatation was performed at >16 atm with a balloon:scaffold diameter >1:1 and balloon ≤scaffold diameter 0.5 mm, no TLF or ST events occurred within three years. CONCLUSIONS: In the ABSORB China trial, BVS and CoCr-EES had similar results up to three-year follow-up, the time at which the scaffold has completely resorbed. BVS outcomes may be further optimised by appropriate lesion selection and implantation technique.