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Phytophthora sojae infection severely impairs soybean production. We previously identified a dirigent protein, GmDRR1 (Glycine max Disease Resistant Response 1), that increases soybean resistance to P. sojae. However, the molecular basis of GmDRR1 function remained largely uncharacterized. In the present study, analysis of GmDRR1-RNAi, GmDRR1-overexpressing, and CRISPR/Cas9-derived Gmdrr1 mutant lines revealed that GmDRR1 expression significantly restricted P. sojae growth. Combining co-immunoprecipitation with liquid chromatography–tandem mass spectrometry revealed a GmDRR1-interacting protein, GmDRR2, which is homologous to GmDRR1. An E-coniferyl alcohol coupling assay indicated that GmDRR1 promotes the synthesis of (+)-pinoresinol, which helps to protect plants from P. sojae. The GmNAC1 (Glyma.05G025500) transcription factor bound to the GmDRR1 promoter both in vitro and in vivo to upregulate GmDRR1 expression. Soybean resistance to P. sojae was increased by overexpression of GmNAC1. Our findings suggest a novel signaling pathway involving a NAC transcription factor that mediates soybean resistance to P. sojae. Specifically, GmNAC1 directly induces GmDRR1 expression to increase resistance of soybean plants to P. sojae.

The binding energies of ACdSeNRs and ZCdSeNRs vary as a function of nanoribbon width. With comparable width, the binding energies of ACdSeNRs are significantly greater than those of ZCdSeNRs, indicating that armchair nanoribbons are more stable.

Mesenchymal stem cell–derived exosomes (MSC-Exos) have been shown to promote angiogenesis. Treating MSCs with ischemic rat brain extracts was sufficient to augment their benefits in stroke. However, no similar analyses of ischemic heart extracts have been performed to date. We aim to determine whether MSC-Exos derived from MSCs pretreated with ischemic rat heart extract were able to promote angiogenesis and to clarify underlying mechanisms. ELISA (enzyme-linked immunosorbent assay) of heart extracts revealed a significant increase of vascular endothelial growth factor (VEGF) at 24 h post-MI (myocardial infarction) modeling, and time-dependent decreases in hypoxia inducible factor–1α (HIF-1α). MTT and wound healing assays revealed human umbilical vein endothelial cells (HUVECs) migration and proliferation increased following MSCE-Exo treatment (exosomes derived from MSC pretreated with ischemic heart extracts of 24 h post-MI) relative to MSCN-Exo treatment (exosomes derived from MSC pretreated with normal heart extracts). Proteomic analyses of MSCE-Exo and MSCN-Exo were conducted to screen for cargo proteins promoting angiogenesis. Result revealed several angiogenesis-related proteins were upregulated in MSCE-Exo, including DMBT1 (deleted in malignant brain tumors 1). When DMBT1 was silenced in MSCs, HUVECs with MSCDMBT1 RNAi-Exo treatment exhibited impaired proliferative and migratory activity and reductions of DMBT1, p-Akt, β-catenin, and VEGF. To explore how ischemic heart extracts took effects, ELISA was conducted showing a significant increase of IL-22 at 24 h post-MI modeling. P-STAT3, IL22RA1, DMBT1, and VEGF proteins were increased in MSCE relative to MSCN, and VEGF and DMBT1 were increased in MSCE-Exos. Together, these suggest that IL-22 upregulation in ischemic heart extracts can increase DMBT1 in MSCs. Exosomes derived from those MSCs deliver DMBT1 to HUVECs, thereby enhancing their migratory and proliferative activity.

Graphical abstract, Highlights • Polyploidization events were the main driving force for GRASs expansion. • Evolutionary analysis reveals that inter-species GRASs functions may be conserved. • GRASs helped plants resist stress by regulating flavonoids pathway. • GRASs regulate flavonoid synthesis by crosstalk with auxin and photosynthetic pathway. • Polyploidized GRASs play key roles in environment adaption, growth and development., Introduction Environmental stress is both a major force of natural selection and a prime factor affecting crop qualities and yields. The impact of the GRAS [gibberellic acid-insensitive (GAI), repressor of GA1–3 mutant (RGA), and scarecrow (SCR)] family on plant development and the potential to resist environmental stress needs much emphasis. Objectives This study aims to investigate the evolution, expansion, and adaptive mechanisms of GRASs of important representative plants during polyploidization. Methods We explored the evolutionary characteristics of GRASs in 15 representative plant species by systematic biological analysis of the genome, transcriptome, metabolite, protein complex map and phenotype. Results The GRAS family was systematically identified from 15 representative plant species of scientific and agricultural importance. The detection of gene duplication types of GRASs in all species showed that the widespread expansion of GRASs in these species was mainly contributed by polyploidization events. Evolutionary analysis reveals that most species experience independent genome-wide duplication (WGD) events and that interspecies GRAS functions may be broadly conserved. Polyploidy-related Chenopodium quinoa GRASs (CqGRASs) and Arabidopsis thaliana GRASs (AtGRASs) formed robust networks with flavonoid pathways by crosstalk with auxin and photosynthetic pathways. Furthermore, Arabidopsis thaliana population transcriptomes and the 1000 Plants (OneKP) project confirmed that GRASs are components of flavonoid biosynthesis, which enables plants to adapt to the environment by promoting flavonoid accumulation. More importantly, the GRASs of important species that may potentially improve important agronomic traits were mapped through TAIR and RARGE-II publicly available phenotypic data. Determining protein interactions and target genes contributes to determining GRAS functions. Conclusion The results of this study suggest that polyploidy-related GRASs in multiple species may be a target for improving plant growth, development, and environmental adaptation.

The computing method of the average optimal position is one of the most important factors that affect the optimization performance of the QPSO algorithm. Therefore, a particle position weight computing method based on particle fitness value grading is proposed, which is called HWQPSO (hierarchical weight QPSO). In this method, the higher the fitness value of a particle, the higher the level of the particle, and the greater the weight. Particles at different levels have different weights, while particles at the same level have the same weight. Through this method, the excellent particles have higher average optimal position weight, and at the same time, the absolute weight of a few particles is avoided, so that the algorithm can quickly and stably converge to the optimal solution, and improve the optimization ability and efficiency of the algorithm. In order to verify the effectiveness of the method, five standard test functions are selected to test the performance of HWQPSO, QPSO, DWC-QPSO and LTQPSO algorithm, and the algorithms are applied to the task scheduling of the cloud computing platform. Through the test experiment and application comparison, the results show that the HWQPSO algorithm can converge to the optimal solution of the test function faster than the other three algorithms. It can also find the task scheduling scheme with the shortest time consumption and the most balanced computing resource load in the cloud platform. In the experiment, compared with QPSO, DWC-QPSO and LTQPSO algorithm, HWQPSO execution time of the maximum task scheduling was reduced by 35%, 23% and 21% respectively.

Abnormal environmental conditions induce polyploidization and exacerbate vulnerability to agricultural production. Polyploidization is a pivotal event for plant adaption to stress and the expansion of transcription factors. NACs play key roles in plant stress resistance and growth and development, but the adaptive mechanism of NACs during plant polyploidization remain to be explored. Here, we identified and analyzed NACs from 15 species and found that the expansion of NACs was contributed by polyploidization. The regulatory networks were systematically analyzed based on polyomics. NACs might influence plant phenotypes and were correlated with amino acids acting as nitrogen source, indicating that NACs play a vital role in plant development. More importantly, in quinoa and Arabidopsis thaliana, NACs enabled plants to resist stress by regulating flavonoid pathways, and the universality was further confirmed by the Arabidopsis population. Our study provides a cornerstone for future research into improvement of important agronomic traits by transcription factors in a changing global environment.

Statins are first-line drugs used to control patient lipid levels, but there is recent evidence that statin treatment can lower colorectal cancer (CRC) incidence by 50% and prolong CRC patient survival through mechanisms that are poorly understood. In this study, we found that the treatment of APCmin mice by the mevalonate pathway inhibitor lovastatin significantly reduced the number of colonic masses and improved hypersplenism and peripheral anemia. Furthermore, reverse transcription polymerase chain reaction (RT-PCR) analysis of colonic mass tissues showed a potent inhibitory effect in both Wnt/β-catenin signaling and YAP/TAZ signaling in the lovastatin treatment group. The results of our transcriptomic analyses in RKO indicated that lovastatin regulated several proliferation-related signaling pathways. Moreover, lovastatin suppressed important genes and proteins related to the canonical Wnt/β-catenin and alternative Wnt-YAP/TAZ signaling pathways in RKO and SW480 cells, and these effects were rescued by mevalonic acid (MVA), as confirmed through a series of Western blotting, RT-PCR, and reporter assays. Given that statins suppress oncogenic processes primarily through the inhibition of Rho GTPase in the mevalonate pathway, we speculate that lovastatin can inhibit certain Rho GTPases to suppress both canonical Wnt/β-catenin signaling and alternative Wnt-YAP/TAZ signaling. In RKO cells, lovastatin showed similar inhibitory properties as the RhoA inhibitor CCG1423, being able to inhibit β-catenin, TAZ, and p-LATS1 protein activity. Our results revealed that lovastatin inhibited RhoA activity, thereby suppressing the downstream canonical Wnt/β-catenin and alternative Wnt-YAP/TAZ pathways in colon cancer cells. These inhibitory properties suggest the promise of statins as a treatment for CRC. Altogether, the present findings support the potential clinical use of statins in non-cardiovascular contexts and highlight novel targets for anticancer treatments.

Maintaining phosphorus (Pi) homeostasis in nodules is the key to nodule development and nitrogen fixation, an important source of nitrogen for agriculture and ecosystems. PHOSPHATE-TRANSPORTER1 (PHT1) and its regulator PHOSPHATE-STARVATION-RESPONSE1 (PHR1), which constitute the PHR1-PHT1 module, play important roles in maintaining Pi homeostasis in different organs. However, the PHR1-PHT1 module and its functions in nodules remain unknown. We identified one PHT1 (GmPHT1;11) and four PHR1 (GmPHR1) homologs in soybean (Glycine max) plants, which displayed specific expression patterns in different tissues in nodules, similar to previously reported GmPHT1;1 and GmPHT1;4. Through the integration of different approaches, GmPHR-GmPHT1 modules were confirmed. Combining our results and previous reports, we established multiple GmPHR-GmPHT1 modules acting in the infected or noninfected tissues in nodules. A single GmPHR had more than one GmPHT1 target, and vice versa. Therefore, overlapping and cross-talking modules monitored the wave of available Pi to maintain Pi homeostasis in nodules, which sequentially regulated nodule initiation and development. High levels of GmPHT1;11 enhanced Pi accumulation in nodules, increased nodule size, but decreased nodule number. Nitrogenase activity was also enhanced by GmPHT1;11. Our findings uncover GmPHR-GmPHT1 modules in nodules, which expands our understanding of the mechanism of maintaining Pi homeostasis in soybean plants.

In soybean (Glycine max)-rhizobium interactions, the type III secretion system (T3SS) of rhizobium plays a key role in regulating host specificity. However, the lack of information on the role of T3SS in signaling networks limits our understanding of symbiosis. Here, we conducted an RNA sequencing analysis of three soybean chromosome segment substituted lines, one female parent and two derived lines with different chromosome-substituted segments of wild soybean and opposite nodulation patterns. By analyzing chromosome-linked differentially expressed genes in the substituted segments and quantitative trait loci (QTL)-assisted selection in the substituted-segment region, genes that may respond to type III effectors to mediate plant immunity–related signaling were identified. To narrow down the number of candidate genes, QTL assistant was used to identify the candidate region consistent with the substituted segments. Furthermore, one candidate gene, GmDRR1, was identified in the substituted segment. To investigate the role of GmDRR1 in symbiosis establishment, GmDRR1-overexpression and RNA interference soybean lines were constructed. The nodule number increased in the former compared with wild-type soybean. Additionally, the T3SS-regulated effectors appeared to interact with the GmDDR1 signaling pathway. This finding will allow the detection of T3SS-regulated effectors involved in legume-rhizobium interactions.

In plants, the spatiotemporal expression of circadian oscillators provides adaptive advantages in diverse species. However, the molecular basis of circadian clock in soybean is not known. In this study, we used soybean hairy roots expression system to monitor endogenous circadian rhythms and the sensitivity of circadian clock to environmental stimuli. We discovered in experiments with constant light and temperature conditions that the promoters of clock genes GmLCLb2 and GmPRR9b1 drive a self-sustained, robust oscillation of about 24-h in soybean hairy roots. Moreover, we demonstrate that circadian clock is entrainable by ambient light/dark or temperature cycles. Specifically, we show that light and cold temperature pulses can induce phase shifts of circadian rhythm, and we found that the magnitude and direction of phase responses depends on the specific time of these two zeitgeber stimuli. We obtained a quadruple mutant lacking the soybean gene GmLCLa1, LCLa2, LCLb1, and LCLb2 using CRISPR, and found that loss-of-function of these four GmLCL orthologs leads to an extreme short-period circadian rhythm and late-flowering phenotype in transgenic soybean. Our study establishes that the morning-phased GmLCLs genes act constitutively to maintain circadian rhythmicity and demonstrates that their absence delays the transition from vegetative growth to reproductive development.

HIV subtypes convey important epidemiological information and possibly influence the rate of disease progression. In this study, HIV disease progression in patients infected with CRF01_AE, CRF07_BC, and subtype B was compared in the largest HIV molecular epidemiology study ever done in China. A national data set of HIV pol sequences was assembled by pooling sequences from public databases and the Beijing HIV laboratory network. Logistic regression was used to assess factors associated with the risk of AIDS at diagnosis ([AIDSAD], defined as a CD4 count

Guangdong Province is one of the most developed and populous provinces in southern China. The subtype situation of hepatitis C virus (HCV) in Guangdong remains unknown. The aim of this study was to investigate and estimate the HCV subtypes in drug users (DU) using a city-based sampling strategy to better understand the characteristics of HCV transmission in Guangdong. Archived plasma samples (n = 1074) from DU who were anti-HCV positive in 2014 were selected randomly from 20 cities in Guangdong Province. Subtypes were determined based on core and/or E1 sequences using phylogenetic analysis. The distributions of HCV subtypes in DU and different regions were analyzed. A total of 8 genotypes were identified. The three main HCV subtypes in DU in Guangdong were 6a (63.0%), 3a (15.2%), and 3b (11.8%). Significant differences were discovered among different registered residency and regions but not among genders, marital status, education level, or drug use patterns. HCV subtype 3b was significantly higher in Guangdong residents than in non-Guangdong residents. In contrast, HCV subtype 6a was significantly lower in Guangdong residents than in non-Guangdong residents. Subtype 1b in eastern Guangdong (eastern) was significantly lower, while 6a was significantly higher when compared with other regions. Subtype 3a in the Pearl River Delta (PRD) region was significantly higher, while 3b was significantly lower when compared with other regions. In western Guangdong, HCV subtype 3a was significantly lower when compared with other regions. Additionally, in northern Guangdong subtypes 1b and 3b were significantly higher, while 6a was significantly lower when compared with other regions. Our study revealed the diversity and distribution of HCV subtypes in DU in nearly all the cities in Guangdong. The results provide essential information that will allow the establishment of specific intervention strategies that may help prevent HCV transmission.

The CRF01_AE and CRF07_BC clades dominate the human immunodeficiency virus (HIV) epidemics in China. Both clades have been identified in the men who have sex with men (MSM) population in Guangdong province, raising a serious concern of possible complex recombination events ahead. Here, we report the first case of CRF01_AE/CRF07_BC recombinant sampled from a MSM patient in southern China. The genomic structure of this case is a mosaic with some regions resembling the CRF01_AE and CRF07_BC clades. Our phylogenetic analyses show that the two parental lineages of this recombinant virus were mainly found in the MSM population. This case has a different genomic composition compared with other recombinants descended from the same parental clades CRF01_AE and CRF07_BC. Our finding suggests that the MSM populations have become a hotspot for expanding viral diversity through the viral recombination mechanism. Therefore, further epidemiologic surveillance and monitoring should be conducted within the MSM populations to help advance our knowledge of viral transmission mechanisms. Additionally, these measures will serve to enhance the control and prevention of HIV/acquired immunodeficiency syndrome in China.

Long noncoding RNA SOX2OT is associated with myocardial fibrosis (MF) in heart failure (HF). This article aims to investigate the role of SOX2OT in MF. We constructed HF mouse models by subcutaneous injection of isoprenaline (ISO). Cardiac fibroblasts (CFs) were treated with ISO to induce MF.Hematoxylin-eosin, Masson, and Sirius-red staining were used to identify myocardial injury and collagen deposition in heart tissues. The relationship among SOX2OT, miR-138-5p, TGF-β1, and Smad3 were evaluated by chromatin immunoprecipitation and luciferase reporter assay. The gene and protein expression were verified by quantitative real-time PCR and western blot. We found that SOX2OT was up-regulated in HF mice and ISO-induced CFs. SOX2OT knockdown reduced myocardial injury and collagen deposition in HF mice. The expression of collagen I, α-SMA, TGF-β1, and p-Smad3 were inhibited by SOX2OT down-regulation in HF mice and ISO-induced CFs. Furthermore, TGF-β1 was a target gene of miR-138-5p and indirectly regulated by SOX2OT. SOX2OT promoted MF in HF by activating TGF-β1/Smad3, and then Smad3 interacted with the SOX2OT promoter and formed a positive feedback loop. In conclusion, our work verifies that SOX2OT/Smad3 feedback loop promotes MF in HF. Thus, SOX2OT is potentially a novel therapeutic target for MF in HF.

Reindeer (Rangifer tarandus) have lengthy seasonal migrations on land and their feet possess excellent locomotor characteristics that can adapt to complex terrains. In this study, the kinematics and vertical ground reaction force (GRF) of reindeer forelimb joints (interphalangeal joint b, metacarpophalangeal joint c, and wrist joint d) under walk, trot 1, and trot 2 were measured using a motion tracking system and Footscan pressure plates. Significant differences among different locomotor activities were observed in the joint angles, but not in changes of the joint angles (αb, αc, αd) during the stance phase. Peak vertical GRF increased as locomotor speed increased. Net joint moment, power, and work at the forelimb joints were calculated via inverse dynamics. The peak joint moment and net joint power related to the vertical GRF increased as locomotor speed increased. The feet absorbed and generated more energy at the joints. During different locomotor activities, the contribution of work of the forelimbs changed with both gait and speed. In the stance phase, the metacarpophalangeal joint absorbed more energy than the other two joints while trotting and thus performed better in elastic energy storage. The joint angles changed very little (∼5°) from 0 to 75% of the stance phase, which reflected the stability of reindeer wrist joints. Compared to typical ungulates, reindeer toe joints are more stable and the stability and energy storage of forelimb joints contribute to locomotor performance in reindeer.

In soybean (

Supplemental material, Raw_data for Bionic research on spikes based on the tractive characteristics of ostrich foot toenail by Rui Zhang, Dianlei Han, Guolong Yu, Haitao Wang, Haibao Liu, Haibin Yu and Jianqiao Li in SIMULATION

Background: HIV-1 CRF55_01B was first reported in 2013. At present, no report is available regarding this new clade’s polymorphisms in its functionally critical regions protease and reverse transcriptase. Objective: To identify the diversity difference in protease and reverse transcriptase between CRF55_01B and its parental clades CRF01_AE and subtype B; and to investigate CRF55_01B’s drug resistance mutations associated with the protease inhibition and reverse transcriptase inhibition. Methods: HIV-1 RNA was extracted from plasma derived from a MSM population. The reverse transcription and nested PCR amplification were performed following our in-house PCR procedure. Genotyping and drug resistant-associated mutations and polymorphisms were identified based on polygenetic analyses and the usage of the HIV Drug Resistance Database, respectively. Results: A total of 9.24 % of the identified CRF55_01B sequences bear the primary drug resistance. CRF55_01B contains polymorphisms I13I/V, G16E and E35D that differ from those in CRF01_AE. Among the 11 polymorphisms in the RT region, seven were statistically different from CRF01_AE’s. Another three polymorphisms, R211K (98.3%), F214L (98.3%), and V245A/E (98.3 %.), were identified in the RT region and they all were statistically different with that of the subtype B. The V179E/D mutation, responsible for 100% potential low-level drug resistance, was found in all CRF55_01B sequences. Lastly, the phylogenetic analyses demonstrated 18 distinct clusters that account for 35% of the samples. Conclusions: CRF55_01B’s pol has different genetic diversity comparing to its counterpart in CRF55_01B’s parental clades. CRF55_01B has a high primary drug resistance presence and the V179E/D mutation may confer more vulnerability to drug resistance.

Maintaining phosphorus (Pi) homeostasis in nodules is the key to nodule development and nitrogen fixation, an important source of nitrogen for agriculture and ecosystems. PHOSPHATE-TRANSPORTER1 (PHT1) and its regulator PHOSPHATE-STARVATION-RESPONSE1 (PHR1), which constitute the PHR1-PHT1 module, play important roles in maintaining Pi homeostasis in different organs. However, the PHR1-PHT1 module and its functions in nodules remain unknown. We identified one PHT1 (GmPHT1;11) and four PHR1 (GmPHR1) homologs in soybean (Glycine max) plants, which displayed specific expression patterns in different tissues in nodules, similar to previously reported GmPHT1;1 and GmPHT1;4. Through the integration of different approaches, GmPHR-GmPHT1 modules were confirmed. Combining our results and previous reports, we established multiple GmPHR-GmPHT1 modules acting in the infected or noninfected tissues in nodules. A single GmPHR had more than one GmPHT1 target, and vice versa. Therefore, overlapping and cross-talking modules monitored the wave of available Pi to maintain Pi homeostasis in nodules, which sequentially regulated nodule initiation and development. High levels of GmPHT1;11 enhanced Pi accumulation in nodules, increased nodule size, but decreased nodule number. Nitrogenase activity was also enhanced by GmPHT1;11. Our findings uncover GmPHR-GmPHT1 modules in nodules, which expands our understanding of the mechanism of maintaining Pi homeostasis in soybean plants.

Abstract Background:Cardiovascular disease patients associated with psychological disorders are very common clinically.It has been demonstrated in previous study that a higher prevalence of psychiatric disorders in the patients with CVD than the general population.Anxiety and depression are found to be the most common types of psychiatric disorders in the patients with CVD.Objective:Exploring the clinical characteristics and relating factors of somatization symptoms of the outpatients with psychological disorders. Methods:From August 2017 to July 2018,we used the General Anxiety Disorder-7, Patient Health Questionnaire, Patient Health Questionnaire-15 and self-made general demographic data questionnaire to investigate the outpatients suspected with psychiatric disorders in cardiology department in a general hospital,who were screened with the"three questions"method.Results:Among the 508 effective patients, the total detection rate of anxiety/depression was 81.1%(412/508),and the detection rate of somatization symptoms was 93.1%(473/508).The positive number of PHQ-15 symptom items was 8.54±2.67,and the detection rate of anxiety/depression was 78.7% in 473 patients with somatization symptoms.Among the patients with mild,moderate and severe somatization symptoms,there were significant differences in the proportion of women, the average number of the patient visits and hospitalizations in the past year(P=0.0341, 0.023),and also in GAD-7 and PHQ-9 scale scores(P=0.0282, 0.0011).Linear correlation analysis showed PHQ-15 score was significantly correlated with GAD-7(r=0.4787, P

As the main actuator of high-speed running, the ostrich feet are highly capable of cushioning and shock absorption. In this study, based on the elastic modulus scales and assembly order of the 3rd toe soft tissues and the functions of the metatarsophalangeal (MTP) joint, we designed fourteen bio-inspired feet. The impact process on loose sand was simulated on the finite element software Abaqus. Also the stress distributions and deformations of each component of the bio-inspired feet were clarified. With the peak acceleration as the index, the cushioning performances of the bio-inspired feet were compared on both loose sand and solid ground through height-variable impact tests. The 15-15-15 HA (hardness unit) bio-inspired foot showed lower peak acceleration and thereby better cushioning performance, but larger deformation, less-uniform stress distribution and thereby lower stability than the 15-35-55 HA bio-inspired foot. In fact, the silicon rubbers with different hardness degrees (which simulate the elasticity modulus scales of the digital cushions, fascia and skin) and the spring mechanism (which simulates the functions of the MTP joint) work as an "integrated system" of cushioning and shock absorption.

Table S1 Representative evaluation of genotyped samples by city in the study. (PDF 87 kb)

Table S2 Estimated number of HIV-1 genotype in different cities and risk groups. (PDF 215 kb)

Major advances in crop yield are eternally needed to cope with population growth. To balance vegetative and reproductive growth plays an important role in agricultural yield. To extend vegetative phase can increase crop yield, however, this strategy risks loss of yield in the field as crops may not mature in time before winter come. Here, we identified a repression feedback loop between GmFTL/GmFDL and GmGRF5-1 (Glycine-max-Flowering-Locus-T/Glycine-max-FDL and Glycine-max-GROWTH-REGULATING-FACTOR5-1), which functions as a pivotal regulator in balancing vegetative and reproductive phases in soybean. GmFTL/GmFDL and GmGRF5-1 directly repress gene expression each other. Additionally, GmGRF5-1 enhances vegetative growth by directly enhancing expression of photosynthesis- and auxin synthesis-related genes. To modulate the loop, such as fine-tuning GmFTL expression to trade-off vegetative and reproductive growth, increases substantially soybean yield in the field. Our findings not only uncover the mechanism balancing vegetative and reproductive growth, but open a new window to improve crop yield.

Transplantation of stem cells, including mesenchymal stromal cells (MSCs), improves the recovery of cardiac function after myocardial infarction (MI) in experimental studies using animal models and in patients. However, the improvement of cardiac function following MSC transplantation remains suboptimal in both preclinical and clinical studies. Understanding the mechanism of cell therapy may improve its therapeutic outcomes, but the mode of action mediating stem cell promotion of cardiac repair is complex and not fully understood. Recent studies suggest that the immunomodulatory effects of MSCs on the macrophage M1/M2 subtype transition allow the transplanted stem cells to inhibit inflammation-induced injury and promote cardiac repair in acute MI. However, equally compelling evidence shows that there is poor survival and minimal graft persistence of transplanted MSCs within the infarcted heart tissues, negating the view that graft survival per se is required for the observed high rate and long duration of the transition from proinflammatory M1 to reparative M2 macrophages in the infarcted myocardium. Therefore, we raised a novel hypothesis that the therapeutic effects of MSC transplantation for acute MI depends not primarily on the grafted cells in infarct myocardium, but that MSCs migrating to and being lodged in the extracardiac organs, demonstrating good graft survival and persistence, may render the therapeutic effects in MI. More specifically, MSC transplantation promotes the transition from M1 to M2 in extracardiac organs, such as spleen and bone marrow, and therapeutic effects are conferred to the infarcted myocardium via paracrine effects. In MSC transplantation, the conversion from proinflammatory M1 to anti-inflammatory M2 monocytes may occur remotely from the heart and may serve as one of the major pathways in regulating the dual effects of inflammation. This hypothesis, if proven valid, may represent an important new mechanism of action to be considered for the future of MSC transplantation in the treatment of MI.

Background Guangdong Province is one of the most developed and populous provinces in southern China, with frequent foreign exchanges and large transient population. The annual number of cases of HIV/AIDS reported in Guangdong has been higher than most of provinces in China for several successive years. HIV infection by heterosexual transmission occurs across the province, with transmission among men who have sex with men occurring mainly in larger urban centers. There is a lack of widespread and representative data on the distribution of HIV subtypes in Guangdong. This study aimed to thoroughly investigate and estimate the prevalence and distribution of HIV-1 subtypes using a city-based sampling strategy to better understand the characteristics of HIV transmission in Guangdong. Methods Archived plasma samples (n = 1205) from individuals diagnosed as HIV-1 infection in 2013 were selected randomly from all 21 cities in Guangdong Province. Genotypes were determined using env and/or gag sequences using phylogenetic analysis. The distributions of HIV genotypes in different risk groups and different cities were analyzed. Results A total of 15 genotypes, including six discordant genotypes, were identified. The four main HIV-1 subtypes in Guangdong were CRF01_AE (43.2%), CRF07_BC (26.3%), CRF55_01B (8.5%), and CRF08_BC (8.4%). CRF01_AE was the predominant subtype in all risk populations. The high mobility of people shaped the complexity of the HIV genotypes, while the switch of risk factors affected the distribution and future trend of HIV-1 genotypes in Guangdong. Another epicenter located in the western region in addition to the known epicenter cities in the Pearl River Delta region of Guangdong may exist. Conclusions Our study provides a comprehensive molecular epidemiologic dataset to understand the diversity and distribution of HIV genotypes in Guangdong, as well as to clarify the unique region- and risk group-specific transmission dynamics. The results provide critical and insightful information for more effective intervention strategies to limit HIV transmission in the future. Electronic supplementary material The online version of this article (10.1186/s12879-019-3788-7) contains supplementary material, which is available to authorized users.

First-principles Density Functional Theory (DFT) calculations were carried out on electronic and magnetic properties of cadmium selenide nanoribbons (CdSeNRs) with both zigzag and armchair edges. All armchair nanoribbons exhibit nonmagnetic and semiconducting behavior, regardless of ribbon widths and their edge passivation status. Bare zigzag nanoribbons are found to be metallic and have non-zero net magnetic moments. The net magnetic moment of these ribbons increases as ribbon width increases. However, when zigzag edges are passivated with hydrogen, a degeneracy between the up and down spin was found, which turns ribbons into nonmagnetic ones.

BACKGROUND Although there are several reported evidences for a pathogenic role of sphingolipid signaling in atherosclerosis, peripheral blood levels of ceramide and secretory acid sphingomyelinase (S-SMase) activity in patients with acute coronary syndromes (ACS) have not been evaluated. METHODS AND RESULTS A total of 304 CAD patients and 52 healthy individuals were divided into four groups: control group (n=52), stable angina pectoris (SAP) group (n=98), unstable angina pectoris (UAP) group (n=92), and acute myocardial infarction (AMI) group (n=114). Plasma levels of sphingomyelin (SPM) were elevated in patients with UAP and AMI compared with those in the control and SAP participants. Plasma ceramide levels and S-SMase activity in patients with ACS (including UAP and AMI) on day 0 were significantly higher than those in the control and SAP participants. Elevation in plasma ceramide levels in patients with UAP and AMI was sustained until a day after percutaneous coronary intervention or day 7, respectively. Moreover, in patients with UAP, S-SMase activity elevation on day 0 was followed by a gradual decrease toward the SAP range up to a day after percutaneous coronary intervention. In patients with AMI, elevation in S-SMase activity showed a peak on day 3. CONCLUSION Serial changes in plasma ceramide and S-SMase activity were documented in patients with ACS. These findings provide an insight into the molecular mechanism of plaque destabilization.

We report a first principles study on the electronic structure of CdSe nanosheet under strain. Our results suggest that the band structure of CdSe nanosheet experiences a transition from being semiconducting to metallic with increased symmetrical strain. Such transition is not found under asymmetrical (along zigzag or armchair direction) strain. Moreover, the band gap of CdSe nanosheet responds differently among symmetrical, zigzag and armchair strain. A detailed discussion on the strain dependence effect is also presented via the electron localization function, the charge transfer between Cd and Se atoms, and the evolution of energy states at Γ and K point.

The electronic and optical properties of CdSe nanosheet under uniform strain are investigated using first-principles calculations. The band structure, density of states and optical spectra of CdSe nanosheet are calculated. The conduction bands are found to move towards the Fermi energy when strain changes from compressive to tensile. This leads to a decrease in the energy bandgap. Optical properties also show strong dependence on strain. The peaks of the dielectric function are mapped with corresponding electron transitions between the bands. All peaks experiences redshifts under increasing strain. This phenomenon is explained via the analysis on the band structures. Other optical properties including the index of refraction, the extinction coefficient, the reflectivity, the absorption coefficient, and the energy-loss function were also calculated to investigate the mechanism of optical transitions of CdSe nanosheet.

African ostrich (Struthio camelus) is the largest and fastest extent bipedal animal. The ostrich mainly relies on the 3rd toe to support the entire body under high-speed motion. The short and severe impact concentrated on the limited area would produce tremendous momentary internal stress and strain, which may contribute to the phalanges disloaction, soft tissue damage and the like. The vibration and excessive negative acceleration caused by the ground reaction force also affect the stability of the touching process. Therefore, ostrich toe pads are required to have excellent cushion characteristics. However, current studies often explains the cushion properties by analyzing the macro-microscopic structure of the pad organism, and there is a paucity of research on its biomechanical behaviour. Consequently, from the perspective of multi-layer structure and biomaterial assembly, this study aims to explain the biomechanical characteristics of the ostrich toe pads by FEM (Finite Element Method) analysis. Based on results, we deem that the ostrich toe pad could absorb energy and reduce vibration effectively. Firstly, the multi-layer structure of the pads make the stress and strain decay from outside to inside. Secondly, the minimal response frequency of the pad is 164.22 Hz, making it effectively avoid resonance phenomenon. Finally, the composite material model has the best performance in decreasing the negative acceleration peak value, the impact force peak value and the maximal equivalent stress value at velocities of 0.669 m/s and 1.339 m/s. These results help to further understand the buffer mechanism of the ostrich toe pad, and also have important inter-species reference value for the pathogenesis of human foot soft tissue injury.

In current work highly sensitive and stable electrochemical sensor for simultaneous detection of ascorbic acid (AA), dopamine (DA), and uric acid (UA) is constructed based on the hierarchical nanoporous (HNP) PtTi alloy. The HNP-PtTi alloy is simply fabricated by two-step dealloying process, characterized by the bimodal ligament/pore size distributions and interconnected hollow channels. The HNP structure with the advantages of large surface area, excellent structure stability, and rich pore channels is used for facilitating the electron conductivity and the mass transfer. Combined with the dual effects of the bimodal nanoporous architecture and the excellent electrocatalytic activity of PtTi alloy, the constructed sensor exhibits high electrochemical sensing activity with wide linear responses from 0.2 to 1mM, 0.004 to 0.5mM, and 0.1 to 1mM for simultaneous detection of AA, DA, and UA, respectively. In addition, HNP-PtTi alloy also shows long-term sensing stability towards the AA, DA, and UA detection and behaves as a good anti-interference towards NaCl, KCl, FeCl3, CuCl2, AlCl3, glucose, and H2O2. The HNP-PtTi alloy manifests intriguing application potential as the candidate for the application of the electrochemical sensor for simultaneous detection of AA, DA, and UA.

This study assessed the potential of intravenous transplantation of human umbilical cord blood (HUCB) CD34+ cells transfected with glial cell line-derived neurotrophic factor (GDNF) gene to exert therapeutic benefits in spontaneous hypertensive rats (SHR) exposed to transient middle cerebral artery occlusion (MCAO). SHR with MCAO were randomly assigned to receive intravenously transplantation of vehicle, the plasmid containing the enhanced green fluorescent protein (pEGFP)-CD34+ cells or pEGFP-GDNF-CD34+ cells at 6h after stroke. The CD34+ cells transfected with GDNF gene expressed higher levels of GDNF mRNA and protein than nontransfected HUCB CD34+ cells in vitro. At 28 days after transplantation of GDNF gene modified CD34+ cells, significantly more GFP positive cells, neurons, and astrocytes, likely derived from the grafted cells, populated the peri-infarct area compared to those injected with pEGFP-CD34+ cells or vehicle. Furthermore, the stroke animals transplanted with GDNF gene modified CD34+ cells showed a significant increase in GDNF level in the infarcted hemisphere, reduced brain infarction volume, and enhanced functional recovery compared with those that received pEGFP-CD34+ cells. This study supports the use of a combined gene and stem cell therapy for treating stroke.

We recently demonstrated that blood–brain barrier permeabilization using mannitol enhances the therapeutic efficacy of systemically administered human umbilical cord blood (HUCB) by facilitating the entry of neurotrophic factors from the periphery into the adult stroke brain. Here, we examined whether the same blood–brain barrier manipulation approach increases the therapeutic effects of intravenously delivered HUCB in a neonatal hypoxic-ischaemic (HI) injury model. Seven-day-old Sprague–Dawley rats were subjected to unilateral HI injury and then at day 7 after the insult, animals intravenously received vehicle alone, mannitol alone, HUCB cells (15k mononuclear fraction) alone or a combination of mannitol and HUCB cells. Behavioural tests at post-transplantation days 7 and 14 showed that HI animals that received HUCB cells alone or when combined with mannitol were significantly less impaired in motor asymmetry and motor coordination compared with those that received vehicle alone or mannitol alone. Brain tissues from a separate animal cohort from the four treatment conditions were processed for enzyme-linked immunosorbent assay at day 3 post-transplantation, and revealed elevated levels of GDNF, NGF and BDNF in those that received HUCB cells alone or when combined with mannitol compared with those that received vehicle or mannitol alone, with the combined HUCB cells and mannitol exhibiting the most robust neurotropic factor up-regulation. Histological assays revealed only sporadic detection of HUCB cells, suggesting that the trophic factor–mediated mechanism, rather than cell replacement per se, principally contributed to the behavioural improvement. These findings extend the utility of blood–brain barrier permeabilization in facilitating cell therapy for treating neonatal HI injury.

To study genetic diversity and drug resistance of HIV-1 CRF_BC among drug users in Guangdong Province, 67 circulating recombinant form 07_BC (CRF_07BC) and 32 circulating recombinant form 08_BC(CRF_08BC) HIV-1 pol genes were amplified and sequenced. In the protease gene region (PR), 31 CRF_08BC isolates were amplified and 10 high polymorphism positions were identified. The polymorphisms L19I, M36I, R41K, D60E, L63P, H69K, and I93L were complete substitutions, and were followed by T12S (94%), I15V (90%), and L89M (81%) separately. Five high polymorphisms were found in CRF_07BC isolates; there were E35D (88%), R41K (100%), D60E (96%), L63P (99%), and I93L (91%). Four of the identified polymorphism positions (R41K, D60E, L63P, and I93L) were the same in the PR region of both subtypes. In the reverse transcriptase (RT) region six high polymorphism positions, V35T, E36A, T39D/E/N, S48T, V60I, and V245Q, were identified in both subtypes. E53D (97%), I135V/T/R (81%), S162C (94%), Q207E (100%), and R211K (97%) were primarily in CRF_08BC subtypes and D121Y/H (97%) were primarily in CRF_07BC. The NRTI resistance mutation T69S was 94% (30/32) in CRF_08BC. To now, we have found no related reports concerning such high polymorphisms in the position. Polymorphisms V77M (PI) and K201Q (RT) were not found in the mutation profiles; therefore it may have been a new mutation in HIV-1. This study analyzed the difference between CRF_08BC and 07BC polymorphisms among drug users in Guangdong Province, which may help to guide recommendations for diagnostic assays, vaccine design, and antiretroviral regimen strategies in China.

Neural stem cells (NSCs) possess high potencies of self-renewal and neuronal differentiation. We explored here whether transplantation of human NSCs cloned by v-mycgene transfer, HB1.F3 cells, is a feasible therapeutic option for Parkinson's disease.In vivo, green fluorescent protein-labeled HB1.F3 cells (200,000 viable cells in 3 μl of PBS) when stereotaxically transplanted (same-day lesion-transplant paradigm) into the 6-hydroxydopamine-lesioned striatum of rats significantly ameliorated parkinsonian behavioral symptoms compared with controls (vehicle, single bolus, or continuous minipump infusion of trophic factor, or killed cell grafts). Such graft-derived functional effects were accompanied by preservation of tyrosine hydroxylase (TH) immunoreactivity along the nigrostriatal pathway. Grafted HB1.F3 cells survived in the lesioned brain with some labeled with neuronal marker mitogen-activated protein 2 and decorated with synaptophysin-positive terminals. Furthermore, endogenous neurogenesis was activated in the subventricular zone of transplanted rats. To further explore the neuroprotective mechanisms underlying HB1.F3 cell transplantation, we performed cell culture studies and found that a modest number of HB1.F3 cells were TH and dopamine and cAMP-regulated phosphoprotein 32 positive, although most cells were nestin positive, suggesting a mixed population of mature and immature cells. Administration of the HB1.F3 supernatant to human derived dopaminergic SH-SY5Y cells and fetal rat ventral mesencephalic dopaminergic neurons protected against 6-hydroxydopamine neurotoxicity by suppressing apoptosis through Bcl-2 upregulation, which was blocked by anti-stem cell factor antibody alone, the phosphatidylinositol 3-kinase/Akt inhibitor LY294002 [2-(4-morpholinyl)-8-phenyl-1(4H)-benzopyran-4-one] alone, or a combination of both. These results suggest that HB1.F3 cell transplantation exerts neuroprotective effects against dopaminergic depletionin vitroandin vivobecause of trophic factor secretion and neuronal differentiation.

Children born with hypoxic-ischemic (HI) brain injury account for a significant number of live births wherein no clinical treatment is available. Limited clinical trials of stem cell therapy have been initiated in a number of neurological disorders, but the preclinical evidence of a cell-based therapy for neonatal HI injury remains in its infancy. One major postulated mechanism underlying therapeutic benefits of stem cell therapy involves stimulation of endogenous neurogenesis via transplantation of exogenous stem cells. To this end, transplantation has targeted neurogenic sites, such as the hippocampus, for brain protection and repair. The hippocampus has been shown to secrete growth factors, especially during the postnatal period, suggesting that this brain region presents as highly conducive microenvironment for cell survival. Based on its neurogenic and neurotrophic factor-secreting features, the hippocampus stands as an appealing target for stem cell therapy. Here, we investigated the efficacy of intrahippocampal transplantation of multipotent progenitor cells (MPCs), which are pluripotent progenitor cells with the ability to differentiate into a neuronal lineage. Seven-day-old Sprague-Dawley rats were initially subjected to unilateral HI injury, which involved permanent ligation of the right common carotid artery and subsequent exposure to hypoxic environment. At day 7 after HI injury, animals received stereotaxic hippocampal injections of vehicle or cryopreserved MPCs (thawed just prior to transplantation) derived either from Sprague-Dawley rats (syngeneic) or Fisher rats (allogeneic). All animals were treated with daily immunosuppression throughout the survival period. Behavioral tests were conducted on posttransplantation days 7 and 14 using the elevated body swing test and the rotarod to reveal general and coordinated motor functions. MPC transplanted animals exhibited reduced motor asymmetry and longer time spent on the rotarod than those that received the vehicle infusion. Both syngeneic and allogeneic MPC transplanted injured animals did not significantly differ in their behavioral improvements at both test periods. Immunohistochemical evaluations of graft survival after behavioral testing at day 14 posttransplantation revealed that syngeneic and allogeneic transplanted MPCs survived in the hippocampal region. These results demonstrate for the first time that transplantation of MPCs ameliorated motor deficits associated with HI injury. In view of comparable behavioral recovery produced by syngeneic and allogeneic MPC grafts, allogeneic transplantation poses as a feasible and efficacious cell replacement strategy with direct clinical application. An equally major finding is the observation lending support to the hippocampus as an excellent target brain region for stem cell therapy in treating HI injury.

Based on density functional theory method, we have investigated structural, electronic, and magnetic properties of lithium (Li) atom adsorbed on silicon carbide (SiC) zigzag (9,0) and armchair (5,5) nanotubes. Effective adsorptions are found on both inner- and outer-side of the SiC nanotubes, with adsorption energies ranging from 1.03 to 1.71 eV. Interestingly, we have found that SiC nanotubes exhibit different behaviors with several Li adsorption sites. Li adsorptions on the s-Si and s-H sites of the outer surface and all the five sites of the inner surface in zigzag (9,0) nanotube emerge metallic features, whereas adsorptions on other sides of (9,0) and all sites of armchair (5,5) SiC nanotubes show semiconducting characters. The calculating results also indicate that lithium adsorptions on most sites of SiC nanotubes yield spontaneous magnetization, where net magnetic moment is 1 μ B . Additionally, spin density of states, spin density distribution, and charge density difference are also calculated to investigate the electronic and magnetic properties of SiC nanotubes induced by Li adsorption.

In PWM rectifier control strategy, Direct Power Control (DPC) has been used more and more widely in order to solve the problem of complex rotating coordinate transformation of Vector Control. Traditional DPC method with variable switching frequency is applied based on instantaneous power theory and switching table. This approach requires more voltage and current sensors to calculate active and reactive power, leading to low anti-jamming capability. And the use of bang-bang control results in large power fluctuation. For these problems, an improved DPC strategy with fixed switching frequency is proposed based on virtual flux and Space Voltage Modulation (SVM). This method simplifies the circuit structure by omitting the voltage sensors and obtains continuous control by SVM instead of switching table. A comprehensive theoretical analysis of two DPC methods above is given and the comparison of simulation results is presented in Matlab/simulink. The simulation results show that DPC based on virtual flux and SVM has better dynamic and static control performance.

The Modular Multilevel Converter (MMC), based on cascaded multi-module structure, is suitable for highvoltage/power applications. However, among hundreds of modules, their voltage-balancing is a key problem which is attracting scholars' much attention. Therefore, in this paper, a control strategy based on PI controller is proposed for balancing capacitor voltages of Modular Multilevel Converter (MMC). The proposed control strategy includes the voltage-balancing and circulating current-limiting links. The effectiveness of the strategy is conformed using Matlab/Simulink platform. The simulation results show that the fluctuation of capacitor voltages as well as the circulating current can be confined into acceptable range. In addition, the MMC's switching frequency and system loss can be reduced significantly, since the equivalent switching frequency is promoted to a great extent.

Laboratory and clinical studies have shown that intracerebral transplantation of carotid body (CB) cells ameliorate Parkinsonian deficits. The recent clinical study by Arjona and colleagues indicated that CB autograft transplantation is a relatively simple, safe, and viable treatment for PD patients. In particular, Espejo and colleagues demonstrated that the therapeutic efficacy of intracerebral transplantation of the CB in PD was likely obtained through secretion of neurotrophic factors rather than the local release of dopamine, which suggests it possible and reasonable to extend the use of the CB as an efficacious graft source for neural transplantation. Thus, we transplanted CB cell suspensions into the ischemic penumbra within 1 h after stroke surgery. The results revealed that CB transplantation also significantly reduced stroke-induced behavioral deficits and cerebral infarction. In this review, we focus on summarizing the physiological properties of the CB related to transplantation, describing briefly possible mechanisms responsible for the effect of CB transplantation, and introducing recent studies of the CB as a donor source for neural transplantation.

Ceramide is involved in apoptosis, inflammation, and stress responses, which are among the pathogenic components of chronic heart failure (CHF). However, no one has documented the levels of ceramide itself in CHF or determined its potential prognostic value.In this study we recruited patients with heart failure consecutively from the hospital, of whom 423 stable patients were eventually selected to participate in this study after an observation period of at least 3 months after hospital discharge. All patents were followed up for all-cause death to December 31, 2013.Plasma ceramide levels were increased stepwise with New York Heart Association functional class (I, 5.32 ± 1.98; II, 5.81 ± 1.63; III, 6.14 ± 2.14; IV, 6.66 ± 2.61 ng/mL). During a mean follow-up of 4.4 years (interquartile range: 3.5-5.3 years), a total of 200 CHF patients died. The optimal threshold value of ceramide was 6.05 ng/mL. Ceramide levels as continuous and as dichotomous variables are risk factors for mortality in CHF (adjusted hazard ratio, 1.31; 95% confidence interval, 1.16-1.47; P0.001 and adjusted hazard ratio, 2.07, 95% confidence interval, 1.53-2.81; P0.001, respectively). When ceramide levels were combined with conventional CHF risk factors, the area under the curve increased from 0.68 (0.63-0.72) to 0.72 (0.68-0.76); P = 0.047. The continuous net reclassification index and integrated discrimination improvement index were 17.2% (5.0-29.9%; P = 0.027) and 0.04 (0.01-0.08; P = 0.020), respectively.Plasma ceramide levels were increased and correlated with the severity of CHF, and were an independent risk factor of mortality in patients with CHF and reduced left ventricular systolic function. Ceramide levels might provide additional predictive value after conventional risk assessment.

This study was designed to investigate diverse effects of angiotensin II (AngII) type I receptor antagonists, losartan, angiotensin converting enzyme (ACE) inhibitors, fosinopril, and calcium channel blockade, amlodipine on cardiomyocyte apoptosis and AngII in the left ventricle of spontaneously hypertensive rats (SHR). The SHRs were randomized to four groups: SHR-L (treated with losartan, 30 mg x kg(-1) x d(-1)), SHR-F (with fosinopril, 10 mg x kg(-1) x d(-1)), SHR-A (with amlodipine, 10 mg x kg(-1) x d(-1)) and SHR-C (with placebo). The cardiomyocyte apoptosis was examined by in situ TDT-mediated dUTP nick end labeling, AngII concentrations of plasma and myocardium were measured by radio immunoassay at 8 and 16 weeks of the study respectively. The results showed that: (1) compared with SHR-C at 8 and 16 weeks respectively; the systolic blood pressure was decreased similarly in the three treatment groups. Left ventricular weight and mass indexes were reduced in the three treatment groups. The latter parameter at 16 weeks was lower in SHR-F than that in the other two treatment groups. (2) Compared with SHR-C, the cardiomyocyte apoptotic index (APOI) was reduced significantly at 8 weeks only in SHR-F, and at 16 weeks in all three treatment groups. The APOI of SHR-F was lowest among the three treatment groups examined at latter endpoint. (3) Compared with SHR-C at both endpoints of this study, plasma and myocardium AngII levels were increased in SHR-L. However, plasma AngII concentrations were not altered in SHR-F and SHR-A, myocardium AngII concentrations were reduced significantly at 8 weeks only in SHR-F, and at 16 weeks in SHR-F and SHR-A. Meanwhile, myocardium AngII in SHR-F at 16 weeks was lower than that in SHR-A. The results of this study indicate that losartan, fosinopril, and amlodipine each effectively reverses heart hypertrophy and inhibits cardiomyocyte apoptosis, and fosinopril may be most effective in these cardioprotective effects. These findings suggest that the effects of the three blockers on myocardiocyte apoptosis and left ventricular hypertrophy were related to inhibition of the myocardium rennin-angiotensin-aldsterone system.

To explore the effects of compound Danshen dripping pills (CDDP) and CDDP combined with transplantation of human umbilical cord blood cells (HUMNCs) on the inflammatory response, oxidative stress, myocardial cell apoptosis and cardiac function, and also to investigate the possible mechanisms of the combined therapy in the acute myocardial infarction (AMI).Rabbit model of AMI successfully established by ligation of the left anterior coronary artery (LAD). Forty rabbits were randomly divided into 4 groups (n=10 per group): a control group, injected with 0.5 mL of saline in 24 h after AMI and then gavaged with 5 mL of saline daily; a CDDP group, injected with saline 0.5 mL after AMI and then gavaged with CDDP (270 mg/d) daily; a transplantation group, injected with 0.5 mL of saline contained 3 × 10(7) HUCBMCs [labeled with green fluorescent protein (GFP)] and then gavaged with 5 mL of saline daily; a combined group, injected with 0.5 mL of saline contained 3 × 10(7) HUCBMCs (labeled with GFP) and then gavaged with CDDP (270 mg/d) daily. Cardiac function index such as left ventricular fractional shorting (LVFS) and ejection fraction(LVEF) were measured by echocardiography; the pathological changes were observed by HE staining and the white blood cells in the myocardium were determined by light microscopy. The superoxide dismutase (SOD) activity and malondialdehyde (MDA) content in myocardium were detected by nitrotetrazolium blue chloride (NBT) and thiobarbituric acid colorimetric measurement respectively. The number of transplanted cells in the myocardium was examined by GFP positive cells counted with fluorescence microscopy.1) Compared with the control group (at 1 or 4 week), LVEF and LVFS were significant improved in the CDDP group, the transplantation group and the combined groups (all P0.05), the improvement degree of cardiac function in the combined group was the most significance. There was no significant difference between the CDDP group and the transplantation group. 2) Compared with the control group (at 1 or 4 week), the number of white blood cell, myocardial cell apoptosis ratio were decreased significantly in the CDDP group, the transplantation group and the combined groups (all P0.05), this decrease in the combined group was the most significance, and there was no significant difference between the CDDP group and the transplantation group. 3) Compared with control (at 4 week), the SOD activity was increased significantly, and MDA content in myocardium was decreased in the CDDP group, this change in the combined group was the most significance. 4) GFP-positive cells were found to be present in the peri-myocardial infarction area in the transplantation group and the combined group at 1, 4 weeks post-transplantation. The number of the GFP positive cells in the combined group was more than that in the transplantation group (P0.05).The intravenous transplantation of HUMNCs combined with the CDDP in the treatment of rabbits with AMI could increase the survival rate of transplanted cells and inhibit the myocardial cell apoptosis, therefore improve the heart function. The possible mechanism of the combined treatment may be involved in the inhibition of the inflammatory response and oxidative stress in the myocardium following AMI.