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The ability to solve the mathematical equation problem is very important for the thinking development of middle school students. “How to solve it” of George Polya is famous in the world. 6 questions cognitive model proposed by Professor Zhou are monitored through metacognition, and the 6 questions are coherent, complete and sequential. This paper found that the 6 questions cognitive model can help implement “How to solve it” of George Polya and reduce students' cognitive load. At the same time, this study found that 6 questions cognitive model can help students solve the mathematical equation problem better.

The phase transition from vegetative to reproductive growth is triggered by internal and external signals that participate in circadian clock in plants. We identified a rice floral inhibitor OsPRR73 encoding a CONSTANS protein. Overexpression of OsPRR73 resulted in late heading under both long-day (LD) and short-day (SD) conditions. Knockout mutants led to early heading under LD conditions but no change under SD. OsPRR73 mRNA accumulated at noon and exhibited a robust oscillation under constant light (LL) and constant darkness (DD) conditions. OsPRR73 overexpression exerted negative feedback on endogenous OsPRR73 expression and altered diurnal expressions of key flowering genes and circadian clock genes. OsPRR73 bound to the promoters of the floral gene Ehd1 and the circadian gene OsLHY, and significantly suppressed their expression at dawn. In LL and DD, the oscillatory patterns of the circadian genes OsLHY, OsTOC1, OsGI and OsELF3 were varied in OsPRR73OX and osprr73 mutants. OsPRR73 expression was decreased in osphyb mutants, and overexpression of OsPRR73 complemented the early heading date phenotype of osphyb, indicating OsPRR73 works downstream of OsPhyB. Therefore, OsPRR73 is involved in a feedback loop of the rice clock and connects the photoperiod flowering pathway by binding to the Ehd1 promoter in rice.

The human cardiovascular system has adapted to function optimally in Earth's 1G gravity, and microgravity conditions cause myocardial abnormalities, including atrophy and dysfunction. However, the underlying mechanisms linking microgravity and cardiac anomalies are incompletely understood. In this study, we investigated whether and how calpain activation promotes myocardial abnormalities under simulated microgravity conditions. Simulated microgravity was induced by tail suspension in mice with cardiomyocyte-specific deletion of Capns1, which disrupts activity and stability of calpain-1 and calpain-2, and their WT littermates. Tail suspension time-dependently reduced cardiomyocyte size, heart weight, and myocardial function in WT mice, and these changes were accompanied by calpain activation, NADPH oxidase activation, and oxidative stress in heart tissues. The effects of tail suspension were attenuated by deletion of Capns1. Notably, the protective effects of Capns1 deletion were associated with the prevention of phosphorylation of Ser-345 on p47phox and attenuation of ERK1/2 and p38 activation in hearts of tail-suspended mice. Using a rotary cell culture system, we simulated microgravity in cultured neonatal mouse cardiomyocytes and observed decreased total protein/DNA ratio and induced calpain activation, phosphorylation of Ser-345 on p47phox, and activation of ERK1/2 and p38, all of which were prevented by calpain inhibitor-III. Furthermore, inhibition of ERK1/2 or p38 attenuated phosphorylation of Ser-345 on p47phox in cardiomyocytes under simulated microgravity. This study demonstrates for the first time that calpain promotes NADPH oxidase activation and myocardial abnormalities under microgravity by facilitating p47phox phosphorylation via ERK1/2 and p38 pathways. Thus, calpain inhibition may be an effective therapeutic approach to reduce microgravity-induced myocardial abnormalities.

Background Cardiac rehabilitation is a medically supervised program after coronary events that involves exercise and dietary modification. We evaluated the comparative benefits and harms of cardiac rehabilitation strategies via a network meta-analysis. Methods We followed a pre-specified protocol (PROSPERO: CRD42018094998). We searched Embase, MEDLINE, and Cochrane Central Register of Randomized Trials databases for randomized controlled trials that evaluated cardiac rehabilitation vs a second form of rehabilitation or standard/usual care in adults after myocardial infarction, coronary artery bypass grafting, percutaneous coronary intervention, or angiography. Risk of bias and evidence quality was evaluated using the Cochrane tool and Grading of Recommendations Assessment, Development and Evaluation (GRADE), respectively. Pairwise and Bayesian network meta-analyses were performed for 11 clinical outcomes. Results We included 134 randomized controlled trials involving 62,322 participants. Compared with standard care, exercise-only cardiac rehabilitation reduced the odds of cardiovascular mortality (odds ratio [OR], 0.70; 95% credibility interval [CrI], 0.51-0.96; moderate-quality evidence), major adverse cardiovascular events (OR, 0.57; 95% CrI, 0.40-0.78; low-quality evidence), nonfatal myocardial infarction (OR, 0.71; 95% CrI, 0.54-0.93; moderate-quality evidence), all-cause hospitalization (OR, 0.74; 95% CrI, 0.54-0.98; moderate-quality evidence), and cardiovascular hospitalization (OR, 0.69; 95% CrI, 0.51-0.88; moderate-quality evidence). Exercise-only cardiac rehabilitation was associated with lower cardiovascular hospitalization risk relative to cardiac rehabilitation without exercise (OR, 0.68; 95% CrI, 0.48-0.97; moderate-quality evidence). Conclusions Cardiac rehabilitation programs containing exercise might provide broader cardiovascular benefits compared with those without exercise.

Background: Peripheral atherosclerotic disease (PAD) is the narrowing or blockage of arteries that supply blood to the lower limbs. Given its complex nature, bioinformatics can help identify crucial genes involved in the progression of peripheral atherosclerosis.Materials and Methods: Raw human gene expression data for 462 PAD arterial plaque and 23 normal arterial samples were obtained from the GEO database. The data was analyzed using an integrated, multi-layer approach involving differentially-expressed gene analysis, KEGG pathway analysis, GO term enrichment analysis, weighted gene correlation network analysis, and protein-protein interaction analysis. The monocyte/macrophage-expressed leukocyte immunoglobulin-like receptor B2 (LILRB2) was strongly associated with the human PAD phenotype. To explore the role of the murine LILRB2 homologue PirB in vivo, we created a myeloid-specific PirB-knockout Apoe−/− murine model of PAD (PirBMΦKO) to analyze femoral atherosclerotic burden, plaque features of vulnerability, and monocyte recruitment to femoral atherosclerotic lesions. The phenotypes of PirBMΦKO macrophages under various stimuli were also investigated in vitro.Results:PirBMΦKO mice displayed increased femoral atherogenesis, a more vulnerable plaque phenotype, and enhanced monocyte recruitment into lesions. PirBMΦKO macrophages showed enhanced pro-inflammatory responses and a shift toward M1 over M2 polarization under interferon-γ and oxidized LDL exposure. PirBMΦKO macrophages also displayed enhanced efferocytosis and reduced lipid efflux under lipid exposure.Conclusion: Macrophage PirB reduces peripheral atherosclerotic burden, stabilizes peripheral plaque composition, and suppresses macrophage accumulation in peripheral lesions. Macrophage PirB inhibits pro-inflammatory activation, inhibits efferocytosis, and promotes lipid efflux, characteristics critical to suppressing peripheral atherogenesis.

Background Spaceflight or microgravity conditions cause myocardial atrophy and dysfunction, contributing to post-flight orthostatic intolerance. However, the underlying mechanisms remain incompletely understood and preventive approaches are limited. This study investigated whether and how losartan, a blocker of angiotensin-II receptor, preserved cardiomyocyte size and prevented myocardial dysfunction during microgravity. Method Adult male mice were suspended with their tails to simulate microgravity. Echocardiography was performed to assess myocardial function. Heart weight and cardiomyocyte size were measured. NADPH oxidase activation was determined by analyzing membrane translocation of its cytosolic subunits including p47 phox , p67 phox and Rac1. Heart tissues were also assayed for oxidative stress, p47 phox phosphorylation (Ser345), MuRF1 protein levels and angiotensin-II production. Results Tail-suspension for 28 days increased angiotensin-II production in hearts, decreased cardiomyocyte size and heart weight, and induced myocardial dysfunction. Administration of losartan preserved cardiomyocyte size and heart weight, and prevented myocardial dysfunction in tail-suspended mice. These cardioprotective effects of losartan were associated with inhibition of p47 phox phosphorylation (Ser345), NADPH oxidase and oxidative stress in tail-suspended mouse hearts. Additionally, the NADPH oxidase inhibitor, apocynin, also reduced oxidative stress, preserved cardiomyocyte size and heart weight, and improved myocardial function in tail-suspended mice. Furthermore, losartan but not apocynin attenuated tail-suspension-induced up-regulation of MuRF1 protein in mouse hearts. Conclusions Administration of losartan preserves cardiomyocyte size and prevents myocardial dysfunction under microgravity by blocking p47 phox phosphorylation and NADPH oxidase activation, and by inhibiting MuRF1 expression. Thus, losartan may be a useful drug to prevent microgravity-induced myocardial abnormalities.

Background Atherosclerosis is a hyperlipidemia-induced condition affecting the arterial wall that damages healthy endothelial cell (EC) function, leading to enhanced risk of atherothrombotic events. Certain microRNAs regulate EC dysfunction in response to hyperlipidemia and may be suitable therapeutic targets to combat atherosclerosis. Methods miRNA expression in human ECs was analyzed under various conditions to identify key microRNAs. High-cholesterol diet (HCD)-fed Mir652−/−Apoe−/− (Mir652−/−) mice and matching Mir652+/+Apoe−/− (Mir652+/+) mice were subjected to carotid injury to analyze the effects of miR-652 knockdown on endothelial repair. In silico analysis followed by in vitro and in vivo experiments were applied to identify miR-652's target gene Ccnd2 and investigate the pair's effects on ECs. miR-652-5p and miR-652-3p antagomir therapies were tested in Mir652+/+ mice under normal and HCD diet to assess their effect on endothelial repair. Findings miR-652-3p, which is upregulated in human and murine atherosclerotic plaques, suppresses expression of the endothelial repair gene Ccnd2, thereby enhancing atherosclerotic lesion formation. Post-denudation recovery of ECs was promoted in Mir652−/− mice due to enhanced EC proliferation attributable to de-repression of miR-652-3p's (but not miR-652-5p's) regulation of Ccnd2 expression. Under hyperlipidemic conditions at non-predilection sites, miR-652-3p produces anti-proliferative effects in ECs, such that Mir652−/− mice display reduced atherosclerotic progression. In contrast, neither miR-652-3p nor Ccnd2 displayed significant effects on the endothelium at predilection sites or under disturbed flow conditions. Administration of a miR-652-3p antagomir rescued the proliferation of ECs in vivo, thereby limiting atherosclerotic development. Interpretation miR-652-3p blockade may be a potential therapeutic strategy against atherosclerosis., Highlights • miR-652-3p is upregulated in human and murine atherosclerotic plaques. • miR-652 knockdown promotes endothelial repair in injured arteries. • miR-652-3p suppresses expression of the endothelial repair gene Ccnd2. • miR-652-3p antagomir rescues EC proliferation under hyperlipidemic stress.

Microgravity conditions cause myocardial abnormalities with limited therapeutic approaches. We reported that NADPH oxidase-derived reactive oxygen species contribute to microgravity-induced myocardial abnormalities. This study investigated whether pharmacological inhibition of Rac1 protected the heart during microgravity. Simulated microgravity was induced by tail-suspension in mice. Tail-suspension for 28 days increased Rac1 activity in hearts, reduced heart weight and cross-sectional areas of cardiomyocytes, indicative of myocardial atrophy, and myocardial dysfunction. Administration of NSC23766, a selective inhibitor of Rac1, or atorvastatin reported to inhibit Rac1 activation, attenuated myocardial atrophy and preserved myocardial function in tail-suspended mice. These protective effects of Rac1 inhibition were associated with inhibition of NADPH oxidase activation and a reduction of oxidative stress. Our finding may inform a future clinical trial using atorvastatin to prevent myocardial abnormalities under microgravity conditions.

Cardiac rehabilitation (CR) in China has not been widely adopted for a variety of reasons, including healthcare provider (HCP)s' lack of awareness and beliefs.To explore HCP's perceptions of CR in China.An exploratory, sequential design was used in this mixed-methods study. Face-to-face semi-structured interviews were performed; this was followed by a cross-sectional survey.The interviews were conducted in a university-affiliated hospital and a rehabilitation hospital in Shanghai. The survey was conducted in the cardiac departments of primary, secondary, or tertiary hospitals in Shanghai or Yunnan Province, China.Saturation was achieved upon interviewing 13 HCPs (5 doctors, and 8 nurses). A total of 610 HCPs (185 doctors [30.5%], 417 nurses [68.8%]) completed the survey.Analysis of the interviews revealed 4 themes: the perceived value of CR, the need for pro-CR policy, variability in CR awareness, and obstacles to CR delivery. HCP approaches to the treatment of patients with cardiac conditions did not universally include exercise training (only approximately 60% of HCPs), or all other recommended domains of secondary prevention, and assessment of the major risk factors was quite low. Familiarity with CR was moderate (48.7%). HCPs perceived that philosophies of Traditional Chinese Medicine (TCM) were highly compatible with, and could add value to, CR. HCP approaches to secondary preventive care and CR perceptions varied significantly according to their highest level of education, clinical profession, job seniority, type of hospital where they worked, whether the hospital had a CR program and the hospital's location.HCPs recognize the value of CR, particularly considering secondary preventive care practices were not comprehensive. Education is needed to improve HCPs CR awareness.

Cardiac hypertrophy, characterized by the enlargement of cardiomyocytes, is initially an adaptive response to physiological and pathological stimuli. Decompensated cardiac hypertrophy is related to fibrosis, inflammatory cytokine, maladaptive remodeling, and heart failure. Although pathological myocardial hypertrophy is the main cause of hypertrophy-related morbidity and mortality, our understanding of its mechanism is still poor. Long noncoding RNAs (lncRNAs) are noncoding RNAs that regulate various physiological and pathological processes through multiple molecular mechanisms. Recently, accumulating evidence has indicated that lncRNA-H19 is a potent regulator of the progression of cardiac hypertrophy. For the first time, this review summarizes the current studies about the role of lncRNA-H19 in cardiac hypertrophy, including its pathophysiological processes and underlying pathological mechanism, including calcium regulation, fibrosis, apoptosis, angiogenesis, inflammation, and methylation. The context within which lncRNA-H19 might be developed as a target for cardiac hypertrophy treatment is then discussed to gain better insight into the possible biological functions of lncRNA-H19 in cardiac hypertrophy.

Background: Regulatory T cells (Tregs) play a crucial role in suppressing immune response and maintaining hemostasis and immune tolerance. Tregs are enriched in the tumor microenvironment (TME) and suppress anti-tumor immunity. Therefore, specific depletion of Tregs in the TME is expected to reduce anti-tumor immune suppression without affecting hemostasis in the periphery. The C-C motif chemokine receptor 8 (CCR8), highly expressed on Tregs from TME but significantly lower expressed on Tregs from peripheral blood, provides an ideal target for preferentially deletion of Tregs within tumors. GB2101 is a novel anti-CCR8 monoclonal antibody generated from hybridoma. The data from in vitro and in vivo studies indicated that GB2101 is a good PCC molecule with great potential for clinical development. Methods: GB2101 was generated by immunization of CCR8 gene plus CCR8 over-expressing cells in mice followed by hybridoma technology. The binding of the antibody to CCR8-expressing cells was detected by flow cytometry. CCL1 ligand blocking was assessed by flow cytometry and calcium flux assay. Antibody-dependent cell-mediated cytotoxicity (ADCC) function was evaluated by Jurkat-CD16A-NFAT reporter system. In vivo anti-tumor efficacy was assessed in syngeneic model using human CCR8 knock-in mice. Results: GB2101 displayed potent binding to cells expressing CCR8. GB2101 efficiently blocked CCL1 binding and CCL1-induced signals in CCR8 expressing cells. ADCC activity against target cells was observed and afucosylated version of GB2101 improved ADCC response. GB2101 significantly inhibited tumor growth in syngeneic model. Conclusions: GB2101 is a novel monoclonal antibody specifically binding to CCR8 with high affinity, and efficiently blocked CCL1-CCR8 pathway and suppressed tumor growth in vivo. Therefore, it is a very promising preclinical candidate that may be used in the treatment of multiple tumor types. Citation Format: Qinglin Du, Yiqi Cao, Xueyan Yang, Jing Lu, Fei Peng, Wenming Zhou, Liwen Liang, James Li, Shuhua Han. Development of GB2101, a novel anti-CCR8 antibody for cancer treatment [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr LB534.

Background: The EGFR tyrosine kinase inhibitors (TKIs) have been effectively used for non-small cell lung cancer (NSCLC) driven by EGFR mutations. However, patients eventually develop drug resistance via various mechanisms such as secondary EGFR mutations and activation of alternative pathways. The cMET amplification is one of the resistant mechanisms. Amivantamab, a bispecific antibody to EGFR/c-Met has shown that concurrent inhibition of EGFR and c-Met can overcome resistance of EGFR-TKIs and improve patient outcomes. Thus, amivantamab has been approved for the treatment of advanced NSCLC patients with EGFR exon20ins mutations in the US. GB263T is a novel EGFR/cMET/cMET tri-specific antibody with enhanced ADCC function. The current study has demonstrated GB263T exhibited robust anti-tumor activity by in vitro and in vivo studies. Methods: GB263T has been extensively characterized. The binding/blocking activities were analyzed by SPR and ELISA. The protein levels and phosphorylation of EGFR/cMET were detected by Western Blot. Internalization ability was evaluated by confocal microscope. ADCC function was tested by Jurkat-CD16A-NFAT-Luc reporter system. Various CDX and PDX models were used to evaluate the in vivo efficacy in tumor inhibition. Results: GB263T showed high affinity binding to EGFR and cMET, with robust blocking activity. Moreover, GB263T induced receptor internalization and EGFR/cMET phosphorylation in NSCLC cell lines. GB263T dose-dependently inhibited the proliferation of cells containing EGFR exon 20 insertion mutations and C797S mutations. In addition, potent ADCC function against NSCLC cell lines was observed. Significant in vivo anti-tumor efficacy was demonstrated by multiple tumor models of EGFR exon 20 insertion, EGFR C797S mutation, cMET amplification, and cMET exon 14 skipping mutation. Conclusions: GB263T is a novel tri-specific antibody that exhibited robust anti-tumor activity. The preclinical data indicate that GB263T has great potential to become an effective therapeutics in the treatment of NSCLC. Citation Format: Qinglin Du, Wengang Zeng, Xueyan Yang, Liwen Liang, Xueqin Li, Yan Li, Yiqi Cao, Zongjun Xia, Jing Zhang, Qian Ding, Shuhua Han. Characterization of GB263T, a tri-specific antibody against EGFR/cMET/cMET for NSCLC [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr LB538.

Isolated ventricular noncompaction is an unclassified cardiomyopathy due to intrauterine arrest of compaction of the loose interwoven meshwork. Its mortality and morbidity are high, including heart failure, thromboembolic events, and ventricular arrhythmias. Isolated right ventricular noncompaction was reported rarely, especially that causes pulmonary embolism and ventricular tachycardia. We describe a case of isolated noncompaction of the right ventricular causing pulmonary embolism and ventricular tachycardia.

Many genes encoding CCT domain-containing proteins regulate flowering time. In rice (Oryza sativa), 41 such genes have been identified, but only a few have been shown to regulate heading date. Here, to test whether and how additional CCT family genes regulate heading date in rice, we classified these genes into five groups based on their diurnal expression patterns. The expression patterns of genes in the same subfamily or in close phylogenetic clades tended to be similar. We generated knockout mutants of the entire gene family via CRISPR/Cas9. The heading dates of knockout mutants of only 4 of 14 genes previously shown to regulate heading date were altered, pointing to functional redundancy of CCT family genes in regulating this trait. Analysis of mutants of four other genes showed that OsCCT22, OsCCT38, and OsCCT41 suppress heading under long-day conditions and promote heading under short-day conditions. OsCCT03 promotes heading under both conditions and upregulates the expression of Hd1 and Ehd1, a phenomenon not previously reported for other such genes. To date, at least 18 CCT domain-containing genes involved in regulating heading have been identified, providing diverse, flexible gene combinations for generating rice varieties with a given heading date.

Inorganic-organic co-assembly of anionic polyoxometalates (POMs) with zwitterions provides a facile way to fabricate functional soft materials. In this paper, a translucent, photoluminescent polymer hydrogel was fabricated from Weakley-type POM Na9EuW10O36 (EuW10) and polymerizable imidazole-type zwitterion 3-(1-vinyl-3-imidazolio)propanesulfonate (VIPS) via a one-step synthesis method. Detailed characterization indicated that the polymerization of double bonds in VIPS and electrostatic interactions between EuW10 and VIPS play important roles in the formation of the hydrogels. Additionally, the introduction of non-polymerizable zwitterions 3-(1-methyl-3-imidazolio)propanesulfonate (MIPS) or 3-(1-decyl-3-imidazolio)propanesulfonate (C10IPS) can improve the mechanical and luminous performances of the hydrogels. Especially, C10IPS with a long alkyl chain would more significantly alter the coordination environment of EuW10, and consequently resulted in a more efficient energy transfer process. Further investigations revealed that the chemical environment around the Eu3+ can be highly influenced by organic solvents with stronger coordination abilities than water molecules, such as acetone. The translucency and luminescence intensity of the hydrogels can be reversibly transformed after alternately immersing in acetone or H2O for several minutes. Our results provided a useful strategy for the fabrication of luminescent hydrogels by regulating the noncovalent interactions between POMs and zwitterions.

Artificial photocatalytic systems represent a promising and available technology to directly convert sunlight into usable energy resources. Unfortunately, the current photocatalysts often absorb an only small range of sunlight spectra, hence greatly limiting the utilization efficiency of solar energy. Herein, we firstly developed a hybrid system that combines carbon dots (CDs) and oxygen-deficient WO3-x nanodots through a mild solvothermal method. This hybrid system features the heterojunction structure with dimensions smaller than 15 nm and can effectively utilize the full spectrum of solar radiation in photocatalytic oxidative reactions. In hybrid system, the CDs can enhance visible light harvesting ability of WO3-x nanodots and deliver their photoinduced carriers to the intermediate energy bands induced by oxygen-deficient of WO3-x. After further excitation with low energy photons, then more chemically useful carriers can be generated to participate fully in catalytic activation and reaction processes, resulting in 3.2 times higher photocatalytic activities of CDs@WO3-x than WO3-x nanodots.

The prevalence of hepatitis C virus (HCV) infection in Asian countries is high. This study assessed the efficacy and safety of elbasvir/grazoprevir (EBR/GZR) in participants with HCV infection from Asia-Pacific countries and Russia. In this phase 3, randomized, placebo-controlled, double-blind study, treatment-naive participants with HCV genotype (GT) 1, 4, or 6 infection were randomized to EBR 50 mg/GZR 100 mg (immediate-treatment group [ITG]) or placebo (deferred-treatment group [DTG]) once daily for 12 weeks (Protocol PN-5172-067, NCT02251990). The primary efficacy variable was a nonrandomized comparison of sustained virologic response at 12 weeks after the end of therapy (SVR12) for the ITG with a historical control. The primary safety outcome was a randomized comparison between the ITG and DTG. Three hundred thirty-seven participants were randomized to the ITG (n = 251) or DTG (n = 86); 199 (59.2%) participants were Asian, and 250 (74.4%) had HCV GT1b infection. Overall, 232/250 (92.8%) participants in the ITG achieved SVR12 (97.5% confidence interval, 89.1, 96.5). Of the 18 participants who failed to attain SVR12, 1 was lost to follow-up and 17 had virologic failure, 13 of whom had HCV GT6 infection. The incidence of adverse events was similar between participants receiving EBR/GZR and placebo (50.8% versus 51.2%; difference, -0.3%; 95% confidence interval, -12.3, 11.9). Conclusion: EBR/GZR for 12 weeks provides an effective and well-tolerated regimen for chronic HCV GT1 infection in treatment-naive people from Asia-Pacific countries and Russia, particularly for the large population with GT1b infection. EBR/GZR is not recommended for the treatment of individuals with HCV GT6 infection. (Hepatology Communications 2018;2:595-606).

Coronary artery bypass graft (CABG) is one of the primary methods of treating coronary heart disease (CHD); however, vein graft restenosis is a major limiting factor of the effectiveness of CABG. Emerging evidence has indicated that miR-423 is associated with vascular diseases. Additionally, upregulation of a disintegrin and metalloproteinase with thrombospondin motifs-7 (ADAMTS-7) contributes to neointima formation by promoting the proliferation and migration of vascular smooth muscle cells and inhibiting the proliferation and migration of endothelial cells. The aim of the present study was to examine the effects of miR-423 target, ADAMTS-7, on regulating vein graft disease and identify novel biomarkers for use in therapy of vein graft failure (VGF). Aberrant expression of miR-423 in plasma of patients with CHD prior to and following CABG confirms that miR-423 may be a suitable target for preventing VGF. Furthermore, a dual-luciferase reporter gene assay indicated that miR-423 directly interacted with ADAMTS-7 and suppressed its expression. Ectopic expression of miR-423 suppressed ADAMTS-7, resulting in decreased proliferation and migration rates of human umbilical vein smooth muscle cells by targeting ADAMTS-7, but resulted in increased proliferation and migration of human umbilical vein endothelial cells in vitro. Overexpression of miR-423 also enhanced re-endothelialization and decreased neointimal formation in a rat vein graft model. In conclusion, the results of the present study demonstrated that the miR-423/ADAMTS-7 axis may possess potential clinical value for the prevention and treatment of restenosis in patients with CHD following CABG.

Seed germination is a complex process involving various physical and biochemical cues, determined by exogenous and endogenous factors. Here, we identified a gene, OsMFT2, that negatively regulates seed germination in rice. OsMFT2 knock-out lines exhibited pre-harvest sprouting, whereas OsMFT2 overexpression lines showed delayed germination. RNA expression profiling showed that OsMFT2 was specifically expressed in seeds. Subcellular localization indicated that OsMFT2 was a nuclear protein. Exogenous abscisic acid (ABA) treatment of imbibed seeds and seedlings indicated that OsMFT2 altered ABA sensitivity during seed germination and post-germination growth. In vivo and in vitro assays showed that three bZIP transcription factors, OsbZIP23, OsbZIP66 and OsbZIP72, interacted with OsMFT2. OsbZIP23/66/72 bound to the promoter of Rab16A, a typical gene containing the ABA-responsive element, and OsMFT2 enhanced the binding to the Rab16A promoter. Moreover, several ABA-responsive genes were differentially expressed in the imbibed seeds of OsMFT2 transgenic lines and the wild type. The performance of the transgenic plants demonstrated that overexpressing OsbZIP23 rescued the pre-harvest sprouting phenotype and the decrease in ABA-signaling genes expression caused by OsMFT2 knock-out. All of these results demonstrate that OsMFT2 positively regulates ABA-responsive genes through interacting with OsbZIP23/66/72 and functions in seed germination.

Background The most dangerous atherosclerotic plaques, referred to as “vulnerable,” are most likely to trigger acute atherothrombotic events such as myocardial infarction (heart attack) and stroke. Our goal was to uncover the molecular drivers of vulnerable plaque formation. Methods To elucidate the functional gene modules that drive vulnerable plaque formation, we performed a weighted gene coexpression network analysis integrated with a protein-protein interaction network analysis in human atherosclerotic carotid samples, which identified the candidate gene granulocyte-macrophage colony-stimulating factor 2 (GM-CSF) receptor alpha subunit (CSF2RA). Follow-up in vitro experiments were performed to elucidate the regulatory relationship between CSF2RA and the microRNA miR-532-3p as well as modifiers of macrophagic miR-532-3p-CSF2RA axis expression. Microarray and quantitative reverse transcription polymerase chain reaction (qRT-PCR) studies elucidated the effect of statins on carotid miR-532-3p-CSF2RA axis expression in patients with carotid atherosclerotic disease. Apoe−/−, Ldlr−/−, and Csf2ra mutant Apoe−/− mouse models of atherosclerosis were employed to assess the effects of agomiR-532-3p therapy in vivo. Results The integrated weighted gene coexpression network analysis/protein-protein interaction network analysis revealed that the macrophagic GM-CSF receptor CSF2RA is significantly upregulated in macrophage-rich vulnerable plaques. Follow-up analysis identified the miR-532-3p-CSF2RA axis, as miR-532-3p downregulates CSF2RA via binding to CSF2RA’s 3′UTR. Macrophagic miR-532-3p-CSF2RA dysregulation was enhanced via modified low-density lipoprotein or tumor necrosis factor α exposure in vitro. Moreover, this miR-532-3p-CSF2RA dysregulation was observed in human vulnerable plaques and Apoe−/− mouse plaques, effects rescued by statin therapy. In vivo, agomiR-532-3p therapy suppressed murine plaque formation and promoted plaque stabilization in a Csf2ra-dependent manner. Conclusion Macrophagic miR-532-3p-CSF2RA axis dysregulation is a key driver in vulnerable plaque formation.

The co-assembly of zwitterionic amphiphile and polyoxometalate is a new and promising technique to construct a hierarchical and multifunctional supramolecular hydrogel. To comprehensively investigate the assemble mechanism, zwitterionic amphiphiles with different cations, namely, 3-(1-hexadecyl-3-imidazolio) propanesulfonate (C

Additional file 1: Figure S1. Effect of losartan on caspase-3 activity. Tail-suspended mice were given losartan or vehicle for 28 days. Caspase-3 activity was measured in heart tissue lysates. Data are mean ± SD, n = 6 in each group. Figure S2. Effect of losartan on SOD activity. Tail-suspended mice were given losartan or vehicle for 28 days. SOD activity was measured in heart tissue lysates. Data are mean ± SD, n =6 in each group.

In this work, we synthesized hierarchical flower-like structures by using lipase and papain as organic components and Cu3(PO4)2·3H2O as the inorganic component. These hybrid-nanoflower structures were confirmed by Fourier transform infrared spectroscopy, X-ray diffraction, and energy-dispersive X-ray spectroscopy. By changing the synthesis conditions, including enzyme concentration, pH, and temperature for the nanoflowers, we can control the morphology and enzymatic activity of nanoflower. Enzyme concentration and synthesis temperature affect nanoflower size and petal density, whereas pH influences petal density only. Furthermore, we found the optimal conditions to improve the enzymatic activity of lipase-Cu3(PO4)2·3H2O and papain-Cu3(PO4)2·3H2O nanoflowers. The appropriate enzyme content, flower size, and flower density were the critical factors for high enzymatic activity.

We have synthesized a novel composite material with a hierarchical flower-like structure and extremely high enzyme activity. The spherical, hierarchical flower-like structure with numerous small flowers was formed through self-assembly using papain as the organic component and Cu3(PO4)2·3H2O as the inorganic component. This hybrid-nanoflower structure was confirmed by Fourier transform infrared spectroscopy, and X-ray diffraction. The enzyme activity of papain embedded in the hybrid nanoflowers was further evaluated using BAEE as a substrate. Compared with free papain in solution, the hybrid materials exhibited extremely high enzyme activity (∼4510%). A study on the relationship of enzyme weight percentage and pattern structure with enzyme activity revealed that enzyme activity was mainly affected by the material structure. These results demonstrate that this hierarchical structure can effectively increase enzyme activity.

For the problem that the traditional static positioning algorithms can not locate the mobile network node accurately, and the traditional Monte Carlo localization algorithm features low positioning accuracy and poor positioning accuracy due to the low sampling efficiency of the nodes, an improved Monte Carlo (Higher Monte Carlo, HMCL) localization algorithm is thereby proposed. The RSSI distance measured model is used to optimize the sampling weight and the position of the node is predicted by the least squares fitting nodes. At the same time, the cross algorithm is introduced to improve the particle activity; finally, the sampling area is optimized and the sampling interval is determined. It is found that the modified Monte Carlo algorithm can greatly reduce the number of sampling times and the positioning error of the nodes; at meanwhile, the positioning error is stable.

Introduction: This study aimed to investigate whether epigallocatechin-3-gallate (EGCG) shows antioxidant activity against angiotensin II (Ang II)-induced human umbilical vein endothelial cell (HUVEC) apoptosis. Materials and Methods: The viability of HUVECs was revealed by MTT and LDH assay. The cell apoptosis was detected by FITC-PI assay. A fluorescent probe assay was used to measure the reactive oxygen species (ROS) generation in HUVECs. Mitochondrial permeability transition pore (MPTP) opening, mitochondrial membrane potential, and caspase-3, -4, -8, -9 activities were also measured. Results: We found that Ang II treatment increased the generation of ROS, enhanced MPTP opening and cytochrome c release, activated caspase-3/9, and consequently induced HUVEC apoptosis. EGCG treatment-suppressed Ang II induces the oxidative stress of HUVECs and mitochondria-related cell apoptosis. We also showed that the antioxidant activity pathway, including cytochrome c release, MPTP opening, and caspase-3/9 activation, is a key endogenous defensive system in HUVECs, provoking Ang II exposure. Our study revealed that increased expression of Nrf2 by EGCG could partially repress Ang II-induced injury effects. Conclusions: All of our findings indicated that EGCG treatment provides a protective effect for Ang II-induced HUVEC apoptosis by decreasing oxidative stress and ameliorating mitochondrial injury.

A method for quantitative analysis of diclofenac sodium powder on the basis of near-infrared (NIR) spectroscopy is investigated by using of orthogonal projection to latent structures (O-PLS) combined with artificial neural network (ANN). 148 batches of different concentrations diclofenac sodium samples were divided into three groups: 80 training samples, 46 validation samples and 22 test samples. The average concentration of diclofenac sodium was 27.80%, and the concentration range of all the samples was 15.01-40.55%. O-PLS method was applied to remove systematic orthogonal variation from original NIR spectra of diclofenac sodium samples, and the filtered signal was used to establish ANN model. In this model, the concentration of diclofenac sodium was determined. The degree of approximation was employed as selective criterion of the optimum network parameters. In order to compare with O-PLS-ANN model, principal component artificial neural network (PC-ANN) model and calibration models that use different preprocessing methods (first derivative, standard normal variate (SNV) and multiplicative scatter correction (MSC)) of the original spectra were also designed. In addition, partial least squares regression (PLS) models were also established to compare with ANN models. Experimental results show that O-PLS-ANN model is the best.

This paper is concerned with the rapid and non-destructive quantitative analysis of cimetidine in single intact tablets by diffuse reflectance spectroscopy. Support vector machines (SVM) are introduced to model multivariate, non-linear systems of calibration samples by radical basis functions. Short-wave near-infrared spectra ranging 760–1100 nm are processed by SVM. Wavelet method has been employed to minimize the influence of noise. Measurement errors of independent testing set by SVM compared to partial least squares (PLS) give relatively reasonable results. Experiments show that SVM with wavelet denoising pretreatment is an effective method and requires less number of calibration samples.

The correspondence between five precipitation products, including CMORPH, GPCP-2, TRMM 3B43, GPCC, and ITPCAS, and ground-based measurements of precipitation were evaluated on annual, seasonal, and monthly scales during 2000–2014 in the Qinling-Daba Mountains over China, which is a significant area with vital value of climate and hydrology. Performances of the precipitation products in the relatively arid/humid years were also analyzed. In general, ITPCAS data displayed the highest accuracy, GPCP-2 and CMORPH data showed relatively poor performance, and GPCC and TRMM 3B43 data were average at different temporal scales among the five precipitation products. The Pearson correlation coefficient of each station had minor fluctuations for the five precipitation products. A larger deviation was found at Wudu station, most likely due to the undulating terrain. The performances of the precipitation products from highest to least accuracy are as follows: ITPCAS > TRMM 3B43 > GPCC > GPCP-2 > CMORPH. Except for CMORPH (-20.76%), the percentage precipitation differences (PPDs) of the other four precipitation products fluctuated in the range of 10% during the relatively arid (2001) and humid (2011) years. In addition, all precipitation products and ground gauge observed precipitation did not show an obvious gradient with altitude, which is different from that in other mountainous areas and is perhaps due to complex terrain, lack of observation in high altitudes, and precipitation undercatch. In consideration of the significance of Qinling-Daba Mountains as the geographic and ecological dividing lines, the present study may provide a new perspective for hydrological, climatic, and ecological researches and practices in local and other mountainous areas.