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This study aimed to assess the risk of side branch (SB) occlusion using the V-RESOLVE (The Visual Estimation for Risk prEdiction of Side Branch OccLusion in Coronary Bifurcation interVEntion) score in unprotected left main (LM) bifurcation percutaneous coronary intervention (PCI).The V-RESOLVE score is a validated score system, based on visual estimation of angiographic data, for prediction of the risk of SB occlusion after main vessel (MV) stenting in non-LM bifurcation lesions. However, its predictive value for unprotected LM bifurcation lesions remains to be validated.From January 2014 to December 2016, 855 patients undergoing unprotected LM bifurcation PCI using a provisional strategy were included. Baseline and prestenting angiographic data were analyzed, and the V-RESOLVE score was calculated. SB occlusion was defined as any decrease in thrombolysis in myocardial infarction (TIMI) flow grade or the absence of flow in the SB after MV stenting. The predictive performance of the V-RESOLVE score was judged by discrimination, calibration, and clinical application.vSB occlusion occurred in 19 (2.2%) of 855 unprotected LM bifurcation PCI procedures using a provisional strategy. The V-RESOLVE score for SB occlusion had brilliant discrimination (the area under the receiver operating characteristic curve = 0.80, 95% confidence interval [CI]: 0.77-0.84) and good calibration (Hosmer-Lemeshow: p = 0.154). Stratified by the V-RESOLVE score, significantly higher rates of SB occlusion were observed in the high-risk group (score: 12-43) compared with the nonhigh-risk group (score: 0-11) (4.4% vs. 0.6%, p 0.001).The V-RESOLVE score is a promising tool to predict the risk of SB occlusion and facilitate decision-making for unprotected LM bifurcation PCI.

Background Prediabetes is common and associated with poor prognosis in patients with acute coronary syndrome and those undergoing revascularization. However, the impact of prediabetes on prognosis in patients with coronary intermediate lesions remains unclear. The objective of the current study is to explore the impact of prediabetes and compare the prognostic value of the different definitions of prediabetes in patients with coronary intermediate lesions. Methods A total of 1532 patients with intermediate coronary lesions on coronary angiography and not undergoing revascularization were enrolled in the current study. Patients were classified as normal glucose tolerance (NGT), prediabetes and diabetes according to various definitions based on HbA1c or admission fasting glucose. The primary endpoint was defined as major adverse cardiovascular events (MACE), the composite endpoint of all-cause death, non-fatal myocardial infarction and repeated revascularization therapy. Multivariate cox regression model was used to explore the association between categories of abnormal glucose category and MACE risk. Results The proportion of patients defined as prediabetes ranged from 3.92–47.06% depending on the definition used. A total of 197 MACE occurred during a median follow-up time of 6.1 years. Multivariate cox analysis showed that prediabetes according to the International Expert Committee (IEC) guideline (6.0 ≤ HbA1c

Background LncRNAs take various effects mostly through sponging with miRNAs. Based on public databases and integrating bioinformatics analyses and further validated in BC tissue and cell lines, the effect of lncRNA AFAP1-AS1 on breast cancer cells proliferation and migration was verified and might work via miR-21/PTEN axis. Methods The expression of AFAP1-AS1, miR-21, PTEN in BC tissues and cell lines were analyzed by qRT-PCR. BC cell proliferation and migration were examined using EdU, colony formation assays and wound healing, transwell assays, respectively. The cellular localization of AFAP1-AS1 was analyzed using FISH. RNA pull down assay was performed to analyze the binding of AFAP1-AS1 to miR-21. The interaction between miR-21 and PTEN was examined using a dual luciferase reporter assay. The effect of AFAP1-AS1 on BC tumor growth in vivo was analyzed using a tumor xenograft mouse model. Results The expression of AFAP1-AS1, which was significantly upregulated in BC tissues and cell lines. The higher expression of AFAP1-AS1 was correlated with old age and lymph node metastasis of patients with BC. AFAP1-AS1 knockdown BC cells exhibited decreased proliferation and migration in vitro and in vivo. Additionally, AFAP1-AS1 knockdown downregulated miR-21 expression and upregulated PTEN expression. Mechanistically, the interaction between AFAP1-AS1 and miR-21 promotes BC cell proliferation and migration. AFAP1-AS1 knockdown decreased BC cell proliferation and migration, which are regulated by PTEN, through miR-21 regulation. Conclusions The knockdown of lncRNA AFAP1-AS1 upregulated PTEN expression and consequently attenuated miR-21-mediated enhanced BC cell proliferation and migration. LncRNA AFAP1-AS1 is a potential prognostic biomarker for BC patients.

Up to now, the applications of nanofiltration membranes for removal of organic molecules from wastewater have still be restricted due to the improper channel distribution, inherent low chemical stability and easy fouling of the membranes. In this study, a new kind of Ti3C2Tx-deviated hybrid nanomaterial membranes is fabricated by a vacuum-filtration strategy on a cellulose acetate support. Ti3C2Tx nanosheets, together with the self-derivated TiO2, are found to play a key role to establish continuous water transmission channels. With the incorporation of TiO2 nanoparticles, the surface roughness of the prepared membranes also decreases apparently. By this new design, the water flux of the Ti3C2Tx-TiO2 membrane increases to a maximum value of 75.4 L/m2 h bar 4 times higher than that of the pristine Ti3C2Tx membrane, together with a high removal ratio of above 99% for one typical small molecule organic contaminant of rhodamine B (RhB). The composite membranes also exhibit a good anti-fouling performance, since the adsorption tendency of pollutants on the surface of the membrane or the blockage of the pores was decreased. In addition, the excellent photocatalytic self-cleaning ability of the membranes under UV light, with the improved possibility of highly efficient recycling, was also validated, which was ascribed to the in situ formation of Ti3C2Tx/TiO2 heterojunctions. This study provides a new prospective for providing multi-functional nanofiltration membranes in the field of wastewater treatment.

Pseudomonas stutzeri A1501 is a model strain used to study associative nitrogen fixation, and it possesses the nitrogen regulatory NtrC protein in the core genome. Nitrogen sources represent one of the important factors affecting the efficiency of biological nitrogen fixation in the natural environment. However, the regulation of NtrC during nitrogen metabolism in P. stutzeri A1501 has not been clarified. In this work, a phenotypic analysis of the ntrC mutant characterized the roles of NtrC in nitrogen metabolism and the oxidative stress response of P. stutzeri A1501. To systematically identify NtrC-controlled gene expression, RNA-seq was performed to further analyse the gene expression differences between the wild-type strain and the ∆ntrC mutant under nitrogen fixation conditions. A total of 1431 genes were found to be significantly altered by ntrC deletion, among which 147 associative genes had NtrC-binding sites, and the pathways for nitrogen fixation regulation, nitrogenous compound acquisition and catabolism and nitrate assimilation were discussed. Furthermore, the oxidative stress-related gene (katB), which was upregulated by ntrC deletion, was suggested to be a potential target gene of NtrC, thus highlighting the importance of NtrC in nitrogenase protection against oxygen damage. Based on these findings, we propose that NtrC is a high-ranking element in the regulatory network of P. stutzeri A1501 that controls a variety of nitrogen metabolic and oxidative stress responsive traits required for adaptation to complex rhizosphere environments.

Nineteen TH03 analogues were designed and synthesized as tubulin colchicine-binding site inhibitors with potent antiproliferative activities. Among these compounds, 3,5-dimethoxyphenylpyridines 8j bearing a 4-methoxybenzyl aniline side-chain displayed the best antiproliferative activities against glioma (U87MG and U251). In addition, the trimethoxyphenylpyridine 8o bearing a 4-methyl-N-methyl aniline side-chain showed the best antiproliferative activities against colon carcinoma and lung cancer with the lowest IC

Till now, the prognostic value of lipoprotein(a) [Lp(a)] in patients with coronary artery disease (CAD) who underwent percutaneous coronary intervention (PCI) remains controversial. We therefore conducted this study to evaluate the effect of Lp(a) levels on clinical outcomes in this population.A total of 10,059 CAD patients who underwent PCI were prospectively enrolled in this cohort study, of which 6564 patients had Lp(a) ≤30 mg/dl and 3495 patients had Lp(a) 30 mg/dl. The primary endpoint was major adverse cardiovascular and cerebrovascular event (MACCE), defined as a composite of all-cause death, myocardial infarction, stroke or unplanned revascularization. Multivariate Cox regression analysis and propensity-score matching analysis were performed. After propensity-score matching, 3449 pairs of patients were identified, and post-matching absolute standardized differences were10% for all the covariates. At 2.4 years, the risk of MACCE was significantly higher in patients with elevated Lp(a) levels than those with normal Lp(a) levels in both overall population (13.0% vs. 11.4%; adjusted hazard ratio [HR] 1.142, 95% confidence interval [CI] 1.009-1.293; P = 0.040) and propensity-matched cohorts (13.0% vs. 11.2%; HR 1.167, 95%CI 1.019-1.337; P = 0.026). Of note, the predictive value of Lp(a) levels on MACCE tended to be more evident in individuals65 years or those with left main and/or three-vessel disease. On the contrary, elevated Lp(a) levels had almost no effect on clinical outcomes in patients ≤65 years (PIn CAD patients who underwent PCI, elevated Lp(a) levels were positively related to higher risk of MACCE at 2.4-year follow-up, especially in patients65 years and those with left main and/or three-vessel disease.not applicable.

PURPOSE: We investigated the combination of tivantinib, a c-MET tyrosine kinase inhibitor (TKI), and bevacizumab, an anti-VEGF-A antibody. METHODS: Patients with advanced solid tumors received bevacizumab (10 mg/kg intravenously every 2 weeks) and escalating doses of tivantinib (120–360 mg orally twice daily). In addition to safety and preliminary efficacy, we evaluated pharmacokinetics of tivantinib and its metabolites, as well as pharmacodynamic biomarkers in peripheral blood and skin. RESULTS: Eleven patients received the combination treatment, which was generally well tolerated. The main dose-limiting toxicity was grade 3 hypertension, which was observed in four patients. Other toxicities included lymphopenia and electrolyte disturbances. No exposure-toxicity relationship was observed for tivantinib or metabolites. No clinical responses were observed. Mean levels of the serum cytokine bFGF increased (p = 0.008) after the bevacizumab-only lead-in and decreased back to baseline (p = 0.047) after addition of tivantinib. Tivantinib reduced levels of both phospho-MET (7/11 patients) and tubulin (4/11 patients) in skin. CONCLUSIONS: The combination of tivantinib and bevacizumab produced toxicities that were largely consistent with the safety profiles of the individual drugs. The study was terminated prior to establishment of the recommended phase II dose (RP2D) due to concerns regarding the mechanism of tivantinib, as well as lack of clinical efficacy seen in this and other studies. Tivantinib reversed the upregulation of bFGF caused by bevacizumab, which has been considered a potential mechanism of resistance to therapies targeting the VEGF pathway. The findings from this study suggest that the mechanism of action of tivantinib in humans may involve inhibition of both c-MET and tubulin expression. TRIAL REGISTRATION: NCT01749384 (First posted 12/13/2012).

Pseudomonas stutzeri A1501 is the model strain for studying associative nitrogen fixation and possesses the nitrogen regulatory NtrC protein in the core genome. Nitrogen source is one of the important factors affecting the efficiency of biological nitrogen fixation in the natural environment. However, the regulation of NtrC in nitrogen metabolism of P. stutzeri A1501 is not clear. In this work, phenotypic analysis of the ntrC mutant characterized the roles of NtrC for the nitrogen metabolism and oxidative stress response of P. stutzeri A1501. To systematically identify NtrC-controlled gene expression, RNA-seq was performed to further analyze the gene expression differences between the wild type strain and the ∆ntrC mutant under nitrogen fixation conditions. A total of 1431 genes were found to be significantly altered by the ntrC deletion, among which 147 associative genes had NtrC-binding sites, and pathways for nitrogen fixation regulation, the acquisition and catabolism of nitrogenous compounds and nitrate assimilation were particularly discussed. Furthermore, the oxidative stress-related gene (katB), upregulated by the ntrC deletion, was suggested to be the potential target gene of NtrC, underlining the importance of NtrC to nitrogenase protection against oxygen damage. Based on these findings, we propose that NtrC is a high-ranked element in the regulatory network of P. stutzeri A1501 that controls a variety of nitrogen metabolic and oxidative stress responsive traits required for adaptation to complex rhizosphere environment.

Most chronic kidney diseases (CKDs) develop to end-stage renal disease (ESRD), which is characterized by fibrosis and permanent tissue and function loss. As a result, better and more effective remedies are essential. Kaempferol (KAE) is a common flavonoid extracted from plants. It can control the progression of kidney fibrosis and the epithelial-to-mesenchymal transition (EMT) of the renal tubular system.We aim to investigate the effect of KAE therapy on extracellular matrix deposition and stimulation of EMT in vitro and in vivo to elucidate the treatment mechanisms regulating these effects.Chronic hypertension-induced kidney fibrosis was studied in spontaneously hypertensive rats with chronic kidney disease. Biochemical analysis, histological staining, and the expression level of relative proteins were used to assess the effect of KAE on renal function and fibrosis. The direct impact of KAE on proliferation and migration was evaluated using human renal tubular epithelial cells (HK-2) induced by transforming growth factor-β1 (TGF-β1), which can then induce EMT. The molecular mechanism of KAE was verified using co-IP assay and immunofluorescence.KAE could reduce blood pressure and decrease the extracellular matrix (ECM) components (including collagen I and collagen Ш), TGF-β1, and α-SMA in the kidneys of hypertension-induced rats with chronic kidney disease. Moreover, in HK-2 cell treated with TGF-β1, KAE administration significantly suppressed proliferation, migration, and EMT via increasing the expression of E-cadherin, while reducing the N-cadherin and α-SMA. Sufu was exceedingly repressed in HK-2 cells treated with TGF-β1. KAE inhibited the activation of Shh and Gli through increasing the expression of Sufu, thereby blocking the nuclear translocation of Gli1 in vitro.KAE ameliorated kidney fibrosis and EMT by inhibiting the sonic hedgehog signaling pathway, thereby to attenuate the pathological progression of hypertensive kidney fibrosis.

Current therapeutic approaches have a limited effect on cardiac remodeling, which is characteristic of cardiac fibrosis and myocardial hypertrophy. In this study, we examined whether Danshenol A (DA), an active ingredient extracted from the traditional Chinese medicine Radix Salviae, can attenuate cardiac remodeling and clarified the underlying mechanisms. Using the spontaneously hypertensive rat (SHR) as a cardiac remodeling model, DA ameliorated blood pressure, cardiac injury, and myocardial collagen volume and improved cardiac function. Bioinformatics analysis revealed that DA might attenuate cardiac remodeling through modulating mitochondrial dysfunction and reactive oxygen species. DA repaired the structure/function of the mitochondria, alleviated oxidative stress in the myocardium, and restored apoptosis of cardiomyocytes induced by angiotensin II. Besides, DA inhibited mitochondrial redox signaling pathways in both the myocardium and cardiomyocytes. Thus, our study suggested that DA attenuates cardiac remodeling induced by hypertension through modulating mitochondrial dysfunction and reactive oxygen species.

To assess the infection eradication rate when using two types of articulating spacers (prosthetic articulating spacers and all-cement articulating spacers) in two-stage revision of infected total knee arthroplasty (TKA). We comprehensively searched PubMed, Embase, and the Cochrane Library databases and performed a systematic review and meta-analysis of retrospective comparative studies assessing two types of articulating spacers. A quality assessment of the included studies was performed following the STROBE statement. Thirty retrospective studies, including a total of 821 knees, were identified. The pooled infection control rates in stage I were as follows: 0.98 (95% confidence interval [CI], 0.97 to 1.00) and 0.98 (95% CI, 0.96 to 0.99) for the prosthetic articulating spacer group and all-cement articulating spacer group, respectively. The pooled postoperative reinfection rate was 0.05 (95% CI, 0.03 to 0.08) for the prosthetic spacer group and 0.03 (95% CI, 0.01 to 0.06) for the all-cement spacer group. Results of the subgroup analyses showed that the weight of the antibiotic cement, antibiotic type, mean period of spacers in situ, postoperative antibiotic treatment period, and postoperative antibiotic treatment approach had no effect on the reinfection rates (p

Chronic kidney disease (CKD) is becoming a notable health concern globally. The combination of Scutellaria baicalensis Georgi (SB) and Sophora japonica L. (SJ) has been demonstrated to have anti-hypertensive effects and improve kidney injury clinically. This study aimed to explore the renal protective effect of the combination of SB and SJ against CKD and clarify the potential mechanisms. Male spontaneously hypertensive rats (SHR) were used to induce hypertensive nephropathy and were treated with SB or SJ separately or in combination for 15 weeks, and an antibiotic group was used for a rescue experiment. Blood pressure, serum or urine biochemical markers, serum inflammation factors, short-chain fatty acids (SCFAs), indoxyl sulfate (IS), and oxidative stress indicators were assessed. Western blot analysis was performed to determine the expression of intestinal tight junction proteins, including occludin and ZO-1. The mRNA expression of the SCFAs receptors olfactory 78 (Olfr78) and G protein-coupled receptor 41 (GPR41) was determined by quantitative real-time PCR. Gut microbiota profiles were established via high-throughput sequencing of the V3-V4 region of the bacterial 16S rRNA gene. SB and SJ significantly ameliorated the severity of renal injury induced by hypertension. The combination also decreased the ratio of Firmicutes/Bacteroidetes, increased the relative abundance of Lactobacillus, and reduced that of Clostridiaceae. The intestinal barrier was improved, and the change in dominant bacteria reduced IS accumulation and further inhibited oxidative stress activation in kidneys. SB and SJ increased SCFAs production, inhibited inflammatory factor release, and regulated blood pressure by decreasing the expression of Olfr78 and increasing that of GPR41, then alleviated kidney damage. This research demonstrated the positive effects of SB and SJ in a rat model of hypertensive nephropathy, indicated that the treatment of SB and SJ by improving the intestinal barrier function, increasing SCFAs, reducing inflammation, decreasing IS, and inhibiting oxidative stress reactions.

To compare the prognostic implication of post-percutaneous coronary intervention (PCI) quantitative flow ratio (QFR) assessment in patients with and without diabetes enrolled in the all-comers, multicenter, randomized controlled PANDA III trial.All treated vessels in PANDA III trial were retrospectively assessed for post-PCI QFR. Vessels with available post-PCI QFR were further stratified into DM and non-DM cohorts, and prognostic performance of post-PCI QFR was compared in 2 cohorts. The primary outcome was 2-year vessel-oriented composite endpoint (VOCE), defined as composite of vessel-related cardiac death, vessel-related non-procedural myocardial infarction, and ischemia-driven target vessel revascularization.Of 2,989 treated vessels, 2,227 (74.5%) with available post-PCI QFR were included, while 548 were presence of DM and 1,679 were not. The performance of post-PCI QFR to predict 2-year VOCE were moderate in both DM (area under the curve [AUC] 0.77, 95% confidence interval [CI]: 0.68 to 0.87) and non-DM cohorts (AUC 0.74, 95% CI: 0.67 to 0.82), while between-cohorts AUC difference was not significant (ΔAUC 0.03, P = 0.65). After multivariate adjustment, vessels with suboptimal post-PCI QFR results (≤0.92) were associated with higher risk of 2-year VOCE in both DM (adjusted HR 6.24, 95% CI: 2.40 to 16.2) and non-DM cohorts (adjusted HR 5.92, 95% CI: 3.28 to 10.7) without significant interaction (P for interaction 0.91).This study, the first to directly compare clinical value of post-PCI QFR assessments in patients with and without DM, showed that a higher post-PCI QFR value was associated with improved long-term prognosis regardless of the presence of DM. Clinical Trial Registration Information URL: https://www.gov; Unique identifier: NCT02017275.

The composition of microtubules involving several steps, including the polymerization and depolymerization of α-tubulin and β-tubulin heterodimers. Microtubule-targeting agents can increase or inhibit microtubule polymerization, thereby disrupting the dynamic process and stalling cells in G2/M phase. Microtubule-targeting agents are generally cytotoxic, which neurological toxicity being one of the significant adverse events associated. We recently reported a novel 5-arylalkynyl-2-benzoyl thiophene (PST-3) that exhibited broad-spectrum cellular cytotoxicity and in vivo potency with high safety. PST-3 was a substrate of p-gp, which could not cross the blood-brain barrier and lead to less neurotoxicity. The antitumor activities in vitro demonstrated that PST-3 combined with the colchicine-binding site on microtubule, induces morphological changes, disrupts microtubule networks, inhibits polymerization of tubulin, arrests breast cancer cells in the G2/M phase of the cell cycle and induces apoptosis. Evaluation of the antitumor effect in vivo demonstrated that PST-3 elicited MDA-MB-468 tumor %T/C of 11.75%, whereas elicited MCF7 tumor %T/C of 44.38% in breast cancer xenograft models. Besides, in vivo experiments of a higher dose (60 mg/kg) of PST-3 treatment for 21 days did not produce any significant neurotoxicity. These results provide evidence that PST-3 might possess the potential to be developed into a new microtubule inhibitor without neurological toxicity.

Background: Breast cancer is one of the most common malignant tumors with the highest morbidity and mortality among women. Compared with the other breast cancer subtypes, Triple-negative breast cancer (TNBC) has a higher probability of recurrence and is prone to distant metastasis. To reveal the underlying disease mechanisms and identify more effective biomarkers for TNBC and breast cancer metastasis. Methods: Gene Ontology and KEGG pathway analysis were used for investigating the role of overlapping differentially expressed genes (DEGs). Hub genes among these DEGs were determined by the protein-protein interactions network analysis and CytoHubba. Oncomine databases were used for verifying the clinical relevance of hub genes. Furthermore, the differences in the expression of these genes in cancer and normal tissues were validated in the cellular, animal and human tissue.Results: Seven hub genes, including TTK, KIF11, SPAG5, RRM2, BUB1, CDCA8 and CDC25C, were identified that might be associated with TNBC and breast cancer metastasis. Meanwhile, these genes have been verified highly expressed in tumor cells and tumor tissues, and patients with higher expression of these genes have a poorer prognosis. Conclusions: Seven hub genes were potential biomarkers for the diagnosis and therapy of TNBC and breast cancer metastasis.

In this paper, we designed and synthesized two analog compounds M1 and T1 that have a Michael acceptor warhead. Although only slightly diversity existed in the structures of M1 and T1, their inhibitory activities against wild type epidermal growth factor receptor (EGFRWT) and T790M/L858R mutant epidermal growth factor receptor (EGFRT790M/L858R) were significant different. Thus, multiple computational approaches were applied to investigate the interactions between the compounds with EGFRWT and EGFRT790M/L858R in order to explore the effect of different compounds. The molecular docking and MD simulations were performed to study the intermolecular interactions between compounds and EGFR. The binding free energy revealed that M1-EGFRWT and M1-EGFRT790M/L858R complexes have stronger binding affinity compared with the corresponding T1-EGFRWT and T1-EGFRT790M/L858R complexes, respectively. And the binding free energy decompositions for each residue analysis indicated that the van der Waals interactions are the major contributor to enhance the compounds to bind with EGFR. In addition, covalent binding complexes of M1-EGFRWT and M1-EGFRT790M/L858R were constructed and studied. Moreover, quantum mechanics method was applied to investigate the reaction mechanism of covalent binding of the compound and EGFR. The results will provide the details of structural and energetic information to develop potent covalent EGFR inhibitors in the future.

Receptor Tyrosine Kinase inhibitors are the most popular anti-cancer drug types. But the resistance is the major challenge. Our study on the network with 1334 proteins and their 2623 interactions which retrieved from 52 RTKs indicated that most RTKs proteins were the key controllers of the protein-protein network. Direct or indirect interactions with RTKs (shortest path of 2) were often associated with resistance to RTKs inhibitors in the literature. The results based on the KEGG pathway analysis demonstrated the Rap1 signal pathway would also contribute to the resistance of RTKs inhibitor as well as the known Ras pathway and PI3K/Akt pathway. The pathways can crosstalk within and between complex signals transduction networks, then activate the upstream or downstream pathway, and/or activate the other oncogenes, which lead to the acquired resistance. Our results gave a systematically global view to understand the drug resistance and provided a clue to how to combine the different targets or pathways for synergy of targeted RTKs inhibitors.

Pulsed electromagnetic fields (PEMFs) are effective in healing fractures and improving osteoporosis. However, their effect on mesenchymal cells remains largely unknown. In this study, the effects of PEMF on osteoblastogenesis and its underlying molecular signaling mechanisms were systematically investigated in C3H10T1/2 cells. C3H10T1/2 mesenchymal cells were exposed to 30-Hz PEMF bursts at various intensities for 3 consecutive days. The optimal PEMF exposure (30 Hz, 1 mT, 2 h/day) was applied in subsequent experiments. Our results suggest that intracellular [Ca2+]i in C3H10T1/2 cells can be upregulated upon exposure to PEMF and that PEMF-induced C3H10T1/2 cell differentiation was Ca2+-dependent. The pro-osteogenic effect of PEMF on Ca2+-dependent osteoblast differentiation was then verified by alkaline phosphatase (ALP) and von Kossa staining. Furthermore, PEMF promoted the gene expression and protein synthesis of the Wnt/β-catenin pathway. Increased [Ca2+]i in the nucleoplasm was followed by the mobilization and translocation of β-catenin into the nucleus in C3H10T1/2 cells. A model of Wnt/β-catenin signaling and the Wnt/Ca2+ signaling network is proposed. Taken together, these findings indicated for the first time that PEMF induces osteoblastogenesis through increased intracellular [Ca2+]i and the Wnt-Ca2+/Wnt-β-catenin signaling pathway in C3H10T1/2 mesenchymal cells.

In this study, folic acid-conjugated lipid nanoparticles were successfully prepared to enhance the active targeting of capsaicin (CAP) in ovarian cancers. The particles were nanosized and exhibited a controlled release of drug in the physiological conditions. The folic acid (FA)-conjugated system exhibited a remarkably higher uptake of nanoparticles in the cancer cells compared to that of non-targeted system. The folate-conjugated CAP-loaded lipid nanoparticles (CFLN) upon interacting with cancer cells were internalized via receptor-mediated endocytosis mechanism and resulted in higher concentration in the cancer cells. Consistently, CFLN showed a remarkably higher toxic effect compared to that of non-targeted nanoparticle system. CFLN showed significantly higher cancer cell apoptosis with nearly 39% of cells in apoptosis chamber (early and late) compared to only ∼21% and ∼11% for CAP-loaded lipid nanoparticles (CLN) and CAP. The loading of drug in the lipid nanoparticle system extended the drug retention in the blood circulation and allowed the active targeting to specific cancer cells. The prolonged circulation of drug attributed to the antifouling property of polyethylene glycol molecule in the structure. Overall, study highlights that using targeting moiety could enhance the therapeutic response of nanomedicines in the treatment of solid tumors.

Purpose This paper aims to analyze the impact of the degree of local government decision-making competition on the optimal investment amount, investment location and investment failure of innovative investment enterprise under multiple risk appetite type of innovative investment enterprise. This paper also points out three regulation paths that central government could use to avoid the influence of local government decision-making competition on the validity of enterprise innovation investment (EII). Design/methodology/approach Based on analysis frame of government competition about unitary government states, this paper builds duopoly decision model to analyze influence of local government decision-making competition on EII. Considering information asymmetry and multiple risk appetite type of decision-maker, this paper analyzes influence of local government decision-making competition on location selection, the optimal investment amount, identification of investment failure and exit mechanism of EII according to different relationship between reference points of local government decision-making competition and EII. Finding The optimal investment amount of EII has positive correlation with risk appetite type of decision-maker, local government decision-making competition. Identification of investment failure and exit are divided into three phases. The boundary conditions are directly related to risk appetite type and amount of local government subsidy. Regional factor endowment and degree of preferential policy are main factors attracting enterprise investment. Local governments should analyze the interests of EII. There are three paths to avoid vicious competition among local governments: unified planning, revising of audit index, increasing penalties for failure of policies. Originality/value With rapid development of China's new urbanization process, urban economy has become an important carrier of economic development. Attracting foreign direct investment is an important measure to promote urban economic growth, and EII is the most important one. However new urbanization would lead to local government decision-making competition and then influence EII. Through analyzing influence of local government decision-making competition on EII, theory guidance could be provided to decision makers of innovation investment.

The particularity of the Web application of catering O2O platform makes its testing challenging, but the current research on its testing is relatively weak compared with the research on its design and development.This paper summarizes the research progress of Web platform testing methods in recent years.The Basic test contents and technologies, typical test models and automated testing tools of existing platforms are summarized.The current research hotspots and difficulties are analyzed, including the optimization of test models, the improvement and development of automated testing tools, the guarantee of test comprehensiveness, safety, stability and efficiency.Finally, the future research directions of the testing methods of catering O2O Web platform are discussed from three aspects: testing content, testing methods and testing tools.