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Background Previous studies proved that pyrin domain-containing protein 3 (NLRP3)-induced pyroptosis plays an important role in Myocardial ischemia-reperfusion injury (MIRI). Insulin can inhibit the activation of NLRP3 inflammasome, although the exact mechanism remains unclear. The aim of this study was to determine whether insulin reduces NLRP3-induced pyroptosis by regulating pyruvate dehydrogenase E1alpha subunit (PDHA1) dephosphorylation during MIRI. Methods Rat hearts were subject to 30 min global ischemia followed by 60 min reperfusion, with or without 0.5 IU/L insulin. Myocardial ischemia-reperfusion injury was evaluated by measuring myocardial enzymes release, Cardiac hemodynamics, pathological changes, infarct size, and apoptosis rate. Cardiac aerobic glycolysis was evaluated by measuring ATP, lactic acid content, and pyruvate dehydrogenase complex (PDHc) activity in myocardial tissue. Recombinant adenoviral vectors for PDHA1 knockdown were constructed. Pyroptosis-related proteins were measured by Western blotting analysis, immunohistochemistry staining, and ELISA assay, respectively. Results It was found that insulin significantly reduced the area of myocardial infarction, apoptosis rate, and improved cardiac hemodynamics, pathological changes, energy metabolism. Insulin inhibits pyroptosis-induced inflammation during MIRI. Subsequently, Adeno-associated virus was used to knock down cardiac PDHA1 expression. Knockdown PDHA1 not only promoted the expression of NLRP3 but also blocked the inhibitory effect of insulin on NLRP3-mediated pyroptosis in MIRI. Conclusions Results suggest that insulin protects against MIRI by regulating PDHA1 dephosphorylation, its mechanism is not only to improve myocardial energy metabolism but also to reduce the NLRP3-induced pyroptosis.

Senecavirus A (SVA) is an oncolytic RNA virus, and it is the ideal oncolytic virus that can be genetically engineered for editing. However, there has not been much exploration into creating SVA viruses that carry antitumor genes to increase their oncolytic potential. The construction of SVA viruses carrying antitumor genes that enhance oncolytic potential has not been fully explored. In this study, a recombinant SVA-CH-01-2015 virus (p15A-SVA-clone) expressing the human p16INK4A protein, also known as cell cycle-dependent protein kinase inhibitor 2A (CDKN2A), was successfully rescued and characterized. The recombinant virus, called SVA-p16, exhibited similar viral replication kinetics to the parent virus, was genetically stable, and demonstrated enhanced antitumor effects in Ishikawa cells. Additionally, another recombinant SVA virus carrying a reporter gene (iLOV), SVA-iLOV, was constructed and identified using the same construction method as an auxiliary validation. Collectively, this study successfully created a new recombinant virus, SVA-p16, that showed increased antitumor effects and could serve as a model for further exploring the antitumor potential of SVA as an oncolytic virus.

Background Uric acid is the end product of purine metabolism. Previous studies have found that serum uric acid (SUA) levels are associated with the total cancer risk. However, due to the dual effect of uric acid on cancer, the relationship between the SUA levels and most specific-site cancer remains unclear. Aim To investigate the associations between the SUA levels and incidence of hepatobiliary-pancreatic cancer. Methods In this prospective cohort study, 444462 participants free of cancer from the UK Biobank were included. The SUA levels were measured at baseline, and the incidence of hepatobiliary-pancreatic cancer was determined by contacting the cancer registry. The hazard ratios (HRs) and 95% confidence intervals (CIs) between the SUA levels and hepatobiliary-pancreatic cancer were investigated using multiple adjusted Cox regression models adjusted for potential confounders. Results In total, 920 participants developed liver, gallbladder, biliary tract or pancreatic cancer during a median of 6.6 yrs of follow-up. We found that the HR of pancreatic cancer in the highest SUA group was 1.77 (95%CI: 1.29-2.42) compared with that in the lowest group. After stratifying by gender, we further found that SUA was associated with an increased risk of pancreatic cancer only among the females (highest quartile vs lowest quartile HR 2.04, 95%CI: 1.35-3.08). Among the males, the SUA levels were positively associated with the gallbladder cancer risk (highest quartile vs lowest quartile HR 3.09, 95%CI: 1.28-7.46), but a U-shaped association with the liver cancer risk was observed (P-nonlinear = 0.03). Conclusion SUA is likely to have gender-specific effects on hepatobiliary-pancreatic cancer. High SUA levels are a risk factor for pancreatic cancer in females and gallbladder cancer in males. A U-shaped association with the liver cancer risk was identified.

Stem-cell therapy has been proved as a promising strategy for myocardial infarction (MI) treatment. However, the therapeutic efficacy is mainly limited by the cellular activity of transplanted mesenchymal stem cells (MSCs). In this study, a novel bioglass (BG)/γ-polyglutamic acid (γ-PGA)/chitosan (CS) hydrogel was obtained by in situ adding BG to stimulate the imine bond formation. And the effect of the composite hydrogel on MI therapeutic efficacy was evaluated in a rat acute myocardial infarction (AMI) model in vivo and the possible mechanism of the BG/γ-PGA/CS hydrogel for the stimulation of the intercellular interaction between MSCs and cardiomyocytes (CMs) was explored by a MSC and CM co-culture experiment in vitro. The implantation of the MSC loaded BG/γ-PGA/CS composite hydrogel in the mice AMI model showed a significant improvement in the therapeutic efficacy with improved cardiac function, attenuation of heart remodeling, reduced cardiomyocyte apoptosis and accelerated vascularization. The in vitro cell experiments demonstrated that the BG/γ-PGA/CS hydrogel activated the intercellular interaction between MSCs and CMs, which resulted in reduced cell apoptosis and enhanced angiogenesis. Silicate based bioactive hydrogels activated MSCs and cell-cell interactions in cardiac tissue after AMI and significantly enhanced the efficacy, which suggests that this bioactive hydrogel based approach is an effective way to enhance stem-cell therapy.

Background: Coronary artery disease (CAD) in octogenarians (age of ≥80 years) has a high risk of mortality and high medical expenses. Research shows that the prevalence of CAD is higher among octogenarians than that among younger people, but few such patients undergo percutaneous coronary intervention (PCI) or coronary artery bypass grafting (CABG). This study aimed to evaluate different treatments with respect to their clinical effects and impacts on quality of life of octogenarians with CAD. Methods: Data of 519 octogenarians with CAD consecutively treated at Beijing Anzhen Hospital, Capital Medical University (Beijing, China) from January 2010 to January 2016 were collected in this study. The patients were categorized into three groups based on the treatments they received: the PCI group (n = 292), CABG group (n = 110), and medical treatment group (n = 117). The followings were recorded during follow-up: clinical data, death (all-cause and cardiovascular-related), re-hospitalization time, Seattle Angina Questionnaire (SAQ) score, and occurrence of hemorrhagic events (cerebral bleeding, gastrointestinal bleeding, and dermal ecchymosis). Results: The median follow-up duration was 25.0 (25th, 75th percentile: 17.0, 55.5) months among 417 patients. The all-cause death rates (28.2% vs. 12.0% and 14.6%, respectively) and cardiovascular-related death rates (15.4% vs. 3.8% and 6.4%, respectively) were significantly higher in the medical treatment group than those in the PCI group and CABG group (all P < 0.05). The re-hospitalization rate for cardiovascular events was significantly lower in the CABG group than those in the PCI group and medical treatment group (3.8% vs. 12.8% and 14.9%, respectively) (χ2 = 8.238, P = 0.018). The SAQ scores of physical limitation, angina frequency, treatment satisfaction, and disease perception were significantly higher in the PCI group and CABG group than those in the medical treatment group (all P < 0.05). No significant difference in the angina stability score was observed among the three groups (F = 3.179, P = 0.204). Conclusion: PCI and CABG result in reduced mortality and better quality of life in octogenarians with CAD. Key words: Coronary artery disease; Octogenarian; Percutaneous coronary intervention; Coronary artery bypass graft; Death; Life quality

Bacterial contamination often impairs uterine function in cattle leading to uterine diseases such as endometritis. Inflammatory responses to bacterial infections in the uterus of cattle are generated through pattern recognition receptors, including Toll-like receptor 2 (TLR2), which is responsible for Pam3CSK4 recognition. This cellular response induces inflammatory responses through stimulation of mitogen-activated protein kinases (MAPKs) and nuclear factor (NF)-κB signaling activation, stimulating the expression of inflammatory mediators. Prostaglandin (PG) E2 has important actions in bacterial endometritis, although details through which these mechanisms regulate Pam3CSK4-induced inflammatory responses in cattle endometrial epithelial cells (bEECs) remain unclear. In the present study there was examination of the actions of exogenous PGE2 in Pam3CSK4-induced inflammatory responses. The bEECs pre-treated with exogenous PGE2 prior to Pam3CSK4 treatment had an augmented Pam3CSK4-stimulated phosphorylation of protein kinase A (PKA), extracellular signal-regulated kinase (ERK), and IκB-α; stimulation of TLR2, cyclooxygenase-2, and interleukin-6 functions; and suppression of the activation of PGE2 receptor 4. Thus, Pam3CSK4-induced inflammatory responses through TLR2 signaling in bEECs were enhanced by exogenous PGE2 pre-treatment.

Bone cements have been used in the clinical setting to fill bone defects resulting from bone tumors. However, traditional bone cements do not have the function to kill tumor cells. This study develops a new type of tricalcium silicate (CS) based functional bone cement with excellent photothermal performance for the minimally invasive therapy of bone defects as well as bone tumors. Graphene oxide (GO) was introduced into the CS cement by co-precipitation of CS particles with GO nanosheets to form a CS/GO composite material based on charge interactions between the CS and GO. The incorporation of GO enhanced the self-setting properties of CS and endowed the cement with excellent photothermal performance with the irradiation of near-infrared light. Besides this, the temperature of the composite cement could be regulated by adjusting the laser power and the GO content, where the rising temperature significantly inhibited the growth of subcutaneous tumor tissue in vivo. In addition, the hydration process and development of the early compressive strength of the composite cement could be modulated based on its photothermal performance. Moreover, the CS/GO composite cement retained the bioactivity of CS to promote cell proliferation and the alkaline phosphate activity of MC3T3-E1. Therefore, the CS/GO composite cement holds great promise as a new type of functional bone cement with photothermal performance for bone tumor therapy and bone defect repair.

BACKGROUND The development and progression of hepatocellular carcinoma (HCC) are associated with obesity and hepatosteatosis. AMP-activated protein kinase (AMPK) regulates metabolic homeostasis. This study aimed to investigate the effects of treatment with the adenosine monophosphate (AMP) analog, 5-aminoimidazole-4-carboxamide ribonucleotide (AICAR) on hepatosteatosis in a mouse model fed a high-fat diet (HFD), and on hepatocellular carcinoma (HCC) induced by diethylnitrosamine (DEN) in the HFD mouse model. MATERIAL AND METHODS Male C57BL/6 male mice from two weeks of age were fed a high-fat diet, resulting in hepatosteatosis. HFD mice (15-20 per group) were treated with AICAR and without AICAR. HFD mice were treated with DEN, with and without AICAR. Mouse liver tissues were examined histologically using lipid histochemical stains, immunohistochemistry, and immunofluorescence. Levels of cytokines, alanine transaminase (ALT), triacylglyceride (TAG), and apoptosis were determined. Western blot was used to detect AMPK, pAMPK, STAT3, and pSTAT3. Real-time polymerase chain reaction (RT-PCR) detected expression of the ACL, FAS, CD36, ATGL, CPT1, and IL6 genes. RESULTS In the HFD mouse model, AICAR treatment inhibited hepatic lipid synthesis and IL-6 expression. In the DEN-treated mice, AICAR treatment reduced tumorigenesis, IL-6 signaling, and STAT3 activation. Short-term AICAR treatment had no significant effect in advanced HCC. CONCLUSIONS In an HFD mouse model, treatment with AICAR reduced the development of hepatosteatosis, and following treatment with the liver carcinogen, DEN, AICAR reduced the development of HCC. These preliminary findings support further studies on the role of AICAR in fatty liver disease and HCC.

Five new cholestane glycosides, named parisfargosides A-E (1-5), were isolated from the rhizomes of Paris fargesii. Their structures were elucidated on the basis of UV, HR-ESI-MS, 1D and 2D NMR data as well as chemical methods. The structures of all compounds contained α, β-unsaturated ketone unit. Compounds 3-5 possessed a 16,23-cyclocholest skeleton with 6/6/6/5/5 condensed ring, and the absolute configurations of C-16 and C-23 were confirmed according to ROESY spectra with pyridine‑d

Background We studied the efficacy and safety of ustekinumab (UST) vs adalimumab (ADA) through 1 year in biologic-naïve patients (pts) with moderate-to-severe Crohn’s disease. Methods SEAVUE was a multicenter, randomized, blinded, parallel-group, active-controlled study in adults with CD Activity Index (CDAI) scores ≥220/≤450. Biologic-naïve pts failing/intolerant to conventional therapy with any size ulcer on baseline (BL) ileocolonoscopy were eligible. Pts were randomized 1:1 to UST (⁓6mg/kg IV at BL then 90mg SC every 8 weeks [Ws]) or ADA (160/80mg SC at BL/W2, then 40mg SC every 2 Ws) per US-approved regimens (no dose modifications). Primary endpoint was clinical remission at W52 (CDAI Results 386 pts were randomized to UST or ADA. BL demographics and disease characteristics were balanced between groups and indicative of pts with early, moderate-to-severe CD (median CD duration, 2.58 years; CDAI, 289.5; SES-CD, 8.0). At W52, 65% of UST-treated and 61% of ADA-treated pts achieved clinical remission (Δ=4.0%; 95% CI, -5.5%, 13.5%; p=0.417). Major secondary endpoints, including endoscopic remission, were similar between groups (Table 1), as were remission rates at assessment points through W52. Some other secondary endpoints showed numerical (not statistical) differences between UST and ADA (Table 1). Key safety events are summarized in Table 2. Among UST-treated and ADA-treated pts, 34.0% and 40.5% had infections, 2.6% and 7.2% had serious adverse events (AEs) of worsening CD, and 6.3% and 11.3% had AEs that led to discontinuation (DC) of study drug, respectively. One ADA-treated pt had active pulmonary TB. Injection-site reactions associated with active treatment occurred in 1.0% of UST-treated and 10.3% of ADA-treated pts. Overall, 15.2% of UST-treated and 23.6% of ADA-treated pts DC before W52. Reasons for DC were primarily lack of efficacy (UST, 2.1% vs ADA, 5.1%), AEs (UST, 5.7% vs ADA, 10.7%), and withdrawal of consent (UST, 5.8% vs ADA, 5.1%). Time to treatment DC was longer with UST vs ADA (post hoc analysis). Conclusion Both UST and ADA were highly effective in this population of biologic-naïve pts. Rates of clinical remission at W52 were not statistically significantly different between treatment groups. DC rates were numerically lower for UST. Safety results were consistent with prior experience for both treatments.

Background: Gallbladder drainage plays a key role in the management of acute cholecystitis (AC) patients. Percutaneous transhepatic gallbladder drainage (PTGBD) is commonly used while endoscopic naso-gallbladder drainage (ENGBD) serves as an alternative. Methods: A single center, prospective randomized controlled trial was performed. Eligible AC patients were randomly assigned to ENGBD or PTGBD group. Randomization was a computer-generated list with 1:1 allocation. All patients received cholecystectomy 2–3 months after drainage. The primary endpoint was abdominal pain score, and the intention-to-treat population was analyzed. (ClinicalTrials.gov: NCT03701464). Findings: Between Oct 1, 2018 and Feb 29, 2020, 22 out of 61 consecutive AC patients were enrolled in the final analysis. The mean abdominal pain scores before drainage, and at 24, 48, and 72 h after drainage in ENGBD were 6.9 ± 1.1, 4.3 ± 1.2, 2.2 ± 0.8 and 1.5 ± 0.5, respectively, while those of PTGBD were 7.4 ± 1.2, 6.2 ± 1.2, 5.3 ± 1.0 and 3.7 ± 0.9; and the mean gallbladder area tenderness scores were 8.4 ± 1.2, 5.7 ± 0.9, 3.5 ± 0.7, 2.5 ± 0.5 for ENGBD and 8.6 ± 0.9, 7.3 ± 1.0, 7.4 ± 0.5, 4.8 ± 0.9 for PTGBD. The mean abdominal pain and gallbladder area tenderness scores of the ENGBD significantly decreased than the PTGBD (group × time interaction P

Background To date, the literature directly comparing the translabyrinthine approach and retrosigmoid approach in the operation of patients with vestibular schwannoma was limited. We aimed to evaluate postoperative complications between translabyrinthine approach and retrosigmoid approach for treating vestibular schwannoma patients. Material and Method Potential publications were selected from PubMed, Web of Science and Cochrane Library. Gray relevant studies were manually searched. We set the searching time spanning from the creation date of electronic engines to February 2020. STATA version 12.0 was exerted to process the pooled data. Results A total of 9 literature included in the study, involving 2429 patients, hails from the Germany, USA, Canada, Italy, and France. Of these 2429 patients with vestibular schwannoma, there were 1628 cases from the translabyrinthine approach group versus 801 cases from the retrosigmoid approach group. The results demonstrated that the translabyrinthine approach group was associated with a lower rate of tinnitus (OR = 2.687; 95 %CI, 1.167−6.191; P = 0.02) and cranial nerve deficit (OR = 2.946; 95 %CI, 1.562−5.557; P = 0.001). And the translabyrinthine approach group was associated with a higher total resection rate (OR = 0.246; 95 %CI (0.071−0.848); P = 0.026). However, no statistic differences were found in the incidence of the near total (OR = 0.751; P = 0.351), subtotal resection (OR = 3.664; P = 0.109), postoperative facial nerve dysfunctions (OR, 0.763; P = 0.626), postoperative meningitis (OR = 2.7; P = 0.279), cerebrospinal fluid leak (OR = 1.225; P = 0.777), postoperative headache (OR = 1.412; P = 0.339), ophthalmic complications (OR = 0.87; P = 0.59), and vascular complications (OR = 2.501; P = 0.139). Conclusion Based on current evidence, the translabyrinthine approach was associated with a higher rate of total resection and a lower rate of the tinnitus and cranial nerve deficit. But the risk of cranial nerve deficit was clearly affected by the preoperative status. And a translabyrintine approach could imply a complete sensorineural hearing loss, which contribute to the lower rate of postoperative tinnitus. Consequently, more evidence-based researches are needed to supplement this opinion.

Teeth are important for our life, and enamel, as the outermost layer of the tooth, plays a key role in maintaining the function and health of the tooth. Regeneration of acid eroded enamel is a big challenge due to the lack of living cells in the enamel. Here, we propose a novel way to chemically synthesize the enamel structure by mimicking the interaction of amorphous calcium phosphate (ACP) and acidic proteins during the formation of natural enamel. The process includes the formation of ACP in situ by acid etching and then the formation of a Ca-rich polypeptide-ACP complex on acid etched enamel apatite crystals, the oriented nucleation and growth of apatite nano-crystals along the acid etched enamel apatite crystals, and infiltration of a regenerated enamel apatite structure with dental resin. The synthesized enamel reveals not only excellent mechanical properties, which are highly close to those of original natural enamel, but also reveals high chemical stability against acid erosion. This innovative method may create potential applications of the functional artificial enamel for repairing damaged tooth enamel.

BACKGROUND: Chronic hepatitis B virus infection remains a major global public health problem. Peginterferon-alpha-2a (PEG-IFN) has direct antiviral and immunoregulatory effects, and it has become one of the first choice drugs for the treatment of chronic hepatitis B (CHB). Cytokines play an important role in immunity, and they directly inhibit viral replication and indirectly determine the predominant pattern of the host immune response. AIM: To determine the correlation between cytokine/chemokine expression levels and response to PEG-IFN treatment in patients with CHB. METHODS: Forty-six kinds of cytokines were analyzed before PEG-IFN therapy and at 24 wk during therapy in 26 CHB patients. RESULTS: The monokine induced by INF-γ (CXCL9) and serum interferon-inducible protein 10 ( IP-10) levels at baseline were higher in virological responders than in non-virological responders (NRs) and decreased during treatment, whereas the NRs did not exhibit significant changes. The macrophage inflammatory protein 1d (MIP-1d) levels at baseline and during treatment were significantly higher in the virological responders than in the NRs, while thymus and activation-regulated chemokine (TARC) levels at baseline and during treatment were significantly lower in the virological responders than in the NRs. The CXCL9, IP-10, MIP-1d, and TARC baseline levels exhibited the expected effects for interferon treatment. The area under the receiver operating characteristic curve values of CXCL9, IP-10, MIP-1d, and TARC for predicting virological responses were 0.787, 0.799, 0.787, and 0.77 (P = 0.01, 0.013, 0.01, and 0.021), respectively. CONCLUSION: We found that cytokine levels before and during treatment may represent potential biomarkers to select CHB patients who can respond to PEG-IFN. Therefore, cytokines can be used as an indicator of antiviral drug selection before CHB treatment.

Background: Unfractionated heparin (UFH), despite its limitations, has been used as the primary anticoagulant alternative during the percutaneous coronary intervention (PCI). Some studies indicated that intravenous enoxaparin could be an effective and safe option. Our team used enoxaparin alone at one time according to the guidelines (Class IIA) and found a little catheter thrombosis during PCI. We recommend a new anticoagulation strategy using enoxaparin in combination with UFH. Enoxaparin has a more predictable anticoagulant response with no need of repeatedly monitoring anticoagulation during PCI. This retrospective study aimed to evaluate the efficacy and safety of using enoxaparin in combination with UFH in PCI patients with complex coronary artery disease. Methods: Between January 2015 and April 2017, 600 PCI patients who received intravenous UFH at an initial dose of 3000 U plus intravenous enoxaparin at a dose of 0.75 mg/kg (observation group) and 600 PCI patients who received UFH at a dose of 100 U/kg (control group) were consecutively included in this retrospective study. The endpoints were postoperative 48-h thrombolysis in myocardial infarction (TIMI) bleeding and transfusion and 30-day and 1-year major adverse cardio-cerebrovascular events (MACCE). Results: Baseline clinical, angiographic, and procedural characteristics were similar between groups, except there was less stent implantation per patient in the observation group (2.13 vs. 2.25 in the control group, P = 0.002). TIMI bleeding (3.3% vs. 4.7%) showed no significant difference between the observation group and control group. During the 30-day follow-up, the rate of MACCE was 0.9% in the observation group and 1.5% in the control group. There was no significant difference in the rates of MACCE, death, myocardial infarction, target vessel revascularization, cerebrovascular event, and angina within 30 days and 1 year after PCI between groups as well as in the subgroup analysis of transfemoral approach. Conclusions: UFH with sequential enoxaparin has similar anticoagulant effect and safety as UFH in PCI of complex coronary artery disease. Key words: Complex Coronary Heart Disease; Enoxaparin; Percutaneous Coronary Intervention; Unfractionated Heparin

Forward genetic analysis, widely used to find new gene functions, benefits from the availability of mutants. At present, based on Agrobacterium-mediated plant transformation technology, many transfer (T)-DNA transformants have been created. However, cloning their T-DNA insertion sites, which enables identification of the mutated genes, is still challenging. In this study, we improved adapter ligation-mediated polymerase chain reaction (A-PCR), which mainly utilizes the Thermal Asymmetric interlaced reaction and Degenerate sequence-recognizing restriction Endonucleases (TADE). Using the new method TADE-mediated A-PCR (TADEA-PCR), we successfully cloned 22 of all the 24 junction sites in 10 Arabidopsis thaliana L. transformants that contained 12 T-DNA insertions in total, giving a success rate of 91.7%. In most cases, the two junction sites resulting from a single T-DNA insertion were simultaneously cloned. In addition, TADEA-PCR was able to clone more than two junction sites present in one transformant containing several T-DNA insertions. Overall, TADEA-PCR is a powerful technique for cloning T-DNA insertion sites.

Background and Aims We assessed the effect of ustekinumab on health-related quality of life [HRQOL] in adults with Crohn's disease [CD]. Methods Patients with moderately to severely active CD and inadequate response or intolerance to tumour necrosis factor antagonists [UNITI-1, n = 741], or conventional therapy [UNITI-2, n = 627] were randomised to placebo, ustekinumab 130 mg, or 6 mg/kg intravenous induction therapy. At Week 8, ustekinumab-treated responders (Crohn's Disease Activity Index [CDAI] reduction ≥100 or CDAI

The effect of Ni interlayer thickness on chemical composition, microstructure and mechanical properties of laser welding of Mo and stainless steel was analyzed systematically. Experimental results indicated that with the increase in thickness of Ni interlayer, the number of Mo Fe IMCs, the hardness at the Mo-FZ interface, the width and grain size in the heat affected zone of Mo side and the thickness of Mo Fe IMCs layer decreased significantly. The maximum tensile strength attained 351 MPa for joints with 0.1 mm thick Ni interlayer. With excessive (>0.1 mm) Ni addition in the welded joint, the mechanical properties deteriorated due to the formation incomplete fusion, void and crack defects. The tensile investigation showed that the weakest area of the joint was Mo Fe IMCs layer. When an appropriate thickness of Ni interlayer is used, the Mo Fe IMCs layer can be strengthened by increasing diffusion ability of Mo to FZ and Ni concentration in the Mo Fe IMCs and restraining of Mo Fe IMCs, consequently producing high-quality welded joints.

The prostaglandin E2 receptor 2 (PTGER2) is present in the endometrium and its gene expression is accompanied with endometrial growth, however, it is unknown whether there is endometrial repair through stimulation of growth factor gene expression that is promoted by PTGER2 activation in cattle. The aim of this study was to investigate whether PTGER2 activation can induce prostaglandin-endoperoxide synthase-2 (PTGS-2) and growth factor gene expression by activating PKA and ERK signaling pathways in endometrial epithelial cells of cattle. Results demonstrated that the PTGER2 agonist, butaprost, induced cAMP/PKA and ERK activation and up-regulated PTGS-2, VEGF, CTGF, TGF-β1 and IL-8 gene expression. These activations were less after PTGER2 antagonist, AH6809, treatment. Data suggested that PTGS-2 gene expression was induced by PTGER2 activation through the PKA and ERK pathways. Furthermore, PTGER2 activation promoted several growth factor gene expressions in endometrial epithelial cells. One potential implication of this finding is that PTGER2 activation in the endometrium of cattle could induce endometrial repair by stimulating VEGF, CTGF, TGF-β1 and IL-8 gene expression.

Background Therapeutic drug monitoring is an important adjunct in optimising IBD management in patients treated with anti-TNF therapies. However, it remains unclear whether these principles apply to non-anti-TNF biologic therapies, such as the anti-IL12/23 agent, ustekinumab (UST). A follow-up analysis of the ‘mUST-DECIDE’ study explores the correlation between UST drug level and clinical outcomes. Methods 111 consecutive UST-treated adult CD patients across 11 sites in Canada from April 2017 to January 2018 were evaluated. Clinical decisions were recorded for all subjects at the single study visit and blood was drawn for TDM (Sanquin, radioimmunoassay). A retrospective chart review was completed in patients who had a follow-up visit ≥ 30 days after the baseline visit. Improved disease control (primary outcome) was defined as a composite assessment outcome meeting ≥ 1 disease control criterion (symptomatic, endoscopic/imaging, biochemical) without any of the non-response criteria (inadequate or loss of response, worsening of any disease control criteria, initiation of any CD-related medications and adverse events). Serum [UST] were categorised as therapeutic, subtherapeutic or uninterpretable based on their position in a 2 compartment PK model [subjects on Q8W dosing were assessed as per the log-linear model which projected a therapeutic level of ≥4.5 µg/ml at 4 weeks and ≥1.0 µg/ml at 8 weeks]. Results 53 patients had a clinical follow-up visit and an interpretable serum [UST]. Patients had refractory disease (89% anti-TNF-exposed, median 16.4 years since diagnosis), but clinically well (66% had baseline HBI Conclusion The sub-study did not detect any association between routine serum [UST] and short-term clinical outcomes at the next patient visit. These data broadly suggests that the routine measurement of serum UST in CD patients does not aid in disease management, though further studies across different clinical scenarios (e.g. loss of response) are warranted.

Phospholipase D4 (PLD4) is a newly identified protein expressed in microglia. However, the function of PLD4 in tumor-associated macrophages (TAMs) is unknown. In the present study, we revealed that the expression of PLD4 was located in macrophages in the colon cancer mesenchymal and lymph nodes as shown by immunohistochemical analysis. furthermore, its expression was associated with clinical staging of colon cancer. Then, THP-1 as a cell model induced into TAMs. Western blot and RT-PCR analysis showed that PLD4 was mainly presented in M1 phenotype TAMs. The secretion of pro-inflammatory cytokines in M1 macrophages was significantly reduced after the expression of PLD4 inhibited by PLD4-siRNA. Furthermore, co-cultured with condition-medium from control or PLD4-siRNA M1 macrophages for 24 h, cell apoptosis, cycle and proliferation of cancer cells improved compared to control. These results indicated that PLD4 could be involved in the activation process of M1 phenotype macrophages.

Objective To evaluate the safety and cost of early discharge compared with ordinary discharge in patients with diabetes mellitus (DM) following percutaneous coronary intervention (PCI) for acute coronary syndrome. Methods We performed a retrospective analysis of prospectively collected data from 474 patients with DM who were discharged from hospital following PCI at a regional center between 2012 and 2015. Results A total of 192 patients (40.5%) were included in the early discharge group and 282 patients (59.5%) were included in the ordinary group. Mortality and morbidity after PCI were recorded. Kaplan–Meier analysis showed similar prognosis between the two groups at 30 days and at 1 year after discharge. However, hospitalization expenses for the regular discharge group were significantly higher than those of the early discharge group (RMB65,750 vs. RMB50,983). Conclusion Our findings demonstrate that early discharge of patients with DM following PCI for acute coronary syndrome is safe compared with ordinary discharge, and may reduce hospitalization costs.

Background: The new emerging application of decompression combined with fusion comes with a concern of cost performance, however, it is a lack of big data support. We aimed to evaluate the necessity or not of the addition of fusion for decompression in patients with lumbar degenerative spondylolisthesis. Methods: Potential studies were selected from PubMed, Web of Science, and Cochrane Library, and gray relevant studies were manually searched. We set the searching time spanning from the creating date of electronic engines to August 2020. STATA version 11.0 was exerted to process the pooled data. Results: Six RCTs were included in this study. A total of 650 patients were divided into 275 in the decompression group and 375 in the fusion group. No statistic differences were found in the visual analog scales (VAS) score for low back pain (weighted mean difference [WMD], –0.045; 95% confidence interval [CI], –1.259–1.169; P = .942) and leg pain (WMD, 0.075; 95% CI, –1.201–1.35; P = .908), Oswestry Disability Index (ODI) score (WMD, 1.489; 95% CI, –7.232–10.211; P = .738), European Quality of Life-5 Dimensions (EQ-5D) score (WMD, 0.03; 95% CI, –0.05–0.12; P = .43), Odom classification (OR, 0.353; 95% CI 0.113–1.099; P = .072), postoperative complications (OR, 0.437; 95% CI, 0.065–2.949; P = .395), secondary operation (OR, 2.541; 95% CI 0.897–7.198; P = .079), and postoperative degenerative spondylolisthesis (OR = 8.59, P = .27). Subgroup analysis of VAS score on low back pain (OR = 0.77, 95% CI, 0.36–1.65; P = .50) was demonstrated as no significant difference as well. Conclusion: The overall efficacy of the decompression combined with fusion is not revealed to be superior to decompression alone. At the same time, more evidence-based performance is needed to supplement this opinion.

Studies have shown that stromal interaction molecule 1 (STIM1) is expressed in a variety of cancers and is related to tumor growth. The present study aimed to investigate the expression and roles of STIM1 in gastric carcinoma. Immunohistochemistry and western blotting revealed that STIM1 was expressed at higher levels in gastric cancer tissues (82%) than these levels in normal gastric tissues (42%). In addition, STIM1 was also expressed in tumor vascular endothelial cells. The effects of STIM1 on proliferation, apoptosis, adhesion, invasion and migration of gastric cancer cells were detected by MTT assay, flow cytometry, cell adhesion assay and Transwell assay, respectively. The results shown that STIM1 knockdown did not alter proliferation or apoptosis, but promoted cell adhesion and inhibited migration and invasion in the gastric cancer cells. In addition, STIM1 knockdown did not alter the expression or phosphorylation of mitogen-activated protein kinase (MEK) or extracellular signal-regulated kinase (ERK), implying that STIM1 affected gastric cancer cell migration through a pathway independent of the MEK/ERK pathway.

Direct welding of Mo and stainless steel is exceptionally difficult due to intrinsic brittleness of Mo and the formation of brittle Fe-Mo phases. To explore the feasibility of welding of Mo and stainless steel, the laser offset method was used in this study. Experimental results show that the offset of the laser beam toward stainless steel has a positive effect for the quality of Mo/Fe dissimilar joint. As the laser beam shifts from the Mo side to the stainless steel side, the formation of welding defects and Fe-Mo intermetallic compounds (IMCs) are effectively restricted because of the decrease amount of molten Mo. The decrease of Fe-Mo IMCs contributes to the reduction of hardness in the joints. With an increase of laser offset, the thickness of Fe-Mo IMCs layer decreased, consequently the tensile strength of joints increased first and then decreased in the laser offset range of 0.2–0.5 mm. The highest tensile strength of the joints is 290 MPa at the laser offset of 0.3 mm. All joints failed in the Fe-Mo IMCs layer with brittle fracture mode during tensile tests, indicating the weakest zone of the joint was Fe-Mo IMCs layer. A sound weld of Mo and stainless steel can be obtained if an appropriate thickness of Fe-Mo IMCs layer is produced by adjusting the laser offset.

Four new sesquiterpenoids, conyterpenols A − D (1–4), along with nineteen known analogues (5–23) were isolated from the aerial parts of Conyza japonica. The structures of 1–4 were determined through spectroscopic analysis, while their absolute configurations were determined by comparison of calculated and experimental electronic circular dichroism (ECD) spectra. Conyterpenol D (4) was a new type of sesquiterpenoid with a seven-membered lactone ring. Compounds 1–23 were evaluated for their inhibitory activity against LPS-induced nitric oxide production in RAW264.7 macrophages and cytotoxicity against human hepatoma cell line (HepG2) and human breast adenocarcinoma cell line (MCF-7). Compounds 3, 4, and 12 displayed moderate inhibition against NO production with IC50 values in the range of 26.4–33.6 μM. And all compounds showed no obvious cytotoxicity against these two cancer cell lines at 100 μM.

The uptake and distribution of four heavy metals, including copper (Cu), cadmium (Cd), lead (Pb) and zinc (Zn), and those of total phosphorus (TP) in 30 plants in North China were investigated through pot trial experiments. Accumulation and distribution of heavy metals or TP were associated with plant species, tissues, metal elements and pollutant loading. The highest amount of heavy metal and TP accumulation was found in the whole plants of Hylotelephium erythrostictum (Miq.) H. Ohba (C1) and Chlorophytum laxum R. Br. (L4), respectively. Considering the biological concentration factor, translocation factor, retention factor and biomass indices, C1 is the suitable plant for Cd and Cu uptake, whereas Hosta plantaginea (Lam.) Aschers (L3) and Viola verecunda A. Gray (V1) are the suitable plants for Pb removal. Rehmannia glutinosa (Gaetn.) Libosch. ex Fisch. (S1) and L4 can be chosen for Zn and TP removal, respectively. Cluster analysis was applied to select suitable plants for heavy metal and TP removal. Results showed that C1, L4 and Pennisetum alopecuroides (L.) Spreng (G1) have a good capability of accumulating heavy metals and TP. Results demonstrated that the plant species rather than the families considerably influenced the accumulation of pollutants.

Multipotent human bone marrow mesenchymal stem cells (hBMSCs) are commonly used as seed cells in bone tissue engineering, but their clinical application is limited due to two challenges. One is the expansion of hBMSCs without loss of the stemness, and the other is the stimulation of osteogenic differentiation of hBMSCs when combined with biomaterials. In this study we demonstrated an approach by firstly elucidating the functional effects and optimal concentrations of Si and Sr ions on the proliferation and osteogenic differentiation of hBMSCs, and then designing bioactive bioceramic/alginate hydrogels which could release Si and Sr bioactive ions in the same optimal concentrations range for activation of the cells in vivo. The results showed that Si and Sr ions could synergistically stimulate cell proliferation without losing the stemness. Furthermore, at higher concentrations, Si and Sr ions stimulated osteogenic differentiation instead of enhancing proliferation. The designed bioactive hydrogels revealed activity to stimulate not only the osteogenic differentiation of encapsulated hBMSCs, but also the blood vessel formation in vivo. These results suggested that the design of biomaterials based on the biological function of different material elements was an effective approach for bone tissue engineering applications. Statement of Significance The clinical application of multipotent human bone marrow mesenchymal stem cells (hBMSCs) in bone tissue engineering is limited due to two challenges. One is the expansion of cells without loss of the stemness, and the other is the stimulation of osteogenic differentiation of hBMSCs within the biomaterial scaffolds. Herein, we demonstrated an approach by firstly elucidating the functional effects and optimal concentrations of Si and Sr ions on the proliferation without losing stemness and osteogenic differentiation of hBMSCs, and then designing a bioactive bioceramic/alginate hydrogel which could release Si and Sr ions for in vivo activation of cells. The bioactive hydrogels revealed activity to stimulate not only osteogenic differentiation of encapsulated hBMSCs, but also the blood vessel formation in vivo. Our work provided an effective approach to design effective biomaterials for tissue engineering.

Phospholipid hydroperoxide glutathione peroxidases (PHGPXs) are essential enzymes of the cellular antioxidant defense system during insect-plant interactions. However, little attention has been devoted to the functional characterization of PHGXPs in the whitefly Bemisia tabaci. Here, we report the identification and characterization of two PHGPX genes, designated as BtQ-PHGPX1 and BtQ-PHGPX2 from the Mediterranean species of the B. tabaci complex. Sequence analysis indicated that the length of BtQ-PHGPX1 is of 942 bp with a 729 bp open-reading frame (ORF) encoding 242 amino acids, and BtQ-PHGPX2 is of 699 bp with a 567 bp ORF encoding 188 amino acids. Sequence alignment analysis showed that BtQ-PHGPX1 and BtQ-PHGPX2 shared high similarity with other known PHGPXs. The NVASXCGXT, FPCNQFXXQEPG, and IKWNFXKFLV surrounded the reactive cysteine, glutamine, and tryptophan residues, respectively. Recombinant BtQ-PHGPX1 and BtQ-PHGPX2 were overexpressed in Escherichia coli and purified. quantitative reverse transcription-polymerase chain reaction (qRT-PCR) analysis with whiteflies of different development stages showed that the mRNA levels of BtQ-PHGPX2 were significantly higher in larvae than in other stages. The mRNA levels of BtQ-PHGPX2 were significantly higher than BtQ-PHGPX1 during all the developmental stages. The mRNA levels of BtQ-PHGPX1 and BtQ-PHGPX2 in female adults were relatively higher than in male adults. The expression of BtQ-PHGPX1 and BtQ-PHGPX2 was induced by the insecticide imidacloprid. These results suggest that BtQ-PHGPX1 and BtQ-PHGPX2 may participate in detoxification of oxidative hazards in B. tabaci.

With the wind power developing fast in the world, the large scale of wind power integration in power system leads to great challenges, and the wind power forecasting will play a key role in dealing with these challenges. A wind power short-term forecasting method based on grey system is introduced in this paper. Firstly, a basic model of grey prediction method is given. Then, in order to smoothen the basic data for the grey modeling, a self adaptive grey prediction method is developed. Finally, the result of prediction for a test system of wind power are presented and the effectiveness of the method given by the paper has been proved.

In order to improve the modeling efficiency of RBF neural network, an Artificial Fish Swarm Algorithm (AFSA) training algorithm with an adaptive mechanism is proposed. In the training algorithm, the search step size and visible domain of AFSA algorithm can be adjusted dynamically according to the convergence characteristics of artificial fish swarm, and then the improved AFSA algorithm is used to optimize the parameters of RBF neural network. The example shows that, the proposed model is a better approximation performance for the nonlinear function.

Some engineering materials have excellent performances, but the machining of these materials is a problem. It is very inadequate to meet machining requirement only using traditional cutting tool materials. Therefore, exploring the machinability of difficult-to-machine materials and applying appropriate cutting tool materials have drawn much attention in metal cutting industry for guarantied product quality and productivity. Cubic boron nitride (CBN) has been recognized as one of the most suitable cutting tool materials due to its high hardness, high wear resistance, high chemical inertness, and excellent chemical stability in high temperature. Research on various aspects of CBN cutting performances has been conducted in recent years. This paper presents the progress on machining difficult-to-machine materials using CBN cutting tools.

Smooth Support Vector Regression (SSVR) is new modified edition of traditional support vector regression for better performance. To further improve the modeling capability of SSVR, it is necessary to take into account the feature extraction based on Independent Component Analysis (ICA) before SSVR. Simulation on the example of function approximation shows that the result of SSVR based on ICA feature extraction is better than that of SSVR without ICA preprocess.

To predict the fault severity of aircraft and its equipments, a modeling and predicting method based on Relevance Vector Machine (RVM) under Bayesian framework is proposed to solve the problem. First the principle and realization step of RVM are detailed, and then RVM is introduced in prediction of fault severity of aircraft and its equipments. The prediction result indicates that the proposed model has a good prediction to fault severity of aircraft and its equipments.

Gangmin Wang,1,* XiaoLong Gao,2,* GuoJun Gu,2 ZhiHong Shao,2 MingHua Li,2 PeiJun Wang,2 JianRong Yang,3 XiaoJun Cai,4 YongYong Li4 1Department of Urology, Huashan Hospital, Fudan University, 2Department of Radiology, Tongji Hospital, School of Medicine, Tongji University, Shanghai, 3Department of Hepatobiliary Surgery, Third People’s Hospital of Guangxi Zhuang Autonomous Region, Nanning, 4Institute for Advanced Materials and Nano Biomedicine, School of Material Science and Engineering, Tongji University, Shanghai, People’s Republic of China *These authors contributed equally to this work Abstract: A polyethylene glycol–poly(ε-benzyloxycarbonyl-l-lysine) (PEG-SS-PLL) block copolymer based on a disulfide-linked, novel biodegradable catiomer bearing a PEG-sheddable shell was developed to avoid “PEG dilemma” in nanoparticle intracellular tracking of PEG-PLL where PEG was nondegradable. However, PEG-SS-PLL catiomers have not been used to deliver small interfering VEGF RNA (siVEGF) in antiangiogenesis gene therapy. In this study, we aimed to investigate whether this novel biodegradable catiomer can deliver siVEGF into cancer cells and at the same time have an antitumor effect in a xenograft mouse model. It was found that PEG-SS-PLL efficiently delivered siVEGF with negligible cytotoxicity, and significantly decreased the expression of VEGF at both the messenger-RNA and protein levels both in vitro and in vivo, and thus tumor growth was inhibited. Our findings demonstrated that PEG-SS-PLL/siVEGF could potentially be applied to antiangiogenesis gene therapy for hepatocellular carcinoma. Keywords: polyethylene glycol, poly lysine, disulfide, VEGF, antiangiogenesis, hepatocellular carcinoma, siRNA

Objectives To evaluate regulation of the endoplasmic reticulum stress (ERS) response by acupuncture and to investigate its neuroprotective effect on brain injury caused by heroin addiction. Methods A total of 48 male Sprague-Dawley rats were randomly divided into a healthy control group (Control), an untreated heroin exposed group (Heroin) and a heroin exposed group receiving electroacupuncture (EA) treatment at GV14 and GV20 (Heroin+acupuncture) with n=16 rats per group. A rat model of heroin addiction was established by intramuscular injection of incremental doses of heroin for 8 consecutive days. A rat model of heroin relapse was established according to the exposure (addiction) → detoxification method. Apoptotic changes in nerve cells in the hippocampus and ventral tegmental area (VTA) were evaluated in each group of rats using terminal deoxynucleotidyl transferase dUTP nick end labelling (TUNEL) assay. PERK, eIF2a, CHOP, IRE1 and JNK gene expression and protein expression were measured using quantitative real-time PCR (RT-qPCR) assay and immunohistochemical assay, respectively. Results The total number of positive nerve cells in the hippocampus and VTA was significantly lower in the Heroin+acupuncture group than in the Heroin group (pConclusion The acupuncture-regulated ERS response appears to mediate the neuroprotective effect of acupuncture in heroin-addicted rats with brain injury. Inhibition of CHOP and JNK upregulation and reduction of nerve cell apoptosis may be the main mechanisms underlying the effects of acupuncture on heroin addiction-induced brain injury.

Using a soil column experiments to analyze the influence of different density of one dimension vertical infiltration of water infiltration rate, cumulative infiltration and wetting front. The experimental results showed that the bulk density of the infiltration rate, cumulative infiltration and wetting front has a significant impact. Infiltration rate, cumulative infiltration and wetting front were decreased with increasing density in the same period of infiltration. The greater the soil bulk capacity, the larger the infiltration decrease ration μ and η, respectively compared to the based accumulative infiltration and the based wetting front depth.

To improve the ability of fault diagnosis for mechanical equipment, a Radial Basis Function Neural Network (RBFNN) diagnosis method based on Unscented Kalman Filter (UKF) algorithm is proposed. In the algorithm, at first, UKF algorithm is used to estimate the parameters of RBFNN, and then the proposed method is introduced into the fault diagnosis of mechanical equipment. The simulation indicates that the established model has a good diagnosis performance for mechanical fault diagnosis.

To describe the complex nonlinear characteristics of a system accurately, a Wavelet Neural Network (WNN) identification model based on Artificial Fish Swarm (AFS) algorithm is proposed. In the identification model, AFS algorithm is introduced to optimize the parameters combination of the network for the satisfactory WNN model. The simulation shows that, the proposed method is a good nonlinear identification capability, and is feasible to identify the nonlinear system.

To accurately depict the dynamic characteristics for aircraft stall by aerodynamic model, a Wavelet Neural Network (WNN) stall aerodynamic modeling method based on Particle Swarm Optimization (PSO) algorithm and Artificial Fish Swarm (AFS) algorithm is proposed. Numerical examples show that the proposed method has a good prediction precision, and it is also effective and feasible to build the aerodynamic model from flight data for aircraft stall.

To understand the characteristics of aircraft stall for better aerodynamic model, the physical essence of the stall phenomena of aircraft is first introduced, and then a Wavelet Neural Network (WNN) is proposed to set up the stall aerodynamic model. Numerical examples indicates that through the deep cognition of the stall phenomena of aircraft the proposed stall aerodynamic method has a better accuracy than the traditional neural network and is also effective and feasible.

To accurately identify the nonlinear model for aircraft, maximum likelihood method is introduced to analyze the flight test data for compatibility check, which can satisfy the kinematics equations of aircraft at the same time. The experiment shows that the proposed method has a good compatibility check effect, and it is also effective and feasible for flight test data for aircraft.

It is difficult to realize an accurate and reliable diagnosis in the rotating machinery. To solve this problem, a Wavelet Neural Network (WNN) diagnosis model based on EKF algorithm is proposed. In the model, EKF algorithm is introduced to optimize the parameters of WNN, and then the built WNN model is used to diagnose the faults of the rotating machinery. The experiment shows that, the proposed model has a good diagnosis capability in the field of the rotating machinery.

For the aerodynamic modeling problem from measured flight data for aircraft stall, a WNN aerodynamic modeling method is proposed. According to the aerodynamic modeling flow from flight data for aircraft stall, WNN is introduced to establish the aerodynamic model of aircraft for stall phenomenon. Experiment shows that the method can improve the modeling ability of WNN, and is suitable for actual aerodynamic modeling for aircraft stall.

The urban rail transport is the backbone of urban public transport. It alleviates urban traffic congestion and plays an important role. Survey and determination of the passenger walking time in urban rail transit station passages is the basic work to realize train coordination between lines and to reduce the passenger waiting time in transferring. The paper focuses on the passenger walking time on transfer pedestrians from the statistical point of view. Finally, Beijing Dongdan transfer station is selected as an example. This study has some practical applications.

An aerodynamic modeling method based on WNN with Partial Least Squares (PLS) is proposed. In the method, PLS first is applied to extract the feature of original aerodynamic data samples, and then the obtained feature is used to establish the WNN aerodynamic model for aircraft stall from flight test data. Simulation results are given to illustrate that the proposed method is effective and feasible.