Search

With the development of building materials manufacturing enterprises, the ordering, transportation and storage of raw materials have become important factors affecting the production of manufacturing enterprises. In order to ensure the normal production and operation activities and reduce the production cost as much as possible, enterprises need to reasonably adjust the relevant raw material ordering scheme and transportation scheme to ensure both the considerable production efficiency and the healthy and sustainable production. In this paper, a mathematical model based on sequential heuristic algorithm and integer programming is established to develop the most economical ordering scheme and the least lossy transportation scheme for raw materials in the process of production operation.

One of the main obstacles in biocatalysis is the substrate inhibition (SI) of enzymes that play important roles in biosynthesis and metabolic regulation in organisms. The promiscuous glycosyltransferase UGT72AY1 from Nicotiana benthamiana is strongly substrate-inhibited by hydroxycoumarins (inhibitory constant Ki < 20 µM), but only weakly inhibited when monolignols are glucosylated (Ki > 1000 µM). Apocarotenoid effectors reduce the inherent UDP-glucose glucohydrolase activity of the enzyme and attenuate the SI by scopoletin derivatives, which could also be achieved by mutations. Here, we studied the kinetic profiles of different phenols and used the substrate analog vanillin, which has shown atypical Michaelis–Menten kinetics in previous studies, to examine the effects of different ligands and mutations on the SI of NbUGT72AY1. Coumarins had no effect on enzymatic activity, whereas apocarotenoids and fatty acids strongly affected SI kinetics by increasing the inhibition constant Ki. Only the F87I mutant and a chimeric version of the enzyme showed weak SI with the substrate vanillin, but all mutants exhibited mild SI when sinapaldehyde was used as an acceptor. In contrast, stearic acid reduced the transferase activity of the mutants to varying degrees. The results not only confirm the multi-substrate functionality of NbUGT72AY1, but also reveal that the enzymatic activity of this protein can be fine-tuned by external metabolites such as apocarotenoids and fatty acids that affect SI. Since these signals are generated during plant cell destruction, NbUGT72AY1 likely plays an important role in plant defense by participating in the production of lignin in the cell wall and providing direct protection through the formation of toxic phytoalexins.

The notions ofos{o}_{s}-convergence andS∗{S}^{\ast }-doubly quasicontinuous posets are introduced, which can be viewed as common generalizations of Birkhoff’s order-convergence andS∗{S}^{\ast }-doubly continuous posets, respectively. We first consider the relationship betweenos{o}_{s}-convergence and B-topology and show that the topology induced byos{o}_{s}-convergence according to the standard topological approach is the B-topology precisely. Then, the topological characterization for theS∗{S}^{\ast }-doubly quasicontinuity is presented. It is proved that a poset isS∗{S}^{\ast }-doubly quasicontinuous iff the poset equipped with the B-topology is locally hyperclosed iff the lattice of all B-open subsets of the poset is hypercontinuous. Finally, the order theoretical condition for theos{o}_{s}-convergence being topological is given and the complete regularity of B-topology onS∗{S}^{\ast }-doubly quasicontinuous posets is explored.

Uridine diphosphate-dependent glycosyltransferases (UGTs) mediate the glycosylation of plant metabolites, thereby altering their physicochemical properties and bioactivities. Plants possess numerous UGT genes, with the encoded enzymes often glycosylating multiple substrates and some exhibiting substrate inhibition kinetics, but the biological function and molecular basis of these phenomena are not fully understood. Since the promiscuous monolignol/phytoalexin NbUGT72AY1 exhibits substrate inhibition (K

To explore the potential role of Lin28a in the development of restenosis after percutaneous transluminal angioplasty, double‐balloon injury surgery and mono‐balloon injury surgery were used to establish restenosis and atherosclerosis models, respectively, so as to better distinguish restenosis from atherosclerotic lesions. Immunohistochemical analysis revealed that significantly higher expression of Lin28a was observed in the iliac arteries of restenosis plaques than that of atherosclerosis plaques. Immunofluorescence studies showed the colocalization of Lin28a with α‐smooth muscle actin in restenosis plaques, rather than in atherosclerosis plaques, which suggested that Lin28a might be related to the unique behaviour of vascular smooth muscle cells (VSMCs) in restenosis. To further confirm above hypothesis, Lin28a expression was up‐regulated by transfection of Lenti‐Lin28a and inhibited by Lenti‐Lin28a‐shRNA transfection in cultured VSMCs, and then the proliferation and migration capability of VSMCs were detected by EdU and Transwell assays, respectively. Results showed that the proliferation and migration of VSMCs were significantly increased in accordance with the up‐regulation of Lin28a expression, while above behaviours of VSMCs were significantly suppressed after inhibiting the expression of Lin28a. In conclusion, the up‐regulation of Lin28a exerts its modulatory effect on VSMCs’ proliferation and migration, which may play a critical role in contributing to pathological formation of restenosis.

This study explored whether sufentanil, a lipophilic opioid, can protect against myocardial ischemia-reperfusion (I/R) injury via regulating Sestrin 2 (Sesn2) expression. The expression of Sesn2 was measured in the blood of patients with myocardial I/R after sufentanil administration. H9c2 cells were applied to establish I/R injury by oxygen-glucose deprivation and reoxygenation (OGD/R). After treatment with 5, 10 and 20 μmol/L sufentanil, the expression of Sesn2 was examined. Then, shRNA-Sesn2 was transfected into H9c2 cells. The concentrations of creatine kinase (CK), CK isoenzymes (CK-MB), cardiac troponin I (cTnI), inflammation-related factors and oxidative-related factors were sequentially determined by kits. Western blotting was exploited to determine the expression of AMP-activated protein kinase (AMPK) pathway proteins. The results revealed that the expression of Sesn2 was increased in patients after administration with sufentanil. OGD/R intervention upregulated the expression of Sesn2, which continued to increase in a dose-dependent manner following treatment with sufentanil. Moreover, sufentanil attenuated the concentrations of CK, CK-MB and cTnl induced by OGD/R in H9c2 cells. This effect was reversed after Sesn2 silencing. Meanwhile, the levels of inflammatory factors and oxidative stress were notably decreased when cells were treated with sufentanil, and these inhibitory effects were alleviated after transfection with shRNA-Sesn2. Furthermore, sufentanil enhanced the phosphorylation of AMPK and its downstream acetyl CoA carboxylase (ACC), whereas Sesn2 silencing inhibited the expression of the above proteins. These findings demonstrated that sufentanil could attenuate inflammation and oxidative stress in myocardial I/R injury via upregulating Sesn2 expression and activating the AMPK pathway.

One of the malignant transformation hallmarks is metabolism reprogramming, which plays a critical role in the biosynthetic needs of unchecked proliferation, abrogating cell death programs, and immunologic escape. However, the mechanism of the metabolic switch is not fully understood. Here, we found that the S-nitrosoproteomic profile of endogenous nitrogen oxide in ovarian cancer cells targeted multiple components in metabolism processes. Phosphofructokinase (PFKM), one of the most important regulatory enzymes of glycolysis, was S-nitrosylated by nitric oxide synthase NOS1 at Cys351. S-nitrosylation at Cys351 stabilized the tetramer of PFKM, leading to resist negative feedback of downstream metabolic intermediates. The PFKM-C351S mutation decreased the proliferation rate of cultured cancer cells, and reduced tumor growth and metastasis in the mouse xenograft model. These findings indicated that S-nitrosylation at Cys351 of PFKM by NOS1 contributes to the metabolic reprogramming of ovarian cancer cells, highlighting a critical role of endogenous nitrogen oxide on metabolism regulations in tumor progression.

Background: The excessive proliferation and migration of VSMCs is the main cause of restenosis (RS). Our previous results suggested that overexpression of Lin28a is responsible for this “malignant” behaver of VSMCs. However, the mechanisms driving the specific VSMCs behavior in RS are far less understood. Methods and Findings: Using an atherosclerosis followed by PTA treatment rats as RS model, we discovered a decreased expression of let-7c, let-7g, let-7i, miR98 and miR202, that associated with an increased expression of Lin28a in RS plaques compared to those of atherosclerosis. Combined with in vitro results, we demonstrated that let-7c, let-7g, and miR98 were Lin28a downstream targets in RS. More importantly, the decreased expression of let-7c, let-7g, in turn, will enhance the expression of Lin28a, indicating a double-negative feedback loop between Lin28a and let-7c/let-7g, which may be responsible for the vicious behavior of the VSMCs in RS. Transfection of let-7c and let-7g in vivo by AAV9 attenuated the aggregation of VSMCs and decreased the RS plaque size. In addition, unlike the other member of let-7, let-7d downregulates Lin28a and plays a restrictive regulator on the Lin28a/let-7 loop, that may bias VSMCs fate decision. Conclusion: In this study, by using a “two-step lesion” protocol to create RS models, we discovered that the double negative feedback system of Lin28a/let-7 axis act as a regulation center in vicious behavior of VSMCs in RS. These discoveries give us a better understanding of RS in lower extremity arterial disease and expected to present opportunities for discovering new therapeutic approaches. Funding: This work was supported by the National Natural Science Foundation of China Grants (No. 81670757, 81770822, 81800732, 81900685), Shandong Provincial Natural Science Foundation of China Grants (No. ZR2017LH025, ZR2020MH101), Shandong Provincial Medicine and Health Science and Technology Development Program (No. 2017WS461), China Postdoctoral Science Foundation (No. 2020M682193). Declaration of Interest: The authors confirm that there are no conflicts of interest. Ethical Approval: The protocol was authorized by the Ethics Committee of Qilu Hospital, Shandong University.

Experiments were performed to investigate the filtration efficiency of electret filters in external electric field. The electret filter layer was located between two conductive nonwovens (electrodes). The top conductive fibrous layer was applied to a DC voltage ranging from 0 to 6.5 kV while the bottom one was grounded. At the DC voltage, a strong external electric field was generated between the two conductive electrodes, and the electret filter layer can be charged more effectively. The filtration efficiency and the quality factor (QF) were obviously increased with an increase of the applied voltage or electric field in each filter.

Objective The goal of this systematic review was to provide guidelines for treatment parameters regarding electrical stimulation by investigating its efficacy in improving muscle strength and decreasing pain in patients with knee osteoarthritis. Design Following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses standard, three electronic databases (CINAHL, PubMed, and PEDro) and gray literature were used. Randomized control trials comparing electrical stimulation and conservative physical therapy were critically appraised using the 2005 University of Oxford standard. Results Nine randomized control trials were included in our review. First, our review confirmed that neuromuscular electrical stimulation is the most effective electrical stimulation treatment in the management of knee OA, and its efficiency is higher when combined with a strengthening program. Second, frequency of at least 50 Hz and no more than 75 Hz with a pulse duration between 200 and 400 μs and a treatment duration of 20 mins is necessary for successful treatment. Conclusions For the first time, our review provides standardized clinical treatment parameters for neuromuscular electrical stimulation to be included in a strengthening program for the adult patient with knee OA. To claim cme credits Complete the self-assessment activity and evaluation online at http://www.physiatry.org/JournalCME CME OBJECTIVES: Upon completion of this article, the reader should be able to: (1) Recall the impact of quadriceps femoris weakness on joint stability; (2) Summarize the mechanism of action of neuromuscular electrical stimulation (NMES) on reducing pain and increasing muscle strength; and (3) Plan the clinical treatment parameters of NMES to be included in a strengthening program for an adult patient with knee osteoarthritis. Level Advanced. Accreditation The Association of Academic Physiatrists is accredited by the Accreditation Council for Continuing Medical Education to provide continuing medical education for physicians.The Association of Academic Physiatrists designates this Journal-based CME activity for a maximum of 1.0 AMA PRA Category 1 Credit(s)™. Physicians should only claim credit commensurate with the extent of their participation in the activity.

Background and purpose Sulfonylureas (SUs) have been suggested to have an insulin-independent blood glucose-decreasing activity due to an extrapancreatic effect. However, a lack of adequate in vivo evidence makes this statement controversial. Here, we aimed to evaluate whether glimepiride has extrapancreatic blood glucose-lowering activity in vivo. Experimental approach Sulfonylurea receptor 1 deficient (SUR1-/- ) rats were created by means of transcription activator-like effector nucleases (TALEN)-mediated gene targeting technology. Type 2 diabetic models were established by feeding a high-fat diet and administering a low-dose of streptozotocin. These rats were then randomly divided into four groups: glimepiride, gliclazide, metformin and saline. All rats were treated for 2 weeks. Key results Glimepiride decreased blood glucose levels and increased insulin sensitivity without elevating insulin levels. Gliclazide showed similar effects as glimepiride. Both agents were weaker than metformin. Further mechanistic investigations revealed that glimepiride increased hepatic glycogen synthesis and decreased gluconeogenesis, which were accompanied by the activation of Akt in the liver. Moreover, glimepiride increased both total and membrane glucose transporter 4 (GLUT4) levels in muscle and fat, which might be attributed to insulin receptor-independent IRS1/Akt activation. Conclusion and implications Glimepiride possesses an extrapancreatic blood glucose-lowering effect in vivo, which might be attributed to its direct effect on insulin-sensitive tissues. Therefore, the combination of glimepiride with multiple insulin injections should not be excluded per se.

Nitric oxide synthase 1 (NOS1) has been reported to promote various cancer processes including chemoresistance. However, the role of NOS1 in chemoresistance has remained unclear. ATP-binding cassette, subfamily G, member 2 (ABCG2) has been identified as a molecular cause of multidrug resistance in a number of cancer types, including ovarian cancer. The present study observed that in ovarian cancer cells, the expression of ABCG2 was significantly upregulated in response to cis-diamminedichloroplatinum (cisplatin/DDP) treatment, in addition the expression of NOS1 exhibited an increasing trend. Additionally, the levels of NOS1 and ABCG2 in chemoresistant ovarian cancer profiles in Gene Expression Omnibus datasets (GSE26712 and GSE51373) were higher than in chemosensitive profiles. Furthermore, overexpression of NOS1 could upregulate ABCG2 expression, and expression of ABCG2 was inhibited by NOS1 selective inhibitor (N-PLA). In assays of cell survival, NOS1 appeared to increase the potential for DDP resistance, and this effect was reversed by addition of ABCG2 inhibitor (verapamil). The present study indicated that NOS1-induced chemoresistance was partly mediated by the upregulation of ABCG2 expression. This result suggests a link between the expression of NOS1 and the ABCG2-associated chemoresistance in ovarian cancer.

The nanostructured Al 2 O 3 –13 wt% TiO 2 coatings were fabricated by atmospheric plasma spraying (APS) on the surface of resin-based composites. The mechanical and tribological properties of coatings were investigated systematically. The results reveal that the hardness and bonding strength of the coatings reach the optimization when the spraying current is 650 A. The friction coefficient of the coatings remains at 0.2 during the steady wear stage. The wear resistance of the coatings is the highest at spraying current range from 600 A to 650 A.

// Chunmei Xu 1, * , Junyu Zhao 1, * , Xiaojun Zhou 1 , Rui Zhang 1 , Tianyue Xie 3 , Zhiwei Zou 2 , Lin Liao 1 and Jianjun Dong 2 1 Department of Endocrinology, Shandong Provincial Qianfoshan Hospital, Shandong University, Jinan, China 2 Department of Medicine, Division of Endocrinology, Qilu Hospital of Shandong University, Shandong University, Jinan, China 3 Department of Endocrinology, Shandong Provincial Qianfoshan Hospital, Shandong University of Traditional Chinese Medicine, Jinan, China * Co-first authors and equal contribution to this work Correspondence to: Lin Liao, email: liaolin009@sina.com Jianjun Dong, email: cwc_ll@sdu.edu.cn Keywords: liver enzyme abnormalities; thiazolidinediones; metformin; randomized controlled trials; meta-analysis Received: August 01, 2017 Accepted: December 05, 2017 Published: January 13, 2018 ABSTRACT Background: Liver enzyme abnormalities are common in patients with type 2 diabetes. Currently, the inverse relationship between elevated liver enzymes and antidiabetics intake may be explained by rigorous treatment and good control. However, few studies have directly explored the influence of antidiabetics on abnormal liver function, especially the comparison between two insulin sensitizers—thiazolidinediones and metformin. Materials And Methods: Databases, including PubMed, Cochrane, CNKI, Wanfang and VIP were searched. Two reviewers performed independently. Meta-analysis was used when studies were homogeneous enough. Results: Six studies, including 4726 patients with type 2 diabetes, were involved in this systematic review. Compared with metformin, thiazolidinediones significantly reduced the alanine transaminase, aspartate aminotransferase and gamma-glutamyl transpeptidase. Further subgroup analysis suggested that pioglitazone-treated participants showed vast improvement in decreasing alanine transaminase (MD = -13.70; 95% CI = -16.91 to -10.52; P < 0.00001; I² = 1%), aspartate aminotransferase (MD = -3.51; 95% CI = -5.74 to –1.28; P = 0.002; I² = 0%) and gamma-glutamyl transpeptidase (MD = -5.41; 95% CI = -9.40 to -1.42; P = 0.008; I² = 0%), while rosiglitazone exhibited no difference in lowering corresponding liver enzyme levels. Besides, thiazolidinediones similarly decreased fasting plasma glucose. However, thiazolidinediones were inferior to metformin in lowering HbA1C and alkaline phosphatase. Additionally, no significant publication bias was seen. Conclusions: Thiazolidinediones may confer modest biological improvement of liver function in people with type 2 diabetes than metformin. But owing to the limited methodological quality, more clinical researches are warranted in the future.

In this paper, we introduce the notion of super finitely separating functions which gives a characterization of RB-domains. Then we prove that FS-domains and RB-domains are equivalent in some special cases by the following three claims: a dcpo is an RB-domain if and only if there exists an approximate identity for it consisting of super finitely separating functions; a consistent join-semilattice is an FS-domain if and only if it is an RB-domain; an L-domain is an FS-domain if and only if it is an RB-domain. These results are expected to provide useful hints to the open problem of whether FS-domains are identical with RB-domains.

Nitric oxide (NO), an important chemical messenger, serves a dual role in tumor progression. Nitric oxide synthase isoform 1 (NOS1) was observed to be increasingly expressed in various types of cancer, and its expression has been associated with tumor progression. However, the level of NOS1 expression and the associated functions of NOS1 in human ovarian cancer remain undefined. Using gene expression profiles of ovarian cancer from the Gene Expression Omnibus (GEO) database, the present study revealed that NOS1 was increasingly expressed in ovarian cancer tissues. The present study investigated the level of NOS1 expression and its effects on in vitro cell function, including proliferation, migration and invasion as well as chemoresistance to cispatin (DDP) treatment in OVCAR3 cells. Reverse transcription-quantitative polymerase chain reaction demonstrated that the level of NOS1 mRNA expression varied in different ovarian cancer lines. However, immunoblotting indicated that the level of NOS1 protein expression was constitutively high in ovarian cancer cell lines. Treatment with NOS inhibitor NG-nitro-L-arginine methyl ester or transfection with NOS1 short hairpin RNA significantly inhibited cell proliferation, migration and invasion compared with the control, whereas the sensitivity of OVCAR3 cells to DDP treatment was increased. The results of the present study indicated that NOS1 promoted the function of ovarian cancer cells, including proliferation, invasion and chemoresistance, providing a potential target for ovarian cancer therapeutic.

BackgroundHyperlipidaemia causes kidney damage over the long term. We investigated the effect of the administration of endothelial progenitor cells (EPCs) on the progression of kidney damage in a mouse model of hyperlipidaemia.MethodsApolipoprotein E-knockout (ApoE−/−) mice were treated with a high-cholesterol diet after spleen resection. Twenty-four weeks later, the mice were divided into two groups and intravenously injected with PBS or EPCs. Six weeks later, the recruitment of EPCs to the kidney was monitored by immunofluorescence. The lipid, endothelial cell, and collagen contents in the kidney were evaluated by specific immunostaining. The protein expression levels of transforming growth factor-β (TGF-β), Smad2/3, and phospho-Smad3 (p-smad3) were detected by western blot analysis.ResultsApoE−/−mice treated with a high-fat diet demonstrated glomerular lipid deposition, enlargement of the glomerular mesangial matrix, endothelial cell enlargement accompanied by vacuolar degeneration and an area of interstitial collagen in the kidney. Six weeks after EPC treatment, only a few EPCs were detected in the kidney tissues of ApoE−/−mice, mainly in the kidney interstitial area. No significant differences in TGF-β, p-smad3 or smad2/3 expression were found between the PBS group and the EPC treatment group (TGF-β expression, PBS group: 1.06 ± 0.09, EPC treatment group: 1.09 ± 0.17,P = 0.787; p-smad3/smad2/3 expression: PBS group: 1.11 ± 0.41, EPC treatment group: 1.05 ± 0.33,P = 0.861).ConclusionsOur findings demonstrate that hyperlipidaemia causes basement membrane thickening, glomerulosclerosis and the vascular degeneration of endothelial cells. The long-term administration of EPCs substantially has limited effect in the progression of kidney damage in a mouse model of hyperlipidaemia.

Background: Our previous research revealed that the apoptosis of proximal tubular epithelial cells (PTECs) occupied a vital position in the early change of diabetic nephropathy (DN) and Bcl-interacting mediator (Bim) was the key factor to be involved in it. Whereas, Bim could also control T cell activation and play a specific regulatory role in other aspects besides inducing cell apoptosis. Changes of podocytes are classic hallmarks of the lesions of DN. Here, the study aims to investigate the specific influence of PTECs which have been damaged on the podocyte injury. Methods: Bim expression in PTECs was modulated, and subsequently podocyte cytoskeleton was determined at different points of time (24, 48, 72 hours) by building transwell co-culture system under high glucose (40mmol/l HG). Results: HG exposure for 48 hours induced the significant changes in podocyte cytoskeleton accompanied with high expression of Bim in PTECs. When co-cultured with PTECs, exacerbated filamentous actin (F-actin) rearrangement and markedly reduced synaptopodin level in podocytes were found compared with single cultured podocytes under HG. Gene knockdown of Bim in PTECs ameliorated above abnormalities in podocytes. Further screening for NFAT subtypes, the key downstream factors of Bim, found that NFAT2 level in PTECs was obviously decreased when suppressing Bim expression. Upregulating NFAT2 disrupted beneficial effects on podocyte F-actin arrangement which was achieved by inhibiting Bim in PTECs. Conclusion: Our preliminary data have indicated that the apoptosis of PTECs mediates the early lesion of DN. It seemed corroborative that there exists crosstalk between PTECs and podocytes; Bim, the pivotal factor related to apoptosis of PTECs participates in the crosstalk by promoting NFAT2 activation, then contributes to injury of podocyte cytoskeleton, emphasizing the role of Bim/NFAT2 pathway in the control of early DN progression from tubular lesions to glomerular abnormalities. Disclosure C. Xu: None. X. Zhou: None. X. Shen: None. S. Jiang: None. T. Xie: None. Z. Zou: None. Q. Zhang: None. R. Zhang: None. Y. Xing: None. L. Liao: None. J. Dong: None. Funding National Natural Science Foundation of China (81570742, 81670757, 81770822, 81800732); Shandong Provincial Natural Science Foundation of China (ZR2017LH025); Shandong Provincial Medicine and Health Science and Technology Development Program (2017WS461)

Background: Restenosis (RS) after percutaneous transluminal angioplasty severely affects the curative effect of patients with lower extremity peripheral arterial disease. Our previous research indicated that abnormal proliferation and migration of vascular smooth muscle cells (VSMCs) was the key factor in the RS plaque formation. The process of Lin28a regulating cell proliferation demonstrates similarities with the proliferation of VSMCs in RS. Here, we aim to explore the specific role of Lin28a in RS. Methods: To distinguish from atherosclerotic lesions, RS and atherosclerosis (AS) models were simultaneously established in type 2 diabetic rats. Lin28a level in VSMCs was detected by immunofluorescence double staining. The changes of VSMCs were determined when modulating Lin28a in vivo and vitro and downstream mechanism was further explored. Results: Thirty-two folds higher level of Lin28a was found in VSMCs in RS compared with AS (P Conclusion: The present study demonstrated that Lin28a is critically involved in the progression of RS via facilitating the proliferation and migration of VSMCs. A double negative feedback loop is often present in Let7 and Lin28a, thus Let7 subtypes were detected and Let7c could be the direct downstream of Lin28a in regulating VSMCs in RS. Combined with the fact that Lin28a was also regulated by Let7c, we inferred a feedback loop could be formed between Let7c and Lin28a. Above all, the interaction in Lin28a and Let7c may contribute to rapid formation of RS. Disclosure Q. Zhang: None. X. Zhou: None. X. Shen: None. S. Jiang: None. T. Xie: None. Z. Zou: None. C. Xu: None. R. Zhang: None. Y. Cui: None. P. Gong: None. J. Dong: None. L. Liao: None. Funding National Natural Science Foundation of China (81670757, 81570742, 81770822, 81800732); Shandong Provincial Natural Science Foundation of China (ZR2017LH025); Shandong Provincial Medicine and Health Science and Technology Development Program (2017WS461)

Duchenne muscular dystrophy (DMD) is an X-linked recessive genetic disease in which the dystrophin coding for a membrane stabilizing protein is mutated. Recently, the vasculature has also shown to be perturbed in DMD and DMD modelmdxmice. Data-mining DMD transcriptomics revealed the defects were correlated to a vascular endothelial growth factor (VEGF) signaling pathway. To reveal the relationship between DMD and VEGF signaling,mdxmice were crossed with constitutive (CAG/CreERTM:Flt1LoxP/LoxP) and endothelial cell-specific conditional gene knockout mice (Cdh5CreERT2:Flt1LoxP/LoxP) forFlt1which is a decoy receptor for VEGF. Previous work demonstrated that heterozygous globalFlt1knockout mice increased vascular density and improved DMD phenotypes when crossed with DMD modelmdxandmdx:utrn-/-mice. Here, we showed that while constitutive deletion ofFlt1is detrimental to the skeletal muscle function, endothelial cell-specificFlt1deletion resulted in increased vascular density and improvement in the DMD-associated phenotype in themdxmice. These decreases in pathology, including improved muscle histology and function, were recapitulated inmdxmice given anti-FLT1 peptides or monoclonal antibodies, which blocked VEGF-FLT1 binding. The histological and functional improvement of dystrophic muscle by FLT1 blockade provides a novel pharmacological strategy for the potential treatment of DMD.

It was brought to the attention of the Editors that there had been an accidental duplication of the western blot images during the preparation of Figs. 1b and c. The authors were notified about the error and have supplied the correct image for Fig. 1c (below). We apologize for any inconvenience this may have caused readers.

In the present paper, we mainly focus on the symmetry of the solutions of a given PDE via Lie group method. Meanwhile we transfer the given PDE to ODEs by making use of similarity reductions. Furthermore, it is shown that the given PDE is self-adjoining, and we also study the conservation law via multiplier approach.

In this study, a one-step rapid heating novel process was used to prepare high-purity anhydrous scandium chloride molten salt with low-purity scandium oxide. High-purity anhydrous ScCl3 molten salt was used as the Sc-bearing raw material for preparing the Sc-bearing master alloy. Inert gas was used to enhance the purity of anhydrous scandium chloride and reduce the hydrolysis rate of scandium. The results show that high-purity scandium chloride (purity, 99.69%) with the scandium content of 29.61%, was obtained, and the hydrolysis rate of scandium was 1.19% under the conditions used: removing ammonium chloride, residual crystal water temperature of 400 &deg, C, m(Sc2O3):m(NH4Cl) = 1:2.5, holding-time of 90 min, heating-rate of 12 &deg, C/min, and argon flow of 7.5 L/min. XRD, SEM, and EPMA analyses further verified that anhydrous scandium chloride crystallization condition was relatively good and the purity of high-purity anhydrous scandium chloride approached the theory purity of anhydrous scandium chloride.

Background/aims Diabetes affects the entire vascular system and accelerates atherosclerosis and ischemia. Percutaneous transluminal angioplasty with or without stenting is the main therapeutic strategies; however, the restenosis rate is high in diabetics. Sulfonylureas (SUs) are widely prescribed agents for the treatment of type 2 diabetes (T2DM) and function by interacting with sulfonylurea receptors (SURs), which also exists in vascular smooth muscle cells (VSMCs), give rise to the potential that SUs influence VSMCs. The proliferation and migration of VSMCs play important roles in the formations of primary stenosis and restenosis, especially the latter. However, there are no data about the exact effects of SUs on these processes. Methods Human aortic smooth muscle cells (HASMCs) were exposed to SUs prior to exposure to 30mM glucose. Cell proliferation was detected by CCK8 assay. Cell migration was detected by wound healing assay and transwell assay. Protein expression was determined by immunofluorescence and western blot. Diazoxide was used to evaluate the role of KATP channel in these processes. Results The proliferation and migration of HASMCs were significantly aggravated by glibenclamide and glimepiride, and their effects were reversed by diazoxide. In contrast, above characteristics of HASMCs were apparently inhibited by gliclazide, and this was maintained after opening the KATP channel. Conclusion These results imply that KATP channels play an important part in proliferation and migration of VSMCs induced by glibenclamide and glimepiride. In contrast, the inhibitory effect of gliclazide on VSMCs appeared to have more potential for the prevention of vascular obstructive diseases in T2DM.

Background Sulfonylureas (SUs) are widely prescribed for the treatment of type 2 diabetes (T2DM). Sulfonylurea receptors (SURs) are their main functional receptors. These receptors are also found in kidney, especially the tubular cells. However, the effects of SUs on renal proximal tubular epithelial cells (PTECs) were unclear. Methods Three commonly used SUs were included in this study to investigate if different SUs have different effects on the apoptosis of PTECs. HK-2 cells were exposed to SUs for 24 h prior to exposure to 30 mM glucose, the apoptosis rate was evaluated by Annexin/PI flow cytometry. Bcl-2, Bax and the ratio of LC3II to LC3I were also studied by western blot in vitro. Diazoxide was used to evaluate the role of KATP channel in SUs-induced apoptosis of PTECs. A Student’s t-test was used to assess significance for data within two groups. Results Treatment with glibenclamide aggravated the apoptosis of HK-2 cells in high-glucose, as indicated by a significant decrease in the expression of Bcl-2 and increase in Bax. Additionally, the decreased LC3II/LC3I reflects that the autophagy was inhibited by glibenclamide. Similar but less pronounced change was found in glimepiride group, however, nearly opposite effects were found in gliclazide group. Further, the effects of glibenclamide on apoptosis promotion and the decreased LC3II/LC3I were ameliorated obviously by treatment with 100uM diazoxide. The potential protection effect of gliclazide was also inhibited after opening the KATP channel. Conclusion Our results suggest that, the effects of glibenclamide and glimepiride on PTECs apoptosis, especially the former, were achieved in part by closing the KATP channel. In contrast to glibenclamide and glimepiride, therapeutic concentrations of gliclazide showed an inhibitory effect on apoptosis of PTECs, which may have a benefit in the preservation of functional PTECs mass.

Background A low-protein diet (LPD) is believed to be beneficial in slowing the progression of kidney disease. It is reported that low protein diet can improve protein, sugar and lipid metabolism, and reduce the symptoms and complications of renal insufficiency. However, there has been controversial regarding the effects of protein restriction on diabetic nephropathy (DN). Objective To investigate the efficacy of LPD on renal function in patients with type 1 or 2 DN by meta-analysis of randomized controlled trials (RCTs). Design PubMed, MEDLINE, EMBASE and China National Knowledge Infrastructure databases were searched. Eleven randomized controlled trials met the inclusion criteria, of which 10 were English and 1 was Chinese. The primary outcome was a change in glomerular filtration rate (GFR). The secondary outcome was a change in proteinuria. Random-effects models were used to calculate the standardized mean difference (SMD) and the corresponding 95% confidence intervals (CI). Subgroup analyses were also performed. Results Our research indicated that LPD was not associated with a significant improvement in GFR (1.59 ml · min−1 · 1.73 m−2, 95% CI -0.57, 3.75, I2 = 76%; p = 0.15). This effect was consistent across the subgroups regardless of type of diabetes, course of diabetes and intervention period. Our results also showed that there was no significant difference on improvement of proteinuria in patients of LPD and those in normal-protein diet groups (− 0.48, 95%CI-1.70, 0.74, I2 = 94%, p = 0.44). Subgroup analysis revealed that LPD resulted in increased excretion of proteinuria in patients with type 2 diabetes (1.32, 95% CI 0.17, 2.47, I2 = 86%, p = 0.02). Conclusion The present research showed that LPD was not significantly associated with improvement of renal function in patients with either type 1 or 2 diabetic nephropathy. Although these results do not completely eliminate the possibility that LPD is beneficial for patients with diabetic nephropathy, it does not seem to be significant benefit to renal function.

Fe⿿Cr⿿B hardfacing alloys with different nano-additives content were investigated. The effects of nano-additives on the microstructures of hardfacing alloy were studied by using optical microscope, scanning electron microscope, X-ray diffractometer. The hardness and the fracture toughness of hardfacing alloys were measured, respectively. The sliding wear tests were carried out using a ball-on-disc tribometer. The experimental results showed that primary carbide of hardfacing alloys was refined and its distribution became uniform with content of nano-additives increased. The hardfacing alloys are composed of Cr 7 C 3 , Fe 7 C 3 , α-Fe and Fe 2 B according to the results of X-ray diffraction. The hardness of hardfacing alloys increased linearly with the increase of nano-additives. The hardness of the hardfacing alloy with 1.5 wt.% nano-additives increased 54.8% than that of the hardfacing alloy without nano-additives and reached to 1011HV. The K IC of the hardfacing alloy with 0.65 wt.% nano-additives was 15.4 MPam 1/2 , which reached a maximum. The value increased 57.1% than that of the hardfacing alloy without nano-additives. The wear rates of the hardfacing layer with 0.65 wt.% and 1.0 wt.% nano-additives decreased about 88% than that of the hardfacing layer without nano-additives. The main wear mechanism was adhesion wear.

In this study, the solid-particle erosion behavior of carbidic austempered ductile iron (CADI) containing different amounts of ceria nanoparticles was investigated. Attempt was made to correlate the erosion resistance of the material to its microstructure and mechanical properties. It was demonstrated that the erosion resistance of CADI was improved by adding ceria nanoparticles. The maximum erosion rate of unmodified CADI occurred at the impact angle of 60–75°, which slightly shifted to lower angles when ceria nanoparticles were added, corresponding to more ductile characteristic. During erosion tests, the retained austenite in CADI partially transformed to martensite although the transformation was suppressed by the addition of ceria nanoparticles. The ceria-modified CADI showed a considerably increased erosion resistance at various impact angles.

Rare earth (RE)-modified NiCrAlY powders were prepared by ultrasonic gas atomization and deposited on stainless steel substrate by high-velocity oxygen fuel spraying. The effects of the RE on the microstructure, properties, and thermal shock resistance of the NiCrAlY coatings were investigated. The results showed that the NiCrAlY powders were refined and distributed uniformly after adding RE, while the number of unmelted particles in the coatings was reduced. Moreover, the RE-modified coatings showed improved microhardness and distribution uniformity. The microhardness of the coating reached a maximum after adding 0.9 wt.% RE, being 34.4 % higher than that of coatings without RE. The adhesive strength increased and reached a maximum after adding 0.6 wt.% RE, being 18.8 % higher than that of coatings without RE. Excessive RE decreased the adhesive strength. The thermal cycle life of NiCrAlY coatings increased drastically with RE addition. The coating with 0.9 wt.% RE showed optimum thermal shock resistance, being 21.2 % higher than that of coatings without RE.