Vitamin D attenuates TGF-β1-induced lung fibroblast proliferation and migration through repression of RasGRP3

Background:Transforming growth factor-β1(TGF-β1)is a pleiotropic cytokine that plays a central role in the pathogenesis of idiopathic pulmonary fibrosis(IPF).While previous studies have revealed a cross-talk between vitamin D and TGF-β1 signaling,it is still unclear how they interact with each other to regulate the progression of IPF.Methods:In this work,we searched for a novel mediator of TGF-β1 activity in lung fibroblasts and examined its regulation by vitamin D.In addition,we investigated the mechanism underlying the interaction between vitamin D and TGF-β1 signaling in lung fibroblast activation.Bioinformatic analysis was performed to identify TGF-β1 downstream target genes.Knockdown and overexpression expression experiments were conducted to determine gene function in the regulation of lung fibroblast proliferation and migration.Results:Analysis of publicly available datasets revealed that RAS guanyl releasing protein 3(RasGRP3)was upregulated in TGF-β1-treated lung fibroblasts and lung tissues from IPF patients relative to healthy controls.Our data confirmed the upregulation of RasGRP3 by TGF-β1 in human MRC5 lung fibroblasts.Overexpression of RasGRP3 enhanced MRC5 cell proliferation and migration.Knockdown of RasGRP3 blocked TGF-β1-induced MRC5 proliferation and migration.Vitamin D abolished TGF-β1-induced RasGRP3 upregulation,which was reversed by inhibition of the vitamin D receptor(VDR).Mechanistically,vitamin D promoted VDR enrichment and prevented mothers against decapentaplegic homolog(SMAD)2 and 3 occupancy at the promoter of RasGRP3.Additionally,overexpression of RasGRP3 reversed the suppressive effect of vitamin D on MRC5 cell proliferation and migration.Conclusion:In conclusion,vitamin D antagonizes TGF-β1-induced lung fibroblast activation by repressing RasGRP3 transcription.

Personalized targeted therapy for esophageal squamous cell carcinoma

Esophageal squamous cell carcinoma continues to heavily burden clinicians worldwide. Researchers have discovered the genomic landscape of esophageal squamous cell carcinoma, which holds promise for an era of personalized oncology care. One of the most pressing problems facing this issue is to improve the understanding of the newly available genomic data, and identify the driver-gene mutations, pathways, and networks. The emergence of a legion of novel targeted agents has generated much hope and hype regarding more potent treatment regimens, but the accuracy of drug selection is still arguable. Other problems, such as cancer heterogeneity, drug resistance, exceptional responders, and side effects, have to be surmounted. Evolving topics in personalized oncology, such as interpretation of genomics data, issues in targeted therapy, research approaches for targeted therapy, and future perspectives, will be discussed in this editorial.

Busting the efficiency of SAPO-34 catalysts for the methanol-to-olefin conversion by post-synthesis methods

As an effective non-petroleum based process for producing light olefins, the methanol-to-olefin(MTO) route has become an indispensable alternative to the industrial production of light olefins. The silicoaluminophosphate SAPO-34 zeolite(CHA-type structure) has proven to be an efficient industrial catalyst for the production of ethylene and propylene by the MTO reaction. However, the inherent structure and related diffusion limitations of SAPO-34 limit the mass transport and thus cause rapid deactivation of the catalyst. Fabrication of hierarchical SAPO-34 zeolite is one of the most effective strategies to address the intrinsic diffusion limitation. As simple, inexpensive, and efficient approach, the post-synthetic route has attracted considerable attention and widely used to introduce secondary meso-/macropores into the microporous SAPO-34 material. Significant effort has been dedicated to the development of post-synthesis strategies to prepare hierarchical SAPO-34 zeolite, thereby enhancing its catalytic performance in the MTO process. This mini-review addresses the post-synthesis preparation of hierarchical SAPO-34 catalysts and their MTO performance. Furthermore, some current problems and prospects of the post-synthesis route to hierarchical SAPO-34 catalysts are also revised. We expect this minireview to inspire the more efficient preparation of hierarchical SAPO-34 catalysts for the MTO process.

The synthetic strategies of hierarchical TS-1 zeolites for the oxidative desulfurization reactions

With the increasingly stringent standards for limiting sulfide content in liquid fuels,oxidative desulfurization(ODS)has become a promising ultra-deep desulfurization process in fuel desulfurization.TS-1 zeolites show great potential as catalysts for ODS reactions,due to its remarkable oxidation activity at low temperatures and pressure.However,the inherent microporous structure of conventional TS-1 zeolites restricts the mass transportation and renders the active sites in the microporous space of TS-1 zeolites inaccessible for bulky aromatic organosulfur compounds.Fabrication of hierarchical TS-1 zeolites by incorporating meso-/macropores into microporous TS-1 zeolites is an effective strategy to improve mass transportability.In recent years,abundant efforts have been dedicated to developing synthetic strategies of hierarchical TS-1 zeolite,thereby improving its catalytic performance in the ODS process.This mini-review addresses the synthetic methods of hierarchical TS-1 catalysts and their catalytic performance in the ODS reactions.In addition,some current problems and prospects of synthesis routes for constructing hierarchical TS-1 catalysts have also been revised.We expect this mini-review to shed light on the more efficient preparation strategies of hierarchical TS-1 zeolites for the ODS process.

Robust decentralized adaptive output feedback fuzzy controller design and application to AHS

A novel decentralized indirect adaptive output feedback fuzzy controller is developed for a class of large-scale uncertain nonlinear systems using error filtering.By the properly filtering of the observation error dynamics,the strictly positive-real condition is guaranteed to hold such that the proposed output feedback and adaptation mechanisms are practicable in practice owing to the fact that its implementation does not require the observation error vector itself any more,which corrects the impracticable schemes in the previous literature involved.The presented control algorithm can ensure that all the signals of the closed-loop large-scale system keep uniformly ultimately bounded and that the tracking error converges to zero asymptotically.The decentralized output feedback fuzzy controller can be applied to address the longitudinal control problem of a string of vehicles within an automated highway system（AHS） and the effectiveness of the design procedure is supported by simulation results.

Environmentally benign synthesis of crystalline nanosized molecular sieves

Zeolites and zeo-type materials with nanosized dimensions are of great practical interest owing to their favorable transport properties,faster adsorption kinetics,and large external surface area.This mini-review presents recent developments in the organic template-free synthesis of nanosized zeolites and related materials.The advantages and challenges of these methods are addressed with particular attention to the green synthesis of nanozeolites.

Investigation of lead-free BiFeO_(3)–BaTiO_(3)piezoelectric ceramics through precise composition control

BiFeO_(3)-BaTiO_(3)is a promising lead-free piezoelectric ceramic,exhibiting high Curie temperature and superior electrochemical characteristics.In this work,e_(1-x)TBiFeO_(3)-xBaTiO_(3)(BF-xBT,x=0.26,0.28,0.30,0.32,0.34,0.36)ceramics were fabricated using the conventional solid-state reaction method through precise composition control.Multiple characterization techniques,including X-ray powder diffraction(XRD),scanning electron microscope(SEM),and electrical property testing systems,were applied to systematically examine the crystallographic structure,microstructure,as well as the dielectric,ferroelectric and piezoelectric properties of the BF-xBT ceramics.The XRD results confirm that all compositions exhibit a typical perovskite structure,transitioning from a single rhombohedral phase to a rhombohedral-cubic phase mixture as the BT content increases.SEM shows apparent core-shell microstructures in the ceramics.Notably,the results demonstrated that the BF-0.30BT ceramic exhibits the maximum piezoelectric constant(d_(33))-217 pC/N,while the BF-0.34BT ceramic displays the maximum converse piezoelectric constant(d_(33)^(*))-323 pm/V,which highlights the suitability of BF-BT ceramics for high-performance piezoelectric applications.

双金属MOF衍生的Ru掺杂Cu基电催化材料在碱性介质中的高效析氢性能

合理设计和制备廉价且高效的电催化析氢(HER)材料对电解水有着十分重要的意义.本文开发了一种通过热解基于Ru离子交换方法得到的双金属Ru-Cu-BTC金属有机骨架简易制备Ru掺杂Cu负载的多孔碳材料(Ru-Cu@C)的方法.该催化剂在碱性电解液中表现出了优异的HER性能,电流密度为10 mA cm^(-2)时的过电位低至20 mV,且Tafel斜率仅有37 mV dec^(-1),该性能甚至超越了商用Pt/C催化剂.同时,密度泛函理论计算(DFT)结果表明,在Cu纳米晶的晶格中引入Ru原子后,H_(2)的吸附能接近于零,这极大地促进了H2在催化剂表面的脱附,显著改善了HER性能.该策略为开发廉价高效的碱性HER电催化剂提供了新的思路.

Dissipation behavior, residue distribution and dietary risk assessment of chlorfenapyr and clothianidin in leek using RRLC-QqQ-MS/MS technique

Commercial suspension emulsion(SE) of(8% chlorfenapyr + 20% clothianidin), as a pre-registered product in China, was firstly investigated under Chinese open-field conditions. A MWCNTs-based QuEChERS method for simultaneous determination of chlorfenapyr and clothianidin in leek was established and validated through rapid resolution liquid chromatography triples quadrupole tandem mass spectrometry(RRLC-QqQ-MS/MS). Based on this method, the dissipation behaviors, residue distributions and dietary risk probability of these fungicides in leek from two representative locations in China in 2016, which were previously treated with these insecticides at the doses of 420–630 g a.i./ha twice applications, were further investigated for food safety. Dissipation behavior of chlorfenapyr and clothianidin in leek followed first-order kinetics with the half-lives of 2.9–7.2 days, and the highest residues(HR) of these insecticides in leek were below 0.3811 mg/kg and 0.2989 mg/kg, respectively, at the pre-harvest interval(PHI, 7 days). For dietary risk assessments, the risk quotients(RQs) of chlorfenapyr and clothianidin in leek were evaluated by comparing the value of national estimated daily intake(NEDI) with acceptable daily intake(ADI), based on the trials data under good agricultural practices(GAP) conditions. The results indicated that RQs of chlorfenapyr and clothianidin in leek were21.5% and 0.29%, respectively, which exhibited an acceptably low health risk to leek consumption. The current study could not only guide reasonable usage of the formulation, but also facilitate the setting of maximum residue limits(MRLs) of chlorfenapyr and clothianidin in leek for Chinese

Design, synthesis and pharmacological evaluation of 4-(3-chloro-4-(3-cyclopropylthioureido)-2-fluorophenoxy)-7-methoxyquinoline-6-carboxamide (WXFL-152):a novel triple angiokinase inhibitor for cancer therapy

Angiokinases, such as vascular endothelial-, fibroblast-and platelet-derived growth factor receptors(VEGFRs, FGFRs and PDGFRs) play crucial roles in tumor angiogenesis. Anti-angiogenesis therapy using multi-angiokinase inhibitor has achieved great success in recent years. In this study, we presented the design, synthesis, target identification, molecular mechanism, pharmacodynamics(PD)and pharmacokinetics(PK) research of a novel triple-angiokinase inhibitor WXFL-152. WXFL-152,identified from a series of 4-oxyquinoline derivatives based on a structureeactivity relationship study,inhibited the proliferation of vascular endothelial cells(ECs) and pericytes by blocking the angiokinase signals VEGF/VEGFR2, FGF/FGFRs and PDGF/PDGFRβ simultaneously in vitro. Significant anticancer effects of WXFL-152 were confirmed in multiple preclinical tumor xenograft models, including a patientderived tumor xenograft(PDX) model. Pharmacokinetic studies of WXFL-152 demonstrated high favourable bioavailability with single-dose and continuous multi-dose by oral administration in rats and beagles.In conclusion, WXFL-152, which is currently in phase Ib clinical trials, is a novel and effective tripleangiokinase inhibitor with clear PD and PK in tumor therapy.