激光诱导羟基磷灰石夹层纸表面碳化实现无墨打印

传统的油墨打印具有方便快捷的优势,但打印过程中墨水或碳粉的大量使用对人体和环境造成了不可忽视的危害。基于激光的高能粒子特性和光热辐射热效应,利用激光欠焦和聚焦两种工作模式,可实现激光无墨打印和微区加工。本文报道了一种基于羟基磷灰石的“有机-无机-有机”三明治结构多功能纸,并利用激光的光热辐射效应使功能纸表层有机材料——纤维素纤维表面温度升高,实现表层均匀碳化,夹层无机材料——羟基磷灰石阻挡能量继续传导防止纸张烧穿,以此来达到无墨打印的效果。基于激光烧蚀的无墨打印,能够显著降低打印成本,有利于激光烧蚀打印技术的推广。此外,采用激光烧蚀打印技术作用于功能纸上的打印效果具有稳定、绿色环保等特点,在档案存储用纸、食品包装用纸和后天致盲患者阅读等方面具有广泛的应用。

Feasibility of CT-CT fusion imaging for evaluation of the cryoablation margins in visible hepatocellular carcinoma on unenhanced CT images:Initial experience

Objective:To demonstrate the feasibility of CT-CT fusion imaging for assessment of the cryoablation margins in visible hepatocellular carcinoma(HCC)on unenhanced CT images.Methods:This retrospective study analyzed 14 patients with 14 HCC lesions treated with CT-guided cryoablation.Nine lesions in nine patients who developed local tumor progression(LTP)during the follow-up period of at least8 months were reviewed.The unenhanced CT data were used to retrospectively create fusion images of the intraoperative CT images on a workstation.The minimal ablative margin(MAM)was assessed on the fusion images.The concordance between the site of LTP and the MAM area was also assessed.Results:Eight of the nine lesions with LTP were in the subcapsular region of the liver.Seven of the nine cases were treated by cryoablation combined with transcatheter arterial chemoembolization.The median time required to fuse the images for the nine lesions was 5:17 min(range,5:04-7:37 min).The site of LTP relative to the HCC lesion was craniocaudal in nine,dorsoventral in six,and lateral in seven lesions.In all lesions,the site of LTP was congruent with the MAM area.Conclusions:CT-CT fusion imaging enables a real-time intraoperative treatment evaluation for HCC lesions visible on unenhanced CT images.Fused imaging evaluation has proved to be an accurate and useful tool for assessment of the cryoablation margins.

Nanoparticle-stabilized Alkenyl Succinic Anhydride(ASA)Emulsions:A Review

Alkenyl succinic anhydride(ASA) is a popular paper-sizing agent that is generally added to papermaking systems as an aqueous emulsion. Herein, we reviewed the recent work focusing on ASA emulsions stabilized by solid particles. Solid particle-stabilized ASA emulsions generally possess high ASA content and exhibit good sizing performance. The particles that have been used to stabilize ASA emulsions typically include montmorillonite, laponite, alumina, TiO_2, Fe_3O_4, polyaluminum sulfate(PAS), and cellulose nanocrystals(CNCs). Montmorillonite is the first extensively studied particle stabilizer for ASA emulsions. Laponite is undoubtedly the most competent particle stabilizer for preparing ASA emulsions with high sizing efficiency. Montmorillonite and laponite can be used individually as stabilizers after modification or as co-stabilizers with other particles or polymers. TiO_2, alumina, PAS, and CNCs are commonly used as stabilizers either individually or with other particles.

Micro thermoelectric devices:From principles to innovative applications

Thermoelectric devices(TEDs),including thermoelectric generators(TEGs) and thermoelectric coolers(TECs) based on the Seebeck and Peltier effects,respectively,are capable of converting heat directly into electricity and vice versa.Tough suffering from low energy conversion efficiency and relatively high capital cost,TEDs have found niche applications,such as the remote power source for spacecraft,solid-state refrigerators,waste heat recycling,and so on.In particular,onchip integrable micro thermoelectric devices(μ-TEDs),which can realize local thermal management,on-site temperature sensing,and energy harvesting under minor temperature gradient,could play an important role in biological sensing and cell cultivation,self-powered Internet of Things(IoT),and wearable electronics.In this review,starting from the basic principles of thermoelectric devices,we summarize the most critical parameters for μ-TEDs,design guidelines,and most recent advances in the fabrication process.In addition,some innovative applications of μ-TEDs,such as in combination with microfluidics and photonics,are demonstrated in detail.

High-Pressure Synthesis and Thermal Transport Properties of Polycrystalline BAs_x

Polycrystalline BAsx(x=0.80-1.10)compounds with different boron-to-arsenic elemental molar ratios were synthesized by a high-pressure and high-temperature sintering method.Compared with other ambient-pressure synthesis methods,high pressure can significantly promote the reaction speed as well as the reaction yield.As the content of arsenic increases from x=0.91 to 1.10,the thermal conductivity of BAsx gradually increases from 53 to 65 W·m-1·K-1.Furthermore,the temperature dependence of thermal conductivities of these samples reveals an Umklapp scattering due to the increasing phonon population.This work provides a highly efficient method for polycrystalline BAs synthesis.

Integrative analysis of the metabolome and transcriptome reveals the potential mechanism of fruit flavor formation in wild hawthorn(Crataegus chungtienensis)

Hawthorns are important medicinal and edible plants with a long history of health protection in China.Besides cultivated hawthorn,other wild hawthorns may also have excellent medicinal and edible value,such as Crataegus chungtienensis,an endemic species distributed in the Southwest of China.In this study,by integrating the flavor-related metabolome and transcriptome data of the ripening fruit of C.chungtienensis,we have developed an understanding of the formation of hawthorn fruit quality.The results show that a total of 849 metabolites were detected in the young and mature fruit of C.chungtienensis,of which flavonoids were the most detected metabolites.Among the differentially accumulated metabolites,stachyose,maltotetraose and cis-aconitic acid were significantly increased during fruit ripening,and these may be important metabolites affecting fruit flavor change.Moreover,several flavonoids and terpenoids were reduced after fruit ripening compared with young fruit.Therefore,using the unripe fruit of C.chungtienensis may allow us to obtain more medicinal active ingredients such as flavonoids and terpenoids.Furthermore,we screened out some differentially expressed genes(DEGs)related to fruit quality formation,which had important relationships with differentially accumulated sugars,acids,flavonoids and terpenoids.Our study provides new insights into flavor formation in wild hawthorn during fruit development and ripening,and at the same time this study lays the foundation for the improvement of hawthorn fruit flavor.

Exploring exosomes to provide evidence for the treatment and prediction of Alzheimer’s disease

Exosomes are extracellular vesicles with a 30–150 nm diameter originating from endosomes.In recent years,scientists have regarded exosomes as an ideal small molecule carrier for the targeted treatment of Alzheimer’s disease(AD)across the blood-brain barrier due to their nanoscale size and low immunogenicity.A large amount of evidence shows that exosomes are rich in biomarkers,and it has been found that the changes in biomarker content in blood,cerebrospinal fluid,and urine are often associated with the onset of AD patients.In this paper,some recent advances in the use of exosomes in the treatment of AD are reviewed,and various exosome markers and some latest detection methods are summarized to provide some evidence for the detection or treatment of AD by exosomes.

Hemin blocks TIGIT/PVR interaction and induces ferroptosis to elicit synergistic effects of cancer immunotherapy

The immune checkpoint TIGIT/PVR blockade exhibits significant antitumor effects through activation of NK and CD8^(+)T cell-mediated cytotoxicity.Immune checkpoint blockade(ICB)could induce tumor ferroptosis through IFN-γreleased by immune cells,indicating the synergetic effects of ICB with ferroptosis in inhibiting tumor growth.However,the development of TIGIT/PVR inhibitors with ferroptosis-inducing effects has not been explored yet.In this study,the small molecule Hemin that could bind withTIGIT to block TIGIT/PVR interaction was screened by virtual molecular docking and cell-based blocking assay.Hemin could effectively restore the IL-2 secretion from Jurkat-hTIGIT cells.Hemin reinvigorated the function of CD8^(+)T cells to secrete IFN-γand the elevated IFN-γcould synergize with Hemin to induce ferroptosis in tumor cells.Hemin inhibited tumor growth by boosting CD8^(+)T cell immune response and inducing ferroptosis in CT26 tumor model.More importantly,Hemin in combination with PD-1/PD-L1 blockade exhibited more effective antitumor efficacy in anti-PD-1 resistant B16 tumor model.In summary,our finding indicated that Hemin blocked TIGIT/PVR interaction and induced tumor cell ferroptosis,which provided a new therapeutic strategy to combine immunotherapy and ferroptosis for cancer treatment.

重组人血管内皮抑制素窗口期联合化疗治疗晚期大肠癌的临床疗效

目的:观察重组人血管内皮抑制素(恩度)窗口期联合化疗治疗晚期大肠癌的临床疗效。方法:选取2014年6月至2018年6月于贵州省肿瘤医院就诊的不可手术的晚期大肠癌患者120例,随机分为重组人血管内皮抑制素窗口期联合化疗组(试验组)及重组人血管内皮抑制素常规方案联合化疗组(对照组)各60例。试验组方案:重组人血管内皮抑制素15 mg/d,d1~d7,间歇7天重复,用药14天为1个周期,化疗于每周期使用重组人血管内皮抑制素第5天(窗口期)开始;对照组方案:重组人血管内皮抑制素15 mg/d,d1~d14,间歇7天重复,21天为1个周期,化疗于重组人血管内皮抑制素治疗第1天开始;两组均采用m FOLFOX6或FOLFIRI方案化疗。对比分析两组的临床疗效。结果:1)试验组与对照组客观有效率(objective response rate,ORR)分别为25.0%和18.3%,疾病控制率(disease control rate,DCR)分别为80.0%和73.3%,差异均无统计学意义(P=0.375,P=0.388);2)试验组与对照组1、2、3年生存率分别为(69.6%vs.62.5%)(39.7%vs.21.3%)(26.8%vs.13.3%),中位生存时间为22个月(95%CI:16.817~27.183)vs.16个月(95%CI:11.890~20.110),试验组较对照组生存率提高、生存时间延长,差异具有统计学意义(P=0.033)。3)试验组与对照组中位疾病进展时间(time to progression,TTP)分别为9、8个月,差异无统计学意义(P>0.05)。结论:重组人血管内皮抑制素窗口期联合化疗较常规应用方案联合化疗提高晚期大肠癌患者的1、2、3年生存率,延长中位生存时间。

氮硫共掺杂高比表面中空碳球的制备及其在电催化二氧化碳还原中的应用

化石燃料是现代能源体系的重要支柱,其大量使用导致大气中CO2浓度不断增加,加剧了全球变暖和环境恶化.因此,各国研究人员开发了大量技术手段以捕获和重新再利用CO2这一丰富的碳资源.其中, CO2电催化还原(CO2RR)技术在减少CO2排放和将其转化为有用化学品等方面极具潜力.但是, CO2RR具有反应能垒高和动力学过程缓慢等特点,进而限制其转化效率,故使用传统的贵金属材料(Ag, Au, Cu及Pd等)作为CO2RR高效的催化剂.然而,贵金属材料的大规模应用受限于它们成本高昂、稳定性差及环境毒性等缺点.在各类可替代贵金属催化剂中,碳材料因其廉价丰富、结构可调和导电性高的特点在CO2RR应用上展现出诱人的前景,因此,探索合适的碳基催化剂在高效催化二氧化碳领域具有重要的研究价值和意义.本文通过简单有效的方法制备了一种氮硫共掺杂的高比表面的碳基催化剂(SZ-HCN)用于CO2RR.首先利用表面活性剂胶束Triton X-100作为模板诱导调控,合成了具有中空结构的苯胺-吡咯共聚物,并以此为碳前驱体,通过一步热解共聚物和硫粉获得N和S共掺杂多孔碳,材料的高比表面积(1510 m2g–1)得益于中空结构和ZnCl2盐造成的纳米孔结构.值得注意的是,高比表面的多孔结构且有效共掺杂N/S,能提供更多的高活性催化位点和有利于相关反应物种的传输.通过扫描电子显微镜、高分辨透射电子显微镜、高角环形暗场-扫描透射-元素分布、N2吸脱附等温分析及X射线光电子能谱等物理表征证实了催化剂材料的中孔结构和N/S共掺杂组分.进一步通过电化学测试分析和产物测试分析可知,电催化剂SZ-HCN在-0.60 V还原CO2为CO的法拉第效率高达93%,明显抑制竞争反应HER.此外,在-0.60 V恒电位下连续20 h测试,依旧保持稳定的电流密度(-5.2 m A cm–2)和高的CO选择性,显示了出色的耐久性和潜在应用性.我们采用密度泛函数理论探究N和S掺杂的影响,模拟计算可知,相比单一N掺杂的催化剂, N, S共掺杂可以提供更多的活性位点,降低CO2还原为CO反应中决速步生成COOH*的吉布斯自由能垒,进而提高催化活性.SZ-HCN催化剂展现出的优异CO2RR活性和稳定性主要归因于:(1)N和S元素均匀掺杂到碳基体中,两者的协同效应导致碳电荷再分布形成高活性位点,提高本征活性;(2)高比表面的多级孔结构提供了丰富的三相接触界面和有利的传输通道,便于反应相关物种的快速转移.该碳基催化剂材料在替代贵金属应用于CO2RR展示了一定的潜力.

SOD1^(G93A) Induces a Unique PSAP-Dependent Mitochondrial Apoptosis Pathway via Bax-Bak Interaction

Amyotrophic lateral syndrome(ALS)is a progressive degenerative disorder characterized by motor neuron death and axon degeneration.Mitochondrial dysfunction plays a key role in the pathogenesis of ALS,the mechanism of which remains poorly understood.The B-cell lymphoma-2(Bcl-2)family of proteins that control and mediate mitochondrial function and apoptosis,including the pro-apoptotic members Bcl2-Associated X(Bax),are involved in ALS development.The death receptor 6(DR6)regulates motor neuron death in ALS,and DR6 antibodies can prevent axon degeneration and motor neuron damage by blocking DR6.Previous studies demonstrated that PSAP localized to mitochondria and was required for DR6-induced apoptosis.In this study,SOD1^(G93A) was transfected into the motor neuron cell line NSC-34 to serve as an ALS cell model in vitro.The data assessed the role of PSAP in SOD1^(G93A)induced apoptosis and demonstrated that the overexpression of SOD1^(G93A),but not wtSOD1,induced PARP cleavage,caspase-3 activation,cytochrome c release,and Bax translocation.PSAP,Bax,and Bak were necessary for SOD1^(G93A)induced apoptosis,as silencing PSAP inhibited SOD1^(G93A)-mediated cell death that was dependent on Bax-Bak interaction.

Chromium trioxide modified spiro-OMeTAD for highly efficient and stable planar perovskite solar cells

Hole transporting materials(HTMs)play an unparalleled role in heightening the stability and photovoltaic performance of perovskite solar cells(PSCs).The organic small molecule spiro-OMeTAD is frequently utilized for HTM in PSCs.However,the raw spiro-OMeTAD without dopant would be harmful to the development of highly efficient PSCs,due to its unsatisfied hole mobility and conductivity.Therefore,we introduce an inorganic dopant(chromium trioxide,CrO_(3))into the lithium-salt doped spiro-OMeTAD.Because of the exclamatory oxidizability of CrO_(3),it can accelerate the oxidation of spiro-OMeTAD and thereby enhancing the hole mobility of HTM.The introduction of CrO_(3) not only substantially decreases the density of defects,but also adjusts spiro-OMeTAD energy band,and thus effectively suppresses the hysteresis and improving stability of PSCs.In the end,we obtained a power conversion efficiency(PCE)as high as 22.6%after doping CrO_(3) in spiro-OMeTAD.The facile,low cost and outstanding photovoltaic performance render CrO_(3) an excellent dopant for HTMs in PSCs.

Recent advances in bimetallic metal-organic frameworks and their derivatives for thermal catalysis

Compared with monometallic metal-organic frameworks(MOFs)that are synthesized by reacting inorganic metal ions or clusters with bidentate or multidentate ligands via hydrothermal or solvothermal methods,the construction of heterogeneous frameworks like at least two kinds of metal sites in the individual nodes is proved to be an effective way to modulate their properties for advanced catalysis,especially for selective catalysis and multifunctional catalysis.However,it is still very challenging to precisely characterize their microstructures and reveal the relationship among the composition,structure,and their performances.Therefore,it is necessary to summarize the recent progress on bimetallic MOFs for thermal catalysis.First,we summarize the synthesis strategies and characterization methods of bimetallic MOFs and their derivatives.Second,the application of bimetallic MOFs and their derivatives as catalysts in thermal catalysis is discussed,and the relationship among the active components,structures,and their properties is elucidated.Third,the potential challenges and prospects of bimetallic MOF based nanocatalysts are proposed.This review will bring some insights into the design and preparation of bimetallic MOFs based nanocatalysts in the future.

Artificial intelligence-aided discovery of prolyl hydroxylase 2 inhibitors to stabilize hypoxia inducible factor-1α and promote angiogenesis

From ZINC database with a total of 1.8 million small molecules, four compounds are identified as prolyl hydroxylase 2 inhibitors through a virtual screening workflow that sequentially incorporates machine learning, molecular docking, and molecular dynamics. Among them, compound 103,(E)-5-(5-((2-(1Htetrazol-5-yl)hydrazineylidene)methyl)furan-2-yl)isoindoline-1,3-dione, promotes the migration and capillary tube formation capacity of human umbilical vein endothelial cells through enhancing the stability of hypoxia inducible factor-1α and increasing the level of vascular endothelial growth factor.

IL-33 Downregulates Hepatic Carboxylesterase 1 in Acute Liver Injury via Macrophage-derived Exosomal miR-27b-3p

Background and Aims:We previously reported that carboxylesterase 1(CES1)expression was suppressed following liver injury.The study aimed to explore the role of interleukin(IL)-33 in liver injury and examine the mechanism by which IL-33 regulates CES1.Methods:IL-33 and CES1 levels were determined in the livers of patients and lipopolysaccharide(LPS)-,acetaminophen(APAP)-treated mice.We constructed IL-33 and ST2 knockout(KO)mice.ST2-enriched immune cells in livers were screened to identify the responsible cells.Macrophage-derived exosome(MDE)activity was tested by adding exosome inhibitors.Micro-RNAs(miRs)were extracted from control and IL-33-stimulated MDEs(IL-33-MDEs)and subjected miR sequencing(miR-Seq).Candidate miR was tested in vitro and in vivo and its binding of a target gene was assessed by luciferase reporter assays.Lentivirus-vector cellular transfection and transcript silencing were used to examine pathways mediating IL-33 suppression of miR-27b-3p.Results:Patient liver IL-33 and CES1 expression levels were inversely correlated.CES1 downregulation in liver injury was rescued in both IL-33–deficient and ST2 KO mice.Macrophages were shown to be responsible for IL-33 effects.IL-33-MDEs reduced CES1 levels in hepatocytes.Exosomal miR-Seq and qRT-PCR demonstrated increased miR-27b-3p levels in IL-33-MDEs;miR-27b-3p was implicated in Nrf2 targeting.IL-33 inhibition of miR-27b-3p was found to be GATA3-dependent.Conclusions:IL-33–ST2–GATA3 pathway signaling increases miR-27b-3p content in MDEs,which upon being internalized by hepatocytes reduce CES1 expression by inhibiting Nrf2.The elucidation of this mechanism in this study contributes to a better understanding of CES1 dysregulation in liver injury.

Farnesoid X receptor,the bile acid sensing nuclear receptor,in liver regeneration

The liver is unique in regenerative potential, which could recover the lost mass and function after injury from ischemia and resection. The underlying molecular mechanisms of liver regeneration have been extensively studied in the past using the partial hepatectomy(PH) model in rodents, where 2/3 PH is carried out by removing two lobes. The whole process of liver regeneration is complicated, orchestrated event involving a network of connected interactions, which still remain fully elusive. Bile acids(BAs) are ligands of farnesoid X receptor(FXR), a nuclear receptor of ligand-activated transcription factor. FXR has been shown to be highly involved in liver regeneration. BAs and FXR not only interact with each other but also regulate various downstream targets independently during liver regeneration. Moreover, recent findings suggest that tissue-specific FXR also contributes to liver regeneration significantly. These novel findings suggest that FXR has much broader role than regulating BA, cholesterol, lipid and glucose metabolism. Therefore, these researches highlight FXR as an important pharmaceutical target for potentialuse of FXR ligands to regulate liver regeneration in clinic. This review focuses on the roles of BAs and FXR in liver regeneration and the current underlying molecular mechanisms which contribute to liver regeneration.

A novel cyclic peptide targeting LAG-3 for cancer immunotherapy by activating antigenspecific CD8^+ T cell responses

PD-1 and CTLA-4 antibodies offer great hope for cancer immunotherapy.However,many patients are incapable of responding to PD-1 and CTLA-4 blockade and show low response rates due to insufficient immune activation.The combination of checkpoint blockers has been proposed to increase the response rates.Besides,antibody drugs have disadvantages such as inclined to cause immune-related adverse events and infiltration problems.In this study,we developed a cyclic peptide C25 by using Ph.D.-C7C phage display technology targeting LAG-3.As a result,C25 showed a relative high affinity with human LAG-3 protein and could effectively interfere the binding between LAG-3 and HLA-DR(MHC-II).Additionally,C25 could significantly stimulate CD8^+T cell activation in human PBMCs.The results also demonstrated that C25 could inhibit tumor growth of CT26,B16 and B 16-OVA bearing mice,and the infiltration of CD8^+T cells was significantly increased while FOXP3^+Tregs significantly decreased in the tumor site.Furthermore,the secretion of IFN-γby CD8^+T cells in spleen,draining lymph nodes and especially in the tumors was promoted.Simultaneously,we exploited T cells depletion models to study the anti-tumor mechanisms for C25 peptide,and the results combined with MTT assay confirmed that C25 exerted anti-tumor effects via CD8+T cells but not direct killing.In conclusion,cyclic peptide C25 provides a rationale for targeting the immune checkpoint,by blockade of LAG-3/HLA-DR interaction in order to enhance anti-tumor immunity,and C25 may provide an alternative for cancer immunotherapy besides antibody drugs.

Inhibition of the CDK9-cyclin T1 protein-protein interaction as a new approach against triple-negative breast cancer

Cyclin-dependent kinase 9(CDK9) activity is correlated with worse outcomes of triplenegative breast cancer(TNBC) patients. The heterodimer between CDK9 with cyclin T1 is essential for maintaining the active state of the kinase and targeting this protein-protein interaction(PPI) may offer promising avenues for selective CDK9 inhibition. Herein, we designed and generated a library of metal complexes bearing the 7-chloro-2-phenylquinoline CN ligand and tested their activity against the CDK9cyclin T1 PPI. Complex 1 bound to CDK9 via an enthalpically-driven binding mode, leading to disruption of the CDK9-cyclin T1 interaction in vitro and in cellulo. Importantly, complex 1 showed promising anti-metastatic activity against TNBC allografts in mice and was comparably active compared to cisplatin. To our knowledge, 1 is the first CDK9-cyclin T1 PPI inhibitor with anti-metastatic activity against TNBC. Complex 1 could serve as a new platform for the future design of more efficacious kinase inhibitors against cancer, including TNBC.

Synthesis of Phenanthridine and Quinoxaline Derivatives via Copper-Catalyzed Radical Cyanoalkylation of Cyclobutanone Oxime Esters and Vinyl Azides

Main observation and conclusion A copper-catalyzed radical cyclization of cyclobutanone oxime esters and vinyl azide is described.This method provides facile access to cyanoalkyl-substituted phenanthridines and quinoxalines with excellent isolated yields.Moreover,these reactions proceed under mild conditions with a board substrate scope and excellent functional group tolerance.

Comprehensive evaluation model of wind power accommodation ability based on macroscopic and microscopic indicators

This article explores and establishes comprehensive evaluation index system of wind power accommodation ability considering microscopic index and macroscopic index, and the index system includes conventional evaluation indexes such as forecast deviation, simultaneity factor and anti-peak rate, also newly introduced evaluation indexes such as installed capacity, power adequacy and accommodation space. Bayesian weight modified method is used for solving index weights of 8 wind power accommodation indexes. The paper puts forward a comprehensive evaluation model of wind power accommodation ability based on improved radar chart method, and this model changes traditional radar chart fan-shaped sector to quadrilateral evaluation region, and increasing angle bisector can solve the problem that evaluation results are not unique. It constructs new area and perimeter vectors of radar chart, which make the evaluation results give consideration to level of aggregation and balance degree of evaluation objectives, and case study results show that this model has a certain practical value.