Fiber Bundle Topology Optimization for Surface Flows

This paper presents a topology optimization approach for the surface flows on variable design domains.Via this approach,the matching between the pattern of a surface flow and the 2-manifold used to define the pattern can be optimized,where the 2-manifold is implicitly defined on another fixed 2-manifold named as the base manifold.The fiber bundle topology optimization approach is developed based on the description of the topological structure of the surface flow by using the differential geometry concept of the fiber bundle.The material distribution method is used to achieve the evolution of the pattern of the surface flow.The evolution of the implicit 2-manifold is realized via a homeomorphous map.The design variable of the pattern of the surface flow and that of the implicit 2-manifold are regularized by two sequentially implemented surface-PDE filters.The two surface-PDE filters are coupled,because they are defined on the implicit 2-manifold and base manifold,respectively.The surface Navier-Stokes equations,defined on the implicit 2-manifold,are used to describe the surface flow.The fiber bundle topology optimization problem is analyzed using the continuous adjoint method implemented on the first-order Sobolev space.Several numerical examples have been provided to demonstrate this approach,where the combination of the viscous dissipation and pressure drop is used as the design objective.

An origami shield with supporting frame structures optimized by a feature-driven topology optimization method

In this paper,the design,manufacture and testing of an origami protective shield with a supporting frame structure are presented.It consists of an origami shield surface and a deployable supporting frame structure that needs to be portable and sufficiently stiff.First,for the design of the shield surface,a threestage origami crease pattern is developed to reduce the shield size in the folded state.The shield surface consists of several stiff modular panels and layered with flexible fabric.The modular panels are made of a multi-layer composite where a ceramic layer is made of small pieces to improve durability as those small pieces enable restriction of crack propagation.Then,the supporting frame structure is designed as a chain-of-bars structure in order to fold into a highly compact state as a bundle of bars and deploy in sequence.Thus,a feature-driven topology structural optimization method preserving component sequence is developed where the inter-dependence of sub-structures is taken into account.A bar with semi-circular ends is used as a basic design feature.The positions of the bar’s end points are treated as design variables and the width of the bars is kept constant.Then,a constraint on the total length of the chain of bars is introduced.Finally,the modular panels made of multi-layer composite and the full-scale prototype of the origami shield are fabricated and tested to verify the bullet-proof performance.

Study of the Ballistic Impact Behavior of Protective Multi-Layer Composite Armor

The abalone shell,a composite material whose cross-section is composed of inorganic and organic layers,has high strength and toughness.Inspired by the abalone shell,several multi-layer composite plates with different layer sequences and thicknesses are studied as bullet-proof material in this paper.To investigate the ballistic performance of this multi-layer structure,the complete characterization model and related material parameters of large deformation,failure and fracture ofAl_(2)O_(3)ceramics andCarbon Fiber Reinforced Polymer(CFRP)are studied.Then,3D finite element models of the proposed composite plates with different layer sequences and thicknesses impacted by a 12.7 mm armor-piercing incendiary(API)are built using Abaqus to predict failure.The simulation results show that the CFRP/Al2O3 ceramic/Ultrahigh Molecular Weight Polyethylene(UHMWPE)/CFRP(1 mm/4 mm/4 mm/1 mm)composite is the optimized stack of layers.The simulation results under specified layer sequence and thickness have a reasonable correlation with the experimental results and reflect the failure and fracture of the multi-layer composite protective armor.

An NBS-LRR-encoding gene CsRPM1 confers resistance to the fungus Colletotrichum camelliae in tea plant

Nucleotide binding site,leucine-rich repeat(NBS-LRR)proteins are the main types of disease resistance proteins in plants,which can perceive plant pathogens.Anthracnose,caused by the fungus Colletotrichum camelliae,is one of the most severe diseases in tea plant.Here,we identified an NBS-LRR-encoding gene,CsRPM1,probably conferring resistance of tea plant to C.camelliae.Phylogenetic analysis showed that CsRPM1 was clustered with RPM1 in Arabidopsis and grouped into CC-NBS-LRR(CNL).It contained a signal peptide,a NB-ARC domain,and multiple LRR motifs.RNA-seq and qRT-PCR analysis showed that the transcript level of CsRPM1 was significantly up-regulated after inoculation with C.camelliae.Transiently silencing of CsRPM1 in tea leaves comprised the resistance to C.camelliae,indicating that CsRPM1 was required for plant defense against the pathogen.The subcellular localization showed that CsRPM1 protein was localized in the nucleus,cytoplasm,and cell membrane.Furthermore,the promoter region of CsRPM1 gene contained MeJA-responsive elements,and the expression of CsRPM1 was induced by exogenous methyl jasmonate,suggesting that CsRPM1 gene may be closely related to JA signaling pathway.A total of 17 transcription factors might be responsible for the expression of CsRPM1.Our data indicates that CsRPM1 is required for disease resistance to C.camelliae in tea plant.The characterization of this disease resistance gene sheds light on NLR protein function in tea plant and may facilitate breeding to control the severe anthracnose.

Temporal and Spatial Distribution Characteristics of Lightning Activity in the Pan-Pearl River Delta

Based on the lightning data acquired by a lightning imaging sensor(LIS)carried on the TRMM satellite from 1998 to 2013,the spatial distribution,seasonal,monthly,and diurnal characteristics of lightning activity in the Pan-Pearl River Delta were analyzed.The results show that in the Pan-Pearl River Delta,lightning activity was more in the south and less in the north.Near 23°N,lightning density was high from Guangdong and Guangxi to the southern edge of Yunnan.Lightning density weakened continuously as the latitude increased.Among the provinces in the Pan-Pearl River Delta,the maximum and average of lightning density in Hainan Province was greater than that of other provinces.Besides,the lightning activity showed obvious seasonal changes.In the whole year,lightning activity was the weakest in November and next February.Lightning activity in most areas of the Pan-Pearl River Delta was the strongest in August.The peak of lightning activity in most areas of the Pan-Pearl River Delta occurred from 12:00 to 20:00.Lightning activity was the weakest between 07:00 and 10:00 in most areas.

Amplifying protection against acute lung injury:Targeting both inflammasome and cGAS-STING pathway by Lonicerae Japonicae Flos-Forsythiae Fructus drug pair

Objective:Acute lung injury(ALI)is characterized by inflammation and currently lacks an efficacious pharmacological intervention.The medicine combination of Lonicerae Japonicae Flos(LJF)and Forsythiae Fructus(FF)demonstrates combined properties in its anti-infective,anti-inflammatory,and therapeutic effects,particularly in alleviating respiratory symptoms.In previous studies,Chinese medicine has shown promising efficacy in lipopolysaccharides(LPS)-induced ALI.However,there have been no reports of LJF and FF pairing for lung injury.The aim of this study is to compare the efficacy of herb pair Lonicerae Japonicae Flos-Forsythiae Fructus(LF)with LJF or FF alone in the treatment of ALI,and to explore whether LJF and FF have a combined effect in the treatment of lung injury,along with the underlying mechanism involved.Methods:A total of 36 mice were divided into six groups(control,model,LJF,FF,LF,dexamethasone)based on the treatments they received after undergoing sham-operation/LPS tracheal instillation.H&E staining and pulmonary edema indexes were used to evaluate lung injury severity.Alveolar exudate cells(AECs)were counted based on cell count in bronchoalveolar lavage fluid(BALF),and neutrophil percentage in BALF was measured using flow cytometry.Myeloperoxidase(MPO)activity in BALF was measured using enzyme-linked immunosorbent assay(ELISA),while the production of IL-1β,TNF-α,and IL-6 in the lung and secretion level of them in BALF were detected by quantitative polymerase chain reaction(qPCR)and ELISA.The effect of LJF,FF,and LF on the expression of Caspase-1 and IL-1βproteins in bone marrow derived macrophages(BMDMs)supernatant was assessed using Western blot method under various inflammasome activation conditions.In addition,the concentration of IL-1βand changes in lactatedehydrogenase(LDH)release levels in BMDMs supernatant after LJF,FF,and LF administration,respectively,were measured using ELISA.Furthermore,the effects of LJF,FF and LF on STING and IRF3 phosphorylation in BMDMs were detected by Western blot,and the mRNA changes of IFN-β,TNF-α,IL-6 and CXCL10 in BMDMs were detected by qPCR.Results:LF significantly attenuated the damage to alveolar structures,pulmonary hemorrhage,and infiltration of inflammatory cells induced by LPS.This was evidenced by a decrease in lung index score and wet/dry weight ratio.Treatment with LF significantly reduced the total number of neutrophil infiltration by 75%as well as MPO activity by 88%.The efficacy of LF in reducing inflammatory factors IL-1β,TNF-α,and IL-6 in the lungs surpasses that of LJF or FF,approaching the effectiveness of dexamethasone.In BMDMs,the co-administration of 0.2 mg/mL of LJF and FF demonstrated superior inhibitory effects on the expression of nigericin-stimulated Caspase-1 and IL-1β,as well as the release levels of LDH,compared to individual treatments.Similarly,the combination of 0.5 mg/mL LJF and FF could better inhibit the phosphorylation levels of STING and IRF3 and the production of IFN-β,TNF-α,IL-6,and CXCL10 in response to ISD stimulation.Conclusion:The combination of LJF and FF increases the therapeutic effect on LPS-induced ALI,which may be mechanistically related to the combined effect inhibition of cyclic-GMP-AMP synthase(cGAS)-stimulator of interferon genes(STING)and NOD-like receptor family protein 3(NLRP3)inflammasomes pathways by LJF and FF.Our study provides new medicine candidates for the clinical treatment of ALI.

NSUN2-mediated mRNA m^(5)C Modification Regulates the Progression of Hepatocellular Carcinoma

RNA modifications affect many biological processes and physiological diseases.The 5-methylcytosine(m^(5)C)modification regulates the progression of multiple tumors.However,its characteristics and functions in hepatocellular carcinoma(HCC)remain largely unknown.Here,we found that HCC tissues had a higher m^(5)C methylation level than the adjacent normal tissues.Transcriptome analysis revealed that the hypermethylated genes mainly participated in the phosphokinase signaling pathways,such as the Ras and PI3K-Akt pathways.The m^(5)C methyltransferase NSUN2 was highly expressed in HCC tissues.Interestingly,the expression of many genes was positively correlated with the expression of NSUN2,including GRB2,RNF115,AATF,ADAM15,RTN3,and HDGF.Real-time PCR assays further revealed that the expression of the mRNAs of GRB2,RNF115,and AATF decreased significantly with the down-regulation of NSUN2 expression in HCC cells.Furthermore,NSUN2 could regulate the cellular sensitivity of HCC cells to sorafenib via modulating the Ras signaling pathway.Moreover,knocking down NSUN2 caused cell cycle arrest.Taken together,our study demonstrates the vital role of NSUN2 in the progression of HCC.

抗SARS-CoV-2变异株的广谱mRNA疫苗RQ3013的临床前研究

全球SARS-CoV-2病毒的不同变异株导致已接种疫苗的人群中突破性感染的比例上升,迫切需要研发更为有效和广谱的COVID-19疫苗.本研究报告了一项mRNA疫苗RQ3013的临床前研究结果,旨在提供对SARS-CoV-2各种变异株(VOCs)的广谱保护.RQ3013疫苗包含经过假尿苷修饰的mRNA,制备成脂质纳米颗粒的形式.该mRNA编码了SARS-CoV-2的刺突(S)蛋白嵌合体,包含与免疫逃逸有关的重要突变位点.我们在多种动物模型中对RQ3013的免疫原性、保护效果和安全性进行了评估.RQ3013在小鼠、仓鼠和非人灵长类动物(NHP)中引发了显著的免疫反应.它能够诱导高滴度的抗体产生,具备对野生型、B.1.1.7、B.1.351、B.1.617.2和奥密克戎系列变异株的广泛中和能力.在小鼠和NHP中,两剂RQ3013疫苗能够有效保护上呼吸道和下呼吸道免受SARS-CoV-2及其变异株的感染.此外,在NHP中对RQ3013的安全性进行了评估,未观察到不良反应.这些结果为在临床试验中评估RQ3013提供了有力的支持,表明它可能成为对抗COVID-19及其变种的广泛保护的有希望的候选疫苗.

中药白及在口腔疾病中的研究与应用

白及作为我国传统的中药材,分布广泛、价廉易得。随着中医药的蓬勃发展,白及在临床医学上的应用也更为深入,包括抗菌、抗肿瘤、治疗消化道溃疡、胃黏膜病变和体内外出血等。本文对白及的药理特性、化学成分做一总结,同时分析各成分在治疗中的机制和通路,着重归纳整理了白及在口腔疾病领域的应用,包括口腔黏膜类疾病、龋病、髓腔内屏障材料和牙周组织工程支架材料等,证明了白及无论是单味用药还是配伍用药,都能依靠其自身特性发挥重要功效,为进一步推广白及在口腔疾病治疗中的研究应用提供参考。

Improving ModeⅡdelamination resistance of curved CFRP laminates by a Pre-Hole Z-pinning(PHZ)process

This paper presents an experimental investigation of the ModeⅡdelamination resistance of curved CFRP laminates reinforced with Z-pins.A Pre-Hole Z-pinning(PHZ)process is developed to reduce the in-plane damage of the Z-pinned laminates.The microstructural observation of the Z-pinned laminate specimens indicates that the PHZ process can effectively decrease the defects including the Z-pin offset angle and the area of eyelet zone.The influences of the volume fraction and diameter of Z-pin on the fracture toughness and the delamination crack growth rate of the specimens under End Notch Flexure(ENF)loading are then determined experimentally.The test results show that Z-pin increases the interlayer stiffness of the laminate.The delamination crack growth rate is reduced with the increase of Z-pin diameter and volume fraction,and a reduction up to 40%is achieved compared with the specimens without pins.Furthermore,the ModeⅡfracture toughness is significantly improved with the increase of Z-pin volume fraction.When Z-pin volume fraction increases by 1%,the achieved fracture toughness is about 200%higher compared to the unpinned laminates.

Self-assembly of polysarcosine amphiphilic polymers-tethered gold nanoparticles for precise photo-controlled synergistic therapy

Polymer-induced self-assembly of inorganic nanoparticles has emerged as a powerful strategy for fabrication of stimuliresponsive drug delivery nanosystems.Herein,we designed and synthesized a series of lipoic acid-capped polysarcosine-bpolycaprolactone(PSar-b-PCL)block copolymers.The self-assembly of gold nanoparticles drove by these block copolymers was systematically investigated,and the preparation of near-infrared(NIR)light-responsive PSar-decorated gold nanovesicle(PSGV)was optimized.DOX as anticancer drug was efficiently encapsulated within the cavity of PSGV.The PSGV greatly prevented doxorubicin(DOX)from premature leakage.While upon 808 nm laser irradiation,most of loaded DOX was rapidly released,along with the recovery of DOX fluorescence.Impressively,the DOX-loaded PSGV(DOX-PSGV)exhibited much higher cell uptake efficiency when compared to DOX-loaded polyethylene glycol(PEG)-coated gold nanovesicle(DOX-PEGV).Thanks to the synergistic photothermal/chemo therapy,the DOX-PSGV had highly superior antitumor efficacy in established 4T1 tumor model.

金属配位(螯合)型离子液体在二氧化碳吸收和转化中的研究进展

金属配位型离子液体(ionic liquids, ILs)是一类由金属离子与有机或无机配体通过配位作用形成的低温熔盐.其中,当金属离子与配体具有多齿配位点时,将其称为金属螯合型ILs.目前,金属配位(螯合)型ILs已经被广泛用于气体吸收和有机催化等领域,显示出了优异的性能.本文首先对近年来金属阴离子配位型ILs和金属阳离子螯合型ILs在二氧化碳(CO_(2))吸收中的应用进行综述,重点讨论了金属离子、配体和阴离子种类对CO_(2)吸收性能的影响;其次,总结了金属阴离子配位型ILs、金属阳离子配位型ILs、金属阴阳离子配位型ILs和金属阳离子螯合型ILs催化CO_(2)化学转化的研究进展,分析比较了不同类型金属配位(螯合)型ILs催化CO_(2)与环氧、末端炔烃、炔丙醇等底物的反应性能与机理;最后,阐述了金属配位(螯合)型ILs应用于CO_(2)吸收与化学转化时存在的问题与面临的挑战与机遇.

非瓣膜病房颤患者口服新型抗凝药依从性的调查

目的调查非瓣膜病房颤患者服用新型口服抗凝药的依从性及其影响因素,并分析停药原因。方法采用便利抽样法,对2016年3月—2018年3月某三级甲等医院服用新型口服抗凝药的133例非瓣膜病房颤患者进行调查,统计患者持续服药时间、停药原因和不良事件发生率。采用Kaplan-Meier法和Cox回归分析患者服用新型口服抗凝药的依从性及影响因素。结果服用达比加群酯和利伐沙班的患者分别为101例(75.9%)和32例(24.1%)。患者持续服药中位时间为182 d,达比加群酯和利伐沙班的持续服药中位时间分别为182 d和305 d。生存分析显示,患者在3个月、6个月和1年时仍坚持服药的累积比例分别为72.5%,50.6%和32.3%。阵发性房颤、无心力衰竭和无脑卒中史是服药依从性差的主要因素,患者自行停药是抗凝终止的首要原因。结论非瓣膜病房颤患者服用新型口服抗凝药的依从性差,服药3~6个月时需加强关注,提示应进行多学科合作,对阵发性房颤、无心力衰竭和无脑卒中史的患者加强抗凝管理,改善抗凝质量。

企业社会责任治理:成因、模式与机制

自企业社会责任概念提出以来已逾百年,此后企业社会责任思想也走过了CSR1.0、CSR2.0、CSR3.0时代,而与企业社会责任理论不断向前演绎与发展相悖的事实是社会和环境问题日益突出,企业社会责任缺失行为事件、伪社会责任行为、企业伪善行为与社会责任寻租行为此起彼伏,企业社会责任评价市场乱象丛生,这在客观上说明企业社会责任实践本身需要社会责任治理理论加以回应。企业社会责任治理是对传统社会责任管理的延续与引申,更是推进企业履责生态圈良性发展的一种范式转换。本文分析了企业社会责任治理前置因素,即从认知层面、行为层面与环境层面分析了企业社会责任治理的必要性,并探讨比较了三种主要的企业社会责任治理模式,最后重点从治理主体、治理模式、治理目标等方面探究企业社会责任异化行为分类治理的综合机制,本次研究有利于规范企业社会责任履责实践。

Improvement of impact resistance of plain-woven composite by embedding superelastic shape memory alloy wires

Carbon fiber reinforced polymer (CFRP) composites have excellent mechanical properties, specifically, high specific stiffness and strength. However, most CFRP composites exhibit poor impact resistance. To overcome this limitation, this study presents a new plain-woven CFRP composite embedded with superelastic shape memory alloy (SMA) wires. Composite specimens are fabricated using the vacuum-assisted resin injection method. Drop-weight impact tests are conducted on composite specimens with and without SMA wires to evaluate the improvement of impact resistance. The material models of the CFRP composite and superelastic SMA wire are introduced and implemented into a finite element (FE) software by the explicit user-defined material subroutine. FE simulations of the drop-weight impact tests are performed to reveal the superelastic deformation and debonding failure of the SMA inserts. Improvement of the energy absorption capacity and toughness of the SMA-CFRP composite is confirmed by the comparison results.

Multiscale model of micro curing residual stress evolution in carbon fiber-reinforced thermoset polymer composites

In this study,the micro curing residual stresses of carbon fiber-reinforced thermoset polymer(CFRP)composites are evaluated using a multiscale modeling method.A thermochemical coupling model is developed at the macroscale level to obtain the distributions of temperature and degree of cure.Meanwhile,a representative volume element model of the composites is established at the microscale level.By introducing the information from the macroscale perspective,the curing residual stresses are calculated using the microscale model.The evolution of curing residual stresses reveals the interaction mechanism of fiber,matrix,and interphase period during the curing process.Results show that the curing residual stresses mostly present a tensile state in the matrix and a compressive state in the fiber.Furthermore,the curing residual stresses at different locations in the composites are calculated and discussed.Simulation results provide an important guideline for the analysis and design of CFRP composite structures.

Compressive behavior and energy absorption of polymeric lattice structures made by additive manufacturing

Lattice structures have numerous outstanding characteristics,such as light weight,high strength,excellent shock resistance,and highly efficient heat dissipation.In this work,by combining experimental and numerical methods,we investigate the compressive behavior and energy absorption of lattices made through the stereolithography apparatus process.Four types of lattice structures are considered:(i)Uniform bodycentered-cubic(U-BCC);(ii)graded body-centered-cubic(G-BCC);(iii)uniform body-centered-cubic with z-axis reinforcement(U-BCCz);and(iv)graded body-centeredcubic with z-axis reinforcement(G-BCCz).We conduct compressive tests on these four lattices and numerically simulate the compression process through the finite element method.Analysis results show that BCCz has higher modulus and strength than BCC.In addition,uniform lattices show better energy absorption capabilities at small compression distances,while graded lattices absorb more energy at large compression distances.The good correlation between the simulation results and the experimental phenomena demonstrates the validity and accuracy of the present investigation method.

Genome-wide analysis identify novel germline genetic variations in ADCY1 influencing platinum-based chemotherapy response in nonsmall cell lung cancer

To explore the pharmacogenomic markers that affect the platinum-based chemotherapy response in non-small-cell lung carcinoma(NSCLC),we performed a two-cohort of genome-wide association studies(GWAS),including 34 for WES-based and 433 for microarray-based analyses,as well as two independent validation cohorts.After integrating the results of two studies,the genetic variations related to the platinum-based chemotherapy response were further determined by fine-mapping in 838 samples,and their potential functional impact were investigated by eQTL analysis and in vitro cell experiments.We found that a total of 68 variations were significant at P<1×10^(-3)in cohort 1 discovery stage,of which 3 SNPs were verified in 262 independent samples.A total of541 SNPs were significant at P<1×10^(-4)in cohort 2 discovery stage,of which 8 SNPs were verified in 347 independent samples.Comparing the validated SNPs in two GWAS,ADCY1 gene was verified in both independent studies.The results of fine-mapping showed that the G allele carriers of ADCY1rs2280496 and C allele carriers of rs189178649 were more likely to be resistant to platinum-based chemotherapy.In conclusion,our study found that rs2280496 and rs189178649 in ADCY1 gene were associated the sensitivity of platinum-based chemotherapy in NSCLC patients.

Prohibitin regulates mTOR pathway via interaction with FKBP8

The ability of tumor cells to sustain continuous proliferation is one of the major characteristics of cancer.The activation of oncogenes and the mutation or inactivation of tumor suppressor genes ensure the rapid proliferation of tumor cells.The PI3K-Akt-mTOR axis is one of the most frequently modified signaling pathways whose activation sustains cancer growth.Unsurprisingly,it is also one of the most commonly attempted targets for cancer therapy.FK506 binding protein 8(FKBP8)is an intrinsic inhibitor of mTOR kinase that also exerts an anti-apoptotic function.We aimed to explain these contradictory aspects of FKBP8 in cancer by identifying a“switch”type regulator.We identified through immunoprecipitation--mass spectrometry-based proteomic analysis that the mitochondrial protein prohibitin 1(PHB1)specifically interacts with FKBP8.Furthermore,the downregulation of PHB1 inhibited the proliferation of ovarian cancer cells and the mTOR signaling pathway,whereas the FKBP8 level in the mitochondria was substantially reduced.Moreover,concomitant with these changes,the interaction between FKBP8 and mTOR substantially increased in the absence of PHB1.Collectively,our finding highlights PHB1 as a potential regulator of FKBP8 because of its subcellular localization and mTOR regulating role.

Group 2 innate lymphoid cells can engulf and destroy bacteria

Group 2 innate lymphoid cells(ILC2s)are now known to play prominent roles in many inflammatory responses involving the production of Th2-type cytokines,which contribute to parasitic infections,tissue repair,and metabolic homeostasis[1].More recently,it has emerged that ILC2s may act as antigen-presenting cells,although corresponding evidence of phagocytic activity of these cells is currently scarce[2,3].Herein,we investigated whether ILC2s can phagocytose bacteria,through in vitro experiments.