Influence of heat treatment on microstructure,mechanical and corrosion behavior of WE43 alloy fabricated by laser-beam powder bed fusion

Magnesium(Mg)alloys are considered to be a new generation of revolutionary medical metals.Laser-beam powder bed fusion(PBF-LB)is suitable for fabricating metal implants withpersonalized and complicated structures.However,the as-built part usually exhibits undesirable microstructure and unsatisfactory performance.In this work,WE43 parts were firstly fabricated by PBF-LB and then subjected to heat treatment.Although a high densification rate of 99.91%was achieved using suitable processes,the as-built parts exhibited anisotropic and layeredmicrostructure with heterogeneously precipitated Nd-rich intermetallic.After heat treatment,fine and nano-scaled Mg24Y5particles were precipitated.Meanwhile,theα-Mg grainsunderwent recrystallization and turned coarsened slightly,which effectively weakened thetexture intensity and reduced the anisotropy.As a consequence,the yield strength and ultimate tensile strength were significantly improved to(250.2±3.5)MPa and(312±3.7)MPa,respectively,while the elongation was still maintained at a high level of 15.2%.Furthermore,the homogenized microstructure reduced the tendency of localized corrosion and favoredthe development of uniform passivation film.Thus,the degradation rate of WE43 parts was decreased by an order of magnitude.Besides,in-vitro cell experiments proved their favorable biocompatibility.

Biomedical rare-earth magnesium alloy:Current status and future prospects

Biomedical magnesium(Mg)alloys have garnered significant attention because of their unique biodegradability,favorable biocompatibility,and suitable mechanical properties.The incorporation of rare earth(RE)elements,with their distinct physical and chemical properties,has greatly contributed to enhancing the mechanical performance,degradation behavior,and biological performance of biomedical Mg alloys.Currently,a series of RE-Mg alloys are being designed and investigated for orthopedic implants and cardiovascular stents,achieving substantial and encouraging research progress.In this work,a comprehensive summary of the state-of-the-art in biomedical RE-Mg alloys is provided.The physiological effects and design standards of RE elements in biomedical Mg alloys are discussed.Particularly,the degradation behavior and mechanical properties,including their underlying action are studied in-depth.Furthermore,the preparation techniques and current application status of RE-Mg alloys are reviewed.Finally,we address the ongoing challenges and propose future prospects to guide the development of high-performance biomedical Mg-RE alloys.

Effect of dielectric material on the uniformity of nanosecond pulsed dielectric barrier discharge

Dielectric barrier discharge(DBD)is considered as a promising technique to produce large volume uniform plasma at atmospheric pressure,and the dielectric barrier layer between the electrodes plays a key role in the DBD processes and enhancing discharge uniformity.In this work,the uniformity and discharge characteristics of the nanosecond(ns)pulsed DBD with dielectric barrier layers made of alumina,quartz glass,polycarbonate(PC),and polypropylene(PP)are investigated via discharge image observation,voltage-current waveform measurement and optical emission spectral diagnosis.Through analyzing discharge image by gray value standard deviation method,the discharge uniformity is quantitatively calculated.The effects of the space electric field intensity,the electron density(Ne),and the space reactive species on the uniformity are studied with quantifying the gap voltage Ug and the discharge current Ig,analyzing the recorded optical emission spectra,and simulating the temporal distribution of Ne with a one-dimensional fluid model.It is found that as the relative permittivity of the dielectric materials increases,the space electric field intensity is enhanced,which results in a higher Ne and electron temperature(Te).Therefore,an appropriate value of space electric field intensity can promote electron avalanches,resulting in uniform and stable plasma by the merging of electron avalanches.However,an excessive value of space electric field intensity leads to the aggregation of space charges and the distortion of the space electric field,which reduce the discharge uniformity.The surface roughness and the surface charge decay are measured to explain the influences of the surface properties and the second electron emission on the discharge uniformity.The results in this work give a comprehensive understanding of the effect of the dielectric materials on the DBD uniformity,and contribute to the selection of dielectric materials for DBD reactor and the realization of atmospheric pressure uniform,stable,and reactive plasma sources.

How does network intermediary affect collaborative innovation?Evidence from Chinese listed companies

Purpose:This study aims to explore how network intermediaries influence collaborative innovation performance within inter-organizational technological collaboration networks.Design/methodology/approach:This study employs a mixed-method approach,combining quantitative social network analysis with regression techniques to investigate the role of network intermediaries in collaborative innovation performance.Using a patent dataset of Chinese industrial enterprises,the research constructs the collaboration networks and analyzes their structural positions,particularly focusing on their role as intermediaries,characterized by betweenness centrality.Negative binomial regression analysis is employed to assess how these network characteristics shape innovation outcomes.Findings:The study reveals that firms in intermediary positions enhance collaborative innovation performance,but this effect is nuanced.A key finding is that network clustering negatively moderates the intermediary-innovation relationship.Highly clustered networks,while fostering local collaboration,may limit the innovation potential of intermediaries.On the other hand,relationship strength,measured by collaboration intensity and trust among firms,positively moderates the intermediary-innovation link.Research limitations:This study has several limitations that present opportunities for further research.The reliance on quantitative social network analysis may overlook the complexity of intermediaries’roles,and future studies could benefit from incorporating qualitative methods to better understand cultural and institutional factors.Additionally,cross-country comparisons are needed to assess the consistency of these dynamics in different contexts.Practical implications:The study offers practical insights for firms and policymakers.Organizations should strategically position themselves as network intermediaries to access diverse information and resources,thereby improving innovation performance.Building strong trust helps using network intermediary advantages.For firms in highly clustered networks,it is important to seek external partners to avoid limiting their exposure to new ideas and technologies.This research emphasizes the need to balance network diversity with relationship strength for sustained innovation.Originality/value:This research contributes to the literature by offering new insights into the role of network intermediaries,presenting a comprehensive framework for understanding the interaction between network dynamics and firm innovation.

Dynamic Characteristics of Metro Vehicle under Thermal Deformation of Long-Span Cable-Stayed Bridge

In order to study the influence of thermal deformation of long-span cable- stayed bridge (LSCSB) on the dynamic characteristics of metro vehicle on the bridge, based on the theory of vehicle-track coupled dynamics, the rigid-flexible coupled dynamic model of metro vehicle-track-LSCSB system is established by using finite element method and multi-rigid-body dynamics. Adopting this model, the deformation of LSCSB subject to temperature is analyzed, then the comprehensive effect of track random irregularity and rail deformation caused by temperature load is considered to study the dynamic characteristics of metro vehicle running through the bridge, and finally the influences of temperature increment and running speed on concerned dynamic indices of vehicle are studied. The results show that the LSCSB deforms obviously subject to temperature load, and the overall performance is that the cooling is arched, and the heating is bent, and the shape variable changes almost linearly with the temperature load. According to the parameters studied in this paper, the rail deformation caused by temperature load increases the wheel-rail vertical force, derailment coefficient and wheel load reduction rate by 1.5%, 3.1% and 5% respectively. The vertical acceleration of the vehicle body decreases by 2.4% under the cooling condition, while increases by 3.7% under the heating condition. The dynamic response of the bridge changes under temperature load. The maximum vertical and horizontal displacement in the middle of the main beam span are 6.24 mm and 2.19 mm respectively, and the maximum vertical and horizontal acceleration are 1.29 cm/s2 and 2.54cm/s2 respectively. The derailment coefficient and vertical acceleration of vehicle body are more affected by temperature load, and the wheel load reduction rate and wheel-rail vertical force are more affected by speed. The conclusion of this paper provides a reference for subsequent scholars to study the influence of thermal deformation on the dynamic response of vehicles on LSCSB.

5-氟尿嘧啶和卡培他滨对中国患者的心脏毒性:一项前瞻性研究

背景与目的已有许多研究报道5-氟尿嘧啶(5-Fluorouracil,5-FU)和卡培他滨相关的心脏毒性,严重程度从无症状心电图(electrocardiography,ECG)异常到严重心肌梗塞而不同。目前为止,对中国恶性肿瘤患者的这种心脏毒性尚无研究。本研究旨在前瞻性地对多个中心招募的癌症患者进行5-FU和卡培他滨相关心脏毒性的发生率和临床表现进行评估。方法在完成研究的527例患者中,196例接受基于5-FU的化疗,331例接受基于卡培他滨的化疗并以其为一线或辅助治疗。在治疗期间和长达28 d的随访期间对所发生的不良反应进行记录。疗效测量指标包括心电图、心肌酶、心肌肌钙蛋白、脑钠肽和超声心动图。使用单因素分析和logistic回归方法进行亚组分析和鉴定与两种药物的心脏毒性相关的显著性独立变量。结果 527例患者中有161例(30.6%)出现心脏毒性。卡培他滨组的心脏毒性发生率为33.8%(112/331),显著高于5-FU组25%(49/196)的发生率(P=0.0042)。110/527患者(20.9%)发生心律失常,105/527(19.9%)发生缺血性改变,而只有20/527患者(3.8%)出现心力衰竭,6/527患者(1.1%)出现心肌梗塞。既往的心脏病、高血压、卡培他滨为基础的化疗和治疗时间被确定为与心脏毒性相关的显著风险因素。优势比分别为15.7(心脏病史vs.无病史)、1.86(卡培他滨vs. 5-FU)、1.06(5–8个化疗周期vs. 1–4个化疗周期)和1.58(高血压vs.无高血压)。结论氟嘧啶类药物在中国人群中引起的心脏毒性可能在临床实践中被低估。建议密切监测患者,尤其是对心脏毒性高风险的患者。可能的风险因素包括治疗持续时间、基于卡培他滨的化疗、既往心脏病史和高血压史。

An Interactive Online Platform for Algorithms Teaching

Learning programming has become an important part of education.However,most students have extreme difficulty learning programming and complex algorithms.This is because programming has a hierarchical logic.Solving complex problems requires students to develop skills in decomposing problems.To this end,this paper describes an effective method to develop an online platform for teaching complex algorithms.

Incorporation of Mg-phenolic networks as a protective coating for magnesium alloy to enhance corrosion resistance and osteogenesis in vivo

Magnesium(Mg) and its alloys have been intensively studied to develop the next generation of bone implants recently, but their clinical application is restricted by rapid degradation and unsatisfied osteogenic effect in vivo. A bioactive chemical conversion Mg-phenolic networks complex coating(e EGCG) was stepwise incorporated by epigallocatechin-3-gallate(EGCG) and exogenous Mg^(2+)on Mg-2Zn magnesium alloy. Simplex EGCG induced chemical conversion coating(c EGCG) was set as compare group. The in vitro corrosion behavior of Mg-2Zn alloy, c EGCG and e EGCG was evaluated in SBF using electrochemical(PDP, EIS) and immersion test. The cytocompatibility was investigated with rat bone marrow mesenchymal stem cells(r BMSCs). Furthermore, the in vivo tests using a rabbit model involved micro computed tomography(Micro-CT) analysis, histological observation, and interface analysis. The results showed that the e EGCG is Mgphenolic multilayer coating incorporated Mg-phenolic networks, which is rougher, more compact and much thicker than c EGCG. The e EGCG highly improved the corrosion resistance of Mg-2Zn alloy, combined with its lower average hemolytic ratios, continuous high scavenging effect ability and relatively moderate contact angle features, resulting in a stable and suitable biological environment, obviously promoted r BMSCs adhesion and proliferation. More importantly, Micro-CT, histological and interface elements distribution evaluations all revealed that the e EGCG effectively inhibited degradation and enhanced bone tissue formation of Mg alloy implants. This study puts forward a promising bioactive chemical conversion coating with Mg-phenolic networks for the application of biodegradable orthopedic implants.

PICOTEES:a privacy-preserving online service of phenotype exploration for genetic-diagnostic variants from Chinese children cohorts

The growth in biomedical data resources has raised potential privacy concerns and risks of genetic information leakage. For instance, exome sequencing aids clinical decisions by comparing data through web services, but it requires significant trust between users and providers. To alleviate privacy concerns, the most commonly used strategy is to anonymize sensitive data. Unfortunately, studies have shown that anonymization is insufficient to protect against reidentification attacks. Recently, privacy-preserving technologies have been applied to preserve application utility while protecting the privacy of biomedical data. We present the PICOTEES framework, a privacy-preserving online service of phenotype exploration for genetic-diagnostic variants (https://birthdefectlab.cn:3000/). PICOTEES enables privacy-preserving queries of the phenotype spectrum for a single variant by utilizing trusted execution environment technology, which can protect the privacy of the user's query information, backend models, and data, as well as the final results. We demonstrate the utility and performance of PICOTEES by exploring a bioinformatics dataset. The dataset is from a cohort containing 20,909 genetic testing patients with 3,152,508 variants from the Children's Hospital of Fudan University in China, dominated by the Chinese Han population (>99.9%). Our query results yield a large number of unreported diagnostic variants and previously reported pathogenicity.

Effect of cobalt substitution for nickel on microstructural evolution and hydrogen storage properties of La_(0.66)Mg_(0.34)Ni_(3.5-x)Co_(x) alloys

Superlattice hydrogen storage alloys offer a compelling advantage with rapid hydriding rate and high storage capacity.However,its practical applications face challenges including complex structure,low dehydriding capacity,and cyclic instability.In this work,we successfully prepared La_(0.66)Mg_(0.34)Ni_(3.5-x)Co_(x) superlattice hydrogen storage alloys with enhanced dehydriding capacity and stability by partially substituting Co for Ni.X-ray diffraction(XRD)refinements analysis reveals the presence of(La,Mg)_(3)Ni_(9),(La,Mg)_5Ni_(19),and LaNi_(5) phases within the alloy.Following Co substitution in the La_(0.06)Mg_(0.34)Ni_(3.4)Co_(0.1)alloy,there is a significant increase in content of the(La,Mg)_(3)Ni_(9) phase and a reduction in the hysteresis factor,resulting in an improved reversible hydrogen storage capacity from 1.45 wt%to 1.60 wt%.The dehydriding kinetics of the alloy is controlled by diffusion model with an activation energy of 8.40 kJ/mol.Furthermore,the dehydriding enthalpy value of the Co-substituted alloy decreases from 30.84 to 29.85 kJ/mol.Impressively,the cycling performance of the alloy after Co substitution exhibits excellent stability,with a capacity retention rate of 92.3%after 100 cycles.These findings provide valuable insights for the development of cost-effective hydrogen storage materials.

A Novel Rolling and Fractional-ordered Grey System Model and Its Application for Predicting Industrial Electricity Consumption

Accurate and reasonable prediction of industrial electricity consumption is of great significance for promoting regional green transformation and optimizing the energy structure.However,the regional power system is complicated and uncertain,affected by multiple factors including climate,population and economy.This paper incorporates structure expansion,parameter optimization and rolling mechanism into a system forecasting framework,and designs a novel rolling and fractional-ordered grey system model to forecast the industrial electricity consumption,improving the accuracy of the traditional grey models.The optimal fractional order is obtained by using the particle swarm optimization algorithm,which enhances the model adaptability.Then,the proposed model is employed to forecast and analyze the changing trend of industrial electricity consumption in Fujian province.Experimental results show that industrial electricity consumption in Fujian will maintain an upward growth and it is expected to 186.312 billion kWh in 2026.Compared with other seven benchmark prediction models,the proposed grey system model performs best in terms of both simulation and prediction performance metrics,providing scientific reference for regional energy planning and electricity market operation.

Genomic landscapes of Chinese sporadic autism spectrum disordersrevealed by whole-genome sequencing

Autism spectrum disorder (ASD) is a neurodevelopmental disorder with considerable clinical and genetic heterogeneity.In this study,we identified all classes of genomic variants from whole-genome sequencing (WGS) dataset of 32 Chinese trios with ASD,including de novo mutations,inherited variants,copy number variants (CNVs) and genomic structural variants.A higher mutation rate (Poisson test,P<2.2×10^(-16)) in exonic (1.37×10^(-8)) and 3'-UTR regions (1.42×10^(-8)) was revealed in comparison with that of whole genome (1.05×10^(-8)).Using an integrated model,we identified 87 potentially risk genes (P<0.01) from 4832 genes harboring various rare deleterious variants,including CHD8 and NRXN2,implying that the disorders may be in favor to multiple-hit.In particular,frequent rare inherited mutations of several microcephaly-associated genes (ASPM,WDR62,and ZNF335)were found in ASD.In chromosomal structure analyses,we found four de novo CNVs and one de novo chromosomal rearrangement event,including a de novo duplication of UBE3A-containing region at 15q11.2-q13.1,which causes Angelman syndrome and microcephaly,and a disrupted TNR due to de novo chromosomal translocation t (1;5) (q25.1;q33.2).Taken together,our results suggest that abnormalities of centrosomal function and chromatin remodeling of the microcephaly-associated genes may be implicated in pathogenesis of ASD.Adoption of WGS as a new yet efficient technique to illustrate the full genetic spectrum in complex disorders,such as ASD,could provide novel insights into pathogenesis,diagnosis and treatment.

影响Omicron变异株感染轻型和普通型COVID-19患儿核酸转阴时间缩短因素分析

目的探讨Omicron变异株感染轻型与普通型新型冠状病毒疾病(COVID-19)患儿的临床特征及影响其核酸检测结果转为阴性(以下简称为"核酸转阴")时间缩短因素。方法选取2022年4月7日至5月20日上海交通大学医学院附属仁济医院南院区"亲子病房"集中收治的150例Omicron变异株感染轻型和普通型COVID-19患儿为研究对象。采用回顾性分析方法,根据这150例患儿的核酸转阴中位时间为13 d,将其分别纳入快转阴组(n=84,核酸转阴时间<13 d)和慢转阴组(n=66,核酸转阴时间≥13 d)。对2组患儿年龄、性别、轻型与普通型COVID-19患儿构成比、疫苗接种率、COVID-19相关临床表现及COVID-19发病48 h内系统炎症指数(SII)、中性粒细胞与淋巴细胞比值(NLR)、淋巴细胞与单核细胞比值(LMR)、血小板与淋巴细胞比值(PLR)等,进行成组t检验、Mann-Whitney U检验或χ2检验。采用多因素非条件logistic回归分析方法,分析影响Omicron变异株感染轻型与普通型COVID-19患儿核酸转阴时间缩短的因素。2组患儿合并基础疾病占比、采取对症治疗率等一般临床资料分别比较,差异均无统计学意义(P>0.05)。本研究遵循的程序符合2013修订的《世界医学协会赫尔辛基宣言》要求。结果①快转阴组患儿年龄、女性患儿比例、普通型COVID-19患儿比例、疫苗接种率,发热、咽痛、胃肠道症状发生率,均显著高于慢转阴组,而热峰、肌肉酸痛发生率,则均显著低于慢转阴组,2组比较,差异均有统计学意义(P<0.05)。②多因素非条件logistic回归分析结果显示,伴有咽痛、接种疫苗是轻型与普通型COVID-19患儿核酸转阴时间缩短的独立保护因素(OR=14.609、7.866,95%CI:1.108~192.697、1.313~47.121,P=0.042、0.024),而伴有肌肉酸痛、男性患儿则是其独立危险因素(OR=0.275、0.206,95%CI:0.087~0.874、0.083~0.511,P=0.029、0.001)。③快转阴组患儿SII为250.9×109/L(111.1×109/L,466.9×109/L),NLR为1.0(0.6,2.2),均分别显著高于慢转阴组的109.8×109/L(47.2×109/L,266.7×109/L)与0.5(0.2,1.2),并且差异均有统计学意义(Z=6.48、5.34,P=0.011、0.021)。快转阴组患儿LMR为4.1(2.5,9.4),显著低于慢转阴组的8.2(3.4,11.1),并且差异有统计学意义(Z=4.50,P=0.034)。结论轻型与普通型COVID-19患儿临床表现不典型,以发热、咳嗽为主,高SII、NLR及低LMR患儿核酸转阴时间较短,接种疫苗、伴有咽痛是促进核酸转阴时间缩短的保护性因素,伴有肌肉酸痛及男性是影响核酸转阴时间缩短的危险因素。

Magnesium surface-activated 3D printed porous PEEK scaffolds for in vivo osseointegration by promoting angiogenesis and osteogenesis

Polyetheretherketone(PEEK)has been an alternative material for titanium in bone defect repair,but its clinical application is limited by its poor osseointegration.In this study,a porous structural design and activated surface modification were used to enhance the osseointegration capacity of PEEK materials.Porous PEEK scaffolds were manufactured via fused deposition modeling and a polydopamine(PDA)coating chelated with magnesium ions(Mg^(2+))was utilized on the surface.After surface modification,the hydrophilicity of PEEK scaffolds was significantly enhanced,and bioactive Mg^(2+)could be released.In vitro results showed that the activated surface could promote cell proliferation and adhesion and contribute to osteoblast differentiation and mineralization;the released Mg^(2+)promoted angiogenesis and might contribute to the formation of osteogenic H-type vessels.Furthermore,porous PEEK scaffolds were implanted in rabbit femoral condyles for in vivo evaluation of osseointegration.The results showed that the customized three-dimensional porous structure facilitated vascular ingrowth and bone ingrowth within the PEEK scaffolds.The PDA coating enhanced the interfacial osseointegration of porous PEEK scaffolds and the released Mg^(2+)accelerated early bone ingrowth by promoting early angiogenesis during the coating degradation process.This study provides an efficient solution for enhancing the osseointegration of PEEK materials,which has high potential for translational clinical applications.

Polydopamine-assisted functionalization of heparin and vancomycin onto microarc-oxidized 3D printed porous Ti6Al4V for improved hemocompatibility,osteogenic and anti-infection potencies

Enhanced antiinfection activities, improved hemocompatibility and osteo-compatibility, and reinforced osseointegration are among the most important considerations in designing multifunctional orthopedic biomaterials.Hereby, anti-infective and osteogenic multifunctional 3 D printed porous Ti6 Al4 V implant with excellent hemocompatibility was successfully designed and fabricated. In brief, osteogenic micro-arc oxidation（MAO） coatings with micro/nanoscale porous topography were generated in situ on3 D printed Ti6 Al4 V scaffolds, on which heparin and vancomycin were easily immobilized. The surface microstructure,morphology, and chemical compositions were characterized employing scanning electron microscopy（SEM）, X-ray photoelectron spectroscopy（XPS） and Fourier transform infrared spectroscopy（FTIR）. High loading capacity and sustained vancomycin release profiles were revealed using high performance liquid chromatography（HPLC）. Favorable antibacterial and antibiofilm performances against pathogenic Staphylococcus aureus（S. aureus） were validated in vitro through microbial viability assays, Live/Dead bacterial staining, and crystal violet staining. Human mesenchymal stem cells（h MSCs） were seeded on the scaffolds and their proliferation and viability were assessed using Cell Counting Kit and Live/Dead cell viability kit. Further, osteoblastic differentiation abilities were evaluated using alkaline phosphatase（ALP） activity as a hall marker. Additionally, the improved hemocompatibility of the heparinized scaffolds was confirmed by activated partial thromboplastin time（APTT）, prothrombin time（PT） and thrombin time（TT）. Overall, our results show that the surface-modified 3 D printed porous Ti6 Al4 V possesses balanced antibacterial and osteogenic functions while exhibiting extra anticlotting effects, boding well for future application in customized functional reconstruction of intricate bone defects.

Three-dimensional-printed individualized porous implants:A new“implant-bone”interface fusion concept for large bone defect treatment

Bone defect repairs are based on bone graft fusion or replacement.Current large bone defect treatments are inadequate and lack of reliable technology.Therefore,we aimed to investigate a simple technique using three-dimensional(3D)-printed individualized porous implants without any bone grafts,osteoinductive agents,or surface biofunctionalization to treat large bone defects,and systematically study its long-term therapeutic effects and osseointegration characteristics.Twenty-six patients with large bone defects caused by tumor,infection,or trauma received treatment with individualized porous implants;among them,three typical cases underwent a detailed study.Additionally,a large segmental femur defect sheep model was used to study the osseointegration characteristics.Immediate and long-term biomechanical stability was achieved,and the animal study revealed that the bone grew into the pores with gradual remodeling,resulting in a long-term mechanically stable implant-bone complex.Advantages of 3D-printed microporous implants for the repair of bone defects included 1)that the stabilization devices were immediately designed and constructed to achieve early postoperative mobility,and 2)that osseointegration between the host bone and implants was achieved without bone grafting.Our osseointegration method,in which the“implant-bone”interface fusion concept was used instead of“bone-bone”fusion,subverts the traditional idea of osseointegration.

Biomimetic AgNPs@antimicrobial peptide/silk fibroin coating for infection-trigger antibacterial capability and enhanced osseointegration

Endowing implant surfaces with combined antibacterial and osteogenic properties by drug-loaded coatings has made great strides,but how to achieve the combined excellence of infection-triggered bactericidal and in vivo-proven osteogenic activities without causing bacterial resistance still remains a formidable challenge.Herein,antimicrobial peptides(AMPs)with osteogenic fragments were designed and complexed on the surface of silver nanoparticle(AgNP)through hydrogen bonding,and the collagen structure-bionic silk fibroin(SF)was applied to carry AgNPs@AMPs to achieve infection-triggered antibacterial and osteointegration.As verified by TEM,AMPs contributed to the dispersion and size-regulation of AgNPs,with a particle size of about 20 nm,and a clear protein corona structure was observed on the particle surface.The release curve of silver ion displayed that the SF-based coating owned sensitive pH-responsive properties.In the antibacterial test against S.aureus for up to 21 days,the antibacterial rate had always remained above 99%.Meanwhile,the underlying mechanism was revealed,originating from the destruction of the bacterial cell membranes and ROS generation.The SF-based coating was conducive to the adhesion,diffusion,and proliferation of bone marrow stem cells(BMSCs)on the surface,and promoted the expression of osteogenic genes and collagen secretion.The in vivo implantation results showed that compared with the untreated Ti implants,SF-based coating enhanced osseointegration at week 4 and 8.Overall,the AgNPs@AMPs-loaded SF-based coating presented the ability to synergistically inhibit bacteria and promote osseointegration,possessing tremendous potential application prospects in bone defects and related-infection treatments.

In vitro degradation and biocompatibility evaluation of typical biodegradable metals (Mg/Zn/Fe) for the application of tracheobronchial stenosis

Tracheobronchial obstruction in children due to benign stenosis or tracheobronchomalacia still remains a challenging matter of concern.Currently,there is 10%–20%complication rate in clinical treatment.The nonbiodegradable property of silicone stents and nickel-titanium memory alloy stents take the primary responsibility for drawbacks including stimulating local granulation tissue proliferation,displacement,and stent-related infections.Permanent tracheobronchial stent will be a persistent foreign object for a long time,causing excessive secretion of tracheal mucosa,ulceration and even perforation,which is particularly unsuitable for young children with persistent tracheal growth.In this study,the degradation and biocompatibility performance of three typical biodegradable metals were investigated as potential tracheobronchial stent materials.The results exhibited that these materials showed different degradation behaviors in the simulating respiratory fluid environment compared with SBF.Except for pure iron group,high purity magnesium and zinc showed favorable cell adhesion and proliferation in three culture methodologies(direct culture,indirect culture and extraction culture).The proper corrosion rate and good biocompatibility indicated that high purity magnesium and zinc may be good candidates as tracheobronchial stent materials.

Cardiotoxicity of 5-fluorouracil and capecitabine in Chinese patients: a prospective study

Background:5-Fluorouracil(5-FU)and capecitabine-associated cardiotoxicity ranging from asymptomatic electro-cardiography(ECG)abnormalities to severe myocardial infarction has been reported in a number of studies,but such cardiotoxicity in Chinese patients with malignant diseases has not been investigated to date.In the present study,we aimed to prospectively evaluate the incidence rates and clinical manifestations of 5-FU-and capecitabine-associated cardiotoxicity in cancer patients recruited from multiple centers in China.Methods:Among the 527 patients who completed the study,196 received 5-FU-based chemotherapy and 331 received capecitabine-based chemotherapy as either first-line or adjuvant therapy.Adverse events were reported during the treatment and up to 28 days of follow-up.Outcome measures included ECG,myocardial enzymes,cardiac troponin,brain natriuretic peptide and echocardiography.Univariate analysis and logistic regression were performed for subgroup analysis and identification of significant independent variables that are associated with cardiotoxicity of both agents.Results:In total,161 of 527 patients(30.6%)experienced cardiotoxicity.The incidence rate of cardiotoxicity was 33.8%(112/331)in the capecitabine group,which was significantly higher than the rate of 25%(49/196)in the 5-FU group(P=0.0042).110/527 patients(20.9%)suffered arrhythmia,105/527(19.9%)developed ischemic changes,while only 20/527 patients(3.8%)presented heart failure and 6/527 patients(1.1%)had myocardial infarction.Pre-existing cardiac disease,hypertension,capecitabine-based chemotherapy and duration of treatment were identified as sig-nificant risk factors associated with cardiotoxicity.The odds ratio were 15.7(prior history of cardiac disease versus no history),1.86(capecitabine versus 5-FU),1.06(5-8 versus 1-4 chemotherapy cycles)and 1.58(hypertension versus no hypertension),respectively.Conclusions:Cardiotoxicity induced by fluoropyrimidines in the Chinese population may be underestimated in clini-cal practice.Close monitoring of patients is recommended,especially for those patients at high risk for cardiotoxicity.Possible risk factors are duration of treatment,capecitabine-based chemotherapy,pre-existing cardiac diseases and hypertension.Trial registration This study was initiated on January 22,2014 and has been retrospectively registered with the registra-tion number ChiCTR1800015434 .

The Epigenetic Switches for Neural Development and Psychiatric Disorders

The most remarkable feature of the nervous system is that the development and functions of the brain are largely reshaped by postnatal experiences, in joint with genetic landscapes. The nature vs. nurture argument reminds us that both genetic and epigenetic information is indispensable for the normal function of the brain. The epigenetic regulatory mechanisms in the central nervous system have been revealed over last a decade. Moreover, the mutations of epigenetic modulator genes have been shown to be implicated in neuropsychiatric disorders, such as autism spectrum disorders. The epigenetic study has initiated in the neuroscience field for a relative short period of time. In this review, we will summarize recent discoveries about epigenetic regulation on neural development, synaptic plasticity, learning and memory, as well as neuropsychiatric disorders. Although the comprehensive view of how epigenetic regulation contributes to the function of the brain is still not completed, the notion that brain, the most complicated organ of organisms, is profoundly shaped by epigenetic switches is widely accepted.