Advanced surface engineering of titanium materials for biomedical applications:From static modification to dynamic responsive regulation

Titanium(Ti)and its alloys have been widely used as orthopedic implants,because of their favorable mechanical properties,corrosion resistance and biocompatibility.Despite their significant success in various clinical applications,the probability of failure,degradation and revision is undesirably high,especially for the patients with low bone density,insufficient quantity of bone or osteoporosis,which renders the studies on surface modification of Ti still active to further improve clinical results.It is discerned that surface physicochemical properties directly influence and even control the dynamic interaction that subsequently determines the success or rejection of orthopedic implants.Therefore,it is crucial to endow bulk materials with specific surface properties of high bioactivity that can be performed by surface modification to realize the osseointegration.This article first reviews surface characteristics of Ti materials and various conventional surface modification techniques involving mechanical,physical and chemical treatments based on the formation mechanism of the modified coatings.Such conventional methods are able to improve bioactivity of Ti implants,but the surfaces with static state cannot respond to the dynamic biological cascades from the living cells and tissues.Hence,beyond traditional static design,dynamic responsive avenues are then emerging.The dynamic stimuli sources for surface functionalization can originate from environmental triggers or physiological triggers.In short,this review surveys recent developments in the surface engineering of Ti materials,with a specific emphasis on advances in static to dynamic functionality,which provides perspectives for improving bioactivity and biocompatibility of Ti implants.

Long noncoding RNA negative regulator of antiviral response contributes to pancreatic ductal adenocarcinoma progression via targeting miR-299-3p

BACKGROUND Pancreatic ductal cancer(PDAC)has high malignancy and poor prognosis.Long noncoding RNAs(lncRNAs)are associated with high levels of malignancy,including PDAC.However,the biological and clinical significance of negative regulator of antiviral response(NRAV)in PDAC is unclear.AIM To study the regulatory role of lncRNA NRAV in PDAC.METHODS GEPIA analyzed lncRNA NRAV and miRNA(miR-299-3p)expression levels in PDAC tissues and measured them in PDAC cells by quantitative measurements in real time.The specific role of NRAV and miR-299-3p in cell proliferation and transfer potential was evaluated by cell formation analysis,Cell Counting Kit-8 and Transwell analysis.The relationship between NRAV and miR-299-3p was studied by predictive bioinformatics,RNA immunoassay,and fluorescence enzyme analysis.In vivo experiments included transplantation of simulated tumor cells under naked mice.RESULTS The expression level of lncRNA NRAV was higher in both tumor tissues and cell lines of PDAC and was negatively associated with the clinical survival of PDAC patients.Functionally,overexpression of NRAV promoted cell proliferation and metastasis of PDAC cells,while knockdown of NRAV reversed these effects.Finally,NRAV was performed as a molecular sponge of miR-299-3p.Moreover,overexpression of miR-299-3p could reverse the promoting effects of NRAV on cell proliferation and metastasis of PDAC cells.CONCLUSION NRAV facilitates progression of PDAC as a molecular sponge of miR-299-3p and may be a potential molecular marker for diagnosis and treatment of PDAC.

Hydrological Services by Mountain Ecosystems in Qilian Mountain of China: A Review

Hydrological service is a hot issue in the current researches of ecosystem service, particularly in the upper reaches of mountain rivers in dry land areas, where the Qilian Mountain is a representative one. The Qilian Mountain, where forest, shrubland and grassland consist of its main ecosystems, can provide fresh water and many other ecosystem services, through a series of eco-hydrological process such as precipitation interception, soil water storage, and fresh water provision. Thus, monitoring water regulation and assessing the hydrological service of the Qilian Mountain are meaningful and helpful for the healthy development of the lower reaches of arid and semi-arid areas. In recent 10 years, hydrological services have been widely researched in terms of scale and landscape pattern, including water conservation, hydrological responses to afforestation and their ecological effects. This study, after analyzing lots of current models and applications of geographical information system（GIS） in hydrological services, gave a scientific and reasonable evaluation of mountain ecosystem in eco-hydrological services, by employing the combination of international forefronts and contentious issues into the Qilian Mountain. Assessments of hydrological services at regional or larger scales are limited compared with studies within watershed scale in the Qilian Mountain. In our evaluation results of forest ecosystems, it is concluded that long-term observation and dynamic monitoring of different types of ecosystem are indispensable, and the hydrological services and the potential variation in water supplement on regional and large scales should be central issues in the future research.v

The molecular characteristics of soybean ARR-B transcription factors

The Type-B authentic response regulator(ARR-Bs)gene family is one of the important plant-specific transcription factor families involved in variety of physiological processes.However,study of ARR-Bs gene family in soybean is limited.Genome-wide analysis and expression profiling of the ARR-Bs gene family were performed in the soybean genome.31 ARR-Bs genes(namely GmARR-B1-31)were identified,containing conserved catalytic domains with protein lengths and molecular weights ranging from 246 to 699 amino acids(aa)and 28.30 to 76.86 kDa,respectively.Phylogenetic analysis grouped ARR-Bs genes into three clusters—Cluster I,Cluster II,and Cluster III—which included 15,12,and 4 genes,respectively,and were asymmetrically distributed on 17 chromosomes.Tissue specific expression analysis of GmARR-Bs family revealed a high transcription level in flowers,roots and seeds.The subcellular localization of GmARR5,GmARR14 were observed in the nucleus,and the promoter region of them included low-temperature responsive element(LTR),the C-repeat/dehydration responsive element(DRE),MBS,ABRE,MYB,MEJA and TCA-elements,which possibly participate in abiotic stress and hormones responses.qRTPCR analysis showed that the expression of GmARR-B genes were affected by different abiotic stresses,especially cold stress and salt stress,and GmARR-B5 and GmARR-B14 were significantly induced by cold stress.This suggested that ARR-Bs genes were involved in multiple abiotic stress response pathways and acted as a positive factor under cold stress.

Fermentation Production of Ganoderma lucidum by Bacillus subtilis Ameliorated Ceftriaxone-induced Intestinal Dysbiosis and Improved Intestinal Mucosal Barrier Function in Mice

Objective This study aimed to develop a type of Ganoderma lucidum(G.lucidum)-probiotic fermentation broth that can effectively improve the intestinal mucosal barrier function of mice with ceftriaxone-induced intestinal dysbiosis.Methods By means of absorbance of optical density(OD)value and phenol-concentrated sulfuric acid measurement of polysaccharide content,the probiotic species can grow on the medium of G.lucidum were screened out,and the concentration of the medium of G.lucidum was determined,and the fermentation broth was prepared for subsequent experiments.Thirty-two SPF grade male BALB/c mice were randomly divided into four groups(eight mice in each group),namely control group(CON),intestinal mucosal barrier damage model group(CS),fermentation broth intervention group(FT)and G.lucidum medium intervention group(GL),respectively.The intestinal dysregulation model was induced by intra-gastric administration of 0.2 mL ceftriaxone sodium(twice a day for seven consecutive days).From day 8,the FT group and GL group were gavage with 0.2 mL fermentation broth and G.lucidum medium,respectively.On day 15,all mice were sacrificed.To draw the weight curve and measure the cecal index;pathological examination of colon tissues with HE staining;serum levels of LPS,IL-10,TNF and IL-6 were detected by ELISA.Flow cytometry was used to analyze the changes of CD3+T cells,CD4+T cells,CD8+T cells and macrophages in spleen.16S rRNA sequencing was performed to detect the intestinal microbiota structure of mice.Results Bacillus subtilis can decompose and utilize G.lucidum fruiting body medium,and the suitable concentration of G.lucidum fruiting body medium is 33.2 mg/mL.The effect of Bacillus subtilis-G.lucidum fermentation broth on the damage of intestinal mucosal barrier caused by ceftriaxone sodium was reduced,the body weight of mice recovered and colon swelling improved,colon histopathological injury was alleviated,inflammatory cell infiltration was alleviated,serum IL-10 increased significantly,LPS、TNF-αand IL-6 decreased significantly compared with model group,and the proportion of T cells and intestinal dysbiosis was improved.Conclusions The experimental results suggest that Bacillus subtilis-G.lucidum fermentation broth can effectively improve the intestinal barrier function damage,immune dysfunction and intestinal dysbiosis caused by antibiotic overdose,and has a certain regulatory effect on intestinal mucosal barrier function.

Neuregulin-1:a novel regulator of glial response in spinal cord injury

Spinal cord injury （SCI） results in a dysregulated microenvi- ronment that is largely driven by the immediate and robust response of resident astrocytes and microglia （Filous and Silver, 2016）.

Engineering a fumaric acid-responsive two-component biosensor for dynamic range improvement in Escherichia coli

Due to the selective permeability of the cytomembrane,high-yield fumaric acid strains form a steep difference between intra-and extracellular concentrations.Intracellular biosensors cannot detect the real concentration change of extracellular fumaric acid.To overcome this limitation,a two-component biosensor(TCB)that could respond to extracellular fumaric acid was designed based on the DcuS-DcuR two-component system.The two-component system consists of a histidine kinase(SK)and response regulator.SK is a transmembrane histidine kinase sensor that can detect concentration changes in extracellular compounds.To improve the dynamic range of the constructed fumaric acid TCB,we optimized the expression ratio and expression intensity of dcuS and dcuR.We found that the optimum expression ratio of dcuS:dcuR was 46:54.Under this ratio,the higher was the expression level,the greater the dynamic range.In addition,we modified the ATP-binding site on the DcuS,and the final dynamic range of the TCB reached 6.6-fold.Overall,the obtained fumaric acid-responsive TCB with a high dynamic range is reported for the first time,providing a synthetic biology tool for high-throughput screening and dynamic metabolic regulation of fumaric acid cell factories.

GmJAZ3 interacts with GmRR18a and GmMYC2a to regulate seed traits in soybean

Seed weight is usually associated with seed size and is one of the important agronomic traits that determine yield.Understanding of seed weight control is limited,especially in soybean plants.Here we show that Glycine max JASMONATEZIM DOMAIN 3(GmJAZ3),a gene identified through gene co-expression network analysis,regulates seed-related traits in soybean.Overexpression of GmJAZ3 promotes seed size/weight and other organ sizes in stable transgenic soybean plants likely by increasing cell proliferation.GmJAZ3 interacted with both G.max RESPONSE REGULATOR 18a(GmRR18a)and GmMYC2a to inhibit their transcriptional activation of cytokinin oxidase gene G.max CYTOKININ OXIDASE 3-4(GmCKX3-4),which usually affects seed traits.Meanwhile,the GmRR18a binds to the promoter of GmMYC2a and activates GmMYC2a gene expression.In GmJAZ3-overexpressing soybean seeds,the protein contents were increased while the fatty acid contents were reduced compared to those in the control seeds,indicating that the GmJAZ3 affects seed size/weight and compositions.Natural variation in JAZ3 promoter region was further analyzed and Hap3 promoter correlates with higher promoter activity,higher gene expression and higher seed weight.The Hap3 promoter may be selected and fixed during soybean domestication.JAZ3 orthologs from other plants/crops may also control seed size and weight.Taken together,our study reveals a novel molecular module GmJAZ3-GmRR18a/GmMYC2a-GmCKXs for seed size and weight control,providing promising targets during soybean molecular breeding for better seed traits.

Type-B response regulator OsRR22 forms a transcriptional activation complex with OsSLR1 to modulate OsHKT2;1 expression in rice

Soil salinity severely limits crop yields and quality.Plants have evolved several strategies to mitigate the adverse effects of salinity,including redistribution and compartmentalization of toxic ions using ion-specific transporters.However,the mechanisms underlying the regulation of these ion transporters have not been fully elucidated.Loss-of-function mutants of OsHKT2;1,which is involved in sodium uptake,exhibit strong salt stress-resistant phenotypes.In this study,OsHKT2;1 was identified as a transcriptional target of the type-B response regulator OsRR22.Loss-of-function osrr22 mutants showed resilience to salt stress,and OsRR22-overexpression plants were sensitive to salt stress.OsRR22 was found to activate the expression of OsHKT2;1 by directly binding to the promoter region of OsHKT2;1 via a consensus cis-element of type-B response regulators.Moreover,rice DELLA protein OsSLR1 directly interacted with OsRR22 and functioned as a transcriptional co-activator.This study has uncovered a novel transcriptional regulatory mechanism by which a type-B response regulator controls sodium transport under salinity stress.

Wind-farm and hydrogen-storage co-location system optimization for dynamic frequency response in the UK

The continuous development of hydrogen-electrolyser and fuel-cell technologies not only reduces their investment and operating costs but also improves their technical performance to meet fast-acting requirements of electrical grid balancing services such as frequency-response services.In order to project the feasibility of co-locating a hydrogen-storage system with a wind farm for the dynamic regulation frequency-response provision in Great Britain,this paper develops a modelling framework to coordinate the wind export and frequency responses to the main grid and manage the interaction of the electrolyser,compressor,storage tank and fuel cell within the hydrogen-storage system by respecting the market mechanisms and the balance and conversion of power and hydrogen flows.Then the revenue of frequency-response service provision and a variety of costs induced by the hydrogen-storage system are translated into the net profit of the co-location system,which is maximized by optimizing the capacities of hydrogen-storage-system components,hydrogen-storage levels that guide the hydrogen restoration via operational baselines and the power interchange between a wind-farm and hydrogen-storage system,as well as the capacities tendered for low-and high-frequency dynamic regulation services.The developed modelling framework is tested based on a particular 432-MW offshore wind farm in Great Britain combined with the techno-economics of electrolysers and fuel cells projected for 2030 and 2050 scenarios.The optimized system configuration and operation are compared between different operating scenarios and discussed alongside the prospect of applying hydrogen-storage systems for frequency-response provision.

Cell sheet formation enhances the therapeutic effects of human umbilical cord mesenchymal stem cells on myocardial infarction as a bioactive material

Stem cell-based therapy has been used to treat ischaemic heart diseases for two decades.However,optimal cell types and transplantation methods remain unclear.This study evaluated the therapeutic effects of human umbilical cord mesenchymal stem cell(hUCMSC)sheet on myocardial infarction(MI).Methods:hUCMSCs expressing luciferase were generated by lentiviral transduction for in vivo bio-luminescent imaging tracking of cells.We applied a temperature-responsive cell culture surface-based method to form the hUCMSC sheet.Cell retention was evaluated using an in vivo bio-luminescent imaging tracking system.Unbiased transcriptional profiling of infarcted hearts and further immunohistochemical assessment of monocyte and macrophage subtypes were used to determine the mechanisms underlying the therapeutic effects of the hUCMSC sheet.Echocardiography and pathological analyses of heart sections were performed to evaluate cardiac function,angiogenesis and left ventricular remodelling.Results:When transplanted to the infarcted mouse hearts,hUCMSC sheet significantly improved the retention and survival compared with cell suspension.At the early stage of MI,hUCMSC sheet modulated inflammation by decreasing Mcp1-positive monocytes and CD68-positive macrophages and increasing Cx3cr1-positive non-classical macrophages,preserving the cardiomyocytes from acute injury.Moreover,the extracellular matrix produced by hUCMSC sheet then served as bioactive scaffold for the host cells to graft and generate new epicardial tissue,providing mechanical support and routes for revascularsation.These effects of hUCMSC sheet treatment significantly improved the cardiac function at days 7 and 28 post-MI.Conclusions:hUCMSC sheet formation dramatically improved the biological functions of hUCMSCs,mitigating adverse post-MI remodelling by modulating the inflammatory response and providing bioactive scaffold upon transplantation into the heart.Translational perspective:Due to its excellent availability as well as superior local cellular retention and survival,allogenic transplantation of hUCMSC sheets can more effectively acquire the biological functions of hUCMSCs,such as modulating inflammation and enhancing angiogenesis.Moreover,the hUCMSC sheet method allows the transfer of an intact extracellular matrix without introducing exogenous or synthetic biomaterial,further improving its clinical applicability.

Structural Aspects of Multistep Phosphorelay- Mediated Signaling in Plants

The multistep phosphorelay （MSP） is a central signaling pathway in plants integrating a wide spectrum of hormonal and environmental inputs and controlling numerous developmental adaptations. For the thor- ough comprehension of the molecular mechanisms underlying the MSP-mediated signal recognition and transduction, the detailed structural characterization of individual members of the pathway is critical. In this review we describe and discuss the recently known crystal and nuclear magnetic resonance structures of proteins acting in MSP signaling in higher plants, focusing particularly on cytokinin and ethylene signaling in Arabidopsis thaliana. We discuss the range of functional aspects of available structural infor- mation including determination of ligand specificity, activation of the receptor via its autophosphorylaUon, and downstream signal transduction through the phosphorelay. We compare the plant structures with their bacterial counterparts and show that although the overall similarity is high, the differences in structural de- tails are frequent and functionally important. Finally, we discuss emerging knowledge on molecular recog- nition mechanisms in the MSP, and mention the latest findings regarding structural determinants of signaling specificity in the Arabidopsis MSP that could serve as a general model of this pathway in all higher plants.

Deletion of the Initial 45 Residues of ARR18 Induces Cytokinin Response in Arabidopsis

The plant hormone cytokinin plays important roles in various aspects of plant growth and development. Cytokinin signaling is mediated by a multistep phosphorelay similar to bacterial two-component system. Type-B ARRs lie at the end of the cytokinin signaling, typically mediating tile output response. However, it is still unclear how type-B ARRs are regulated in response to cytokinin. Typical type-B ARR contains an N-terminal receiver domain and a C-terminal effector domain. In this study, we performed a genome-wild comparative analysis by overexpressing full length and C-terminal effector domain of seven representative type-B ARRs. Our results indicated that overexpression of C-terminal effector domain causes short primary roots and short hypocotyls without the addition of cytokinin, sug- gesting that the inhibitory role of the receiver domain in the activity of the effector domain is a common mechanism in type-B ARRs. To investigate how the receiver domain inhibits the activity of the effector domain, we performed a deletion analysis. We found that deletion of the initial 45 residues of ARR18 （the 45 residues from N-terminus） causes pleiotropic growth defects by directly inducing cytokinin responsive genes. Together, our results suggest that the initial 45 residues are critical for the inhibitory role of the receiver domain to the effector domain in ARRI8.

Phosphatidic acid plays key roles regulating plant development and stress responses

Phospholipids, including phosphatidic acid （PA）, phosphatidylcholine （PC）, phosphatidylethanolamine （PE）, phosphatidylglycerol （PC）, phosphatidylserine （PS） and phosphoinositides, have emerged as an important class of cellular messenger molecules in various cellular and physiological processes, of which PA attracts much attention of researchers. In addition to its effect on stimulating vesicle trafficking, many studies have demonstrated that PA plays a crucial role in various signaling pathways by binding target proteins and regulating their activity and subcellular localization. Here, we summarize the functional mechanisms and target proteins underlying PA-mediated regulation of cellular signaling, development, hormonal responses, and stress responses in plants.

Solution conformation of the response regulator proteins from Deinococcus radiodurans studied by SAXS

In this paper the solution conformation of the response regulator proteins from Deinococcus radiodurans was studied by small-angle X-ray scattering （SAXS）. The SAXS curves of Dr-rrA in solutions were obtained at Beamline 1W2A of Beijing Synchrotron Radiation Facility （BSRF）. Two possible conformations of the response regulator proteins, compact and incompact conformations, have been represented by the known crystallographic structures. And theoretical solution scattering curves of the two possible conformations were calculated and fitted to the experimental scattering curve of Dr-rrA, respectively. The result indicates that the solution conformation of the response regulator proteins is inclined to the compact one, which is in agreement with the result of biochemical experiments.

A fully on-chip fast-transient NMOS low dropout voltage regulator with quasi floating gate pass element

This paper presents a fully on-chip NMOS low-dropout regulator（LDO） for portable applications with quasi floating gate pass element and fast transient response.The quasi floating gate structure makes the gate of the NMOS transistor only periodically charged or refreshed by the charge pump,which allows the charge pump to be a small economical circuit with small silicon area.In addition,a variable reference circuit is introduced enlarging the dynamic range of error amplifier during load transient.The proposed LDO has been implemented in a 0.35 μm BCD process.From experimental results,the regulator can operate with a minimum dropout voltage of 250 mV at a maximum 1 A load and Iq of 395 μA.Under full-range load current step,the voltage undershoot and overshoot of the proposed LDO are reduced to 50 and 26 mV,respectively.