The emerging role of nitric oxide in the synaptic dysfunction of vascular dementia

With an increase in global aging,the number of people affected by cerebrovascular diseases is also increasing,and the incidence of vascular dementia-closely related to cerebrovascular risk-is increasing at an epidemic rate.However,few therapeutic options exist that can markedly improve the cognitive impairment and prognosis of vascular dementia patients.Similarly in Alzheimer’s disease and other neurological disorders,synaptic dysfunction is recognized as the main reason for cognitive decline.Nitric oxide is one of the ubiquitous gaseous cellular messengers involved in multiple physiological and pathological processes of the central nervous system.Recently,nitric oxide has been implicated in regulating synaptic plasticity and plays an important role in the pathogenesis of vascular dementia.This review introduces in detail the emerging role of nitric oxide in physiological and pathological states of vascular dementia and summarizes the diverse effects of nitric oxide on different aspects of synaptic dysfunction,neuroinflammation,oxidative stress,and blood-brain barrier dysfunction that underlie the progress of vascular dementia.Additionally,we propose that targeting the nitric oxide-sGC-cGMP pathway using certain specific approaches may provide a novel therapeutic strategy for vascular dementia.

PtCoNi ternary intermetallic compounds anchored on Co,Ni and N co-doped mesoporous carbon:Synergetic effect between PtCoNi nanoparticles and doped mesoporous carbon promotes the catalytic activity

Highly active and robust electrocatalysts are desired for proton exchange membrane fuel cells.Pt-based intermetallic compounds(IMCs) have been recognized as one of the most promising low-platinum catalysts for fuel cells(FCs).Herein,we report a high-performance IMCs by anchoring ordered PtCoNi ternary nanoparticles on the N,Co and Ni co-doped dodecahedral mesoporous carbon(DMC).While the introduced Co and Ni participate in the formation of PtCoNi IMCs,some of them are doped in the mesoporous carbon and coordinated by N to form Co-N_(y)/Ni-N_(z)dual active centers,which further enhances the electrocatalytic activity towards oxygen reduction reaction.Moreover,the addition of Ni results in a negative shift of the d-band center of Pt as compared to the Pt/DMC and Pt_(3)Co/DMC,making it easier to adsorb oxygen on the surface.As expected,our optimal sample Pt_(3)Co_(0.7)Ni_(0.3)/DMC exhibits excellent performance with mass activity and specific activity of 1.32 A mgPt-1and 1.98 mA cm^(-2)at 0.9 V,which are 7.33and 6.19 times that of commercial Pt/C,respectively.The Pt_(3)Co_(0.7)Ni_(0.3)/DMC also reveals much better cathodic performance in an H2-air single fuel cell than commercial Pt/C catalyst with a power density of0.802 W cm^(-2).This work provides critical sights into constructing efficient catalysts by ternary intermetallic strategy and synergetic effect between active components and support.

A Self-Healing and Nonflammable Cross-Linked Network Polymer Electrolyte with the Combination of Hydrogen Bonds and Dynamic Disulfide Bonds for Lithium Metal Batteries

The self-healing solid polymer electrolytes(SHSPEs)can spontaneously eliminate mechanical damages or micro-cracks generated during the assembly or operation of lithium-ion batteries(LIBs),significantly improving cycling performance and extending service life of LIBs.Here,we report a novel cross-linked network SHSPE(PDDP)containing hydrogen bonds and dynamic disulfide bonds with excellent self-healing properties and nonflammability.The combination of hydrogen bonding between urea groups and the metathesis reaction of dynamic disulfide bonds endows PDDP with rapid self-healing capacity at 28°C without external stimulation.Furthermore,the addition of 1-ethyl-3-methylimidazolium bis(trifluoromethylsulfonyl)imide(EMIMTFSI)improves the ionic conductivity(1.13×10^(−4)S cm^(−1)at 28°C)and non-flammability of PDDP.The assembled Li/PDDP/LiFePO_(4)cell exhibits excellent cycling performance with a discharge capacity of 137 mA h g^(−1)after 300 cycles at 0.2 C.More importantly,the self-healed PDDP can recover almost the same ionic conductivity and cycling performance as the original PDDP.

The Research Progress of Hexafluorobutadiene Synthesis

Hexafluorobutadiene is a new plasma etching gas for semiconductor molectron which has perfect properties and also is a preceding monomer that can be used for synthesizing many fluorinated compounds. This paper described the different synthesis methods of perflurobutadiene from different materials, and contrasted the characteristic of each synthetic method. The route from tetrafluoroethylene has more industrialization prospects.

Preparation and toughening mechanism of Al_(2)O_(3) composite ceramics toughened by B_(4)C@TiB_(2) core–shell units

In this paper, the concept of incorporating core–shell structured units as secondary phases totoughen Al_(2)O_(3) ceramics is proposed. Al_(2)O_(3) composite ceramics toughened by B_(4)C@TiB_(2) core–shellunits are successfully synthesized using a combination of molten salt methodology and spark plasmasintering. The synthesis of B_(4)C@TiB_(2) core–shell toughening units stems from the prior production ofcore–shell structural B_(4)C@TiB_(2) powders, and this core–shell structure is effectively preserved withinthe Al_(2)O_(3) matrix after sintering. The B_(4)C@TiB_(2) core–shell toughening unit consists of a micron-sizedB4C core enclosed by a shell approximately 500 nm in thickness, composed of numerous nanosizedTiB2 grains. The regions surrounding these core–shell units exhibit distinct geometric structures andencompass multidimensional variations in phase composition, grain dimensions, and thermal expansioncoefficients. Consequently, intricate stress distributions emerge, fostering the propagation of cracks inmultiple dimensions. This behavior consumes a considerable amount of crack propagation energy,thereby enhancing the fracture toughness of the Al_(2)O_(3) matrix. The resulting Al_(2)O_(3) composite ceramicsdisplay relative density of 99.7%±0.2%, Vickers hardness of 21.5±0.8 GPa, and fracture toughness6.92±0.22 MPa·m1/2.

秀丽隐杆线虫RNA结合蛋白复合物AMG-1/SLRP-1通过线粒体稳态维持实现调控生殖腺发育和精子发生

RNA结合蛋白(mtRBP)介导的mRNA转录后调节对精子发生必不可少但却鲜有报道.在本文中,我们鉴定到一个在生殖腺中特异性表达的线粒体RNA结合蛋白AMG-1,它是秀丽隐杆线虫精子发生过程中必需的蛋白,同时与哺乳动物LRPPRC蛋白同源.amg-1突变会阻碍生殖腺的发育,最终导致生殖细胞的线粒体形态和结构异常以及线粒体功能障碍.通过测序鉴定RNA结合蛋白的靶点发现,AMG-1更倾向于与mtDNA编码的参与线粒体核糖体组装的12S和16S核糖体RNA(rRNA)结合,12S rRNA对于维持生殖细胞线粒体蛋白稳态至关重要,而12S rRNA的表达却受AMG-1蛋白调节.此外,哺乳动物SLIRP在秀丽线虫中的同源蛋白SLRP-1蛋白与AMG-1在遗传上存在互作关系,它们可共同调节秀丽线虫的精子发生和育性.综上所述,这些发现揭示了mtRBP蛋白AMG-1在线粒体调控中的新机制,这可能为由线粒体功能障碍引发的男性不育治疗提供新的理论基础.

金属/非金属元素掺杂提升原子级分散碳基催化剂的氧还原性能

原子级别分散的过渡金属和氮共掺杂碳基催化剂(M-N_(x)-C)具有反应活性好、选择性高、制备容易等优点,被认为是最有可能取代价格昂贵的铂催化剂用作燃料电池阴极的一类非贵金属催化剂。然而,该类催化剂在阴极侧氧还原反应过程中存在活性位点密度较低、耐久性不足的问题制约了其在燃料电池中的实际应用。研究表明,通过多种金属/非金属元素的掺杂调控活性位点的电子结构与空间构型可显著提升M-N_(x)-C催化剂的氧还原活性和稳定性,已成为掺杂碳基催化剂领域的热门研究课题。本文综述了近年来国内外在多种金属/非金属元素掺杂提升M-N_(x)-C碳基催化剂性能方面的主要研究工作,包括金属元素掺杂、非金属元素掺杂等研究。文章进一步总结和指出了M-N_(x)-C碳基催化剂面临的问题及挑战,并对其发展前景和未来研究方向进行了展望。

Platelet-rich plasma accelerates skin wound healing by promoting re-epithelialization

Background:Autologous platelet-rich plasma(PRP)has been suggested to be effective for wound healing.However,evidence for its use in patients with acute and chronic wounds remains insufficient.The aims of this study were to comprehensively examine the effectiveness,synergy and possible mechanism of PRP-mediated improvement of acute skin wound repair.Methods:Full-thickness wounds were made on the back of C57/BL6 mice.PRP or saline solution as a control was administered to the wound area.Wound healing rate,local inflammation,angiogenesis,re-epithelialization and collagen deposition were measured at days 3,5,7 and 14 after skin injury.The biological character of epidermal stem cells(ESCs),which reflect the potential for re-epithelialization,was further evaluated in vitro and in vivo.Results:PRP strongly improved skin wound healing,which was associated with regulation of local inflammation,enhancement of angiogenesis and re-epithelialization.PRP treatment significantly reduced the production of inflammatory cytokines interleukin-17A and interleukin-1β.An increase in the local vessel intensity and enhancement of re-epithelialization were also observed in animals with PRP administration and were associated with enhanced secretion of growth factors such as vascular endothelial growth factor and insulin-like growth factor-1.Moreover,PRP treatment ameliorated the survival and activated the migration and proliferation of primary cultured ESCs,and these effects were accompanied by the differentiation of ESCs into adult cells following the changes of CD49f and keratin 10 and keratin 14.Conclusion:PRP improved skin wound healing by modulating inflammation and increasing angiogenesis and re-epithelialization.However,the underlying regulatory mechanism needs to be investigated in the future.Our data provide a preliminary theoretical foundation for the clinical administration of PRP in wound healing and skin regeneration.

Neutralization of interleukin-17A alleviates burn-induced intestinal barrier disruption via reducing pro-inflammatory cytokines in a mouse model

Background:The intestinal barrier integrity can be disrupted due to burn injury,which is responsible for local and systemic inflammatory responses.Anti-inflammation strategy is one of the proposed therapeutic approaches to control inflammatory cascade at an early stage.Interleukin-17A(IL-17A)plays a critical role in inflammatory diseases.However,the role of IL-17A in the progression of burn-induced intestinal inflammation is poorly understood.In this study,we aimed to investigate the effect of IL-17A and associated pro-inflammatory cytokines that were deeply involved in the pathogenesis of burn-induced intestinal inflammatory injury,and furthermore,we sought to determine the early source of IL-17A in the intestine.Methods:Mouse burn model was successfully established with infliction of 30%total body surface area scald burn.The histopathological manifestation,intestinal permeability,zonula occludens-1 expression,pro-inflammatory cytokines were determined with or without IL-17A-neutralization.Flow cytometry was used to detect the major source of IL-17A^(+)cells in the intestine.Results:Burn caused intestinal barrier damage,increase of intestinal permeability,alteration of zonula occludens-1 expressions,elevation of IL-17A,IL-6,IL-1βand tumor necrosis factor-α(TNF-α),whereas IL-17A neutralization dramatically alleviated burn-induced intestinal barrier disruption,maintained zonula occludens-1 expression,and noticeably,inhibited pro-inflammatory cytokines elevation.In addition,we observed that the proportion of intestinal IL-17A^(+)Vγ4^(+)T subtype cells(but not IL-17A^(+)Vγ1^(+)T subtype cells)were increased in burn group,and neutralization of IL-17A suppressed this increase.Conclusions:The main original findings of this study are intestinal mucosa barrier is disrupted after burn through affecting the expression of pro-inflammatory cytokines,and a protective role of IL-17A neutralization for intestinal mucosa barrier is determined.Furthermore,Vγ4^(+)T cells are identified as the major early producers of IL-17A that orchestrate an inflammatory response in the burn model.These data suggest that IL-17A blockage may provide a unique target for therapeutic intervention to treat intestinal insult after burn.

Photodynamic therapy accelerates skin wound healing through promoting re-epithelialization

Background:Epidermal stem cells(EpSCs)that reside in cutaneous hair follicles and the basal layer of the epidermis are indispensable for wound healing and skin homeostasis.Little is known about the effects of photochemical activation on EpSC differentiation,proliferation and migration during wound healing.The present study aimed to determine the effects of photodynamic therapy(PDT)on wound healing in vivo and in vitro.Methods:We created mouse full-thickness skin resection models and applied 5-aminolevulinic acid(ALA)for PDT to the wound beds.Wound healing was analysed by gross evaluation and haematoxylin–eosin staining in vivo.In cultured EpSCs,protein expression was measured using flow cytometry and immunohistochemistry.Cell migration was examined using a scratch model;apoptosis and differentiation were measured using flow cytometry.Results:PDT accelerated wound closure by enhancing EpSC differentiation,proliferation and migration,thereby promoting re-epithelialization and angiogenesis.PDT inhibited inflammatory infiltration and expression of proinflammatory cytokines,whereas the secretion of growth factors was greater than in other groups.The proportion of transient amplifying cells was significantly greater in vivo and in vitro in the PDT groups.EpSC migration was markedly enhanced after ALAinduced PDT.Conclusions:Topical ALA-induced PDT stimulates wound healing by enhancing re-epithelialization,promoting angiogenesis as well as modulating skin homeostasis.This work provides a preliminary theoretical foundation for the clinical administration of topical ALA-induced PDT in skin wound healing.

Oncogenic lncRNA LINC00973 promotes Warburg effect by enhancing LDHA enzyme activity

Aerobic glycolysis,also known as the Warburg effect,is a hallmark of cancer and essential for metabolism in malignancies,but its regulation and modulation in cancer cells remain poorly understood.Here,using large-scale functional screening,we identified a tumor-associated and broadly expressed oncogenic long noncoding RNA LINC00973.Notably,knocking down LINC00973 significantly inhibits the proliferation of multiple types of cancer cells and reduces tumor growth in vivo.Mechanistically,LINC00973 directly binds to lactate dehydrogenase A(LDHA),an essential glycolytic enzyme,and enhances its enzymatic activity,thereby promoting glycolysis.Clinically,high expression of LINC00973 is significantly associated with poor prognosis in many types of human cancers.This work demonstrates that LINC00973 modulates cancer-specific regulation of the Warburg effect,and may represent a potential target for broad-acting anti-cancer therapies.

Hypoxia-mimicking 3D bioglass-nanoclay scaffolds promote endogenous bone regeneration

Large bone defect repair requires biomaterials that promote angiogenesis and osteogenesis.In present work,a nanoclay(Laponite,XLS)-functionalized 3D bioglass(BG)scaffold with hypoxia mimicking property was prepared by foam replication coupled with UV photopolymerization methods.Our data revealed that the incorporation of XLS can significantly promote the mechanical property of the scaffold and the osteogenic differentiation of human adipose mesenchymal stem cells(ADSCs)compared to the properties of the neat BG scaffold.Desferoxamine,a hypoxia mimicking agent,encourages bone regeneration via activating hypoxia-inducible factor-1 alpha(HIF-1α)-mediated angiogenesis.GelMA-DFO immobilization onto BG-XLS scaffold achieved sustained DFO release and inhibited DFO degradation.Furthermore,in vitro data demonstrated increased HIF-1αand vascular endothelial growth factor(VEGF)expressions on human adipose mesenchymal stem cells(ADSCs).Moreover,BG-XLS/GelMA-DFO scaffolds also significantly promoted the osteogenic differentiation of ADSCs.Most importantly,our in vivo data indicated BG-XLS/GelMA-DFO scaffolds strongly increased bone healing in a critical-sized mouse cranial bone defect model.Therefore,we developed a novel BG-XLS/GelMA-DFO scaffold which can not only induce the expression of VEGF,but also promote osteogenic differentiation of ADSCs to promote endogenous bone regeneration.

Interactive Web-based Annotation of Plant MicroRNAs with iwa-miRNA

MicroRNAs(miRNAs) are important regulators of gene expression. The large-scale detection and profiling of miRNAs have been accelerated with the development of highthroughput small RNA sequencing(sRNA-Seq) techniques and bioinformatics tools. However,generating high-quality comprehensive miRNA annotations remains challenging due to the intrinsic complexity of sRNA-Seq data and inherent limitations of existing miRNA prediction tools. Here,we present iwa-miRNA, a Galaxy-based framework that can facilitate miRNA annotation in plant species by combining computational analysis and manual curation. iwa-miRNA is specifically designed to generate a comprehensive list of miRNA candidates, bridging the gap between already annotated miRNAs provided by public miRNA databases and new predictions from sRNA-Seq datasets. It can also assist users in selecting promising miRNA candidates in an interactive mode,contributing to the accessibility and reproducibility of genome-wide miRNA annotation. iwamiRNA is user-friendly and can be easily deployed as a web application for researchers without programming experience. With fexible, interactive, and easy-to-use features, iwa-miRNA is a valuable tool for the annotation of miRNAs in plant species with reference genomes. We also illustrate the application of iwa-miRNA for miRNA annotation using data from plant species with varying genomic complexity. The source codes and web server of iwa-miRNA are freely accessible at http://iwa-miRNA.omicstudio.cloud/.

P311 promotes typeⅡtransforming growth factor-βreceptor mediated fibroblast activation and granulation tissue formation in wound healing

Background:P311,a highly conserved 8 kDa intracellular protein,has recently been reported to play an important role in aggravating hypertrophic scaring by promoting the differentiation and secretion of fibroblasts.Nevertheless,how P311 regulates the differentiation and function of fibroblasts to affect granulation tissue formation remains unclear.In this work,we studied the underlying mechanisms via which P311 affects fibroblasts and promotes acute skin wound repair.Methods:To explore the role of P311,both in vitro and in vivo wound-healing models were used.Full-thickness skin excisional wounds were made in wild-type and P311−/−C57 adult mice.Wound healing rate,re-epithelialization,granulation tissue formation and collagen deposition were measured at days 3,6 and 9 after skin injury.The biological phenotypes of fibroblasts,the expression of target proteins and relevant signaling pathways were examined both in vitro and in vivo.Results:P311 could promote the proliferation and differentiation of fibroblasts,enhance the ability of myofibroblasts to secrete extracellular matrix and promote cell contraction,and then facilitate the formation of granulation tissue and eventually accelerate skin wound closure.Importantly,we discovered that P311 acts via up-regulating the expression of type II transforming growth factor-βreceptor(TGF-βRII)in fibroblasts and promoting the activation of the TGF-βRII-Smad signaling pathway.Mechanistically,the mammalian target of rapamycin signaling pathway is closely implicated in the regulation of the TGF-βRII-Smad pathway in fibroblasts mediated by P311.Conclusions:P311 plays a critical role in activation of the TGF-βRII-Smad pathway to promote fibroblast proliferation and differentiation as well as granulation tissue formation in the process of skin wound repair.

Epidemiological and clinical characteristics of burns in the older person:a seven-year retrospective analysis of 693 cases at a burn center in south-west China

Background:Burns are one of the major traumas that may affect older individuals.The purpose of this study was to investigate the epidemiological and clinical characteristics of geriatric burns at a major center in south-west China.Methods:This retrospective study was conducted at the Institute of Burn Research,Southwest Hospital of Army Medical University between 2010 and 2016,and the data collected from medical records included admission date,age,gender,premorbid disease,burn etiology,injured anatomical location,burn area and depth,inhalation injury,number of surgeries,length of stay(LOS),clinical outcome,and medical cost.Results:Of the 693 older burn patients included,60.75%were male and 56.85%were aged 60–69 years.Burns peaked in December–March and June.Flamewas the most common cause of burns,making up 51.95%of all cases,and also dominated in the burn patients aged 60–69 years.Limbs were the most common anatomical sites of burns(69.41%),and the median total body surface area(TBSA)was 5%(interquartile range[IQR]:2%–15%).The percentage of the patients who underwent surgeries and number of surgeries significantly increased in the cases of contact burns,younger age and full-thickness burns.Six deaths resulted in a mortality of 0.9%.The median LOSwas 16 days(IQR:8–29 days),and the main risk factors were more surgeries,better outcomes,and full-thickness burns.The median costwas 20,228 CNY(IQR:10,457–46,581.5 CNY),and major risk factors included longer LOS,larger TBSA,and more surgeries.Furthermore,compared to the earlier data from our center,the proportion of older adults among all burns(7.50%vs.4.15%),proportion of flame burns(51.95%vs.33.90%),and mean age(69.05 years vs.65.10 years)were significantly higher,while the proportion of premorbidities(16.9%vs.83.9%),mortality(0.9%vs.7.5%)and median TBSA(5%vs.21%)were significantly lower.Conclusions:This study suggested that closer attention should be paid to prevent burn injuries in older people aged 60–69 years,especially males,regarding incidents in the summer and winter,and flame burns.Moreover,tailored intervention strategies based on related risk factors should be under special consideration.

Obstruction of the formation of granulation tissue leads to delayed wound healing after scald burn injury in mice

Background:Delayed wound healing remains a common but challenging problem in patients with acute or chronic wound following accidental scald burn injury.However,the systematic and detailed evaluation of the scald burn injury,including second-degree deep scald(SDDS)and thirddegree scald(TDS),is still unclear.The present study aims to analyze the wound-healing speed,the formation of granulation tissue,and the healing quality after cutaneous damage.Methods:In order to assess SDDS and TDS,the models of SDDS and TDS were established using a scald instrument in C57BL/6 mice.Furthermore,an excisional wound was administered on the dorsal surface in mice(Cut group).The wound-healing rate was first analyzed at days 0,3,5,7,15 and 27,with the Cut group as a control.Then,on the full-thickness wounds,hematoxylin and eosin(H&E)staining,Masson staining,Sirius red staining,Victoria blue staining and immunohistochemistry were performed to examine re-epithelialization,the formation of granulation tissue,vascularization,inflammatory infiltration and the healing quality at different time points in the Cut,SDDS and TDS groups.Results:The presented data revealed that the wound-healing rate was higher in the Cut group,when compared with the SDDS and TDS groups.H&E staining showed that re-epithelialization,formation of granulation tissue and inflammatory infiltration were greater in the Cut group,when compared with the SDDS and TDS groups.Immunohistochemistry revealed that the number of CD31,vascular endothelial growth factor A,transforming growth factor-βandα-smooth muscle actin reached preferential peak in the Cut group,when compared with other groups.In addition,Masson staining,Sirius red staining,Victoria blue staining,Gordon-Sweets staining and stress analysis indicated that the ratio of collagen I to III,reticular fibers,failure stress,Young’s modulus and failure length in the SDDS group were similar to those in the normal group,suggesting that healing quality was better in the SDDS group,when compared with the Cut and TDS groups.Conclusion:Overall,the investigators first administered a comprehensive analysis in the Cut,SDDS and TDS groups through in vivo experiments,which further proved that the obstacle of the formation of granulation tissue leads to delayed wound healing after scald burn injury in mice.

Natural multimodal interaction in immersive flow visualization

In the immersive flow visualization based on virtual reality,how to meet the needs of complex professional flow visualization analysis by natural human–computer interaction is a pressing problem.In order to achieve the natural and efficient human–computer interaction,we analyze the interaction requirements of flow visualization and study the characteristics of four human–computer interaction channels:hand,head,eye and voice.We give out some multimodal interaction design suggestions and then propose three multimodal interaction methods:head&hand,head&hand&eye and head&hand&eye&voice.The freedom of gestures,the stability of the head,the convenience of eyes and the rapid retrieval of voices are used to improve the accuracy and efficiency of interaction.The interaction load is balanced by multimodal interaction to reduce fatigue.The evaluation shows that our multimodal interaction has higher accuracy,faster time efficiency and much lower fatigue than the traditional joystick interaction.

A systematic and quantitative method for wound-dressing evaluation

Background:For patients with skin defects such as burns,wound dressing plays important roles in protecting the wound.Before a novel wound dressing is applied to a patient,a series of tests should be performed to ensure its safety and efficacy.Different types of animal wound-healing models have been used to study the bio-function of different wound dressings;however,a systematic way to evaluate the effect of a wound dressing on wound healing and cutaneous regeneration is lacking.Methods:In the study presented here,full-thickness wound models were established in mice,and a systematic way to quantitatively analyze the wound-healing process and the histological results is described.Results:It was found that the rate of wound healing in the tested wound dressing(TWD)group was higher than that in the control group,and the re-epithelialization and the formation of granulation tissue were enhanced when the TWD was applied.Meanwhile,the inflammatory response was attenuated in the TWD group,and more mature and better aligned collagen fibers in the healed wound tissue was found in the TWD group compared with that in the control group.Conclusions:A systematic,quantitative way to analyze the effect of a wound dressing on wound healing was established.And it might be helpful for the design of wound dressing in the future.