Gabapentinoids for the treatment of stroke

Gabapentinoid drugs(pregabalin and gabapentin) have been successfully used in the treatment of neuro pathic pain and in focal seizure prevention.Recent research has demonstrated their potent activities in modulating neurotransmitter release in neuronal tissue,oxidative stress,and inflammation,which matches the mechanism of action via voltage-gated calcium channels.In this review,we briefly elaborate on the medicinal history and ligand-binding sites of gabapentinoids.We systematically summarize the preclinical and clinical research on gabapentinoids in stroke,including ischemic stro ke,intracerebral hemorrhage,subarachnoid hemorrhage,seizures after stro ke,cortical spreading depolarization after stroke,pain after stroke,and nerve regeneration after stro ke.This review also discusses the potential to rgets of gabapentinoids in stroke;however,the existing results are still unce rtain regarding the effect of gabapentinoids on stroke and related diseases.Further preclinical and clinical trials are needed to test the therapeutic potential of gabapentinoids in stroke.Therefore,gabapentinoids have both opportunities and challenges in the treatment of stroke.

非小细胞肺癌新辅助免疫治疗的研究进展、获益人群、治疗周期和疗效预测

免疫检查点抑制剂(immune checkpoint inhibitors, ICIs)的出现极大程度上改变了非小细胞肺癌(nonsmall cell lung cancer, NSCLC)患者的治疗前景,术前新辅助免疫治疗方案作为一种有效、安全的治疗方案逐渐受到重视。然而,新辅助免疫治疗方案相关的研究起步时间较晚,研究成果相对较少且主要集中于样本量较小的I期、II期研究,治疗方案本身存在也许多尚不明确的地方,在获益人群的筛选、治疗周期的选择和疗效预测等方面也尚未达成广泛的共识。本文综述了与新辅助免疫治疗相关的重要研究和新近成果,旨在以这些研究的成果为基础,从获益人群、治疗周期和疗效预测三个方面全方位探讨该类治疗的流程及存在的问题。

Low Transmission Overhead for Polar Coding Physical-Layer Encryption

In this paper, for physical-layer security(PLS), a novel scheme of polar coding encryption is introduced in the wiretap channel(WTC) model. To decrease transmission overhead of the shared secret information and enhance the security performance against an attacker, we have employed the two following encryption technologies: Firstly, randomization of output bits is not dependent on the traditional randomized bit-channels but they are directly flipped through the random bit sequence. Secondly, for employing Advanced Encryption Standard(AES), we utilize the secret seed to extend an initial secret key of AES cryptosystem, which it appears a good avalanche performance. Result analyses demonstrate that the proposed scheme is strongly resistant against conventional attacks.

环状RNA在肿瘤免疫治疗中的研究进展

肿瘤免疫治疗是近年来发展起来的全新治疗方法,极大地改变了癌症的治疗方案,为癌症患者带来了新的选择,但并不是所有患者在应用免疫治疗后都疗效明显,因此如何更加有效地选择适用免疫治疗的患者和提高免疫治疗疗效是十分值得探讨的问题。随着对环状RNA(circular RNAs,circRNAs)不断深入研究发现,circRNA不仅在肿瘤标志物、肿瘤进展和预后领域中作用显著,还可以在多种肿瘤中异常表达,进而通过多种途径影响肿瘤免疫。因此检测circRNA的表达量不仅可能作为筛选适用免疫治疗的患者的补充手段,还可能用于预测肿瘤免疫治疗的疗效。本文总结了circRNA在以肺癌为首的多种肿瘤免疫治疗中的研究进展,并讨论了其在肿瘤免疫治疗中潜在的作用,意在为circRNA的临床应用提供参考。

Assistant radiotherapeutic effect of Jiaqi Mixture on tumor-bearing mice

Objective:The aim was to study the assistant radiotherapeutic effect of Jiaqi Mixture (JQM) on Ehrlich's ascites carcinoma (EAC) mice.Methods:The EAC-cancer model was made up with Kunming mice.The tumor-bearing mice were treated with whole body exposure (8 Gy) and intragastric administration of JQM,and the changes of tumor weight,the total number of white blood cells (WBC) and immune system were observed.Results:The average tumor weight,WBC,spleen coefficient,the stimulation index (SI) of Con A and LPS and the natural killing (NK) cell activity of mice decreased in some degree after radiotherapy,but the average tumor weight decreased more obviously in radiotherapy + medicine groups (compared with tumor control group,P < 0.05);and the other above indexes were much higher in radiotherapy + medicine groups than those in radiotherapy groups (P < 0.05-0.01).Conclusion:It was suggested that JQM can enhance the effect of radiation therapy and protect the normal immune system caused by radiation therapy.

Design and Implementation of Automatic Following Balancing Vehicle Based on UWB Positioning Principle

With the modernization of industrial production,various automatic following technologies have gradually penetrated into people's lives.Among them,the application fields that follow mobile balancing vehicles range from the structured environment of factories to the daily living environment.The purpose of this subject is to be able to use UWB positioning technology to realize that the balanced trolley is an automatic following function,which mainly uses the ranging function in UWB positioning technology,uses the TOF ranging principle and embedded basic knowledge,and changes the positioning algorithm to a following algorithm.The distance between the target object and the person is effectively determined by two tags set on the trolley and a base station in the hand to determine the distance,and the distance information is transmitted through the serial port.By writing an algorithm,the distance information is converted to the driving information of the trolley,and the driving information is sent to the trolley to control the trolley,thereby realizing the task of balancing the trolley to follow the specified target in a simple indoor environment.

基于K-Medoids算法的大学生体质分类评价模型研究

大学生是国家发展重要的后备力量。然而缺乏科学规律的身体锻炼以及熬夜等生活习惯问题使得大学生体质健康检测结果不理想。为了深入分析大学生体质情况现状,建立了一种基于K-medoids算法的大学生体质健康分类评价模型。以某高校的实际体测数据为样本,进行了案例分析,所得结果可应用于学生体质改善方案的制定中。

Oxygen uptake response to switching stairs exercise by non-parametric modeling

Oxygen uptake plays a crucial role in the evaluation of endurance performance during exercise and is extensively utilized for metabolic assessment. This study records the oxygen uptake during the exercise phase (i.e., ascending or descending) of the stair exercise, utilizing an experimental dataset that includes ten participants and covers various exercise periods. Based on the designed experiment protocol, a non-parametric modeling method with kernel-based regularization is generally applied to estimate the oxygen uptake changes during the switching stairs exercise, which closely resembles daily life activities. The modeling results indicate the effectiveness of the non-parametric modeling approach when compared to fixed-order models in terms of accuracy, stability, and compatibility. The influence of exercise duration on estimated fitness reveals that the model of the phase-oxygen uptake system is not time-invariant related to respiratory metabolism regulation and muscle fatigue. Consequently, it allows us to study the humans’ conversion mechanism at different metabolic rates and facilitates the standardization and development of exercise prescriptions.

An osteosarcoma-on-a-chip model for studying osteosarcoma matrix-cell interactions and drug responses

Marrow niches in osteosarcoma(OS)are a specialized microenvironment that is essential for the maintenance and regulation of OS cells.However,existing animal xenograft models are plagued by variability,complexity,and high cost.Herein,we used a decellularized osteosarcoma extracellular matrix(dOsEM)loaded with extracellular vesicles from human bone marrow-derived stem cells(hBMSC-EVs)and OS cells as a bioink to construct a micro-osteosarcoma(micro-OS)through 3D printing.The micro-OS was further combined with a microfluidic system to develop into an OS-on-a-chip(OOC)with a built-in recirculating perfusion system.The OOC system successfully integrated bone marrow niches,cell‒cell and cell-matrix crosstalk,and circulation,allowing a more accurate representation of OS characteristics in vivo.Moreover,the OOC system may serve as a valuable research platform for studying OS biological mechanisms compared with traditional xenograft models and is expected to enable precise and rapid evaluation and consequently more effective and comprehensive treatments for OS.

Current Immunotherapy Strategies for Rheumatoid Arthritis:The Immunoengineering and Delivery Systems

Rheumatoid arthritis (RA) is a chronic inflammatory autoimmune disease accompanied by persistent multiarticular synovitis and cartilage degradation. The present clinical treatments are limited to disease-modifying anti-rheumatic drugs (DMARDs) and aims to relieve pain and control the inflammation of RA. Despite considerable advances in the research of RA, the employment of current clinical procedure is enormous, hindered by systemic side effect, frequent administration, tolerance from long-lasting administration, and high costs. Emerging immunoengineering-based strategies, such as multiple immune-active nanotechnologies via mechanism-based immunology approaches, have been developed to improve specific targeting and to reduce adverse reactions for RA treatments. Here, we review recent studies in immunoengineering for the treatment of RA. The prospect of future immunoengineering treatment for RA has also been discussed.

Temperature action and effect of concrete-filled steel tubular bridges:A review

Concrete-filled steel tube(CFST)has been widely applied in bridges due to its excellent structural and constructional performance.In CFST bridges,temperature action is not only an important but also a special load that must be considered in bridge design,construction and structural evaluation.This paper presents an overview on current researches of the temperature action and effect of CFST bridges.The historical and spatial characteristics as well as corresponding influencing factors of temperature distributions are summarized,and classifications of temperature actions are also reviewed.Results show that in-depth investigations of the contributions of temperature influencing factors can help to effectively reduce the adverse temperature effects on CFST bridges in the design stage.Due to the lack of long-term measurements and insufficient use of historical meteorological data,research on the representative value along with correlation analysis of CFST temperature actions and meteorological parameters have to be further carried out.In the meanwhile,a decomposition method of temperature distribution is proposed based on structural effects of CFST bridges in this paper.The decomposed temperature actions can be used for more accurate effect calculation than traditional temperature action classification method,especially for CFST truss bridges.At last,specific temperature action patterns still need to be investigated in some of the special problems,such as longitudinal temperature differences along the CFST arch rib and thermal debonding in the CFST interface.Further investigations are required on the accurate simulation of temperature distribution of CFST bridges considering the shading effects of components and terrain.

Three-dimensional bioprinting of multicell-laden scaffolds containing bone morphogenic protein-4 for promoting M2 macrophage polarization and accelerating bone defect repair in diabetes mellitus

Critical-sized bone defect repair in patients with diabetes mellitus remains a challenge in clinical treatment because of dysfunction of macrophage polarization and the inflammatory microenvironment in the bone defect region.Three-dimensional(3D)bioprinted scaffolds loaded with live cells and bioactive factors can improve cell viability and the inflammatory microenvironment and further accelerating bone repair.Here,we used modified bioinks comprising gelatin,gelatin methacryloyl(GelMA),and 4-arm poly(ethylene glycol)acrylate(PEG)to fabricate 3D bioprinted scaffolds containing BMSCs,RAW264.7 macrophages,and BMP-4-loaded mesoporous silica nanoparticles(MSNs).Addition of MSNs effectively improved the mechanical strength of GelMA/gelatin/PEG scaffolds.Moreover,MSNs sustainably released BMP-4 for long-term effectiveness.In 3D bioprinted scaffolds,BMP-4 promoted the polarization of RAW264.7 to M2 macrophages,which secrete anti-inflammatory factors and thereby reduce the levels of pro-inflammatory factors.BMP-4 released from MSNs and BMP-2 secreted from M2 macrophages collectively stimulated the osteogenic differentiation of BMSCs in the 3D bioprinted scaffolds.Furthermore,in calvarial critical-size defect models of diabetic rats,3D bioprinted scaffolds loaded with MSNs/BMP-4 induced M2 macrophage polarization and improved the inflammatory microenvironment.And 3D bioprinted scaffolds with MSNs/BMP-4,BMSCs,and RAW264.7 cells significantly accelerated bone repair.In conclusion,our results indicated that implanting 3D bioprinted scaffolds containing MSNs/BMP-4,BMSCs,and RAW264.7 cells in bone defects may be an effective method for improving diabetic bone repair,owing to the direct effects of BMP-4 on promoting osteogenesis of BMSCs and regulating M2 type macrophage polarization to improve the inflammatory microenvironment and secrete BMP-2.

The effect of affiliated analysts on stock recommendations: Evidence from share pledges in China

We use the share pledge context in China to examine how affiliated analysts whose securities companies are pledgees of share pledge firms issue stock recommendations on these listed firms.We find that their recommendations are more optimistic than those of non-affiliated analysts,and they are more likely to issue Buy and Add recommendations,suggesting that they issue optimistic rating reports for share pledge firms due to their conflicts of interest.We also find a dynamic adjustment in the stock recommendation behavior of these analysts,and their probability after issuing optimistic stock recommendations is significantly reduced before and after the years that the affiliation relationship between them and share pledge firms both began and ended.These affiliated analysts continue to issue optimistic stock recommendations after visiting the share pledge firms if they work in the same location as the firms,or if they are star analysts among New Fortune’s‘‘top five analysts,"and when the information transparency of the share pledge firms is higher.In addition,the optimistic stock recommendation behavior of affiliated analysts is more significant in our sample of firms with high share pledge ratios and downward stock price pressure.The earnings forecast quality of affiliated analysts is also found to be lower,and they are less inclined to downgrade stock recommendations for these share pledge firms.Buy recommendations issued by both nonaffiliated and affiliated analysts can bring cumulative excess returns in the short event window,but those issued by affiliated analysts are significantly negative in the long-term event window,and significantly lower than those issued by non-affiliated analysts.Overall,our study shows that affiliated analysts issue optimistic rating reports on share pledge firms due to conflicts of interest,which leads to decision-making bias in investors and thus decreases the stock price crash risk of the firms.Our findings further reveal the economic consequences of share pledging and extend our understanding of the behavior of analysts in a conflict of interest situation from the share pledge perspective.

Serum mitochondrial tsRNA serves as a novel biomarker for hepatocarcinoma diagnosis

Hepatocellular carcinoma(HCC),which makes up the majority of liver cancer,is induced by the infection of hepatitis B/C virus.Biomarkers are needed to facilitate the early detection of HCC,which is often diagnosed too late for effective therapy.The tRNA-derived small RNAs(tsRNAs)play vital roles in tumorigenesis and are stable in circulation.However,the diagnostic values and biological functions of circulating tsRNAs,especially for HCC,are still unknown.In this study,we first utilized RNA sequencing followed by quantitative reverse-transcription PCR to analyze tsRNA signatures in HCC serum.We identified tRF-Gln-TTG-006,which was remarkably upregulated in HCC serum(training cohort:24 HCC patients vs.24 healthy controls).In the validation stage,we found that tRF-Gln-TTG-006 signature could distinguish HCC cases from healthy subjects with high sensitivity(80.4%)and specificity(79.4%)even in the early stage(Stage I:sensitivity,79.0%;specificity,74.8%;155 healthy controls vs.153 HCC patients from two cohorts).Moreover,in vitro studies indicated that circulating tRF-Gln-TTG-006 was released from tumor cells,and its biological function was predicted by bioinformatics assay and validated by colony formation and apoptosis assays.In summary,our study demonstrated that serum tsRNA signature may serve as a novel biomarker of HCC.

Synergetic Improvement of Interlaminar Fracture Toughness in Carbon Fiber/Epoxy Composites Interleaved with PES/PEK‑C Hybrid Nanofiber Veils

In this study,two types of soluble thermoplastic resins were added to epoxy resin at a fixed weight ratio to prepare a three-phase cast body.The cast was then manufactured into hybrid nanofiber as interleaves for interlaminar toughening of carbon fiber/epoxy resin(CF/EP)composites using a co-solvent method.The results revealed that when the hybrid components reached 15 wt%,Polyethersulfone(PES)and polyaryletherketone cardo(PEK-C)exhibited the best synergistic toughening effect,and the fracture toughness increased by 99.8%and 39.8%,respectively,compared with the reference or the same proportion of the single PES toughened sample.We used PES/PEK-C hybrid nanofibers with an areal density of 19.2 g per square meter(gsm)as composite toughening layers.Apart from the lack of significant influence of PES nanofiber on CF/EP composites,the interlaminar fracture toughness of mode I and mode II layers increased by 88.3%and 46.9%,respectively,compared to the reference sample.Scanning Electron Microscopy of the fracture surface and cross-section micromorphology of the laminate displayed that the thermoplastic microspheres of different sizes contribute differently to crack resistance:PEK-C consumes more energy due to the debonding and extraction of microspheres and resin,whereas the presence of the PES phase can induce more plastic deformation and crack deflection.

The HIF-1A/miR-17-5p/PDCD4 axis contributes to the tumor growth and metastasis of gastric cancer

Dear Editor,Gastric cancer(GC)is one of the most common malignant tumors of the digestive system and the second leading cause of cancer death worldwide1.Despite the gradually declining morbidity and mortality,GC still burdens many countries in East Asia1.Understanding the GC pathological process is vital for the successful diagnosis,treatment and prevention of this disease.

MicroRNA-29a modulates axon branching by targeting doublecortin in primary neurons

MicroRNAs （miRNAs） are endogenously expressed small, non-coding transcripts that regulate protein expression. Substantial evidences suggest that miRNAs are enriched in central nervous system, where they are hypothesized to play pivotal roles during neural devel- opment. In the present study, we analyzed miRNAs expression in mice cerebral cortex and hippocampus at different developmental stages and found miR-29a increased dramatically at postnatal stages. In addition, we provided strong evidences that miR-29a is enriched in mature neurons both in vitro and in v/vo. Further investigation demonstrated that the activation of gluta- mate receptors induced endogenous miR-29a level in primary neurons. Moreover, we showed that miR-29a directly regulated its target protein Doublecortin （DCX） expression, which further modulated axon branching in primary culture. Together, our results suggested that miR-29a play an important role in neuronal development of mice cerebrum.

Official rotation and corporate innovation: Evidence from the governor rotation

Rotation is a practice whereby officials are regularly moved between equally ranked positions.Focusing on governor rotation,this paper examines the effect of official rotation on corporate innovation in China.First,we find that official rotation significantly promotes corporate innovation,including enterprises’innovation investment,quantity,and quality.Second,we find that the effect of official rotation on corporate innovation varies because of official and regional heterogeneity.Officials rotating from other provinces significantly stimulate corporate innovation,but officials rotating from the central government have an insignificant influence on corporate innovation.In addition,offi-cials rotating to non-eastern regions significantly enhance corporate innovation,while officials rotating to eastern regions have a negligible impact on corporate innovation.We further examine the driving mechanism behind the effect of official rotation on corporate innovation and find that officials rotating from eastern regions to non-eastern regions can significantly promote corporate innovation,but officials rotating from non-eastern regions to eastern regions do not boost corporate innovation.These findings imply that the different effects of official rotation on corporate innovation are due to the official experience effect.We also find that official rotation can promote corporate innovation through reducing corporate charitable donations and increasing corporate innovation subsidies.In a supplementary analysis,we find that GDP-oriented performance appraisal pressure weakens the effect of official rotation on corporate innovation.The lower the pressure on officials regarding their performance,the more significant the effect of official rotation on corporate innovation.In addition,official rotation can significantly promote the development of the regional economy and improve the GDP growth rate via corporate innovation,which is a micro-level economic growth effect of official rotation.Overall,our findings further verify the economic effect of official rotation and extend our understanding of the influencing factors of corporate inno-vation from the perspective of the official governance system.Our findings also have clear policy implications for how the government can improve the official governance model to promote corporate innovation during the transition period of the national innovation system.

Paternal environmental exposure-induced spermatozoal small noncoding RNA alteration meditates the intergenerational epigenetic inheritance of multiple diseases

Studies of human and mammalian have revealed that environmental exposure can affect paternal health conditions as well as those of the offspring.However,studies that explore the mechanisms that meditate this transmission are rare.Recently,small noncoding RNAs(sncRNAs)in sperm have seemed crucial to this transmission due to their alteration in sperm in response to environmental exposure,and the methodology of microinjection of isolated total RNA or sncRNAs or synthetically identified sncRNAs gradually lifted the veil of sncRNA regulation during intergenerational inheritance along the male line.Hence,by reviewing relevant literature,this study intends to answer the following research concepts:(1)paternal environmental factors that can be passed on to offspring and are attributed to spermatozoal sncRNAs,(2)potential role of paternal spermatozoal sncRNAs during the intergenerational inheritance process,and(3)the potential mechanism by which spermatozoal sncRNAs meditate intergenerational inheritance.In summary,increased attention highlights the hidden wonder of spermatozoal sncRNAs during intergenerational inheritance.Therefore,in the future,more studies should focus on the origin of RNA alteration,the target of RNA regulation,and how sncRNA regulation during embryonic development can be sustained even in adult offspring.

Predicative value of urinary protein biomarkers on delayed renal involvement in children with Henoch-Sch?nlein purpura

Dear Editor,Henoch-Schonlein purpura(HSP)is one of the most common vasculitides in children with the incidence of 10-30 cases per 100,000 per year(Chen and Mao,2015)and its prognosis primarily depends on the extent of renal involvement.However,the onset of renal involvement may be delayed for weeks or months after the appearance of acute symptoms in HSP patients and easily be omitted(Mao et al.,2014).The increased urine protein biomarkers were remarkable indicators of early renal damage or early renal tubular function damage(Zulu et al.,2016)and had a great potential for early prognosis of HSP,but seldom do relationship between these biomarkers and later renal impairments of HSP were analyzed.This study aimed to investigate the relationship of several urinary protein levels during the acute stage of HSP,including N-acetyl-beta-D-glucosaminidase(NAG),p2-microglobulin(P2-MG),retinol-binding protein(RBP),transferrin(TRF),immunoglobulin G(IgG)and microalbumin(MA),with the risk of subsequent renal involvement after acute phase in HSP.