High-frequency repetitive transcranial magnetic stimulation promotes neural stem cell proliferation after ischemic stroke

Prolife ration of neural stem cells is crucial for promoting neuronal regeneration and repairing cerebral infarction damage.Transcranial magnetic stimulation(TMS)has recently emerged as a tool for inducing endogenous neural stem cell regeneration,but its underlying mechanisms remain unclea r In this study,we found that repetitive TMS effectively promotes the proliferation of oxygen-glucose deprived neural stem cells.Additionally,repetitive TMS reduced the volume of cerebral infa rction in a rat model of ischemic stro ke caused by middle cerebral artery occlusion,im p roved rat cognitive function,and promoted the proliferation of neural stem cells in the ischemic penumbra.RNA-sequencing found that repetitive TMS activated the Wnt signaling pathway in the ischemic penumbra of rats with cerebral ischemia.Furthermore,PCR analysis revealed that repetitive TMS promoted AKT phosphorylation,leading to an increase in mRNA levels of cell cycle-related proteins such as Cdk2 and Cdk4.This effect was also associated with activation of the glycogen synthase kinase 3β/β-catenin signaling pathway,which ultimately promotes the prolife ration of neural stem cells.Subsequently,we validated the effect of repetitive TMS on AKT phosphorylation.We found that repetitive TMS promoted Ca2+influx into neural stem cells by activating the P2 calcium channel/calmodulin pathway,thereby promoting AKT phosphorylation and activating the glycogen synthase kinase 3β/β-catenin pathway.These findings indicate that repetitive TMS can promote the proliferation of endogenous neural stem cells through a Ca2+influx-dependent phosphorylated AKT/glycogen synthase kinase 3β/β-catenin signaling pathway.This study has produced pioneering res ults on the intrinsic mechanism of repetitive TMS to promote neural function recove ry after ischemic stro ke.These results provide a stro ng scientific foundation for the clinical application of repetitive TMS.Moreover,repetitive TMS treatment may not only be an efficient and potential approach to support neurogenesis for further therapeutic applications,but also provide an effective platform for the expansion of neural stem cells.

乳酸促脂溢性脱发小鼠毛发生长研究

通过除去C57BL/6小鼠背部毛发及涂抹睾酮建立脂溢性脱发模型,研究乳酸对脂溢性脱发小鼠毛发生长,毛囊生长周期及生长因子的影响。将60只C57BL/6小鼠随机分为正常组,模型组,米诺地尔酊阳性组,乳酸高、中、低剂量组,并分别在脱毛区涂抹相对应的药物。连续给药24天,记录小鼠皮肤颜色变化时间、脱毛区毛发生长状况以及毛囊组织学特征和毛囊数目的变化;使用Elisa试剂盒检测小鼠体内KGF,VEGF和TGF-β1的质量浓度。结果表明,与模型组、正常组相比较,乳酸能显著促进脂溢性脱发小鼠毛发生长,增加小鼠毛发重量和给药实验区域皮肤毛囊数量,同时上调小鼠皮肤中KGF和VEGF质量浓度,降低小鼠皮肤中TGF-β1质量浓度,差异有统计学意义(P<0.05),其中以中剂量10g/L乳酸溶液效果最佳,可加快小鼠毛发生长、促进小鼠毛囊生长期转化进程,抑制脂溢性脱发症状,其疗效与阳性药米诺地尔酊效果相当(P>0.05),可制成日用洗护产品预防脱发,为脂溢性脱发患者提供更多选择。

Kaempferol improves glucose uptake in skeletal muscle via an AMPK-dependent mechanism

Insulin resistance is a hallmark of type-2 diabetes(T2D)pathogenesis.Because skeletal muscle(SkM)is the major tissue for insulin-mediated glucose disposal,insulin resistance in SkM is considered a major risk factor for developing T2D.Thus,the identifi cation of compounds that enhance the ability of SkM to take up glucose is a promising strategy for preventing T2D.Our previous work showed that kaempferol,a fl avonol present in many foods,improves insulin sensitivity in obese mice,however,the mechanism underlying this beneficial action remains unclear.Here,we show that kaempferol directly stimulates glucose uptake and prevents lipotoxicity-impaired glucose uptake in primary human SkM.Kaempferol stimulates Akt phosphorylation in a time-dependent manner in human SkM cells.The effect of kaempferol on glucose uptake was blunted by inhibition of glucose transporter 4,phosphoinositide 3-kinase(PI3K),or AMPK.In addition,kaempferol induced AMPK phosphorylation,and inhibition of AMPK prevented kaempferol-stimulated Akt phosphorylation.In vivo,kaempferol administration induced rapid glucose disposal accompanied with increased Akt and AMPK phosphorylation in SkM tissue of the mice.Taken together,these fi ndings suggest that kaempferol stimulates glucose uptake in SkM via an AMPK/Akt dependent mechanism,and it may be a viable therapeutic agent for insulin resistance.

ENST00000535926 is an unfavorable prognosis-related and tumorpromoting transcript of the CHPF gene in luminal A and B breast cancer

Chondroitin sulfate synthase 2(CHPF)is characterized as an oncogenic and poor prognosis-related gene in breast cancer.However,this gene has alternative splicing products encoding proteins of different lengths.Breast cancer is a group of heterogeneous tumors with distinct clinical and genomic characteristics.In this study,we explored the expression profile and prognostic value of the two transcripts of CHPF using data from The Cancer Genome Atlas(TCGA)-BRCA.The functional regulation of the two transcripts was also studied in MCF-7 and BT-474 cells.Among the two transcripts of CHPF,ENST00000535926 expression was significantly upregulated in the tumor samples and was the dominant isoform.ENST00000535926,but not ENST00000243776 upregulation,was associated with significantly worse progression-free survival(PFS)and disease-specific survival(DSS)in luminal A/B cases.However,no significant association was observed in PFS or DSS in other Prediction Analysis of Microarray 50(PAM50)subgroups.CHPF isoform 2 protein(encoded by ENST00000535926)significantly elevated the expression of P3H1 and RCN3 at the mRNA and protein levels in MCF-7 and BT-474 cells.The effect of ENST00000535926 was significantly stronger than ENST00000243776 in promoting tumor cell colony formation.The expression of P3H1 and RCN3 was negatively correlated with CD8+T cell infiltration but was positively correlated with cancer-associated fibroblast infiltration in luminal A/B tumors.In summary,this study revealed that ENST00000535926 is an unfavorable prognosis-related and tumor-promoting transcript of the CHPF gene in luminal A/B breast cancer.

Eosinophilic fasciitis difficult to differentiate from scleroderma:A case report

BACKGROUND Eosinophilic fasciitis(EF)is a rare connective tissue disease that can cause swelling and sclerosis of the extremities,and special attention is needed to differentiate EF from systemic sclerosis.Misdiagnosis or omission markedly delays treatment of EF,and severe skin sclerosis in advanced stages can cause joint contracture and tendon retraction,worsening the patient's prognosis and quality of life.CASE SUMMARY We report a case of EF in a young woman diagnosed by tissue biopsy,confirming the difficulty of differential diagnosis with scleroderma.CONCLUSION Focusing on skin manifestations,completing tissue biopsy and radiography can help diagnose EF effectively.Clinicians should enhance their understanding of the differences between EF and scleroderma,and early diagnosis and standardized treatment can improve the prognosis of patients with EF.

Simultaneous integrated dose reduction intensity-modulated radiotherapy effectively reduces cardiac toxicity in limited-stage small cell lung cancer

Objective:To assess the clinical outcomes and toxicities of once daily(QD)simultaneous dose reduction intensity-modulated radiotherapy(SDR-IMRT-QD;SDR-QD)versus conventional QD IMRT(C-QD)and twice daily(BID)IMRT in patients with limited-stage small cell lung cancer(LS-SCLC).Methods:After propensity score matching(PSM),a retrospective analysis involving 300 patients with LS-SCLC treated using SDR-QD,C-QD,or BID was performed from January 1,2014 to December 31,2019.The prescribed irradiation dose in the SDR-QD cohort was 60 Gy/PGTV and 54 Gy/PTV QD.The radiation dose was 60 Gy for both PGTV and PTV QD in the C-QD cohort.The radiation dose was 45 Gy for both PGTV and PTV in the BID cohort.Toxicities,short-term effects,and survival outcomes were recorded.A meta-analysis on the protective effects of pharmaceuticals for cardiac toxicities induced by anti-tumor therapy was performed.Results:The median overall survival time(MST)in the 3 cohorts were 32.7 months(SDR-QD),26.3 months(C-QD),and 33.6 months(BID);the differences between groups were statistically significant.Lower toxicities and doses to organs-at-risk(OARs)occurred in the SDR-QD and BID cohorts.Further,the cardiac dose dosimetric parameter Vheart40 was negatively associated with survival(r=-0.35,P=0.007).A Vheart40 value of 16.5%was recommended as a cut-off point,which yielded 54.7%sensitivity and 85.7%specificity for predicting negative survival outcomes.The meta-analysis indicated that pharmaceuticals significantly reduced the cardiac toxicities induced by chemotherapy,but not radiotherapy.Conclusions:SDR-QD was shown to have similar toxicities and survival compared with BID,but fewer toxicities and better survival than C-QD.In addition,cardiac dose exposure was negatively associated with survival.Thus,16.5%of the cardiac dosimetric parameter Vheart40 is recommended as the cut-off point,and a Vheart40>16.5%predicts poor survival.

High-resolution assessment of retrogressive thaw slump susceptibility in the Qinghai-Tibet Engineering Corridor

Under the rapidly warming climate in the Arctic and high mountain areas,permafrost is thawing,leading to various hazards at a global scale.One common permafrost hazard termed retrogressive thaw slump(RTS)occurs extensively in ice-rich permafrost areas.Understanding the spatial and temporal distributive features of RTSs in a changing climate is crucial to assessing the damage to infrastructure and decision-making.To this end,we used a machine learning-based model to investigate the environmental factors that could lead to RTS occurrence and create a susceptibility map for RTS along the Qinghai-Tibet Engineering Corridor(QTEC)at a local scale.The results indicate that extreme summer climate events(e.g.,maximum air temperature and rainfall)contributes the most to the RTS occurrence over the flat areas with fine-grained soils.The model predicts that 13%(ca.22,948 km^(2))of the QTEC falls into high to very high susceptibility categories under the current climate over the permafrost areas with mean annual ground temperature at 10 m depth ranging from-3 to-1℃.This study provides insights into the impacts of permafrost thaw on the stability of landscape,carbon stock,and infrastructure,and the results are of value for engineering planning and maintenance.

Connectome-based predictive modelling can predict follow-up craving after abstinence in individuals with opioid use disorders

Background Individual differences have been detected in individuals with opioid use disorders(OUD)in rehabilitation following protracted abstinence.Recent studies suggested that prediction models were effective for individual-level prognosis based on neuroimage data in substance use disorders(SUD).Aims This prospective cohort study aimed to assess neuroimaging biomarkers for individual response to protracted abstinence in opioid users using connectome-based predictive modelling(CPM).Methods One hundred and eight inpatients with OUD underwent structural and functional magnetic resonance imaging(fMRI)scans at baseline.The Heroin Craving Questionnaire(HCQ)was used to assess craving levels at baseline and at the 8-month follow-up of abstinence.CPM with leave-one-out cross-validation was used to identify baseline networks that could predict follow-up HCQ scores and changes in HCQ(HCQtolow V-up-HCQpa baseline).Then,the follow-up aseline predictive ability of identified networks was tested in a separate,heterogeneous sample of methamphetamine individuals who underwent MRI scanning before abstinence for SUD.Results CPM could predict craving changes induced by long-term abstinence,as shown by a significant correlation between predicted and actual HCQ fllow-up(r=0.417,p<0.001)and changes in HCQ(negative:r=0.334,p=0.002;positive:r=0.233,p=0.038).Identified craving-related prediction networks included the somato-motor network(SMN),salience network(SALN),default mode network(DMN),medial frontal network,visual network and auditory network.In addition,decreased connectivity of frontal-parietal network(FPN)-SMN,FPN-DMN and FPN-SALN and increased connectivity of subcortical network(SCN)-DMN,SCN-SALNandSCN-SMN were positively correlated with craving levels.Conclusions These findings highlight the potential applications of CPM to predict the craving level of individuals after protracted abstinence,as well as the generalisation ability;the identified brain networks might be the focus of innovative therapies in the future.

金属有机框架MOF-808-X高效催化CO_2和甲醇直接合成碳酸二甲酯（英文）

碳酸二甲酯(DMC)是一种重要的绿色无毒化工原料,其分子结构中含有甲基、甲氧基和羰基等官能团.DMC既可以替代卤代甲烷和硫酸二甲酯用作甲基化试剂,替代剧毒的光气用作羰基化试剂,也可以与醇类、酯类及氨基醇类进行酯交换反应用于合成树脂和精细化学品.此外, DMC因具有相容性好、含氧量高和饱和蒸气压低等特点,还可用作低毒溶剂和燃油添加剂.目前,已报道的DMC合成方法主要包括光气法、甲醇氧化羰基化法、酯交换法、尿素醇解法和直接合成法.其中,以CO_2和甲醇为原料直接合成DMC的方法受到广泛关注.该方法不仅具有原料价格低廉、工艺简单、原子经济性高的优点,还可以将温室气体CO_2资源化利用,有望成为未来生产DMC的一条全新的高效途径.目前,用于该反应的催化剂研究主要集中在金属氧化物和改性金属氧化物上,这些催化剂存在比表面积较小、活性位点数量不足以及活性不高的缺点.本文针对传统金属氧化物的缺点,合成了一系列锆基金属有机框架催化剂MOF-808-X(X为ZrOCl_2·8H_2O/均苯三甲酸(BTC)的摩尔比),并将其用于催化CO_2和甲醇合成DMC,系统考察了MOF-808-X合成过程中ZrOCl_2·8H_2O/BTC摩尔比对MOF-808-X催化剂组成、比表面积、孔道结构以及酸碱位点数量的影响,探讨了MOF-808-X催化剂物化性质与其催化性能之间的关系.结果表明,通过调控ZrOCl_2·8H_2O/BTC摩尔比,可以减少堵塞在MOF-808-X微孔中未反应的配体BTC或氧化锆原子簇的量,提高MOF-808-X的比表面积、微孔孔径以及酸碱位点数量,从而显著提升MOF-808-X催化剂的催化活性.当ZrOCl_2·8H_2O/BTC摩尔比=4时, MOF-808-4催化剂具有最大的比表面积、最大的微孔孔径和最多的酸碱性位点,因而表现出最高的催化活性.与我们之前报道的UiO-6-24相比,虽然MOF-808-4的比表面积和酸碱位点数更小,但由于MOF-808-4具有更大的微孔孔径(1.8nm),其微孔内的活性位点具有更高的催化效率, MOF-808-4表现出了更高的催化活性.原位红外光谱结果表明,酸性位点活化甲醇生成甲基阳离子的过程是该反应的速率控制步骤,由于MOF-808-4中Zr6原子簇上酸碱位点相互邻近,吸附在相邻碱性位点上的中间产物羰基甲氧基可以与酸性位点上的甲基阳离子迅速反应,促进甲基阳离子和DMC的生成,从而进一步提高MOF-808-4的催化活性.此外,催化剂重复利用实验结果表明, MOF-808-X催化剂结晶度越好,催化剂重复利用性能越好.MOF-808-X催化剂在CO_2和甲醇直接合成DMC反应中的成功应用可为开发用于该反应的高效非均相催化剂提供新的思路.

V_(2)O_(5)纳米片固载Pt纳米粒子催化剂的构建及其增强催化空气氧化脱硫性能

以铂系金属为代表的贵金属催化剂在工业反应中通常表现出优异的催化性能,这是因为其具有独特的d带电子结构和较高的价电子比.近年来,由于大气排放法规愈发严苛,铂系贵金属催化剂在催化空气氧化燃油脱硫方面的研究引起了广泛关注.在该催化反应中,铂系金属纳米粒子可以有效活化空气中的氧气,产生的活性氧物种可以将油品中的噻吩类硫化物氧化为其对应的强极性砜类物质,从而可以将其从非极性的油品中分离出来,有效实现油品中硫化物的深度氧化脱除.然而,在反应过程中铂系贵金属纳米粒子易发生流失和烧结,从而导致催化剂的失活.因此,急需寻找一类可以有效固载铂系贵金属纳米粒子的载体.在目前已报道的众多载体中,以ZrO_(2)、TiO_(2)、CeO_(2)、ZnO等为代表的过渡金属氧化物引起了广泛的关注.通常认为,铂系贵金属纳米粒子的d轨道电子和过渡金属氧化物之间可形成金属-载体强相互作用.然而,目前所使用的过渡金属氧化物载体的比表面积较小,从而导致铂系贵金属纳米粒子难以有效且均匀地分散于其表面.本文采用热膨胀气相剥离法制备了超薄V2O5纳米片,并通过超声辅助沉积法将Pt纳米粒子固载于其表面,从而得到一系列可高效活化空气氧化脱硫的催化剂(Pt NPs-n/V_(2)O_(5)纳米片).通过电感耦合等离子体光谱、高倍透射电镜、原子力显微镜、X射线光电子能谱、X射线衍射、拉曼光谱和氮气吸附脱附等方法对催化剂的结构和形貌进行了表征.结果表明,尺寸为4-5 nm的Pt纳米粒子可有效均匀分散于层数约为6层的V2O5纳米片表面;在空气氧化脱硫反应中,当催化剂中Pt理论负载量为2 wt%时,反应5 h后,油品的脱硫率可达99.1%,实现了硫化物的深度氧化脱除.该反应体系对不同硫浓度、不同含硫底物的油品均有较好的脱除效果,但对含有烯烃、芳烃的油品脱除效果较差.此外,催化剂循环使用7次后,其脱硫活性仍无明显下降,表现出优异的重复使用性能.对反应后的催化剂进行表征,发现Pt几乎不发生流失,这可能是由于Pt纳米粒子和V_(2)O_(5)纳米片之间形成了金属-载体强相互作用.该结果为其他空气氧化反应的有效进行提供了新思路.

长链非编码RNA在宫颈癌中的表达及预后价值

目的研究长链非编码RNA(lncRNA)在宫颈癌中的表达水平,鉴定在宫颈癌组织中异常表达的lncRNA,初步分析其功能,并评估其预后价值。方法宫颈癌组织和癌旁组织的转录组数据下载自癌症基因组图谱(TCGA),结合Genecode数据库中lncRNA注释信息,获取lncRNA的表达数据。通过limma软件包鉴定在宫颈癌组织和癌旁组织中差异表达的lncRNA;同时对存在差异表达的lncRNA进行生存分析和功能预测。结果在宫颈癌组织和癌旁组织中差异表达的lncRNA有554个,其中在宫颈癌组织中表达下调245个,上调309个(校正后P<0.05,倍数变化绝对值>2)。生存分析鉴定出11个与宫颈癌患者总体生存率相关的差异表达lncRNA(P<0.01)。京都基因与基因组百科全书(KEGG)代谢途径富集分析显示这些lncRNA参与到环磷酸鸟苷酸-环磷酸鸟苷酸依赖的蛋白激酶(cGMP-PKG)信号通路、钙信号通路和细胞间隙连接等肿瘤发生、发展相关代谢途径。结论通过对宫颈癌lncRNA数据的分析,鉴定11个具有预后意义的lncRNA,这些lncRNA有可能为宫颈癌治疗提供新的靶点和预后监测标志物。

全腹腔镜与腹腔镜辅助行远端胃癌毕Ⅰ式吻合术后并发症的影响因素分析

目的探讨腹腔镜远端胃癌根治术行毕I式吻合术后并发症发生的危险因素。方法选取2014年6月-2016年12月该院收治的134例远端胃癌患者,其中83例行腹腔镜辅助远端胃癌根治术,51例行全腹腔镜远端胃癌根治术;比较两种手术方式术后并发症发生率并分析术后并发症发生率的高危因素。结果术后共16例(11.94%)出现并发症,其中严重并发症3例(2.24%)。两种手术方式术后并发症发生率比较有差异(10.84%vs 13.73%;χ~2=0.250,P=0.617)。术后并发症与年龄、术前合并症、手术时间及手术出血量和术者经验有关(P<0.05),而与性别、体重指数(BMI)、术前白蛋白、术前血红蛋白、手术方式、病理分化类型、肿瘤大小、肿瘤T分期、N分期及TNM分期无关(P>0.05)。中度、重度术前合并症和术者经验是影响术后并发症发生的危险因素(P<0.05)。结论全腹腔镜下毕Ⅰ式吻合治疗远端胃癌安全可行。但对中度、重度术前合并症及术者经验缺乏的患者,需警惕术后并发症的发生。

A journey to understand wheat Fusarium head blight resistance in the Chinese wheat landrace Wangshuibai

Fusarium head blight(FHB) or scab caused by Fusarium graminearum is a major threat to wheat production in China as well as in the world. To combat this disease, multiple efforts have been carried out internationally. In this article, we review our long-time effort in identifying the resistance genes and dissecting the resistance mechanisms by both forward and reverse genetics approaches in the last two decades. We present recent progress in resistance QTL identification, candidate functional gene discovery, marker-assisted improvement of FHB resistant varieties, and findings in investigating association of signal molecules, such as Ca^(++),SA, JA, and ET, with FHB response, with the assistance from rapidly growing genomics platforms. The information will be helpful for designing novel and efficient approaches to curb FHB.

Vertical profile of aerosol extinction based on the measurement of O4 of multi-elevation angles with MAX-DOAS

A method for aerosol extinction profile retrieval using ground-based multi-axis differential optical absorption spectroscopy(MAX-DOAS)is studied,which is based on a look-up table algorithm.The algorithm uses parametric method to represent aerosol extinction profiles and simulate different atmospheric aerosol states through atmospheric radiation transfer model.Based on the method,aerosol extinction profile was obtained during six cloud-free days.The O4 differential air mass factor(dAMF)measured by MAX-DOAS is compared with the corresponding model results under different atmospheric conditions(R^2=0.78).The aerosol optical thickness,aerosol weight factor in boundary layer,and the height of the boundary layer are obtained after the process of minimization and look-up table method.The retrieved aerosol extinction in boundary layer is compared with PM2.5 data measured by ground point instrument.The diurnal variation trends of the two methods are in good agreement.The correlation coefficients of the two methods are 0.71 when the aerosol optical thickness is smaller than 0.5.The results show that the look-up table method can obtain the aerosol state of the troposphere and provide validation for other instrument data.

Prevalence of amblyopia among preschool children in central south China

AIM: To determine the prevalence and factors associated with amblyopia among children aged 30-83 mo in central south of China.METHODS: A population-based, cross-sectional study was conducted in children aged 30-83 mo in Changsha(an urban city) and Zhangjiajie(a rural area) in central south of China. Clinical examinations including ocular alignment, ocular motility, visual acuity(VA), prism cover test, cycloplegic refraction, slit lamp examination and fundus examination were performed by trained study ophthalmologists and optometrists. Unilateral amblyopia was defined as a 2-line difference between eyes with VA<20/32 in the worse eye and with coexisting anisometropia [≥1.00 D spherical eutivalent(SE) for hyperopia, ≥3.00 D SE for myopia, and ≥1.50 D for astigmatism], strabismus, or past or present visual axis obstruction. Bilateral amblyopia was defined as VA in both eyes <20/40(≥ 48-month-old) and <20/50(< 48-month-old), with coexisting hyperopia ≥4.00 D SE, myopia ≤-6.00 D SE, and astigmatism ≥2.50 D, or past or present visual axis obstruction.RESULTS: There were 8042 children enrolled and 7713 children were screened. The amblyopia prevalence in children aged 30-83 mo was 1.09%(95% confidence interval, 0.86%-1.35%) with no age(P=0.81), gender(P=0.46) or area distribution(P=0.93) differences. Of these, 0.68% were unilateral cases and 0.41% were bilateral cases. Underlying causes included anisometropia(40%), binocular refractive error(36%), strabismus(14%) and deprivation(10%). Hyperopia combined with astigmatism was the frequent refractive error for ametropic and anisometropic amblyopia.CONCLUSION: In this rural and urban Chinese population, 1.09% of children with 30-83 mo of age had amblyopia, a prevalence rate similar to that of many other studies. Anisometropia and refractive error are the most common causes of unilateral and bilateral amblyopia respectively.

Shallow Water Modal Evolution Due to Nonlinear Internal Waves

Acoustic modal behavior is reported for an L-shape hydrophone array during the passage of a strong nonlinear internal wave packet. Acoustic track is nearly parallel to the front of nonlinear internal waves. Through modal decomposition at the vertical array, acoustic modes are identified. Modal evolution along the horizontal array then is examined during a passing internal wave. Strong intensity fluctuations of individual modes are observed before and during the internal waves packet passes the fixed acoustic track showing a detailed evolution of the waveguide modal behavior. Acoustic refraction created either uneven distribution of modal energy over the horizontal array or additional returns observable at the entire L-shape array. Acoustic ray-mode simulations are used to phenomenologically explain the observed modal behavior.

C-C chemokine receptor type 2-overexpressing exosomes alleviated experimental post-stroke cognitive impairment by enhancing microglia/macrophage M2 polarization

BACKGROUND Human-derived mesenchymal stromal cells have been shown to improve cognitive function following experimental stroke.The activity of exosomes has been verified to be comparable to the therapeutic effects of mesenchymal stromal cells.However,the effects of exosomes derived from human umbilical cord mesenchymal stem cells(HUC-MSCs)(ExoCtrl)on post-stroke cognitive impairment(PSCI)have rarely been reported.Moreover,whether exosomes derived from C-C chemokine receptor type 2(CCR2)-overexpressing HUC-MSCs(ExoCCR2)can enhance the therapeutic effects on PSCI and the possible underlying mechanisms have not been studied.AIM To investigate the effects of ExoCtrl on PSCI and whether ExoCCR2 can enhance therapeutic effects on PSCI.METHODS Transmission electron microscopy,qNano®particles analyzer,and Western blotting were employed to determine the morphology and CCR2 expression of ExoCtrl or ExoCCR2.ELISA was used to study the binding capacity of exosomes to CC chemokine ligand 2(CCL2)in vivo.After the intravenous injection of ExoCtrl or ExoCCR2 into experimental rats,the effect of ExoCtrl and ExoCCR2 on PSCI was assessed by Morris water maze.Remyelination and oligodendrogenesis were analyzed by Western blotting and immunofluorescence microscopy.QRT-PCR and immunofluorescence microscopy were conducted to compare the microglia/macrophage polarization.The infiltration and activation of hematogenous macrophages were analyzed by Western blotting and transwell migration analysis.RESULTS CCR2-overexpressing HUC-MSCs loaded the CCR2 receptor into their exosomes.The morphology and diameter distribution between ExoCtrl and ExoCCR2 showed no significant difference.ExoCCR2 bound significantly to CCL2 but ExoCtrl showed little CCL2 binding.Although both ExoCCR2 and ExoCtrl showed beneficial effects on PSCI,oligodendrogenesis,remyelination,and microglia/macrophage polarization,ExoCCR2 exhibited a significantly superior beneficial effect.We also found that ExoCCR2 could suppress the CCL2-induced macrophage migration and activation in vivo and in vitro,compared with ExoCtrl treated group.CONCLUSION CCR2 over-expression enhanced the therapeutic effects of exosomes on the experimental PSCI by promoting M2 microglia/macrophage polarization,enhancing oligodendrogenesis and remyelination.These therapeutic effects are likely through suppressing the CCL2-induced hematogenous macrophage migration and activation.Key words:Cognitive impairment;Stroke;Exosomes;C-C chemokine receptor type 2;Microglia/macrophage polarization;Remyelination.

Intravitreal injection of resveratrol inhibits laser-induced murine choroidal neovascularization

AIM:To determine the effects of intravitreal resveratrol(RSV)on murine laser-induced choroidal neovascularization(CNV).METHODS:The toxicity of RSV to choroidal endothelial cell(CEC)was measured using thiazolyl blue tetrazolium bromide(M一)assay.Effects of RSV on choroidal endothelial cell(CEC)migration were evaluated with a modified Boyden chamber assay,while tube formation was evaluated in a 2-D gel assay.CNV was induced by laser photocoagulation in mice.The effects of intravitreal injection of RSV on CNV development were evaluated by fluorescein angiography(FA),confocal analysis of isolectin B4 labeled choroidal flat mounts,and histologic examination of CNV membranes.Immunostaining was used to analyze the expression and phosphorylation of vascular endothelial growth factor receptor 2(VEGFR2).RESULTS:No significant cell toxicity was observed in CEC if the concentration of RSV was less than 200 pmol/L(P>0.05).RSV inhibited vascular endothelial growth factor(VEGF)-induced CEC migration(P<0.05)and tube formation(P<0.05)invitro.Furthermore,intravitrealinjectionof RSV significantly inhibited laser induced CNV formation in mice.The FA leakage,CNV volume and CNV area analysis revealed that there were 41%,45%,and 58%reduction in RSV-treated eyes(1.691±0.1032,178163±78623μm^3 and 6508±619.0μm^2,respectively)compared with those in control(2.724±0.08447,379676±98382μm3and16576±2646μm^2,respectively;P<0.05).Phospho-VEGFR2expression was much weaker in the sections of CNV lesions in RSV injected mice compared with that in control(P<0.05).CONCLUSION:Intravitreal injection of RSV exerts an inhibitory effect on CNV,which may through suppressing endothelial cell migration,tube formation and VEGFR2 phosphorylation.

Influence of Collective Esophageal Speech Training on Self-efficacy in Chinese Laryngectomees:A Pretest-posttest Group Study

Total laryngectomy affects the speaking functions of many patients.Speech deprivation has great impacts on the quality of life of patients,especially on self-efficacy.Learning esophageal speech represents a way to help laryngectomees speak again.The purpose of this study was to determine the influence of collective esophageal speech training on self-efficacy of laryngectomees.In this study,28 patients and 30 family members were included.The participants received information about training via telephone or a WeChat group.Collective esophageal speech training was used to educate laryngectomees on esophageal speech.Before and after collective esophageal speech training,all participants completed the General Self-Efficacy Scale(GSES)to assess their perceptions on self-efficacy.Through the training,laryngectomees recovered their speech.After the training,the self-efficacy scores of laryngectomees were higher than those before the training,with significant differences noted(P<0.05).However,family members'scores did not change significantly.In conclusion,collective esophageal speech training is not only convenient and economical,but also improves self-efficacy and confidence of laryngectomees.Greater self-efficacy is helpful for laryngectomees to master esophageal speech and improve their quality of life.In addition,more attention should be focused on improving the self-efficacy of family members and making them give full play to their talent and potential on laryngectomees'voice rehabilitation.

In-situ testing study on convection and temperature characteristics of a new crushed-rock slope embankment design in a permafrost region

For the purpose of enhancing air convection and controlling solar radiation, a new crushed-rock slope embankment design combined with a sun-shade measure is proposed. A newly designed embankment was constructed in the Tuotuohe section of the Qinghai-Tibet Railway and a field-testing experiment was carried out to determine its convection and temperature characteristics. The results show that distinct air convection occurred in the crushed-rock layer of the new embankment, especially in cold seasons, which was enhanced when it flowed upwards along the slope. This preliminarily indicated that the new design of the embankment slope was good for reinforcing air convection in the crushed-rock layer. The frequent fluctuations of the convection speed and the environmental wind speed were in good agreement, suggesting that the convection in the crushed rock primarily came from the ambient wind. It was also preliminarily determined that the new embankment had a better cooling effect and sun-shade effect for decreasing the temperature of the embankment slope compared with a traditional crushed-rock slope embankment, and the mean temperature difference between them was up to 1.7 °C. The mean annual temperature at the bottom boundary of the crushed-rock layer was obviously lower than that at the top boundary, and heat flux calculation showed that the shallow soil beneath the embankment slope was weakly releasing heat, all of which indicated that the new embankment slope design was beneficial to the thermal stability of the embankment. This study is helpful in providing some references for improved engineering design and maintenance of roadbeds in permafrost regions.