Efficient Humoral and Cellular Immune Responses Induced by a Chimeric Virus-like Particle Displaying the Epitope of EV71 without Adjuvant

Objective To eliminate the side effects of aluminum adjuvant and His-tag,we constructed chimeric VLPs displaying the epitope of EV71（SP70） without His-tagged.Then evaluating whether the VLPs could efficiently evoke not only humoral but also cellular immune responses against EV71 without adjuvant.Methods The fusion protein was constructed by inserting SP70 into the MIR of truncated HBc Ag sequence,expressed in E.Coli,and purified through ion exchange chromatography and density gradient centrifugation.Mice were immunized with the VLPs and sera were collected afterwards.The specific antibody titers,Ig G subtypes and neutralizing efficacy were detected by ELISA,neutralization assay,and EV71 lethal challenge.IFN-γ and IL-4 secreted by splenocytes were tested by ELISPOT assay.Results HBc-SP70 proteins can self-assemble into empty VLPs.After immunization with HBc-SP70 VLPs,the detectable anti-EV71 antibodies were effective in neutralizing EV71 and protected newborn mice from EV71 lethal challenge.There was no significant difference for the immune efficacy whether the aluminum adjuvant was added or not.The specific Ig G subtypes were mainly IgG1 and IgG2 b and splenocytes from the mice immunized produced high levels of IFN-γ and IL-4.Conclusion The fusion proteins without His-tagged was expressed and purified as soluble chimeric HBc-SP70 VLPs without renaturation.In the absence of adjuvant,they were efficient to elicit high levels of Th1/Th2 mixed immune response as well as assisted by aluminum adjuvant.Furthermore,the chimeric VLPs have potential to prevent HBV and EV71 infection simultaneously.

中国特色植物原料图鉴解读

“鼓励和支持运用现代科学技术,结合我国传统优势项目和特色植物资源研究开发化妆品。”这是《化妆品监督管理条例》中相当明确的表态,常被拿来当做中国特色植物资源备受国家推崇、具备良好发展环境的依据。工信部、发改委和商务部联合印发的《轻工业稳增长工作方案(2023-2024年)》也曾指出:“加强特色植物原料开发创新,推动活性原料生物制造规模化生产,加大在食品、化妆品等行业的应用。”

Anti-OX40 Antibody Combined with HBc VLPs Delays Tumor Growth in a Mouse Colon Cancer Model

Objective Combination immunotherapy strategies targeting OX40,a co-stimulatory molecule that can enhance antitumor immunity by modulating the proliferation,differentiation,and effector function of tumor-infiltrating T cells,have attracted much attention for their excellent therapeutic effects.In this study,we aimed to evaluate the antitumor efficacy of combined anti-OX40 and hepatitis B core viruslike particles(HBc VLPs)therapy using a mouse colon cancer model.Methods Humanized B-h OX40 mice were injected subcutaneously with MC38 colon tumor cells and treated with HBc VLPs+anti-h OX40 antibody.Tumor growth was monitored.Flow cytometric analysis was performed to evaluate the populations of T cell subsets in the tumors.Results The combination of anti-OX40 with HBc VLPs resulted in a significant delay in tumor growth,suggesting that a potent antitumor immunity was induced by the combination therapy.Further studies revealed that HBc VLPs+anti-OX40 treatment induced a significant increase in effector T cells(Teffs)and a significant decrease in regulatory T cells(Tregs)in the tumor microenvironment(TME),which accounted for the synergistic antitumor effect of anti-OX40 in combination with HBc VLPs.Conclusion Combination therapy of anti-h OX40 and HBc VLPs provides synergistic antitumor activity in colon cancer-bearing mice,which may represent a potential design strategy for cancer immunotherapy.

Effects of PEAR1 gene polymorphism on big endothelin-1 levels in Chinese patients with acute myocardial infarction after percutaneous coronary intervention

Acute myocardial infarction (AMI) has been associated with poor prognosis,even after revascularization with percutaneous coronary intervention (PCI),likely due to coronary endothelial cell dysfunction and injury.^([1,2])Endothelin-1 (ET-1),a peptide that serves as a vasoconstrictor of smooth muscle cell proliferation,can reflect endothelial cell functional states.Due to low circulation levels and short plasma half-life time,measuring plasma ET-1 levels is difficult.In contrast,big ET-1.

不等厚互层顺层滑坡典型工程案例研究

文中以G4216仁沐高速不等厚互层顺层滑坡典型工程为例,进行了滑坡成因机制分析及边坡稳定性评价,针对高边坡、不等厚顺层边坡、产状变化为特征的路堑边坡提出了分段设计、固脚强腰、分级(分层)逐级、坡体整体稳定兼顾局部边坡稳定的治理思路。实践证明,设计方案取得了较好的治理效果,为同类型边坡提供了设计思路,尽量规避工期风险与投资风险。

化妆品新原料引爆创新“奇点”

《大辞海》中,将大爆炸宇宙论所追溯的宇宙演化的起点,称作“奇点”。按照宇宙学的推论,奇点具有无限大的物质密度、无限弯曲的时空,它是无形的,也是无限的。这些特性,好比人类在创新层面的想象力。化妆品原料的创新,也存在无限演化的可能。比如在近几年,化妆品行业对于原料端科研升维的推崇,就颇为积极。上到原料企业,下到品牌公司,在原料创新上的投入也以可见的速度加强。

New Raw Materials Ignite the Singularity of Cosmetic Innovation

As traced by the Big Bang theory,the starting point of the universe,is called the“Singularity”in Da Ci Hai,an unabridged,comprehensive dictionary.According to cosmological reasoning,the singularity has an infinite density of matter,an infinite curvature of space and time,and it is invisible and infinite.These characteristics are analogous to the human imagination at the level of innovation.For the innovation of cosmetic raw materials,there is also the possibility of infinite evolution.For example,in recent years,the scientific research in cosmetic industry the for promoting upgrade in raw materials is quite proactive.From the raw material enterprises,down to the brand company,the investment in raw material innovation is also strengthened at a visible rate.

Ⅱ类射线装置审批权限下放及管理可行性研究——以广西为例

党的十八大明确提出:“深化行政审批制度改革,继续简政放权,推动政府职能向创造良好发展环境、提供优质公共服务、维护社会公平正义转变。”为进一步深化生态环境领域简政放权改革,推动辐射环境领域“放管服”改革,服务广西社会经济高质量发展,广西拟将Ⅱ类射线装置核技术利用项目的审批权限下放至各设区市。本文通过调查、分析广西各设区市审批、监管能力,确定该项目审批权限下放的可行性。

Long noncoding RNA H19 regulates degeneration and regeneration of injured peripheral nerves

Our previous studies have shown that long noncoding RNA(lncRNA)H19 is upregulated in injured rat sciatic nerve during the process of Wallerian degeneration,and that it promotes the migration of Schwann cells and slows down the growth of dorsal root ganglion axons.However,the mechanism by which lncRNA H19 regulates neural repair and regeneration after peripheral nerve injury remains unclear.In this study,we established a Sprague-Dawley rat model of sciatic nerve transection injury.We performed in situ hybridization and found that at 4–7 days after sciatic nerve injury,lncRNA H19 was highly expressed.At 14 days before injury,adeno-associated virus was intrathecally injected into the L4–L5 foramina to disrupt or overexpress lncRNA H19.After overexpression of lncRNA H19,the growth of newly formed axons from the sciatic nerve was inhibited,whereas myelination was enhanced.Then,we performed gait analysis and thermal pain analysis to evaluate rat behavior.We found that lncRNA H19 overexpression delayed the recovery of rat behavior function,whereas interfering with lncRNA H19 expression improved functional recovery.Finally,we examined the expression of lncRNA H19 downstream target SEMA6D,and found that after lncRNA H19 overexpression,the SEMA6D protein level was increased.These findings suggest that lncRNA H19 regulates peripheral nerve degeneration and regeneration through activating SEMA6D in injured nerves.This provides a new clue to understand the role of lncRNA H19 in peripheral nerve degeneration and regeneration.

CsSnBr_(3)钙钛矿微晶体的化学气相沉淀生长、结构、稳定性及光学性能的系统研究

尽管铅基卤化物钙钛矿在光电器件中的应用前景广阔,但这些应用严格受限于材料的毒性,因此有必要开发无铅的全无机替代物,锡基卤化物钙钛矿虽然在可控合成和稳定性方面存在巨大挑战,但依然是理想的选择之一,本文利用化学气相沉积法进行了高质量的CsSnBr_(3)微晶体在SiO_(2)/Si表面的可控生长.制备的新鲜产物主要呈现三角星和钉状棒两种形貌,二者均具有立方相结构,产物在空气中暴露后有SnO_(2)生成,表明CsSnBra_(3)钙钛矿具有结构不稳定性,通过调变生长温度实现了对CsSnBr_(3)微晶体的成核密度及尺寸的控制.变功率和变温的光致发光结果表明,不同形貌的CsSnBr_(3)微晶体具有不同的激子结合能,而且由于量子限域效应对电子-空穴相互作用的影响而产生了不同的光激发物种。

Prolonged dual antiplatelet therapy after drug-eluting stent implantation improves long-term prognosis for acute coronary syndrome:five-year results from a large cohort study

BACKGROUND:To investigate the most appropriate dual antiplatelet therapy(DAPT)duration for patients with acute coronary syndrome(ACS)after drug-eluting stent(DES)implantation in the largest cardiovascular center of China.METHODS:We enrolled 5,187 consecutive patients with ACS who received DES from January to December 2013.Patients were divided into four groups based on DAPT duration:standard DAPT group(11-13 months,n=1,568)and prolonged DAPT groups(13-18 months[n=308],18-24 months[n=2,125],and>24 months[n=1,186]).Baseline characteristics and 5-year clinical outcomes were recorded.RESULTS:Baseline characteristics were similar across the four groups.Among the four groups,those with prolonged DAPT(18-24 months)had the lowest incidence of major adverse cardiovascular and cerebrovascular events(MACCEs)(14.1%vs.11.7%vs.9.6%vs.24.2%,P<0.001),all-cause death(4.8%vs.3.9%vs.2.1%vs.2.6%,P<0.001),cardiac death(3.1%vs.2.6%vs.1.4%vs.1.9%,P=0.004),and myocardial infarction(MI)(3.8%vs.4.2%vs.2.5%vs.5.8%,P<0.001).The incidence of bleeding was not different among the four groups(9.9%vs.9.4%vs.11.0%vs.9.4%,P=0.449).Cox multivariable analysis showed that prolonged DAPT(18-24 months)was an independent protective factor for MACCEs(hazard ratio[HR]0.802,95%confidence interval[CI]0.729-0.882,P<0.001),all-cause death(HR 0.660,95%CI 0.547-0.795,P<0.001),cardiac death(HR 0.663,95%CI 0.526-0.835,P<0.001),MI(HR 0.796,95%CI 0.662-0.957,P=0.015),and target vessel revascularization(HR 0.867,95%CI 0.755-0.996,P=0.044).Subgroup analysis for high bleeding risk showed that prolonged DAPT remained an independent protective factor for all-cause death and MACCEs.CONCLUSION:For patients with ACS after DES,appropriately prolonging the DAPT duration may be associated with a reduced risk of adverse ischemic events without increasing the bleeding risk.

Prolonging dual antiplatelet therapy improves the long-term prognosis in patients with diabetes mellitus undergoing complex percutaneous coronary intervention

OBJECTIVE To investigate the optimal duration of dual antiplatelet therapy(DAPT)in patients with diabetes mellitus(DM)requiring complex percutaneous coronary intervention(PCI).METHODS A total of 2403 patients with DM who underwent complex PCI from January to December 2013 were consecutively enrolled in this observational cohort study and divided according to DAPT duration into a standard group(11-13 months,n=689)and two prolonged groups(13-24 months,n=1133;>24 months,n=581).RESULTS Baseline characteristics,angiographic findings,and complexity of PCI were comparable regardless of DAPT duration.The incidence of major adverse cardiac and cerebrovascular event was lower when DAPT was 13-24 months than when it was 11-13 months or>24 months(4.6%vs.8.1%vs.6.0%,P=0.008),as was the incidence of all-cause death(1.9%vs.4.6%vs.2.2%,P=0.002)and cardiac death(1.0%vs.3.0%vs.1.2%,P=0.002).After adjustment for confounders,DAPT for 13-24 months was associated with a lower risk of major adverse cardiac and cerebrovascular event[hazard ratio(HR)=0.544,95%CI:0.373-0.795]and all-cause death(HR=0.605,95%CI:0.387-0.944).DAPT for>24 months was associated with a lower risk of all-cause death(HR=0.681,95%CI:0.493-0.942)and cardiac death(HR=0.620,95%CI:0.403-0.952).The risk of major bleeding was not increased by prolonging DAPT to 13-24 months(HR=1.356,95%CI:0.766-2.401)or>24 months(HR=0.967,95%CI:0.682-1.371).CONCLUSIONS For patients with DM undergoing complex PCI,prolonging DAPT might improve the long-term prognosis by reducing the risk of adverse ischemic events without increasing the bleeding risk.

Linked color imaging vs Lugol chromoendoscopy for esophageal squamous cell cancer and precancerous lesion screening: A noninferiority study

BACKGROUND Lugol chromoendoscopy(LCE)has served as a standard screening technique in high-risk patients with esophageal cancer.Nevertheless,LCE is not suitable for general population screening given its side effects.Linked color imaging(LCI)is a novel image-enhanced endoscopic technique that can distinguish subtle differences in mucosal color.AIM To compare the diagnostic performance of LCI with LCE in detecting esophageal squamous cell cancer and precancerous lesions and to evaluate whether LCE can be replaced by LCI in detecting esophageal neoplastic lesions.METHODS In this prospective study,we enrolled 543 patients who underwent white light imaging(WLI),LCI and LCE successively.We compared the sensitivity and specificity of LCI and LCE in the detection of esophageal neoplastic lesions.Clinicopathological features and color analysis of lesions were assessed.RESULTS In total,43 patients(45 neoplastic lesions)were analyzed.Among them,36 patients(38 neoplastic lesions)were diagnosed with LCI,and 39 patients(41 neoplastic lesions)were diagnosed with LCE.The sensitivity of LCI was similar to that of LCE(83.7%vs 90.7%,P=0.520),whereas the specificity of LCI was greater than that of LCE(92.4%vs 87.0%,P=0.007).The LCI procedure time in the esophageal examination was significantly shorter than that of LCE[42(34,50)s vs 160(130,189)s,P<0.001].The color difference between the lesion and surrounding mucosa in LCI was significantly greater than that observed with WLI.However,the color difference in LCI was similar in different pathological types of esophageal squamous cell cancer.CONCLUSION LCI offers greater specificity than LCE in the detection of esophageal squamous cell cancer and precancerous lesions,and LCI represents a promising screening strategy for general populations.

Controllable Modulation of Morphology and Property of CsPbCl_(3)Perovskite Microcrystals by Vapor Deposition Method

As a direct wide bandgap semiconductor,CsPbCl_(3)has great potential applications in the eld of near-ultraviolet photodetectors,lasers and higher-order multiphoton uores-cent detectors.In this work,we synthesized CsPbCl_(3)micro/nanocrystals by vapor depo-sition method with CsCl and PbCl_(2)powders as the source materials.It was con rmed that the formation of CsPbCl_(3)perovskite through the chemical reaction of CsCl with PbCl_(2)occurred in the quartz boat before the source evaporation,not in vapor or on sub-strate surface.The evaporated CsPbCl_(3)can form micro/nanocrystals on substrate surfaces under appropriate conditions.Various morphologies including irregular polyhedrons,rods and pyramids could be observed at lower temperature,while stable and uniform CsPbCl_(3)single crystal microplatelets were controllably synthesized at 450℃.Prolonging the growth time could modulate the size and density of the microcrystals,but could not change the morphology.Substrate types made little di erence to the morphology of CsPbCl_(3)crystals.The photoluminescence spectra indicated that the crystallinity and morphology of CsPbCl_(3)micro/nanocrystals have signi cant e ects on their optical properties.The work is expected to be helpful to the development of optoelectronic devices based on individual CsPbCl_(3)microcrystal.

Per-oral endoscopic myotomy is safe and effective for pediatric patients with achalasia:A long-term follow-up study

BACKGROUND Per-oral endoscopic myotomy(POEM)is emerging as a prefer treatment option for pediatric achalasia.However,data are limited on the long-term efficacy of POEM in children and adolescents with achalasia.AIM To evaluate the safety and long-term efficacy of POEM for pediatric patients with achalasia and compare those outcomes with adult patients.METHODS This retrospective cohort study was conducted in patients with achalasia who underwent POEM.Patients aged under 18 years were included in the pediatric group;patients aged between 18 to 65 years who underwent POEM in the same period were assigned to the control group.For investigation of long-term followup,the pediatric group were matched with patients from the control group in a 1:1 ratio.The procedure-related parameters,adverse events,clinical success,gastroesophageal reflux disease(GERD)after POEM,and quality of life(QoL)were evaluated.RESULTS From January 2012 to March 2020,POEM was performed in 1025 patients aged under 65 years old(48 in the pediatric group,1025 in the control group).No significant differences were observed in the occurrence of POEM complications between the two groups(14.6%vs 14.6%;P=0.99).Among the 34 pediatric patients(70.8%)who underwent follow-up for 5.7 years(range 2.6-10.6 years),clinical success was achieved in 35 patients(35/36;97.2%).No differences were observed in post-POEM GERD occurrence(17.6%vs 35.3%;P=0.10).QoL was significantly improved in both groups after POEM.CONCLUSION POEM is safe and effective for pediatric patients with achalasia.It can achieve significant symptoms relief and improve QoL.

抗氧化治疗在放射性肺损伤中的研究进展

放射性肺损伤(radiation induced lung injury, RILI)是临床上胸部肿瘤患者放疗后发生的严重并发症,主要表现为气短、低热、咳嗽等,严重影响患者生存,如何更好地防治RILI是亟待探索的问题。RILI的发生机制主要包括靶细胞学说、细胞因子学说、自由基学说、血管内皮细胞损伤学说。其中放疗产生的活性氧(reactive oxygen species, ROS)对组织的损伤贯穿整个RILI病程,对放射性肺炎和放射性肺纤维化均具有直接促进作用。包括巯基化合物、抗氧化酶、植物抗氧化剂等在内的治疗手段已被用于防治RILI,本文即就抗氧化治疗在RILI中的研究与应用作一综述。

一种深度图像帧内编码单元快速划分算法

新一代的三维视频编码标准——3D-HEVC (3D High Efficient Video Coding)为了显著减少视点个数,增加了包含视频场景几何信息的深度图像,但深度图像编码的计算复杂度非常高,其编码时间是彩色图像的4倍左右。为了降低深度图像编码的计算复杂度,文中提出了一种基于纹理特征分析的深度图像帧内编码单元(CU)快速划分算法。首先,对深度图像的编码树单元(CTU)进行初级纹理特征分析,根据深度图像的纹理变化特征,在大津法的基础上对全局灰度进行分级,再通过判断CTU内采样点的纹理复杂度以及纹理方向标识来确定当前CTU的划分趋势。然后,对纹理复杂度高的CTU进行CU级别的精细纹理特征分析,利用CU内部像素分布的统计特征,自底向上计算不同尺寸的CU的纹理划分标识。最后,根据CTU的纹理复杂度、纹理方向标识以及CU的纹理划分标识预测当前CTU的划分深度范围,并判断是否提前终止CU划分。实验结果表明,与3D-HEVC参考模型中的原始算法相比,所提算法在平均增加0.8%左右码率的同时,能够降低45%左右的编码时间,同时保持了良好的编码率失真性能;与现有的3种快速算法相比,所提算法在整体序列上分别降低了约12%,3%,4%的编码时间,而在大分辨率序列上则分别降低了14%,11%,10%的编码时间,并具有相近的编码率失真性能。

全基因组DNA甲基化揭示西方蜜蜂表观遗传印迹

【目的】旨在研究全基因组甲基化在蜜蜂体内的表观遗传印迹。【方法】以西方蜜蜂(Apis mellifera)作为试验材料,对G0代蜂王进行单雄授精,待G0代蜂王产卵后,以卵(E)、1日龄工蜂幼虫(L1)、2日龄幼虫(L2)分别培育出以卵培育的G1代蜂王(G1E)、以1日龄幼虫培育的G1代蜂王(G1L1)、以2日龄幼虫培育的G1代蜂王(G1L2),选取以上3种G1代蜂王分别产卵培育G1E产的G2代雄蜂(G2DE)、G1L1产的G2代雄蜂(G2DL1)及G1L2产的G2代雄蜂(G2DL2)。利用全基因组Bisulfite甲基化测序技术,对G0代蜂王、G1代蜂王、G2代雄蜂进行全基因组DNA甲基化测序。使用one-way ANOVA分析和高甲基化位点比对揭示西方蜜蜂(A. mellifera)DNA甲基化印迹特性以及移虫日龄对西方蜜蜂DNA甲基化遗传的影响。【结果】西方蜜蜂(A. mellifera)原有高甲基化位点和突变高甲基化位点均存在表观遗传印迹现象;同时发现随着移虫日龄增加,原有高甲基化位点和突变高甲基化位点遗传印迹数量都是逐步增加;3个调控蜜蜂级型分化的高甲基化遗传印迹模式进一步表明移虫日龄会调控蜂王的高甲基化水平,且蜂王高甲基化位点数目越多,所育雄蜂后代也将获得更多额高甲基化位点。【结论】DNA甲基化遗传印迹能够在西方蜜蜂(A. mellifera)这一模式生物体内稳定遗传,为解析蜜蜂DNA甲基化遗传调控机制提供科学依据。

电冰箱智能除菌、净化功能测试和评价方法标准解读

基于目前冰箱智能除菌、净化功能,从用户使用体验、智能化程度、除菌净化效果等方面,对智能除菌、净化功能测试和评价方法进行解读,给带有智能除菌、净化功能产品评价提供参考。

Effect of alprostadil combined with Diammonium glycyrrhizinate on renal interstitial fibrosis in SD rats

Objective:To observe effect of alprostadil combined with Diammonium glycyrrhizinate on renal interstitial fibrosis in SD rate.Methods:A total of 75 SD rate were randomly divided into A,B,C,D,E groups with 15 in each group.Rats in group A served as the control group received just only but tissue separation without modeling operation,while model of unilateral ureteral obstruction(UUO) was established in B,C,D,E groups.Rats in A,B group were given saline lavage placebo treatment,while rats in C,D,E groups were given dianunonium glycyrrhizinate and alprostadil injection.Five rats were sacrificed 1,2,3 weeks after modeling,serum creatinine level of femoral venous blood was determined.Transforming growth factor- β1(TCF- β1) and concentration of connective tissue growth factor(CTGF) were also detected by using ELISA.Line renal interstitial tissue was taken after HE staining,renal interstitial TGF- β1 and CTGF expression were detected by using immunohistochemical method.Results:Serum creatinine levels of B,C,D,E group at different time points in were significantly higher than that of group A(P<0.05);serum creatinine levels in group B were significantly higher than that of C,D,E group at each time point(P<0.05).Serum creatinine level of Croup E was significantly lower than C,D group after 2,3 weeks(P<0.05).Rate in A group at each time point showed no significant changes in TGF- β1 and CREA concentration in serum and kidney tissues(P>0.05);while serum and kidney tissue TGF- β1,concentration of CREA.expression of rats in B,C,D,E groups showed a gradual increasing trend over time.TCF- β1 and CREF of Group B in serum and kidney tissues at each time point were significantly higher than that of the other groups(P<0.05).TCF- β1 and CREF of Group E in serum and kidney tissues at each time point were significantly lower than that of B,C,D group at all time points in serum and kidney tissues(P<0.05).Conclusions:Alprostadil combined with diammonium glycyrrhizinate can significantly lower the expression of TGF- β1 and CTGF in serum and tissues of SD rat with renal interstitial fibrosis,thus inhibit rat renal interstitial fibrosis process.It has synergy protective effect.