Nanomedicine-boosting icaritin-based immunotherapy of advanced hepatocellular carcinoma

Traditional treatments for advanced hepatocellular carcinoma(HCC),such as surgical resection,transplantation,radiofrequency ablation,and chemotherapy are unsatisfactory,and therefore the exploration of powerful therapeutic strategies is urgently needed.Immunotherapy has emerged as a promising strategy for advanced HCC treatment due to its minimal side effects and long-lasting therapeutic memory effects.Recent studies have demonstrated that icaritin could serve as an immunomodulator for effective immunotherapy of advanced HCC.Encouragingly,in 2022,icaritin soft capsules were approved by the National Medical Products Administration(NMPA)of China for the immunotherapy of advanced HCC.However,the therapeutic efficacy of icaritin in clinical practice is impaired by its poor bioavailability and unfavorable in vivo delivery efficiency.Recently,functionalized drug delivery systems including stimuli-responsive nanocarriers,cell membrane-coated nanocarriers,and living cell-nanocarrier systems have been designed to overcome the shortcomings of drugs,including the low bioavailability and limited delivery efficiency as well as side effects.Taken together,the development of icaritin-based nanomedicines is expected to further improve the immunotherapy of advanced HCC.Herein,we compared the different preparation methods for icaritin,interpreted the HCC immune microenvironment and the mechanisms underlying icaritin for treatment of advanced HCC,and discussed both the design of icaritin-based nanomedicines with high icaritin loading and the latest progress in icaritinbased nanomedicines for advanced HCC immunotherapy.Finally,the prospects to promote further clinical translation of icaritin-based nanomedicines for the immunotherapy of advanced HCC were proposed.

Experimental research on influence mechanism of loading rates on rock pressure stimulated currents

The study of pressure stimulated current(PSC)changes of rocks is significant to monitor dynamic disasters in mines and rock masses.The existing studies focus on change laws and mechanism of currents generated under the loading of rocks.An electrical and mechanics test system was established in this paper to explore the impacts of loading rates on PSCs.The results indicated that PSC curves of different rocks had different change laws under low/high loading rates.When the loading rate was relatively low,PSC curves firstly changed gently and then increased exponentially.Under high loading rates,PSC curves experienced the rapid increase stage,gentle increase stage and sudden change stage.The compressive strength could greatly affect the peak PSC in case of rock failure.The loading rate was a key factor in average PSC.Under low loading rates,the variations of PSCs conformed to the damage charge model of fracture mechanics,while they did not at the fracture moment.Under high loading rates,the PSCs at low stress didn’t fit the model due to the stress impact effects.The experimental results could provide theoretical basis for the influence of loading rates on PSCs.

国家智慧教育平台赋能高校课堂数字化转型探析

以国家智慧教育平台为抓手,赋能高校课堂数字化转型,落实立德树人根本任务,提高人才培养质量,是高等教育改革发展的新方向。顺应国家教育数字化战略行动,围绕高校课堂数字化转型“为何转”“转什么”“如何转”三个核心问题开展理论研究,分析高校课堂数字化转型的价值旨归,厘清高校课堂数字化转型的要素流转,明晰国家智慧教育平台赋能高校课堂数字化转型的逻辑理路。然后,以学习理论和教学理论为指导进行实践探析,提出国家智慧教育平台赋能高校课堂数字化转型的教学设计方法,即教学目标科学化定制、教学内容动态化供给、教学活动弹性化调整、教学评价智能化开展;并构建具体实施路径,即转变课堂教学观念、关注数字素养提升、凸显数字技术赋能、注重实践融合创新。在此基础上,结合高校一流课程建设的教学现实,提出国家智慧教育平台赋能高校课堂数字化转型的关键要点:强化思政融入,数智赋能育人育才;深化“两性一度”,数实融合变革课堂;注重可持续发展,数字驱动终身成长。

我国国际消费中心城市发展水平测度及动态演进

国际消费中心城市是消费的高级形态载体。从国际知名度、消费繁荣度、商业活跃度、到达便利度和消费满意度五个维度构建我国国际消费中心城市发展评价指标体系,借助熵权TOPSIS法对其发展水平进行测度,运用核密度估计、收敛性分析、修正的引力模型以及社会网络分析方法,以北京、天津、上海、重庆、广州等25个具有竞争力的城市为样本,剖析我国国际消费中心城市发展的动态演进特征。研究发现,2017—2022年我国国际消费中心城市发展水平逐年上升但处于低水平发展阶段,城市间发展差距大且呈现出梯队层级分布态势;从各维度看,国际知名度、消费繁荣度、商业活跃度和消费满意度四个维度发展水平表现为上升趋势,消费繁荣度涨幅最大,到达便利度发展水平较低;国际消费中心城市间发展的绝对差距较大,但城市的追赶效应使得相对差距缩小;从空间格局看,城市初步形成了北部“北京+天津”集聚圈、南部“广州+深圳”集聚圈以及以上海为首的长江联系带的“两圈一带”总体空间网络格局,表现出“高者全局集聚、低者局部扩散”的集散效应特征,城市间有着“核心城市占据主导,边缘城市结构优化”的非均衡空间联系。因此,应立足城市比较优势、深入挖掘并梯次培育特色消费增长点,完善城市交通基础设施建设、突出重点打造现代综合立体交通网络,积极把握我国国际消费中心城市发展的动态变化过程、多层级优化城市消费资源空间配置,重视我国国际消费中心城市发展的空间网络结构特征,逐步形成以点带面、以圈扩容、结构优化的消费空间发展格局。

抗接触蛋白相关蛋白-2抗体相关脑炎临床特征分析

目的 总结抗接触蛋白相关蛋白-2(CASPR2)抗体相关脑炎的临床特征。方法与结果收集2017年8月至2022年8月中山大学附属第三医院诊断与治疗的13例抗CASPR2抗体相关脑炎患者。首发表现:9例表现为边缘系统症状,2例表现为周围神经症状(均为肢体疼痛),1例为小脑性共济失调,1例肢体乏力。抗CASPR2抗体检测:13例患者均进行血清抗CASPR2抗体检测,均呈阳性;10例患者接受脑脊液抗CASPR2抗体检测,5例呈阳性;有3例患者合并其他自身抗体阳性。头部MRI检查:13例患者中2例表现为单侧或双侧颞叶内侧T2-FLAIR成像高信号;2例存在脑微出血灶。治疗:2例仅单纯采用激素治疗,4例仅静脉注射免疫球蛋白,5例则先后接受激素+静脉注射免疫球蛋白治疗,1例仅接受利妥昔单抗治疗,1例先后接受静脉注射免疫球蛋白+激素+蛋白A免疫吸附+利妥昔单抗。随访:进行1~5年的随访,2例失访;1例患者自行停药后复发,经治疗后改良Rankin量表(mRS)评分为零;余10例患者中1例症状未见改善,1例部分症状存在不能正常生活,6例正常生活,2例死亡。结论 抗CASPR2抗体相关脑炎临床特征复杂,血清抗体检测对于明确诊断至关重要。

全球稀土产业链贸易格局演化与出口竞争力研究

稀土是战略性矿产资源,在全球经济发展与产业结构升级中发挥重要作用。西方国家加快稀土产业链“去中国化”的步伐,中国的稀土产业安全面临严峻挑战,正确认识全球稀土产业链中不同产品贸易格局演化及主要出口国(地区)出口竞争力有利于中国稀土产业贸易的优化。本文以2000—2022年全球稀土产业链贸易额为数据,运用复杂网络方法,通过4类稀土产品建立稀土产业链上游阶段、中游阶段、下游阶段产品贸易随机网络和加权网络,对全球稀土产业链上游阶段、中游阶段、下游阶段产品贸易格局演变及各阶段主要出口国(地区)出口贸易竞争力进行研究。通过分析得出:稀土产业链上游阶段、中游阶段、下游阶段产品贸易呈现少数国家掌握着极大贸易量的特征,各阶段贸易网络呈小世界特征,且中下游稀土产品网络紧密程度明显高于上游稀土原矿;中国稀土原矿的出口寡占指数呈下降趋势,中下游稀土产品寡占方面具有绝对出口优势;中国的中介控制能力与贸易渠道在稀土产业链中都相对具有优势,但美国、德国在这两方面的出口竞争力也较强。因此,中国需要加强上游稀土原矿的储备,中下游环节需要加强原矿加工能力与下游高端材料与技术的研发投入,并朝贸易全球化方向发展。

Optimization Study of Outburst Prevention Measures for Tuzhu Coal Mine Based on Fixed Weight Clustering Analysis

Affected by many involved factors, different dimensions, data with large difference, incomplete information and so on, the most optimal selection of regional outburst prevention measures for outburst mine has become a complicated system project. The traditional way of outburst prevention measure selection belongs to qualitative method, which may cause high-cost of gas control, huge quantities of drilling work, long construction time and even secondary disaster. To solve the above-mentioned problems, in light of occurrence status of coal seam gas in No. 21 mining area of Jinzhushan Tuzhu Mine, through grey fixed weight clustering theory and a combination method of qualitative and quantitative analysis, the judging model with multi-objective classification for optimization of outburst prevention measures was established. The three weight coefficients of outburst prevention technology scheme are sorted, in order to determine the advantages and disadvantages of each outburst prevention technology scheme under the comprehensive evaluation of multi-target. Finally, the problem of quantitative selection for regional outburst prevention technology scheme is solved under the situation of multi-factor mode and incomplete information, which provides reasonable and effective technical measures for prevention of coal and gas outburst disaster.

Layered Potassium Titanium Niobate/Reduced Graphene Oxide Nanocomposite as a Potassium‑Ion Battery Anode

With graphite currently leading as the most viable anode for potassium-ion batteries(KIBs),other materials have been left relatively underexamined.Transition metal oxides are among these,with many positive attributes such as synthetic maturity,longterm cycling stability and fast redox kinetics.Therefore,to address this research deficiency we report herein a layered potassium titanium niobate KTiNbO5(KTNO)and its rGO nanocomposite(KTNO/rGO)synthesised via solvothermal methods as a high-performance anode for KIBs.Through effective distribution across the electrically conductive rGO,the electrochemical performance of the KTNO nanoparticles was enhanced.The potassium storage performance of the KTNO/rGO was demonstrated by its first charge capacity of 128.1 mAh g^(−1) and reversible capacity of 97.5 mAh g^(−1) after 500 cycles at 20 mA g^(−1),retaining 76.1%of the initial capacity,with an exceptional rate performance of 54.2 mAh g^(−1)at 1 A g^(−1).Furthermore,to investigate the attributes of KTNO in-situ XRD was performed,indicating a low-strain material.Ex-situ X-ray photoelectron spectra further investigated the mechanism of charge storage,with the titanium showing greater redox reversibility than the niobium.This work suggests this lowstrain nature is a highly advantageous property and well worth regarding KTNO as a promising anode for future high-performance KIBs.

农业碳补偿率的空间格局及其驱动因素--来自长江经济带108个地级及以上城市的经验证据

减排是基础,增汇是保障,农业领域减排增汇是实现碳中和目标的潜力所在。为探索农业碳中和的有效路径,该研究基于2011—2021年长江经济带108个地级及以上城市的面板数据,测度农业碳补偿率,运用点度中心度、隶属度模型和Moran's I分析其空间分布、空间辐射和空间集聚格局;进一步结合收敛模型和空间计量模型分析其空间收敛特征;并运用空间计量模型识别农业碳补偿率的驱动因素及溢出效应。研究发现:①长江经济带农业碳补偿率上升趋势明显,但总碳汇仍不足以覆盖碳排放,且上、下游领先,中游落后;②中心城市自东向西演化趋势明显,分布格局演变为成都一极,苏州、长沙、武汉等八核心,杭州、岳阳等多点联动的“一极八核,多点带动”格局,上、中、下游“分区域,多核心”的趋势越加明朗;③空间集聚特征明显,且整体呈现协同演进的格局,上游城市协同互动减排增汇的趋势更加显著;④农业内部结构和绿色技术创新能力对碳补偿率的促进作用不仅来自直接效应,还有部分来自反馈效应,且邻近城市的农业内部结构、绿色技术创新能力和农业劳动力规模均有利于本地区碳补偿率的提升。基于该研究结论,建议创立农业碳中和示范区,领先城市与追随城市、边缘城市“强弱扶持”,加大区域间协同互动减排增汇力度,以“小区域”带动“大区域”实现农业碳中和。

动态有权图上的随机游走概率计算

图上的随机游走概率计算是传统图论与现代数据挖掘领域普遍关注的问题之一.现有工作普遍关注静态图上的随机游走概率计算,却鲜少关注与实际应用场景更贴合的权重动态图.针对动态有权图上的随机游走概率计算问题,提出了一种基于硬币翻转采样的随机游走概率计算方法.相比于传统的基于权重采样的随机游走概率计算方法,所提方法可以在保证随机游走概率计算结果无偏的前提下,同时做到近似最优的随机游走概率计算复杂度和最优的采样结构更新复杂度.作为对比,现有方法或具有较大的计算时间复杂度,或依赖于复杂的索引结构而难以在动态图上即时更新.对所提方法做出了详细的理论分析,并在真实图数据集上进行模拟实验,实验结果证实了所提方法的有效性.

Spatiotemporal dynamics of the social structure of Indo-Pacific humpback dolphins(Sousa chinensis)in Xiamen waters from 2007 to 2019

As highly social animals,Indo-Pacific humpback dolphins(Sousa chinensis)exhibit community differentiation.Nevertheless,our understanding of the external and internal factors influencing these dynamics,as well as their spatiotemporal variations,is still limited.In the present study,variations in the social structure of an endangered Indo-Pacific humpback dolphin population in Xiamen Bay,China,were monitored over two distinct periods(2007–2010 and 2017–2019)to analyze the effects of habitat utilization and the composition of individuals within the population.In both periods,the population demonstrated a strikingly similar pattern of social differentiation,characterized by the division of individuals into two main clusters and one small cluster.Spatially,the two primary clusters occupied the eastern and western waters,respectively,although the core distribution area of the eastern cluster shifted further eastward between the two periods.Despite this distribution shift,the temporal stability of the social structure and inter-associations within the eastern cluster remained unaffected.A subset of 16individuals observed in both periods,comprising 51.6%and 43.2%of the population in each respective period,emerged as a foundational element of the social structure and may be responsible for sustaining social structure stability,especially during the 2007–2010 period.These observations suggest that the composition of dominant individuals,an internal factor,had a more substantial influence on the formation of the social network than changes in habitat use,an external factor.Consequently,the study proposes distinct conservation measures tailored to each of the two main clusters.

Icariin ameliorates viral myocarditis by inhibiting TLR4-mediated ferroptosis

Objective:To explore the mechanism by which icariin alleviates viral myocarditis.Methods:CVB3-induced cardiomyocytes were used as an in vitro model of viral myocarditis to assess the effects of icariin treatment on cell viability,inflammation,and apoptosis.Moreover,the effects of icariin on ferroptosis and TLR4 signaling were assessed.After AC16 cells were transfected with TLR4 overexpression plasmids,the role of TLR4 in mediating the regulatory effect of icariin in viral myocarditis was investigated.Results:Icariin significantly elevated cell viability and reduced inflammatory factors TNF-α,IL-1β,IL-6,and IL-18.Flow cytometry revealed that icariin decreased apoptosis rate,and the protein expression of Bax and cleaved caspase 3 and 9 in CVB3-induced cardiomyocytes.Additionally,it suppressed ferroptosis including lipid peroxidation and ferrous ion,as well as the TLR4 signaling.However,TLR4 overexpression abrogated the modulatory effects of icariin.Conclusions:Icariin mitigates CVB3-induced myocardial injury by inhibiting TLR4-mediated ferroptosis.Further animal study is needed to verify its efficacy.

Human bone marrow mesenchymal stem cell-derived exosomes loaded with gemcitabine inhibit pancreatic cancer cell proliferation by enhancing apoptosis

BACKGROUND Pancreatic cancer remains one of the most lethal malignancies,and has limited effective treatment.Gemcitabine(GEM),a chemotherapeutic agent,is commonly used for clinical treatment of pancreatic cancer,but it has characteristics of low drug delivery efficiency and significant side effects.The study tested the hypothesis that human bone marrow mesenchymal stem cell(MSC)-derived exosomes loaded with GEM(Exo-GEM)would have a higher cytotoxicity against human pancreatic cancer cells by enhancing their apoptosis.AIM To investigate the cytotoxicity of MSC-derived Exo-GEM against pancreatic cancer cells in vitro.METHODS Exosomes were isolated from MSCs and characterized by transmission electron microscopy and nanoparticle tracking analysis.Exo-GEM through electroporation,sonication,or incubation,and the loading efficiency was evaluated.The cytotoxicity of Exo-GEM or GEM alone against human pancreatic cancer Panc-1 and MiaPaca-2 cells was assessed by MTT and flow cytometry assays.RESULTS The isolated exosomes had an average size of 76.7 nm.The encapsulation efficacy and loading efficiency of GEM by electroporation and sonication were similar and significantly better than incubation.The cytotoxicity of Exo-GEM against pancreatic cancer cells was stronger than free GEM and treatment with 0.02μM Exo-GEM significantly reduced the viability of both Panc-1 and MiaPaca-2 cells.Moreover,Exo-GEM enhanced the frequency of GEMinduced apoptosis in both cell lines.CONCLUSION Human bone marrow MSC-derived Exo-GEM have a potent cytotoxicity against human pancreatic cancer cells by enhancing their apoptosis,offering a promising drug delivery system for improving therapeutic outcomes.

Modified Xiaoyao powder for postpartum depression:A systematic review and meta-analysis

Objective:To evaluate the effectiveness and safety of modified Xiaoyao powder for postpartum depression(PPD)by conducting a systematic review of randomized controlled trials(RCTs).Methods:The Chinese National Knowledge Infrastructure Databases(CNKI),the Chinese Scientific Journals Database(VIP),Wanfang,Google Scholar,the SinoMed,Embase,Cochrane Library,and PubMed databases were searched from their inception to April 25,2023.The Cochrane Risk of Bias tool was used to assess the quality of the trials.We applied the risk ratio to present dichotomous data and the mean difference to present continuous data.Data with similar characteristics were pooled for meta-analysis and heterogeneity was assessed using I2.Results:This review included 35 trials involving 2848 participants.The quality of the included studies was low(unclear randomization processes and insufficient reporting of blinding).Participants treated with modified Xiaoyao powder plus Western medicine showed lower Hamilton Depression Scale(HAMD)depression score than those who used Western medicine alone(mean difference=-2.15;95%confidence interval:-2.52 to 1.78;P<.00001),and higher effective rate(relative risk=1.19;95%confidence interval:1.15 to 1.24;P<.00001),When comparing modified Xiaoyao alone with Western medicine,the HAMD depression score remained low,however,the efficacy rate was higher in the modified Xiaoyao group.Regarding adverse events,the modified Xiaoyao group reported weight gain,nausea,and diarrhea,but no severe adverse events were reported.Conclusion:Modified Xiaoyao may help relieve depression in PPD when used alone or in combination with Western medicine,with minor side effects.Therefore,future high-quality,large-sample size RCTs are warranted.

Transient Damping of Virtual Synchronous Generator for Enhancing Synchronization Stability during Voltage Dips

Virtual synchronous generators(VSGs)are widely introduced to the renewable power generation,the variablespeed pumped storage units,and so on,as a promising gridforming solution.It is noted that VSGs can provide virtual inertia for frequency support,but the larger inertia would worsen the synchronization stability,referring to keeping synchronization with the grid during voltage dips.Thus,this paper presents a transient damping method of VSGs for enhancing the synchronization stability during voltage dips.It is revealed that the loss of synchronization(LOS)of VSGs always accompanies with the positive frequency deviation and the damping is the key factor to remove LOS when the equilibrium point exists.In order to enhance synchronization stability during voltage dips,the transient damping is proposed,which is generated by the frequency deviation in active power loop.Additionally,the proposed method can realize seamless switching between normal state and grid fault.Moreover,detailed control design for transient damping gain is given to ensure the synchronization stability under different inertia requirements during voltage dips.Finally,the experimental results are presented to validate the analysis and the effectiveness of the improved transient damping method.

Debt,sleep deprivation and psychological distress among online ride-hailing drivers:evidence from China

An online ride-hailing driver(ORHD)refers to a driver who takes orders and provides rental car services to passengers via an online service platform.1 ORHD plays a significant role in the urban transport system worldwide,operating through many platforms.According to official data from the Chinese Ministry of Transport,a total of 1.6 million vehicle transport permits were issued by the end of March 2022.

儿童可成长性产品设计方法研究

可成长性产品设计是实现儿童产品可持续设计理念的重要方式。研究其设计方法可进一步延续产品生命周期,减少材料与资源浪费,降低生产成本,满足不同年龄阶段儿童成长需求。文章通过文献研究和案例分析对儿童可成长性产品设计方法进行梳理与总结。儿童产品设计主要可通过模块组合、调节转换、结构延伸三大方法达到使用功能可成长性的目的,从而促进了联合国永续发展目标的有效实现。

Coordinated Voltage Control of Distribution Network ConsideringMultiple Types of Electric Vehicles

The couple between the power network and the transportation network(TN)is deepening gradually with the increasing penetration rate of electric vehicles(EV),which also poses a great challenge to the traditional voltage control scheme.In this paper,we propose a coordinated voltage control strategy for the active distribution networks considering multiple types of EV.In the first stage,the action of on-load tap changer and capacitor banks,etc.,are determined by optimal power flow calculation,and the node electricity price is also determined based on dynamic time-of-use tariff mechanism.In the second stage,multiple operating scenarios of multiple types of EVs such as cabs,private cars and buses are considered,and the scheduling results of each EV are solved by building an optimization model based on constraints such as queuing theory,Floyd-Warshall algorithm and traffic flow information.In the third stage,the output power of photovoltaic and energy storage systems is fine-tuned in the normal control mode.The charging power of EVs is also regulated in the emergency control mode to reduce the voltage deviation,and the amount of regulation is calculated based on the fair voltage control mode of EVs.Finally,we test the modified IEEE 33-bus distribution system coupled with the 24-bus Beijing TN.The simulation results show that the proposed scheme can mitigate voltage violations well.

应用于程序化操作的隔离开关位置自动确认算法

采用目前算法确认隔离开关的位置时,未对采集的图像进行相关预处理,导致算法存在时间复杂度高、定位误差大和定位检测率方差大的问题。提出应用于程序化操作的隔离开关位置自动确认算法,考虑连续函数的基础上,采用直方图均衡法对图像进行均衡处理,采用灰度变换方法,根据灰度直方图对隔离开关图像进行灰度拉伸变换,利用脊回归问题描述隔离开关位置的自动确认问题,采用目标样本的循环位移,通过二维高斯函数获取隔离开关图像对应的标签,并采用核相关滤波方法实现隔离开关位置的自动确认。实验结果表明,所提算法的时间复杂度低、定位误差小、定位检测率方差小。

施氏整颈三步九法联合针刺颈夹脊穴治疗神经根型颈椎病患者的效果

目的:观察施氏整颈三步九法联合针刺颈夹脊穴治疗神经根型颈椎病(CSR)患者的效果。方法:选取2019年5月至2021年5月该院收治的100例CSR患者进行前瞻性研究,按照随机数字表法分为研究组与对照组各50例。对照组采用针刺颈夹脊穴治疗,研究组在对照组基础上加用施氏整颈三步九法治疗,比较两组治疗总有效率、视觉模拟评分法(VAS)评分、CSR生命质量量表评分和血清炎性因子[肿瘤坏死因子(TNF)-α、白细胞介素(IL)-1β、超敏C反应蛋白(hs-CRP)]水平。结果:研究组治疗总有效率为88.00%,明显高于对照组的56.00%,差异有统计学意义(P<0.05);治疗后,研究组CSR生命质量量表各维度评分高于对照组,VAS评分和血清TNF-α、IL-1β、hs-CRP水平均低于对照组,差异有统计学意义(P<0.05)。结论:施氏整颈三步九法联合针刺颈夹脊穴治疗CSR患者可提高治疗总有效率和生命质量评分,降低VAS评分和炎性因子水平,效果优于单纯针刺颈夹脊穴治疗。