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.

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。

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。

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。

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.

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.

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.

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.

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.

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。

Novel methionyl-tRNA synthetase gene variants/phenotypes in interstitial lung and liver disease: A case report and review of literature

Interstitial lung and liver disease(ILLD) is caused by biallelic mutations in the methionyl-tRNA synthetase(MARS) gene. To date, no genetic changes other than missense variants were reported in the literature. Here, we report a five-month old female infant with typical ILLD(failure to thrive, developmental delay, jaundice, diffuse interstitial lung disease, hepatomegaly with severe steatosis, anemia, and thrombocytosis) showing novel phenotypes such as kidney stones, acetabular dysplasia, prolonged fever, and extreme leukocytosis. Whole exome sequencing revealed a novel truncating variant(c.2158 C>T/p.Gln720 Stop) together with a novel tri-nucleotide insertion(c.893_894 insTCG that caused the insertion of an arginine at amino acid position 299) in the MARS gene.

Enhanced transdermal delivery of meloxicam by nanocrystals: Preparation, in vitro and in vivo evaluation

Meloxicam(MLX) is efficient in relieving pain and inflammatory symptoms, which, however, is limited by the poor solubility and gastrointestinal side effects. The objective of this study is to develop a nanocrystal formulation to enhance transdermal delivery of MLX. MLX nanocrystals were successfully prepared by the nanoprecipitation technique based on acidbase neutralization. With poloxamer 407 and Tween 80(80/20, w/w) as mixed stabilizers,MLX nanocrystals with particle size of 175 nm were obtained. The crystalline structure of MLX nanocrystals was confirmed by both differential scanning calorimetry and X-ray powder diffractometry. However, the nanoprecipitation process reduced the crystallinity of MLX.Nanocrystals increased both in vitro and in vivo transdermal permeation of MLX compared with the solution and suspension counterparts. Due to the enhanced apparent solubility and dissolution as well as the facilitated hair follicular penetration, nanocrystals present a high and prolonged plasma MLX concentration. And 2.58-and 4.4-fold increase in AUC0 →2 4 h was achieved by nanocrystals comparing with solution and suspension, respectively. In conclusion, nanocrystal is advantageous for transdermal delivery of MLX.

Pediatric Wilson disease presenting as acute liver failure:Prognostic indices

BACKGROUND Acute liver failure(ALF)can be a primary presentation of Wilson disease(WD).Mortality rates are high in WD with ALF(WDALF).Predictions of mortality in WDALF vary by model and are sometimes contradictory,perhaps because few patients are studied or WD diagnoses are questionable.AIM To determine the outcomes among well-documented WDALF patients and assess mortality model performance in this cohort.METHODS We reviewed the medical records of our pediatric WDALF patients(n=41 over 6-years-old,single-center retrospective study)and compared seven prognostic models(King’s College Hospital Criteria,model for end-stage liver disease/pediatric end-stage liver disease scoring systems,Liver Injury Unit[LIU]using prothrombin time[PT]or international normalized ratio[INR],admission LIU using PT or INR,and Devarbhavi model)with one another.RESULTS Among the 41 Han Chinese patients with ALF,WD was established by demonstrating ATP7B variants in 36.In 5 others,Kayser-Fleischer rings and Coombs-negative hemolytic anemia permitted diagnosis.Three died during hospitalization and three underwent liver transplantation(LT)within 1 mo of presentation and survived(7.3%each);35(85.4%)survived without LT when given enteral D-penicillamine and zinc-salt therapy with or without urgent plasmapheresis.Parameters significantly correlated with mortality included encephalopathy,coagulopathy,and gamma-glutamyl transpeptidase activity,bilirubin,ammonia,and serum sodium levels.Area under the receiver operating curves varied among seven prognostic models from 0.981 to 0.748 with positive predictive values from 0.214 to 0.429.CONCLUSION WDALF children can survive and recover without LT when given D-penicillamine and Zn with or without plasmapheresis,even after enlisting for LT.

Intelligent Fusion of Infrared and Visible Image Data Based on Convolutional Sparse Representation and Improved Pulse-Coupled Neural Network

Multi-source information can be obtained through the fusion of infrared images and visible light images,which have the characteristics of complementary information.However,the existing acquisition methods of fusion images have disadvantages such as blurred edges,low contrast,and loss of details.Based on convolution sparse representation and improved pulse-coupled neural network this paper proposes an image fusion algorithm that decompose the source images into high-frequency and low-frequency subbands by non-subsampled Shearlet Transform(NSST).Furthermore,the low-frequency subbands were fused by convolutional sparse representation(CSR),and the high-frequency subbands were fused by an improved pulse coupled neural network(IPCNN)algorithm,which can effectively solve the problem of difficulty in setting parameters of the traditional PCNN algorithm,improving the performance of sparse representation with details injection.The result reveals that the proposed method in this paper has more advantages than the existing mainstream fusion algorithms in terms of visual effects and objective indicators.

Robust,fluorine-free and superhydrophobic composite melamine sponge modified with dual silanized SiO_(2) microspheres for oil-water separation

Massive oily wastewater discharged from industrial production and human daily life have been an urgent environmental and ecological challenge.Superhydrophobic materials have attracted tremendous attention due to their unique properties and potential applications in the treatment of wastewater.In this study,a novel superhydrophobic/superoleophilic composite melamine sponge modified with dual silanized SiO_(2) microspheres was fabricated simply by a two-step sol-gel method using vinyltriethoxysilane and hexadecyltrimethoxysilane as functional agent,which exhibited a water contact angle of 153.2°and a water sliding contact angle of 4.8°.Furthermore,the composite sponge showed the excellent oil adsorption performance and the compressive elasticity reaching up to 130 g·g^(-1) of dichloromethane and 33.1 kPa of compressive stress.It was worth noting that the composite sponge presented the excellent separation efficiency(up to 99.5%)in the processes of continuous oil/water separation.The robust superhydrophobic composite melamine sponge provided the possibility with the practical application for oil-water separation.

Study of the morphology evolution of AlN grown on nanopatterned sapphire substrate

This study focused on the evolution of growth front about AlN growth on nano-patterned sapphire substrate by metal-organic chemical vapor deposition.The substrate with concave cones was fabricated by nano-imprint lithography and wet etching.Two samples with different epitaxy procedures were fabricated,manifesting as two-dimensional growth mode and three-dimensional growth mode,respectively.The results showed that growth temperature deeply influenced the growth modes and thus played a critical role in the coalescence of AlN.At a relatively high temperature,the AlN epilayer was progressively coalescence and the growth mode was two-dimensional.In this case,we found that the inclined semi-polar facets arising in the process of coalescence were{112^-1}type.But when decreasing the temperature,the{112^-2}semi-polar facets arose,leading to inverse pyramid morphology and obtaining the three-dimensional growth mode.The 3 D inverse pyramid AlN structure could be used for realizing 3 D semi-polar UV-LED or facet-controlled epitaxial lateral overgrowth of AlN.

The role of inflammatory mediators in severe acute pancreatitis and regulation of glucocorticoids

OBJECTIVE: To investigate the effect of glucocorticoids on systemic inflammatory mediator release in rats with acute pancreatitis and the outcome of dexamethasone in treatment of acute pancreatitis. METHODS: Sixty-eight Wistar rats were divided into sham, acute pancreatitis, and treatment (intravenous dexamethasone 0.5 mg/kg) groups. Experimental acute pancreatitis was induced by the injection of 5% sodium taurocholate (0.1 ml/100 mg body weight) into the pancreatic-biliary duct. The bIood samples were obtained and examined for 6-keto-PGI_1α, TXB_2 and IL-6 postoperatively at 3,6 and 12 hours, respectively. The pancreatic samples were evaluated by a blinded method. Twelve-hour survival rate was determined and compared between the groups. RESULTS: The high serum concentrations of 6-keto-PGI_1α, TXB_2 and IL-6 were noted in the rats with acute pancreatitis associated with pancreatic hemorrhage and necrosis. Their 12-hour survival rate was 42.9%. The rats in the treatment group survived with significantly reduced serum concentrations of 6-keto-PGI_1α, TXB_2 and IL-6 (P<0.05). Their pancreatic morphology was normal. CONCLUSION: Dexamethasone may reduce the serum concentration of 6-keto-PGI_1α, TXB_2, and IL-6, and the severity of acute pancreatitis while increasing the survival rate of rats with acute pancreatitis.