小细胞肺癌免疫治疗的临床研究进展

小细胞肺癌(small cell lung cancer,SCLC)是一种"顽固性癌症",以快速生长和早期广泛转移为特征,大约70%的患者在确诊时就已经处于广泛期。尽管对一线含铂双联化疗反应率高,但是几乎所有患者随后即不可避免地复发且对二线治疗的反应较差。由于SCLC具有高肿瘤突变负荷及免疫源性,这提示免疫治疗也许对其有效。在过去的几年中,一些临床试验评估了以细胞毒性T淋巴细胞相关抗原4(cytotoxic T lymphocyte-associated antigen-4,CTLA-4)和程序性死亡受体1(programmed death 1,PD-1)/程序性死亡配体-1(programmed death ligand-1,PD-L1)抑制剂为主的检查点抑制剂在SCLC患者中的治疗效果,并展示了良好的生存前景。本文总结了这些试验中免疫检查点抑制剂单独或联合应用于SCLC一线治疗、维持治疗和二线或以上治疗的结果,并对其中的预测因素进行了综述以确定其临床价值。

制备用于间充质干细胞成像的荧光成像/磁共振成像/正电子发射断层扫描三模态纳米探针

为了在间充质干细胞移植的各个阶段更好地获取移植干细胞的命运信息,制备了一种能同时实现荧光成像(FI)、磁共振成像(MRI)和正电子发射断层扫描(PET)的影像探针。首先制备了一种新型两亲性嵌段共聚物,第1嵌段为叔丁氧羰基保护的2-((叔丁氧羰基)氨基)丙烯酸乙酯的均聚物,第2嵌段为短链聚乙二醇丙烯酸酯和五氟苯酚丙烯酸酯的无规共聚物,再通过氨解和酰胺化反应为聚合物修饰上双功能螯合剂DOTA和近红外染料Cy5.5,通过核磁共振和凝胶渗透色谱对聚合物结构及相对分子质量进行了表征和分析。聚合物在水中自组装并螯合Gd^(3+)得到1 mg/mL的纳米探针Gd-DOTA-Cy5.5-NP,动态光散射和透射电镜观察到探针为平均粒径30 nm的球形颗粒,并用电感耦合等离子体光谱法测得Gd^(3+)浓度为0.084 mmol/L。将纳米探针与间充质干细胞共孵育,通过Cell Counting Kit-8试剂验证1 mg/mL以下的Gd-DOTA-Cy5.5-NP相对细胞毒性较低,同时激光共聚焦显微镜在675 nm激发波长下观测细胞出现红色荧光,利用3.0 T磁共振成像系统测得探针纵向弛豫率为46.969 mmol/(L·s)。最后Gd-DOTA-Cy5.5-NP螯合^(68)Ga^(3+),得到三模态纳米探针^(68)Ga/Gd-DOTA-Cy5.5-NP,伽马计数仪测得间充质干细胞对该探针的摄取在90 min达到饱和。

Continuous nitrogen-doped carbon nanotube matrix for boosting oxygen electrocatalysis in rechargeable Zn-air batteries

Developing robust oxygen electrocatalyst with high-performance is very significant for practical rechargeable Zn-air battery.We report herein the preparation of three-dimensional continuous nanocarbon network composed of interconnected nitrogen-doped carbon nanotubes and its application as oxygen electrocatalysis in rechargeable Zn-air battery.Except the excellent electrochemical bifunctionality,this carbon nanotube matrix also delivers an impressive battery performance.Specifically,an opencircuit voltage of 1.50 V as well as a high power density of 220 m W cm^(-2) with remarkable cycling stability for 1600 h is achieved in the rechargeable Zn-air battery.The study not only provides an efficient bifunctional oxygen electrocatalyst but more importantly may pave significant concepts in designing robust electrode for long-life rechargeable Zn-air battery and other energy technologies.

A QoE Assessment System in Distance Education

It is a challenging task to improve the real-time property and objectivity of the effect assessment for the distance education. This paper presents a QoE (Quality of Experience) assessment system based on the attention of online user. The system captures the video frames from two cameras periodically and synchronously, using the adaptive image binarization based on the linear average threshold for the pretreatment, then processing with edge detection and filtering in the cross-directions at the same time. System gets the position of computer screen and user eyeball. Analyzing the detection results comprehensively obtains the attention of online user by some judging conditions, and finally acquires the quality of user experience. Experimental results demonstrate the feasibility and efficiency.

Continuous microflow visible-light photocatalytic N-formylation of piperidine and its kinetic study

N-formylation of amines,a class of synthetically important reactions,is typically conducted using metal catalysts that are relatively expensive or not readily available and usually needs harsh conditions to increase the reaction efficiency.Here,an efficient continuous microflow strategy was developed for the gas-liquid visible-light photocatalytic N-formylation of piperidine,which achieved a reaction yield of 82.97%and a selectivity of>99%at 12 min using cheap organic dye photocatalyst under mild reaction conditions.The influence of essential parameters,including light intensity,temperature and equivalents of the gas,additive and photocatalyst,on the reaction yield was systematically studied.Furthermore,kinetic investigations were conducted,exhibiting the dependence of reaction rate and equilibrium yield of N-formylpiperidine on light intensity,temperature and photocatalyst equivalent.The microflow photocatalytic approach established in this work,which realized a markedly higher space-time yield than the conventional batch method(37.9 vs.0.212 mmol h-1 L-1),paves the way for the continuous,green and efficient synthesis of N-formamides.

Burden of epilepsy in China and its provinces,1990 to 2019:findings from the Global Burden of Disease Study 2019

Background: Epilepsy accounts for a significant portion of the global disease burden. However, little is known about the disease burden of epilepsy in China and its provinces. Methods: We assessed the burden of epilepsy in China and its provinces, municipalities, and autonomous regions from 1990 to 2019. Burden was measured as incidence, prevalence, deaths, years lived with disability, years of life lost, and disability-adjusted life years (DALYs), by age, sex, year, and province. We used the Socio-Demographic Index (SDI) to determine the association between the provincial development level and age-standardized DALY rates of epilepsy from 1990 to 2019. Results: In 2019, epilepsy caused 1367.51 thousand (95% uncertainty interval [UI]: 979.92–1837.61 thousand) DALYs, and the age-standardized DALY rate was 99.77 (95% UI: 71.33–133.52)/100,000. The age-standardized incidence and prevalence rates for epilepsy in China were 24.65/100,000 and 219.69/100,000, increased by 45.00% (95% UI: 8.03–98.74%) and 35.72% (95% UI: 0.47–86.19%) compared with that in 1990, respectively. From 1990 to 2019, the proportion of DALY caused by epilepsy in the age group under 25 years steadily decreased. The proportion of DALYs caused by epilepsy in people aged 50 years and over increased from 9.45% and 10.22% in 1990 to 29.01% and 32.72% for male and female individuals in 2019, respectively. The highest age-standardized mortality rates were seen in Tibet (4.26 [95% UI: 1.43–5.66]/100,000), Qinghai (1.80 [95% UI: 1.15–2.36]/100,000), and Yunnan (1.30 [95% UI: 0.88–1.62]/100,000), and the lowest mortality rates were in Guangdong (0.48 [95% UI: 0.39–0.64]/100,000), Zhejiang (0.56 [95% UI: 0.44–0.70]/100,000), and Shanghai (0.57 [95% UI: 0.41–0.73]/100,000). The age-standardized DALY rates across the country and in provinces, municipalities, and autonomous regions generally decreased as their SDI increased. Conclusions: The disease burden of epilepsy is still heavy in China, especially in the western provinces. The incidence and prevalence of epilepsy increased between 1990 and 2019, and the burden of epilepsy in the elderly increases gradually. This study provides evidence on epilepsy prevention and care of different regions in China.

Pulmonary Heart Disease Associated Mortality—China,2014–2021

Introduction:Over the latter half of the previous century,pulmonary heart disease(PHD)emerged as a significant public health issue in China.However,the current mortality rate is unknown.Utilizing the Multiple Cause of Death database,the present study aims to investigate the current state and progression of PHD-associated death in China.Methods:Data from the China National Mortality Surveillance System were used to analyze progression in mortality rates attributable to PHD from 2014 to 2021.To standardize population structure for each year during the investigation period,demographic information from the 2020 census was employed as the reference population.Agestandardized mortality rates(ASMR)were determined based on sex,urban-rural area,and region.To identify trends in ASMR,a joinpoint regression analysis was executed.Results:The ASMR of PHD exhibited a marked decrease,falling from 61.68 per 100,000 in 2014 to 28.53 per 100,000 in 2021.This downward trend was observable in both genders,all regions,and both urban and rural settings.The greatest ASMR values were documented in the western region.Comparative observations revealed a higher ASMR in rural areas versus urban ones and in males versus females.PHDassociated deaths predominantly occurred among older individuals,particularly those aged 80 and above.Chronic obstructive pulmonary disease(COPD)emerged as the principal underlying cause of death PHD-associated mortalities,accounting for between 87.41%and 93.42%of cases throughout the period 2014–2021.Conclusions:There was a declining trend in PHD mortality in China from 2014 to 2021,with COPD accounting for a significant proportion of these deaths.Given the high prevalence of COPD and the escalating population aging in China,PHD remains a significant health concern that warrants further attention.

African swine fever virus S273R protein antagonizes type I interferon production by interfering with TBK1 and IRF3 interaction

African swine fever(ASF)is originally reported in East Africa as an acute hemorrhagic fever.African swine fever virus(ASFV)is a giant and complex DNA virus with icosahedral structure and encodes a variety of virulence factors to resist host innate immune response.S273R protein(pS273R),as a SUMO-1 specific cysteine protease,can affect viral packaging by cutting polymeric proteins.In this study,we found that pS273R was an important antagonistic viral factor that suppressed cGAS-STING-mediated type I interferon(IFN-I)production.A detailed analysis showed that pS273R inhibited IFN-I production by interacting with interferon regulatory factor 3(IRF3).Subsequently,we showed that pS273R disrupted the association between TBK1 and IRF3,leading to the repressed IRF3 phosphorylation and dimerization.Deletion and point mutation analysis verified that pS273R impaired IFN-I production independent of its cysteine protease activity.These findings will help us further understand ASFV pathogenesis.

miR-204 suppresses porcine reproductive and respiratory syndrome virus(PRRSV)replication via inhibiting LC3B-mediated autophagy

Porcine reproductive and respiratory syndrome(PRRS)caused by PRRS virus(PRRSV)has been regarded as a persistent challenge for the swine farms worldwide.microRNAs(miRNAs)play key roles in regulating almost every important biological process,including virus-host interaction.In this study,we found that miR-204 was highly expressed in cells that were not permissive to PRRSV infection compared with cells susceptible to PRRSV infection.Subsequently,we demonstrated that overexpression of miR-204 significantly inhibited PRRSV replication in porcine alveolar macrophages(PAMs).Through bioinformatic analysis,we found that there existed a potential binding site of miR-204 on the 30UTR of microtubule associated protein 1 light chain 3B(MAP1LC3B,LC3B),a hallmark of autophagy.Applying experiments including luciferase reporter assay and UV cross-linking and immunoprecipitation(CLIP)assay,we demonstrated that miR-204 directly targeted LC3B,thereby downregulating autophagy.Meanwhile,we investigated the interplay between autophagy and PRRSV replication in PAMs,confirming that PRRSV infection induces autophagy,which in turn facilitates viral replication.Overall,we verify that miR-204 suppresses PRRSV replication via inhibiting LC3B-mediated autophagy in PAMs.These findings will provide a novel potential approach for us to develop antiviral therapeutic agents and controlling measures for future PRRSV outbreaks.

低、中、高度近视患者行SMILE的角膜切削精确性研究

目的研究不同近视程度患者飞秒激光小切口基质透镜取出术（SMILE）后中央角膜切削误差及其变化趋势,探讨不同近视程度对切削误差的影响.方法：回顾性病例对照研究.选取2017 年1-8 月于温州医科大学附属眼视光医院行SMILE的近视患者61 例（120 眼）,将其按术前屈光度分为低度（24眼,-0.50 D≤低度近视≤-3.00 D）、中度（54眼,-3.00 D 〈中度近视≤-6.00 D）以及高度（42眼,高度近视〉 -6.00 D）近视组.于术前、术后1 个月、3 个月使用Sirius眼前节分析系统测量中央角膜厚度（CCT）并计算切削误差及中央角膜切削偏差率,其中切削误差定义为中央角膜实际切削厚度（A-CCT）与预测切削厚度（P-CCT）的差值（△CCT）,中央角膜切削偏差率定义为△CCT 与P-CCT的比值.采用配对t检验、单因素方差分析、Kruskal-Wallis H检验以及Pearson相关分析对数据进行分析.结果：各组患者中央角膜实际切削厚度均小于预测切削厚度;术后1 个月和3 个月各组间△CCT差异有统计学意义（F=21.047、35.100,均P 〈 0.001）;各组间中央角膜切削偏差率差异无统计学意义.在末次检查时,其中低、中、高度近视组△CCT分别为（-8.9±5.0）μm、（-15.6±6.2）μm、（-21.4±5.9）μm,3 组A-CCT与P-CCT差异均有统计学意义（t =8.67、18.50、23.65,P 〈 0.001）.术后切削误差与术前屈光度、切削直径呈正相关（r =0.649、0.384,均P 〈 0.001）,与术前CCT呈负相关（r=-0.219,P=0.016）.结论：各近视组A-CCT均小于P-CCT;不同近视患者SMILE手术后中央角膜切削误差随着近视程度的增大而增大,但各组间中央角膜切削偏差率保持一致.

An alternating direction algorithm for matrix completion with nonnegative factors

This paper introduces an algorithm for the nonnegative matrix factorization-and-completion problem, which aims to find nonnegative low-rank matrices X and Y so that the product XY approximates a nonnegative data matrix M whose elements are partially known （to a certain accuracy）. This problem aggregates two existing problems： （i） nonnegative matrix factorization where all entries of M are given, and （ii） low-rank matrix completion where non- negativity is not required. By taking the advantages of both nonnegativity and low-rankness, one can generally obtain superior results than those of just using one of the two properties. We propose to solve the non-convex constrained least-squares problem using an algorithm based on tile classical alternating direction augmented Lagrangian method. Preliminary convergence properties of the algorithm and numerical simulation results are presented. Compared to a recent algorithm for nonnegative matrix factorization, the proposed algorithm produces factorizations of similar quality using only about half of the matrix entries. On tasks of recovering incomplete grayscale and hyperspeetral images, the proposed algorithm yields overall better qualities than those produced by two recent matrix-completion algorithms that do not exploit nonnegativity.

MULTITASK n-VEHICLE EXPLORATION PROBLEM:COMPLEXITY AND ALGORITHM

这份报纸扩大单个任务的 n 车辆探索问题到多工 n 车辆探索问题(MTNVEP ) ，由把 n 车辆探索问题与安排问题的工作相结合。起初，作者证明 MTNVEP 为任务的固定数字是 NP 难的，并且它为任务的一般数字是强烈 NP 难的。然后，他们与计算时间 O (n3 n ) 建议一个改进精确算法，它比 O 好(n !) 当 n 变得足够地大。而且，四个启发式的算法被建议。启发式的算法的有效性被实验最后说明。

FAST ALGORITHMS FOR HIGHER-ORDER SINGULAR VALUE DECOMPOSITION FROM INCOMPLETE DATA

Higher-order singular value decomposition （HOSVD） is an efficient way for data reduction and also eliciting intrinsic structure of multi-dimensional array data. It has been used in many applications, and some of them involve incomplete data. To obtain HOSVD of the data with missing values, one can first impute the missing entries through a certain tensor completion method and then perform HOSVD to the reconstructed data. However, the two-step procedure can be inefficient and does not make reliable decomposition. In this paper, we formulate an incomplete HOSVD problem and combine the two steps into solving a single optimization problem, which simultaneously achieves imputation of missing values and also tensor decomposition. We also present one algorithm for solving the problem based on block coordinate update （BCU）. Global convergence of the algorithm is shown under mild assumptions and implies that of the popular higher-order orthogonality iteration （HOOI） method, and thus we, for the first time, give global convergence of HOOI. In addition, we compare the proposed method to state-of-the-art ones for solving incom- plete HOSVD and also low-rank tensor completion problems and demonstrate the superior performance of our method over other compared ones. Furthermore, we apply it to face recognition and MRI image reconstruction to show its practical performance.

On the Convergence of Asynchronous Parallel Iteration with Unbounded Delays

Recent years have witnessed the surge of asynchronous parallel(asyncparallel)iterative algorithms due to problems involving very large-scale data and a large number of decision variables.Because of asynchrony,the iterates are computed with outdated information,and the age of the outdated information,which we call delay,is the number of times it has been updated since its creation.Almost all recent works prove convergence under the assumption of a finite maximum delay and set their stepsize parameters accordingly.However,the maximum delay is practically unknown.This paper presents convergence analysis of an async-parallel method from a probabilistic viewpoint,and it allows for large unbounded delays.An explicit formula of stepsize that guarantees convergence is given depending on delays’statistics.With p+1 identical processors,we empirically measured that delays closely follow the Poisson distribution with parameter p,matching our theoretical model,and thus,the stepsize can be set accordingly.Simulations on both convex and nonconvex optimization problems demonstrate the validness of our analysis and also show that the existing maximum-delay-induced stepsize is too conservative,often slows down the convergence of the algorithm.

Hierarchical Voronoi Structure Inspired by Cat Paw Pads Substantially Enhances Landing Impact Energy Dissipation

When a human lands from a high drop,there is a high risk of serious injury to the lower limbs.On the other hand,cats can withstand jumps and falls from heights without being fatally wounded,largely due to their impact-resistant paw pads.The aim of the present study was to investigate the biomechanism of impact resistance in cat paw pads,propose an optimal hierarchical Voronoi structure inspired by the paw pads,and apply the structure to bionic cushioning shoes to reduce the impact force of landing for humans.The microstructure of cat paw pads was observed via tissue section staining,and a simulation model was reconstructed based on CT to verify and optimize the structural cushioning capacity.The distribution pattern,wall thickness of compartments,thickness ratio of epidermis and dermis,and number of compartments in the model were changed and simulated to achieve an optimal composed structure.A bionic sole was 3D-printed,and its performance was evaluated via compression test and a jumping-landing experiment.The results show that cat paw pads are a spherical cap structure,divided from the outside to the inside into the epidermis,dermis,and compartments,each with different cushioning capacities.A finite element simulation of different cushioning structures was conducted in a cylinder with a diameter of 20 mm and a height of 10 mm,featuring a three-layer structure.The optimal configuration of the three layers should have a uniform distribution with 0.3–0.5 mm wall thickness,a 1:1–2 thickness ratio of epidermis and dermis,and 100–150 compartments.A bionic sole with an optimized structure can reduce the peak impact force and delay the peak arrival time.Its energy absorption rate is about 4 times that of standard sole.When jumping 80,100,and 120 cm,the normalized ground reaction force is also reduced by 8.7%,12.6%and 15.1%compared with standard shoes.This study provides theoretical and technical support for effective protection against human lower limb landing injuries.