Progress,implications,and challenges in using humanized immune system mice in CAR-T therapy-Application evaluation and improvement

In recent years,humanized immune system(HIS)mice have been gradually used as models for preclinical research in pharmacotherapies and cell therapies with major breakthroughs in tumor and other fields,better mimicking the human immune system and the tumor immune microenvironment,compared to traditional immunodeficient mice.To better promote the application of HIS mice in preclinical research,we se-lectively summarize the current prevalent and breakthrough research and evaluation of chimeric antigen receptor(CAR)-T cells in various antiviral and antitumor treat-ments.By exploring its application in preclinical research,we find that it can better reflect the actual clinical patient condition,with the advantages of providing high-efficiency detection indicators,even for progressive research and development.We believe that it has better clinical patient simulation and promotion for the updated design of CAR-T cell therapy than directly transplanted immunodeficient mice.The characteristics of the main models are proposed to improve the use defects of the existing models by reducing the limitation of antihost reaction,combining multiple models,and unifying sources and organoid substitution.Strategy study of relapse and toxicity after CAR-T treatment also provides more possibilities for application and development.

Atom-efficient coupling reaction of aryl bromides with sodium tetraphenylborate catalyzed by reusable Pd/C in water under focused microwave irradiation

由钠 tetraphenylborate 的芳基溴化物的快速、异构的 Pd/C-catalyzed 原子有效的 phenylation 在水里发生在集中的微波照耀下面。钯催化剂能容易被恢复并且再使用。

Successful Applications of Generic Atmospheric Correction Online Service for InSAR (GACOS) to the Reduction of Atmospheric Effects on InSAR Observations

The tremendous development of Synthetic Aperture Radar(SAR)missions in recent years facilitates the study of smaller amplitude ground deformation over greater spatial scales using longer time series.However,this poses greater challenges for correcting atmospheric effects due to the wider coverage of SAR imagery than ever.Previous attempts have used observations from Global Positioning System(GPS)and Numerical Weather Models(NWMs)to separate atmospheric delays,but they are limited by(1)The availability(and distribution)of GPS stations;(2)The low spatial resolution of NWM;And(3)The difficulties in quantifying their performance.To overcome these limitations,we have developed the Generic Atmospheric Correction Online Service for InSAR(GACOS)which utilizes the high-resolution European Centre for Medium-Range Weather Forecasts(ECMWF)products using an Iterative Tropospheric Decomposition(ITD)model.This enables the reduction of the coupling effects of the troposphere turbulence and stratification and hence achieves equivalent performances over flat and mountainous terrains.GACOS comprises a range of notable features:(1)Global coverage;(2)All-weather,all-time usability;(3)Available with a maximum of two-day latency;And(4)Indicators available to assess the model’s performance and feasibility.In this paper,we demonstrate some successful applications of the GACOS online service to a variety of geophysical studies.

清代旅蒙晋商与归化城民族“三交”

旅蒙晋商在归化城土默特地区行商坐贾,展开多种经营,几乎掌控了当地的商业。在此过程中,归化城由早期蒙古族人占绝大多数,变为汉人居多、多民族同生共处的格局。晋商在归化城的经贸开发与扩展虽然伴随着一些民族摩擦与冲突,但总体上充当着民族“三交”的枢纽、桥梁与助推器,这着重体现在不同民族、特别是汉蒙之间在经济发展、生活习俗、语言文字、信仰观念等方面的相互学习和影响上。通过对相关史实的梳理与分析,得出以下结论与启示:一支体量大、能力强的商业劲旅在带动民族地区市场化发展的同时,往往也会成为推动民族“三交”最为经济、持续和有效的力量;而商人群体得以充分发挥积极作用的前提是市场开放和市场秩序的建立和维护;商人群体经贸活动带动下不同民族混居共生的模式,有助于各民族在物质、精神层面不断重塑与交融。

Trajectory Planning for OTFS-Based UAV Communications

Unmanned aerial vehicles(UAVs)have attracted growing research interests in recent years,which can be used as cost-effective aerial platforms to transmit collected data packets to ground access points(APs).Thus,it is crucial to investigate robust airto-ground(A2G)wireless links for high-speed UAVs.However,the A2G wireless link is unstable as it suffers from large path-loss and severe Doppler effect due to the high mobility of UAVs.In order to meet these challenges,we propose an orthogonal time frequency space(OTFS)-based UAV communication system to relief the Doppler effect.Besides,considering that the energy of UAV is limited,we optimize the trajectory planning of UAV to minimize the energy consumption under the constraints of bit error rate(BER)and transmission rate,where the Doppler compensation is taken into account.Simulation results show that the performance of OTFS-based UAV system is superior to orthogonal frequency division multiplexing(OFDM)-based UAV systems,which can accomplish transmission tasks over shorter distances with lower energy consumption.

基于语音识别的电磁调控智能超表面

本文提出并实现了一种基于人类语音识别的智能超表面,用于对电磁波束进行可编程调控。该智能超表面平台由数字编码超表面、语音识别模块、单片机和数模转换器(DAC)电路组成,可根据预先存储的语音指令对电磁波进行智能控制。所构建的数字编码超表面包含6×6个超级子单元,每个超级子单元由4×4个嵌入了变容二极管的有源数字单元组成。语音识别模块配合DAC和单片机对语音指令进行识别,并生成对应的电压序列来控制超表面。此外,在超表面的设计过程中引入遗传算法,可有效优化超表面相位分布。为了验证智能超表面平台的性能,演示了雷达散射截面积缩减、涡旋波束生成和波束分裂三种典型功能。所提出的方案为调控电磁波提供了一种新的途径,并在电磁和声学通信之间架起了连接桥梁。

Regional brain structural abnormality in ischemic stroke patients:a voxel-based morphometry study

Our previous study used regional homogeneity analysis and found that activity in some brain areas of patients with ischemic stroke changed significantly.In the current study,we examined structural changes in these brain regions by taking structural magnetic resonance imaging scans of 11 ischemic stroke patients and 15 healthy participants,and analyzing the data using voxel-based morphometry.Compared with healthy participants,patients exhibited higher gray matter density in the left inferior occipital gyrus and right anterior white matter tract.In contrast,gray matter density in the right cerebellum,left precentral gyrus,right middle frontal gyrus,and left middle temporal gyrus was less in ischemic stroke patients.The changes of gray matter density in the middle frontal gyrus were negatively associated with the clinical rating scales of the Fugl-Meyer Motor Assessment(r=–0.609,P=0.047) and the left middle temporal gyrus was negatively correlated with the clinical rating scales of the nervous functional deficiency scale(r=–0.737,P=0.010).Our findings can objectively identify the functional abnormality in some brain regions of ischemic stroke patients.

Long noncoding RNAs in neurodevelopment and Parkinson’s disease

Long noncoding RNAs(lnc RNAs) are RNA molecules comprising more than 200 nucleotides, which are not translated into proteins. Many studies have shown that lnc RNAs are involved in regulating a variety of biological processes, including immune, cancer, stress, development and differentiation at the transcriptional, epigenetic or post-transcriptional levels. Here, we review the role of lnc RNAs in the process of neurodevelopment, neural differentiation, synaptic function, and pathogenesis of Parkinson’s disease(PD). These pathomechanisms include protein misfolding and aggregation, disordered protein degradation, mitochondrial dysfunction, oxidative stress, autophagy, apoptosis, and neuroinflammation. This information will provide the basis of lnc RNA-based disease diagnosis and drug treatment for PD.

Nampt is involved in DNA double-strand break repair

DNA double-strand break(DSB) is the most severe form of DNA damage,which is repaired mainly through high-fidelity homologous recombination(HR) or error-prone non-homologous end joining(NHEJ).Defects in the DNA damage response lead to genomic instability and ultimately predispose organs to cancer.Nicotinamide phosphoribosyltransferase(Nampt),which is involved in nicotinamide adenine dinucleotide metabolism,is overexpressed in a variety of tumors.In this report,we found that Nampt physically associated with CtIP and DNA-PKcs/Ku80,which are key factors in HR and NHEJ,respectively.Depletion of Nampt by small interfering RNA(siRNA) led to defective NHEJ-mediated DSB repair and enhanced HR-mediated repair.Furthermore,the inhibition of Nampt expression promoted proliferation of cancer cells and normal human fibroblasts and decreased β-galactosidase staining,indicating a delay in the onset of cellular senescence in normal human fibroblasts.Taken together,our results suggest that Nampt is a suppressor of HR-mediated DSB repair and an enhancer of NHEJ-mediated DSB repair,contributing to the acceleration of cellular senescence.

Similarities and Differences of Early Pulmonary CT Features of Pneumonia Caused by SARS-CoV-2, SARS-CoV and MERS-CoV: Comparison Based on a Systemic Review

Objective To compare the similarities and differences of early CT manifestations of three types of viral pneumonia induced by SARS-CoV-2(COVID-19),SARS-CoV(SARS)and MERS-CoV(MERS)using a systemic review.Methods Electronic database were searched to identify all original articles and case reports presenting chest CT features for adult patients with COVID-19,SARS and MERS pneumonia respectively.Quality of literature and completeness of presented data were evaluated by consensus reached by three radiologists.Vote-counting method was employed to include cases of each group.Data of patients’manifestations in early chest CT including lesion patterns,distribution of lesions and specific imaging signs for the three groups were extracted and recorded.Data were compared and analyzed using SPSS 22.0.Results A total of 24 studies were included,composing of 10 studies of COVID-19,5 studies of MERS and 9 studies of SARS.The included CT exams were 147,40,and 122 respectively.For the early CT features of the 3 pneumonias,the basic lesion pattern with respect to"mixed ground glass opacity(GGO)and consolidation,GGO mainly,or consolidation mainly"was similar among the 3 groups(χ^2=7.966,P>0.05).There were no significant differences on the lesion distribution(χ^2=13.053,P>0.05)and predominate involvement of the subpleural area of bilateral lower lobes(χ^2=4.809,P>0.05)among the 3 groups.The lesions appeared more focal in COVID-19 pneumonia at early phase(χ^2=23.509,P<0.05).The proportions of crazy-paving pattern(χ^2=23.037,P<0.001),organizing pneumonia pattern(P<0.05)and pleural effusions(P<0.001)in COVID-19 pneumonia were significantly lower than the other two.Although rarely shown in the early CT findings of all three viral pneumonias,the fibrotic changes were more frequent in SARS than COVID-19 and MERS(χ^2=6.275,P<0.05).For other imaging signs,only the MERS pneumonia demonstrated tree-in-buds,cavitation,and its incidence rate of interlobular or intralobular septal thickening presented significantly increased as compared to the other two pneumonia(χ^2=22.412,P<0.05).No pneumothorax,pneumomediastinum and lymphadenopathy was present for each group.Conclusions Imaging findings on early stage of these three coronavirus pneumonias showed similar basic lesion patterns,including GGO and consolidation,bilateral distribution,and predominant involvement of the subpleural area and the lower lobes.Early signs of COVID-19 pneumonia showed less severity of inflammation.Early fibrotic changes appeared in SARS only.MERS had more severe inflammatory changes including cavitation and pleural effusion.The differences may indicate the specific pathophysiological processes for each coronavirus pneumonia.

Stem cell therapy for Alzheimer’s disease:An overview of experimental models and reality

Alzheimer's disease(AD)is a neurodegenerative disorder.The pathology of AD is characterized by extracellular amyloid beta(Aβ)plaques,neurofibrillary tangles com-posed of hyperphosphorylated tau,neuronal death,synapse loss,and brain atrophy.Many therapies have been tested to improve or at least effectively modify the course of AD.Meaningful data indicate that the transplantation of stem cells can alleviate neuropathology and significantly ameliorate cognitive deficits in animal models with Alzheimer's disease.Transplanted stem cells have shown their inherent advantages in improving cognitive impairment and memory dysfunction,although certain weak-nesses or limitations need to be overcome.This review recapitulates rodent models for AD,the therapeutic efficacy of stem cells,influencing factors,and the underlying mechanisms behind these changes.Stem cell therapy provides perspective and chal-lenges for its clinical application in the future.

Graph-Based Dimensionality Reduction for Hyperspectral Imagery: A Review

Hyperspectral image(HSI)contains a wealth of spectral information,which makes fine classification of ground objects possible.In the meanwhile,overly redundant information in HSI brings many challenges.Specifically,the lack of training samples and the high computational cost are the inevitable obstacles in the design of classifier.In order to solve these problems,dimensionality reduction is usually adopted.Recently,graph-based dimensionality reduction has become a hot topic.In this paper,the graph-based methods for HSI dimensionality reduction are summarized from the following aspects.1)The traditional graph-based methods employ Euclidean distance to explore the local information of samples in spectral feature space.2)The dimensionality-reduction methods based on sparse or collaborative representation regard the sparse or collaborative coefficients as graph weights to effectively reduce reconstruction errors and represent most important information of HSI in the dictionary.3)Improved methods based on sparse or collaborative graph have made great progress by considering global low-rank information,local intra-class information and spatial information.In order to compare typical techniques,three real HSI datasets were used to carry out relevant experiments,and then the experimental results were analysed and discussed.Finally,the future development of this research field is prospected.

Rehmannia glutinosa exhibits anti-aging effect through maintaining the quiescence and decreasing the senescence of hematopoietic stem cells

Background: The time-related decline in regenerative capacity and organ homeostasis is a major feature of aging. Rehmannia glutinosa and Astragalus membranaceus have been used as traditional Chinese herbal medicines for enhanced immunity and prolonged life. However, the mechanism by which this herbal medicine slows aging is unknown. In this study, we investigated the mechanism of the herbal anti-aging effect.Methods: Mice were fed diets supplemented with R. glutinosa or A. membranaceus for 10 months; the control group was fed a standard diet. The phenotypes were evaluated using a grading score system and survival analysis. The percentages of the senescence phenotypes of hematopoietic stem cells(HSCs) were determined by fluorescence-activated cell sorting analysis. The function and the mechanism of HSCs were analyzed by clonogenic assay and the real-time polymerase chain reaction.Results: The anti-aging effect of R. glutinosa is due to the enhanced function of HSCs. Mice fed with R. glutinosa displayed characteristics of a slowed aging process,including decreased senescence and increased rate of survival. Flow cytometry analysis showed decreased numbers of Lin–Sca1^+c-kit–(LSK) cells, long-term HSCs(LT-HSCs) and short-term HSCs(ST-HSCs) in the R. glutinosa group. In vitro, clonogenic assays showed increased self-renewal ability of LT-HSCs from the R. glutinosa group as well as maintaining LSK quiescence through upregulated p18 expression. The R. glutinosa group also showed decreased reactive oxygen species levels and the percentage of β-gal^+ cells through downregulation of the cellular senescence-associated protein p53 and p16.Conclusion: Rehmannia glutinosa exerts anti-aging effects by maintaining the quiescence and decreasing the senescence of HSCs.

减沉复合疏桩基础沉降计算法商榷

从《建筑桩基技术规范(JGJ94—2008)》提供的2例减沉复合疏桩基础案例,与该规范用于验证复合疏桩基础沉降计算法的2例案例,以及上海地区有着长期桩土荷载分担原位实测与沉降监测数据的1例复合疏桩基础案例中,发现"减沉复合疏桩基础沉降计算法"的计算可靠度依赖"假想天然地基平均附加压力"的取值,然而"假想天然地基平均附加压力"取值所依据的"承台效应系数"却不适用于常规复合疏桩基础。因此,应用"减沉复合疏桩基础沉降计算法"时需先获得可靠的沉降计算值,然后才能反推得"假想天然地基平均附加压力"。

Revision of Senegalia in China, and notes on introduced species of Acacia, Acaciella, Senegalia and Vachellia(Leguminosae: Mimosoideae)

The present work represents the first comprehensive taxonomic revision of Acacia sens.lat.(Leguminosae:Mimosoideae)in China,focusing on the indigenous species.Critical reassessments of specimens and re-defin让ion of previously recorded species have resulted in recognising 21 indigenous species under Senegalia,a segregate of the former Acacia sens.tat.Detailed botanical profiles are provided for these species,together w让h a diagnostic line drawing and distribution map;photographs of living plants are provided for more than half the species.Terser treatments are also provided for the 15 species from four genera that are regarded as major introductions of Acacia sens.lat.to the country:Acacia Mill.(12 spp.),Acaciella Britton&Rose(1 sp.),Senegalia Raf.(1 sp.)and Vachellia Wight&Arn.(1 sp.).An identification key to all Acacia sens.lat.species in China is provided.The indigenous species of Senegalia in China belong to sect.Monacanthea(Vassal)Maslin,comb,nov.,and the introduced ones to sect.Senegalia.As a consequence of this study,the number of Senegalia species now recognised for China has almost doubled.Six new species are described:Senegalia clandestina Maslin,B.C.Ho,H.Sun&LBai,sp.nov.;Senegalia guangdongensis Maslin,B.C.Ho,H.Sun&LBai,sp.nov.;Senegalia obliqua Maslin,B.C.Ho,H.Sun&LBai,sp.nov.;Senegalia orientalis Maslin,B.C.Ho,H.Sun&LBai,sp.nov.;Senegalia prominens Maslin,B.C.Ho,H.Sun&LBai,sp.nov.;Senegalia stipitata Maslin,B.C.Ho,H.Sun&LBai,sp.nov.Four new combinations are established:Senegalia garrettii(I.C.Nielsen)Maslin,B.C.Ho,H.Sun&LBai,comb.&stat,nov.;Senegalia kerrii(I.C.Nielsen)Maslin,B.C.Ho,H.Sun&LBai,comb.&stat,nov.;Senegalia kunmingensis(C.Chen&H.Sun)Maslin,B.C.Ho,H.Sun&LBai,comb.&stat,nov.;Senegalia macrocephala(Lace)Maslin,B.C.Ho,H.Sun&LBai,comb.nov.Senegalia andamanica(I.C.Nielsen)Maslin,Seigler&Ebinger and S.macrocephala are new records for China.A lectotype is designated for Acacia teniana Harms and 2nd step lectotypifications effected for Acacia delavayi Franch.,Acacia insuavis Lace,Acacia pruinescens Kurz and Acacia yunnanensis Franch.Former holotype citations are corrected to lectotype for Acacia hainanensis Hayata,Acacia macrocephala Lace,Acacia oxyphylla Graham ex Benth.and Acacia philippinarum Benth.A neotype is designated for Acacia arrophula D.Don.China is a principal area of species-richness for Senegalia in Asia.Senegalia displays a high degree of endemism within China and almost half the species are endemic or near-endemic,w让h Yunnan the most species-rich and species-diverse Province.

Local Preserving Graphs Using Intra-Class Competitive Representation for Dimensionality Reduction of Hyperspectral Image

As a key technique in hyperspectral image pre-processing,dimensionality reduction has received a lot of attention.However,most of the graph-based dimensionality reduction methods only consider a single structure in the data and ignore the interfusion of multiple structures.In this paper,we propose two methods for combining intra-class competition for locally preserved graphs by constructing a new dictionary containing neighbourhood information.These two methods explore local information into the collaborative graph through competing constraints,thus effectively improving the overcrowded distribution of intra-class coefficients in the collaborative graph and enhancing the discriminative power of the algorithm.By classifying four benchmark hyperspectral data,the proposed methods are proved to be superior to several advanced algorithms,even under small-sample-size conditions.

Highly Sensitive Mid-Infrared Photodetector Enabled by Plasmonic Hot Carriers in the First Atmospheric Window

The first atmospheric window of 3-5μm in the mid-infrared(MIR)spectral range pertains to crucial application fields,with particular scientific and technological importance.However,conventional narrow-bandgap semiconductors operating at this band,represented by mercury cadmium telluride and indium antimonide,suffer from limited specific detectivity at room temperature and hindered optoelectronic integration.In this study,a plasmonic hot electron-empowered MIR photodetector based on Al-doped ZnO(AZO)/bi-layer graphene heterostructure is demonstrated.Free electrons oscillate coherently in AZO disk arrays,resulting in strong localized surface plasmon resonance(LSPR)in the MIR region.The photoelectric conversion efficiency at 3-5μm is significantly improved due to plasmon-induced hot-electron extraction and LSPR-enhanced light absorption.The specific detectivity reaches about 1.4×10^(11)Jones and responsivity is up to 4712.3 A/W at wavelength of 3μm at room temperature.The device’s specific detectivity is among the highest performance of commercial state-ofthe-art photodetectors and superior to most of the other 2 D materials based photo detectors in the MIR region.These results demonstrate that a plasmonic heavily doped metal oxides/2 D material heterostructure is a suitable architecture for constructing highly sensitive room-temperature MIR photodetectors.

Forest-Fire Recognition by Sparse and Collaborative Subspace Clustering

Traditional forest-fire recognition based on the characteristics of smoke, temperature and light fails to accurately detect and respond to early fires. By analyzing the characteristics of flame, the methods based on aerial image recognition have been widely used, such as RGB-based and HIS-based methods. However, these methods are susceptible to background factors causing interference and false detection. To alleviate these problems, we investigate two subspace clustering methods based on sparse and collaborative representation, respectively, to detect and locate forest fires. Firstly, subspace clustering segments flame from the whole image. Afterwards, sparse or collaborative representation is employed to represent most of the flame information in a dictionary with l1-regularization or l2-regularization term, which results in fewer reconstruction errors. Experimental results show that the proposed SSC and CSC substantially outperform the state-of-the art methods.