Bispecific antibodies targeting immunomodulatory checkpoints for cancer therapy

Advances in antibody engineering have led to the generation of more innovative antibody drugs,such as bispecific antibodies(bs Abs).Following the success associated with blinatumomab,bs Abs have attracted enormous interest in the field of cancer immunotherapy.By specifically targeting two different antigens,bs Abs reduce the distance between tumor and immune cells,thereby enhancing tumor killing directly.There are several mechanisms of action upon which bs Abs have been exploited.Accumulating experience on checkpoint-based therapy has promoted the clinical transformation of bs Abs targeting immunomodulatory checkpoints.Cadonilimab(PD-1×CTLA-4)is the first approved bs Ab targeting dual inhibitory checkpoints,which confirms the feasibility of bs Abs in immunotherapy.In this review we analyzed the mechanisms by which bs Abs targeting immunomodulatory checkpoints and their emerging applications in cancer immunotherapy.

Decoding the complexity of metastasis

Cancer metastasis remains one of the most confounding questions in oncology1,2.Although current cutting-edge techniques enable very early detection of tumors,profiling whether a tumor has already begun to spread and where it has attempted to colonize remains a major hurdle.Indeed,metastatic seeding events exhibit remarkable temporal and spatial heterogeneity,wherein the origin(primary site)and destination(metastatic site)are highly dynamic.For example,liver metastasis is particularly common and remains a leading cause of mortality3.

New development of cognitive diagnosis models

Cognitive diagnosis is the judgment of the student’s cognitive ability, is a wide-spread concern in educational science. The cognitive diagnosis model (CDM) is an essential method to realize cognitive diagnosis measurement. This paper presents new research on the cognitive diagnosis model and introduces four individual aspects of probability-based CDM and deep learning-based CDM. These four aspects are higher-order latent trait, polytomous responses, polytomous attributes, and multilevel latent traits. The paper also sorts on the contained ideas, model structures and respective characteristics, and provides direction for developing cognitive diagnosis in the future.

A sampling method based on forecasting and combinatorial optimization for high performance A/B testing

1 Introduction A/B testing[1]is a popular statistical method for many applications,especially,widely used by Internet companies for user experience research.The sampling algorithm is an important part of A/B testing and has a critical impact on the performance of A/B testing.There are two challenges to achieving high performance in A/B testing.(1)The features of individuals being sampled change over time and the sampling results used for evaluation are valid only for a period of time.(2)The sampling methods in A/B testing require determining whether the two groups of samples have an identical distribution while Simple Random Sampling(SRS)has a different purpose,which only concerns whether the sample distribution is identical to the population.

氢杨梅素改善高脂饮食诱导的肥胖小鼠肝脏脂肪沉积及机制

有文献报道,SIRT1-AMPK信号通路可能在DHM改善肝脏细胞甘油三酯蓄积、胰岛素抵抗等作用中发挥作用。为此,本课题拟进一步观察DHM对高脂饮食诱导的肥胖小鼠肝脏脂肪沉积的影响,并探讨其可能机制。C57BL/6J小鼠采用普通饲料和高脂饲料喂养,同时分别用或不用低剂量(125 mg/kg)或高剂量(250 mg/kg)的DHM处理16周。实验期间,每两周检测体重一次。16周后,眼眶静脉取血并处死动物,同时取肩胛下、附睾与腹股沟的脂肪并用电子秤进行称重,并记录脂肪重量。全自动生化分析仪检测:血清甘油三酯(triglyceride,TG)、血清总胆固醇(totalcholesterol,TC)、血清高密度脂蛋白(high-densitylipoprotein,HDL)、血清低密度脂蛋白(low-densitylipoprotein,LDL)。取肝脏甲醛固定、HE和油红O染色检测肝脏脂肪沉积情况;比色法检测肝脏MDA和SOD含量;Realtime PCR检测相关指标的基因表达:IL-6、IL-8、TNF-α、乙酰辅酶A羧化酶(acetyl-Co A carboxylase,ACC)、固醇调节元件结合蛋白(sterol regulatory element binding protein-1c,SREBP-1)、脂肪酸合成酶(fatty acid synthetase,FAS)、过氧化物酶体增殖物激活受体α(peroxisome proliferator-activated receptor alpha,PPARα)、棕榈酰转移酶1(carnitinepalmitoyltransferase1,CPT1)、SIRT1和AMPK。WesternBlot检测SIRT1、AMPK、SIRT1-AMPK、ACC、SREBP-1、FAS、PPARα和CPT1的蛋白表达水平。与ND组相比,HFD组小鼠体重、体脂显著增加;TG、TC、LDL水平增加,HDL水平降低,肝细胞体积增大,脂滴数量、脂肪沉积、MDA、IL-6、IL-8、TNF-α、SREBP-1c、FAS、ACC1水平显著增加,SOD活力、PPARα、CPT1、SIRT1m RNA和AMPKm RNA、SIRT1、AMPK PPARα、CPT1蛋白水平显著下降。DHM能显著逆转HFD组小鼠上述指标的改变;但DHM对ND小鼠上述指标无显著影响。总之,DHM改善高脂饮食诱导的肥胖小鼠肝脏脂肪沉积,其机制可能与抑制氧化应激、炎症和脂质合成,促进脂质分解有关。

Effects of nano carbon on soil erosion and nutrient loss in a semi-arid loess region of Northwestern China

Since 2005,the application of nano carbon(NC)in agriculture and environmental remediation has received considerable attention with most of the research focusing on plant growth and heavy metal absorption.However,little is known about the potential effects of NC on soil erosion and nutrient loss.In this study,rainfall simulation tests were conducted on a soil plot(1 m×1 m,located in a semi-arid loess region of northwestern China),in which a mixture(5-cm below the soil surface)of NC(0,0.1%,0.5%,0.7% and 1.0% on a mass base)and sandy soil(same as the one in the plot)was embedded as three bands(5 cm wide,1 m long and 5 cm thick)at the three positions(top,middle and bottom of the plot),respectively.Before the rainfall simulation test,a mixed solution of potassium bromide(1.0 mol/L KBr),potassium nitrate(1.0 mol/L KNO_(3)),monopotassium phosphate(1.0 mol/L KH_(2)PQ_(4))was sprayed on the soil surface.Results showed that the sandy soil on the Loess Plateau with 0.7%NC addition(36.47 kg/hm^(2) on a mass basis)could improve soil water runoff,sediment yield,and nutrient loss in the semi-arid loess region of northwestern China,in addition to preventing soil water from deep percolation.Therefore,NC may have a great potential in soil erosion control on the Loess Plateau of China.