Immune checkpoint blockade and its combination therapy with small-molecule inhibitors for cancer treatment

Initially understood for its physiological maintenance of self-tolerance, the immune checkpoint molecule has recently been recognized as a promising anti-cancer target. There has been considerable interest in the biology and the action mechanism of the immune checkpoint therapy, and their incorporation with other therapeutic regimens. Recently the small-molecule inhibitor (SMI) has been identified as an attractive combination partner for immune checkpoint inhibitors (ICIs) and is becoming a novel direction for the field of combination drug design. In this review, we provide a systematic discussion of the biology and function of major immune checkpoint molecules, and their interactions with corresponding targeting agents. With both preclinical studies and clinical trials, we especially highlight the ICI + SMI combination, with its recent advances as well as its application challenges.     

Improvement of almond production using Bombus terrestris (Hymenoptera: Apidae) in Mediterranean conditions

Almond trees are one of the most important crops in the Balearic Islands. The pollination of almonds is limited to the activity of insects, and cross‐pollination is necessary for fruit development. Currently, honey bees and wild bee populations are declining considerably due to multiple causes, such as the use of pesticides, diseases and habitat loss. An alternative to increase the almond production is the use of commercial pollinators. In this long‐term (3 years) study, the effect of the introduction of Bombus terrestris colonies on almond production was evaluated in two orchards. Two experimental designs were carried out to study the best management of this pollinator. For 2 years, all bumble bee colonies were placed in the middle of the plot and during the last year, the bumble bee colonies were distributed homogenously in the plot. Fruit set and the foraging behaviour of bumble bees during the blossoming period was determined, and the effect of different environmental variables on the visitation rate of bumble bees was assessed by means of a generalized linear mixed model (GLMM). Moreover, for the first time, the spatial distribution of fruit set was evaluated. Our results show that fruit set was significantly higher in the fields where B. terrestris had been introduced than in the control plots. This increased production resulted in a positive economic balance for the farmer. Moreover, bumble bees showed to prefer trees in a southwest orientation that were close to their colony. The activity of bumble bees showed to be significantly influenced by wind speed (the higher the speed the more flowers are visited by B. terrestris) and time after flowering (visitation rate decreased with days after flowering). In order to improve its management and obtain the highest possible almond production, it is important to understand the activity and behaviour of this pollinator.     

Nr5a1-Cre-mediated Tspo conditional knockout mice with low growth rate and prediabetes symptoms – A mouse model of stress diabetes

Translocator protein (TSPO) is a high-affinity cholesterol- and drug-binding mitochondrial protein. Nuclear receptor subfamily 5 group A member 1 or steroidogenic factor 1 (Nr5a1)-Cre mice were previously used to generate steroidogenic cell-specific Tspo gene conditional knockout (cKO) mice. TSPO-depleted homozygotes showed no response to adrenocorticotropic hormone (ACTH) in stimulating adrenal cortex corticosterone production but showed increased epinephrine synthesis in the medulla. No other phenotype was observed under normal growth conditions. During these studies, we noted that pairing two cKO mice resulted in the generation of small pups. These pups showed low growth rate at weaning, which has been linked to the development of type 2 diabetes (T2D) in adulthood. Experimental verification of T2D symptoms via blood testing of the adult mice, including glycated hemoglobin and insulin C-peptide measurements, showed that these Tspo cKO mice exhibited sustained hyperglycemia, a sign of prediabetes, likely due to the augmentation of hepatic glucose production mediated by the increased epinephrine. We also observed increased expression of the S100a8 gene, which is upregulated after chronic glucose stimulation. Taken together, the observed prediabetes phenotype and lack of response to ACTH indicate that Tspo cKO mice (Nr5a1-Cre^+/?, Tspo^fl/fl) could provide a useful model to study the link between diabetes and stress.     

Mapping quantitative trait loci associated with southern leaf blight resistance in maize (Zea mays L.)

Southern leaf blight (SLB) caused by the fungus Cochliobolus heterostrophus (Drechs.) Drechs. is a major foliar disease of maize worldwide. Our objectives were to identify quantitative trait loci (QTL) for resistance to SLB and flowering traits in recombinant inbred line (RIL) population derived from the cross of inbred lines LM5 (resistant) and CM140 (susceptible). A set of 207 RILs were phenotyped for resistance to SLB at three time intervals for two consecutive years. Four putative QTL for SLB resistance were detected on chromosomes 3, 8 and 9 that accounted for 54% of the total phenotypic variation. Days to silking and anthesis–silking interval (ASI) QTL were located on chromosomes 6, 7 and 9. A comparison of the obtained results with the published SLB resistance QTL studies suggested that the detected bins 9.03/02 and 8.03/8.02 are the hot spots for SLB resistance whereas novel QTL were identified in bins 3.08 and 8.01/8.04. The linked markers are being utilized for marker‐assisted mobilization of QTL conferring resistance to SLB in elite maize backgrounds. Fine mapping of identified QTL will facilitate identification of candidate genes underlying SLB resistance.     

三种乡土树种在二种林分改造模式下的生理生态比较

在丘陵荒山先锋树种马占相思林的林窗和均匀间伐50％(简称林冠层下)的2种林分改造模式下,研究了降真香、红椎和火力楠3种乡土树种生长初期的生理生态。结果表明,不管是在冬季或夏季,林窗中比林冠层下有更高的光合有效辐射(PAR)和相对湿度(RH),并且有较低的气温(Tair),林窗与林内最主要的差异是PAR的变化。生长在林窗里的植株比林冠层下的叶片小而厚,叶片单位面积干重增加,林窗里的植株叶片有较高的叶绿素含量。冬天,降真香和红椎在林窗里和林冠层下的净光合速率(Pn)日变化曲线都为单峰型,而火力楠在林窗下为双峰型,林冠层下为单峰型。3种树种在林窗里和林冠层下植株的蒸腾速率(Tr)有较相似的日进程,都为单峰型。2种林分改造模式下3种树种叶片气孔导度(GS)的日变化也较相似,与PAR的变化趋势相似,而与RH变化呈相反趋势。冬季。降真香和红椎在林窗的水分利用效率(WUE)比林冠层下稍高,而火力楠在林冠层下则比林窗高．但它们都无显著差异。夏天,3种树种在林窗和林冠层下的Pn与冬天有相似的结果。夏季红椎和降真香在林窗的Tr比林冠层下高,而火力楠在林冠层下的Tr比林窗高。Gs的变化趋势也与PAR相似,与RH变化趋势相反。夏季,降真香和火力楠的WUE在林窗比林冠层下高,但红椎却比林冠层下的低。3个树种中火力楠的WUE最高。3种树种在林窗和林冠层下的wUE都是冬季比夏季高。综合植物各项生理生态指标的分析结果可知,降真香和红椎较适宜种植在林窗里,而火力楠较能适应有一定郁闭度的林冠层下。     

松花湖铜绿微囊藻无菌株和单藻株生长因素的研究

用毛细滴管洗净法从松花湖分离纯化出铜绿微囊藻(Microcystisaeruginosa)的单藻株和无菌株,研究了温度、照度、N、P、Fe各种因素对单藻株和无菌株生长的影响。结果表明,各种因素对单藻株和无菌株最大比增长率的影响差别不大,单藻株和无菌株分别在温度33℃,照度5000Lx(2000Lx)、NO3-N浓度1.2mg·L-1,PO43-P浓度0.06mg·L-1,柠檬酸铁铁浓度0.05mg·L-1(0.04mg·L-1)时,达到最大比增长率。在一定浓度范围内,随着N、P、Fe浓度的增加,单藻株比无菌株的最大增长量高得多,可见附着细菌的存在,能促进铜绿微囊藻的生长。从松花湖湖水中N、P和Fe含量以及温度和照度的情况看,松花湖的某些区域已经基本具备了水华发生的条件。     

水稻亚种间杂种F1光合特性研究

用绵恢725、蜀恢527和蜀恢881三个籼型恢复系、1个美国稻Lemont和1个爪哇稻香大粒作母本,与1个日本特早熟粳稻Kitaake杂交,研究了5个杂种F1及其亲本的光合生理表现.结果表明,在高光通量密度(Photosynthetic flux density,PFD)条件下,5个杂种F1净光合速率(Pn)明显高于双亲或双亲之一,推测亲本与杂种F1之间不同的Pn同叶片中Rubsico活性有关.杂种F1的比较中,在表观量子效率(ψ)、羧化效率(CE)、CO2补偿点(T)等方面,籼粳亚种间杂种F1(绵恢725/Kitaake、蜀恢527/Kitaake、蜀恢881/Kitaake)对2个亚种内杂种F1香大粒/Kitaake(粳爪交)、Lemont/Kitaake(不同生态型的粳粳交,美国稻属于特殊粳稻)具有明显的优势,而蜀恢881含有粳型血缘,蜀恢881/Kitaake也比典型籼粳亚种间杂种F1绵恢725/Kitaake、蜀恢527/Kitaake优势稍逊一筹.5个杂种F1因为具有不同的遗传差异而表现出不同的光合优势,在这方面,典型籼粳亚种间杂交蜀恢527/Kitaake、绵恢725/Kitaake要优于其他杂交种,说明亲本间遗传差异越大,其杂种F1的光合优势越强.     

沙棘果皮多糖清除氧自由基的活性研究

沙棘(Hippophae rhamnosides)果皮经80℃恒温水浴提取,乙醇沉淀得粗多糖.Sevag法去蛋白,经50%和70%乙醇分级,得3种级分沙棘多糖H1、H2和H3;以Fenton反应,即H2O2/Fe2 /水杨酸为·OH产生和检测体系;以邻苯三酚/EDTA/Tris-HCl为O2-.产生体系,对沙棘多糖H1、H2和H3进行抗氧自由基活性研究.结果表明,沙棘多糖对·OH和O2-.有较显著的清除能力.不同级分多糖H1、H2和H3浓度达200μg·mL-1时,对·OH的清除率分别为44.9%、49.0%和26.4%,抗O2-.活性分别为36.9%,15.4%和23.1%.多糖质量浓度增大时,两种自由基清除率增加,且呈量效关系.     

遮光处理对节瓜光合作用特性的影响

在塑料大棚内设置不同光照强度处理[自然光(对照)、遮光40%和遮光60%],研究遮光处理对节瓜(Benincasa hispida Cogn. var. chieh-qua How.)功能叶片光合特性的影响,结果表明节瓜叶片净光合速率(Pn)日变化呈单峰曲线,各处理在11:00达到峰值.节瓜Pn峰值随光照强度的减小而降低,叶片Pn达到峰值之前随遮光程度的增大而降低,而达到峰值之后,遮光40%处理的节瓜叶片Pn比对照高.叶片Pn的日变化幅度随遮光程度的增强而减小,叶片的光饱和点随光照强度的减小而明显降低.结果说明遮光处理通过影响环境因子和节瓜叶片生理特性等内在因素而影响其光合作用.塑料大棚内中午前后用遮光强度适宜的遮阳网覆盖,可提高节瓜功能叶片的光合能力,有利于提高产量.