Induced pluripotent stem cell‐derived myeloid cells expressing OX40 ligand amplify antigen‐specific T cells in advanced melanoma

Immune checkpoint inhibitors improved the survival rate of patients with unresectable melanoma. However, some patients do not respond, and variable immune‐related adverse events have been reported. Therefore, more effective and antigen‐specific immune therapies are urgently needed. We previously reported the efficacy of an immune cell therapy with immortalized myeloid cells derived from induced pluripotent stem cells (iPS‐ML). In this study, we generated OX40L‐overexpressing iPS‐ML (iPS‐ML‐Zsgreen‐OX40L) and investigated their characteristics and in vivo efficacy against mouse melanoma. We found that iPS‐ML‐Zsgreen‐OX40L suppressed the progression of B16‐BL6 melanoma, and prolonged survival of mice with ovalbumin (OVA)‐expressing B16 melanoma (MO4). The number of antigen‐specific CD8⁺ T cells was higher in spleen cells treated with OVA peptide‐pulsed iPS‐ML‐Zsgreen‐OX40L than in those without OX40L. The OVA peptide‐pulsed iPS‐ML‐Zsgreen‐OX40L significantly increased the number of tumor‐infiltrating T lymphocytes (TILs) in MO4 tumor. Flow cytometry showed decreased regulatory T cells but increased effector and effector memory T cells among the TILs. Although we plan to use allogeneic iPS‐ML in the clinical applications, iPS‐ML showed the tumorgenicity in the syngeneic mice model. Incorporating the suicide gene is necessary to ensure the safety in the future study. Collectively, these results indicate that iPS‐ML‐Zsgreen‐OX40L therapy might be a new method for antigen‐specific cancer immunotherapy.     

Effect of woody plant expansion on decomposition of fine root mixtures in a grass-dominated temperate wetland

Wetlands Ecology and Management - Little is known about the effect of woody plant expansion on decomposition of root mixtures in grass-dominant temperate wetlands. Here, we collected fine roots...     

Cold and hungry: combined effects of low temperature and resource scarcity on an edge-of-range temperate primate,the golden snub-nose monkey

Both biotic and abiotic factors play important roles in influencing ecological distributions and niche limits. Where biotic and abiotic stressors co-occur in space and time, homeostatic systems face a scenario in which stressors can compound to impose a challenge that is greater than the sum of the separate factors. We studied the homeostatic strategies of the golden snub-nosed monkey Rhinopithecus roxellana, a species living in temperate deciduous forests at the edge of the global distribution range for folivorous primates, to cope with the co-occurrence of cold temperatures and resource scarcity during winter. We discovered that in winter the monkeys experience a dietary energy deficit of 101 kJ mbm⁻¹ d⁻¹ compared with calculated needs, despite increased feeding. This is partly offset by behavioral changes (reduced locomotion and increased resting) and reducing skin temperature by an average of 3.2°C through a cutaneous vasoconstriction to decrease heat loss. However, their major strategy is ingesting surplus energy and accumulating fat reserves when food was not limiting during summer and autumn. Their 14% of body mass lost over the winter represented an energy yield of 102 kJ mbm⁻¹ d⁻¹, which closely matched the calculated winter energy deficit of 101 kJ mbm⁻¹ d⁻¹. However, the latter value assumes that all the 75.41 kJ mbm⁻¹ d⁻¹ of protein ingested in winter was available for energy metabolism. This is almost certainly an over-estimate, suggesting that the study population was in negative energy balance over the study period. Our study therefore suggests that despite its suit of integrated homeostatic responses, the confluence of low temperatures and resource limitation during winter places this edge-of-range primate close the threshold of what is energetically viable. It also provides a framework for quantitative models predicting the vulnerability of temperate primates to global change.     

Glycine metabolomic changes induced by anticancer agents in A549 cells

Amino Acids - Glycine plays a key role in rapidly proliferating cancer cells such as A549 cells. Targeting glycine metabolism is considered as a potential means for cancer treatment. However, the...     

藏药“榜间”主流品种基原植物的潜在分布研究

“榜间”为常用大宗藏药,但其生境特殊,生态位狭窄,部分品种资源量小,甚至濒危。为了明确“榜间”原植物的生态环境,预测生态适宜区分布,寻找影响适宜性分布的主要生态因子,该文以大花龙胆(Gentiana szechenyii)、高山龙胆(G. algida)、蓝玉簪龙胆(G. veitchiorum)、华丽龙胆(G. sino-ornata)和短柄龙胆(G. stipitata)五个主流品种为研究对象,采用生态学调查方法进行实地调查,以分析各品种的分布特征和生境特点,并应用MaxEnt模型和ArcGIS软件,预测潜在分布区。结果表明:(1)“榜间”五个主流品种的生长均需要较好的土壤肥力条件,大花龙胆和短柄龙胆仅分布于草本层低矮的草甸或草甸灌丛,其余品种因茎有较大的伸长幅度,生态幅较广。(2)海拔是影响“榜间”五个主流品种分布的限制因子,对大花龙胆、高山龙胆、蓝玉簪龙胆、华丽龙胆和短柄龙胆生境适宜性的贡献率分别为56.5%、39.6%、49.4%、48.1%和44.2%,高山龙胆主要分布在海拔1 500 m以上的地区,而另外四个品种主要分布于海拔2 600 m以上的地区。(3)藏药“榜间”五个主流品种生长适宜区主要集中在四川、青海、云南、甘肃和西藏五省(区),但不同基原植物在各省(区)的分布面积和空间格局有差异,大花龙胆和高山龙胆的最适分布区集中在四川、甘肃、青海、西藏四省(区)交界处,后者在新疆地区也有最适分布区; 蓝玉簪龙胆最适生长区位于四川中部、四川北部接壤青海及甘肃处、四川西南部接壤云南处、西藏东部; 华丽龙胆与短柄龙胆最适生长区主要位于四川、青海、甘肃的交界地带,适生区范围较蓝玉簪龙胆狭窄。研究结果与实际调查结果基本相符,可以为“榜间”野生资源的保护及相关植物的人工栽培提供科学依据。     

施硼和赤霉素对‘李广杏’坐果率及果实品质的影响

该研究以8年生盛果期的‘李广杏’植株为试材,于花蕾膨大期喷施0.1%(P1)、0.3%(P2)和0.5%(P3)硼砂和盛花初期喷施50(C1)、100(C2)和150 mg/L(C3)赤霉素,测定不同处理下李广杏的坐果率、果实品质及营养生长指标的变化,并用主成分分析不同处理的效果进行综合评价,为敦煌寒旱区‘李广杏’的栽培提供理论依据。结果表明:(1)‘李广杏’叶面积增长量在C1浓度处理下显著高于CK,不同浓度的硼处理对其均具有抑制作用,但C1、P2浓度下新稍生长量高于其他处理。(2)适宜浓度的硼和赤霉素处理可一定程度减少‘李广杏’花的败育率,从而有效提高果树的坐果率,其中硼处理以P3浓度下最优,但P3与P2处理下坐果率无显著差异,赤霉素处理以C2浓度下最优。(3)适宜浓度硼和赤霉素能够明显提高‘李广杏’果实品质,C1浓度处理下的果实糖酸比、可溶性固形物含量显著高于CK,P2处理下的果实维生素C、可滴定酸含量显著高于其他处理;适宜浓度赤霉素和硼对果实的单果重、果形指数、侧径有明显的促进作用。(4)主成分分析结果显示,各处理效果的综合得分由高到低依次为P2(1.20)>C2(0.91)>P1(0.13)>C1(-1.01)>CK(-1.68)>P3(-2.13)>C3(-7.76);果实可溶性糖、可溶性蛋白、糖酸比等主成分占比较高,可作为评价‘李广杏’果实品质的重要依据。研究发现,花期喷施适宜浓度的硼和赤霉素可有效提高‘李广杏’果树的生长状况、坐果率及果实品质,且甘肃敦煌地区以花蕾膨大期喷施0.3%硼和盛花初期喷施100 mg/L赤霉素效果最佳。     

小麦TaCO9基因的克隆及功能分析

为了明确TaCO9-1A基因在小麦生长发育中的具体调控机理,该研究以同源克隆的方法成功获得了大麦(Hordeum vulgare)光周期基因HvCO9在小麦(Triticum aestivum)中的直系同源基因TaCO9,并对其进行生物信息学分析、亚细胞定位、转录激活以及表达模式分析;利用农杆菌侵染法转化拟南芥,并对过表达株系进行表型分析。结果表明:(1)TaCO9包含2个外显子和1个内含子,CDS区全长876 bp,编码291个氨基酸,蛋白序列含有特有的CCT结构域,且在不同物种间高度保守。(2)生物信息学分析表明,TaCO9基因编码的蛋白质分子量约为30.7 kD,等电点为6.24;TaCO9的启动子区含有光响应、激素应答和胁迫应答等多种顺式作用元件。(3)亚细胞定位和转录活性分析表明,TaCO9主要定位于细胞核中,且具有转录激活活性。(4)qRT-PCR结果表明,TaCO9基因在各个组织中均有表达,叶片中的表达量最高;在光照14 h条件下TaCO9的表达量显著高于光照10 h和12 h条件下的表达量,且TaCO9在大粒小麦‘西农817’子房与籽粒中的表达量显著高于‘中国春’。(5)经潮霉素筛选成功获得3个转基因拟南芥株系;进一步功能鉴定结果表明,过表达转TaCO9基因拟南芥植株的开花期迟于野生型(对照)3~4 d,但角果和籽粒较野生型大。     

大兴安岭泥炭地不同菌根类型木本植物叶片凋落物分解及其温度敏感性差异

以我国大兴安岭多年冻土区泥炭地常见的3种外生菌根木本植物(细叶沼柳Salix rosmarinifolia、白桦Betula platyphylla和柴桦B.fruticosa)和4种欧石楠菌根木本植物(笃斯越桔Vaccinium uliginosum、狭叶杜香Ledum palustre、甸杜Chamaedaphne calyculata和小叶杜鹃Rhododendron parrifolum)为研究对象,通过315天培养试验测定10和20℃叶片凋落物分解过程中的碳(C)累积矿化量和重量损失,并分析其温度敏感性。结果表明:外生菌根植物叶片凋落物的C矿化量和重量损失在10和20℃均高于欧石楠菌根植物;外生菌根植物凋落物分解过程中C矿化量的温度敏感性系数高于欧石楠菌根植物,但重量损失的温度敏感性系数低于欧石楠菌根植物;在每一培养温度下,C矿化量和重量损失均与凋落物全氮(N)和全磷(P)浓度呈正相关,与C/N和C/P呈负相关;尽管C矿化量的温度敏感性系数与凋落物初始化学组成无显著相关性,但重量损失的温度敏感性系数与凋落物全N和全P浓度呈负相关,与C/N和C/P呈正相关。本研究结果为认识和预测气候变暖及其引起的物种组成变化对北方泥炭地植物凋落物分解的影响提供理论依据。     

基于稳定氧同位素确定植物水分来源不同方法的比较

利用稳定同位素技术确定植物水分来源,对提高生态水文过程的认识和对干旱半干旱区的生态管理至关重要。目前基于稳定同位素技术确定植物水分来源的方法众多,但不同方法之间对比的研究较少。本研究基于原位样品采集,室内实验测试,利用直接对比法、多元线性混合模型(IsoSource)、贝叶斯混合模型(MixSIR、MixSIAR)和吸水深度模型分析植物水分来源,并对比各方法的优缺点。结果表明:相对于多元线性混合模型(IsoSource)而言,贝叶斯混合模型(MixSIR、MixSIAR)具有更好的水源区分性能,但对数据要求较高,且植物木质部水和潜在水源同位素组成的标准差越小,模型运行结果的可信度更高。本研究中贝叶斯混合模型(MixSIR)为最优解。在利用稳定氢氧同位素技术确定植物水分来源时,可先通过直接对比法定性判断植物可能利用的潜在水源,然后再用多元线性混合模型(IsoSource)、贝叶斯混合模型(MixSIR、MixSIAR)计算出各潜在水源对植物的贡献率和贡献范围,必要时可评估模型性能,选择出最优模型,定量分析植物的水分来源。若植物主要吸收利用不同土层深度的土壤水,可结合吸水深度模型计算出植物吸收土壤水的平均深度。本研究为干旱半干旱地区利用同位素技术确定植物水分来源方法的选择提供了理论依据。