A durable 4-1BB-based CD19 CAR-T cell for treatment of relapsed or refractory non-Hodgkin lymphoma

Objective:Previous studies reported that 4-1BB-based CD19 chimeric antigen receptor(CAR)-T cells were more beneficial for the clinical outcomes than CD28-based CAR-T cells,especially the lower incidence rate of severe adverse events.However,the median progression-free survival(mPFS)of 4-1BB-based product Kymriah was shorter than that of CD28-based Yescarta(2.9 months vs.5.9 months),suggesting that Kymriah was limited in the long-term efficacy.Thus,a safe and durable 4-1BB-based CD19 CAR-T needs to be developed.Methods:We designed a CD19-targeted CAR-T(named as IM19)which consisted of an FMC63 scFv,4-1BB and CD3ζintracellular domain and was manufactured into a memory T-enriched formulation.A phase I/II clinical trial was launched to evaluate the clinical outcomes of IM19 in relapsed or refractory(r/r)B cell non-Hodgkin lymphoma(B-NHL).Dose-escalation investigation(at a dose of 5×10^(5)/kg,1×10^(6)/kg and 3×106/kg)was performed in 22 r/r B-NHL patients.All patients received a single infusion of IM19 after 3-day conditional regimen.Results:At month 3,the overall response rate(ORR)was 59.1%,the complete response rate(CRR)was 50.0%.The mPFS was 6 months and the 1-year overall survival rate was 77.8%.Cytokine release syndrome(CRS)occurred in 13 patients(59.1%),with 54.5%of grade 1−2 CRS.Only one patient(4.5%)experienced grade 3 CRS and grade 3 neurotoxicity.Conclusions:These results demonstrated the safety and durable efficacy of a 4-1BB-based CD19 CAR-T,IM19,which is promising for further development and clinical investigation.

Influence of superior cervical ganglionectomy on hippocampal neurogenesis and learning and memory in adult rats

BACKGROUND： Studies have shown that neurogenesis in the dentate gyrus plays an important role in learning and memory. However, studies have not determined whether the superior cervical ganglion or the sympathetic nerve system influences hippocampal neurogenesis or learning and memory in adult rats. OBJECTIVE： To observe differences in dentate gyrus neurogenesis, as well as learning and memory, in adult rats following superior cervical ganglionectomy. DESIGN, TIME AND SETTING： A randomized, controlled, animal study was performed at the Immunohistochemistry Laboratory of the School of Life Sciences in Lanzhou University from July 2006 to July 2007. MATERIALS： Doublecortin polyclonal antibody was provided by Santa Cruz Biotechnology, USA; avidin-biotin-peroxidase complex was purchased from Zhongshan Goldenbride Biotechnology, China; Morris water maze was bought from Taimeng Technology, China. METHODS： A total of 20 adult, male, Wistar rats were randomly divided into surgery and control groups, with 10 rats in each group. In the surgery group, the bilateral superior cervical ganglions were transected. In the control group, the superior cervical ganglions were only exposed, but no ganglionectomy was performed. MAIN OUTCOME MEASURES： To examine distribution, morphology, and number of newborn neurons in the dentate gyrus using doublecortin immunohistochemistry at 36 days following surgical procedures. To examine ability of learning and memory in adult rats using the Morris water maze at 30 days following surgical procedures. RESULTS： Doublecortin immunohistochemical results showed that a reduction in the number of doublecortin-positive neurons in the surgery group compared to the control group （P 〈 0.05）, while the distribution of doublecortin-positive neurons was identical in the two groups. The surgery group exhibited significantly worse performance in learning and spatial memory tasks compared to the control group （P 〈 0.05）. CONCLUSION： Superior cervical ganglienectomy inhibited neurogenesis in the dentate gyrus and decreased learning and memory abilities in adult rats.

Interfacial engineering of atomic platinum-doped molybdenum carbide quantum dots for high-rate and stable hydrogen evolution reaction in proton exchange membrane water electrolysis

Platinum(Pt)-based electrocatalysts remain the only practical cathode catalysts for proton exchange membrane water electrolysis(PEMWE),due to their excellent catalytic activity for acidic hydrogen evolution reaction(HER),but are greatly limited by their low reserves and high cost.Here,we report an interfacial engineering strategy to obtain a promising low-Pt loading catalyst with atomically Pt-doped molybdenum carbide quantum dots decorated on conductive porous carbon(Pt-MoCx@C)for high-rate and stable HER in PEMWE.Benefiting from the strong interfacial interaction between Pt atoms and the ultra-small MoCx quantum dots substrate,the Pt-MoCx catalyst exhibits a high mass activity of 8.00 A·mgPt−1,5.6 times higher than that of commercial 20 wt.%Pt/C catalyst.Moreover,the strong interfacial coupling of Pt and MoCx substrate greatly improves the HER stability of the Pt-MoCx catalyst.Density functional theory studies further confirm the strong metal-support interaction on Pt-MoCx,the critical role of MoCx substrate in the stabilization of surface Pt atoms,as well as activation of MoCx substrate by Pt atoms for improving HER durability and activity.The optimized Pt-MoCx@C catalyst demonstrates>2000 h stability under a water-splitting current of 1000 mA·cm^(−2)when applied to the cathode of a PEM water electrolyzer,suggesting the potential for practical applications.

“人体解剖及动物生理学实验”教学中科教融合理念的强化与运用

高等教育承担着人才培养的重大任务。教学和科研是高等学校不可或缺的两大职能,在当前的教育教学中,两者的关系存在失衡、融合度低等问题。本文从人体解剖及动物生理学实验及教学已存在的问题出发,主要从应用科研思政教育提高学生认知能力、结合科研实践开发实验项目、加强课堂教学与科研实践的结合等方面进行探索,树立科教融合发展的基本理念,实现高素质创新人才的培养目标。

Co-delivery of doxorubicin and quercetin via mPEG-PLGA copolymer assembly for synergistic anti-tumor efficacy and reducing cardio-toxicity

橡黄素(Que ) 是自然多功能的 bioflavonoid，并且为减少不利副作用并且提高化学疗法的药的反肿瘤功效显示出大潜力。然而，它的临床的申请在生理的系统由于很低的溶解度和结构的不稳定性被限制。此处，我们共同交付由开发 amphiphilic 聚合物包括的 biocompatible nanocarrier 的恐水病的橡黄素和吸水的 doxorubicin (纪录影片) ， methoxy poly (乙烯乙二醇) 并且 poly (D， L-lactide-co-glycolide ) 分别地。反肿瘤和这个系统的预防功效被评估在细胞并且动物模型。我们说明的调查结果 Dox-Que nanoparticulate 明确的表达保护了正常脉管的 endothelial 房间免受免费的任何一个或 nanoparticulate 的伤害导致 doxorubicin 的 cytotoxicity 和增加的癌症房间死亡。与免费 doxorubicin 和它的 nanoformulation 相比，用我们的 nanosystem 的橡黄素和 doxorubicin 的合作交货 synergistically 禁止了肿瘤生长，当在浆液维持心脏的功能指示物的正常层次并且在心织物恢复组织病理学说的损坏时。这研究为提高反癌症药功效并且减少 nanoparticulate 表明有希望的策略正常纸巾上的导致化疗的毒性。

Anatomical and histological characteristic of the tongue and tongue mucosa linguae in the cattle-yak （Bos taurus × Bos grunniens）

This study presents the first definitive anatomical description of the tongue and lingual papillae of the cattleyak. Data on tongues from 12 healthy cattle-yaks were collected. The results show that five types of papillae were identifiable on the tongue surface of the cattle-yak. Among these, three types were mechanical papillae （filiform, conical, and lenticular）, and two types were gustatory papillae （vallate and fungiform）. Some morphological features of the cattle-yak tongue were similar to those of domestic ruminants, but the lingual prominence was higher and more developed. For example, more mechanical papillae were present and they were covered by a thicker, keratinized epithelium, the conical papillae possibly perform an immune function, the fungiform papillae have more mucus- secreting pores, and the sublingual glands were more developed. This research will provide a further and detailed source of morphological information about the cattle-yak that is currently lacking in species-specific studies on the morphology of the Bovidae family.