摘要：Chimeric antigen receptors(CARs) are artificial recombinant receptors that generally combine the antigen-recognition domain of a monoclonal antibody with T cell activation domains. Recent years have seen great success in clinical trials employing CD19-specific CAR-T cell therapy for B cell leukemia. Nevertheless, solid tumors remain a major challenge for CAR-T cell therapy. This review summarizes the preclinical and clinical studies on the treatment of solid tumors with CAR-T cells. The major hurdles for the success of CAR-T and the novel strategies to address these hurdles have also been described and discussed.

摘要：The effect of formulation variables on in-vitro release and permeation properties of carvedilol from transdermal patch was studied by varying one factor at a time as preliminary *** on these results,design of experiments technique was applied followed by regression analysis and response surface methodology to optimize formulation *** Composite IV model design was used with four formulation variables:drug loading,matrix thickness,adhesive layer thickness,and propylene glycol *** formulations were prepared according to the design;and the effect of formulation variables was studied on in-vitro release and permeation profiles of these *** all cases,the permeation profiles paralleled in-vitro release *** drug released at 7 h and 24 h was used as release response parameters while permeation flux obtained was employed as permeation response *** four formulation variables were found to be significant for release properties and three of these exhibited significant effect on permeation profile of carvedilol across artificial *** optimization,using 47.9%of cumulative carvedilol released at 7 h and 99.8%at 24 h as well as 25.7 mg/cm2/h of permeation flux,was applied to obtain desired release and permeation ***,carvedilol was observed to release from the optimized formulation with 51.4%drug release at 7 h and 98.5%at 24 h with an observed flux value of 27.4 mg/cm2/h across artificial membrane,which showed an excellent agreement with the predicted *** results of this investigation show that the quadratic mathematical model developed could be used to further predict formulations with desirable release and permeation properties.

摘要：The application of thermoelectric devices(TEDs)for personalized thermoregulation is attractive for saving energy while balancing the quality of *** that directly attach to human skin remarkably minimized the energy wasted for cooling the entire ***,facing the extreme dynamic geometry change and strain of human skin,conventional TEDs cannot align with the contour of our bodies for the best thermoregulation ***,we designed a kirigami-based wearable TED with excellent water vapor permeability,flexibility,and *** analysis and experimental results reveal that our product can withstand various types of large mechanical deformation without circuit *** stated outcome and proposed facile approach not only reinforce the development of wearable TEDs but also offer an innovative opportunity for different electronics that require high conformability.

摘要：Background： Smokeless tobacco is widely used by athletes to enhance performance. Nicotine is a central nervous system stimulant and acts on cardiocirculatory and metabolic systems, involving tissue blood flow and circulatory vasoreactivity. The aim of this study was to investigate the effects of the oral smokeless tobacco （Swedish snus （SS）） on the perception of fatigue and time to exhaustion （TTE） during moderate-intensity aerobic exercise. Methods： Fourteen healthy non-tobacco male users were recruited for a double-blind, controlled crossover design （SS vs. snus placebo （SP））. Subjects were tested for 3 sessions： experimental session 1 （Exp 1） consisted of an incremental test to determine the maximal aerobic power out-put （Wmax）, whereas Exp2 and Exp3 consisted of exercising at 65%Wmax until exhaustion in SS or SP conditions. During Exp2 and Exp3, muscle and cerebral oxygenation was assessed by means of near-infrared spectroscopy, and the rating of perceived exertion （RPE） was recorded. Results： Comparing SS with SP tests, significant differences （p 〈 0.05） were found in the values of cerebral （-3%） and muscular tissues oxygenation （-4%） in the first 30 min of exercise. The RPE values were not significantly different between the 2 conditions （SS vs. SP）. No significant difference was found in TTE （SS： 54.25 ± 21.84 min; SP： 50.01 ± 17.03 min）. Conclusion： This study showed that muscular and cerebral oxygenation increased significantly with snus administration during an endurance exercise until exhaustion, but this did not affect fatigue perception and TTE. The results showed that snus could not be considered an ergogenic substance in non-tobacco users.2018 Published by Elsevier B.V. on behalf of Shanghai University of Sport. This is an open access article under the CC BY-NC-ND license. （http：//***/licenses/by-nc-nd/4.0/）.

摘要：Herein,we report a geometrically well-defined prism assembled by two floxuridine(F)integrated RNA strands as a precise nanomedicine for chemodrug *** to the similarity between chemotherapeutic F and uridine(U),all uridines in the component RNA strands are replaced by F during their in vitro transcription *** specifically designing their sequences,F-containing S-shape tiles with the single-stranded loops are constructed and then further assemble into the RNA prism through T-junction interactions and sticky-end *** present study demonstrates that the F-integrated RNA prism can serve as an efficient platform for chemodrug delivery and anticancer *** believe that the study would help the future development of RNA-based nanomedicine in various applications.

摘要：Scaffolds play a crucial role in tissue engineering. Biodegradable polymers with great processing flexibility are the predominant scaffolding materials. Synthetic biodegradable polymers with well-defined structure and without immunological concerns associated with naturally derived polymers are widely used in tissue engineering. The synthetic biodegradable polymers that are widely used in tissue engineering, including polyesters, polyanhydrides, polyphosphazenes, polyurethane, and poly(glycerol sebacate) are summarized in this article. New developments in conducting polymers, photoresponsive polymers, amino-acid-based polymers, enzymatically degradable polymers, and peptide-activated polymers are also discussed. In addition to chemical functionalization, the scaffold designs that mimic the nano and micro features of the extracellular matrix(ECM) are presented as well, and composite and nanocomposite scaffolds are also reviewed.

摘要：We report the development of a metastasis-on-a-chip platform to model and track hepatocellular carcinoma(HCC)-bone metastasis and to analyze the inhibitory effect of an herb-based compound,thymoquinone(TQ),in hindering the migration of liver cancer cells into the bone *** bioreactor consisted of two chambers,one accommodating encapsulated HepG2 cells and one bone-mimetic niche containing hydroxyapatite(HAp).Above these chambers,amicroporous membrane was placed to resemble the vascular barrier,where medium was circulated over the *** was observed that the liver cancer cells proliferated inside the tumor microtissue and disseminated from the HCC chamber to the circulatory flow and eventually entered the bone *** number of metastatic HepG2 cells to the bone compartment was remarkably higher in the presence of HAp in the *** was then used as ametastasis-controlling agent in both free form and encapsulated nanoparticles,to analyze its suppressing effect on HCC *** indicated that the nanoparticle-encapsulated TQ provided a longer period of inhibitory *** summary,HCC-bone metastasis-on-a-chip platform was demonstrated to model certain key aspects of the cancer metastasis process,hence corroborating the potential of enabling investigations on metastasis-associated biology as well as improved anti-metastatic drug screening.

摘要：The three-dimensional (3D)bioprinting technology has progressed tremendously over the past *** controlling the size, shape,and architecture of the bioprinted constructs,3D bioprinting allows for the fabrication of tissue/organ-like constructs with strong structural-functional similarity with their in vivo counterparts at high *** bioink,a blend of biomaterials and living cells possessing both high biocompatibility and printability,is a critical component of *** particular, gelatin methacryloyl (GelMA)has shown its potential as a viable bioink material due to its suitable biocompatibility and readily tunable physicochemical *** GelMA-based bioinks and relevant bioprinting strategies for GelMA bioprinting are briefly reviewed.

摘要：Craniosynostosis is a rare disease in which one or more of the cranial sutures in an infant skull prematurely fuses by turning into bone,with a prevalence of 1 in 2,000—2,500 individuals from reports in Western countries(Wilkie et al.,2017).It may restrict the growth of the brain,leading to some degree of morphological and functional abnormalities,and may affect the neurocognitive function of infants(Lattanzi et al.,2017).Genetic variants underlying craniosynostosis have been identified in cohort studies in Western populations.

摘要：The quest for low‐cost yet efficient non‐Pt electrocatalysts for the oxygen reduction reaction(ORR)has become one of the main focuses of research in the field of catalysis,which has implications for the development of the next generation of greener fuel ***,we comprehensively describe the'big picture'of recent advances made in the rational design of ORR electrocatalysts,including molecule‐based,metal‐oxide‐based,metal‐nanomaterial‐based and two‐dimensional *** metals can fabricate molecular electrocatalysts with N4‐macrocycles such as porphyrin‐class compounds and the so‐formed M-N-C active centre plays a crucial role in determining the catalytic performances towards the ***‐IV and‐V Transition metal oxides represent another class of promising alternative of Pt‐based catalysts for the ORR which catalytic activity largely depends on the surface structure and the introduction of surface *** advances in synthesis of metallic nanoparticles(NPs)allow for precise control over particle sizes and shapes and the crystalline facets exposed to enhance the ORR performance of ***‐dimensional materials such as functionalized grapheme or MoS2are emerging as novel electrocatalysts for the *** review covers various aspects towards the design of future ORR electrocatalysts,including the catalytic performance,stability,durability and *** novel electrocatalysts even surpass commercial Pt/C systems,demonstrating their potential to be alternatives in industrial *** the encouraging progress,challenges,which are also described,remain to be overcome before the real‐world application of novel ORR electrocatalysts.