The first chromosome‐level genome for a marine mammal as a resource to study ecology and evolution

Marine mammals are important models for studying convergent evolution and aquatic adaption, and thus reference genomes of marine mammals can provide evolutionary insights. Here, we present the first chromosome‐level marine mammal genome assembly based on the data generated by the BGISEQ‐500 platform, for a stranded female sperm whale (Physeter macrocephalus). Using this reference genome, we performed chromosome evolution analysis of the sperm whale, including constructing ancestral chromosomes, identifying chromosome rearrangement events and comparing with cattle chromosomes, which provides a resource for exploring marine mammal adaptation and speciation. We detected a high proportion of long interspersed nuclear elements and expanded gene families, and contraction of major histocompatibility complex region genes which were specific to sperm whale. Using comparisons with sheep and cattle, we analysed positively selected genes to identify gene pathways that may be related to adaptation to the marine environment. Further, we identified possible convergent evolution in aquatic mammals by testing for positively selected genes across three orders of marine mammals. In addition, we used publicly available resequencing data to confirm a rapid decline in global population size in the Pliocene to Pleistocene transition. This study sheds light on the chromosome evolution and genetic mechanisms underpinning sperm whale adaptations, providing valuable resources for future comparative genomics.     

An update of the suicide plasmid-mediated genome editing system in Corynebacterium glutamicum

Corynebacterium glutamicum is an important industrial microorganism, but the availability of tools for its genetic modification has lagged compared to other model microorganisms such as Escherichia coli. Despite great progress in CRISPR-based technologies, the most feasible genome editing method in C. glutamicum is suicide plasmid-mediated, the editing efficiency of which is low due to high false-positive rates of sacB counter selection, and the requirement for tedious two-round selection and verification of rare double-cross-over events. In this study, an rpsL mutant conferring streptomycin resistance was harnessed for counter selection, significantly increasing the positive selection rate. More importantly, with the aid of high selection efficiencies through the use of antibiotics, namely kanamycin and streptomycin, the two-step verification strategy can be simplified to just one-step verification of the final edited strain. As proof of concept, a 2.5-kb DNA fragment comprising aroG^fbrpheA^fbr expressing cassettes was integrated into the genome of C. glutamicum, with an efficiency of 20% out of the theoretical 50%. The resulting strain produced 110 mg l⁻¹ l -tyrosine in shake-flask fermentation. This updated suicide plasmid-mediated genome editing system will greatly facilitate genetic manipulations including single nucleotide mutation, gene deletion and gene insertion in C. glutamicum and can be easily applied to other microbes.     

Polymodal Nociception in Drosophila Requires Alternative Splicing of TrpA1

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全膜双垄沟播玉米耗水特性和籽粒产量对不同氮素形态配比的响应

为优化陇中干旱、半干旱地区全膜双垄沟播玉米的氮肥运筹,提高玉米籽粒产量,通过大田试验,研究了不同氮素形态配比(NO₃^--N/NH₄⁺-N)[N₁(1∶0)、N₂(1∶1)、N₃(1∶3)、N₄(3∶1)]对旱地全膜双垄沟播玉米耗水特性、产量和水分利用效率的影响.结果表明: 不同氮素形态配比显著影响玉米0～200 cm土层的土壤贮水量,且N₄处理土壤贮水量最低.N₄处理农田总耗水量最高,较N₁、N₂、N₃分别显著增加了2.9%、1.9%、0.9%(2015)和2.3%、1.4%、2.2%(2017).玉米籽粒产量和水分利用效率(WUE)在3个生长季均表现为N₄处理最高,籽粒产量较其他处理分别高出3.3%～9.9%(2015)、3.5%～24.2%(2016)和8.3%～36.1%(2017),WUE则较其他处理分别高出1.6%～6.8%、4.9%～21.8%和6.6%～32.9%.N₄处理下玉米的氮肥偏生产力显著高于其他处理,然后依次为N₃、N₂和N₁.综合考虑,NO₃^--N/NH₄⁺-N=3∶1是适宜陇中干旱、半干旱地区全膜双垄沟播玉米增产的氮肥运筹措施.     

Photoacoustic assessment of hemodynamic changes in foot vessels

Monitoring the blood supply in the lower extremities is critical for individuals who are vulnerable to vascular dysfunction. Current clinical approaches are ineffective in observing hemodynamic changes in peripheral vessels. In this paper, we investigate the potential of photoacoustic tomography (PAT) as an alternative way to in vivo monitor hemodynamic changes in foot vessels. High spatial and temporal resolution maps of hemoglobin in major arteries and veins are shown. Results from twelve human subjects are presented here to visualize vascular perfusion of healthy volunteers in two age groups (young vs aged). Significant differences between the two groups are observed and verify the declining in vascular function with aging, highlighting the potential of PAT as a new tool to evaluate vascular function in the lower extremities.      

CAR-T联合疗法治疗实体瘤的研究进展

CAR-T疗法(chimeric antigen receptor T-cell immunotherapy)即嵌合抗原受体T细胞免疫疗法,是目前肿瘤免疫治疗中较有潜力的策略之一^[1],已成功应用于多种血液肿瘤的治疗。但CAR-T疗法在治疗实体瘤领域进展缓慢,存在肿瘤微环境的限制、细胞因子释放综合征以及严重的脱靶效应等诸多挑战^[2]。与单一靶向治疗相比,CAR-T联合疗法为改进肿瘤治疗方法提供了新的方向。综述目前常用的CAR-T联合治疗策略,针对CAR-T疗法在实体瘤治疗领域面临的主要挑战,探讨提高CAR-T疗效的潜在方案。