Adaptive T cell immunotherapy in cancer

Impaired tumor-specific effector T cells contribute to tumor progression and unfavorable clinical outcomes. As a compensatory T cell-dependent cancer immunoediting strategy, adoptive T cell therapy(ACT) has achieved encouraging therapeutic results,and this strategy is now on the center stage of cancer treatment and research. ACT involves the ex vivo stimulation and expansion of tumor-infiltrating lymphocytes(TILs) with inherent tumor reactivity or T cells that have been genetically modified to express the cognate chimeric antigen receptor or T cell receptor(CAR/TCR), followed by the passive transfer of these cells into a lymphodepleted host. Primed T cells must provide highly efficient and long-lasting immune defense against transformed cells during ACT. Anin-depth understanding of the basic mechanisms of these living drugs can help us improve upon current strategies and design better next-generation T cell-based immunotherapies. From this perspective, we provide an overview of current developments in different ACT strategies, with a focus on frontier clinical trials that offer a proof of principle. Meanwhile, insights into the determinants of ACT are discussed, which will lead to more rational, potent and widespread applications in the future.     

A practical guide to amplicon and metagenomic analysis of microbiome data

Advances in high-throughput sequencing(HTS)have fostered rapid developments in the field of microbiome research,and massive microbiome datasets are now being generated.However,the diversity of software tools and the complexity of analysis pipelines make it difficult to access this field.Here,we systematically summarize the advantages and limitations of micro-biome methods.Then,we recommend specific pipelines for amplicon and metagenomic analyses,and describe commonly-used software and databases,to help researchers select the appropriate tools.Furthermore,we introduce statistical and visualization methods suit-able for microbiome analysis,including alpha-and beta-diversity,taxonomic composition,difference compar-isons,correlation,networks,machine learning,evolu-tion,source tracing,and common visualization styles to help researchers make informed choices.Finally,a step-by-step reproducible analysis guide is introduced.We hope this review will allow researchers to carry out data analysis more effectively and to quickly select the appropriate tools in order to efficiently mine the bio-logical significance behind the data.     

Altered sperm tsRNAs in aged male contribute to anxiety‐like behavior in offspring

Parental age at first pregnancy is increasing worldwide. The offspring of aged father has been associated with higher risk of several neuropsychiatric disorders, such as schizophrenia and autism, but the underlying mechanism remains elusive. Here we report that advanced paternal age in mice alters the profile of transfer RNA‐derived small RNAs (tsRNAs). Injection of sperm tsRNAs from aged male mice into zygotes induced anxiety‐like behaviors in F1 males. RNA sequencing of the cerebral cortex and hippocampus of those F1 male mice altered the gene expression of dopaminergic synapse and neurotrophin. tsRNAs from aged male mice injection also altered the neuropsychiatry‐related gene expression in two‐cell and blastocyst stage embryos. More importantly, the sperm tsRNA profile changes significantly during aging in human. The up‐regulated sperm tsRNA target genes were involved in neurogenesis and nervous system development. These results suggest that aging‐related changes of sperm tsRNA may contribute to the intergenerational transmission of behavioral traits.     

From signaling to function: how strigolactones regulate plant development

Science China Life Sciences -     

Allotransplantation of adult spinal cord tissues after complete transected spinal cord injury: Long-term survival and functional recovery in canines

Science China Life Sciences - Spinal cord injury (SCI), especially complete transected SCI, leads to loss of cells and extracellular matrix and functional impairments. In a previous study, we...     

MicroRNA‐29b‐3p suppresses oral squamous cell carcinoma cell migration and invasion via IL32/AKT signalling pathway

Oral squamous cell carcinoma (OSCC) is aggressive accompanied with poor prognosis. We previously isolated the most invasive cells resembling the invasive tumour front by microfluidic technology and explored their differentially expressed microRNAs (miRNAs) in our previous work. Here, we verified the miR‐29b‐3p as a guarder that suppressed migration and invasion of OSCC cells and was down‐regulated in the most invasive cells. Besides that, the invasion suppression role of miR‐29b‐3p was achieved through the IL32/AKT pathway. Thus, miR‐29b‐3p and IL32 might serve as therapeutic targets for blocking the progression and improving the outcome of OSCC.     

In vitro and in vivo efficacy of anti‐chikungunya virus monoclonal antibodies produced in wild‐type and glycoengineered Nicotiana benthamiana plants

Chikungunya virus (CHIKV) is a mosquito‐transmitted alphavirus, and its infection can cause long‐term debilitating arthritis in humans. Currently, there are no licensed vaccines or therapeutics for human use to combat CHIKV infections. In this study, we explored the feasibility of using an anti‐CHIKV monoclonal antibody (mAb) produced in wild‐type (WT) and glycoengineered (?XFT) Nicotiana benthamiana plants in treating CHIKV infection in a mouse model. CHIKV mAb was efficiently expressed and assembled in plant leaves and enriched to homogeneity by a simple purification scheme. While mAb produced in ?XFT carried a single N‐glycan species at the Fc domain, namely GnGn structures, WT produced mAb exhibited a mixture of N‐glycans including the typical plant GnGnXF₃ glycans, accompanied by incompletely processed and oligomannosidic structures. Both WT and ?XFT plant‐produced mAbs demonstrated potent in vitro neutralization activity against CHIKV. Notably, both mAb glycoforms showed in vivo efficacy in a mouse model, with a slight increased efficacy by the ?XFT‐produced mAbs. This is the first report of the efficacy of plant‐produced mAbs against CHIKV, which demonstrates the ability of using plants as an effective platform for production of functionally active CHIKV mAbs and implies optimization of in vivo activity by controlling Fc glycosylation.     

The complete mitochondrial genomes of largemouth bass of the northern subspecies (Micropterus salmoides salmoides) and Florida subspecies (Micropterus salmoides floridanus) and their applications in the identification of largemouth bass species

The largemouth bass belongs to the family Centrarchidae, which includes two subspecies: the northern subspecies, Micropterus salmoides salmoides, and the Florida subspecies, Micropterus salmoides floridanus. In this study, the complete mitochondrial genomes of the two subspecies were sequenced, and their genetic differences were identified. The mitogenomes of M. s. salmoides and M. s. floridanus are 16,486 and 16,479?bp in length, respectively. The two subspecies consisted of 37 genes (13 protein-coding genes, 2 ribosomal RNA, and 22 transfer RNA), which are typical for vertebrate mtDNA. Phylogenetic analysis provided statistical support for the monophyly of the family Centrarchidae. Comparison of the two subspecies' mitogenomes revealed a relatively high number (450) of single nucleotide polymorphisms (SNPs) in protein-coding genes. We characterized SNPs in the partial cytochrome c oxidase subunit 1 gene of different individuals from three cultured populations, one wild northern subspecies population, and one wild Florida subspecies population. Twenty-eight SNPs were fixed with alternative nucleotides in the two subspecies, which could be used for differentiating them. Based on this gene, phylogenetic tree and genetic distance analyses supported that cultured largemouth bass in China belongs to the northern subspecies.     

Contrasting hypoxia tolerance and adaptation in Malus species is linked to differences in stomatal behavior and photosynthesis

We examined the potential differences in tolerance to hypoxia by two species of apple rootstocks. Stomatal behavior and photosynthesis were compared between Malus sieversii and Malus hupehensis. Plants were hydroponically grown for 15 days in normoxic or hypoxic nutrient solutions. Those of M. sieversii showed much greater sensitivity, with exposure to hypoxia resulting in higher leaf concentrations of abscisic acid (ABA) that prompted stomatal closure. Compared with the control plants of that species, stomatal density was greater in both new and mature leaves under stress conditions. In contrast, stomatal density was significantly decreased in leaves from M. hupehensis, while stomatal length was unaffected. Under stress, the net photosynthetic rate, stomatal conductance and chlorophyll contents were markedly reduced in M. sieversii. The relatively hypoxia‐tolerant genotype M. hupehensis, however, showed only minor changes in net photosynthesis or chlorophyll content, and only a slight decrease in stomatal conductance due to such treatment. Therefore, we conclude that the more tolerant M. hupehensis utilizes a better protective mechanism for retaining higher photosynthetic capacity than does the hypoxia‐sensitive M. sieversii. Moreover, this contrast in tolerance and adaptation to stress is linked to differences in their stomatal behavior, photosynthetic capacity and possibly their patterns of native distribution.