Springer Science and Business Media LLC

Gastric cancer imposes a considerable health burden worldwide, and its mortality ranks as the second highest for all types of cancers. The limited knowledge of the molecular mechanisms underlying gastric cancer tumorigenesis hinders the development of therapeutic strategies. However, ongoing collaborative sequencing efforts facilitate molecular classification and unveil the genomic landscape of gastric cancer. Several new drivers and tumorigenic pathways in gastric cancer, including chromatin remodeling genes, RhoA-related pathways, TP53 dysregulation, activation of receptor tyrosine kinases, stem cell pathways and abnormal DNA methylation, have been revealed. These newly identified genomic alterations await translation into clinical diagnosis and targeted therapies. Considering that loss-of-function mutations are intractable, synthetic lethality could be employed when discussing feasible therapeutic strategies. Although many challenges remain to be tackled, we are optimistic regarding improvements in the prognosis and treatment of gastric cancer in the near future.

CD19 chimeric antigen receptor (CAR) T cells have shown robust efficacy in relapsed and refractory acute lymphoblastic leukemia (R/R ALL), but compromising result in chronic lymphoblastic leukemia (CLL) and non-Hodgkin’s lymphoma (NHL). CD19 relapse and the lack of CAR-T cell persistence which result in treatment failure are considerable obstacles to overcome. CAR-T targeting CD20 is an option for salvaging CD19 CAR-T failure. Previous studies have established variant structures of bispecific CAR-T which could avoid antigen-loss and immune escape. Here, we constructed tandem and loop CAR structures targeting both CD19 and CD20 antigen. Bispecific CAR-T cells could eliminate either CD19 or CD20 negative lymphoma cells, suggesting they exhibited dual antigen targeting of CD19 and CD20. By comparing the efficiency of four bispecific CAR modified T cells, it was found that loop2019 CAR was the best structure among them to eradicate lymphoma cell lines and patients’ primary lymphoma or CLL cells in a very low dose in vitro and prolong the survival time dramatically in lymphoma xenograft mice model. These data highlighted the potential of loop2019 CAR-T in clinical treatment.

Bacteria need a high degree of genetic stability to maintain their species identities over long evolutionary times while retaining some mutability to adapt to the changing environment. It is a long unanswered question that how bacteria reconcile these seemingly contradictory biological properties. We hypothesized that certain mechanisms must maintain a dynamic balance between genetic stability and mutability for the survival and evolution of bacterial species. To identify such mechanisms, we analyzed bacterial genomes, focusing on the Salmonella mismatch repair (MMR) system. We found that the MMR gene mutL functions as a genetic switch through a slipped-strand mispairing mechanism, modulating and maintaining a dynamic balance between genetic stability and mutability during bacterial evolution. This mechanism allows bacteria to maintain their phylogenetic status, while also adapting to changing environments by acquiring novel traits. In this review, we outline the history of research into this genetic switch, from its discovery to the latest findings, and discuss its potential roles in the genomic evolution of bacteria.

Microarray and deep sequencing technologies have provided unprecedented opportunities for mapping genome mutations, RNA transcripts, transcription factor binding, and histone modifications at high resolution at the genome-wide level. This has revolutionized the way in which transcriptomes, regulatory networks and epigenetic regulations have been studied and large amounts of heterogeneous data have been generated. Although efforts are being made to integrate these datasets unbiasedly and efficiently, how best to do this still remains a challenge. Here we review major impacts of high-throughput genome-wide data generation, their relevance to human diseases, and various bioinformatics approaches for data integration. Finally, we provide a case study on inflammatory diseases.

Growing evidences show a direct link between diarrhea and disorders of gut microbiota in pigs. However, whether there are microbial markers associated with post-weaning diarrhea remains unknown. In the current study, we compared the microbial community, functions and metabolites between healthy weaned piglets (group H, n=7) and piglets with post-weaning diarrhea (group D, n=7), in order to find out diarrhea associated microbial markers. Each of 7 fecal samples was collected from H and D piglets (weaned at 21 d and sampled at 26 d). The metagenomic and untargeted metabolomic analysis revealed that the microbial composition, function and metabolic profile in D pigs was considerably reshaped, including the reduced abundance and number of Bacteroides, which significantly correlated with the diarrhea status of host. The carbohydrate metabolism, biosynthesis and metabolism, lipid metabolism, amino acid metabolism, and the activity of glycan and carbohydrates digestion related enzymes showed extensively down-regulated in D pigs compared with H pigs. Diarrhea significantly changed the metabolic profiles of fecal microbiota, and most of the altered metabolites were negatively or positively correlated with the change in the abundance of Bacteroides. In conclusion, the lower abundance of Bacteroides and its associated metabolic dysfunction may be regarded as microbial markers of physiological post-weaning diarrhea in piglets.