Chinese expert consensus on Bruton tyrosine kinase inhibitors in the treatment of B-cell malignancies.

Targeted therapy with Bruton tyrosine kinase (BTK) inhibitors have revolutionized the treatment of patients with various B-cell malignancies. BTK inhibitors such as ibrutinib, zanubrutinib, orelabrutinib, and acalabrutinib have shown good clinical efficacy and better safety profiles than those of traditional chemotherapy and chemoimmunotherapy regimens. Multiple studies on new BTK inhibitors are ongoing, which may provide more therapeutic options for the treatment of B-cell malignancies. Considering the unmet need of evidence on BTK inhibitors in all clinical settings and to standardize the use of BTK inhibitors available in mainland China, Taiwan, Hong Kong, and Macau regions, this consensus has been formulated for the treatment of various B-cell malignancies based on the clinical practice and available evidences on the use of BTK inhibitors. The recommendations of this consensus will provide guidance to physicians and clinical researchers on the effective treatment of B-cell malignancies with BTK inhibitors.

Genome-Wide Analysis of the UGT Gene Family and Identification of Flavonoids in Broussonetia papyrifera.

Broussonetia papyrifera is a multifunctional deciduous tree that is both a food and a source of traditional Chinese medicine for both humans and animals. Further analysis of the UGT gene family is of great significance to the utilization of B. papyrifera. The substrates of plant UGT genes include highly diverse and complex chemicals, such as flavonoids and terpenes. In order to deepen our understanding of this family, a comprehensive analysis was performed. Phylogenetic analysis showed that 155 BpUGTs were divided into 15 subgroups. A conserved motif analysis showed that BpUGT proteins in the same subgroups possessed similar motif structures. Tandem duplication was the primary driving force for the expansion of the BpUGT gene family. The global promoter analysis indicated that they were associated with complex hormone regulatory networks and the stress response, as well as the synthesis of secondary metabolites. The expression pattern analysis showed that the expression level of BpUGTs in leaves and roots was higher than that in fruits and stems. Next, we determined the composition and content of flavonoids, the main products of the BpUGT reaction. A total of 19 compounds were isolated and analyzed by UPLC-ESI-MS/MS in 3 species of Broussonetia including B. kazinoki, B. papyrifera, and B. kazinoki × B. papyrifera, and the number of compounds was different in these 3 species. The total flavonoid content and antioxidant capacities of the three species were analyzed respectively. All assays exhibited the same trend: the hybrid paper mulberry showed a higher total flavonoid content, a higher total phenol content and higher antioxidant activity than the other two species. Overall, our study provides valuable information for understanding the function of BpUGTs in the biosynthesis of flavonoids.

Genome-Wide Identification of the TCP Gene Family in Broussonetia papyrifera and Functional Analysis of BpTCP8, 14 and 19 in Shoot Branching.

The plant-specific TCP family proteins play an important role in the processes of plant growth and development. Broussonetia papyrifera is a versatile perennial deciduous tree, and its genome data have been published. However, no comprehensive analysis of the TCP gene family in B. papyrifera has been undertaken. In this study, 20 BpTCP genes (BpTCPs) were identified in the B. papyrifera genome. Phylogenetic analysis divided BpTCPs into three subclades, the PCF subclade, the CIN subclade and the CYC/TB1 subclade. Gene structure analysis displayed that all BpTCPs except BpTCP19 contained one coding region. Conserved motif analysis showed that BpTCP proteins in the same subclade possessed similar motif structures. Segmental duplication was the primary driving force for the expansion of BpTCPs. Expression patterns showed that BpTCPs may play diverse biological functions in organ or tissue development. Transcriptional activation activity analysis of BpTCP8, BpTCP14 and BpTCP19 showed that they possessed transcriptional activation ability. The ectopic expression analysis in Arabidopsis wild-type and AtBRC1 ortholog mutant showed that BpTCP8, BpTCP14 and BpTCP19 could prevent rosette branch outgrowth. Collectively, our study not only established the first genome-wide analysis of the B. papyrifera TCP gene family, but also provided valuable information for understanding the function of BpTCPs in shoot branching.

Arabidopsis formin3 directs the formation of actin cables and polarized growth in pollen tubes.

Cytoplasmic actin cables are the most prominent actin structures in plant cells, but the molecular mechanism underlying their formation is unknown. The function of these actin cables, which are proposed to modulate cytoplasmic streaming and intracellular movement of many organelles in plants, has not been studied by genetic means. Here, we show that Arabidopsis thaliana formin3 (AFH3) is an actin nucleation factor responsible for the formation of longitudinal actin cables in pollen tubes. The Arabidopsis AFH3 gene encodes a 785-amino acid polypeptide, which contains a formin homology 1 (FH1) and a FH2 domain. In vitro analysis revealed that the AFH3 FH1FH2 domains interact with the barbed end of actin filaments and have actin nucleation activity in the presence of G-actin or G actin-profilin. Overexpression of AFH3 in tobacco (Nicotiana tabacum) pollen tubes induced excessive actin cables, which extended into the tubes' apices. Specific downregulation of AFH3 eliminated actin cables in Arabidopsis pollen tubes and reduced the level of actin polymers in pollen grains. This led to the disruption of the reverse fountain streaming pattern in pollen tubes, confirming a role for actin cables in the regulation of cytoplasmic streaming. Furthermore, these tubes became wide and short and swelled at their tips, suggesting that actin cables may regulate growth polarity in pollen tubes. Thus, AFH3 regulates the formation of actin cables, which are important for cytoplasmic streaming and polarized growth in pollen tubes.