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Cytochrome P450 (CYP) 4Z1 (CYP4Z1) has recently garnered much interest as its expression predicts a poor prognosis and as a oncogene in breast cancer, and overexpressed in other many cancers. We previously showed that CYP4Z1 acts as a promoter of cancer stem cells (CSCs) to facilitate the occurrence and development of breast cancer. Here, RNA sequencing found that 1‐benzylimidazole (1‐Benzy) held a preferable correlation with breast cancer and suppressed the expression of CSC makers. Further functional experiments, including mammary spheroid formation, wound‐healing, transwell‐invasion, detection of tumor initiation, and metastatic ability, showed that 1‐Benzy suppressed the stemness and metastasis of breast cancer cells. Additionally, we further demonstrated that CYP4Z1 is necessary for 1‐Benzy‐mediated suppression on breast cancer stemness and 1‐Benzy exerted a weaker effect in breast cancer cells with CYP4Z1 knockdown. Taken together, our data suggest that 1‐Benzy might be a potential drug suppressing breast cancer stemness via targeting CYP4Z1. [ABSTRACT FROM AUTHOR]

Cisplatin, a potent chemotherapy agent, is highly effective against various cancers but is hindered by resistance and toxicities. This study aims to investigate the roles of SLC7A11, a cystine/glutamate transporter, in cisplatin resistance, and explored Tanshinone IIA as a therapeutic option. Cisplatin reduced SLC7A11 in renal cells, worsening toxicity. Cisplatin‐resistant gastric cancer cells show increased SLC7A11, driving resistance, while SLC7A11 knockdown curbed resistance. Tanshinone IIA showed promise in alleviating cisplatin toxicity by enhancing SLC7A11 expression and reducing associated adverse effects, while it effectively reversed cisplatin resistance in gastric cancer cells by suppressing SLC7A11. Additionally, Tanshinone IIA counteracted cisplatin resistance by inhibiting PIAS4‐mediated SUMOylation of SLC7A11. Simultaneously, overexpressing miR‐375, which has been shown to target SLC7A11, exacerbated cisplatin toxicity via SLC7A11 downregulation, which Tanshinone IIA attenuates. In summary, our study unveils complex SLC7A11 regulation in cisplatin resistance and toxicity. Tanshinone IIA emerges as a promising modulator of SLC7A11 through individual pathways, offering novel insights into overcoming cisplatin resistance and reducing toxicities in cancer therapy. [ABSTRACT FROM AUTHOR]

Alpha‐2‐glycoprotein 1, zinc‐binding (AZGP1) is a secreted protein, which has been shown to be a potential biomarker of cancer progression; however, its roles in breast cancer are still unclear. Currently, we analyzed the online datasets and found that AZGP1 was highly expressed in breast cancer tissues and its expression was negatively correlated with the survival of breast cancer patients. Functional experiments through AZGP1 knockdown revealed that AZGP1 could promote the proliferation, migration, and invasion ability of breast cancer cells. In vivo experiments obtained a consistent result. Mechanistically, it was found that AZGP1 interacted with tripartite motif‐containing protein 25 (TRIM25), which subsequently promoted AZGP1 degradation through facilitating the ubiquitination. Furthermore, overexpression of TRIM25 partially reversed the promoting effects of AZGP1 overexpression on breast cancer progression. Therefore, this study indicates that AZGP1 might be a potential therapeutic target for breast cancer treatment. [ABSTRACT FROM AUTHOR]

This paper aims to explore how blockchain facilitates supply chain finance (SCF) platform business model reconfiguration. We conduct a case study on a typical Chinese SCF platform to address research questions and propose a blockchain-enabled SCF platform business model framework. The results show that (1) the reconfiguration of the SCF platform business model is driven by internal factors (content, governance, transaction structure) and external factors (sector dynamics, geographical environment, technology) in the context of blockchain. (2) Blockchain influences the SCF platform business model reconfiguration through empowering the operation of SCF information, financial, material, and value flows. (3) The introduction of blockchain changes the business model of the SCF platform significantly, which is mainly reflected in the improved value proposition, expanded value network, strengthened value creation, and generated value appropriation. This study contributes to the existing literature on SCF, business model, and blockchain. The research also provides some important practical implications. [ABSTRACT FROM AUTHOR]

SUMMARY: Fruit size and shape are controlled by genes expressed during the early developmental stages of fruit. Although the function of ASYMMETRIC LEAVES 2 (AS2) in promoting leaf adaxial cell fates has been well characterized in Arabidopsis thaliana, the molecular mechanisms conferring freshy fruit development as a spatial–temporal expression gene in tomato pericarp remain unclear. In the present study, we verified the transcription of SlAS2 and SlAS2L, two homologs of AS2, in the pericarp during early fruit development. Disruption of SlAS2 or SlAS2L caused a significant decrease in pericarp thickness as a result of a reduction in the number of pericarp cell layers and cell area, leading to smaller tomato fruit size, which revealed their critical roles in tomato fruit development. In addition, leaves and stamens exhibited severe morphological defects in slas2 and slas2l single mutants, as well as in the double mutants. These results demonstrated the redundant and pleiotropic functions of SlAS2 and SlAS2L in tomato fruit development. Yeast two‐hybrid and split‐luciferase complementation assays showed that both SlAS2 and SlAS2L physically interact with SlAS1. Molecular analyses further indicated that SlAS2 and SlAS2L regulate various downstream genes in leaf and fruit development, and that some genes participating in the regulation of cell division and cell differentiation in the tomato pericarp are affected by these genes. Our findings demonstrate that SlAS2 and SlAS2L are vital transcription factors required for tomato fruit development. Significance Statement: Understanding early fruit development in tomato is critical since the size and shape of a fruit is largely decided in the early stages. Our previous work identified hundreds of transcription factors specifically expressed in the pericarp of 0–5 days post anthesis fruits in tomato that are likely involved in this complex process. ASYMMETRIC LEAVES 2 (AS2) belongs to the LATERAL ORGAN BOUNDARIES family, and its role in promoting leaf adaxial cell fates in Arabidopsis has been well characterized. SlAS2 and SlAS2L, two homologs of AS2 in tomato, are specifically expressed in the ovary wall/pericarp at early fruit developmental stage, but their functions in fleshy fruit development are still unclear. In the present study, we found that knockout mutations in SlAS2 or SlAS2L caused significantly reduced pericarp thickness, leading to smaller mature fruit size. Histocytological observation of the pericarp revealed that disruption of SlAS2 or SlAS2L inhibited both cell division and expansion, leading to the observed thinner pericarp. Additionally, leaf and stamen defects in single and double mutants suggested that SlAS2 and SlAS2L have redundant functions in plant development. Both SlAS2 and SlAS2L interact with SlAS1 in vitro, which is consistent with Arabidopsis AS2. Molecular analyses revealed that genes regulated by SlAS2 and SlAS2L in leaf and fruit development are different, and were related to cell division and differentiation processes during tomato pericarp development. Our results confirm the vital roles of SlAS2 and SlAS2L in regulating tomato fruit development. [ABSTRACT FROM AUTHOR]

Summary: Seed size is one of the most important agronomic traits determining the yield of crops. Cloning the key genes controlling seed size and pyramiding their elite alleles will facilitate yield improvement. To date, few genes controlling seed size have been identified in soybean, a major crop that provides half of the plant oil and one quarter of the plant protein globally. Here, through a genome‐wide association study of over 1800 soybean accessions, we determined that natural allelic variation at GmST05 (Seed Thickness 05) predominantly controlled seed thickness and size in soybean germplasm. Further analyses suggested that the two major haplotypes of GmST05 differed significantly at the transcriptional level. Transgenic experiments demonstrated that GmST05 positively regulated seed size and influenced oil and protein contents, possibly by regulating the transcription of GmSWEET10a. Population genetic diversity analysis suggested that allelic variations of GmST05 were selected during geographical differentiation but have not been fixed. In summary, natural variation in GmST05 determines transcription levels and influences seed size and quality in soybean, making it an important gene resource for soybean molecular breeding. [ABSTRACT FROM AUTHOR]

Summary: Soybean is one of the most important oilseed and fodder crops. Benefiting from the efforts of soybean breeders and the development of breeding technology, large number of germplasm has been generated over the last 100 years. Nevertheless, soybean breeding needs to be accelerated to meet the needs of a growing world population, to promote sustainable agriculture and to address future environmental changes. The acceleration is highly reliant on the discoveries in gene functional studies. The release of the reference soybean genome in 2010 has significantly facilitated the advance in soybean functional genomics. Here, we review the research progress in soybean omics (genomics, transcriptomics, epigenomics and proteomics), germplasm development (germplasm resources and databases), gene discovery (genes that are responsible for important soybean traits including yield, flowering and maturity, seed quality, stress resistance, nodulation and domestication) and transformation technology during the past decade. At the end, we also briefly discuss current challenges and future directions. [ABSTRACT FROM AUTHOR]

ABSTRACT Gene innovation plays an essential role in trait evolution. Rhizobial symbioses, the most important N2‐fixing agent in agricultural systems that exists mainly in Leguminosae, is one of the most attractive evolution events. However, the gene innovations underlying Leguminosae root nodule symbiosis (RNS) remain largely unknown. Here, we investigated the gene gain event in Leguminosae RNS evolution through comprehensive phylogenomic analyses. We revealed that Leguminosae‐gain genes were acquired by gene duplication and underwent a strong purifying selection. Kyoto Encyclopedia of Genes and Genomes analyses showed that the innovated genes were enriched in flavonoid biosynthesis pathways, particular downstream of chalcone synthase (CHS). Among them, Leguminosae‐gain type Ⅱ chalcone isomerase (CHI) could be further divided into CHI1A and CHI1B clades, which resulted from the products of tandem duplication. Furthermore, the duplicated CHI genes exhibited exon–intron structural divergences evolved through exon/intron gain/loss and insertion/deletion. Knocking down CHI1B significantly reduced nodulation in Glycine max (soybean) and Medicago truncatula; whereas, knocking down its duplication gene CHI1A had no effect on nodulation. Therefore, Leguminosae‐gain type Ⅱ CHI participated in RNS and the duplicated CHI1A and CHI1B genes exhibited RNS functional divergence. This study provides functional insights into Leguminosae‐gain genetic innovation and sub‐functionalization after gene duplication that contribute to the evolution and adaptation of RNS in Leguminosae. [ABSTRACT FROM AUTHOR]

Background: Foxp3 + regulatory T (T reg ) cells facilitate tumor immune evasion by forming a suppressive tumor microenvironment. Therefore, immune therapies promoting T reg fragility may greatly enhance immune checkpoint blockade (ICB) efficacy in cancers., Methods: We have screened 2640 compounds and identified the gut microbial metabolite gallic acid, which promotes Foxp3 degradation and T reg instability by repressing Usp21 gene transcription. In vivo and in vitro experiments have been performed to explore the roles of Usp21 in T reg cells. Importantly, we treated tumor-bearing mice with gallic acid and anti-PD-1 antibody to explore the potential therapeutic value of gallic acid in clinical cancer immunotherapy., Results: Mechanistically, gallic acid prevents STAT3 phosphorylation and the binding of phosphorylated STAT3 to Usp21 gene promoter. The deubiquitinated Usp21 and stabilized PD-L1 proteins boost the function of T reg cells. Combination of gallic acid and anti-PD-1 antibody, in colorectal cancer (CRC) treatment, not only significantly dampen T reg cell function by impairing PD-L1/PD-1 signaling and downregulating Foxp3 stability, but also promote CD8 + T cells' production of IFN-γ and limited tumor growth., Conclusion: Our findings have implications for improving the efficacy of ICB therapy in CRC by inducing T-helper-1-like Foxp3 lo T reg cells., Competing Interests: Competing interests: YL are cofounder of Biotheus and Chairman of its scientific advisory board. The remaining authors declare no competing interests., (© Author(s) (or their employer(s)) 2022. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)