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Background Enhancing rapeseed ( Brassica napus , B. napus ) yield is critical for ensuring global vegetable oil security. However, yield is heavily influenced by silique development and seed size, the enhancement of which is limited by scarce genetic resources. The CRISPR/Cas9 system has emerged as a powerful tool for constructing genome-wide mutant libraries, even in polyploid crops with complex genomes. Results The transcriptome-wide association study (TWAS) data, tissue-specific expression profiles data and reported genes were integrated to identify candidate genes regulating silique development and seed size. We constructed a sgRNA library targeting these genes and generated a CRISPR/Cas9 editing mutant library through genetic transformation. Specifically, 6124 sgRNAs were designed for 1739 candidate genes with ≦ 4 orthologues. 681 T 0 plants were obtained through genetic transformation, which harbor 453 sgRNAs. Of 408 T 0 plants analyzed, 151 (37.00%) exhibited successful gene editing events, targeting 84 candidate genes. Ten homozygous mutant plants were isolated and preliminary phenotypic analysis was performed in mutants targeting the BnaHRDs . The results suggest that mutations in BnaHRD.A03 and BnaHRD.C03 may modulate plant height (PH), main inflorescence length (MIL), silique length (SL), effective silique number per plant (ENS), seed number per silique (SNPS), and thousand-seed weight (TSW). Conclusions This study harnessed the CRISPR/Cas9 technology to establish a preliminary library of gene-edited mutants in B. napus , thereby laying a robust foundation for the future screening of candidate genes pertaining to silique development and seed size. Furthermore, this study provides a methodological framework for rapid functional gene discovery in B. napus through CRISPR-based approaches.

Below are the highlights of this review: This paper explores embedded RRAM development, parameters, and integration tech compatible with CMOS, highlighting advantages in embedded systems and its potential impact on chip process nodes. This paper introduces recent industry developments in embedded RRAM, featuring research from companies like Intel and TSMC, showcasing significant commercial application potential. This paper discusses embedded RRAM’s progress beyond storage, exploring potential applications in FPGA, MCU, CIM, and Neuromorphic Computing, along with challenges and future prospects. Embedded memory, which heavily relies on the manufacturing process, has been widely adopted in various industrial applications. As the field of embedded memory continues to evolve, innovative strategies are emerging to enhance performance. Among them, resistive random access memory (RRAM) has gained significant attention due to its numerous advantages over traditional memory devices, including high speed (<1 ns), high density (4 F 2 ·n −1 ), high scalability (∼nm), and low power consumption (∼pJ). This review focuses on the recent progress of embedded RRAM in industrial manufacturing and its potential applications. It provides a brief introduction to the concepts and advantages of RRAM, discusses the key factors that impact its industrial manufacturing, and presents the commercial progress driven by cutting-edge nanotechnology, which has been pursued by many semiconductor giants. Additionally, it highlights the adoption of embedded RRAM in emerging applications within the realm of the Internet of Things and future intelligent computing, with a particular emphasis on its role in neuromorphic computing. Finally, the review discusses the current challenges and provides insights into the prospects of embedded RRAM in the era of big data and artificial intelligence.

Plant polygalacturonase-inhibiting proteins (PGIPs) play a crucial role in plant defence against phytopathogenic fungi by inhibiting fungal polygalacturonase (PG) activity. We overexpressed BnPGIP2, BnPGIP5, and BnPGIP10 genes in an inbred line 7492 of rapeseed (Brassica napus). Compared with 7492WT, the overexpression of BnPGIP2 lines significantly increased Sclerotinia sclerotiorum resistance in both seedlings and adult plants. BnPGIP5 overexpression lines exhibited decreased S. sclerotiorum disease symptoms in seedlings only, whereas BnPGIP10 overexpression lines did not improve Sclerotinia resistance for seedlings or adult plants. Quantitative real-time PCR analysis of S. sclerotiorum PG1, SsPG3, SsPG5, and SsPG6 genes in overexpressing BnPGIP lines showed that these pathogenic genes in the Sclerotinia resistance transgenic lines exhibited low expression in stem tissues. Split-luciferase complementation experiments confirmed the following: BnPGIP2 interacts with SsPG1 and SsPG6 but not with SsPG3 or SsPG5; BnPGIP5 interacts with SsPG3 and SsPG6 but not with SsPG1 or SsPG5; and BnPGIP10 interacts with SsPG1 but not SsPG3, SsPG5, or SsPG6. Leaf crude protein extracts from BnPGIP2 and BnPGIP5 transgenic lines displayed high inhibitory activity against the SsPG crude protein. BnPGIP-overexpression lines with Sclerotinia resistance displayed a lower accumulation of H2O2 and higher expression of the H2O2-removing gene BnAPX (ascorbate peroxidase) than 7492WT, as well as elevated expression of defence response genes including jasmonic acid/ethylene and salicylic acid pathways after S. sclerotiorum infection. The plants overexpressing BnPGIP exhibited no difference in either agronomic traits or grain yield from 7492WT. This study provides potential target genes for developing S. sclerotiorum resistance in rapeseed.

Background ARID1A, a subunit of the SWI/SNF chromatin remodeling complex, functions as a tumor suppressor and is frequently inactivated across various cancer types. Consequently, ARID1A deficiency has emerged as a promising therapeutic target. Methods In this study, we conducted a high-throughput screening of a microRNA (miRNA) mimic library using ARID1A isogenic colorectal cancer (CRC) cell lines and identified a synthetic lethal interaction between ARID1A and miR-4653-3p. Results MiR-4653-3p selectively inhibited the proliferation of ARID1A-deficient CRC cells. Mechanistically, miR-4653-3p directly targets SLC25A51, a mitochondrial NAD⁺ transporter gene, leading to impaired SIRT3 enzymatic activity. Since both ARID1A and SIRT3 play critical roles in DNA damage repair, their concurrent loss exacerbates DNA damage accumulation and promotes apoptosis. Conclusions In conclusion, our findings reveal a novel synthetic lethality between ARID1A and miR-4653-3p, and suggest that targeting the miR-4653-3p/SLC25A51/SIRT3 axis, in combination with agents that disrupt DNA damage response, may offer a promising therapeutic strategy for ARID1A-deficient CRC.

Early flowering facilitates crops to adapt multiple cropping systems or growing regions with a short frost-free season; however, it usually brings an obvious yield loss. In this study, we identified that the three genes, namely, BnFLC.A2 , BnFLC.C2 , and BnFLC.A3b , are the major determinants for the flowering time (FT) variation of two elite rapeseed ( Brassica napus L.) accessions, i.e., 616A and R11. The early-flowering alleles (i.e., Bnflc.a2 and Bnflc.c2 ) and late-flowering allele (i.e., BnFLC.A3b ) from R11 were introgressed into the recipient parent 616A through a breeding strategy of marker-assisted backcross, giving rise to eight homozygous near-isogenic lines (NILs) associated with these three loci and 19 NIL hybrids produced by the mutual crossing of these NILs. Phenotypic investigations showed that NILs displayed significant variations in both FT and plant yield (PY). Notably, genetic analysis indicated that BnFLC.A2 , BnFLC.C2 , and BnFLC.A3b have additive effects of 1.446, 1.365, and 1.361 g on PY, respectively, while their dominant effects reached 3.504, 2.991, and 3.284 g, respectively, indicating that the yield loss caused by early flowering can be successfully compensated by exploring the heterosis of FT genes in the hybrid NILs. Moreover, we further validated that the heterosis of FT genes in PY was also effective in non-NIL hybrids. The results demonstrate that the exploration of the potential heterosis underlying the FT genes can coordinate early flowering (maturation) and high yield in rapeseed ( B. napus L.), providing an effective strategy for early flowering breeding in crops.

Background This study examined the link between red cell distribution width – coefficient of variation (RDW-CV) levels, colon cancer, and all-cause mortality in the community population. Methods Five thousand one hundred twenty-four participants were included out of 131,030 from the NHANES 1999–2018 survey. Survival differences were analyzed with Kaplan-Meier curves, while multivariate Cox regression, restricted cubic spline models and threshold effect analysis assessed correlations. Subgroup analyses by sex and age were also performed. To ensure the robustness of our findings, sensitivity analyses and the E-value were performed. Results Over a median follow-up of 12.7 [10.3; 15.4] years, 124 deaths occurred. The KM survival curves showed that the greatest risk for colon cancer (Log-rank p  = 0.018) and all-cause mortality (Log-rank p  < 0.001) was at RDW-CV 13.4–13.9 (Q3), while the lowest risk for both was at RDW-CV 12.9–13.3 (Q2). Compared to Q1, there was an increased risk of colon cancer (adjusted HR = 2.43, 95% CI 1.32–4.48, p  = 0.005) and overall mortality (adjusted HR = 2.88, 95% CI 1.54–5.40, p  < 0.001). Adjusted models confirmed a positive association between RDW-CV and both outcomes. Threshold effects associated with RDW-CV and both outcomes were not found. A subgroup analysis revealed no significant interaction between RDW-CV and variables like age and sex for colon cancer and all-cause mortality (all p for interaction > 0.05). Sensitivity analysis indicates that the outcomes are stable. Conclusions RDW-CV is significantly associated with both colon cancer and all-cause mortality in community-dwelling individuals, suggesting a positive correlation. RDW-CV may serve as a simple and cost-effective indicator for assessing colon cancer risk and as a straightforward, economical marker for mortality prediction in the community.

Disulfidptosis, a newly discovered cell death mode distinct from other programmed cell death in lung and kidney cancer cells, is defined as extensive disulfide bonds to actin cytoskeleton proteins, leading to actin contraction and cytoskeletal disruption cell death. New cell death pattern discoveries often drive advances in tumor research. Therefore, the present study attempted to decipher the manifestation and importance of disulfidptosis in pan-cancer. Combining Clinical specimen immunofluorescence staining, single-cell analyses, and spatial transcriptome analyses, we demonstrated the manifestation of disulfidptosis in pan-cancer. Multi-omics analysis has revealed that genomic variants and DNA methylation in DRGs can affect the prognosis of patients with pan-cancer. The nomogram based on the DRGs Score model could accurately predict the prognosis of patients with pan-cancer. PF-562271, EHT-1864, and IPA-3 are potential therapeutic agents targeting disulfidptosis. Collectively, this study deciphered for the first time the importance of disulfidptosis for pan-cancer and developed the DRGs Score model that can assist clinicians in accurately predicting the prognosis and guiding individualized treatment of pan-cancer patients.

For the past few decades, metal–oxide–semiconductor field-effect transistors (MOSFETs) have been the most important application in IC circuits. In certain circuit applications, the breakdown voltage and specific on-resistance serve as key electrical parameters. This article introduces a readily accessible approach to enhance the source–drain breakdown voltage (BVDS) of MOSFETs based on the Bipolar-CMOS-DMOS (BCD) platform without extra costs. By attentively refining the process steps and intricacies of the doping procedures, the breakdown voltages of NMOS and PMOS experienced increments of 3.4 V and 4.6 V, translating to enhancements of 31.5% and 50.3%. Parallel simulations offer insightful mechanistic explanations through simulation tools, facilitating superior outcomes. This initiative lays significant groundwork for the advancement of a comprehensive BCD process development framework.

Colon adenocarcinoma (COAD) remains a major global health challenge with poor prognosis despite advances in treatment, underscoring the need for new biomarkers. As a novel mode of cell death, cuproptosis is thought to be potentially involved in the development of cancer. However, the particularly as the role of cuproptosis-related genes (CRGs) in COAD prognosis and therapy remains unclear. We analyzed RNA sequencing data from The Cancer Genome Atlas for COAD, focusing on CRG expression patterns and their clinicopathological correlations. Using the Weighted Gene Co-expression Network Analysis (WGCNA) method, we identified the gene module most strongly linked to cuproptosis and conducted functional enrichment analysis to explore the roles of genes within this module in COAD tumorigenesis. A novel prognostic risk model based on four CRGs (ORC1, PTTG1, DLAT, PDHB) was developed to stratify COAD patients into high-risk and low-risk groups, assessing overall survival, tumor microenvironment, and mutational landscape differences. We also evaluated the therapeutic effects of ferredoxin 1 (FDX1) and elesclomol in promoting cuproptosis in HCT116 and LoVo cell lines through various experiments, including cell proliferation, apoptosis assessment, mitochondrial membrane potential evaluation, and DLAT lipoylation detection via Western blot. Certain CRGs showed different expressions in COAD normal tissues. WGCNA identified a gene module linked to cuproptosis, crucial for pathways like cell cycle regulation, citrate cycle (TCA cycle), and DNA replication. The novel risk model stratified patients into high and low-risk groups based on risk scores, revealing that high-risk COAD patients had shorter overall survival and distinct immune cell infiltration, while low-risk patients were more sensitive to immunotherapy. Experimental results indicated that FDX1 exerted an inhibitory effect on COAD, and its combination with elesclomol significantly reduced proliferation, promoted apoptosis, increased DLAT lipoylation, and lowered mitochondrial membrane potential in COAD cells. The findings of this study provided a new perspective for the research on biomarkers and therapeutic strategies in COAD, evaluated the prognostic and therapeutic value of CRGs in COAD patients, and laid a theoretical foundation for the future clinical application of CRGs.

Osteosarcoma (OS), the most common primary bone tumor in children and young adults, poses significant clinical challenges. In this study, we investigated the role of exosomes—key mediators of intercellular communication—in OS progression and identified potential therapeutic targets. Functional assays in cellular and animal models demonstrated that OS‐derived exosomes markedly enhanced tumor proliferation, migration, and invasion. Data‐independent acquisition‐based mass spectrometry analysis revealed a notable enrichment of the proto‐oncogene tyrosine‐protein kinase YES1 in these exosomes. Bioinformatics and clinical investigations further showed that YES1 is overexpressed in multiple cancers and correlates with poor outcomes; specifically, in OS, elevated YES1 levels were associated with reduced overall survival and adverse prognoses. PCR, Western blotting, and immunohistochemistry (IHC) of clinical samples confirmed its high expression in OS tissues relative to normal counterparts. Mechanistic studies using YES1 knockdown (shYES1) and overexpression (OE YES1) models, coupled with exosome supplementation and pathway modulators, revealed a critical role for ERK phosphorylation in mediating YES1‐driven oncogenic behaviors. In shYES1 cells, tumor proliferation, migration, and invasion were significantly impaired, partially rescued by exosome supplementation, and further suppressed by the inhibitor of MAPK. Conversely, in OE YES1 cells, these malignant phenotypes were markedly enhanced, exacerbated by exosomes, and further promoted by the agonist of MAPK. Western blot analyses supported these observations, showing reduced p‐MEK and p‐ERK but increased p‐p38 and p‐JNK upon YES1 knockdown, with opposite trends in the OE YES1 group; these phosphorylation changes were reversed or attenuated by EGF/IL‐1beta or U0126/SB‐203580 treatment, respectively, without altering total protein levels of MEK, JNK, p38, and ERK. Finally, multiplex IHC validated bioinformatics predictions, demonstrating that YES1 expression is closely linked to immune‐related pathways in OS tissues. Collectively, these findings underscore the pivotal role of exosomal YES1 in OS progression and tumor immunology, highlighting its promise as a biomarker and therapeutic target. By illuminating its function in cancer behavior and immune interactions, this study offers novel insights into improving patient outcomes in OS. Exosomal YES1 plays an oncogenic role in OS progression via the MAPK pathway.