Correlation between tumor budding and the long-term follow-up outcomes after endoscopic submucosal dissection for superficial esophageal squamous cell carcinoma.

BACKGROUND: The effect of tumor budding (TB) on the prognosis of patients with esophageal squamous cell carcinoma (ESCC) after endoscopic submucosal dissection (ESD) remains unclear. We evaluated the long-term outcomes of patients with superficial ESCC after ESD and the risk factors of TB for the long-term prognosis. METHODS: We conducted a retrospective study in a Chinese hospital. All patients with ESCC treated by ESD and reported TB were included consecutively. Comparative analyses were conducted in three parts: specimen analysis, follow-up analyses of unmatched patients, and propensity score-matched (PSM) patients. Cox proportional hazard regression models were constructed to identify risk factors for overall survival and recurrence-free survival (RFS). RESULTS: A total of 437 patients were enrolled [154 TB and 283 no tumor budding (NTB)], and 258 patients (52 TB and 206 NTB) were included in the follow-up analysis. Results showed that the invasion depth, differentiation type, and positive vascular invasion (all p < 0.001) of the TB group were significantly different from the NTB group. The all-cause mortality and the median RFS time between the two groups were comparable. RFS rate at 5 years were 84.6% and 80.6%, respectively (p = 0.43). Cox analyses identified that having other cancers but not TB, as a risk factor independently associated with overall survival and RFS after ESD. CONCLUSION: TB tends to be associated with invasion depth, differentiation type, and positive vascular invasion. However, it might not affect the long-term outcomes of patients with superficial ESCC after ESD when other high-risk factors are negative.

A novel AP2/ERF transcription factor, NtERF10, positively regulates plant height in tobacco.

Ethylene response factors have been shown to be involved in the effects of plant developmental processes and to regulate stress tolerance. The aim of this study was to recognize the regulatory mechanisms of ethylene response factors on tobacco plant height. In this study, a gene-edited mutant (ERF10-KO) and wild type (WT) were utilized as experimental materials. Transcriptome and metabolome analyses were used to investigate the regulatory mechanism of NtERF10 gene editing on plant height in tobacco. Here, through the analysis of differentially expressed genes (DEGs), 2051 genes were upregulated and 1965 genes were downregulated. We characterized the different ERF10-KO and WT plant heights and identified key genes for photosynthesis, the plant hormone signal transduction pathway and the terpene biosynthesis pathway. NtERF10 was found to affect the growth and development of tobacco by regulating the expression levels of the PSAA, PSBA, GLY17 and GGP3 genes. Amino acid metabolism was analyzed by combining analyses of differentially expressed genes (DEGs) and differentially accumulated metabolites (DAMs). In addition, we found that members of the bHLH, NAC, MYB, and WRKY transcription factor families have vital roles in regulating plant height. This study not only provides important insights into the positive regulation of the ethylene response factor NtERF10 on plant height during plant growth and development but also provides new research ideas for tobacco molecular breeding.

Vitamin B6 prevents heart failure with preserved ejection fraction through downstream of kinase 3 in a mouse model.

BACKGROUND: There is an urgent need to develop an efficient therapeutic strategy for heart failure with preserved ejection fraction (HFpEF), which is mediated by phenotypic changes in cardiac macrophages. We previously reported that vitamin B6 (VB6) inhibits macrophage-mediated inflammasome activation OBJECTIVE: We sought to examine whether the prophylactic use of VB6 prevents HFpEF METHODS: HFpEF model was elicited by a combination of high fat diet and Nω-nitro-l-arginine methyl ester in mice. Cardiac function was assessed using conventional echocardiography and Doppler imaging. Immunohistochemistry and immunoblotting were used to detect changes in the macrophage phenotype and myocardial remodeling-related molecules RESULTS: Co-administration of VB6 with HFpEF mice mitigated HFpEF phenotypes, including diastolic dysfunction, cardiac macrophage phenotypic shifts, fibrosis, and hypertrophy. Echocardiographic improvements were observed, with the E/E' ratio decreasing from 42.0 to 21.6 and the E/A ratio improving from 2.13 to 1.17. The exercise capacity also increased from 295.3 m to 657.7 m. However, these beneficial effects were negated in downstream of kinase 3 (DOK3)-deficient mice. Mechanistically, VB6 increased DOK3 protein levels and inhibited macrophage phenotypic changes, which were abrogated by an AMP-activated protein kinase inhibitor CONCLUSION: VB6 increases DOK3 signaling to lower the risk of HFpEF by inhibiting phenotypic changes in cardiac macrophages.

Congruent or conflicting? The interaction between emoji and textual sentence is not that simple!

As a Japanese graphic symbol widely used in the world, Emoji plays an important role in computer mediated communication. Despite its prevalent use, the interaction dynamics between emoji and textual sentences remain inadequately explored. Based on the emotional function of emoji, this study uses the indirect priming method to explore the emotional impact of emoji on subsequent text in computer mediated communication through two progressive behavioral experiments. The results show that: (1) Emoji positioned at the onset of a sentence induce an emotional priming effect; (2) The processing speed is slowest when emoji and text are emotionally conflicting, while in non-conflicting condition, the type of emoji moderates the processing of combined sentences; (3) The emotional influence of emoji plays an auxiliary role, and the valence of textual sentence plays a decisive role in emotional perception.

Pattern Recognition of Alkaloids by Inhibiting the Catalytic Activity of Dopzymes for Dopamine.

Exploiting the specific recognition probe for all of the biomolecules is difficult in "lock-and-key" biosensors. The cross-reaction or the semispecific probe in pattern recognition mode is an alternative strategy through extracting a multidimensional signal array from recognition elements. Here, we design a pattern recognition sensor array based on the alkaloid-inhibited catalytic activity of dopzymes for the discrimination and determination of six alkaloids. In this sensor array, three different G-rich sequences, i.e., G-triplex (G3), G-quadruplex (GQ1), and the G-quadruplex dimer (2GQ1) possessing various peroxidase activities, conjugated with a dopamine aptamer and the dopzymes (G3-d-apt, GQ1-d-apt, and 2GQ1-d-apt) were obtained with an enhanced catalytic performance for the substrate. Through the interactions between six target alkaloids and G3, GQ1, and 2GQ1 regions, the pattern signal (6 alkaloids × 3 dopzymes × 5 replicates) was obtained from the diverse inhibited effect for the dopzyme activity. In virtue of the statistical method principal component analysis (PCA), the data array was projected into a new dimensional space to acquire the three-dimensional (3D) canonical scores and grouped into their respective clusters. The sensor array exhibited an outstanding discrimination and classification capability for six alkaloids with different concentrations with 100% accuracy. In addition, the nonspecific recognition elements of the sensor array showed high selectivity even though other alkaloids with similar structures to targets existed in the samples. Importantly, the levels of the six targets can be analyzed by the most influential discrimination factor, which represented the vector with the highest variance, evidencing that the sensor array has potential in drug screening and clinical treatment.

A bacteriocin-based coating strategy to prevent vancomycin-resistant Enterococcus faecium biofilm formation on materials of interest for indwelling medical devices.

The ever-increasing use of exogenous materials as indwelling medical devices in modern medicine offers to pathogens new ways to gain access to human body and begin, in some cases, life threatening infections. Biofouling of such materials with bacteria or fungi is a major concern during surgeries, since this is often associated with biofilm formation and difficult to treat, recalcitrant infections. Intense research efforts have therefore developed several strategies to shield the medical devices' surface from colonization by pathogenic microorganisms. Here, we used dopamine as a coupling agent to coat four different materials of medical interest (plastic polyetheretherketone (PEEK), stainless steel, titanium and silicone catheter) with the bacteriocins, enterocin EJ97-short and the thiopeptide micrococcin P1. Water contact angle measurements and x-ray photoelectron spectroscopy were used to verify the effective coating of the materials. The effect of bacteriocins coated on these materials on the biofilm formation by a vancomycin resistant Enterococcus faecium (VRE) strain was studied by biofilm-oriented antimicrobial test (BOAT) and electron scanning microscopy. The in vitro biocompatibility of bacteriocin-modified biomaterials was tested on cultured human cells. The results demonstrated that the binding of the bacteriocins to the implant surfaces is achieved, and the two bacteriocins in combination could inhibit biofilm formation by E. faecium on all four materials. The modified implant showed no cytotoxicity to the human cells tested. Therefore, surface modification with the two bacteriocins may offer a novel and effective way to prevent biofilm formation on a wide range of implant materials.

TMSOTf-Catalyzed C2-Sulfenylation of Indole Alkaloids Using N-Sulfenylsuccinimides: An Approach for the Total Synthesis of Isatindigotindolosides.

A TMSOTf-catalyzed C2-sulfenylation of indole alkaloids with N-sulfenylsuccinimides has been developed. This straightforward, metal-free, and cost-effective catalytic system produces valuable 2-thioindole derivatives with yields ranging from moderate to excellent. The synthetic applicability demonstrated includes the total syntheses of isatindigotindolosides I-IV.

Legacy and alternative perfluoroalkyl acids in the Yellow River on the Qinghai-Tibet Plateau: Levels, spatiotemporal characteristics, and multimedia transport processes.

The source region of the Yellow River (SRYR) located in the northeast of the Qinghai-Tibetan Plateau is not only the largest runoff-producing area in the Yellow River Basin, but also the most important freshwater-supply ecological function area in China. In this study, the short-term spatiotemporal distribution of selected legacy and alternative perfluoroalkyl acids (PFAAs) in the SRYR was first investigated in multiple environmental media. Total PFAA concentrations were in the range of 1.16-14.3 ng/L, 4.25-42.1 pg/L, and 0.21-13.0 pg/g dw in rainwater, surface water, and sediment, respectively. C4-C7 PFAAs were predominant in various environmental matrices. Spatiotemporal characteristics were observed in the concentrations and composition profiles. Particularly, the spatial distribution of rainwater and the temporal distribution of surface water exhibited highly significant differences (p<0.01). Indian monsoon, westerly air masses, and local mountain-valley breeze were the driving factors that contributed to the change of rainwater. Rainwater, meltwater runoff, and precursor degradation were important sources of PFAA pollution in surface water. Organic carbon content was a major factor influencing PFAA distribution in sediment. These results provide a theoretical basis for revealing the regional transport and fate of PFAAs, and are also important prerequisites for effectively protecting the freshwater resource and aquatic environment of the Qinghai-Tibetan Plateau.

A multi-component, multi-target, and multi-pathway prediction method for Chinese medicine based on the combination of mass spectrometry analysis and network analysis: An example using Weifuchun.

Weifuchun, a Chinese medicinal prescription made from herbs of natural origin including Hongshen (Ginseng Radix et Rhizoma Rubra), Xiangchacai (Rabdosia Amethystoides), and Zhiqiao (Aurantii Fructus), has attracted increasing attention for clinically treating chronic atrophic gastritis, which is characterized by the chronic inflammation of the gastric mucosa leading to progressive loss of gastric glandular cells. To investigate the active ingredients and potential mechanisms of WFC, it was analyzed using a novel multi-component, multi-target, and multi-pathway prediction method. High/ultra-performance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry (HPLC/UPLC-Q-TOF-MS) was employed to separate and profile the chemical constituents of WFC with high precision and efficiency. Network analysis and molecular docking were used to predict bioactive compounds and their interactions with biological targets. The results highlight 42 significant compounds potentially contributing to the therapeutic effects of WFC by effecting on several key pathways, including proved PI3K/Akt, NF-κB, and JAK/STAT signaling pathways. This study showcases the efficacy of combining advanced chromatographic techniques with computational methods to elucidate the pharmacological mechanisms of complex botanical drugs.

An intelligent process analysis method for rapidly evaluating the quality of Chinese medicine with near-infrared non-contact hyperspectral imaging: A case study of Weifuchun concentrate.

INTRODUCTION: The quality of Chinese medicine preparations can be greatly influenced by the quality of the intermediates such as extracts or concentrates. However, it is highly challenging to evaluate the quality in a rapid and non-contact manner during manufacturing. Here, we introduce an intelligent hyperspectral analysis method integrating a self-built abnormal region removal algorithm with machine learning and demonstrate its utility using the concentrate of Weifuchun (WFC), a traditional Chinese medicine preparation made from Ginseng Radix et Rhizoma Rubra, Rabdosia Amethystoides, and Aurantii Fructus. OBJECTIVE: To rapidly and non-destructively detect quality attributes of the intermediates in the manufacturing processes of Chinese medicine, an intelligent hyperspectral analysis method was developed for simultaneously quantifying the contents of naringin, neohesperidin, rosmarinic acid, and relative density of WFC concentrates. METHODOLOGY: Samples were evenly spread on solid white flat bottom containers, which were batch placed on a horizontal sample stage. Subsequent to the acquisition of near-infrared (NIR) hyperspectral images, abnormal pixels such as large/small bubbles and fine solids were first removed according to the differential pixel values in the binary grayscale map and the Mahalanobis distance metric. Then, partial least squares (PLS) and support vector machine (SVM) algorithms were used to construct hyperspectral quantitative calibration models for quality attributes. The hyperspectral images were reconstructed based on these models to visually evaluate the quality of the concentrates during manufacturing. RESULTS: As a case study, quality attributes of the WFC concentrates including contents of naringin, neohesperidin, rosmarinic acid, and relative density were determined simultaneously, and coefficients of determination of these quantitative correction models were 0.900, 0.891, 0.851, and 0.920, respectively. CONCLUSION: The method proposed in this study favors real-time determination of multiple attributes in viscous samples with industrial application prospects.

Myxoid Liposarcoma Metastasizing to the Parotid Gland.

Myxoid liposarcoma (MLPS) of the parotid gland is very rare, and only a few cases have been reported worldwide. It can be difficult to diagnose this disease when there is only a single lesion in the patient's body. A 56-year-old man was diagnosed with an MLPS in the left calf and was treated with wide resection. Two months after the surgery, a painless mass appeared in the man's left parotid gland area. Both fine-needle aspiration biopsy before surgery and intraoperative frozen sections suggested that the tumor was likely to be a pleomorphic adenoma. Both parotid ultrasound and CT indicated the same result. However, this mass was confirmed to be metastasis of MLPS through immunohistochemistry and multicolor fluorescence in situ hybridization. The authors report a case in which an MLPS metastasized to the parotid gland; this type of lesion is extremely rare and highly worthy of consideration because the authors misdiagnosed it.

RNAi-mediated knockdown of papilin gene affects the egg hatching in Nilaparvata lugens.

BACKGROUND: The brown planthopper (BPH), Nilaparvata lugens, is one of the most destructive pests of rice. Owing to the rapid adaptation of BPH to many pesticides and resistant varieties, identifying putative gene targets for developing RNA interference (RNAi)-based pest management strategies has received much attention for this pest. The glucoprotein papilin is the most abundant component in the basement membranes of many organisms, and its function is closely linked to development. RESULTS: In this study, we identified a papilin homologous gene in BPH (NlPpn). Quantitative Real-time PCR analysis showed that the transcript of NlPpn was highly accumulated in the egg stage. RNAi of NlPpn in newly emerged BPH females caused nonhatching phenotypes of their eggs, which may be a consequence of the maldevelopment of their embryos. Moreover, the transcriptomic analysis identified 583 differentially expressed genes between eggs from the dsGFP- and dsNlPpn-treated insects. Among them, the 'structural constituent of cuticle' cluster ranked first among the top 15 enriched GO terms. Consistently, ultrastructural analysis unveiled that dsNlPpn-treated eggs displayed a discrete and distorted serosal endocuticle lamellar structure. Furthermore, the hatchability of BPH eggs was also successfully reduced by the topical application of NlPpn-dsRNA-layered double hydroxide nanosheets onto the adults. CONCLUSION: Our findings demonstrate that NlPpn is essential to maintaining the regular structure of the serosal cuticle and the embryonic development in BPH, indicating NlPpn could be a potential target for pest control during the egg stage. © 2024 Society of Chemical Industry.

Beneficial effects of maintaining liver function during hepatic arterial infusion chemotherapy combined with tyrosine kinase and programmed cell death protein-1 inhibitors on the outcomes of patients with unresectable hepatocellular carcinoma.

BACKGROUND AND AIM: Combination therapy is the primary treatment for unresectable hepatocellular carcinoma (u-HCC). The hepatic functional reserve is also critical in the treatment of HCC. In this study, u-HCC was treated with combined hepatic arterial infusion chemotherapy (HAIC), tyrosine kinase inhibitors (TKIs), and programmed cell death protein-1 (PD-1) inhibitors to analyze the therapeutic response, progression-free survival (PFS), and safety. METHODS: One hundred sixty-two (162) patients with u-HCC were treated by combination therapy of HAIC, TKIs, and PD-1 inhibitors. PFS was assessed by Child-Pugh (CP) classification subgroups and the change in the CP score during treatment. RESULTS: The median PFS was 11.7 and 5.1 months for patients with CP class A (CPA) and CP class B (CPB), respectively (p = 0.013), with respective objective response rates of 61.1 and 27.8% (p = 0.002) and conversion rates of 16 and 0% (p = 0.078). During treatment, the CP scores in patients with CPA worsened less in those with complete and partial response than in those with stable and progressive disease. In the CP score 5, patients with an unchanged CP score had longer PFS than those with a worsened score (Not reached vs. 7.9 months, p = 0.018). CPB was an independent factor negatively affecting treatment response and PFS. Patients with CPA responded better to the combination therapy and had fewer adverse events (AEs) than those with CPB. CONCLUSIONS: Thus, triple therapy is more beneficial in patients with good liver function, and it is crucial to maintain liver function during treatment.

Formation of compounds with diverse polyelectrolyte morphologies and nonlinear ion conductance in a two-dimensional nanofluidic channel.

Aqueous electrolytes subjected to angstrom-scale confinement have recently attracted increasing interest because of their distinctive structural and transport properties, as well as their promising applicability in bioinspired nanofluidic iontronics and ion batteries. Here, we performed microsecond-scale molecular dynamics simulations, which provided evidence of nonlinear ionic conductance under an external lateral electric field due to the self-assembly of cations and anions with diverse polyelectrolyte morphologies (e.g., extremely large ion clusters) in aqueous solutions within angstrom-scale slits. Specifically, we found that the cations and anions of Li2SO4 and CaSO4 formed chain-like polyelectrolyte structures, whereas those of Na2SO4 and MgSO4 predominantly formed a monolayer of hydrated salt. Additionally, the cations and anions of K2SO4 assembled into a hexagonal anhydrous ionic crystal. These ion-dependent diverse polyelectrolyte morphologies stemmed from the enhanced Coulomb interactions, weakened hydration and steric constraints within the angstrom-scale slits. More importantly, once the monolayer hydrated salt or ionic crystal structure was formed, the field-induced ion current exhibited an intriguing gating effect at a low field strength. This abnormal ion transport was attributed to the concerted movement of cations and anions within the solid polyelectrolytes, leading to the suppression of ion currents. When the electric field exceeded a critical strength, however, the ion current surged rapidly due to the dissolution of many cations and anions within a few nanoseconds in the aqueous solution.

Draconibacterium aestuarii sp.nov., a Glycolipid-Producing Bacterium Isolated from Tidal Flat Sediment and Emended Description of the Genus Draconibacterium.

A facultatively anaerobic, Gram-negative, curved rod-shaped bacterium (4.0-17.0 µm long, 0.6-0.9 µm wide), designated Z1-6T, was obtained from tidal flat sediment collected from YueAo village in Zhoushan, Zhejiang, People's Republic of China. Strain Z1-6T occurred at 15-45 °C (optimum 28-32 °C), pH 6.0-9.0 (optimum 7.0-7.5), and in the presence of 1-5% (w/v) NaCl (optimum 1-2%). The strain contained iso-C15:0 and antesio-C15:0 as the major fatty acids. An unsaturated menaquinone with seven isoprene units (MK-7) was the predominant respiratory quinone. The polar lipids included phosphatidylethanolamine (PE), one aminophospholipid (APL), two phospholipids (PL1 and PL2), three glycolipids (GL1, GL2, and GL3), and two unidentified lipids (L1 and L2). The genomic DNA G+C content of strain Z1-6T was 39.2%, and the genome size was 6.4 Mb. The strain showed the highest average nucleotide identity (ANI) value of 73.5-74.6%, digital DNA-DNA hybridization (dDDH) value of 19.3-20%, average amino acid identity (AAI) value of 72.0-73.1% with the members of genus Draconibacterium. Phylogenetic analysis based on 16S rRNA gene sequences and genome revealed that strain Z1-6T formed a distinct branch in the clade of the genus Draconibacterium. Based on the phenotypic, phylogenetic, chemotaxonomic analyses and genomic data, strain Z1-6T represents a novel species of the genus Draconibacterium, for which the name Draconibacterium aestuarii sp. nov. (The type strain Z1-6T = MCCC 1K07533T = KCTC 92310T) is proposed.

Comprehensive assessment of drought resistance and recovery in kiwifruit genotypes using multivariate analysis.

As global climate change persists, ongoing warming exposes plants, including kiwifruit, to repeated cycles of drought stress and rewatering, necessitating the identification of drought-resistant genotypes for breeding purposes. To better understand the physiological mechanisms underlying drought resistance and recovery in kiwifruit, moderate (40-45% field capacity) and severe (25-30% field capacity) drought stresses were applied, followed by rewatering (80-85% field capacity) to eight kiwifruit rootstocks in this study. We then conducted a multivariate analysis of 20 indices for the assessment of drought resistance and recovery capabilities. Additionally, we identified four principal components, each playing a vital role in coping with diverse water conditions. Three optimal indicator groups were pinpointed, enhancing precision in kiwifruit drought resistance and recovery assessment and simplifying the evaluation system. Finally, MX-1 and HW were identified as representative rootstocks for future research on kiwifruit's responses to moderate and severe drought stresses. This study not only enhances our understanding of the response mechanisms of kiwifruit rootstocks to progressive drought stress and recovery but also provides theoretical guidance for reliable screening of drought-adaptive kiwifruit genotypes.

Construction of cyclobutane-fused tetracyclic skeletons via substrate-dependent EnT-enabled dearomative [2+2] cycloaddition of benzofurans (benzothiophenes)/maleimides.

Herein, a novel and facile organic photosensitizer (thioxanthone)-mediated energy-transfer-enabled (EnT-enabled) dearomative [2+2] cycloaddition of aromatic heterocycles/maleimides for green synthesis of cyclobutane-fused polycyclic skeletons is reported. Mechanistic investigations revealed that different EnT pathways by triplet thioxanthone were initiated when different aromatic heterocycles participated in the reaction, giving the corresponding excited intermediates, which underwent the subsequent intermolecular [2+2] cycloaddition to access the desired highly functionalized cyclobutane-fused polycyclic skeletons.

Marinobacter albus sp. nov., Isolated from Sand Sediment in a Coastal Intertidal Zone.

A Gram-stain-negative bacterium with a rod-to-ovoid shape, named strain M216T, was isolated from sand sediment from the coastal intertidal zone of Huludao, Liaoning Province, China. Growth was observed at 8-40 °C (optimal, 30 °C), pH 5.5-9.5 (optimal, pH 6.5) and 0.5-14.0% (w/v) NaCl (optimal, 6%). Strain M216T possessed ubiquinone-9 as its sole respiratory quinone and phosphatidylethanolamine, diphosphatidylglycerol, phosphatidylglycerol, one unidentified aminophosphoglycolipid, one unidentified aminophospholipid, two unidentified phosphoglycolipids, three unidentified phospholipids and three unidentified glycolipids as the main polar lipids. C12:0, C16:0, C12:0 3-OH, C16:1 ω9c, C18:1 ω9c and summed features 3 (C16:1 ω7c and/or C16:1 ω6c) were the major fatty acids (> 5%). The 16S rRNA gene sequence of strain M216T exhibited high similarity to those of 'Marinobacter arenosus' CAU 1620T and Marinobacter adhaerens HP15T (99.3% and 98.5%, respectively) and less than 98.5% similarity to those of the other type strains. The ANI and dDDH values between the strain M216T and 'Marinobacter arenosus' CAU 1620T were 87.4% and 33.3%, respectively; these values were the highest among the other type strains but lower than the species threshold. The G+C content of strain M216T was 58.3%. Genomic analysis revealed that strain M216T harbors the major CAZymes of GH13, GH23, GH73, and PL5, which are responsible for polysaccharide degradation and the potential ability to reduce nitrate to ammonia. Through phenotypic, genotypic, and chemotaxonomic analyses, we proposed the name Marinobacter albus sp. nov., a novel species in the genus Marinobacter, with its type strain M216T (= MCCC 1K08600T = KCTC 82894T).

Ultrasound-Based Deep Learning Radiomics Nomogram for the Assessment of Lymphovascular Invasion in Invasive Breast Cancer: A Multicenter Study.

RATIONALE AND OBJECTIVES: The aim of this study was to develop a deep learning radiomics nomogram (DLRN) based on B-mode ultrasound (BMUS) and color doppler flow imaging (CDFI) images for preoperative assessment of lymphovascular invasion (LVI) status in invasive breast cancer (IBC). MATERIALS AND METHODS: In this multicenter, retrospective study, 832 pathologically confirmed IBC patients were recruited from eight hospitals. The samples were divided into training, internal test, and external test sets. Deep learning and handcrafted radiomics features reflecting tumor phenotypes on BMUS and CDFI images were extracted. The BMUS score and CDFI score were calculated after radiomics feature selection. Subsequently, a DLRN was developed based on the scores and independent clinic-ultrasonic risk variables. The performance of the DLRN was evaluated for calibration, discrimination, and clinical usefulness. RESULTS: The DLRN predicted the LVI with accuracy, achieving an area under the receiver operating characteristic curve of 0.93 (95% CI 0.90-0.95), 0.91 (95% CI 0.87-0.95), and 0.91 (95% CI 0.86-0.94) in the training, internal test, and external test sets, respectively, with good calibration. The DLRN demonstrated superior performance compared to the clinical model and single scores across all three sets (p < 0.05). Decision curve analysis and clinical impact curve confirmed the clinical utility of the model. Furthermore, significant enhancements in net reclassification improvement (NRI) and integrated discrimination improvement (IDI) indicated that the two scores could serve as highly valuable biomarkers for assessing LVI. CONCLUSION: The DLRN exhibited strong predictive value for LVI in IBC, providing valuable information for individualized treatment decisions.