Drosophila eIF3f1 mediates host immune defense by targeting dTak1.

Eukaryotic translation initiation factors have long been recognized for their critical roles in governing the translation of coding RNAs into peptides/proteins. However, whether they harbor functional activities at the post-translational level remains poorly understood. Here, we demonstrate that eIF3f1 (eukaryotic translation initiation factor 3 subunit f1), which encodes an archetypal deubiquitinase, is essential for the antimicrobial innate immune defense of Drosophila melanogaster. Our in vitro and in vivo evidence indicate that the immunological function of eIF3f1 is dependent on the N-terminal JAMM (JAB1/MPN/Mov34 metalloenzymes) domain. Mechanistically, eIF3f1 physically associates with dTak1 (Drosophila TGF-beta activating kinase 1), a key regulator of the IMD (immune deficiency) signaling pathway, and mediates the turnover of dTak1 by specifically restricting its K48-linked ubiquitination. Collectively, these results provide compelling insight into a noncanonical molecular function of a translation initiation factor that controls the post-translational modification of a target protein.

A virus-specific monocyte inflammatory phenotype is induced by SARS-CoV-2 at the immune-epithelial interface.

Infection by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) provokes a potentially fatal pneumonia with multiorgan failure, and high systemic inflammation. To gain mechanistic insight and ferret out the root of this immune dysregulation, we modeled, by in vitro coculture, the interactions between infected epithelial cells and immunocytes. A strong response was induced in monocytes and B cells, with a SARS-CoV-2-specific inflammatory gene cluster distinct from that seen in influenza A or Ebola virus-infected cocultures, and which reproduced deviations reported in blood or lung myeloid cells from COVID-19 patients. A substantial fraction of the effect could be reproduced after individual transfection of several SARS-CoV-2 proteins (Spike and some nonstructural proteins), mediated by soluble factors, but not via transcriptional induction. This response was greatly muted in monocytes from healthy children, perhaps a clue to the age dependency of COVID-19. These results suggest that the inflammatory malfunction in COVID-19 is rooted in the earliest perturbations that SARS-CoV-2 induces in epithelia.

E3 ligase Cul2 mediates Drosophila early germ cell differentiation through targeting Bam.

Drosophila ovary has been one of the most mature and excellent systems for studying the in vivo regulatory mechanisms of stem cell fate determination. It has been well-known that the bone morphogenetic protein (BMP) signaling released by the niche cells promotes the maintenance of germline stem cells (GSCs) through inhibiting the transcription of the bag-of-marbles (bam) gene, which encodes a key factor for GSC differentiation. However, whether Bam is regulated at the post-translational level remains largely unknown. Here we show that the E3 ligase Cullin-2 (Cul2) is involved in modulating Bam ubiquitination, which occurs probably at multiple lysine residues of Bam's C-terminal region. Genetic evidence further supports the notion that Cul2-mediated Bam ubiquitination and turnover are essential for GSC maintenance and proper germline development. Collectively, our data not only uncovers a novel regulatory mechanism by which Bam is controlled at the post-translational level, but also provides new insights into how Cullin family protein determines the differentiation fate of early germ cells.

Programmable, Self-Healable, and Photochromic Liquid Crystal Elastomers Based on Dynamic Hindered Urea Bonds for Biomimetic Flowers.

Recently, researchers have been exploring the use of dynamic covalent bonds (DCBs) in the construction of exchangeable liquid crystal elastomers (LCEs) for biomimetic actuators and devices. However, a significant challenge remains in achieving LCEs with both excellent dynamic properties and superior mechanical strength and stability. In this study, a diacrylate-functionalized monomer containing dynamic hindered urea bonds (DA-HUB) is employed to prepare exchangeable LCEs through a self-catalytic Michael addition reaction. By incorporating DA-HUB, the LCE system benefits from DCBs and hydrogen bonding, leading to materials with high mechanical strength and a range of dynamic properties such as programmability, self-healing, and recyclability. Leveraging these characteristics, bilayer LCE actuators with controlled reversible thermal deformation and outstanding dimensional stability are successfully fabricated using a simple welding method. Moreover, a biomimetic triangular plum, inspired by the blooming of flowers, is created to showcase reversible color and shape changes triggered by light and heat. This innovative approach opens new possibilities for the development of biomimetic and smart actuators and devices with multiple functionalities.

The Value of Percutaneous Contrast-Enhanced Ultrasound in Sentinel Lymph Node Identification, Metastatic Status and Burden Diagnosis in Early Breast Cancer.

OBJECTIVE: The aim of this study was to evaluate the value of percutaneous contrast-enhanced ultrasound (PCEUS) in the identification and characterization of sentinel lymph node (SLN). METHODS: A total of 102 breast cancer patients were collected and underwent preoperative PCEUS, which was used to identify SLN and lymphatic drainage. SLNs were classified into 4 enhancement patterns, including 6 subtypes: homogeneous (I), featured inhomogeneous (II) including inhomogeneous hypoenhancement (IIa) and annular or semi-annular enhancement (IIb), focal filling defect (III) including filling defect area < 50% (IIIa) and filling defect area ≥ 50% (IIIb), and no enhancement (IV). The enhancement patterns of SLNs were compared with the final pathological diagnosis. RESULTS: The identification rate of SLNs using PCEUS was 100% (102/102); the rate of identification of LCs was 100% (102/102), and the coincidence rate was 98.0% (100/102). Four lymphatic drainage patterns (LDPs) including 5 subtypes were found: single LC/single SLN(74.5%), multiple LCs/ single SLN (13.7%) including 2 subtypes:2 LCs/1 SLN and 3 LCs/1 SLN, single LC/multiple SLNs (7.8%), and multiple LCs/multiple SLNs (3.9%). A total of 86.3% (44/51) of patients without axillary metastasis could be safely selected for types I, IIa, and IIb, while the axillary metastasis rates of types III and IV were 74.4% and 87.5%, respectively (P < .001). Compared with grayscale US, the PCEUS significant improvement in diagnosing metastatic SLNs (.794 versus .579, P < .001). For the SLN metastatic burden, Types I, IIa, IIb, and IIIa had ≤2 SLNs metastases, with a pathological coincidence rate of (64/67, 95.5%), and types IIIb and IV had >2 SLNs metastases, with a pathological coincidence rate of (25/35, 71.4%) (P < .001). The AUC of PCEUS for the diagnosis of SLN metastatic status and burden was .794 and .879, respectively (P < .001). CONCLUSION: PCEUS has a high identification rate for SLN and has good potential for diagnosing SLN metastatic status and burden by enhancement patterns.

The value of Demetics ultrasound-assisted diagnosis system in diagnosis of breast lesions and in assessment Ki-67 status of breast cancer.

PURPOSE: This study aims to explore the diagnostic efficiency of the Demetics for breast lesions and assessment of Ki-67 status. MATERIAL: This retrospective study included 291 patients. Three combined methods (method 1: upgraded BI-RADS when Demetics classified the breast lesion as malignant; method 2: downgraded BI-RADS when Demetics classified the breast lesion as benign; method 3: BI-RADS was upgraded or downgraded according to Demetrics' diagnosis) were used to compare the diagnostic efficiency of two radiologists with different seniority before and after using Demetics. The correlation between the visual heatmap by Demetics and the Ki-67 expression level of breast cancer was explored. RESULTS: The sensitivity, specificity, and area under curve (AUC) of diagnosis by Demetics, junior radiologist and senior radiologist were 89.5%, 83.1%, 0.863; 76.9%, 82.4%, 0.797 and 81.1%, 89.9%, 0.855, respectively. Method 1 was the best for senior radiologist, which increased AUC from 0.855 to 0.884. For junior radiologist, Method 3 was the best method, improving sensitivity (88.8% vs. 76.9%) and specificity (87.2% vs. 82.4%). Demetics paid more attention to the peripheral area of breast cancer with high expression of Ki-67. CONCLUSION: Demetics has shown good diagnostic efficiency in the assisted diagnosis of breast lesions and is expected to further distinguish Ki-67 status of breast cancer.

Clinical Value of Artificial Intelligence-Based Computer-Aided Diagnosis System Versus Contrast-Enhanced Ultrasound for Differentiation of Benign From Malignant Thyroid Nodules in Different Backgrounds.

OBJECTIVES: The aim of this study was to compare the value of the AI-SONIC ultrasound-assisted diagnosis system versus contrast-enhanced ultrasound (CEUS) for differential diagnosis of thyroid nodules in diffuse and non-diffuse backgrounds. METHODS: A total of 555 thyroid nodules with pathologically confirmed diagnosis were included in this retrospective study. The diagnostic efficacies of AI-SONIC and CEUS for differentiating benign from malignant nodules in diffuse and non-diffuse backgrounds were evaluated, with pathological diagnosis as the gold standard. RESULTS: The agreement between AI-SONIC diagnosis and pathological diagnosis was moderate in diffuse backgrounds (κ = 0.417) and almost perfect in non-diffuse backgrounds (κ = 0.81). The agreement between CEUS diagnosis and pathological diagnosis was substantial in diffuse backgrounds (κ = 0.684) and moderate in non-diffuse backgrounds (κ = 0.407). In diffuse backgrounds, AI-SONIC had slightly higher sensitivity (95.7 vs 89.4%, P = .375), but CEUS had significantly higher specificity (80.0 vs 40.0%, P = .008). In non-diffuse background, AI-SONIC had significantly higher sensitivity (96.2 vs 73.4%, P < .001), specificity (82.9 vs 71.2%, P = .007), and negative predictive value (90.3 vs 53.3%, P < .001). CONCLUSION: In non-diffuse backgrounds, AI-SONIC is superior to CEUS for differentiating malignant from benign thyroid nodules. In diffuse backgrounds, AI-SONIC could be useful for screening of cases to detect suspicious nodules requiring further examination by CEUS.

Evaluating Tumor-Infiltrating Lymphocytes in Breast Cancer: The Role of Conventional Ultrasound and Contrast-Enhanced Ultrasound.

OBJECTIVES: Tumor-infiltrating lymphocytes (TILs) have emerged as an efficient biomarker predicting treatment response and prognosis of breast cancer (BC). This study aimed to evaluate the association between conventional ultrasound and contrast-enhanced ultrasound (CEUS) imaging features with TIL levels in invasive BC patients. METHODS: We retrospectively included 267 women with invasive BC who had undergone conventional ultrasound and CEUS. Patients were divided into low (≤10%) and high (>10%) TIL groups. Conventional ultrasound and CEUS features were analyzed by two sonographers. The associations between the TIL levels and imaging features were evaluated. RESULTS: Of the 267 patients, 122 with high TILs and 145 with low TIL levels. High TIL tumors were more likely to have a circumscribed margin, oval or round shape, and enhanced posterior echoes on ultrasonography (p < 0.05). In contrast, low TIL tumors were more likely to have an irregular shape, un-circumscribed, indistinct and spiculated margin (p < 0.05). In CEUS, high TIL tumors showed a more regular shape, clearer margin, more homogeneous enhancement and higher peak intensity (PI) value (p < 0.05). Logistic analysis indicated that shape, posterior features, PI, and enhanced homogeneity were independent predictors for high TIL tumors. The model combined the four independent predictors have a moderate performance in predicting high TIL tumors with AUC 0.79, sensitivity 0.72, and specificity 0.78. CONCLUSIONS: Conventional ultrasound and CEUS features were associated with TIL levels in invasive BC. Consequently, the results suggested that preoperative conventional ultrasound and CEUS may be a useful noninvasive imaging biomarker for individualized treatment decisions.

Deep learning radiomics of multimodal ultrasound for classifying metastatic cervical lymphadenopathy into primary cancer sites: a feasibility study.

PURPOSE: To investigate the feasibility of deep learning radiomics (DLR) based on multimodal ultrasound to differentiate the primary cancer sites of metastatic cervical lymphadenopathy (CLA). MATERIALS AND METHODS: This study analyzed 280 biopsy-confirmed metastatic CLAs from 280 cancer patients, including 54 from head and neck squamous cell carcinoma (HNSCC), 58 from thyroid cancer (TC), 92 from lung cancer (LC), and 76 from gastrointestinal cancer (GIC). Before biopsy, patients underwent conventional ultrasound (CUS), ultrasound elastography (UE), and contrast-enhanced ultrasound (CEUS). Based on CUS, DLR models using CUS, CUS+UE, CUS+CEUS, and CUS+UE+CEUS data were developed and compared. The best model was integrated with key clinical indicators selected by univariate analysis to achieve the best classification performance. RESULTS: All DLR models achieved similar performance with respect to classifying four primary tumor sites of metastatic CLA (AUC:0.708~0.755). After integrating key clinical indicators (age, sex, and neck level), the US+UE+CEUS+clinical model yielded the best performance with an overall AUC of 0.822 in the validation cohort, but there was no significance compared with the basal CUS+clinical model (P>0.05), both of which identified metastasis from HNSCC, TC, LC, and GIC with 0.869 and 0.911, 0.838 and 0.916, 0.750 and 0.610, and 0.829 and 0.769, respectively. CONCLUSION: The ultrasound-based DLR model can be used to classify the primary cancer sites of metastatic CLA, and the CUS combined with clinical indicators is adequate to provide a high discriminatory performance. The addition of the combination of UE and CEUS data is expected to further improve performance.

Spacecraft Segment Damage Identification Method Based on Fiber Optic Strain Difference Field Reconstruction and Norm Calculation.

Real-time online identification of spacecraft segment damage is of great significance for realizing spacecraft structural health monitoring and life prediction. In this paper, a damage response characteristic field inversion algorithm based on the differential reconstruction of strain response is proposed to solve the problem of not being able to recognize the small damages of spacecraft structure directly by the strain response alone. Four crack damage location identification methods based on vector norm computation are proposed, which realize online identification and precise location of structural damage events without external excitation by means of spacecraft structural working loads only. A spacecraft segment structural damage monitoring system based on fiber optic grating sensors was constructed, and the average error of damage localization based on the curvature vector 2 norm calculation was 2.58 mm, and the root-mean-square error was 1.98 mm. The results show that the method has superior engineering applicability for on-orbit service environments.

Dietary Supplementation of Aspirin Promotes Drosophila Defense against Viral Infection.

Aspirin, also known as acetylsalicylic acid, is widely consumed as a pain reliever and an anti-inflammatory as well as anti-platelet agent. Recently, our studies using the animal model of Drosophila demonstrated that the dietary supplementation of aspirin renovates age-onset intestinal dysfunction and delays organismal aging. Nevertheless, it remains probable that aspirin plays functional roles in other biological activities, for instance antiviral defense reactions. Intriguingly, we observed that the replications of several types of viruses were drastically antagonized in Drosophila macrophage-like S2 cells with the addition of aspirin. Further in vivo experimental approaches illustrate that adult flies consuming aspirin harbor higher resistances to viral infections with respect to flies without aspirin treatment. Mechanistically, aspirin positively contributes to the Drosophila antiviral defense largely through mediating the STING (stimulator of interferon genes) but not the IMD (immune deficiency) signaling pathway. Collectively, our studies uncover a novel biological function of aspirin in modulating Drosophila antiviral immunity and provide theoretical bases for exploring new antiviral treatments in clinical trials.

Deep learning radiomics of dual-modality ultrasound images for hierarchical diagnosis of unexplained cervical lymphadenopathy.

BACKGROUND: Accurate diagnosis of unexplained cervical lymphadenopathy (CLA) using medical images heavily relies on the experience of radiologists, which is even worse for CLA patients in underdeveloped countries and regions, because of lack of expertise and reliable medical history. This study aimed to develop a deep learning (DL) radiomics model based on B-mode and color Doppler ultrasound images for assisting radiologists to improve their diagnoses of the etiology of unexplained CLA. METHODS: Patients with unexplained CLA who received ultrasound examinations from three hospitals located in underdeveloped areas of China were retrospectively enrolled. They were all pathologically confirmed with reactive hyperplasia, tuberculous lymphadenitis, lymphoma, or metastatic carcinoma. By mimicking the diagnosis logic of radiologists, three DL sub-models were developed to achieve the primary diagnosis of benign and malignant, the secondary diagnosis of reactive hyperplasia and tuberculous lymphadenitis in benign candidates, and of lymphoma and metastatic carcinoma in malignant candidates, respectively. Then, a CLA hierarchical diagnostic model (CLA-HDM) integrating all sub-models was proposed to classify the specific etiology of each unexplained CLA. The assistant effectiveness of CLA-HDM was assessed by comparing six radiologists between without and with using the DL-based classification and heatmap guidance. RESULTS: A total of 763 patients with unexplained CLA were enrolled and were split into the training cohort (n=395), internal testing cohort (n=171), and external testing cohorts 1 (n=105) and 2 (n=92). The CLA-HDM for diagnosing four common etiologies of unexplained CLA achieved AUCs of 0.873 (95% CI: 0.838-0.908), 0.837 (95% CI: 0.789-0.889), and 0.840 (95% CI: 0.789-0.898) in the three testing cohorts, respectively, which was systematically more accurate than all the participating radiologists. With its assistance, the accuracy, sensitivity, and specificity of six radiologists with different levels of experience were generally improved, reducing the false-negative rate of 2.2-10% and the false-positive rate of 0.7-3.1%. CONCLUSIONS: Multi-cohort testing demonstrated our DL model integrating dual-modality ultrasound images achieved accurate diagnosis of unexplained CLA. With its assistance, the gap between radiologists with different levels of experience was narrowed, which is potentially of great significance for benefiting CLA patients in underdeveloped countries and regions worldwide.

Microsomal prostaglandin E synthase 2 deficiency is resistant to acetaminophen-induced liver injury.

Acetaminophen (APAP)-induced liver injury is the main cause of acute liver failure. This study investigated the role of microsomal prostaglandin E synthase 2 (mPGES-2), discovered as one of the prostaglandin E2 (PGE2) synthases, in mediating APAP-induced liver injury. Using mPGES-2 wild-type (WT) and knockout (KO) mice, marked resistance to APAP-induced liver damage was found in mPGES-2 KO, as indicated by robust improvement of liver histology, changes in liver enzyme release, and marked decrease in APAP-cysteine adducts (APAP-CYS) and inflammatory markers. Moreover, the results confirmed that increase in liver PGE2 content in KO mice under basal conditions was not critical for the protection from APAP-induced liver injury. Importantly, mPGES-2 deletion inhibited the production of malondialdehyde (MDA), increasing glutathione (GSH) level. Enhanced GSH level may contribute to the inhibition of APAP toxicity in mPGES-2 KO mice. To further elucidate the role of mPGES-2 in the liver injury induced by APAP, adeno-associated viruses (AAV) were used to overexpress mPGES-2 in the liver. The results showed that mPGES-2 overexpression aggravates liver injury associated with an increase in inflammatory markers and chemokines after APAP treatment. Moreover, a lower level of GSH was detected in the mPGES-2 overexpression group compared to the control group. Collectively, our findings indicate that mPGES-2 plays a critical role in regulating APAP-induced liver injury, possibly by regulating GSH and APAP-CYS level, which may provide a potential therapeutic strategy for the prevention and treatment of APAP-induced liver injury.

T follicular helper cells, T follicular regulatory cells and autoimmunity.

CD4(+)T follicular helper (Tfh) cells are recognized as a distinct T-cell subset, which provides help for germinal center (GC) formation, B-cell development and affinity maturation, and immunoglobulin class switching, as an indispensable part of adaptive immunity. Tfh cell differentiation depends on various factors including cell-surface molecule interactions, extracellular cytokines and multiple transcription factors, with B-cell lymphoma 6 (Bcl-6) being the master regulator. T follicular regulatory (Tfr) cells are also located in the GC and share phenotypic characteristics with Tfh cells and regulatory T cells, but function as negative regulators of GC responses. Dysregulation of either Tfh or Tfr cells is linked to the pathogenesis of autoimmune diseases such as systemic lupus erythematosus. This review covers the basic Tfh and Tfr biology including their differentiation and function, and their close relationship with autoimmune diseases.

Inhibition of mitochondrial complex-1 restores the downregulation of aquaporins in obstructive nephropathy.

Obstructive kidney disease is a common complication in the clinic. Downregulation of aquaporins (AQPs) in obstructed kidneys has been thought as a key factor leading to the polyuria and impairment of urine-concentrating capability after the release of kidney obstruction. The present study was to investigate the role of mitochondrial complex-1 in modulating AQPs in obstructive nephropathy. Following 7-day unilateral ureteral obstruction (UUO), AQP1, AQP2, AQP3, and vasopressin 2 (V2) receptor were remarkably reduced as determined by qRT-PCR and/or Western blotting. Notably, inhibition of mitochondrial complex-1 by rotenone markedly reversed the downregulation of AQP1, AQP2, AQP3, and V2 In contrast, AQP4 was not affected by kidney obstruction or rotenone treatment. In a separate study, rotenone also attenuated AQPs' downregulation after 48-h UUO. To study the potential mechanisms in mediating the rotenone effects on AQPs, we examined the regulation of the COX-2/microsomal prostaglandin E synthase (mPGES)-1/PGE2/EP pathway and found that COX-2, mPGES-1, and renal PGE2 content were all significantly elevated in obstructive kidneys, which was not affected by rotenone treatment. For EP receptors, EP2 and EP4 but not EP1 and EP3 were upregulated in obstructive kidneys. Importantly, rotenone strikingly suppressed EP1 and EP4 but not EP2 and EP3 receptors. However, treatment of EP1 antagonist SC-51322 could not affect AQPs' reduction in obstructed kidneys. Collectively, these findings suggested an important role of mitochondrial dysfunction in modulating AQPs and V2 receptor in obstructive nephropathy possibly via prostaglandin-independent mechanisms.

Fibroblast engraftment in the decellularized mouse lung occurs via a ß1-integrin-dependent, FAK-dependent pathway that is mediated by ERK and opposed by AKT.

Creation of bioartificial organs has been enhanced by the development of strategies involving decellularized mammalian lung. Because fibroblasts critically support lung function through a number of mechanisms, study of these cells in the context of the decellularized lung has the potential to improve the structure and function of tissue-engineered lungs. We characterized the engraftment and survival of a mouse fibroblast cell line in decellularized rat lung slices and found a time-dependent increase in cell numbers assessed by hematoxylin and eosin staining, cell proliferation assessed by Ki67 staining, and minimal cell death assessed by TUNEL staining. We developed a repopulation index to allow quantification of cell survival that accounts for variation in cell density throughout the seeded scaffold. We then applied this method to the study of mouse lung scaffolds and found that decellularization of presliced mouse lungs produced matrices with preserved alveolar architecture and proteinaceous components including fibronectin, collagens I and IV, laminin, and elastin. Treatment with a ß1-integrin-neutralizing antibody significantly reduced the repopulation index after 24 h of culture. Treatment with focal adhesion kinase (FAK) inhibitor and extracellular signal-regulated kinase (ERK) inhibitor further reduced initial repopulation scores while treatment with AKT inhibitor increased initial scores. Rho-associated kinase inhibitor had no discernible effect. These data indicate that initial adhesion and survival of mouse fibroblasts in the decellularized mouse lung occur in a ß1-integrin-dependent, FAK/ERK-dependent manner that is opposed by AKT.

Disentangling the mechanism of student engagement in online language classrooms from the perspective of Community of Inquiry.

Previous studies have revealed that students' participation is a complex matter affected by pedagogical, environmental, and individual factors. However, there is still insufficient empirical evidence regarding how those factors work in shaping classroom participation in the online context. In the field of language education, moreover, it still remains unclear as to how social interactions among students and teachers may affect students' cognitive engagement. To further understand the complex relations between language students' online engagement and the influencing factors, the current study conducted in-depth interviews with 24 university students enrolled in three online English courses in an International university in China. Analyses and interpretation of the qualitative data were informed by the Community of Inquiry framework. The findings suggest that students' engagement in online classrooms is a situated process affected by 1) pedagogical practices and support from teachers, which determines students' cognitive presence and perceived teaching presence directly, and 2) students' perceived social presence, which was shaped by both group dynamics and the online environment. Notably, the physically isolated online environment seemed to have played an impeding role in some students' cognitive engagement, but a facilitating a role in some others', as mediated by their preference for social presence or absence. Overall, our study highlights the importance of providing students with a constructive, supportive and interactive environment for online language teaching and learning.

Predictive value for axillary lymph node metastases in early breast cancer: Based on contrast-enhanced ultrasound characteristics of the primary lesion and sentinel lymph node.

OBJECTIVE: To evaluate the value of contrast-enhanced ultrasound (CEUS) characteristics based on primary lesion combined with lymphatic contrast-enhanced ultrasound (LCEUS) patterns of SLN in predicting axillary lymph node metastasis (ALNM) with T1-2N0 breast cancer. METHODS: A retrospective study was conducted in 118 patients with clinically confirmed T1-2N0 breast cancer. Conventional ultrasound (CUS) and CEUS characteristics of the primary lesion and enhancement patterns of SLN were recorded. The risk factors associated with ALNM were selected by univariate and binary logistic regression analysis, and the receiver operating characteristic (ROC) curve was drawn for the evaluation of predictive ALNM metastasis performance. RESULTS: Univariate analysis showed that age, HER-2 status, tumor size, nutrient vessels, extended range of enhancement lesion, and the enhancement patterns of SLN were significant predictive features of ALNM. Further binary logistic regression analysis indicated that the extended range of enhancement lesion (p <  0.001) and the enhancement patterns of SLN (p <  0.001) were independent risk factors for ALNM. ROC analysis showed that the AUC of the combination of these two indicators for predicting ALNM was 0.931 (95% CI: 0.887-0.976, sensitivity: 75.0%, specificity: 99.8%). CONCLUSION: The CEUS characteristics of primary lesion combined with enhancement patterns of SLN are highly valuable in predicting ALNM and can guide clinical axillary surgery decision-making in early breast cancer.

A dynamic atlas of immunocyte migration from the gut.

Dysbiosis in the gut microbiota affects several systemic diseases, possibly by driving the migration of perturbed intestinal immunocytes to extraintestinal tissues. Combining Kaede photoconvertible mice and single-cell genomics, we generated a detailed map of migratory trajectories from the colon, at baseline, and in several models of intestinal and extraintestinal inflammation. All lineages emigrated from the colon in an S1P-dependent manner. B lymphocytes represented the largest contingent, with the unexpected circulation of nonexperienced follicular B cells, which carried a gut-imprinted transcriptomic signature. T cell emigration included distinct groups of RORγ+ and IEL-like CD160+ subsets. Gut inflammation curtailed emigration, except for dendritic cells disseminating to lymph nodes. Colon-emigrating cells distributed differentially to distinct sites of extraintestinal models of inflammation (psoriasis-like skin, arthritic synovium, and tumors). Thus, specific cellular trails originating in the gut and influenced by microbiota may shape peripheral immunity in varied ways.