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.

Iron overload in hypothalamic AgRP neurons contributes to obesity and related metabolic disorders.

Iron overload is closely associated with metabolic dysfunction. However, the role of iron in the hypothalamus remains unclear. Here, we find that hypothalamic iron levels are increased, particularly in agouti-related peptide (AgRP)-expressing neurons in high-fat-diet-fed mice. Using pharmacological or genetic approaches, we reduce iron overload in AgRP neurons by central deferoxamine administration or transferrin receptor 1 (Tfrc) deletion, ameliorating diet-induced obesity and related metabolic dysfunction. Conversely, Tfrc-mediated iron overload in AgRP neurons leads to overeating and adiposity. Mechanistically, the reduction of iron overload in AgRP neurons inhibits AgRP neuron activity; improves insulin and leptin sensitivity; and inhibits iron-induced oxidative stress, endoplasmic reticulum stress, nuclear factor κB signaling, and suppression of cytokine signaling 3 expression. These results highlight the critical role of hypothalamic iron in obesity development and suggest targets for treating obesity and related metabolic disorders.

MDSC-targeting gold nanoparticles enhance PD-1 tumor immunotherapy by inhibiting NLRP3 inflammasomes.

Myeloid-derived suppressor cells (MDSCs) play a crucial role in the immune escape mechanisms that limit the efficacy of immunotherapeutic strategies. In the tumor microenvironment, NLRP3 inflammasome-driven Interleukin-1ß (IL-1ß) production serves to dampen antitumor immune responses, promoting tumor growth, progression, and immunosuppression. In this study, we revealed that gold nanoparticles (Au NPs) with a size of 30 nm disrupted NLRP3 inflammasome, but not other inflammasomes, in bone marrow-derived macrophages through abrogating NLRP3-NEK7 interactions mediated by reactive oxygen species (ROS). Density functional theory (DFT) calculations provided insights into the mechanism underlying the exceptional ROS scavenging capabilities of Au NPs. Additionally, when coupled with H6, a small peptide targeting MDSCs, Au NPs demonstrated the capacity to effectively reduce IL-1ß levels and diminish the MDSCs population in tumor microenvironment, leading to enhanced T cell activation and increased immunotherapeutic efficacy in mouse tumor models that are sensitive and resistant to PD-1 inhibition. Our findings unraveled a novel approach wherein peptide-modified Au NPs relieved the suppressive impact of the tumor microenvironment by inhibiting MDSCs-mediated IL-1ß release, which is the first time reported the employing a nanostrategy at modulating MDSCs to reverse the immunosuppressive microenvironment and may hold promise as a potential therapeutic agent for cancer immunotherapy.

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 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.

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.

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.

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.

Spatiotemporal divergence and convergence test of green total factor productivity of grain in China: based on the dual perspective of carbon emissions and surface source pollution.

The topic of grain production and quality has always been a fundamental issue for the country's livelihood. With the purpose of contributing to high-quality grain development and ensuring national food security, this paper explores the spatial and temporal evolution, regional differences and convergence of grain green total factor productivity (GTFP) in the main grain-producing regions of China from the dual perspectives of carbon emissions and surface pollution with the help of EBM-GML model, kernel density function estimation and convergence methods. The results show that (1) Grain GTFP has generally shown a positive growth trend, although there exists obvious spatial differences. (2) In terms of decomposition indices, technological progress is the source of the increase in grain GTFP. (3) There are σ convergence, absolute ß convergence and conditional ß convergence in the main producing region as well as in the Yellow River basin and the Yangtze River basin; there are only absolute ß convergence and conditional ß convergence in the Songhua River basin. Grain GTFP has a single high-efficiency convergence point, and the grain GTFP is enhancing year by year in each province, and the inter-provincial gap is shrinking.

Regulatory T cells in the face of the intestinal microbiota.

Regulatory T cells (Treg cells) are key players in ensuring a peaceful coexistence with microorganisms and food antigens at intestinal borders. Startling new information has appeared in recent years on their diversity, the importance of the transcription factor FOXP3, how T cell receptors influence their fate and the unexpected and varied cellular partners that influence Treg cell homeostatic setpoints. We also revisit some tenets, maintained by the echo chambers of Reviews, that rest on uncertain foundations or are a subject of debate.

Comparative Study of the Efficacy of the Ovarian-Adnexa Reporting and Data System Ultrasound Combined With Contrast-Enhanced Ultrasound and the ADNEX MR Scoring System in the Diagnosis of Adnexal Masses.

OBJECTIVE: The aims of this study were to develop the Ovarian-Adnexa Reporting and Data System (O-RADS) and O-RADS + contrast-enhanced ultrasound (O-RADS CEUS) scoring system to distinguish adnexal masses (AMs) and to compare the diagnostic efficacy of these systems with that of a magnetic resonance imaging scoring system (ADNEX MR). METHODS: We retrospectively evaluated 278 ovarian masses from 240 patients between May 2017 and July 2022. Pathology and adequate follow-up were used as reference standards for comparing the validity of O-RADS, O-RADS CEUS and ADNEX MR scoring to diagnose AMs. Area under the curve (AUC), sensitivity and specificity were calculated. The inter-class correlation coefficient (ICC) was calculated to evaluate inter-reader agreement (IRA) between the two sonographers and two radiologists who analyzed the findings with the three modalities. RESULTS: The AUCs of O-RADS, O-RADS CEUS and ADNEX MR scores were 0.928 (95% confidence interval [CI]: 0.895-0.956), 0.951(95% CI: 0.919-0.973) and 0.964 (95% CI: 0.935-0.983), respectively. Their sensitivities were 95.7%, 94.3 and 91.4%, and their specificities were 81.3%, 92.3% and 97.1%, respectively. The three modalities had accuracies of 84.9%, 92.8% and 95.7%, respectively. O-RADS had the highest sensitivity but significantly lower specificity (p < 0.001), whereas the ADNEX MR scoring had the highest specificity (p < 0.001) but lower sensitivity (p < 0.001). O-RADS CEUS had intermediate sensitivity and specificity (p < 0.001). CONCLUSION: The addition of CEUS significantly improves the efficacy of O-RADS in diagnosing AMs. The diagnostic efficacy of the combination is comparable to that of the ADNEX MR scoring system.

Ultrasound features combined with tumor-infiltrating lymphocytes for prediction of pathological response to neoadjuvant chemotherapy in breast cancer.

AIM: Neoadjuvant chemotherapy (NAC) plays an important role in the treatment and prognosis of breast cancer. The early identification of patients who can truly benefit from preoperative NAC is crucial in clinical practice. The purpose of this study was to explore whether the ultrasound features and clinical characteristics combined with tumor-infiltrating lymphocyte(TIL) levels can improve the performance of predicting NAC efficacy in breast cancer patients. MATERIAL AND METHODS: In this retrospective study, 202 invasive breast cancer patients who underwent NAC followed by surgery were included. The baseline ultrasound features were reviewed by two radiologists. Miller-Payne Grading (MPG) was used to assess pathological response, and MPG 4-5 was defined as major histologic responders (MHR). Multivariable logistic regression analysis was used to evaluate independent predictors for MHR and build the prediction models. The receiver operating characteristic (ROC) curve was used to evaluate the performance of the models. RESULTS: Of the 202 patients, 104 patients achieved MHR and 98 patients achieved non-MHR. Multivariate logistic regression analysis showed the US size (p=0.042), molecular subtypes (p=0.001), TIL levels (p<0.001), shape (p=0.030), and posterior features (p=0.018) were independent predictors for MHR. The model combined the US features, clinical characteristics, and TIL levels had a better performance with an area under the curve (AUC) of 0.811, a sensitivity of 0.663, and a specificity of 0.847. CONCLUSION: The model combined US features, clinical characteristics, and TIL levels had a better performance in predicting pathological response to NAC in breast cancer.

Parthenolide targets NLRP3 to treat inflammasome-related diseases.

Natural products have attracted extensive attention from researchers in medical fields due to their abundant biological activities. Parthenolide (PTL) is a sesquiterpene lactone originally purified from herb Feverfew (Tanacetum parthenium), recent studies have showed its potential activities of anti-cancer and anti-inflammatory. Acting as the most studied inflammasome, NLRP3 inflammasome played an important role in human diseases including type-2 diabetes (T2D), Alzheimer's disease (AD) and cryopyrin-associated periodic syndromes (CAPS). In this article, we show that PTL specially inhibits the activation of NLRP3 inflammation by block the upstream signal and prevent the assembly of NLRP3 inflammasome complex. Furthermore, we showed the treatment of PTL significantly attenuates the symptoms of lipopolysaccharide (LPS)-induced systemic inflammation and dextran sulfate sodium (DSS)-induced colitis in mice models. Thus, our results demonstrate that PTL alleviates inflammation by targeting NLRP3 inflammasome, which indicate that PTL acting as a promising natural product for the treatment of NLRP3 inflammasome-related diseases.

Comparative study of pathological response evaluation systems after neoadjuvant chemotherapy for breast cancer: developing predictive models of multimodal ultrasound features including shear wave elastography combined with puncture pathology.

Background: This study created a predictive preoperative nomogram dependent on multimodal ultrasound characteristics and primary lesion biopsy results for various pathologic response assessment systems following neoadjuvant chemotherapy (NAC). Methods: This retrospective study included 145 breast cancer patients treated at Gansu Cancer Hospital between January 2021 and June 2022 who underwent shear wave elastography (SWE) prior to completing NAC. Intra- and peritumoral SWE features, including maximum (Emax), mean (Emean), minimum (Emin), and standard deviation (Esd) elasticity, were measured individually and linked with the Miller-Payne grading system and residual cancer burden (RCB) class. Univariate analysis was used for conventional ultrasound and puncture pathology. Binary logistic regression analysis was used to screen for independent risk factors and to develop a prediction model. Results: Intratumor Emean and peritumoral Esd differed significantly from the Miller-Payne grade [intratumor Emean: r=0.129, 95% confidence interval (CI): -0.002 to 0.260; P=0.042; peritumoral Esd: r=0.126, 95% CI: -0.010 to 0.254; P=0.047], RCB class (intratumor Emean: r=-0.184, 95% CI: -0.318 to -0.047; P=0.004; peritumoral Esd: r=-0.139, 95% CI: -0.265 to 0.000; P=0.029) and RCB score components (r=-0.277 to -0.139; P=0.001-0.041). Two prediction model nomograms-pathologic complete response (pCR)/non-pCR and good responder/nonresponder-for the RCB class were developed using binary logistic regression analysis for all significant variables in SWE, conventional ultrasound, and puncture results. The area under the receiver operating characteristic curve for the pCR/non-pCR and good responder/nonresponder models was 0.855 (95% CI: 0.787-0.922) and 0.845 (95% CI: 0.780-0.910), respectively. According to the calibration curve, the nomogram had excellent internal consistency between estimated and actual values. Conclusions: The preoperative nomogram can effectively guide clinicians to predict pathological response of breast cancer after NAC and has the potential to guide individualized treatment.

Neuregulin4 Acts on Hypothalamic ErBb4 to Excite Oxytocin Neurons and Preserve Metabolic Homeostasis.

Neuregulin 4 (Nrg4) is an adipose tissue-enriched secreted factor that modulates glucose and lipid metabolism. Nrg4 is closely associated with obesity and preserves diet-induced metabolic disorders. However, the specific mechanisms via which Nrg4 regulates metabolic homeostasis remain incompletely understood. Here, this work finds that the Nrg4 receptor, ErbB4, is highly expressed in the hypothalamus, and the phosphorylation of hypothalamic ErbB4 is reduced in diet-induced obesity (DIO) mice. Peripheral Nrg4 can act on ErbB4 via blood circulation and excite neurons in the paraventricular nucleus of hypothalamus (PVN). Central administration of recombinant Nrg4 protein (rNrg4) reduces obesity and related metabolic disorders by influencing energy expenditure and intake. Overexpression of ErbB4 in the PVN protects against obesity, whereas its knock down in oxytocin (Oxt) neuron accelerates obesity. Furthermore, Nrg4-ErbB4 signaling excites Oxt release, and ablation of Oxt neuron considerably attenuates the effect of Nrg4 on energy balance. These data suggest that the hypothalamus is a key target of Nrg4, which partially explains the multifaceted roles of Nrg4 in metabolism.