Clotrimazole inhibits growth of multiple myeloma cells in vitro via G0/G1 arrest and mitochondrial apoptosis.

Patients with multiple myeloma (MM) experience relapse and drug resistance; therefore, novel treatments are essential. Clotrimazole (CTZ) is a wide-spectrum antifungal drug with antitumor activity. However, CTZ's effects on MM are unclear. We investigated CTZ's effect on MM cell proliferation and apoptosis induction mechanisms. CTZ's effects on MM.1S, NCI- H929, KMS-11, and U266 cell growth were investigated using Cell Counting Kit-8 (CCK-8) assay. The apoptotic cell percentage was quantified with annexin V-fluorescein isothiocyanate/7-amino actinomycin D staining. Mitochondrial membrane potential (MMP) and cell cycle progression were evaluated. Reactive oxygen species (ROS) levels were measured via fluorescence microscopy. Expression of apoptosis-related and nuclear factor (NF)-κB signaling proteins was analyzed using western blotting. The CCK-8 assay indicated that CTZ inhibited cell proliferation based on both dose and exposure time. Flow cytometry revealed that CTZ decreased apoptosis and MMP and induced G0/G1 arrest. Immunofluorescence demonstrated that CTZ dose-dependently elevated in both total and mitochondrial ROS production. Western blotting showed that CTZ enhanced Bax and cleaved poly ADP-ribose polymerase and caspase-3 while decreasing Bcl-2, p-p65, and p-IκBα. Therefore, CTZ inhibits MM cell proliferation by promoting ROS-mediated mitochondrial apoptosis, inducing G0/G1 arrest, inhibiting the NF-κB pathway, and has the potential for treating MM.

Rapid Mass Spectrometry-Based Multiattribute Method for Glycation Analysis with Integrated Afucosylation Detection Capability.

The multiattribute method (MAM) has emerged as a powerful tool for simultaneously screening multiple product quality attributes of therapeutic antibodies. One such potential critical quality attribute (CQA) is glycation, a common modification that can impact the heterogeneity, functional activity, and immunogenicity of therapeutic antibodies. However, current methods for monitoring glycation levels in MAM are rare and not sufficiently rapid and accurate. In this study, an improved mass spectrometry (MS)-based MAM was developed to simultaneously monitor glycation and other quality attributes including afucosylation. The method was evaluated using two therapeutic antibodies with different glycosylation site numbers. Treatment with IdeS, Endo F2, and dithiothreitol generated three distinct subunits, and the glycation results obtained were similar to those treated with PNGase F, which is routinely used to release glycans; the sample processing time was greatly reduced while providing additional quality attribute information. The MS-based MAM was also employed to assess the glycation progression following forced glycation in various buffer solutions. A significant increase in oxidation was observed when forced glycation was conducted in an ammonium bicarbonate buffer solution, and a total of 23 potential glycation sites and 4 significantly oxidized sites were identified. Notably, we found that ammonium bicarbonate was found to specifically stimulate oxidation, while glycation had a synergistic effect on oxidation. These findings establish this study as a novel methodology for achieving a technologically advanced platform and concept that enhances the efficacy of product development and quality control, characterized by its broad-spectrum, rapid, and accurate nature.

Nasal instillation of polystyrene nanoplastics induce lung injury via mitochondrial DNA release and activation of the cyclic GMP-AMP synthase-stimulator of interferon genes-signaling cascade.

Nanoplastics (NPs) are a common type of degraded plastic material associated with adverse health effects such as pulmonary injury. However, the molecular mechanism(s) underlying lung injury as caused by NPs remains uncertain. Thus, we herein investigated the pulmonary toxicity of NPs on RAW264.7 cells and C57BL/6 mice. Our in vitro study indicated that NPs induced oxidative stress, cell death, inflammation, and the activation of the cyclic GMP-AMP synthase (cGAS)-stimulator of interferon genes (STING)-signaling pathway. Mice in our in vivo study displayed significant pulmonary fibrosis, inflammation, apoptosis, necrosis, and excessive double-stranded DNA release into serum and bronchoalveolar lavage fluid. Our mechanistic exploration uncovered cGAS-STING-signaling activation as the leading cause of NPs-induced pulmonary fibrosis. The current study opens an avenue toward elucidating the role of the cGAS-STING-signaling pathway in NPs-induced pulmonary injury.

A Data Matrix Code Recognition Method Based on L-Shaped Dashed Edge Localization Using Central Prior.

The recognition of data matrix (DM) codes plays a crucial role in industrial production. Significant progress has been made with existing methods. However, for low-quality images with protrusions and interruptions on the L-shaped solid edge (finder pattern) and the dashed edge (timing pattern) of DM codes in industrial production environments, the recognition accuracy rate of existing methods sharply declines due to a lack of consideration for these interference issues. Therefore, ensuring recognition accuracy in the presence of these interference issues is a highly challenging task. To address such interference issues, unlike most existing methods focused on locating the L-shaped solid edge for DM code recognition, we in this paper propose a novel DM code recognition method based on locating the L-shaped dashed edge by incorporating the prior information of the center of the DM code. Specifically, we first use a deep learning-based object detection method to obtain the center of the DM code. Next, to enhance the accuracy of L-shaped dashed edge localization, we design a two-level screening strategy that combines the general constraints and central constraints. The central constraints fully exploit the prior information of the center of the DM code. Finally, we employ libdmtx to decode the content from the precise position image of the DM code. The image is generated by using the L-shaped dashed edge. Experimental results on various types of DM code datasets demonstrate that the proposed method outperforms the compared methods in terms of recognition accuracy rate and time consumption, thus holding significant practical value in an industrial production environment.

Construction and Identification of Eukaryotic Expression Vector pEGFP-N1-MIC-1 for Mouse MIC-1 Gene and Its Effect on Gastric Cancer Cells.

This study aimed to construct an eukaryotic expression vector, pEGFP-N1-MIC-1, for overexpressing the mouse macrophage inhibitory cytokine-1 (MIC-1) gene. Additionally, we transfected the MFC cell line to observe the upregulation of MIC-1 gene expression and assess its impact on macrophage phenotype conversion. Enzyme digestion and DNA sequencing confirmed the successful construction of the pEGFP-N1-MIC-1 vector. The transfected MFC cells exhibited a significant increase in MIC-1 protein expression levels. Furthermore, transfection with pEGFP-N1-MIC-1 increased the migration and colony formation capabilities of MFC cells. These results may contribute to future research and the development of therapeutic interventions targeting MIC-1 in macrophages, particularly in the context of gastric cancer.

Lymph node metastasis in early invasive lung adenocarcinoma: Prediction model establishment and validation based on genomic profiling and clinicopathologic characteristics.

BACKGROUND: The presence of lymph node (LN) metastasis directly affects the treatment strategy for lung adenocarcinoma (LUAD). Next-generation sequencing (NGS) has been widely used in patients with advanced LUAD to identify targeted genes, while early detection of pathologic LN metastasis using NGS has not been assessed. METHODS: Clinicopathologic features and molecular characteristics of 224 patients from Ruijin Hospital were analyzed to detect factors associated with LN metastases. Another 140 patients from Huashan Hospital were set as a test cohort. RESULTS: Twenty-four out of 224 patients were found to have lymph node metastases (10.7%). Pathologic LN-positive tumors showed higher mutant allele tumor heterogeneity (p < 0.05), higher tumor mutation burden (p < 0.001), as well as more frequent KEAP1 (p = 0.001), STK11 (p = 0.004), KRAS (p = 0.007), CTNNB1 (p = 0.017), TP53, and ARID2 mutations (both p = 0.02); whereas low frequency of EGFR mutation (p = 0.005). A predictive nomogram involving male sex, solid tumor morphology, higher T stage, EGFR wild-type, and TP53, STK11, CDKN2A, KEAP1, ARID2, KRAS, SDHA, SPEN, CTNNB1, DICER1 mutations showed outstanding efficiency in both the training cohort (AUC = 0.819) and the test cohort (AUC = 0.780). CONCLUSION: This study suggests that the integration of genomic profiling and clinical features identifies early-invasive LUAD patients at higher risk of LN metastasis. Improved identification of LN metastasis is beneficial for the optimization of the patient's therapy decisions.

Using machine learning to identify environmental factors that collectively determine microbial community structure of activated sludge.

Activated sludge (AS) microbial communities are influenced by various environmental variables. However, a comprehensive analysis of how these variables jointly and nonlinearly shape the AS microbial community remains challenging. In this study, we employed advanced machine learning techniques to elucidate the collective effects of environmental variables on the structure and function of AS microbial communities. Applying Dirichlet multinomial mixtures analysis to 311 global AS samples, we identified four distinct microbial community types (AS-types), each characterized by unique microbial compositions and metabolic profiles. We used 14 classical linear and nonlinear machine learning methods to select a baseline model. The extremely randomized trees demonstrated optimal performance in learning the relationship between environmental factors and AS types (with an accuracy of 71.43%). Feature selection identified critical environmental factors and their importance rankings, including latitude (Lat), longitude (Long), precipitation during sampling (Precip), solids retention time (SRT), effluent total nitrogen (Effluent TN), average temperature during sampling month (Avg Temp), mixed liquor temperature (Mixed Temp), influent biochemical oxygen demand (Influent BOD), and annual precipitation (Annual Precip). Significantly, Lat, Long, Precip, Avg Temp, and Annual Precip, influenced metabolic variations among AS types. These findings emphasize the pivotal role of environmental variables in shaping microbial community structures and enhancing metabolic pathways within activated sludge. Our study encourages the application of machine learning techniques to design artificial activated sludge microbial communities for specific environmental purposes.

Favored Amorphous LixSi Process with Restrained Volume Change Enabling Long Cycling Quasi-solid-state SiOx anode.

Silicon-based anodes are becoming promising materials due to their high specific capacity. However, the intrinsically large volume change brought about by the alloying reaction results in the crushing of the active particles and destruction of the electrode structure, which severely limits its practical application. Various structured and modified silica-based anodes exhibit improved cycling stability and the demonstrated ability to mitigate their volume changes through interfacial and binder strategies. However, the issue of large volume changes in silicon-based anodes remains. Herein, we report a gel polymer electrolyte (GPE) prepared through an in situ thermal polymerization process that is suitable for SiOx anode materials and achieving long-term cycling stability. GPE-based cells essentially mitigate the volume change of SiOx anodes by guiding the unique lithiation/delithiation mechanism that tends to favor the formation and delithiation of amorphous-LixSi (a-LixSi) with smaller volume change, thereby mitigating electrode damage and cracking, and achieving the significant improvement in cycling performance. The prepared GPE-SiOx cells retained 693.80 mAh g-1 reversible capacity after 450 cycles at 500 mA g-1. In addition, the prelithiation process was incorporated to mitigate capacity fluctuations and improve the Initial Coulombic Efficiency (ICE), and a reversible capacity of 641.90 mAh g-1 was retained after 480 cycles.

Neoadjuvant BRAF and MEK inhibitor therapy elicits pathological complete response in stage IIIA non-small cell lung cancer harboring BRAF V600E mutation: A case report.

In recent years, significant improvement has been made in the management of non-small cell lung cancer (NSCLC), primarily driven by advances in targeted therapy and immunotherapy. Research on neoadjuvant targeted therapy has also experienced considerable development, primarily directed towards NSCLC harboring epidermal growth factor receptor or anaplastic lymphoma kinase mutations. Nevertheless, there remains a dearth of studies investigating neoadjuvant targeted therapy in the context of BRAF (V-Raf murine sarcoma viral oncogene homolog B) V600E mutant NSCLC. Herein, we describe the clinical trajectory of a stage IIIA NSCLC patient who underwent a two-month course of neoadjuvant targeted therapy comprising BRAF and MEK (mitogen-activated extracellular signal-regulated kinase) inhibitors prior to surgical intervention, and subsequent postoperative evaluation unveiled a pathological complete response. The case reported here indicates the efficacy and safety of combining BRAF and MEK inhibitors as neoadjuvant targeted therapy in BRAF V600E-mutant NSCLC and suggests the potential viability of such a therapeutic modality in improving treatment outcomes in this subset of NSCLC.

Multi-degradation-adaptation network for fundus image enhancement with degradation representation learning.

Fundus image quality serves a crucial asset for medical diagnosis and applications. However, such images often suffer degradation during image acquisition where multiple types of degradation can occur in each image. Although recent deep learning based methods have shown promising results in image enhancement, they tend to focus on restoring one aspect of degradation and lack generalisability to multiple modes of degradation. We propose an adaptive image enhancement network that can simultaneously handle a mixture of different degradations. The main contribution of this work is to introduce our Multi-Degradation-Adaptive module which dynamically generates filters for different types of degradation. Moreover, we explore degradation representation learning and propose the degradation representation network and Multi-Degradation-Adaptive discriminator for our accompanying image enhancement network. Experimental results demonstrate that our method outperforms several existing state-of-the-art methods in fundus image enhancement. Code will be available at https://github.com/RuoyuGuo/MDA-Net.

Trace of delirium after robotic lower abdominal tumor resection at different end-tidal carbon dioxide: a RCT trial.

BACKGROUND: Postoperative delirium (POD) often occurs in oncology patients, further increasing the medical and financial burden. Robotic technology in lower abdominal tumors resection reduces surgical trauma but increases risks such as carbon dioxide (CO2) absorption. This study aimed to investigate the differences in their occurrence of POD at different end-tidal CO2 levels. METHOD: This study was approved by the Ethics Committee of Affiliated Hospital of He Bei University (HDFY-LL-2022-169). The study was registered with the Chinese Clinical Trials Registry on URL: http://www.chictr.org.cn , Registry Number: ChiCTR2200056019 (Registry Date: 27/08/2022). In patients scheduled robotic lower abdominal tumor resection from September 1, 2022 to December 31, 2022, a comprehensive delirium assessment was performed three days postoperatively using the CAM scale with clinical review records. Intraoperative administration of different etCO2 was performed depending on the randomized grouping after intubation. Group L received lower level etCO2 management (31-40mmHg), and Group H maintained the higher level(41-50mmHg) during pneumoperitoneum. Data were analyzed using Pearson Chi-Square or Wilcoxon Rank Sum tests and multiple logistic regression. Preoperative mental status score, alcohol impairment score, nicotine dependence score, history of hypertension and diabetes, duration of surgery and worst pain score were included in the regression model along with basic patient information for covariate correction analysis. RESULTS: Among the 103 enrolled patients, 19 (18.4%) developed postoperative delirium. The incidence of delirium in different etCO2 groups was 21.6% in Group L and 15.4% in Group H, respectively, with no statistical differences. In adjusted multivariate analysis, age and during of surgery were statistically significant predictors of postoperative delirium. The breath-hold test was significantly lower postoperatively, but no statistical differences were found between two groups. CONCLUSION: With robotic assistant, the incidence of postoperative delirium in patients undergoing lower abdominal tumor resection was not modified by different end-tidal carbon dioxide management, however, age and duration of surgery were positively associated risk factors.

Discovery of Biphenyl Derivatives to Target Hsp70-Bim Protein-Protein Interaction in Chronic Myeloid Leukemia by Scaffold Hopping Strategy.

Hsp70-Bim protein-protein interaction (PPI) is the most recently identified specific target in chronic myeloid leukemia (CML) therapy. Herein, we developed a new class of Hsp70-Bim PPI inhibitors via scaffold hopping of S1g-10, the most potent Hsp70-Bim PPI inhibitor thus far. Through structure-activity relationship (SAR) study, we obtained a biphenyl scaffold compound JL-15 with a 5.6-fold improvement in Hsp70-Bim PPI suppression (Kd = 123 vs 688 nM) and a 4-fold improvement in water solubility (29.42 vs 7.19 µg/mL) compared to S1g-10. It maintains comparable apoptosis induction capability with S1g-10 against both TKI-sensitive and TKI-resistant CML cell lines in an Hsp70-Bim-dependent manner. Additionally, through SAR, 1H-15N TRSOY-NMR, and molecular docking, we revealed that Lys319 is a "hot spot" in the Hsp70-Bim PPI interface. Collectively, these results provide a novel chemical scaffold and structural insights for the rational design of Hsp70-Bim PPI inhibitors.

The effect and potential mechanism of inulin combined with fecal microbiota transplantation on early intestinal immune function in chicks.

Our previous research found that fecal microbiota transplantation (FMT) and inulin synergistically affected the intestinal barrier and immune system function in chicks. However, does it promote the early immunity of the poultry gut-associated lymphoid tissue (GALT)? How does it regulate the immunity? We evaluated immune-related indicators in the serum, cecal tonsil, and intestine to determine whether FMT synergistic inulin had a stronger impact on gut health and which gene expression regulation was affected. The results showed that FMT synergistic inulin increased TGF-ß secretion and intestinal goblet cell number and MUC2 expression on day 14. Expression of BAFFR, PAX5, CXCL12, and IL-2 on day 7 and expression of CXCR4 and IL-2 on day 14 in the cecal tonsils significantly increased. The transcriptome indicated that CD28 and CTLA4 were important regulatory factors in intestinal immunity. Correlation analysis showed that differential genes were related to the immunity and development of the gut and cecal tonsil. FMT synergistic inulin promoted the development of GALT, which improved the early-stage immunity of the intestine by regulating CD28 and CTLA4. This provided new measures for replacing antibiotic use and reducing the use of therapeutic drugs while laying a technical foundation for achieving anti-antibiotic production of poultry products.

Breast Cancer: Multi-b-Value Diffusion Weighted Habitat Imaging in Predicting Pathologic Complete Response to Neoadjuvant Chemotherapy.

RATIONALE AND OBJECTIVES: The aim of this study was to ascertain whether the utilization of multiple b-value diffusion-weighted habitat imaging, a technique that depicts tumor heterogeneity, could aid in identifying breast cancer patients who would derive substantial benefit from neoadjuvant chemotherapy (NAC). MATERIALS AND METHODS: This prospective study enrolled 143 women (II-III breast cancer), who underwent multi-b-value diffusion-weighted imaging (DWI) in 3-T magnetic resonance (MR) before NAC. The patient cohort was partitioned into a training set (consisting of 100 patients, of which 36 demonstrated a pathologic complete response [pCR]) and a test set (featuring 43 patients, 16 of whom exhibited pCR). Utilizing the training set, predictive models for pCR, were constructed using different parameters: whole-tumor radiomics (ModelWH), diffusion-weighted habitat-imaging (ModelHabitats), conventional MRI features (ModelCF), along with combined models ModelHabitats+CF. The performance of these models was assessed based on the area under the receiver operating characteristic curve (AUC) and calibration slope. RESULTS: In the prediction of pCR, ModelWH, ModelHabitats, ModelCF, and ModelHabitats+CF achieved AUCs of 0.733, 0.722, 0.705, and 0.756 respectively, within the training set. These scores corresponded to AUCs of 0.625, 0.801, 0.700, and 0.824 respectively in the test set. The DeLong test revealed no significant difference between ModelWH and ModelHabitats (P = 0.182), between ModelHabitats and ModelHabitats+CF (P = 0.113). CONCLUSION: The habitat model we developed, incorporating first-order features along with conventional MRI features, has demonstrated accurate predication of pCR prior to NAC. This model holds the potential to augment decision-making processes in personalized treatment strategies for breast cancer.

Diagnosis and cardiac transplantation of a Carney syndrome-induced cardiac myxoma combined with dilated cardiomyopathy: a case report.

BACKGROUND: Carney syndrome is an uncommon autosomal disorder closely linked to mutations in the PRKAR1A gene. Skin lesions are the most pronounced feature of Carney syndrome, affecting over 80% of individuals with this condition. This syndrome is characterized by a triad of myxomas, skin pigmentation, and endocrine hyperfunction, featuring multiple endocrine neoplasms with skin and cardiac involvement. Dilated cardiomyopathy, a primary cardiomyopathy, is defined as the dilation and impaired systolic function of the left or both ventricles. Its clinical presentation varies from being asymptomatic to heart failure or sudden cardiac death, making it a leading global cause of heart failure. Currently, Dilated cardiomyopathy has an estimated prevalence of 1/2500-1/250 individuals, predominantly affecting those aged 30-40 years, with a male-to-female ratio of 3:1. This case report describes a heart failure patient with cardiac myxoma caused by Carney syndrome combined with dilated cardiomyopathy. The patient was successfully treated for heart failure by heart transplantation. CASE PRESENTATION: Herein, we report a case of heart failure due to Carney syndrome that resulted in cardiac myxoma combined with dilated cardiomyopathy. A 35-year-old male was admitted to the hospital three years ago because of sudden chest tightness and shortness of breath. Echocardiography indicated myxoma, and a combination of genetic screening and physical examination confirmed Carney syndrome with cardiac myxoma. Following symptomatic management, he was discharged. Surgical interventions were not considered at the time. However, the patient's chest tightness and shortness of breath symptoms worsened, and he returned to the hospital. A New York Heart Association grade IV heart function was confirmed, and echocardiography indicated the presence of dilated cardiomyopathy accompanied by cardiac myxoma. Ultimately, the patient's heart failure was successfully treated with heart transplantation. CONCLUSIONS: Cardiac myxoma caused by Carney syndrome combined with heart failure caused by dilated cardiomyopathy can be resolved by heart transplantation.

Intermediate aminophenol enables hectogram-scale synthesis of highly bright red carbon quantum dots under ambient conditions.

Carbon quantum dots (C-dots) have developed into potential nanomaterials for lighting, catalysis and bioimaging because of their excellent optical properties and good biocompatibility. However, it is still a challenge to produce efficient red emitting carbon quantum dots (R-C-dots) due to their obscure formation mechanism. This work offered a method to reveal the formation process from the precursor o-phenylenediamine (o-PDA) to R-C-dots. Different from traditional hydrothermal reactions, R-C-dots were synthesized at relatively low temperature and ambient pressure. The pre-oxidation intermediate aminophenol played an important role in the synthesis of R-C-dots, which further cross-linked and polymerized with o-PDA in an acid environment to form R-C-dots. The obtained R-C-dots had a photoluminescence quantum yield of up to 33.26% and excellent two-photon fluorescence properties. A white light-emitting diode (WLED) based on R-C-dots as the red phosphor exhibited standard white light CIE color coordinates of (0.33, 0.33) with a correlated color temperature of 5342 K and a high color rendering index (CRI) of 94.5. The obtained rendering index is the highest value among WLEDs with color coordinates of (0.33, 0.33) based on C-dots. This work provides a new perspective for the controllable large-scale synthesis of red C-dots.

Flexible Humidity Sensor Based on a Graphene Oxide-Carbon Nanotube-Modified Co3O4 Nanoparticle-Embedded Laser-Induced Graphene Electrode.

To meet evolving humidity monitoring needs, the development of flexible, high-performance humidity sensors is crucial. This study introduces an innovative flexible humidity sensor using a single-step laser scribing technique to fabricate a flexible in situ Co3O4 nanoparticle-embedded laser-induced graphene (Co3O4-LIG) composite electrode. Compared to conventional LIG electrodes, the Co3O4-LIG electrode exhibits improved conductivity and hydrophilicity, enhancing charge transfer and water molecule affinity. The unique two-dimensional structure and exceptional water permeability of graphene oxide (GO) combine with the rapid water response and high specific surface area of carboxylated multiwalled carbon nanotubes (MWCNTs), thereby assuming a crucial function in the modification and optimization of the performance of humidity sensors. Through the application of a homogenously blended aqueous solution comprising GO and MWCNTs in precise proportions onto the Co3O4-LIG composite electrode, an excellent humidity-responsive layer is established, culminating in the realization of a cutting-edge GO-MWCNTs@Co3O4-LIG flexible humidity sensor. Noteworthy attributes of this sensor include a heightened sensitivity [959.1% (ΔR/R0)], rapid response and recovery times (within 5 and 26 s, respectively), and a noteworthy linearity (R2 = 0.994) across a relative humidity range of 14 to 95%. The findings presented herein offer valuable insights and a practical blueprint for the design and production of flexible humidity sensors.

Covalent Bonding of MXene/COF Heterojunction for Ultralong Cycling Li-Ion Battery Electrodes.

Covalent organic frameworks (COFs) have emerged as promising renewable electrode materials for LIBs and gained significant attention, but their capacity has been limited by the densely packed 2D layer structures, low active site availability, and poor electronic conductivity. Combining COFs with high-conductivity MXenes is an effective strategy to enhance their electrochemical performance. Nevertheless, simply gluing them without conformal growth and covalent linkage restricts the number of redox-active sites and the structural stability of the composite. Therefore, in this study, a covalently assembled 3D COF on Ti3C2 MXenes (Ti3C2@COF) is synthesized and serves as an ultralong cycling electrode material for LIBs. Due to the covalent bonding between the COF and Ti3C2, the Ti3C2@COF composite exhibits excellent stability, good conductivity, and a unique 3D cavity structure that enables stable Li+ storage and rapid ion transport. As a result, the Ti3C2-supported 3D COF nanosheets deliver a high specific capacity of 490 mAh g-1 at 0.1 A g-1, along with an ultralong cyclability of 10,000 cycles at 1 A g-1. This work may inspire a wide range of 3D COF designs for high-performance electrode materials.

Mobilization and activation of tumor-infiltrating dendritic cells inhibits lymph node metastasis in intrahepatic cholangiocarcinoma.

Lymph node metastasis (LNM) facilitates distant tumor colonization and leads to the high mortality in patients with intrahepatic cholangiocarcinoma (ICC). However, it remains elusive how ICC cells subvert immune surveillance within the primary tumor immune microenvironment (TIME) and subsequently metastasize to lymph nodes (LNs). In this study, scRNA-seq and bulk RNA-seq analyses identified decreased infiltration of dendritic cells (DCs) into primary tumor sites of ICC with LNM, which was further validated via dual-color immunofluorescence staining of 219 surgically resected ICC samples. Tumor-infiltrating DCs correlated with increased CD8+ T cell infiltration and better prognoses in ICC patients. Mechanistically, ß-catenin-mediated CXCL12 suppression accounted for the impaired DC recruitment in ICC with LNM. Two mouse ICC cell lines MuCCA1 and mIC-23 cells were established from AKT/NICD or AKT/YAP-induced murine ICCs respectively and were utilized to construct the footpad tumor LNM model. We found that expansion and activation of conventional DCs (cDCs) by combined Flt3L and poly(I:C) (FL-pIC) therapy markedly suppressed the metastasis of mIC-23 cells to popliteal LNs. Moreover, ß-catenin inhibition restored the defective DC infiltration into primary tumor sites and reduced the incidence of LNM in ICC. Collectively, our findings identify tumor cell intrinsic ß-catenin activation as a key mechanism for subverting DC-mediated anti-tumor immunity in ICC with LNM. FL-pIC therapy or ß-catenin inhibitor could merit exploration as a potential regimen for mitigating ICC cell metastasis to LNs and achieving effective tumor immune control.