An integrated network pharmacology approach reveals that Ampelopsis grossedentata improves alcoholic liver disease via TLR4/NF-κB/MLKL pathway.

BACKGROUND: Alcohol-related liver damage is the most prevalent chronic liver disease, which creates a heavy public health burden worldwide. The leaves of Ampelopsis grossedentata have been considered a popular tea and traditional herbal medicine in China for more than one thousand years, and possess anti-inflammatory, antioxidative, hepatoprotective, and antiviral activities. PURPOSE: We explored the protective effects of Ampelopsis grossedentata extract (AGE) against chronic alcohol-induced hepatic injury (alcoholic liver disease, ALD), aiming to elucidate its underlying mechanisms. METHODS: Firstly, UPLC-Q/TOF-MS analysis and network pharmacology were used to identify the constituents and elucidate the potential mechanisms of AGE against ALD. Secondly, C57BL/6 mice were pair-fed the Lieber-DeCarli diet containing either isocaloric maltodextrin or ethanol, AGE (150 and 300 mg/kg/d) and silymarin (200 mg/kg) were administered to chronic ethanol-fed mice for 7 weeks to evaluate the hepatoprotective effects. Serum biochemical parameters were determined, hepatic and ileum sections were used for histologic examination, and levels of inflammatory cytokines and oxidative stress in the liver were examined. The potential molecular mechanisms of AGE in improving ALD were demonstrated by RNA-seq, Western blotting analysis, and immunofluorescence staining. RESULTS: Ten main constituents of AGE were identified using UPLC-Q/TOF-MS and 274 potential ALD-related targets were identified. The enriched KEGG pathways included Toll-like receptor signaling pathway, NF-κB signaling pathway, and necroptosis. Moreover, in vivo experimental studies demonstrated that AGE significantly reduced serum aminotransferase levels and improved pathological abnormalities after chronic ethanol intake. Meanwhile, AGE improved ALD in mice by down-regulating oxidative stress and inflammatory cytokines. Furthermore, AGE notably repaired damaged intestinal epithelial barrier and suppressed the production of gut-derived lipopolysaccharide by elevating intestinal tight junction protein expression. Subsequent RNA-seq and experimental validation indicated that AGE inhibited NF-κB nuclear translocation, suppressed IκB-α, RIPK3 and MLKL phosphorylation and alleviated hepatic necroptosis in mice. CONCLUSION: In this study, we have demonstrated for the first time that AGE protects against alcoholic liver disease by regulating the gut-liver axis and inhibiting the TLR4/NF-κB/MLKL-mediated necroptosis pathway. Therefore, our present work provides important experimental evidence for AGE as a promising candidate for protection against ALD.

Selective activation of IFNγ-ipilimumab enhances the therapeutic effect and safety of ipilimumab.

INTRODUCTION: Immune checkpoint inhibitor therapy is a highly promising strategy for clinical treatment of cancer. Among these inhibitors, ipilimumab stands out for its ability to induce cytotoxic T cell proliferation and activation by binding to CTLA-4. However, ipilimumab also gives rise to systemic immune-related adverse effects and tumor immune evasion, limiting its effectiveness. OBJECTIVES: We developed IFNγ-ipilimumab and confirmed that the addition of INF-γ does not alter the fundamental properties of ipilimumab. RESULTS: IFNγ-ipilimumab can be activated by matrix metalloproteinases, thereby promoting the IFNγ signaling pathway and enhancing the cytotoxicity of T cells. In vivo studies demonstrated that IFNγ-ipilimumab enhances the therapeutic effect of ipilimumab against colorectal cancer by increasing CD8+ and CD4+ lymphocyte infiltration into the tumor area and inducing MHC-I expression in tumor cells. Mice treated with IFNγ-ipilimumab showed higher survival rates and body weight, as well as lower CD4+ and CD8+ lymphocyte activation rates in the blood and reduced organ damage. CONCLUSION: IFNγ-ipilimumab improved the effectiveness of ipilimumab while reducing its side effects. It is likely that future immunotherapies would rely on such antibodies to activate local cancer cells or immune cells, thereby increasing the therapeutic effectiveness of cancer treatments and ensuring their safety.

Exosomal microRNA-92b Is a Diagnostic Biomarker in Breast Cancer and Targets Survival-Related MTSS1L to Promote Tumorigenesis.

Exosomal microRNAs (miRNAs) are novel, non-invasive biomarkers for facilitating communication and diagnosing cancer. However, only a few studies have investigated their function and role in the clinical diagnosis of breast cancer. To address this gap, we established a stable cell line, MDA-MB-231-CD63-RFP, and recruited 112 female participants for serum collection. We screened 88 exosomal miRNAs identified through microarray analysis of 231-CD63 and literature screening using real-time PCR; only exosomal miR-92b-5p was significantly increased in patients with breast cancer. It had a significant correlation with stage and discriminated patients from the control with an AUC of 0.787. Exosomal miR-92b-5p impacted the migration, adhesion, and spreading ability of normal human mammary epithelial recipient cells through the downregulation of the actin dynamics regulator MTSS1L. In clinical breast cancer tissue, the expression of MTSS1L was significantly inversely correlated with tissue miR-92b-5p, and high expression of MTSS1L was associated with better 10-year overall survival rates in patients undergoing hormone therapy. In summary, our studies demonstrated that exosomal miR-92b-5p might function as a non-invasive body fluid biomarker for breast cancer detection and provide a novel therapeutic strategy in the axis of miR-92b-5p to MTSS1L for controlling metastasis and improving patient survival.

Evaluation of three-dimensional dual-energy CT cholangiopancreatography image quality in patients with pancreatobiliary dilatation: Comparison with conventional single-energy CT.

Objective: This study aimed to evaluate three-dimensional (3D) negative-contrast CT cholangiopancreatography (nCTCP) image quality using dual-energy CT (DECT) with iterative reconstruction (IR) technique in patients with pancreatobiliary dilatation compared with single-energy CT (SECT). Methods: Of the patients, 67 and 56 underwent conventional SECT (SECT set) and DECT with IR technique (DECT set), respectively. All patients were retrospectively analyzed during the portal phase to compare objective image quality and other data including patient demographics, hepatic and pancreatic parenchymal enhancement, noise, and attenuation difference (AD) between dilated ducts and enhanced hepatic parenchyma, signal-to-noise ratio (SNR), contrast-to-noise ratio (CNR), and CT volume dose index (CTDIvol). Two radiologists used the five-point Likert scale to evaluate the subjective image quality of 3D nCTCP regarding image noise, sharpness of dilated ducts, and overall image quality. Statistical analyses used the Mann-Whitney U test. Results: No significant difference in patient demographics in either CT set was showed during objective evaluation (p > 0.05). However, higher hepatic and pancreatic parenchymal enhancement, AD, SNR, and CNR and lower hepatic and pancreatic noise (p < 0.005) as well as CTDIvol (p = 0.005) on DECT than on SECT were observed. Higher mean grades on DECT than on SECT were showed for image noise (4.65 vs 3.92), sharpness of dilated ducts (4.52 vs 3.94), and overall image quality (4.45 vs 3.91; p < 0.001), respectively during subjective evaluation. Conclusion: A higher overall image quality and lower radiation dose on 3D nCTCP can be obtained by DECT with IR technique than with conventional SECT in patients with pancreatobiliary dilatation.

SUV39H1 Expression as a Guideline for Omitting Radiotherapy in Lymph Node-positive Triple-negative Breast Cancer Patients.

BACKGROUND/AIM: The role of postoperative radiotherapy (RT) combined with chemotherapy (CT) for lymph node-positive (LN+) triple-negative breast cancer (TNBC) remains controversial. SUV39H1-mediated epigenetic regulation is associated with cancer cell migration, invasion, metastasis, and treatment resistance. This study aims to identify the role of SUV39H1 in TNBCs. MATERIALS AND METHODS: Overall, 498 TNBCs with SUV39H1 RNA-seq profiles were retrieved from TCGA-BRCA and analyzed; the X-tile algorithm was used to stratify the population into low, intermediate, and high SUV39H1. Furthermore, we performed an in vitro clonogenic cell survival assay using the MDA-MB-231 cell line to assess the effects of SUV39H1 on cellular responses. RESULTS: The results showed that SUV39H1 was significantly higher in TNBC than normal tissue and luminal subtype breast cancer. Notably, SUV39H1 is significantly expressed in the basal-like 1 (BL1) and immunomodulatory (IM) subgroups, compared to other subtypes. Compared to patients with a low or medium expression of SUV39H1, omitting RT only worsens disease-free survival (DFS) in those with high SUV39H1 expression. The experimental results showed SUV39H1 was suppressed by si-SUV39H1, and SUV39H1 knockdown in MDA-MB-231-IV2-1 cells enhanced the cellular toxicity of doxorubicin and paclitaxel. CONCLUSION: Targeting SUV39H1 may provide a potential guiding indication of omitting RT to avoid over-treatment and chemosensitivity for TNBC.

Berberine inhibits breast carcinoma proliferation and metastasis under hypoxic microenvironment involving gut microbiota and endogenous metabolites.

A potential role of berberine, a benzyl isoquinoline alkaloid, in cancer therapy is apparent. Its underlying mechanisms of berberine against breast carcinoma under hypoxia have not been elucidated. We focused on the doubt how berberine restrains breast carcinoma under hypoxia in vitro and in vivo. A molecular analysis of the microbiome via 16 S rDNA gene sequencing of DNA from mouse faeces confirmed that the abundances and diversity of gut microbiota were significantly altered in 4T1/Luc mice with higher survival rate following berberine treatment. A metabolome analysis liquid chromatography-mass spectrometer/mass spectrometer (LC-MS/MS) revealed that berberine regulated various endogenous metabolites, especially L-palmitoylcarnitine. Furthermore, the cytotoxicity of berberine was investigated in MDA-MB-231, MCF-7, and 4T1 cells. In vitro to simulate under hypoxic environment, MTT assay showed that berberine inhibited the proliferation of MDA-MB-231, MCF-7, and 4T1 cells with IC50 values of 4.14 ± 0.35 µM, 26.53 ± 3.12 µM and 11.62 ± 1.44 µM, respectively. Wound healing and trans-well invasion studies revealed that berberine inhibited the invasion and migration of breast cancer cells. RT-qPCR analysis shed light that berberine reduced the expression of hypoxia-inducible factor-1α (HIF-1α) gene. Immunofluorescence and western blot demonstrated that berberine decreased the expression of E-cadherin and HIF-1α protein. Taken together, these results provide evidence that berberine efficiently suppresses breast carcinoma growth and metastasis in a hypoxic microenvironment, highlighting the potential of berberine as a promising anti-neoplastic agent to combat breast carcinoma.

Label-Free Imaging of Cell Apoptosis by a Light-Addressable Electrochemical Sensor.

Label-free electrochemical visualization of cancer cell apoptosis is essential for cancer therapies. In this work, we proposed a noninvasive imaging method using a light-addressable electrochemical sensor (LAES) for label-free imaging of drug-induced tumor cell apoptosis. The dynamic AC photocurrent changes on MCF-7 human breast adenocarcinoma cells after inducing by tamoxifen were imaged. And the reasons for photocurrent changes on the cells were explored by monitoring the changes in the ζ potentials of cells and Faradic impedance. The results demonstrated that the AC photocurrent on apoptotic MCF-7 cells increased, and the apoptosis degree of each cell was heterogeneous. Moreover, the AC photocurrent increase was attributed to the increased cell membrane permeability and the increased gap between the cell basal surface and the substrate caused by cell apoptosis. This study provides a brand new approach for label-free visualizing cell apoptosis heterogeneity, which has great potential in apoptosis-associated drug screening or drug efficacy evaluation.

Combination of FAK inhibitor and cytokine-induced killer cell therapy: An alternative therapeutic strategy for patients with triple-negative breast cancer.

Triple-negative breast cancer (TNBC) is characterized by the loss of expression of several biomarkers, which limits treatment strategies for the disease. In recent years, immunotherapy has shown promising results in the treatment of various tumors. Emerging evidence demonstrated that TNBC is an immune-activated cancer, suggesting that immunotherapy could be a feasible treatment option for TNBC. Cytokine-induced killer (CIK) cell therapy is considered as a potential treatment for cancer treatment. However, it is still not approved as a standard treatment in the clinical setting. Our previous study demonstrated that focal adhesion kinase (FAK) plays important role in regulating the sensitivity of TNBC cells to CIK cells. In this study, we further verify the role of FAK in regulating the immune response in vivo. Our in vitro study indicated that knockdown of FAK in TNBC cells or treat with the FAK inhibitor followed by co-culture with CIK cells induced more cell death than CIK cells treatment only. RNA-seq analysis indicated that suppression of FAK could affect several immune-related gene expressions in TNBC cells that affects the immune response in the tumor microenvironment of TNBC cells. The combination of FAK inhibitor and CIK cells significantly suppressed tumor growth than the treatment of FAK inhibitor or CIK cells alone in vivo. Our findings provide new insights into the cytotoxic effect of CIK cell therapy in TNBC treatment and indicate that the combination of CIK cell therapy with FAK inhibitors may be an alternative therapeutic strategy for patients with TNBC.

O → S Acyl Transfer Directing Human Sera Glycoprotein Immobilization for Breast Cancer Diagnosis.

Breast cancer (BC) is one of the most common malignancies in the world with aberrantly expressed glycans. The different types and stages still limit a comprehensive method in the prediagnosis of BC patients. In this research, a synthetic boronic acid-disulfide (BASS) probe has been developed for the two steps of O → S → N acyl transfer in glycoprotein recognition and labeling. The specificity and sensitivity of this method have been carefully studied in the case of immunoglobulin G, and the labeling efficiency was determined up to 60%. The BASS-functionalized slide is a powerful platform for monitoring the alteration of glycan patterns in human sera. Compared to the samples from healthy individuals, sera of BC patients gave specific patterns to eight lectins binding. The BASS-directed glycoprotein strategy promises a rapid sensing platform for a high-throughput screening of clinical BC samples and could be easily applied to other cancer prediagnoses.

Abortion and Female Cancer Risks among Women Aged 20 to 45 Years: A 10-Year Longitudinal Population-Based Cohort Study in Taiwan.

BACKGROUND: Female cancers, including breast, cervical, uterine, and ovarian cancer, remain among the ten most common cancers among women worldwide, but the relationship between female cancers and abortion from previous studies is inconsistent. This study aimed to investigate risks of incident female cancers among women aged 20 to 45 years who underwent abortion in Taiwan compared with those who did not. METHOD: A longitudinal observational cohort study was conducted using three nationwide population-based databases in Taiwan, focusing on 20- to 45-year-old women, with 10 years of follow-up. Matched cohorts were identified with propensity score 1-to-3 matching between 269,050 women who underwent abortion and 807,150 who did not. Multivariable Cox proportional hazard modeling was used for analysis after adjusting for covariates including age, average monthly payroll, fertility, diabetes mellitus, polycystic ovarian syndrome, endometrial hyperplasia, endometriosis, hormone-related drugs, and Charlson comorbidity index. RESULTS: We found lower risk of uterine cancer (hazard ratio [HR]: 0.77, 95% CI: 0.70-0.85) and ovarian cancer (HR: 0.81, 95% CI: 0.75-0.88), but no significant difference in risk of breast cancer or cervical cancer, among matched abortion compared with non-abortion cohorts. Regarding subgroup analysis, cervical cancer risk was higher for parous women who underwent abortion, and uterine cancer risk was lower for nulliparous women who underwent abortion compared with non-abortion groups. CONCLUSIONS: Abortion was related to lower uterine and ovarian cancer risk but was not associated with risks of incident breast cancer or cervical cancer. Longer follow-up may be necessary to observe risks of female cancers at older ages.

Computed Tomography Angiography-Based Thrombus Radiomics for Predicting the Time Since Stroke Onset.

RATIONALE AND OBJECTIVES: The measurement of the time since stroke onset (TSS) is crucial for decision-making in the treatment of acute ischemic stroke (AIS). This study assessed the utility of computed tomography angiography (CTA) radiomics features (RFs) to estimate TSS. MATERIALS AND METHODS: A total of 221 patients with AIS were enrolled in this retrospective study and were divided into a training group (n = 154) and a test group (n = 67). Thrombi in CTA images were manually outlined using ITK-SNAP. Images were aligned, normalized, and pre-processed to extract RFs. The TSS was calculated as the time from stroke onset to CTA completion. The patients were classified into two groups according to estimated TSS: ≤4.5 and >4.5 hours. A total of 944 RFs were extracted from CTA images. Clinical factors associated with TSS were identified using multivariate logistic regression, and a combined model (clinical data and RFs) was constructed. The predictive value of the models was assessed by the area under the receiver operating characteristic curve (AUC). The performance of the models was compared using the DeLong test, and clinical utility was evaluated by decision curve analysis. RESULTS: The AUC of the radiomics model was 0.803 (95% confidence interval [CI]: 0.733-0.873) and 0.803 (95% CI: 0.698-0.908) in the training and test cohorts, respectively. The AUC of the combined model (containing data on age, diabetes, and atrial fibrillation) in the training and test sets was 0.813 (95% CI: 0.750-0.889) and 0.803 (95% CI: 0.699-0.907), respectively. The DeLong test showed no significant difference between the radiomics and combined models. Decision curve analysis showed that both models had clinical utility. CONCLUSION: CTA-based thrombus radiomics can estimate TSS in patients with AIS. The addition of clinical data to the model does not improve predictive performance.

Nomogram Estimating Vessels Encapsulating Tumor Clusters in Hepatocellular Carcinoma From Preoperative Gadoxetate Disodium-Enhanced MRI.

BACKGROUND: Vessels encapsulating tumor clusters (VETC) pattern is a novel microvascular pattern associated with poor outcomes of hepatocellular carcinoma (HCC). Preoperative estimation of VETC has potential to improve treatment decisions. PURPOSE: To develop and validate a nomogram based on gadoxetate disodium-enhanced MRI for estimating VETC in HCC and to evaluate whether the estimations are associated with recurrence after hepatic resection. STUDY TYPE: Retrospective. POPULATION: A total of 320 patients with HCC and histopathologic VETC pattern assessment from three centers (development cohort:validation cohort = 173:147). FIELD STRENGTH/SEQUENCE: A3.0  T/turbo spin-echo T2-weighted, spin-echo echo-planar diffusion-weighted, and 3D T1-weighted gradient-echo sequences. ASSESSMENT: A set of previously reported VETC- and/or prognosis-correlated qualitative and quantitative imaging features were assessed. Clinical and imaging variables were compared based on histopathologic VETC status to investigate factors indicating VETC pattern. A regression-based nomogram was then constructed using the significant factors for VETC pattern. The nomogram-estimated VETC stratification was assessed for its association with recurrence. STATISTICAL TESTS: Fisher exact test, t-test or Mann-Whitney test, logistic regression analyses, Harrell's concordance index (C-index), nomogram, Kaplan-Meier curves and log-rank tests. P value < 0.05 was considered statistically significant. RESULTS: Pathological VETC pattern presence was identified in 156 patients (development cohort:validation cohort = 83:73). Tumor size, presence of heterogeneous enhancement with septations or with irregular ring-like structures, and necrosis were significant factors for estimating VETC pattern. The nomogram incorporating these indicators showed good discrimination with a C-index of 0.870 (development cohort) and 0.862 (validation cohort). Significant differences in recurrence rates between the nomogram-estimated high-risk VETC group and low-risk VETC group were found (2-year recurrence rates, 50.7% vs. 30.3% and 49.6% vs. 31.8% in the development and validation cohorts, respectively). DATA CONCLUSION: The nomogram integrating gadoxetate disodium-enhanced MRI features was associated with VETC pattern preoperatively and with postoperative recurrence in patients with HCC. EVIDENCE LEVEL: 4 TECHNICAL EFFICACY: Stage 2.

Carbonized polydopamine layer-protected silicon substrates for light-addressable electrochemical sensing and imaging.

The application of silicon (Si) substrate as photoelectrode in light-addressable electrochemistry (LAE) is severely limited due to its ease of surface oxidation. The resulted silicon oxide (SiOx) layer is electronically insulating and blocks charge transfer between the electrode and electrolyte. Keeping the Si from being oxidized is a key challenge for its practical use as a semiconductor electrode. In this work, we find that by developing a thin layer of polydopamine film on the surface of Si substrate, followed by carbonization at 550 °C, the natural oxidation of Si substrate can be successfully forestalled. When applied as an electrode, it is further found that the carbonized polydopamine (cPDA) layer can also prevent anodic oxidation of Si. The cPDA layer-modified Si substrate exhibits good photoelectrochemical performance and great stability, with no obvious signal decrease under ambient environment over 32 h. Our work here provides a new modification strategy for anti-oxidation of Si substrate and it is promising in the application of light-addressable electrochemical sensing and imaging.

A CT Radiomics-Based Risk Score for Preoperative Estimation of Intraoperative Superior Mesenteric-Portal Vein Involvement in Pancreatic Ductal Adenocarcinoma.

BACKGROUND: The current radiologic criteria for assessing intraoperative superior mesenteric-portal vein (SMPV) involvement (i.e., presence of tumor-SMPV contact >180° or venous deformity) in pancreatic ductal adenocarcinoma (PDAC) are highly specific but insufficiently sensitive. Therefore, development of improved markers for a more accurate prediction is essential. This study aimed to develop a risk score model to estimate SMPV involvement in PDAC using radiomics analysis of computed tomography (CT) images. METHODS: Data from two institution-based cohorts of PDAC patients undergoing preoperative CT scans were used to develop (n = 173) and validate (n = 156) a radiomics-based risk score of SMPV involvement using clinical and imaging variables. A radiomics signature was developed based on 2436 radiomic features extracted from the semi-automatic three-dimensional segmentation ofn CT images. The SMPV involvement risk score was built using multivariate logistic regression and compared with the current radiologic criteria. RESULTS: The study surgically identified SMPV involvement in 59 (34.1%) and 57(36.5 %) patients with PDAC in the development and validation cohorts, respectively. A 12-feature-based radiomics signature achieved areas under receiver operating characteristics curves (AUCs) of 0.89 or greater for estimating SMPV involvement. Multivariate regression identified the radiomics signature and SMPV deformity as associated with SMPV involvement. The risk score model had significantly improved AUC (0.928 vs. 0.768; P < 0.001) and sensitivity (84.2% vs. 66.7%; P = 0.025) in the radiologic evaluation. CONCLUSIONS: The novel risk score in this study, combining radiomics signature and venous deformity, demonstrated promising performance for estimating SMPV involvement preoperatively for patients with PDAC.

Observation on the efficacy of sublingual immunotherapy with dust mite allergen for perennial allergic rhinitis and the mechanism of action on ILCs with ILC1s and ILC2s and ILC3s.

BACKGROUND: Allergic rhinitis (AR) is considered to be 1 of the most difficult diseases to treat globally. It has a serious impact on the quality of life and social economy of patients and has become an important global health problem. Several drugs have been recommended to treat AR, but their effectiveness and mechanism of action in these patients remain unclear. The purpose of this study will be to compare the efficacy and mechanism of action of 2 drugs for the treatment of AR (moderate to severe): a Dermatophagoides Farinae Drops Sublingual Immunotherapy and a Momethasone Furoate nasal spray as an adjunct to the treatment of subjects with AR. METHODS: A randomized, prospective, double-blind (patient and evaluator) clinical trial. The participants (n = 60) will be randomly distributed into 2 groups. The experimental group will receive a sublingual Immunotherapy for 3 months. The control group will receive the mometasone furoate nasal spray for 3 months. Before treatment, 1 month and 3 months after treatment, total nasal symptom score scale, Visual analogue Scale and Quality of Life questionnaire of rhinoconjunctivitis will be measured and Changes of the serums of IgE, interferon-γ, IL-4, IL-17, tumor necrosis factor-α, IL-5, IL-9, IL-13, IL-25, IL-33, vascular endothelial growth factor, TSLP and IL-22 in both groups. The measurements will be performed by the same researcher who was unaware of the participants' subgroup. DISCUSSION: We believe that the treatment of perennial AR with sublingual Immunotherapy and nasal hormones will be more effective in these patients. Furthermore, the sublingual Immunotherapy mainly acts mostly on the cellular immunity, while nasal hormones mainly act on local inflammatory responses. We expect to clarify which treatments are more effective and how they work in improving perennial AR.

Assessment of Primary Collateral Grades Based on the Integrity of Willis' Circle: Predicting the Prognosis of Acute Intracranial Internal Carotid Artery Occlusion Before Thrombectomy.

OBJECTIVE: Endovascular mechanical thrombectomy (EVMT) has shown significant efficacy in improving neurological functions in patients with intracranial internal carotid artery occlusion (IICAO), but its clinical outcomes are variable. We examined the relationship between favorable clinical outcomes after EVMT in IICAO and a set of predictors. METHODS: In this retrospective study, 189 patients with IICAO treated by EVMT at 3 centers from November 2015 to December 2020 were included and analyzed. Non-contrast computed tomography and computed tomography angiography were evaluated on admission. The morphology of IICAO was categorized into Ia, Ib, L, or T types, depending on the involvement of the posterior communicating artery origin, proximal anterior cerebral artery, and middle cerebral artery. The Willis' circle was categorized as integrated or compromised Willis' circle. In combination with the involvement of the IICAO and the integrity of Willis' circle, we used the primary collateral grade (PCG) to describe the presence of functional Willisian collaterals. Baseline data including demographics, characteristics, vascular risk factors, and initial National Institutes of Health Stroke Scale scores were collected. Hemorrhagic transformation was evaluated using the 24-hour non-contrast computed tomography after EVMT. Favorable outcomes based on modified Rankin scale, were defined as 0-2 at 90 days. RESULTS: A total of 189 patients were included (median age, 69 years; 126 male [66.7%]). 104 patients [55.0%] showed reperfusion after EVMT, but 72 patients [38.1%] achieved favorable outcomes at 90 days. The mortality rate of type Ib was significantly higher than that with type Ia (χ2 = 14.21, P = 0.001). The outcome with different structure of Willis' circle was not statistically different between the 2 groups. A multivariate logistic regression analysis showed that IICAO T-type (odds ratio, 0.028 [95% confidence interval: 0.323-3.829], P = 0.042) and PCG 2 (odds ratio 9.427[95% confidence interval:1.863-47.698], P = 0.007) were predictors of favorable outcomes. CONCLUSIONS: Evaluation of PCG by determining the type of IICAO and the integrity of Willis' circle may serve as a valuable indicator for the prognosis and as an essential reference for screening patients before EVMT.

Comprehensive Transcriptomic and Proteomic Analyses Identify a Candidate Gene Set in Cross-Resistance for Endocrine Therapy in Breast Cancer.

Endocrine therapy (ET) of selective estrogen receptor modulators (SERMs), selective estrogen receptor downregulators (SERDs), and aromatase inhibitors (AIs) has been used as the gold standard treatment for hormone-receptor-positive (HR+) breast cancer. Despite its clinical benefits, approximately 30% of patients develop ET resistance, which remains a major clinical challenge in patients with HR+ breast cancer. The mechanisms of ET resistance mainly focus on mutations in the ER and related pathways; however, other targets still exist from ligand-independent ER reactivation. Moreover, mutations in the ER that confer resistance to SERMs or AIs seldom appear in SERDs. To date, little research has been conducted to identify a critical target that appears in both SERMs/SERDs and AIs. In this study, we conducted comprehensive transcriptomic and proteomic analyses from two cohorts of The Cancer Genome Atlas Breast Invasive Carcinoma (TCGA-BRCA) to identify the critical targets for both SERMs/SERDs and AIs of ET resistance. From a treatment response cohort with treatment response for the initial ET regimen and an endocrine therapy cohort with survival outcomes, we identified candidate gene sets that appeared in both SERMs/SERDs and AIs of ET resistance. The candidate gene sets successfully differentiated progress/resistant groups (PD) from complete response groups (CR) and were significantly correlated with survival outcomes in both cohorts. In summary, this study provides valuable clinical implications for the critical roles played by candidate gene sets in the diagnosis, mechanism, and therapeutic strategy for both SERMs/SERDs and AIs of ET resistance for the future.

Visualization of electrochemical reactions on microelectrodes using light-addressable potentiometric sensor imaging.

Visualization of the electrochemical reaction is essential for comprehensively understanding the electrochemical reaction mechanism and precisely characterizing dynamic electrochemical processes. Herein, we propose a simple device that combines light-addressable potentiometric sensor (LAPS) imaging and microelectrodes to serve as a general electroanalysis platform for the label-free sensing and imaging of electrochemical reactions. In this device, two microelectrodes are assembled on the LAPS chip. Electrochemical reactions occurring on the microelectrodes can be qualitatively and quantitatively observed and visualized using a LAPS chip that is sensitive to the reaction products. Validations were performed to monitor the effect of water electrolysis and potassium ferrocyanide oxidation surrounding the microelectrodes, respectively. We believe that this study will provide an excellent platform for the visualization and monitoring of electrochemical reactions and broaden the application scope of LAPS imaging to a general electroanalysis tool that is widely applicable in several fields.