TRIM65 promotes vascular smooth muscle cell phenotypic transformation by activating PI3K/Akt/mTOR signaling during atherogenesis.

BACKGROUND AND AIMS: Tripartite motif (TRIM65) is an important member of the TRIM protein family, which is a newly discovered E3 ligase that interacts with and ubiquitinates various substrates and is involved in diverse pathological processes. However, the function of TRIM65 in atherosclerosis remains unarticulated. In this study, we investigated the role of TRIM65 in the pathogenesis of atherosclerosis, specifically in vascular smooth muscle cells (VSMCs) phenotype transformation, which plays a crucial role in formation of atherosclerotic lesions. METHODS AND RESULTS: Both non-atherosclerotic and atherosclerotic lesions during autopsy were collected singly or pairwise from each individual (n = 16) to investigate the relationship between TRIM65 and the development of atherosclerosis. In vivo, Western diet-fed ApoE-/- mice overexpressing or lacking TRIM65 were used to assess the physiological function of TRIM65 on VSMCs phenotype, proliferation and atherosclerotic lesion formation. In vitro, VSMCs phenotypic transformation was induced by platelet-derived growth factor-BB (PDGF-BB). TRIM65-overexpressing or TRIM65-abrogated primary mouse aortic smooth muscle cells (MOASMCs) and human aortic smooth muscle cells (HASMCs) were used to investigate the mechanisms underlying the progression of VSMCs phenotypic transformation, proliferation and migration. Increased TRIM65 expression was detected in α-SMA-positive cells in the medial and atherosclerotic lesions of autopsy specimens. TRIM65 overexpression increased, whereas genetic knockdown of TRIM65 remarkably inhibited, atherosclerotic plaque development. Mechanistically, TRIM65 overexpression activated PI3K/Akt/mTOR signaling, resulting in the loss of the VSMCs contractile phenotype, including calponin, α-SMA, and SM22α, as well as cell proliferation and migration. However, opposite phenomena were observed when TRIM65 was deficient in vivo or in vitro. Moreover, in cultured PDGF-BB-induced TRIM65-overexpressing VSMCs, inhibition of PI3K by treatment with the inhibitor LY-294002 for 24 h markedly attenuated PI3K/Akt/mTOR activation, regained the VSMCs contractile phenotype, and blocked the progression of cell proliferation and migration. CONCLUSIONS: TRIM65 overexpression enhances atherosclerosis development by promoting phenotypic transformation of VSMCs from contractile to synthetic state through activation of the PI3K/Akt/mTOR signal pathway.

An atlas of itch-associated neural dynamics in the mouse brain.

The itch-scratching cycle is mediated by neural dynamics in the brain. However, our understanding of the neural dynamics during this cycle remains limited. In this study, we examine the neural dynamics of 126 mouse brain areas by measuring the calcium signal using fiber photometry. We present numerous response patterns in the mouse brain during the itch-scratching cycle. Interestingly, we find that a group of brain areas exhibit activation only at the end of histamine-induced scratching behavior. Additionally, several brain areas exhibit transient activation at the onset of scratching induced by chloroquine. Both histamine- and chloroquine-induced itch evoke diverse response patterns across the mouse brain. In summary, our study provides a comprehensive dataset for the diverse activity pattern of mouse brain during the itch-scratching cycle, paving the way for further exploration into the neural mechanisms underlying the itch-scratching cycle.

TRIM65 Suppresses oxLDL-induced Endothelial Inflammation by Interaction with VCAM-1 in Atherogenesis.

BACKGROUND AND OBJECTIVE: Endothelial cell activation, characterized by increased levels of vascular cell adhesion molecule 1 (VCAM-1), plays a crucial role in the development of atherosclerosis (AS). Therefore, inhibition of VCAM-1-mediated inflammatory response is of great significance in the prevention and treatment of AS. The tripartite motif (TRIM) protein-TRIM65 is involved in the regulation of cancer development, antivirals and inflammation. We aimed to study the functions of TRIM65 in regulating endothelial inflammation by interacting with VCAM-1 in atherogenesis. METHODS AND RESULTS: In vitro, we report that human umbilical vein endothelial cells (HUVECs) treated with oxidized low-density lipoprotein (oxLDL) significantly upregulate the expression of TRIM65 in a time- and dose-dependent manner. Overexpression of TRIM65 reduces oxLDL-triggered VCAM-1 protein expression, decreases monocyte adhesion to HUVECs and inhibits the production of the inflammatory cytokines IL-1ß, IL-6, IL-8, and TNF-α as well as endothelial oxLDL transcytosis. In contrast, siRNA-mediated knockdown of TRIM65 promotes the expression of VCAM-1, resulting in increased adhesion of monocytes and the release of the inflammatory cytokines IL-1ß, IL-6, IL-8, and TNF-α and enhances endothelial oxLDL transcytosis. In vivo, we measured the high expression of TRIM65 in ApoE-/- mouse aortic plaques compared to C57BL/6J mouse aortic plaques. Then, we examined whether the blood levels of VCAM-1 were higher in TRIM65 knockout ApoE-/- mice than in control mice induced by a Western diet. Furthermore, Western blot results showed that the protein expression of VCAM-1 was markedly enhanced in TRIM65 knockout ApoE-/- mouse aortic tissues compared to that of the controls. Immunofluorescence staining revealed that the expression of VCAM-1 was significantly increased in atherosclerotic plaques of TRIM65-/-/ApoE-/- aortic vessels compared to ApoE-/- controls. Mechanistically, TRIM65 specifically interacts with VCAM-1 and targets it for K48-linked ubiquitination. CONCLUSION: Our studies indicate that TRIM65 attenuates the endothelial inflammatory response by targeting VCAM-1 for ubiquitination and provides a potential therapeutic target for the inhibition of endothelial inflammation in AS.

Prediction of Stroke Onset Time With Combined Fast High-Resolution Magnetic Resonance Spectroscopic and Quantitative T2 Mapping.

OBJECTIVE: The purpose of this work is to develop a multispectral imaging approach that combines fast high-resolution 3D magnetic resonance spectroscopic imaging (MRSI) and fast quantitative T2 mapping to capture the multifactorial biochemical changes within stroke lesions and evaluate its potentials for stroke onset time prediction. METHODS: Special imaging sequences combining fast trajectories and sparse sampling were used to obtain whole-brain maps of both neurometabolites (2.0 × 3.0 × 3.0 mm3) and quantitative T2 values (1.9 × 1.9 × 3.0 mm3) within a 9-minute scan. Participants with ischemic stroke at hyperacute (0-24 h, n = 23) or acute (24 h-7d, n = 33) phase were recruited in this study. Lesion N-acetylaspartate (NAA), lactate, choline, creatine, and T2 signals were compared between groups and correlated with patient symptomatic duration. Bayesian regression analyses were employed to compare the predictive models of symptomatic duration using multispectral signals. RESULTS: In both groups, increased T2 and lactate levels, as well as decreased NAA and choline levels were detected within the lesion (all p < 0.001). Changes in T2, NAA, choline, and creatine signals were correlated with symptomatic duration for all patients (all p < 0.005). Predictive models of stroke onset time combining signals from MRSI and T2 mapping achieved the best performance (hyperacute: R2 = 0.438; all: R2 = 0.548). CONCLUSION: The proposed multispectral imaging approach provides a combination of biomarkers that index early pathological changes after stroke in a clinical-feasible time and improves the assessment of the duration of cerebral infarction. SIGNIFICANCE: Developing accurate and efficient neuroimaging techniques to provide sensitive biomarkers for prediction of stroke onset time is of great importance for maximizing the proportion of patients eligible for therapeutic intervention. The proposed method provides a clinically feasible tool for the assessment of symptom onset time post ischemic stroke, which will help guide time-sensitive clinical management.

Metformin regulates expression of DNA methyltransferases through the miR-148/-152 family in non-small lung cancer cells.

BACKGROUND: To understand the molecular mechanisms involved in regulation of DNA methyltransferases (DNMTs) by metformin in non-small cell lung cancer (NSCLC) cells. METHODS: Expression levels of DNMTs in response to metformin were analyzed in NSCLC cells. MicroRNAs regulating expression of DNMTs at the post-transcriptional level were searched using miRNA-target databases (miRDB and miRTarBase), TCGA RNASeqV2 lung cancer data, and miRNA-seq. RESULTS: Metformin dose-dependently downregulated expression of DNMT1 and DNMT3a at the post-transcriptional level and expression of DNMT3b at the transcriptional level in A549 lung cancer cells. Activity of DNMTs was reduced by about 2.6-fold in A549 cells treated with 10 mM metformin for 72 h. miR-148/-152 family members (miR-148a, miR-148b, and miR-152) targeting the 3'UTR of DNMTs were associated with post-transcriptional regulation of DNMTs by metformin. Metformin upregulated expression of miR-148a, miR-148b, and miR-152 in A549 and H1650 cells. Transfection with an miR-148b plasmid or a mimic suppressed expression of DNMT1 and DNMT3b in A549 cells. Transfection with the miR-148a mimic in A549 and H1650 cells decreased the luciferase activity of DNMT1 3'UTR. A combination of metformin and cisplatin synergistically increased expression levels of miR-148/-152 family members but decreased expression of DNMTs in A549 cells. Low expression of miR-148b was associated with poor overall survival (HR = 2.56, 95% CI 1.09-6.47; P = 0.04) but not with recurrence-free survival. CONCLUSIONS: The present study suggests that metformin inhibits expression of DNMTs by upregulating miR-148/-152 family members in NSCLC cells.

Predicting the Onset of Ischemic Stroke With Fast High-Resolution 3D MR Spectroscopic Imaging.

BACKGROUND: Neurometabolite concentrations provide a direct index of infarction progression in stroke. However, their relationship with stroke onset time remains unclear. PURPOSE: To assess the temporal dynamics of N-acetylaspartate (NAA), creatine, choline, and lactate and estimate their value in predicting early (<6 hours) vs. late (6-24 hours) hyperacute stroke groups. STUDY TYPE: Cross-sectional cohort. POPULATION: A total of 73 ischemic stroke patients scanned at 1.8-302.5 hours after symptom onset, including 25 patients with follow-up scans. FIELD STRENGTH/SEQUENCE: A 3 T/magnetization-prepared rapid acquisition gradient echo sequence for anatomical imaging, diffusion-weighted imaging and fluid-attenuated inversion recovery imaging for lesion delineation, and 3D MR spectroscopic imaging (MRSI) for neurometabolic mapping. ASSESSMENT: Patients were divided into hyperacute (0-24 hours), acute (24 hours to 1 week), and subacute (1-2 weeks) groups, and into early (<6 hours) and late (6-24 hours) hyperacute groups. Bayesian logistic regression was used to compare classification performance between early and late hyperacute groups by using different combinations of neurometabolites as inputs. STATISTICAL TESTS: Linear mixed effects modeling was applied for group-wise comparisons between NAA, creatine, choline, and lactate. Pearson's correlation analysis was used for neurometabolites vs. time. P < 0.05 was considered statistically significant. RESULTS: Lesional NAA and creatine were significantly lower in subacute than in acute stroke. The main effects of time were shown on NAA (F = 14.321) and creatine (F = 12.261). NAA was significantly lower in late than early hyperacute patients, and was inversely related to time from symptom onset across both groups (r = -0.440). The decrease of NAA and increase of lactate were correlated with lesion volume (NAA: r = -0.472; lactate: r = 0.366) in hyperacute stroke. Discrimination was improved by combining NAA, creatine, and choline signals (area under the curve [AUC] = 0.90). DATA CONCLUSION: High-resolution 3D MRSI effectively assessed the neurometabolite changes and discriminated early and late hyperacute stroke lesions. EVIDENCE LEVEL: 1. TECHNICAL EFFICACY: Stage 2.

An artificial-intelligence-based age-specific template construction framework for brain structural analysis using magnetic resonance images.

It is an essential task to construct brain templates and analyze their anatomical structures in neurological and cognitive science. Generally, templates constructed from magnetic resonance imaging (MRI) of a group of subjects can provide a standard reference space for analyzing the structural and functional characteristics of the group. With recent development of artificial intelligence (AI) techniques, it is desirable to explore AI registration methods for quantifying age-specific brain variations and tendencies across different ages. In this article, we present an AI-based age-specific template construction (called ASTC) framework for longitudinal structural brain analysis using T1-weighted MRIs of 646 subjects from 18 to 82 years old collected from four medical centers. Altogether, 13 longitudinal templates were constructed at a 5-year age interval using ASTC, and tissue segmentation and substructure parcellation were performed for analysis across different age groups. The results indicated consistent changes in brain structures along with aging and demonstrated the capability of ASTC for longitudinal neuroimaging study.

The role of the immune microenvironment in bone, cartilage, and soft tissue regeneration: from mechanism to therapeutic opportunity.

Bone, cartilage, and soft tissue regeneration is a complex spatiotemporal process recruiting a variety of cell types, whose activity and interplay must be precisely mediated for effective healing post-injury. Although extensive strides have been made in the understanding of the immune microenvironment processes governing bone, cartilage, and soft tissue regeneration, effective clinical translation of these mechanisms remains a challenge. Regulation of the immune microenvironment is increasingly becoming a favorable target for bone, cartilage, and soft tissue regeneration; therefore, an in-depth understanding of the communication between immune cells and functional tissue cells would be valuable. Herein, we review the regulatory role of the immune microenvironment in the promotion and maintenance of stem cell states in the context of bone, cartilage, and soft tissue repair and regeneration. We discuss the roles of various immune cell subsets in bone, cartilage, and soft tissue repair and regeneration processes and introduce novel strategies, for example, biomaterial-targeting of immune cell activity, aimed at regulating healing. Understanding the mechanisms of the crosstalk between the immune microenvironment and regeneration pathways may shed light on new therapeutic opportunities for enhancing bone, cartilage, and soft tissue regeneration through regulation of the immune microenvironment.

Aberrant Methylation of SLIT2 Gene in Plasma Cell-Free DNA of Non-Small Cell Lung Cancer Patients.

This study aimed to understand aberrant methylation of SLITs genes as a biomarker for the early detection and prognosis prediction of non-small cell lung cancer (NSCLC). Methylation levels of SLITs were determined using the Infinium HumanMethylation450 BeadChip or pyrosequencing. Five CpGs at the CpG island of SLIT1, SLIT2 or SLIT3 genes were significantly (Bonferroni corrected p < 0.05) hypermethylated in tumor tissues obtained from 42 NSCLC patients than in matched normal tissues. Methylation levels of these CpGs did not differ significantly between bronchial washings obtained from 76 NSCLC patients and 60 cancer-free patients. However, methylation levels of SLIT2 gene were significantly higher in plasma cell-free DNA of 72 NSCLC patients than in that of 61 cancer-free patients (p = 0.001, Wilcoxon rank sum test). Prediction of NSCLC using SLIT2 methylation was achieved with a sensitivity of 73.7% and a specificity of 61.9% in a plasma test dataset (N = 40). A Cox proportional hazards model showed that SLIT2 hypermethylation in plasma cell-free DNA was significantly associated with poor recurrence-free survival (hazards ratio = 2.19, 95% confidence interval = 1.21-4.36, p = 0.01). The present study suggests that aberrant methylation of SLIT2 in plasma cell-free DNA is a valuable biomarker for the early detection of NSCLC and prediction of recurrence-free survival. However, further research is needed with larger sample size to confirm results.

Real-Time Cerebral Vessel Segmentation in Laser Speckle Contrast Image Based on Unsupervised Domain Adaptation.

Laser speckle contrast imaging (LSCI) is a full-field, high spatiotemporal resolution and low-cost optical technique for measuring blood flow, which has been successfully used for neurovascular imaging. However, due to the low signal-noise ratio and the relatively small sizes, segmenting the cerebral vessels in LSCI has always been a technical challenge. Recently, deep learning has shown its advantages in vascular segmentation. Nonetheless, ground truth by manual labeling is usually required for training the network, which makes it difficult to implement in practice. In this manuscript, we proposed a deep learning-based method for real-time cerebral vessel segmentation of LSCI without ground truth labels, which could be further integrated into intraoperative blood vessel imaging system. Synthetic LSCI images were obtained with a synthesis network from LSCI images and public labeled dataset of Digital Retinal Images for Vessel Extraction, which were then used to train the segmentation network. Using matching strategies to reduce the size discrepancy between retinal images and laser speckle contrast images, we could further significantly improve image synthesis and segmentation performance. In the testing LSCI images of rodent cerebral vessels, the proposed method resulted in a dice similarity coefficient of over 75%.

Controlling Reperfusion Injury With Controlled Reperfusion: Historical Perspectives and New Paradigms.

Cardiac reperfusion injury is a well-established outcome following treatment of acute myocardial infarction and other types of ischemic heart conditions. Numerous cardioprotection protocols and therapies have been pursued with success in pre-clinical models. Unfortunately, there has been lack of successful large-scale clinical translation, perhaps in part due to the multiple pathways that reperfusion can contribute to cell death. The search continues for new cardioprotection protocols based on what has been learned from past results. One class of cardioprotection protocols that remain under active investigation is that of controlled reperfusion. This class consists of those approaches that modify, in a controlled manner, the content of the reperfusate or the mechanical properties of the reperfusate (e.g., pressure and flow). This review article first provides a basic overview of the primary pathways to cell death that have the potential to be addressed by various forms of controlled reperfusion, including no-reflow phenomenon, ion imbalances (particularly calcium overload), and oxidative stress. Descriptions of various controlled reperfusion approaches are described, along with summaries of both mechanistic and outcome-oriented studies at the pre-clinical and clinical phases. This review will constrain itself to approaches that modify endogenously-occurring blood components. These approaches include ischemic postconditioning, gentle reperfusion, controlled hypoxic reperfusion, controlled hyperoxic reperfusion, controlled acidotic reperfusion, and controlled ionic reperfusion. This review concludes with a discussion of the limitations of past approaches and how they point to potential directions of investigation for the future.

A Versatile Nanoplatform for Broad-Spectrum Immunotherapy by Reversing the Tumor Microenvironment.

Immunotherapy is currently an important adjuvant therapy for malignant tumors besides surgical treatment. However, the heterogeneity and low immunogenicity of the tumor are two main challenges of the immunotherapy. Here, we have constructed a nanoplatform (CP@mRBC-PpIX) to realize reversion of the tumor acidosis and hypoxia through alkali and oxygen generation triggered by tumor acidosis. By targeting tumor universal features other than endogenous biomarkers, it was found that CP@mRBC-PpIX could polarize tumor-associated macrophages to anti-tumor M1 phenotype macrophages to enhance tumor immune response. Furthermore, under regional light irradiation, the reactive oxygen species produced by photosensitizers located in CP@mRBC-PpIX could increase the immunogenicity of tumors, so that tumor changes from an immunosuppressive "cold tumor" to an immunogenic "hot tumor," thereby increasing the infiltration and response of T cells, further amplifying the effect of immunotherapy. This strategy circumvented the problem of tumor heterogeneity to realize a kind of broad-spectrum immunotherapy, which could effectively prevent tumor metastasis and recurrence.

Metformin Reduces Histone H3K4me3 at the Promoter Regions of Positive Cell Cycle Regulatory Genes in Lung Cancer Cells.

This study aimed at understanding the effect of metformin on histone H3 methylation, DNA methylation, and chromatin accessibility in lung cancer cells. Metformin significantly reduced H3K4me3 level at the promoters of positive cell cycle regulatory genes such as CCNB2, CDK1, CDK6, and E2F8. Eighty-eight genes involved in cell cycle showed reduced H3K4me3 levels in response to metformin, and 27% of them showed mRNA downregulation. Metformin suppressed the expression of H3K4 methyltransferases MLL1, MLL2, and WDR82. The siRNA-mediated knockdown of MLL2 significantly downregulated global H3K4me3 level and inhibited lung cancer cell proliferation. MLL2 overexpression was found in 14 (33%) of 42 NSCLC patients, and a Cox proportional hazards analysis showed that recurrence-free survival of lung adenocarcinoma patients with MLL2 overexpression was approximately 1.32 (95% CI = 1.08-4.72; p = 0.02) times poorer than in those without it. Metformin showed little effect on DNA methylation and chromatin accessibility at the promoter regions of cell cycle regulatory genes. The present study suggests that metformin reduces H3K4me3 levels at the promoters of positive cell cycle regulatory genes through MLL2 downregulation in lung cancer cells. Additionally, MLL2 may be a potential therapeutic target for reducing the recurrence of lung adenocarcinoma.

Multifunctional Nanostructure RAP-RL Rescues Alzheimer's Cognitive Deficits through Remodeling the Neurovascular Unit.

Cerebrovascular dysfunction characterized by the neurovascular unit (NVU) impairment contributes to the pathogenesis of Alzheimer's disease (AD). In this study, a cerebrovascular-targeting multifunctional lipoprotein-biomimetic nanostructure (RAP-RL) constituted with an antagonist peptide (RAP) of receptor for advanced glycation end-products (RAGE), monosialotetrahexosyl ganglioside, and apolipoprotein E3 is developed to recover the functional NVU and normalize the cerebral vasculature. RAP-RL accumulates along the cerebral microvasculature through the specific binding of RAP to RAGE, which is overexpressed on cerebral endothelial cells in AD. It effectively accelerates the clearance of perivascular Aß, normalizes the morphology and functions of cerebrovasculature, and restores the structural integrity and functions of NVU. RAP-RL markedly rescues the spatial learning and memory in APP/PS1 mice. Collectively, this study demonstrates the potential of the multifunctional nanostructure RAP-RL as a disease-modifying modality for AD treatment and provides the proof of concept that remodeling the functional NVU may represent a promising therapeutic approach toward effective intervention of AD.

Cortical Hemodynamic Response to Multi-afferent Stimulation: an optical imaging study.

Multisensory stimulation plays an important role in the recovery of ischemic stroke. However, little is known about the interactions between neuronal activities with multi-afferent stimulations and their effects on hemodynamic responses. Optogenetics has been a useful tool in neuroscience research to unravel the mechanisms of neurovascular coupling at cell-specific level. In this study, we applied laser speckle contrast imaging (LSCI) to map the cortical hemodynamic response with high spatiotemporal resolution. The results showed that optogenetic inhibition of pyramidal neurons in sensorimotor cortex induced both local and distant increases of cerebral blood flow (CBF) with dual peaks, and the full width at half maximum (FWHM) was significantly larger than that of the CBF response to optogenetic excitation. Furthermore, optogenetic excitation of pyramidal neurons could significantly increase the local CBF response to sensory stimulation, whereas optogenetic inhibition of pyramidal neurons decreased the local CBF response at the early stage after sensory stimulation and increased the distant CBF response during the recovery period. Our work provided useful insights into the mechanisms of brain stimulation, which might help in clinical neurological applications.

Neurovascular Coupling Impairment in Acute Ischemic Stroke by Optogenetics and Optical Brain Imaging.

The coupling between neuronal activity and cerebral blood flow (CBF), known as neurovascular coupling, has been reported to be impaired after stroke. This study aims to investigate the neurovascular coupling impairment at the acute stage after ischemic stroke. Laser speckle contrast imaging (LSCI) was applied to measure the hemodynamic response to optogenetic excitation of sensorimotor neurons in healthy and ischemic brain. The results showed that the hemodynamic response to optogenetic stimulation decreased and the regional CBF response was correlated with the distance from the ischemic core at the acute stage, regardless of the change in resting CBF. Our results also demonstrated that excitatory neuronal stimulation of intact area could promote the recovery of neurovascular coupling, whereas peri-infarct neuronal excitation failed to restore neurovascular function 24 hrs after ischemia. These results suggested the intact periphery of penumbra as the target for excitatory stimulation in aspect of restoring the perfusion after ischemic stroke.

Negative Effect of Reduced NME1 Expression on Recurrence-Free Survival in Early Stage Non-Small Cell Lung Cancer.

This study aimed to understand whether the effect of non-metastatic cells 1 (NME1) on recurrence-free survival (RFS) in early stage non-small cell lung cancer (NSCLC) can be modified by ß-catenin overexpression and cisplatin-based adjuvant chemotherapy. Expression levels of NME1 and ß-catenin were analyzed using immunohistochemistry in formalin-fixed paraffin-embedded tissues from 425 early stage NSCLC patients. Reduced NME1 expression was found in 39% of samples. The median duration of follow-up was 56 months, and recurrence was found in 186 (44%) of 425 patients. The negative effect of reduced NME1 expression on RFS was worsened by cisplatin-based adjuvant chemotherapy (adjusted hazard ratio = 3.26, 95% CI = 1.16-9.17, p = 0.03). ß-catenin overexpression exacerbated the effect of reduced NME1 expression on RFS and the negative effect was greater when receiving cisplatin-based adjuvant chemotherapy: among patients treated with cisplatin-based adjuvant chemotherapy, hazard ratios of patients with reduced NME1 expression increased from 5.59 (95% confidence interval (CI) = 0.62-50.91, p = 0.13) to 15.52 (95% CI = 2.94-82.38, p = 0.001) by ß-catenin overexpression, after adjusting for confounding factors. In conclusion, the present study suggests that cisplatin-based adjuvant chemotherapy needs to be carefully applied to early stage NSCLC patients with overexpressed ß-catenin in combination with reduced NME1 expression.

[Electrocatalytic Oxidation of Sulfadiazine with Ni-Doped Sb-SnO2 Ceramic Ring Particle Electrode].

The excessive use and abuse of antibiotics has brought about serious threats to water environmental safety and human health. It is necessary to develop efficient, cheap, and environmentally friendly treatment technologies for antibiotics. In this work, a Ni-doped Sb-SnO2 microporous ceramic ring particle electrode was prepared by the dipping method and characterized by scanning electron microscopy, energy dispersion spectroscopy, and X-ray diffraction. The electrocatalytic oxidation ability and kinetic characteristics of sulfadiazine (SDZ) were studied using the prepared electrode, and the degradation pathways of SDZ were analyzed preliminarily. The results showed that Ni and Sb-SnO2 crystals were loaded on the particle electrode surface, which is beneficial for electron transfer and SDZ adsorption and improvement of electrocatalytic oxidation efficiency. Under the conditions of 0.02 mol·L-1 NaCl solution (pH 8), 15 mA·cm-2 of current density, and 15 g particle electrode, 50 mg·L-1 SDZ could be completely removed on the three-dimensional electrode within 15 min. The removal efficiency of TOC in the reaction solution reached 80.8% for 3 h degradation and was 17.6% higher than that with two-dimensional electrode. The kinetic process of the electrocatalytic oxidation could be well described by the first-order reaction kinetic model, and the rate constant was 0.329 min-1. The degradation products of SDZ were identified by liquid chromatography-tandem mass spectrometry (LC-MS/MS), and the possible pathways of electrocatalytic degradation mainly include the fractures of S-N bond on sulfamido and C-N bond on pyrimidine ring, desulfonation, deamination, and·OH oxidation.