Machine Alarm Fatigue among Hemodialysis Nurses in 29 Tertiary Hospitals.

Objectives To understand the status quo and related influencing factors of machine alarm fatigue of hemodialysis nurses in tertiary hospitals in XXX. Methods This cross-sectional study employed convenience sampling to select 460 nurses from 29 tertiary hospitals in XXX, who are involved in hemodialysis care. Surveys were conducted using General Information Questionnaire, Alarm Fatigue Scale, National Aeronautics and Space Administration Task Load Index(NASA-TLX) and Maslach Burnout Inventory Scale (MBI). Results The overall machine alarm fatigue score for 460 hemodialysis nurses from 29 tertiary hospitals in XXX was (16.43±6.44), indicating a moderate level. The multiple linear regression analysis shows that years of experience in hemodialysis nursing, the number of patients managed per shift, whether specialized nursing training has been received, self-reported health status, emotional exhaustion, and workload have statistically significant associations with alarm fatigue among hemodialysis nurses (P < 0.05). Among them, years of experience in hemodialysis nursing, the number of patients managed per shift, and workload are positively correlated with alarm fatigue among hemodialysis nurses. Conclusion This study indicates that certain demographic factors, workload, and occupational burnout are associated with machine alarm fatigue among hemodialysis nurses. Therefore, hemodialysis-related managers should establish a Machine Alarm Management System, implement Personalized Thresholds and Delayed Alarms, ensure reasonable staffing arrangements, improve compassion fatigue, and enhance anticipatory care. These measures aim to improve the health and psychological well-being of hemodialysis nurses, provide a conducive environment for professional training in hemodialysis, and ultimately address the current situation of machine alarm fatigue among hemodialysis nurses.

Study on the interaction mechanism between (-)-epigallocatechin-3-gallate and myoglobin: Multi-spectroscopies and molecular simulation.

(-)-Epigallocatechin-3-gallate (EGCG) is remarkably efficacious in inhibiting the browning of red meat. We therefore propose a hypothesis that EGCG forms complexes with myoglobin, thereby stabilizing its structure and thus preventing browning. This study investigated the interaction mechanism between EGCG and myoglobin. EGCG induced static quenching of myoglobin. Noncovalent forces, including hydrogen bonds and van der Waals, primarily governing the interactions between myoglobin and EGCG. The interactions primarily disrupted myoglobin's secondary structure, thus significantly reducing surface hydrophobicity by 53% (P < 0.05). The modification augmented the solubility and thermal stability of myoglobin. The radius of gyration (Rg) value fluctuated between 1.47 and 1.54 nm, and the hydroxyl groups in EGCG formed an average of 2.93 hydrogen bonds with myoglobin. Our findings elucidated the formation of stable myoglobin-EGCG complexes and the myoglobin-EGCG interaction, thus confirming our initial hypothesis.

Th1 cells contribute to retinal ganglion cell loss in glaucoma in a VCAM-1-dependent manner.

Glaucoma is a complex neurodegenerative disorder characterized by the progressive loss of retinal ganglion cells (RGC) and optic nerve axons, leading to irreversible visual impairment. Despite its clinical significance, the underlying mechanisms of glaucoma pathogenesis remain poorly understood. In this study, we aimed to unravel the multifaceted nature of glaucoma by investigating the interaction between T cells and retinas. By utilizing clinical samples, murine glaucoma models, and T cell transfer models, we made several key findings. Firstly, we observed that CD4+ T cells from glaucoma patients displayed enhanced activation and a bias towards T helper (Th) 1 responses, which correlated with visual impairment. Secondly, we identified the infiltration of Th1 cells into the retina, where they targeted RGC and integrated into the pro-inflammatory glial network, contributing to progressive RGC loss. Thirdly, we discovered that circulating Th1 cells upregulated vascular cell adhesion protein 1 (VCAM-1) on retinal microvessels, facilitating their entry into the neural retina. Lastly, we found that Th1 cells underwent functional reprogramming before reaching the retina, acquiring a phenotype associated with lymphocyte migration and neurodegenerative diseases. Our study provides novel insights into the role of peripheral CD4+ T cells in glaucoma pathogenesis, shedding light on the mechanisms underlying their infiltration into the retina and offering potential avenues for innovative therapeutic interventions in this sight-threatening disease.

Exploring the interaction mechanism of chlorogenic acid and myoglobin: Insights from structure and molecular dynamics simulation.

This study focused on non-covalent complex of myoglobin-chlorogenic acid (Mb-CA) and the changes in conformation, oxidation, and microstructure induced by varying concentrations of CA (10-40 µmol/g Mb). Employing molecular docking and dynamics simulations, further insights into the interaction between Mb and CA were obtained. The findings revealed that different CA concentrations enhanced Mb's thermal stability, while diminishing particle size, solubility, and relative content of metmyoglobin (MetMb%). The optimal interaction occurred at 40 µmol/g Mb. Furthermore, CA exhibited static quenching of Mb, with thermodynamic analysis confirming a 1:1 complex formation. These insights deepen our understanding of interaction between Mb and CA, providing valuable clarity.

UBE3C tunes autophagy via ATG4B ubiquitination.

ATG4B is a core protein and essential for cleaving precursor MAP1LC3/LC3 or deconjugating lipidated LC3-II to drive the formation of autophagosomes. The protein stability and activity of ATG4B regulated by post-translational modification (ubiquitination) will directly affect macroautophagy/autophagy. However, the mechanism involved in ATG4B ubiquitination is largely unclear. In this study, a new E3 ligase of ATG4B, UBE3C, was identified by mass spectra. UBE3C mainly assembles K33-branched ubiquitin chains on ATG4B at Lys119 without causing ATG4B degradation. In addition, the increased ubiquitination of ATG4B caused by UBE3C overexpression inhibits autophagy flux in both normal and starvation conditions, which might be due to the reduced activity of ATG4B and ATG4B-LC3 interaction. This reduction could be reversed once the lysine 119 of ATG4B was mutated to arginine. More important, under starvation conditions the interaction between ATG4B and UBE3C apparently decreased followed by the removal of the K33-branched ubiquitin chain of ATG4B. Thus, starvation-induced autophagy could be partially suppressed by an increased ubiquitination level of ATG4B. In conclusion, our research reveals a novel modification mode of ATG4B in which UBE3C can fine tune ATG4B activity by specific ubiquitination regulating autophagy without causing ATG4B degradation.Abbreviation: ATG: autophagy-related; Baf: bafilomycin A1; CBB: Coomassie Brilliant Blue; CM: complete medium; CQ: chloroquine; GFP: green fluorescent protein; HA-Ub: HA-tagged ubiquitin; IF: immunofluorescence; IP: immunoprecipitation; K: lysine; KO: knockout; K0: all K-to-R mutant; MAP1LC3/LC3: microtubule associated protein 1 light chain 3; MS: mass spectrometry; NC: negative control; R: arginine; WCL: whole cell lysate; WT: wild-type.

Thymic stromal lymphopoietin induces platelet mitophagy and promotes thrombosis in Kawasaki disease.

Kawasaki disease (KD) is an acute systemic vasculitis primarily affecting infants and children. Activated platelets predispose patients to coronary artery structural lesions that may lead to thrombotic cardiovascular events. To discover potential proteins underlying platelet activation in KD, we conducted a protein chip assay of 34 cytokines and discovered thymic stromal lymphopoietin (TSLP) was aberrantly expressed, which remained elevated after intravenous immunoglobulin G (IVIG) treatment and during convalescence in KD patients in comparison to healthy controls. Enzyme-linked immunosorbent assay (ELISA) corroborated the upregulation of TSLP in KD patients, which was exacerbated in convalescent patients complicated with thrombosis. TSLP receptors on platelets were also significantly upregulated in KD patients complicated with thrombosis. Platelet activation, apoptosis, and mitochondrial autophagy (mitophagy) were increased in convalescence KD patients complicated with thrombosis. In vitro, TSLP induced platelet activation and platelet mitophagy in healthy blood donors, as observed in KD patients. TSLP, similar to mitophagy agonist carbonyl cyanide 3-chlorophenyl hydrazone (CCCP), promoted thrombosis, which was attenuated by the mitophagy inhibitor Mdivi-1. Co-immunoprecipitation in TSLP-treated platelets revealed TSLP receptor (TSLPR) bound to mitophagy regulators, Parkin and Voltage Dependent Anion Channel Protein 1 (VDAC1).Thus, our results demonstrated that TSLP induced platelet mitophagy via a novel TSLPR/Parkin/VDAC1 pathway that promoted thrombosis in KD. These results suggest TSLP as a novel therapeutic target against KD-associated thrombosis.

KLF2 reduces dexamethasone-induced injury to growth plate chondrocytes by inhibiting the Runx2-mediated PI3K/AKT and ERK signalling pathways.

Dexamethasone (Dex) is a type of glucocorticoid drug. Long term use can induce growth plate chondrocytes (GPCs) apoptosis, impair differentiation, and inhibit cell proliferation and bone growth. It has been reported that Krüppel-like factor 2 (KLF2) inhibits osteoblast damage induced by Dex, but the role in Dex-induced GPCs remains unclear. Dex was used to construct a model of growth plate injury in vitro. CCK-8 and TUNEL kits were used to determine cell viability and apoptosis. A model of growth plate injury was established by intraperitoneal injection of Dex. Immunohistochemistry was used to investigate the expression of KLF2 in rats. The results showed that KLF2 expression of rat tibial GPCs was down-regulated after Dex stimulation. Overexpression of KLF2 promoted cell viability and cell cycle, while inhibited apoptosis of growth plate Dex-induced chondrocytes. Moreover, KLF2 inhibited Runx2-mediated PI3K/AKT and ERK signalling pathways. And PI3K/AKT and ERK signalling pathways, which were involved in the regulation of KLF2 on GPCs. Further studies showed that KLF2 alleviated growth plate injury in vivo. In conclusion, our study found that KLF2 promoted proliferation and inhibited apoptosis of Dex-induced GPCs by targeting the Runx2-mediated PI3K/AKT and ERK signalling pathways.

From Weight Bias Internalization to Health-Related Quality of Life: Self-esteem and Psychopathology in Pre-bariatric Surgery Patients.

INTRODUCTION: It has been reported that people seeking bariatric surgery have poor health-related quality of life (HRQoL). Weight bias internalization (WBI) is prevalent in this population and strongly associated with psychopathology and health status. However, the psychological mechanisms underlying the relationship between WBI and the physical and mental dimensions of HRQoL remain to be clarified. METHODS: A preoperative sample of patients with obesity (N = 246; women = 75.2%; Mage = 32.07) completed validated measures as part of a routine preoperative psychological assessment to assess their WBI, self-esteem, anxiety symptoms, depressive symptoms, and HRQoL. RESULTS: After controlling for the effects of gender, age, and BMI, WBI was linked to poorer physical and mental HRQoL through low self-esteem and increased psychological distress, including anxiety and depressive symptoms. CONCLUSION: In pre-bariatric surgery patients with obesity, high WBI may predict impairments in mental and physical HRQoL by lowering self-esteem, and further increasing anxiety and depressive symptoms. Interventions targeting WBI may be an important aspect to consider in the clinical treatment of pre-bariatric surgery patients. Further longitudinal studies are warranted to determine causality.

A New Model for Predicting Nonsentinel Lymph Node Metastasis in Early-Stage Breast Cancer Using MMP15.

Background: In early-stage breast cancer (BC) patients, 40-70% of lymph node metastases are limited to the sentinel lymph nodes (SLNs). Patients at low risk for nonsentinel lymph node (NSLN) metastasis should be exempt from axillary lymph node dissection (ALND) or regional lymph node radiotherapy (RNI). Methods: The present study included 237 female early-stage BC patients with positive SLNs who received ALND. Based on the clinicopathological factors of the 158 patients in the training cohort, multivariate analysis was used to determine the independent risk factors for NSLN metastasis, which were used to establish the NSLN metastasis prediction model. The calibration and discrimination of this model were tested with the training and validation cohorts and compared to the Memorial Sloan Kettering Cancer Center (MSKCC) model. Results: Tumor size, neural invasion, lymphovascular invasion, expression of matrix metalloproteinase 15 (MMP15) in the cytoplasm, and the number of positive SLNs were statistically significant by multivariate analysis (P < 0.05), which were used to establish the new model. The MSKCC model was verified by the training cohort, and the area under the receiver-operating characteristic (ROC) curve was 0.733 (95% CI: 0.650-0.816), which was less than that of the new model (0.824; 95% CI: 0.760-0.889). The area under the ROC curve in the validation cohort for the new model was 0.773 (95% CI: 0.669-0.877), and the calibration performed well. The false-negative rates were 3.2%, 6.5%, and 14.5% for the predicted probability cut-offs of 50%, 60%, and 70%, respectively. Conclusions: The new model included five variables: tumor size, neural invasion, lymphovascular invasion, cytoplasmic MMP15 expression, and the number of positive SLNs. The model with a cut-off of 60% could accurately identify low-risk patients with NSLN metastasis.

Impact of Platelets to Lymphocytes Ratio and Lymphocytes during Radical Concurrent Radiotherapy and Chemotherapy on Patients with Nonmetastatic Esophageal Squamous Cell Carcinoma.

Purpose: This study examined the importance of hematological parameters as prognostic markers for people with esophageal cancer receiving radical concurrent chemoradiation. Methods: 106 patients with esophageal cancer are included in this study. Cox regression analysis, Kaplan-Meier method, and chi-square test were used to analyze our data. Results: The median follow-up time for patients was 15.5 months (3-55). Univariate and multivariate analyses showed that age, the change of platelet-to-lymphocyte ratio (ΔPLR), and the change rate of circulating lymphocyte count (ΔCLC%) were independent influencing factors of OS and DFS. The patients were grouped according to the median of ΔPLR and ΔCLC%, and analysis showed that a higher ΔPLR and a higher ΔCLC% was related to poor OS and DFS (P < 0.001, P < 0.001 and P < 0.001, P < 0.001). By subgroup analysis, the OS of T1-4N1-2 were better in the low ΔPLR group than the high one (P = 0.03, P < 0.001, P = 0.001, P < 0.001, and P = 0.008). DFS of T3-4N1-2 in the low ΔPLR group were better than the high one (P < 0.001, P = 0.016 and P < 0.001, P = 0.022). For patients with T1-4N0-2, the OS in the low ΔCLC% group were better than in the high ΔCLC% group (P = 0.01, P < 0.001, P < 0.002, P = 0.012, P < 0.001, and P = 0.024). For T1-4N1-2, the DFS were better in the low ΔCLC% group than others (P = 0.042, P < 0.001, P < 0.001, P < 0.001, and P = 0.006). Conclusion: ΔPLR and ΔCLC% are independent factors of OS and DFS, and a lower ΔPLR and ΔCLC% are associated with a better OS and DFS. And T3-4N1-2 patients in the low ΔPLR group and low ΔCLC% group have greater survival benefit.

miR-503-5p inhibits colon cancer tumorigenesis, angiogenesis, and lymphangiogenesis by directly downregulating VEGF-A.

MicroRNAs (miRNAs) are considered important in the pathogenesis of colon cancer. But the mechanism of their role in colon cancer is still largely unknown. Here, we aimed to explore the function of miR-503-5p in the pathogenesis of colon cancer. This study analyzed miRNA microarray of colon cancer. Then, we performed EdU, CCK-8, flow cytometry, Transwell invasion assays and in vivo assays to explore the exact role of miR-503-5p in colon cancer. We observed considerable downregulation of miR-503-5p expression in colon cancer cells and tissues and significant correlation with the TNM stage, differentiation grade and lymph node metastasis of colon cancer. Overexpression of miR-503-5p promoted the apoptosis and G1 arrest of colon cancer cells, and inhibited migration, proliferation, invasion and colony formation. Interestingly, ectopic miR-503-5p overexpression could significantly inhibit vascular endothelial growth factor (VEGF)-A expression and reduce the activity of a luciferase reporter containing the VEGF-A 3'-untranslated region. Furthermore, overexpressed miR-503-5p in human umbilical vein endothelial cells (HUVECs) and colon cancer cells resulted in lower expression levels of VEGFR-2, and subsequently inhibited AKT signaling pathway. Additionally, overexpression of miR-503-5p suppressed both lymphangiogenesis and angiogenesis in vivo and significantly inhibited the tumorigenicity of HT-29 cells in nude mice. In summary, our study shows downregulation of miR-503-5p at least partially contributes to the tumorigenesis of colon cancer through modulating the angiogenesis and lymphangiogenesis by targeting VEGF-A while stimulating AKT signaling pathways. Therapeutic strategies to restore miR-503-5p in colon cancer could be useful to inhibit tumor progression.

Chinese breast cancer patients with CYP2D6*10 mutant genotypes have a better prognosis with toremifene than with tamoxifen.

PURPOSE: To evaluate the prognosis of estrogen receptor-positive breast cancer patients with CYP2D6*10 mutant genotypes under tamoxifen or toremifen therapy. METHODS: Estrogen receptor-positive breast cancer patients were selected and CYP2D6*10 genotypes (C/C, C/T, and T/T) were determined by Sanger sequencing. Patients were divided into tamoxifen, toremifene, or tamoxifen + toremifene groups according to prior therapy. The correlation between CYP2D6*10 genotype and disease-free survival was analyzed. RESULTS: In total, 293 estrogen receptor-positive breast cancer patients treated with tamoxifen or toremifene between 2008 and 2017 were studied. Median follow-up was 39 months (10-141). Of these, 107 (36.52%), 112 (38.23%), and 74 (25.26%) patients had C/C, C/T, and T/T genotypes, respectively. Genotype was significantly associated with disease-free survival in tamoxifen patients. Patients with C/T and T/T genotypes showed worse disease-free survival than patients with a C/C genotype. Genotype and disease-free survival in toremifene and tamoxifen+toremifene patients were not correlated. Of patients with a C/T genotype, toremifene or tamoxifen+toremifene groups showed better disease-free survival than tamoxifen patients. Although disease-free survival of patients with a T/T genotype in the three groups was not statistically different, tamoxifen patients showed worse disease-free survival. There was no correlation between different treatments and disease-free survival in patients with a C/C genotype. Cox proportional hazard analysis revealed toremifene patients had a better prognosis than tamoxifen patients; toremifene was an independent protective factoremifene for disease-free survival. CONCLUSIONS: Tamoxifen was less effective in patients with CYP2D6*10 C/T and T/T genotypes. Estrogen receptor-positive breast cancer patients with a CYP2D6*10 mutation genotype have a better prognosis with toremifen than tamoxifen.

Involvement of Gut Microbiota in the Development of Psoriasis Vulgaris.

Objectives: Psoriasis is a common chronic recurrent dermatitis. Accumulating observations show gut microbiota dysbiosis in psoriasis. We intend to further investigate the relationship between intestinal microbiota and psoriasis development. Design: We first performed an epidemiological investigation on differences of gastrointestinal discomfort symptoms between patients with psoriasis and general population. Then variation of gut microbiota in patients with psoriasis (un)treated with acitretin plus narrow-band ultraviolet B (NB-UVB) was analyzed by 16S rRNA sequencing. We last compared recovery status and vital cytokines (lesion and intestine) of mouse psoriasiform models, which were transplanted with fecal microbiota from patients with psoriasis or healthy controls. Results: (1) About 85.5% of patients with psoriasis vs. 58.1% of healthy controls presented with at least one gastrointestinal symptom. The prevalence of investigated symptoms (e.g., abdominal distension and constipation) were significantly higher in patients, compared with controls (p < 0.05). Passing flatus and constipation were significantly correlated with psoriasis (p < 0.05 in both cases). (2) The abundance of Ruminococcaceae family, Coprococcus_1 genus, and Blautia genus were decreased with psoriasis improvement (p < 0.05, respectively), which had been demonstrated significantly increased in psoriasis. (3) Mice receiving psoriatic microbes transplantation showed delayed recovery of psoriasiform dermatitis and less reduction of interleukin (IL)-17A than those receiving healthy microbiota or blank control (p < 0.05 and p < 0.01, respectively). Conclusion: Multiple evidence we provided here preliminarily demonstrates the involvement of gut microbiota in the different degree of psoriasis activity. The strategy based on overall microbial communities is expected to be a promising supplementary for long-term management of psoriasis.

miR-9-5p regulates immunometabolic and epigenetic pathways in ß-glucan-trained immunity via IDH3α.

Trained immunity, induced by ß-glucan in monocytes, is mediated by activating metabolic pathways that result in epigenetic rewiring of cellular functional programs; however, molecular mechanisms underlying these changes remain unclear. Here, we report a key immunometabolic and epigenetic pathway mediated by the miR-9-5p-isocitrate dehydrogenase 3α (IDH3α) axis in trained immunity. We found that ß-glucan-trained miR-9-5p-/- monocytes showed decreased IL-1ß, IL-6, and TNF-α production after LPS stimulation. Trained miR-9-5p-/- mice produced decreased levels of proinflammatory cytokines upon rechallenge in vivo and had worse protection against Candida albicans infection. miR-9-5p targeted IDH3α and reduced α-ketoglutarate (α-KG) levels to stabilize HIF-1α, which promoted glycolysis. Accumulating succinate and fumarate via miR-9-5p action integrated immunometabolic circuits to induce histone modifications by inhibiting KDM5 demethylases. ß-Glucan-trained monocytes exhibited low IDH3α levels, and IDH3α overexpression blocked the induction of trained immunity by monocytes. Monocytes with IDH3α variants from autosomal recessive retinitis pigmentosa patients showed a trained immunity phenotype at immunometabolic and epigenetic levels. These findings suggest that miR-9-5p and IDH3α act as critical metabolic and epigenetic switches in trained immunity.

Development of a quantum dot nanobead-based fluorescent strip immunosensor for on-site detection of aflatoxin B1 in lotus seeds.

Owing to the serious threat of aflatoxin B1 (AFB1) to public health, development of a reliable method for accurate determination of it is extremely necessary and urgent. In this study, a simple, rapid and highly-sensitive quantum dot nanobeads (QBs) based lateral flow fluorescent strip immunosensor was developed for on-site detection of AFB1 in edible and medicinal lotus seeds. Carboxylated QBs were used as the fluorescent markers to prepare the fluorescent probe through coupling QBs with anti-AFB1 antibodies. Bovine serum albumin (BSA)-AFB1 antigens and goat anti-mouse IgG antibodies were coated on the nitrocellulose (NC) membrane to prepare the test (T) and control (C) lines, respectively. Qualitative analysis of AFB1 was realized by naked eye, and the quantitative determination was achieved with a portable strip reader. Results showed that the newly-developed test strip sensor could achieve rapid detection of AFB1 within 15 min, allowing a limit of detection (LOD) of 1 ng/mL (2 µg/kg) and a linear range of 1-19 ng/mL (2-38 µg/kg). Recovery rates from the fortified lotus seeds with low, medium and high spiking concentrations (2.5, 5 and 10 µg/kg) ranged from 94.0% to 116.0% with relative standard deviations less than 10%. All the results were confirmed by a standard LC-MS/MS method. The QBs-based fluorescent strip immunosensor with high sensitivity, easy operation, and low cost provided a preferred solution for rapid, on-site screening and highly-sensitive quantitation of AFB1 in a large number of lotus seed samples.

PTHR1 in osteosarcoma: Specific molecular mechanisms and comprehensive functional perspective.

Osteosarcoma occurs largely in children and adolescents and is the most common primary malignant tumour of bone. Although surgical advances and neoadjuvant chemotherapy have made great strides in recent years, rates of local recurrence and lung metastasis remain high, with a plateau in overall survival during the past decade. It is thus urgent to explore the pathogenesis of osteosarcoma and identify potential therapeutic targets. Parathyroid hormone receptor 1 (PTHR1) belongs to the broad family of G protein-coupled receptors, binding both parathyroid hormone (PTH) and parathyroid hormone-related peptide (PTHrP, a paracrine factor). Previous studies have shown that in tissues and cells of osteosarcoma, expression of PTHR1 is markedly increased, correlating with aggressive biologic behaviour and a poor prognosis. PTHR1 expression also correlates closely with epigenetic regulation, transcriptional regulation, post-translational modification and protein interaction. Herein, we have summarized the latest research on the role played by PTHR1 in progression of osteosarcoma, assessing its clinical utility as a novel biomarker and its therapeutic ramifications.

The nerve injuries attenuate the persistence of psoriatic lesions.

BACKGROUND: The involvement of the nerve in psoriasis development was suggested by sporadic case reports. OBJECTIVES: To provide multiple evidence for the nerve in psoriasis development with a retrospective case review, a literature review and a mouse-based experimental experiment. METHODS: Psoriatic patients who had concomitant nerve injuries and such cases from literatures were reviewed. And, on wild-type mouse level, unilateral denervation surgery was performed on the dorsal skin before and after the induction of psoriasiform dermatitis, respectively. Lesion visual scores were calculated, and biopsies were taken for hematoxylin-eosin (HE) staining, immunofluorescence analysis, and RNA sequencing & bioinformatics analysis before denervation surgery and the 2nd, 4th, 6th, 8th day after the surgery. RESULTS: All clinical cases (20/20) showed that local lesions under the control of injured nerves relieved spontaneously or even cleared/spared, and only about 1/3 experienced partial recurrence. Next, mouse psoriasiform experiments demonstrated that unilateral denervation prior to imiquimod application attenuated the enhancement of inflammatory reactions (e.g. adaptive immune response and Th17 cell differentiation pathway) and the induction of ipsilateral psoriasiform dermatitis. On the other hand, unilateral denervation after psoriasiform dermatitis induction promoted the regression of inflammatory reactions (e.g. T cell activation, TNF signaling, and Th17 cell differentiation pathway) and ipsilateral dermatitis recovery. CONCLUSION: Our study based on both retrospective clinical case review and wild-type mouse experiments provides multiple evidence for the involvement of the nerve in psoriasis development. Regulation of immune events, including TNF signaling and Th17 cell differentiation, may be the mechanisms of the nerve in psoriasis.

Mitochondria-Associated Endoplasmic Reticulum Membranes in Breast Cancer.

Mitochondria-associated ER membranes (MAMs) represent a crucial intracellular signaling hub, that regulates various cellular events including Ca2+ homeostasis, lipid metabolism, mitochondrial function, and cellular survival and death. All of these MAM-mediated cellular events contribute to carcinogenesis. Indeed, altered functions of MAMs in several types of cancers have been documented, in particular for breast cancer. Over the past years, altered expression of many MAM-resident proteins have been reported in breast cancer. These MAM-resident proteins play an important role in regulation of breast cancer initiation and progression. In the current review, we discuss our current knowledge about the functions of MAMs, and address the underlying mechanisms through which MAM-resident proteins regulate breast cancer. A fuller understanding of the pathways through which MAMs regulate breast cancer, and identification of breast cancer-specific MAM-resident proteins may help to develop novel therapeutic strategies for breast cancer.

Development of a multi-channel magnetic bead micro-probe assay for high-throughput detection of zearalenone in edible and medicinal Coix seed.

A multi-channel magnetic bead micro-probes assay (MBPA) based on indirect competitive principle was developed for high-throughput detection of zearalenone (ZEA) in edible and medicinal Coix seed. This strategy introduced magnetic beads as the carriers, the specific primary antibodies as the capture probes for targets and the secondary antibodies functionalized goat anti-mouse immunoglobulin G labeled fluorescein isothiocyanate as the fluorescence signal probes. Through the competitive reaction of ZEA in Coix seed samples and that covalently coupled on the surface of MBs with their specific antibodies, as well as fast magnetic separation and sensitive fluorescence detection, the developed MBPA strategy allowed low limit of detection (2.03 ng/mL) with broad dynamic range (2.03-440.67 ng/mL), as well as excellent accuracy with the average recovery rate of 96.39% and relative standard deviation (RSD) of 5.48% for ZEA. 36 samples could realize simultaneous analysis in one operation within less than 20 min only needing 50 µL of solution and 30 s of sampling, avoiding large consumption of time and organic solvents. Multiple centrifugation and cleanup steps were omitted because of magnetic separation, avoiding the loss of targets. Diverse capture and fluorescent probes can be randomly bound onto the surface of MBs, making the MBPA strategy a promising tool for on-site high-throughput monitoring of various trace hazard factors in food safety, and environmental monitoring.