Salsolinol as an RNA m6A methylation inducer mediates dopaminergic neuronal death by regulating YAP1 and autophagy.

JOURNAL/nrgr/04.03/01300535-202503000-00032/figure1/v/2024-06-17T092413Z/r/image-tiff Salsolinol (1-methyl-6,7-dihydroxy-1,2,3,4-tetrahydroisoquinoline, Sal) is a catechol isoquinoline that causes neurotoxicity and shares structural similarity with 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine, an environmental toxin that causes Parkinson's disease. However, the mechanism by which Sal mediates dopaminergic neuronal death remains unclear. In this study, we found that Sal significantly enhanced the global level of N6-methyladenosine (m6A) RNA methylation in PC12 cells, mainly by inducing the downregulation of the expression of m6A demethylases fat mass and obesity-associated protein (FTO) and alkB homolog 5 (ALKBH5). RNA sequencing analysis showed that Sal downregulated the Hippo signaling pathway. The m6A reader YTH domain-containing family protein 2 (YTHDF2) promoted the degradation of m6A-containing Yes-associated protein 1 (YAP1) mRNA, which is a downstream key effector in the Hippo signaling pathway. Additionally, downregulation of YAP1 promoted autophagy, indicating that the mutual regulation between YAP1 and autophagy can lead to neurotoxicity. These findings reveal the role of Sal on m6A RNA methylation and suggest that Sal may act as an RNA methylation inducer mediating dopaminergic neuronal death through YAP1 and autophagy. Our results provide greater insights into the neurotoxic effects of catechol isoquinolines compared with other studies and may be a reference for assessing the involvement of RNA methylation in the pathogenesis of Parkinson's disease.

γδT Cells Induce the Inflammatory Response of Human Fibroblast-Like Synoviocytes Directly or by Stimulating B Cells to Activate IL-17/STAT3 Signaling Pathway.

INTRODUCTION: Rheumatoid arthritis (RA) combined with hashimoto thyroiditis (HT) is an important cause of various fatal comorbidities of RA. There is no precise conclusion about the cause of this disease. METHODS: Peripheral blood and synovial tissue were collected from healthy participants, patients with RA, and patients with both RA and HT. Immunofluorescence staining and Pearson correlation analysis were used to detect the levels of γδTCR and the correlation between IL-17 and p-STAT3, respectively. ELISA, chemiluminescence assays, qRT-PCR and Western blot were performed to detect the levels of IgG, IgM, IFN-γ, IL-1ß, TNF-α, Tg-Ab, Tpo-Ab, IL-17, IL-2, p-SATA3, and STAT3, respectively. RESULTS: There was increased proportion of γδT cells, IL-17, and p-STAT3 levels in RA and HT patients. IL-17 was positively correlated with p-STAT3. γδT cells significantly promoted the expression of IgG, Tg-Ab, Tpo-Ab, and IL-17. When γδT and human fibroblast-like synoviocytes (FLSs) were co-cultured, the levels of IL-2, IFN-γ, IL-1ß, TNF-α, and IL-17 were increased, and the IL-17/STAT3 signaling pathway was activated. When IL-17-silenced γδT cells and STAT3-silenced FLSs were co-cultured, the levels of IL-1ß and TNF-α in FLSs were significantly decreased. Furthermore, when STAT3-silenced FLSs were added to the co-culture medium of B cells and γδT cells, the levels of IL-1ß and TNF-α were also decreased significantly. CONCLUSION: γδT cells induced RA directly or by stimulating B cells to activate STAT3 through IL-17.

Early growth response factor 3 regulates coronary atherosclerosis through the NF-κB signaling pathway and VEGF expression.

AIM: The present study was conducted to measure the expression of early growth response factor 3 (Egr3), inflammatory cytokines (IL-1ß, IL-6), vascular endothelial growth factor (VEGF) and NF-κB in patients with coronary artery disease (CAD) to investigate the relationships of these molecules and Egr3 gene expression. METHODS: We recruited 132 CAD patients and 63 healthy individuals. The expression levels of Egr3, VEGF, p50 and p65 were measured by reverse transcription quantitative polymerase chain reaction and the levels of Egr3, IL-1ß and IL-6 in patients serum and in human coronary artery endothelial cells (HCAECs) were measured by enzyme-linked immunosorbent assay (ELISAs) in CAD patients. HCAECs were treated with ox-LDL to establish an in vitro atherosclerosis model. An oil red O staining assay was used to assess the lipid droplet formation. A colloidal external lumen formed by Matrigel was used to test the migration of HCAECs. The expression of Egr3, VEGF and NF-κB was determined by Western blotting. RESULTS: The levels of serum Egr3 and IL-6 in the severe stenosis group were greater than those in the mild stenosis group and controls (p < 0.05). The level of serum IL-1ß in the severe stenosis group was greater than that in the control group (p < 0.05). Moreover, Egr3 expression was positively associated with IL-6 levels (r= 0.55, p < 0.001), IL-1ß levels (r=0.21, p=0.004) and the Gensini score (r=0.20, p=0.02). We also found that Egr3 expression was significantly greater in CAD patients than that in controls. And its expression was highest in the mild patients. The expression of VEGF, P50 and P65 was also greater in CAD patients. In the in vitro experiment, we found that the inhibition of Egr3 expression significantly reduced the expression levels of p50, p65, IL-6 and CRP. Moreover, the inhibition of Egr3 expression significantly reduced the lipid droplet formation and decreased capability of lumen formation. CONCLUSIONS: In the pathogenesis of atherosclerosis, Egr3 gene expression may induce the expression of inflammatory factors and lipid droplet formation and lumen formation, which could promote the atherosclerosis development.

Copper-Catalyzed P-H Bond Functionalization to Construct Biaryl Phosphafluorene Oxides.

In this study, in the presence of a certain amount of cuprous chloride catalyst and the synergistic action of ligand and base, the P-H bond activation of secondary biarylphosphine oxides and the attack on the ß-site of orthoaryl groups were investigated. Phosphafluorene oxide was synthesized by C-H bond activation and an intramolecular dehydrogenation coupling reaction to construct a C-P bond. Subsequently, we conducted a control experiment and made reasonable speculations about its mechanism. In addition, the use of phosphafluorene as a ligand in some synthetic catalytic reactions has shown excellent results, demonstrating its excellent catalytic properties.

The Reconstruction of Bi 2 Te 4 O 11 Nanorods for Efficient and pH-universal Electrochemical CO 2 Reduction.

The practical application of electrochemical CO2 reduction reaction (CO2RR) is hindered by the competing CO production, hydrogen evolution reaction (HER), and the lack of pH-universal catalysts. Here, Te-modified Bi nanorods (Te-Bi NRs) were synthesized through in situ reconstruction of Bi2Te4O11 NRs under the CO2RR condition. Our study illustrates that the complex reconstruction process of Bi2Te4O11 NRs during CO2RR could be decoupled into three distinct steps, i.e., the destruction of Bi2Te4O11, the formation of Te/Bi phases, and the dissolution of Te. The thus-obtained Te-Bi NRs exhibit remarkably high performance in CO2RR towards formate production, showing high activity, selectivity, and stability across all pH conditions (acidic, neutral, and alkaline). In a flow cell reactor under neutral, alkaline, or acidic conditions, the catalysts achieved HCOOH Faradaic efficiencies of up to 94.3%, 96.4%, and 91.0%, respectively, at a high current density of 300 mA cm-2. DFT calculations, along with operando spectral measurements, reveal that Te manipulates the Bi sites to an electron-deficient state, enhancing the adsorption strength of the *OCHO intermediate, and significantly suppressing the competing HER and CO production. This study highlights the substantial influence of catalyst reconstruction under operational conditions and offers insights into designing highly active and stable electrocatalysts towards CO2RR.

Qualitative exploration of home life experiences and care needs among elderly patients with temporary intestinal stomas.

BACKGROUND: This study employed a phenomenological research approach within qualitative research to explore the challenges encountered by elderly individuals with temporary colostomies in managing their daily lives and care needs. Protecting the anus surgery combined with temporary colostomy has emerged as a prevalent treatment modality for low rectal cancer. However, the ileostomy is susceptible to peri-stoma skin complications, as well as fluid, electrolyte, and nutritional imbalances, posing challenges to effective management. The successful self-management of patients is intricately linked to their adjustment to temporary colostomy; nonetheless, there remains a dearth of research examining the factors influencing self-care among temporary colostomy patients and the obstacles they confront. AIM: To investigate the lived experiences, perceptions, and care requirements of temporary colostomy patients within their home environment, with the ultimate goal of formulating a standardized management protocol. METHODS: Over the period of June to August 2023, a purposive sampling technique was utilized to select 12 patients with temporary intestinal stomas from a tertiary hospital in Shanghai, China. Employing a phenomenological research approach, a semi-structured interview guide was developed, and qualitative interviews were conducted using in-depth interview techniques. The acquired data underwent coding, analysis, organization, and summarization following Colaizzi's seven-step method. RESULTS: The findings of this study revealed that the experiences and needs of patients with temporary intestinal stomas can be delineated into four principal themes: Firstly, Temporary colostomy patients bear various burdens and concerns about the uncertainty of disease progression; secondly, patients exhibit limited self-care capabilities and face information deficits, resulting in heightened reliance on healthcare professionals; thirdly, patients demonstrate the potential for internal motivation through proactive self-adjustment; and finally, patients express a significant need for emotional and social support. CONCLUSION: Home-living patients with temporary intestinal stomas confront multifaceted challenges encompassing burdens, inadequate self-care abilities, informational deficits, and emotional needs. Identifying factors influencing patients' self-care at home and proposing strategies to mitigate barriers can serve as a foundational framework for developing and implementing nursing interventions tailored to the needs of patients with temporary intestinal stomas.

Secretion of WNT7A by UC-MSCs assist in promoting the endometrial epithelial regeneration.

Stem cell therapy for intrauterine adhesions (IUAs) has been widely used in clinical treatment. However, intravenous injection lacks sufficient targeting capabilities, while in situ injection poses challenges in ensuring the effective survival of stem cells. Furthermore, the mechanism underlying the interaction between stem cells and endometrial cells in vivo remains poorly understood, and there is a lack of suitable in vitro models for studying these problems. Here, we designed an extracellular matrix (ECM)-adhesion mimic hydrogel for intrauterine administration, which was more effective than direct injection in treating IUAs. Additionally, we analyzed the epithelial-mesenchymal transition (EMT) and confirmed that the activation of endometrial epithelial stem cells is pivotal. Our findings demonstrated that umbilical cord mesenchymal stem cells (UC-MSCs) secrete WNT7A to activate endometrial epithelial stem cells, thereby accelerating regeneration of the endometrial epithelium. Concurrently, under transforming growth factor alpha (TGFA) stimulation secreted by the EMT epithelium, UC-MSCs upregulate E-cadherin while partially implanting into the endometrial epithelium.

CuxO decorated Ti3C2Tx MXene composites for non-enzymatic glucose sensing with large linear ranges.

Ti3C2Tx MXene/CuxO composites were prepared by acid etching combined with electrochemical technique. The abundant active sites on the surface of MXene greatly increase the loading of CuxO nanoparticles, and the synergistic effect between the different components of the composite can accelerate the oxidation reaction of glucose. The results indicate that at the working potential of 0.55 V (vs. Ag/AgCl), the glucose sensor based on Ti3C2Tx MXene/CuxO composite presents large linear concentration ranges from 1 µM to 4.655 mM (sensitivity of 361 µA mM-1 cm-2) and from 5.155 mM to 16.155 mM (sensitivity of 133 µA mM-1 cm-2). The limit of detection is 0.065 µM. In addition, the sensor effectively avoids the oxidative interference of common interfering species such as ascorbic acid, dopamine and uric acid. The sensor has good reproducibility, stability and acceptable recoveries for the detection of glucose in human sweat sample (97.5-103.3%) with RSD values less than 4%. Based on these excellent properties it has great potential for the detection of glucose in real samples.

Multiple small-dose infusions of G-CSF-mobilized haploidentical lymphocytes after autologous haematopoietic stem cell transplantation for acute myeloid leukaemia.

This retrospective study analysed 106 acute myeloid leukaemia (AML) patients undergoing autologous haematopoietic stem cell transplantation (ASCT) to assess the impact of multiple small-dose infusions of granulocyte-colony-stimulating factor (G-CSF)-mobilized haploidentical lymphocytes as post-ASCT maintenance therapy. Among them, 50 patients received lymphocyte maintenance therapy, 21 received alternative maintenance therapy, and 35 received no maintenance therapy. Patients receiving lymphocyte maintenance therapy demonstrated significantly higher overall survival (OS) and disease-free survival (DFS) compared to those without maintenance therapy, with 4-year OS and DFS rates notably elevated. While there were no significant differences in recurrence rates among the three groups, lymphocyte maintenance therapy showcased particular benefits for intermediate-risk AML patients, yielding significantly higher OS and DFS rates and lower relapse rates compared to alternative maintenance therapy and no maintenance therapy. The study suggests that multiple small-dose infusions of G-CSF-mobilized haploidentical lymphocytes may offer promising outcomes for AML patients after ASCT, particularly for those classified as intermediate-risk. These findings underscore the potential efficacy of lymphocyte maintenance therapy in reducing disease relapse and improving long-term prognosis in this patient population.

4D-QSAR, ADMET properties, and molecular dynamics simulations for designing N-substituted urea/thioureas as human glutaminyl cyclase inhibitors.

Human glutaminyl cyclase (hQC) inhibitors have great potential to be used as anti- Alzheimer's disease (AD) agents by reducing the toxic pyroform of ß-amyloid in the brains of AD patients. The four-dimensional quantitative structure activity relationship (4D-QSAR) model of N-substituted urea/thioureas was established with satisfying predictive ability and statistical reliability (Q2 = 0.521, R2 = 0.933, R2prep = 0.619). By utilizing the developed 4D-QSAR model, a set of new N-substituted urea/thioureas was designed and evaluated for their Absorption Distribution Metabolism Excretion and Toxicity (ADMET) properties. The results of molecular dynamics (MD) simulations, Principal component analysis (PCA), free energy landscape (FEL), dynamic cross-correlation matrix (DCCM) and molecular mechanics generalized Born Poisson-Boltzmann surface area (MM-PBSA) free energy calculations, revealed that the designed compounds were remained stable in protein binding pocket and compounds b ∼ f (-35.1 to -44.55 kcal/mol) showed higher binding free energy than that of compound 14 (-33.51 kcal/mol). The findings of this work will be a theoretical foundation for further research and experimental validation of urea/thiourea derivatives as hQC inhibitors.

Thiostrepton induces oxidative stress, mitochondrial dysfunction and ferroptosis in HaCaT cells.

TST has been mainly studied for its anti-tumor proliferation and antimicrobial effects, but not widely used in dermatological diseases. The mechanism of cellular damage by TST in response to H2O2-mediated oxidative stress was investigated in human skin immortalized keratinocytes (HaCaT) as an in vitro model. The findings reveal that TST treatment leads to increased oxidative stress in the cells by reducing levels of superoxide dismutase (SOD), glutathione (GSH), and catalase (CAT). This effect is further supported by an upsurge in the expression of malondialdehyde (MDA, a pivotal marker of lipid peroxidation). Additionally, dysregulation of FoxM1 at both gene and protein levels corroborates its involvement TST associated effects. Analysis of ferroptosis-related genes confirms dysregulation following TST treatment in HaCaT cells. Furthermore, TST treatment exhibits effects on mitochondrial morphology and function, affirming its induction of apoptosis in the cells through heightened oxidative stress due to mitochondrial damage and dysregulation of mitochondrial membrane potential.

La3+@BC500-S2O82- system for removal of sulfonamide antibiotics in water.

Sulfonamide antibiotics (SAs) widely used have potentially negative effects on human beings and ecosystems. Adsorption and advanced oxidation methods have been extensively applied in SAs wastewater treatment. In this study, compared with Al3+@BC500 and Fe3+@BC500, La3+@BC500 for activating persulfate (S2O82-) had the best effect removal performance of sulfadiazine (SDZ) and sulfamethoxazole (SMX). Morphology, acidity, oxygen-containing functional groups, and loading of La3+@BC500 were analyzed by techniques, including EA, BET, XRD, XPS, FT-IR. XRD results show that with the increase of La3+ loading, the surface characteristics of biochar gradually changed from CaCO3 to LaCO3OH. Through EPR technology, it is proved that LaCO3OH on the surface of La3+@BC500 can not only activate S2O82- to generate SO4-•, but also to produce •OH. In the optimization experiment, the optimal dosage of La3+ is between 0.05 and 0.2 (mol/L)/g. SDZ had a good removal effect at pH (5-9), but SMX had a good removal effect only at pH=3. Zeta potential also proves that the material is more stable under acidic conditions. The removal process of SDZ is more in accord with pseudo-first-order kinetics (R2=0.9869), while SMX is more in line with pseudo-second order kinetics (R2=0.9926).

miR-107 reverses the multidrug resistance of gastric cancer by targeting the CGA/EGFR/GATA2 positive feedback circuit.

Chemotherapy is still the main therapeutic strategy for gastric cancer (GC). However, most patients eventually acquire multidrug resistance (MDR). Hyperactivation of the EGFR signaling pathway contributes to MDR by promoting cancer cell proliferation and inhibiting apoptosis. We previously identified the secreted protein CGA as a novel ligand of EGFR and revealed a CGA/EGFR/GATA2 positive feedback circuit that confers MDR in GC. Herein, we outline a microRNA-based treatment approach for MDR reversal that targets both CGA and GATA2. We observed increased expression of CGA and GATA2 and increased activation of EGFR in GC samples. Bioinformatic analysis revealed that miR-107 could simultaneously target CGA and GATA2, and the low expression of miR-107 was correlated with poor prognosis in GC patients. The direct interactions between miR-107 and CGA or GATA2 were validated by luciferase reporter assays and western blot analysis. Overexpression of miR-107 in MDR GC cells increased their susceptibility to chemotherapeutic agents, including fluorouracil, adriamycin and vincristine, in vitro. Notably, intratumor injection of the miR-107 prodrug enhanced MDR xenograft sensitivity to chemotherapies in vivo. Molecularly, targeting CGA and GATA2 with miR-107 inhibited EGFR downstream signaling, as evidenced by the reduced phosphorylation of ERK and AKT. These results suggest that miR-107 may contribute to the development of a promising therapeutic approach for the treatment of MDR in GC.

The bidirectional relationship between benign/malicious envy and subjective well-being in adolescents: The mediating effect of self-esteem.

INTRODUCTION: Subjective well-being, an important index for measuring mental health, is presently declining among junior high school students. Envy, one of their common emotions, is inextricably linked to subjective well-being. Based on the Dual Envy Theory, our research explores the bidirectional relationship between benign-malicious envy and subjective well-being. The mediating role of self-esteem, as well as the related gender differences, is examined. METHODS: Chinese middle school students (n = 1566, boys 50.3%, age = 13.96 ± 0.88 years old) were assessed at two time points over a 3-month interval. Structural equation modeling was used to examine the longitudinal relationships among the variables. RESULTS: (1) Cross-lagged analysis showed a positive bidirectional relationship between benign envy and subjective well-being and a negative bidirectional relationship between malicious envy and subjective well-being in the total sample. However, the path from T1 subjective well-being to T2 malicious envy in boys was not significant. (2) Self-esteem mediated the relationship between both benign and malicious envy and subjective well-being among both boys and girls. A Wald chi-square test showed that T2 self-esteem was a stronger predictor of T2 benign envy in boys than in girls. CONCLUSION: The results reveal a virtuous cycle of benign envy and subjective well-being, and a vicious cycle of malicious envy and subjective well-being, while emphasizing the role of self-esteem in this process. Gender differences were also noted. These findings have important implications for improving the subjective well-being of secondary school students and exploring the positive effects of envy.

Knowledge, attitudes, and practices among patients with combined dentition defect and non-functional impacted teeth toward tooth autotransplantation.

BACKGROUND: Tooth autotransplantation (TAT) is a surgical procedure involving the extraction of a tooth from one location and its subsequent transplantation into another alveolar socket within the same individual. This innovative treatment approach holds significant promise. Nonetheless, the potential recipients exhibit a limited level of awareness and understanding of this procedure. This study investigated the knowledge, attitudes, and practices (KAP) among patients with combined dentition defects and non-functional impacted teeth toward TAT. METHODS: This web-based cross-sectional study was conducted between December 2022 and February 2023 at one hospital. A self-designed questionnaire was developed to collect demographic information of the patients and assess their knowledge, attitudes, and practices toward TAT. RESULTS: A total of 533 valid questionnaires were collected. The mean knowledge, attitude, and practice scores were 5.55 ± 2.38 (possible range: 0-10), 26.82 ± 2.46 (possible range, 8-40), and 27.45 ± 7.40 (possible range, 9-45), respectively. CONCLUSION: The participants had insufficient knowledge, negative attitudes, and passive practices toward TAT. Targeted interventions should be implemented to improve the understanding and practice of TAT among patients with dentition defects.

Integrated transcriptome and metabolome analysis reveals the molecular responses of Pardosa pseudoannulata to hypoxic environments.

Terrestrial organisms are likely to face hypoxic stress during natural disasters such as floods or landslides, which can lead to inevitable hypoxic conditions for those commonly residing within soil. Pardosa pseudoannulata often inhabits soil crevices and has been extensively studied, yet research on its response to hypoxic stress remains unclear. Therefore, we investigated the adaptive strategies of Pardosa pseudoannulata under hypoxic stress using metabolomics and transcriptomics approaches. The results indicated that under hypoxic stress, metabolites related to energy and antioxidants such as ATP, D-glucose 6-phosphate, flavin adenine dinucleotide (FAD), and reduced L-glutathione were significantly differentially expressed. Pathways such as the citric acid (TCA) cycle and oxidative phosphorylation were significantly enriched. Transcriptome analysis and related assessments also revealed a significant enrichment of pathways associated with energy metabolism, suggesting that Pardosa pseudoannulata primarily copes with hypoxic environments by modulating energy metabolism and antioxidant-related substances.

Wearable and Multiplexed Biosensors based on Oxide Field-Effect Transistors.

Wearable sensors designed for continuous, non-invasive monitoring of physicochemical signals are important for portable healthcare. Oxide field-effect transistor (FET)-type biosensors provide high sensitivity and scalability. However, they face challenges in mechanical flexibility, multiplexed sensing of different modules, and the absence of integrated on-site signal processing and wireless transmission functionalities for wearable sensing. In this work, a fully integrated wearable oxide FET-based biosensor array is developed to facilitate the multiplexed and simultaneous measurement of ion concentrations (H+, Na+, K+) and temperature. The FET-sensor array is achieved by utilizing a solution-processed ultrathin (≈6 nm thick) In2O3 active channel layer, exhibiting high compatibility with standard semiconductor technology, good mechanical flexibility, high uniformity, and low operational voltage of 0.005 V. This work provides an effective method to enable oxide FET-based biosensors for the fusion of multiplexed physicochemical information and wearable health monitoring applications.

Risk assessment of environmental and bystander exposure from agricultural unmanned aerial vehicle sprayers in golden coconut plantations: Effects of droplet size and spray volume.

Unmanned aerial vehicle (UAV) sprayers are widely utilized in commercial aerial application of plant protection products (PPPs) in East Asian countries due to their high flexibility, high efficiency and low cost, but spray drift can lead to low utilization of UAV sprayers application, environmental pollution and bystander exposure risk. Droplet size and spray volume are critical factors affecting spray drift. Currently, the high temperature and humidity environment under the influence of the tropical monsoon climate brings new challenges for UAV sprayers. Therefore, in this study, pesticides were simulated with seduction red solution, and spraying trials were conducted using the DJI commercial T40 UAV sprayers for a typical tropical crop, coconut. In this study, the spray drift distribution of droplets on the ground and in the air, as well as the bystander exposure risk, were comparatively analyzed using droplet size (VF, M, and C) and spray volume (75 L/hm2 and 60 L/hm2) as trial variables. The results indicated that the spray drift characteristics of UAV sprayers were significantly affected by droplet size and spray volume. The spray drift percentage was negatively correlated with the downwind distance and the sampling height. The smaller the droplet size, the farther the buffer zone distance, up to more than 30 m, and the cumulative drift percentage is also greater, resulting in a significant risk of spray drift. The reduction in spray volume helped to reduce the spray drift, and the cumulative drift percentage was reduced by 73.87 % with a droplet size of M. The region of the body where spray drift is deposited the most on bystanders is near chest height. This study provides a reference for the rational and safe use of multirotor UAV sprayers application operations in the tropics and enriches the spray drift database in the tropics.

Distribution characteristics of antinuclear antibodies in Guillain-Barré syndrome and its relationship with disease severity.

BACKGROUND: Guillain-Barré syndrome (GBS), an acquired immune-mediated autoimmune disorder affecting the peripheral nervous system (PNS), is associated with autoimmunity. The presence of autoantibodies in the blood is an important feature of autoimmune diseases. Herein, we explored the distribution characteristics of the antinuclear antibodies (ANAs) in GBS and the correlation between ANAs and disease severity. MATERIALS AND METHODS: We retrospectively analyzed the clinical data of 170 GBS patients. According to ANAs, GBS patients were divided into ANAs positive and negative groups. The clinical characteristics of these two groups were compared. The distribution difference was also compared between male and female GBS patients. In addition, all enrolled patients were divided into more severe group and milder group according to whether the Hughes score at nadir ≥ 3 or not. Gender, age, and ANAs were compared between the two groups. RESULTS: In this study, the positive rate of ANAs was 27.1 % in 170 GBS patients, among which anti-SSA-52/Ro52 antibody and antimitochondrial antibody M2 made up the largest proportion. In the ANAs positive group, GBS patients had longer days of hospitalization, more respiratory function involvement, and higher level of CSF IgG than the ANAs negative group. Compared to the ANAs negative group, Medical Research Council (MRC) scores on admission and at nadir were lower, and Hughes functional Grading Scale (HFGS) scores on admission and at nadir were higher in GBS patients with ANAs positive group. Erasmus GBS Respiratory Insufficiency Score (EGRIS) in ANAs positive GBS patients group was significantly higher than ANAs negative group. Gender had no effects on the distribution of ANAs in GBS patients. Moreover, we found that the anti-SSA-60 antibodies and age were positively correlated with GBS severity. In addition, in the anti-SSA-60 antibody positive group, GBS patients had longer days of hospitalization, more respiratory function involvement, higher HFGS scores on admission/at nadir, and lower MRC scores at nadir compared with the anti-SSA-60 antibody negative group. CONCLUSION: Anti-SSA-52/Ro52 antibody and antimitochondrial antibody M2 were the most common ANAs in GBS patients. Anti-SSA-60 antibodies and age positively correlated with GBS severity. Positive anti-SSA-60 antibodies and age were independent predictors of GBS patient severity.

Dual-recognition colorimetric platform based on porous Au@Pt nanozymes for highly sensitive washing-free detection of Staphylococcus aureus.

A dual-recognition strategy is reported to construct a one-step washing and highly efficient signal-transduction tag system for high-sensitivity colorimetric detection of Staphylococcus aureus (S. aureus). The porous (gold core)@(platinum shell) nanozymes (Au@PtNEs) as the signal labels show highly efficient peroxidase mimetic activity and are robust. For the sake of simplicity the detection involved the use of a vancomycin-immobilized magnetic bead (MB) and aptamer-functionalized Au@PtNEs for dual-recognition detection in the presence of S. aureus. In addition, we designed a magnetic plate to fit the 96-well microplate to ensure consistent magnetic properties of each well, which can quickly remove unreacted Au@PtNEs and sample matrix while avoiding tedious washing steps. Subsequently, Au@PtNEs catalyze hydrogen peroxide (H2O2) to oxidize 3,3',5,5'-tetramethylbenzidine (TMB) generating a color signal. Finally, the developed Au@PtNEs-based dual-recognition washing-free colorimetric assay displayed a response in the range of S. aureus of 5 × 101-5 × 105 CFU/mL, and the detection limit was 40 CFU/mL within 1.5 h. In addition, S. aureus-fortified samples were analyzed to further evaluate the performance of the proposed method, which yielded average recoveries ranging from 93.66 to 112.44% and coefficients of variation (CVs) within the range 2.72-9.01%. These results furnish a novel horizon for the exploitation of a different mode of recognition and inexpensive enzyme-free assay platforms as an alternative to traditional enzyme-based immunoassays for the detection of other Gram-positive pathogenic bacteria.