A peptide-based pH-sensitive antibacterial hydrogel for healing drug-resistant biofilm-infected diabetic wounds.

Diabetic foot ulcers are a significant complication affecting roughly 15% of diabetic patients. These chronic wounds can be incredibly burdensome, leading to high treatment costs, potential amputations, and additional health complications. Microbiological studies reveal that bacterial infections are the primary culprit behind delayed wound healing. To solve the problem of infection at the wound site, the most fundamental thing is to kill the pathogenic bacteria. Herein, a neoteric strategy to construct novel antibacterial hydrogel COA-T3 that combined photosensitizers (PSs) and antimicrobial peptides (AMPs) via covalent coupling was proposed. Hydrogel COA-T3 composed of quaternized chitosan (QCS) and oxidized dextran (OD) was constructed for co-delivery of the photosensitizer TPI-PN and the antimicrobial peptide HHC10. In vitro and in vivo experiments demonstrated remarkable effectiveness of COA-T3 against drug-resistant bacteria. Furthermore, the hydrogel significantly promoted healing of diabetic infected wounds. This enhanced antibacterial activity is attributed to the pH-sensitive release of both PSs and AMPs within the hydrogel. Additionally, COA-T3 exhibits excellent biocompatibility, making it a promising candidate for wound dressing materials. These findings indicated that the COA-T3 hydrogel is a promising wound dressing material for promoting the healing of diabetic foot ulcers by providing an environment conducive to improved wound healing in diabetic patients.

Development and evaluation of a multi-target droplet digital PCR assay for highly sensitive and specific detection of Yersinia pestis.

BACKGROUND: Plague, caused by the bacterium Yersinia pestis, is a zoonotic disease that poses considerable threats to human health. Nucleic acid tests are crucial for plague surveillance and the rapid detection of Y. pestis. However, inhibitors in complex samples such as soil and animal tissues often hamper nucleic acid detection, leading to a reduced rate of identifying low concentrations of Y. pestis. To address this challenge, we developed a sensitive and specific droplet digital polymerase chain reaction (ddPCR) assay for detecting Y. pestis DNA from soil and animal tissue samples. METHODS: Three genes (ypo2088, caf1, and pla) from Y. pestis were used to develop a multi-target ddPCR assay. The limits of detection (LoD), reproducibility, and specificity were assessed for bacterial genomic DNA samples. The ability of the assay to detect low concentrations of Y. pestis DNA from simulated soil and mouse liver tissue samples was respectively evaluated and compared with that of quantitative real-time PCR (qPCR). RESULTS: The results showed that the ddPCR LoDs ranged from 6.2 to 15.4 copies/reaction for the target genes, with good reproducibility and high specificity for Y. pestis. By testing 130 soil and mouse liver tissue samples spiked with Y. pestis, the ddPCR assay exhibited a better sensitivity than that of the qPCR assay used in the study, with LoDs of 102 colony forming units (CFU)/100 mg soil and 103 CFU/20 mg liver. Moreover, the assay presented good quantitative linearity (R2 = 0.99) for Y. pestis at 103-106 CFU/sample for soil and liver samples. CONCLUSION: The ddPCR assay presented good performance for detecting Y. pestis DNA from soil and mouse tissue samples, showing great potential for improving the detection rate of low concentrations of Y. pestis in plague surveillance and facilitating the early diagnosis of plague cases.

Association between PM2.5 constituents and cardiometabolic risk factors: exploring individual and combined effects, and mediating inflammation.

BACKGROUND: The individual and combined effects of PM2.5 constituents on cardiometabolic risk factors are sparsely investigated. Besides, the key cardiometabolic risk factor that PM2.5 constituents targeted and the biological mechanisms remain unclear. METHOD: A multistage, stratified cluster sampling survey was conducted in two typically air-polluted Chinese cities. The PM2.5 and its constituents including sulfate, nitrate, ammonium, organic matter, and black carbon were predicted using a machine learning model. Twenty biomarkers in three category were simultaneously adopted as cardiometabolic risk factors. We explored the individual and mixture association of long-term PM2.5 constituents with these markers using generalized additive model and quantile-based g-computation, respectively. To minimize potential confounding effects, we accounted for covariates including demographic, lifestyle, meteorological, temporal trends, and disease-related information. We further used ROC curve and mediation analysis to identify the key subclinical indicators and explore whether inflammatory mediators mediate such association, respectively. RESULT: PM2.5 constituents was positively correlated with HOMA-B, TC, TG, LDL-C and LCI, and negatively correlated with PP and RC. Further, PM2.5 constituent mixture was positive associated with DBP, MAP, HbA1c, HOMA-B, AC, CRI-1 and CRI-2, and negative associated with PP and HDL-C. The ROC analysis further reveals that multiple cardiometabolic risk factors can collectively discriminate exposure to PM2.5 constituents (AUC>0.9), among which PP and CRI-2 as individual indicators exhibit better identifiable performance for nitrate and ammonium (AUC>0.75). We also found that multiple blood lipid indicators may be affected by PM2.5 and its constituents, possibly mediated through complement C3 or hsCRP. CONCLUSION: Our study suggested associations of individual and combined PM2.5 constituents exposure with cardiometabolic risk factors. PP and CRI-2 were the targeted markers of long-term exposure to nitrate and ammonium. Inflammation may serve as a mediating factor between PM2.5 constituents and dyslipidemia, which enhance current understanding of potential pathways for PM2.5-induced preclinical cardiovascular responses.

The alteration of the structure and macroscopic mechanical response of porcine patellar tendon by elastase digestion.

Background: The treatment of patellar tendon injury has always been an unsolved problem, and mechanical characterization is very important for its repair and reconstruction. Elastin is a contributor to mechanics, but it is not clear how it affects the elasticity, viscoelastic properties, and structure of patellar tendon. Methods: The patellar tendons from six fresh adult experimental pigs were used in this study and they were made into 77 samples. The patellar tendon was specifically degraded by elastase, and the regional mechanical response and structural changes were investigated by: (1) Based on the previous study of elastase treatment conditions, the biochemical quantification of collagen, glycosaminoglycan and total protein was carried out; (2) The patellar tendon was divided into the proximal, central, and distal regions, and then the axial tensile test and stress relaxation test were performed before and after phosphate-buffered saline (PBS) or elastase treatment; (3) The dynamic constitutive model was established by the obtained mechanical data; (4) The structural relationship between elastin and collagen fibers was analyzed by two-photon microscopy and histology. Results: There was no statistical difference in mechanics between patellar tendon regions. Compared with those before elastase treatment, the low tensile modulus decreased by 75%-80%, the high tensile modulus decreased by 38%-47%, and the transition strain was prolonged after treatment. For viscoelastic behavior, the stress relaxation increased, the initial slope increased by 55%, the saturation slope increased by 44%, and the transition time increased by 25% after enzyme treatment. Elastin degradation made the collagen fibers of patellar tendon become disordered and looser, and the fiber wavelength increased significantly. Conclusion: The results of this study show that elastin plays an important role in the mechanical properties and fiber structure stability of patellar tendon, which supplements the structure-function relationship information of patellar tendon. The established constitutive model is of great significance to the prediction, repair and replacement of patellar tendon injury. In addition, human patellar tendon has a higher elastin content, so the results of this study can provide supporting information on the natural properties of tendon elastin degradation and guide the development of artificial patellar tendon biomaterials.

Associations of metals and metal mixtures with glucose homeostasis: A combined bibliometric and epidemiological study.

This study employs a combination of bibliometric and epidemiological methodologies to investigate the relationship between metal exposure and glucose homeostasis. The bibliometric analysis quantitatively assessed this field, focusing on study design, predominant metals, analytical techniques, and citation trends. Furthermore, we analyzed cross-sectional data from Beijing, examining the associations between 14 blood metals and 6 glucose homeostasis markers using generalized linear models (GLM). Key metals were identified using LASSO-PIPs criteria, and Bayesian kernel machine regression (BKMR) was applied to assess metal mixtures, introducing an "Overall Positive/Negative Effect" concept for deeper analysis. Our findings reveal an increasing research interest, particularly in selenium, zinc, cadmium, lead, and manganese. Urine (27.6%), serum (19.0%), and whole blood (19.0%) were the primary sample types, with cross-sectional studies (49.5%) as the dominant design. Epidemiologically, significant associations were found between 9 metals-cobalt, copper, lithium, manganese, nickel, lead, selenium, vanadium, zinc-and glucose homeostasis. Notably, positive-metal mixtures exhibited a significant overall positive effect on insulin levels, and notable interactions involving nickel were identified. These finding not only map the knowledge landscape of research in this domain but also introduces a novel perspective on the analysis strategies for metal mixtures.

FLNA overexpression promotes papillary thyroid cancer aggression via the FAK/AKT signaling pathway.

Background: Filamin A (FLNA) is a member of the filamin family and has been found to be critical for the progression of several cancers. However, its biological function in papillary thyroid cancer (PTC) remains largely unexplored. Methods: Data from The Cancer Genome Atlas (TCGA) databases were utilized to analyze the FLNA expression level and its influence on the clinical implications of patients with PTC. Gene Expression Omnibus (GEO) and qRT-PCR was used to verify the expression levels of FLNA in PTC. Kaplan-Meier survival analysis was conducted to evaluate the prognostic value of FLNA in PTC. Transwell assays and wound healing were performed to examine the biological function of FLNA knockdown in PTC cells. Gene set enrichment analysis (GSEA) and Western blotting were conducted to investigate the potential mechanisms underlying the role of FLNA in PTC progression. In addition, the relationship between FLNA expression and the tumor immune microenvironment (TME) in PTC was explored. Results: FLNA was significantly upregulated in PTC tissues. High expression levels of FLNA was correlated with advanced TNM stage, T stage, and N stage, as well as poor disease-free interval (DFI) and progression-free interval (PFI) time in PTC patients. Moreover, we found that FLNA knockdown inhibited the migration and invasion of PTC cells. Mechanistically, FLNA knockdown inhibited epithelial-mesenchymal transition (EMT) in PTC and affected the activation of the FAK/AKT signaling pathway. In addition, FLNA expression was associated with TME in PTC. Conclusion: FLNA may be regarded as a new therapeutic target for PTC patients.

Adaptive Metabolic Responses Facilitate Blood-Brain Barrier Repair in Ischemic Stroke via BHB-Mediated Epigenetic Modification of ZO-1 Expression.

Adaptive metabolic responses and innate metabolites hold promising therapeutic potential for stroke, while targeted interventions require a thorough understanding of underlying mechanisms. Adiposity is a noted modifiable metabolic risk factor for stroke, and recent research suggests that it benefits neurological rehabilitation. During the early phase of experimental stroke, the lipidomic results showed that fat depots underwent pronounced lipolysis and released fatty acids (FAs) that feed into consequent hepatic FA oxidation and ketogenesis. Systemic supplementation with the predominant ketone beta-hydroxybutyrate (BHB) is found to exert discernible effects on preserving blood-brain barrier (BBB) integrity and facilitating neuroinflammation resolution. Meanwhile, blocking FAO-ketogenesis processes by administration of CPT1α antagonist or shRNA targeting HMGCS2 exacerbated endothelial damage and aggravated stroke severity, whereas BHB supplementation blunted these injuries. Mechanistically, it is unveiled that BHB infusion is taken up by monocarboxylic acid transporter 1 (MCT1) specifically expressed in cerebral endothelium and upregulated the expression of tight junction protein ZO-1 by enhancing local ß-hydroxybutyrylation of H3K9 at the promoter of TJP1 gene. Conclusively, an adaptive metabolic mechanism is elucidated by which acute lipolysis stimulates FAO-ketogenesis processes to restore BBB integrity after stroke. Ketogenesis functions as an early metabolic responder to restrain stroke progression, providing novel prospectives for clinical translation.

Identification of pathogen composition in a Chinese population with iatrogenic and native vertebral osteomyelitis by using mNGS.

BACKGROUND: Early antimicrobial therapy is crucial regarding the prognosis of vertebral osteomyelitis, but early pathogen diagnosis remains challenging. OBJECTIVE: In this study, we aimed to differentiate the types of pathogens in iatrogenic vertebral osteomyelitis (IVO) and native vertebral osteomyelitis (NVO) to guide early antibiotic treatment. METHODS: A total of 145 patients, who had confirmed spinal infection and underwent metagenomic next-generation sequencing (mNGS) testing, were included, with 114 in the NVO group and 31 in the IVO group. Using mNGS, we detected and classified 53 pathogens in the 31 patients in the IVO group and 169 pathogens in the 114 patients in the NVO group. To further distinguish IVO from NVO, we employed machine learning algorithms to select serum biomarkers and developed a nomogram model. RESULTS: The results revealed that the proportion of the Actinobacteria phylum in the NVO group was approximately 28.40%, which was significantly higher than the 15.09% in the IVO group. Conversely, the proportion of the Firmicutes phylum (39.62%) in the IVO group was markedly increased compared to the 21.30% in the NVO group. Further genus-level classification demonstrated that Staphylococcus was the most common pathogen in the IVO group, whereas Mycobacterium was predominant in the NVO group. Through LASSO regression and random forest algorithms, we identified 5 serum biomarkers including percentage of basophils (BASO%), percentage of monocytes (Mono%), platelet volume (PCT), globulin (G), activated partial thromboplastin time (APTT) for distinguishing IVO from NVO. Based on these biomarkers, we established a nomogram model capable of accurately discriminating between the two conditions. CONCLUSION: The results of this study hold promise in providing valuable guidance to clinical practitioners for the differential diagnosis and early antimicrobial treatment of vertebral osteomyelitis.

Harnessing antimicrobial peptide-coupled photosensitizer to combat drug-resistant biofilm infections through enhanced photodynamic therapy.

Bacterial biofilm-associated infection was one of the most serious threats to human health. However, effective drugs for drug-resistance bacteria or biofilms remain rarely reported. Here, we propose an innovative strategy to develop a multifunctional antimicrobial agent with broad-spectrum antibacterial activity by coupling photosensitizers (PSs) with antimicrobial peptides (AMPs). This strategy capitalizes on the ability of PSs to generate reactive oxygen species (ROS) and the membrane-targeting property of AMPs (KRWWKWIRW, a peptide screened by an artificial neural network), synergistically enhancing the antimicrobial activity. In addition, unlike conventional aggregation-caused quenching (ACQ) photosensitizers, aggregation-induced emission (AIE) PSs show stronger fluorescence emission in the aggregated state to help visualize the antibacterial mechanism. In vitro antibacterial experiments demonstrated the excellent killing effects of the developed agent against both Gram-positive (G+) and Gram-negative (G-) bacteria. The bacterial-aggregations induced ability enhanced the photoactivatable antibacterial activity against G- bacteria. Notably, it exhibited a significant effect on destroying MRSA biofilms. Moreover, it also showed remarkable efficacy in treating wound infections in mice in vivo. This multifunctional antimicrobial agent holds significant potential in addressing the challenges posed by bacterial biofilm-associated infections and drug-resistant bacteria.

Rumor detection based on Attention Graph Adversarial Dual Contrast Learning.

It is becoming harder to tell rumors from non-rumors as social media becomes a key news source, which invites malicious manipulation that could do harm to the public's health or cause financial loss. When faced with situations when the session structure of comment sections is deliberately disrupted, traditional models do not handle them adequately. In order to do this, we provide a novel rumor detection architecture that combines dual comparison learning, adversarial training, and attention filters. We suggest the attention filter module to achieve the filtering of some dangerous comments as well as the filtering of some useless comments, allowing the nodes to enter the GAT graph neural network with greater structural information. The adversarial training module (ADV) simulates the occurrence of malicious comments through perturbation, giving the comments some defense against malicious comments. It also serves as a hard negative sample to aid double contrast learning (DCL), which aims to learn the differences between various comments, and incorporates the final loss in the form of a loss function to strengthen the model. According to experimental findings, our AGAD (Attention Graph Adversarial Dual Contrast Learning) model outperforms other cutting-edge algorithms on a number of rumor detection tasks. The code is available at https://github.com/icezhangGG/AGAD.git.

Higher cardiovascular disease risks in people living with HIV: A systematic review and meta-analysis.

Background: The prognosis of AIDS after active antiretroviral therapy (ART) and the quality of life of people living with HIV (PLWH) are both affected by non-AIDS-related diseases such as cardiovascular disease (CVD). However, the specific risk ratios between PLWH and individuals negative for HIV are poorly understood. We aimed to systematically review and investigate the CVD risk factors associated with HIV. Methods: We searched PubMed, Embase, Web of Science, and Cochrane Library databases between 1 January 2015, and 12 May 2023 for articles reported the prevalence and risk factors of CVD such as hypertension, dyslipidaemia, coronary artery disease (CAD), and myocardial infarction (MI). Due to the high heterogeneity, we used a random-effects model to analyse the data. All statistical analyses were performed using Stata/MP 17.0 with 95% confidence intervals (CIs). Results: We analysed 31 eligible studies including 312 913 PLWH. People living with HIV had higher risks of dyslipidaemia (hazard ratio (HR) = 1.53; 95% CI = 1.29, 1.82), CAD (HR = 1.37; 95% CI = 1.24, 1.51), and MI (HR = 1.47; 95% CI = 1.28, 1.68) compared to individuals without HIV. However, there were no significant differences in the prevalence of hypertension between groups (HR = 1.17; 95% CI = 0.97, 1.41). Subgroup analysis revealed that men with HIV, PLWH who smoked and the elderly PLWH had a high prevalence of CVD. Moreover, the disease prevalence patterns varied among regions. In the USA and Europe, for instance, some HRs for CVD were higher than in other regions. Active ART initiation after 2015 appears to have a lower risk of CVD (hypertension, hyperlipidaemia, CAD). All outcomes under analysis showed significant heterogeneity (I2>70%, P < 0.001), which the available study-level variables could only partially account for. Conclusions: People living with HIV had a higher CVD risk than the general population; thus, CVD prevention in PLWH requires further attention. Rapid initiation of ART may reduce the incidence of CVD in PLWH. For timely screening of CVD high-risk individuals and thorough disease management to prevent CVD, further studies are required to evaluate the risk factors for CVD among PLWH, such as age, region, etc. Registration: PROSPERO (CRD42021255508).

Evolution of H7N9 highly pathogenic avian influenza virus in the context of vaccination.

Human infections with the H7N9 influenza virus have been eliminated in China through vaccination of poultry; however, the H7N9 virus has not yet been eradicated from poultry. Carefully analysis of H7N9 viruses in poultry that have sub-optimal immunity may provide a unique opportunity to witness the evolution of highly pathogenic avian influenza virus in the context of vaccination. Between January 2020 and June 2023, we isolated 16 H7N9 viruses from samples we collected during surveillance and samples that were sent to us for disease diagnosis. Genetic analysis indicated that these viruses belonged to a single genotype previously detected in poultry. Antigenic analysis indicated that 12 of the 16 viruses were antigenically close to the H7-Re4 vaccine virus that has been used since January 2022, and the other four viruses showed reduced reactivity with the vaccine. Animal studies indicated that all 16 viruses were nonlethal in mice, and four of six viruses showed reduced virulence in chickens upon intranasally inoculation. Importantly, the H7N9 viruses detected in this study exclusively bound to the avian-type receptors, having lost the capacity to bind to human-type receptors. Our study shows that vaccination slows the evolution of H7N9 virus by preventing its reassortment with other viruses and eliminates a harmful characteristic of H7N9 virus, namely its ability to bind to human-type receptors.

Three-dimensional analysis of puncture needle path through safety triangle approach PLD and design of puncture positioning guide plate.

OBJECTIVE: In this study, the three-dimensional relationship between the optimal puncture needle path and the lumbar spinous process was discussed using digital technology. Additionally, the positioning guide plate was designed and 3D printed in order to simulate the surgical puncture of specimens. This plate served as an important reference for the preoperative simulation and clinical application of percutaneous laser decompression (PLD). METHOD: The CT data were imported into the Mimics program, the 3D model was rebuilt, the ideal puncture line N and the associated central axis M were developed, and the required data were measured. All of these steps were completed. A total of five adult specimens were chosen for CT scanning; the data were imported into the Mimics program; positioning guide plates were generated and 3D printed; a simulated surgical puncture of the specimens was carried out; an X-ray inspection was carried out; and an analysis of the puncture accuracy was carried out. RESULTS: (1) The angle between line N and line M was 42°~55°, and the angles between the line M and 3D plane were 1°~2°, 5°~12°, and 78°~84°, respectively; (2) As the level of the lumbar intervertebral disc decreases, the distance from point to line and point to surface changes regularly; (3) The positioning guide was designed with the end of the lumbar spinous process and the posterior superior iliac spine on both sides as supporting points. (4) Five specimens were punctured 40 times by using the guide to simulate surgical puncture, and the success rate was 97.5% . CONCLUSION: By analyzing the three-dimensional relationship between the optimal puncture needle path and the lumbar spinous process, the guide plate was designed to simulate surgical puncture, and the individualized safety positioning of percutaneous puncture was obtained.

Comparison of the Biomechanical Properties between Healthy and Whole Human and Porcine Stomachs.

Gastric cancer poses a societal and economic burden, prompting an exploration into the development of materials suitable for gastric reconstruction. However, there is a dearth of studies on the mechanical properties of porcine and human stomachs. Therefore, this study was conducted to elucidate their mechanical properties, focusing on interspecies correlations. Stress relaxation and tensile tests assessed the hyperelastic and viscoelastic characteristics of porcine and human stomachs. The thickness, stress-strain curve, elastic modulus, and stress relaxation were assessed. Porcine stomachs were significantly thicker than human stomachs. The stiffness contrast between porcine and human stomachs was evident. Porcine stomachs demonstrated varying elastic modulus values, with the highest in the longitudinal mucosa layer of the corpus and the lowest in the longitudinal intact layer of the fundus. In human stomachs, the elastic modulus of the longitudinal muscular layer of the antrum was the highest, whereas that of the circumferential muscularis layer of the corpus was the lowest. The degree of stress relaxation was higher in human stomachs than in porcine stomachs. This study comprehensively elucidated the differences between porcine and human stomachs attributable to variations across different regions and tissue layers, providing essential biomechanical support for subsequent studies in this field.

Decreased circulating dipeptidyl peptidase-4 activity after short-term intensive insulin therapy predicts clinical outcomes in patients with newly diagnosed type 2 diabetes.

Background: This study aims to investigate the changes in circulating dipeptidyl peptidase-4 (DPP-4) activity following short-term intensive insulin therapy (SIIT) in newly diagnosed type 2 diabetes (T2D) patients and to assess its potential in predicting long-term remission. Methods: Ninety-five patients underwent SIIT for 2-3 weeks to attain and sustain near-normal glycemia. Insulin was then discontinued, and patients were followed for a year to evaluate glycemic outcomes. Biochemical tests, serum DPP-4 activity, and mixed meal tolerance tests were conducted at baseline, post-SIIT, and the 3-month follow-up. Results: DPP-4 activity decreased from 44.08 ± 9.58 to 40.53 ± 8.83 nmol/min/mL after SIIT (P<0.001). After three months post-SIIT, DPP-4 activity remained stable in the remission group (39.63 ± 8.53 nmol/L) but increased in the non-remission group (42.34 ± 6.64 nmol/L). This resulted in a more pronounced decrease in DPP-4 activity from baseline in the remission group (-3.39 ± 8.90 vs. -1.10 ± 8.95, P = 0.035). Logistic regression analyses showed that patients with greater DPP-4 activity reduction had a higher likelihood of 1-year remission (70% vs. 51.1%, OR: 7.939 [1.829, 34.467], P = 0.006 in the fully adjusted model). A non-linear relationship between △DPP-4 and 1-year remission rate was observed, with a clear threshold and saturation effect. Conclusion: Circulating DPP-4 activity significantly decreases after SIIT. The change in circulating DPP-4 activity during the 3-month post-treatment phase has the potential to predict long-term remission.

Graves' disease and systemic lupus erythematosus: a Mendelian randomization study.

Introduction: Previous observational studies have established a correlation between Graves' disease(GD) and systemic lupus erythematosus(SLE). However, whether a causal relationship exists between these two diseases remains unknown.We utilized Mendelian randomization to infer the causal association between GD and SLE. Methods: This study employed GWAS summary statistics of GD and SLE in individuals of Asian descent. The random effect inverse variance weighted (IVW) method was utilized to aggregate the causal effect estimates of all SNPs. Cochran's Q values were computed to evaluate the heterogeneity among instrumental variables. Sensitivity analyses such as MR-Egger method, median weighting method, leave-one-out method, and MR-PRESSO method were used to test whether there was horizontal pleiotropy of instrumental variables. Results: Our study found genetically predicted GD may increase risk of SLE (OR=1.17, 95% CI 0.99-1.40, p=0.069). Additionally, genetically predicted SLE elevated the risk of developing GD by 15% (OR=1.15, 95% CI 1.05-1.27, p= 0.004). After correcting for possible horizontal pleiotropy by excluding outlier SNPs, the results suggested that GD increased the risk of SLE (OR=1.27, 95% CI 1.09-1.48, p =0.018), while SLE also increased the risk of developing GD (OR=1.13, 95% CI 1.05-1.22, p =0.003). Conclusion: The findings of the study indicate that there may be a correlation between GD and SLE, with each potentially increasing the risk of the other. These results have important implications for the screening and treatment of patients with co-morbidities in clinical settings, as well as for further research into the molecular mechanisms underlying the relationship between GD and SLE.

Comparison of plasma aldosterone measured by chemiluminescence immunoassay and liquid chromatography-tandem mass spectrometry in screening test for primary aldosteronism.

Background: Whether chemiluminescence immunoassay (CLIA) and liquid chromatography-tandem mass spectrometry (LC-MS/MS) for plasma aldosterone concentration (PAC) measurement can be used interchangeably in primary aldosteronism (PA) screening is still controversial. The purpose of this study was to compare CLIA to LC-MS/MS for PAC measurement in PA screening. Methods: All participants underwent aldosterone-to-renin ratio (ARR) testing. PA was diagnosed by captopril challenge test or saline infusion test. PAC in screening test was measured with CLIA and LC-MS/MS. Plasma direct renin concentration in screening and confirmatory test was measured with CLIA. The concordance between CLIA and LC-MS/MS for PAC measurement in PA screening was analyzed. Results: Twenty-one healthy volunteers, 61 patients with essential hypertension (EH) and 43 PA patients were enrolled. Median PAC by CLIA was 84.7 % higher than that by LC-MS/MS in screening test (P < 0.001). A positive correlation of PAC was observed between the two assays (Pearson r coefficient 0.770, P < 0.001). When ARR was used in differentiating PA from EH, there was no difference in the area under the receiver operating characteristic curve between CLIA and LC-MS/MS for PAC measurement (0.968 vs 0.950, P = 0.249). Conclusion: CLIA and LC-MS/MS for PAC measurement exhibited high and comparable efficacy in PA screening. CLIA is a reliable and feasible alternative in PA screening test.

PFKFB3 facilitates cell proliferation and migration in anaplastic thyroid carcinoma via the WNT/ß-catenin signaling pathway.

PURPOSE: Despite the involvement of 6-phosphofructo-2-kinase/fructose-2,6-biphosphatase3 (PFKFB3) in the proliferation and metastasis of diverse tumor types, its biological functions and related molecular mechanisms in anaplastic thyroid carcinoma (ATC) remain largely unclear. METHODS: Datasets from the Gene Expression Omnibus, the Cancer Genome Atlas and immunohistochemistry (IHC) analyses were employed to measure the expression level of PFKFB3 in ATC. A series of assays were performed to analyze the role of PFKFB3 and its inhibitor KAN0438757 in ATC cell proliferation and migration. Furthermore, Western blotting (WB), IHC and luciferase reporter assay were conducted to investigate the potential mechanisms underlying the involvement of PFKFB3 and KAN0438757 in ATC. Additionally, we established a subcutaneous xenograft tumor model in nude mice to evaluate the in vivo tumor growth. RESULTS: PFKFB3 exhibited a significant increase in its expression level in ATC tissues. The overexpression of PFKFB3 resulted in the stimulation of ATC cell proliferation and migration. Furthermore, this overexpression was associated with the elevated expression levels of p-AKT (ser473), p-GSK3α/ß (ser21/9), nuclear ß-catenin, fibronectin1 (FN1), matrix metallopeptidase 9 (MMP-9) and cyclin D1. It also promoted the nuclear translocation of ß-catenin and the transcription of downstream molecules. Conversely, contrasting results were observed with the downregulation or KAN0438757-mediated inhibition of PFKFB3 in ATC cells. The selective AKT inhibitor MK2206 was noted to reverse the increased expression of p-AKT (ser473) and p-GSK3α/ß (ser21/9) induced by PFKFB3 overexpression. The level of lactate was increased in PFKFB3-overexpressing ATC cells, while the presence of KAN0438757 inhibited lactate production. Moreover, the simultaneous use of PFKFB3 downregulation and KAN0438757 was found to suppress subcutaneous tumor growth in vivo. CONCLUSION: PFKFB3 can enhance ATC cell proliferation and migration via the WNT/ß-catenin signaling pathway and plays a crucial role in the regulation of aerobic glycolysis in ATC cells.

Overexpression of FHL1 suppresses papillary thyroid cancer proliferation and progression via inhibiting Wnt/ß-catenin pathway.

PURPOSE: The four and a half LIM domain protein 1 (FHL1) has been found to act as a tumor suppressor in several cancers. However, the clinical and functional significance, as well as underlying molecular mechanisms of FHL1 in papillary thyroid cancer (PTC) are largely unknown. METHODS: Bioinformatics analyses, qRT-PCR and Western blotting were used to investigate the expression of FHL1 in PTC. Cell proliferation was measured using CCK8, Edu, colony formation, and flow cytometry assays. Cell migration and invasion were examined by wound healing and Transwell assays. qRT-PCR, Western blot, immunofluorescence and Top/Fop reporter assays were performed to assess the underlying mechanisms. RESULTS: FHL1 expression was significantly downregulated in PTC. FHL1 downregulation negatively correlated with stage, T classification, and N classification of the patients. The downregulation of FHL1 is associated with poor prognosis. Overexpression of FHL1 inhibited PTC cells' proliferation, invasion, migration and Wnt/ß-catenin pathway activity. LiCl partially restored the inhibitory effects of FHL1 on aggressive phenotypes and Wnt/ß-catenin pathway activity of PTC cells. CONCLUSION: FHL1 is downregulated in PTC and its expression is associated with better clinical outcomes for patients with the disease. FHL1 acts as a tumor suppressor via, at least partially, suppressing Wnt/ß-catenin pathway.

Recombinant duck enteritis virus bearing the hemagglutinin genes of H5 and H7 influenza viruses is an ideal multivalent live vaccine in ducks.

Due to the fact that many avian influenza viruses that kill chickens are not lethal to ducks, farmers are reluctant to use avian influenza inactivated vaccines on ducks. Large numbers of unvaccinated ducks play an important role in the transmission of avian influenza viruses from wild birds to domestic poultry, creating a substantial challenge to vaccination strategies for avian influenza control. To solve this problem, we constructed a recombinant duck enteritis virus (DEV), rDEV-dH5/H7, using a live attenuated DEV vaccine strain (vDEV) as a vector. rDEV-dH5/H7 carries the hemagglutinin gene of two H5 viruses [GZ/S4184/17 (H5N6) (clade 2.3.4.4 h) and LN/SD007/17 (H5N1) (clade 2.3.2.1d)] and an H7 virus [GX/SD098/17 (H7N9)]. These three hemagglutinin genes were stably inherited in rDEV-dH5/H7 and expressed in rDEV-dH5/H7-infected cells. Animal studies revealed that rDEV-dH5/H7 and vDEV induced similar neutralizing antibody responses and protection against lethal DEV challenge. Importantly, rDEV-dH5/H7 induced strong and long-lasting hemagglutinin inhibition antibodies against different H5 and H7 viruses and provided complete protection against challenges with homologous and heterologous highly pathogenic H5 and H7 influenza viruses in ducks. Our study shows that rDEV-dH5/H7 could serve as an ideal live attenuated vaccine to protect ducks against infection with lethal DEV and highly pathogenic avian influenza viruses.