Development of simultaneous quantitation method for 20 free advanced glycation end products using UPLC-MS/MS and clinical application in kidney injury.

Advanced glycation end products (AGEs), derived from the non-enzymatic glycation reaction, are defined as glycotoxins in various diseases including aging, diabetes and kidney injury. Exploring AGEs as potential biomarkers for these diseases holds paramount significance. Nevertheless, the high chemical structural similarity and great heterogeneity among AGEs present a formidable challenge when it comes to the comprehensive, simultaneous, and accurate detection of multiple AGEs in biological samples. In this study, an UPLC/MS/MS method for simultaneous quantification of 20 free AGEs in human serum was firstly established and applied to quantification of clinical samples from individuals with kidney injury. Simple sample preparation method through protein precipitation without derivatization was used. Method performances including imprecision, accuracy, sensitivity, linearity, and carryover were systematically validated. Intra- and inter- imprecision of 20 free AGEs were 1.93-5.94 % and 2.30-8.55 %, respectively. The method accuracy was confirmed with good recoveries ranging from 96.40 % to 103.25 %. The LOD and LOQ were 0.1-3.13 ng/mL and 0.5-6.25 ng/mL, respectively. Additionally, the 20 free AGEs displayed excellent linearity (R2 >0.9974) across a wide linear range (1.56-400 ng/mL). Finally, through simultaneous quantitation of 20 Free AGEs in 100 participants including kidney injury patient and healthy controls, we identified six free AGEs, including N6-carboxyethyl-L-arginine (CEA), N6-carboxymethyl-L-lysine (CML), methylglyoxal-derived hydroimidazolones (MG-H), N6-formyl-lysine, N6-carboxymethyl-L-arginine (CMA), and glyoxal-derived hydroimidazolone (G-H), could well distinguish kidney injury patients and healthy individuals. Among them, the levels of four free AGEs including CML, CEA, MG-H, and G-H strongly correlate with traditionally clinical markers of kidney disease. The high area under the curve (AUC) values (AUC=0.965) in receiver operating characteristic (ROC) curve indicated that these four free AGEs can be served as combined diagnostic biomarkers for the diagnosis of kidney disease.

Comparison of common human respiratory pathogens among hospitalized children aged ≤ 6 years in Hainan Island, China, during spring and early summer in 2019-2021.

The coronavirus disease 2019 (COVID-19) pandemic and related public health intervention measures have been reported to have resulted in the reduction of infections caused by influenza viruses and other common respiratory viruses. However, the influence may be varied in areas that have different ecological, economic, and social conditions. This study investigated the changing epidemiology of 8 common respiratory pathogens, including Influenza A (IFVA), Influenza B (IFVB), Respiratory syncytial virus (HRSV), rhinovirus (RV), Human metapneumovirus Adenovirus, Human bocavirus, and Mycoplasma pneumoniae, among hospitalized children during spring and early summer in 2019-2021 in two hospitals in Hainan Island, China, in the COVID-19 pandemic era. The results revealed a significant reduction in the prevalence of IFVA and IFVB in 2020 and 2021 than in 2019, whereas the prevalence of HRSV increased, and it became the dominant viral pathogen in 2021. RV was one of the leading pathogens in the 3 year period, where no significant difference was observed. Phylogenetic analysis revealed close relationships among the circulating respiratory viruses. Large scale studies are needed to study the changing epidemiology of seasonal respiratory viruses to inform responses to future respiratory virus pandemics.

A damage-associated molecular patterns-related gene signature for the prediction of prognosis and immune microenvironment in children stage III acute lymphoblastic leukemia.

Background: Immunogenic cell death (ICD)-mediated immune response provides a strong rationale to overcome immune evasion in acute lymphoblastic leukemia (ALL). ICD will produce damage-associated molecular patterns (DAMPs) in tumor microenvironment. However, there are few studies on the application of DAMPs-related molecular subtypes in clinically predicting stage III of ALL prognosis. The current study is to identify the DAMPs-associated genes and their molecular subtypes in the stage III of ALL and construct a reliable risk model for prognosis as well as exploring the potential immune-related mechanism. Materials and methods: We used Target and EBI database for differentially expressed genes (DEGs) analysis of the stage III pediatric ALL samples. Three clusters were identified based on a consistent clustering analysis. By using Cox regression and LASSO analysis, we determined DEGs that attribute to survival benefit. In addition, the Gene Set Enrichment Analysis (GSEA) was performed to identify potential molecular pathways regulated by the DAMPs-related gene signatures. ESTIMATE was employed for evaluating the composition of immune cell populations. Results: A sum of 146 DAMPs-associated DEGs in ALL were determined and seven transcripts among them were selected to establish a risk model. The DAMPs-associated gene signature significantly contributed to worse prognosis in the high-risk group. We also found that the high-risk group exhibited low immune cell infiltration and high expression of immune checkpoints. Conclusion: In summary, our study showed that the DAMPs-related DEGs in the stage III of children ALL could be used to predict their prognosis. The risk model of DAMPs we established may be more sensitive to immunotherapy prediction.

Suzuki C-C Coupling in Paper Spray Ionization: Microsynthesis of Biaryls and High-Sensitivity MS Detection of Aryl Bromides.

Suzuki-Miyaura cross-coupling is one of the most powerful strategies for constructing biaryl compounds. However, classic Suzuki-Miyaura coupling suffers from hour-scale reaction time and competitive protodeboronation. To address these problems, a mild nonaqueous potassium trimethylsilanolate (TMSOK)-assisted Suzuki-Miyaura coupling strategy was designed for the microsynthesis of biaryls in paper spray ionization (PSI). Due to the acceleration power facilitated by microdroplet chemistry in reactive PSI, the microsynthesis of biaryls by reactive PSI was accomplished within minutes with comparable yields to the bulk, showing good substrate applicability from 32 Suzuki-Miyaura reactions of aryl bromides and aryl boronic acid/borates bearing different substituents. Based on the above TMSOK-assisted Suzuki-Miyaura coupling strategy, we further developed a high-sensitivity and selective PSI mass spectrometry (MS) method for quantitative analysis of aryl bromides, a class of environmentally persistent organic pollutants that cannot be directly detected by ambient mass spectrometry due to their low ionization efficiency. In situ derivatization of aryl bromides was achieved with aryl borates bearing quaternary ammonium groups in PSI. The proposed PSI-MS method shows good linearity over the 0.01-10 µmol L-1 range with low detection limits of 1.8-4.8 nmol L-1 as well as good applicability to the rapid determination of six aryl bromides in three environmental water samples. The proposed PSI-MS method also shows good applicability to brominated flame retardants (polybrominated diphenyls/diphenyl esters). Overall, this study provides a simple, rapid, low-cost, high-sensitivity, and high-selectivity strategy for trace aryl bromides and other brominated pollutants in real samples with minimal/no sample pretreatment.

Role of Mitophagy-based TLR9 Signal Pathway in Neonatal Ventilator-induced Lung Injury.

The study focused on the role of mitophagy in neonatal ventilator-induced lung injury (VILI). Immunoassays were used to study the TLR9 signaling pathway of neonatal VILI, expected to provide a feasible solution for neonatal VILI. The mice were randomly divided into four groups, group A: spontaneous breathing group; group B: normal tidal volume (VT) group (VT=9mL/kg); group C: high VT group (VT=39mL/kg); and group D: ODN2088 (400µg/ Only) intervention + high VT group. The four groups were compared for the expression of inflammatory factors. It was found that as the culture time increased, the expression of TLR9, MyD88, and NF-κBp65 in the lung tissue of the large VT group was significantly higher than those in the spontaneous breathing group and normal VT group, and the differences were statistically significant; and TLR9 inhibitors could activate the TLR9-MyD88 signaling pathway to up-regulate the expression of NF-κB, mediating the release of inflammatory factors to cause VILI.

Clinical and epidemiological investigation of a child with asymptomatic COVID-19 infection following reoccurrence.

Objective: To investigate the case of a child infected with coronavirus disease 2019 (COVID-19) who had subsequent viral reactivation. Methods: We retrospectively analyzed the clinical manifestations, epidemiological data, laboratory and imaging examinations, treatment, and follow-up of the child. And then, we searched related literature using PubMed. Results: The 9-year-old boy was exposed to COVID-19 in Malawi and tested positive for NAT in Haikou, China. He was asymptomatic and admitted to our hospital. After six negative NATs, he was discharged from the hospital and quarantined in a hotel. His infection was reactivated again after 22 days (interval between first and last positive NATs). The cycle threshold (Ct) values of positive tests were 25 and 31, and the gene sequencing viral loads were very low. The viral strain Kenya/P2601/2020, a variant of the hCoV-19/Wuhan/IVDC-HB-01/2019 genome (GISAID accession IL: EPI_ISL_402119), was found when polymerase chain reaction enrichment was used to sequence the virus. However, people around him tested negative for COVID-19. Conclusion: First, we confirmed the reactivation of COVID-19 in a child. The risk of recurrent infection with SARS-CoV-2 was low, and the policy of strictly isolating patients carrying long-term viral ribonucleic acid should be reconsidered. The interval positivity was most likely due to incorrect sampling and/or testing methods. SGS and aB testing are recommended for children with viral reactivation. Second, SARS-CoV-2 viral reactivation cannot be ruled out. The possible mechanisms, such as prolonged infection and viral latent reactivation, need further investigation.

Pediatric Pan-Central Nervous System Tumor Methylome Analyses Reveal Immune-Related LncRNAs.

Pediatric central nervous system (CNS) tumors are the second most common cancer diagnosis among children. Long noncoding RNAs (lncRNAs) emerge as critical regulators of gene expression, and they play fundamental roles in immune regulation. However, knowledge on epigenetic changes in lncRNAs in diverse types of pediatric CNS tumors is lacking. Here, we integrated the DNA methylation profiles of 2,257 pediatric CNS tumors across 61 subtypes with lncRNA annotations and presented the epigenetically regulated landscape of lncRNAs. We revealed the prevalent lncRNA methylation heterogeneity across pediatric pan-CNS tumors. Based on lncRNA methylation profiles, we refined 14 lncRNA methylation clusters with distinct immune microenvironment patterns. Moreover, we found that lncRNA methylations were significantly correlated with immune cell infiltrations in diverse tumor subtypes. Immune-related lncRNAs were further identified by investigating their correlation with immune cell infiltrations and potentially regulated target genes. LncRNA with methylation perturbations potentially regulate the genes in immune-related pathways. We finally identified several candidate immune-related lncRNA biomarkers (i.e., SSTR5-AS1, CNTN4-AS1, and OSTM1-AS1) in pediatric cancer for further functional validation. In summary, our study represents a comprehensive repertoire of epigenetically regulated immune-related lncRNAs in pediatric pan-CNS tumors, and will facilitate the development of immunotherapeutic targets.

Automatic segmentation model of intercondylar fossa based on deep learning: a novel and effective assessment method for the notch volume.

BACKGROUND: Notch volume is associated with anterior cruciate ligament (ACL) injury. Manual tracking of intercondylar notch on MR images is time-consuming and laborious. Deep learning has become a powerful tool for processing medical images. This study aims to develop an MRI segmentation model of intercondylar fossa based on deep learning to automatically measure notch volume, and explore its correlation with ACL injury. METHODS: The MRI data of 363 subjects (311 males and 52 females) with ACL injuries incurred during non-contact sports and 232 subjects (147 males and 85 females) with intact ACL were retrospectively analyzed. Each layer of intercondylar fossa was manually traced by radiologists on axial MR images. Notch volume was then calculated. We constructed an automatic segmentation system based on the architecture of Res-UNet for intercondylar fossa and used dice similarity coefficient (DSC) to compare the performance of segmentation systems by different networks. Unpaired t-test was performed to determine differences in notch volume between ACL-injured and intact groups, and between males and females. RESULTS: The DSCs of intercondylar fossa based on different networks were all more than 0.90, and Res-UNet showed the best performance. The notch volume was significantly lower in the ACL-injured group than in the control group (6.12 ± 1.34 cm3 vs. 6.95 ± 1.75 cm3, P < 0.001). Females had lower notch volume than males (5.41 ± 1.30 cm3 vs. 6.76 ± 1.51 cm3, P < 0.001). Males and females who had ACL injuries had smaller notch than those with intact ACL (p < 0.001 and p < 0.005). Men had larger notches than women, regardless of the ACL injuries (p < 0.001). CONCLUSION: Using a deep neural network to segment intercondylar fossa automatically provides a technical support for the clinical prediction and prevention of ACL injury and re-injury after surgery.

Understanding the Role of Polyvinylpyrrolidone on Ultrafine Low-Rank Coal Flotation.

Effective regulation reagents are essential in low-rank coal flotation for improving the floatability of ultrafine particles. Polymer regulators have great potential in the surface modification of ultrafine coal particles. A novel nonionic polymer, polyvinylpyrrolidone (PVP), is evaluated in this study to determine its effectiveness as a regulator in floating ultrafine low-rank coal. Laser particle size analysis is used to discern both the size distribution of coal particles and the change in size distribution. Contact angle tests are carried out to evaluate the wettability of low-rank coal. Surface functional groups of low-rank coal are analyzed by Fourier transform infrared spectroscopy, and the surface interaction energy is tested by X-ray photoelectron spectroscopy. The results show effective adsorption of PVP and demonstrate the effects of PVP at the coal surface. The adsorption of PVP changes the proportion of exposed carbon and oxygen-containing functional groups on the surface of low-rank coal, regulating the size distribution of low-rank coal particles in suspension. The success of polyvinylpyrrolidone as a regulator in low-rank coal flotation is demonstrated, and the mechanisms by which PVP can affect ultrafine low-rank coal flotation are elucidated.

Exosomal circular RNA hsa_circ_007293 promotes proliferation, migration, invasion, and epithelial-mesenchymal transition of papillary thyroid carcinoma cells through regulation of the microRNA-653-5p/paired box 6 axis.

Circular RNAs (circRNAs) or exosomes have been reported to exert key regulatory and/or communication functions in human cancer. Nevertheless, current literature on the effects of exosomal circRNAs on tumor invasion and metastasis in thyroid cancer is incomplete. The role of tumor-derived exosomes in driving in vitro papillary thyroid carcinoma (PTC) progression and metastasis requires further investigation. In our study, Exosomes were harvested from PTC patient serum and PTC cell culture medium. Gene expression analysis in PTC cell lines and exosomes was performed with quantitative reverse-transcription polymerase chain reaction. Transwell, wound healing, Western blot assays, and the cell counting kit-8 were applied for functional analysis. Dual-luciferase reporter assay was used to examine the interaction between hsa_circ_007293 (circ007293), microRNA (miR)-653-5p, and paired box 6 (PAX6). Results showed that circ007293 was enriched in exosomes derived from PTC patient serum and cell culture media. Moreover, circ007293 could enter PTC cells through exosomes, and exosomal circ007293 promoted PTC cell epithelial-mesenchymal transition, invasion, migration, and proliferation. circ007293 knockdown reversed the malignant phenotype of PTC cells in vitro. Additionally, circ007293 could competitively bind with miR-653-5p to regulate PAX6 expression. Notably, miR-653-5p overexpression or PAX6 inhibition suppressed the malignant effects of exosomal circ007293. These results evidenced that exosomal circ007293 induced EMT and augmented the invasive and migratory abilities of PTC cells via the miR-653-5p/PAX6 axis, suggesting that it may serve as a promising biomarker for cancer progression.

Activation of the TGF-ß1/Smad signaling by KIF2C contributes to the malignant phenotype of thyroid carcinoma cells.

Kinesin family member 2C (KIF2C) has been identified as a potential oncogene in various types of human cancers; however, the role of KIF2C in thyroid cancer has not yet been elucidated. Quantitative real-time polymerase chain reaction and western blotting were employed for gene expression analysis. Cell Counting Kit-8 and ethynyl-2'-deoxyuridine assays were performed to examine cell proliferation. Cell migration and invasion were assessed by wound-healing and transwell invasion assays. Results showed that KIF2C expression was upregulated in thyroid carcinoma cell lines. In addition, upregulation of KIF2C promoted the proliferation, migration, and invasion of thyroid carcinoma cells, while downregulation of KIF2C exerted the opposite effects. Overexpression of KIF2C induced the activation of transforming growth factor-ß1 (TGF-ß1)/Smad signaling in thyroid carcinoma cells. However, inhibition of TGF-ß1/Smad signaling through silencing TGF-ß1 attenuated the promoting effects of KIF2C overexpression on the malignant phenotype of thyroid carcinoma cells. Besides, overexpression of TGF-ß1 suppressed the inhibitory effect of KIF2C knockdown on the proliferation and metastasis of thyroid carcinoma cells. In conclusion, our findings demonstrated that KIF2C contributed to the malignant phenotype of thyroid carcinoma cells by inducing the activation of TGF-ß1/Smad signaling, thus uncovering a novel mechanism for thyroid carcinoma progression.

Mediastinal and subglottic hemangioma in an infant: a case report and literature review.

We performed a retrospective analysis of the clinical manifestations, laboratory and imaging examinations, treatment, and prognosis of a male infant who was diagnosed with mediastinal and subglottic hemangioma in our hospital. The clinical features of this patient were coughing, wheezing, and dyspnea. Enhanced computed tomography of the neck and chest showed a diffuse abnormality in the right-upper mediastinum. He was diagnosed with a hemangioma after a physical examination combined with bronchoscopy. The clinical symptoms were relieved by oral propranolol. We also investigated the clinical characteristics, treatment, and prognosis of mediastinal and subglottic hemangioma in infants in the previous literature, and searched for case reports of this disease in China and in other countries. We only identified three previous cases of mediastinal and subglottic hemangioma in infants, indicating that this condition is rare. In the proliferative stage, surrounding organs and tissues are compressed, which can be life-threatening. Most of these children develop wheezing, shortness of breath, dyspnea, cyanosis, and other symptoms within 2 months. Enhanced computed tomography and magnetic resonance imaging combined with soft bronchoscopy can confirm the diagnosis of this disease, and oral propranolol achieves a favorable effect.

Correlation Analysis between Gut Microbiota and Metabolites in Children with Systemic Lupus Erythematosus.

Systemic lupus erythematosus (SLE) is an autoimmune-mediated diffuse connective tissue disease characterized by immune inflammation with an unclear aetiology and pathogenesis. This work profiled the intestinal flora and faecal metabolome of patients with SLE using 16S RNA sequencing and gas chromatography-mass spectrometry (GC-MS). We identified unchanged alpha diversity and partially altered beta diversity of the intestinal flora. Another important finding was the increase in Proteobacteria and Enterobacteriales and the decrease in Ruminococcaceae among SLE patients. For metabolites, amino acids and short-chain fatty acids were enriched when long-chain fatty acids were downregulated in SLE faecal samples. KEGG analysis showed the significance of the protein digestion and absorption pathway, and association analysis revealed the key role of 3-phenylpropanoic acid and Sphingomonas. Sphingomonas were reported to be less abundant in healthy periodontal sites of SLE patients than in those of HCs, indicating transmission of oral species to the gut. This study contributes to the understanding of the pathogenesis of SLE disease from the perspective of intestinal microorganisms, explains the pathogenesis of SLE, and serves as a basis for exploring potential treatments for the disease.

Application of Pet-CT Fusion Deep Learning Imaging in Precise Radiotherapy of Thyroid Cancer.

This article explores the value of wall F-FDG PET/Cr imaging in the diagnosis of thyroid cancer, studies its ability to distinguish benign and malignant thyroid lesions, and seeks ways to improve the accuracy of diagnosis. The normal control group selected 40 patients who came to our center for physical examination. In the normal control group, the average value of the standard uptake value of both sides of the thyroid was used as the SUV of the thyroid gland and the highest SUV value of the patient's lesion (SUV max) represented the SUV of the lesion. After injection of imaging agent 18F-FD1G, routine imaging was performed at 1h, time-lapse imaging was performed at 2.5 h, and the changes with conventional imaging were compared to infer the benign and malignant lesions. We used SPSS software to carry out statistical analysis, respectively, carrying out analysis of variance, paired t-test, independent sample t-test, and linear correlation analysis. In the thyroid cancer group, 87.5% of the delayed imaging SUV was higher than the conventional imaging SUV, while 83.33% of the benign disease group had a lower SUV than the conventional imaging SUV. 18F-FDG PET/CT imaging has higher sensitivity and specificity for the diagnosis of recurrence or metastasis in patients with Tg positive. However, it has lower sensitivity and specificity for the diagnosis of 131I-Dx-WBS negative DTC and 18F-FDG PET/CT. The specificity increases with the increase of serum Tg level. The above results confirm that 18F-FDG PET/CT imaging is of great significance for the diagnosis of recurrence or metastasis in patients; with PET/CT imaging, the results changed 16.13% of the Tg-positive and 131I-Dx-WBS negative DTC patients' later treatment decision. The decision-making and curative effect evaluation have certain value.

Silencing of AHNAK2 restricts thyroid carcinoma progression by inhibiting the Wnt/ß-catenin pathway.

AHNAK nucleoprotein 2 (AHNAK2) has been proposed to have an oncogenic role in various human cancers. However, the functional role of AHNAK2 in thyroid carcinoma (TC) progression has never been explored. In this study, quantitative real-time polymerase chain reaction and western blot were conducted to evaluate the expression of genes. The functional role of AHNAK2 was elucidated by cell count kit-8, colony-forming assay, wound-healing assay, and Transwell invasion assay. We found that AHNAK2 was highly expressed in thyroid carcinoma, and it was tightly correlated with the pathological stage in TC. The mRNA and protein levels of AHNAK2 were increased in TC cells. Silencing of AHNAK2 restricted the proliferation, metastasis, and epithelial-mesenchymal transition (EMT) of TC cells. AHNAK2 silencing inhibited the protein expression of ß-catenin and cyclin D1, and AHNAK2 overexpression had the opposite effects. Moreover, LiCl or ICG-001 exposure counteracted the effects of AHNAK2 silencing or upregulation on malignant phenotypes of TC cells. In conclusion, the knockdown of AHNAK2 restrained the proliferation, metastasis, and EMT of TC cells by inhibiting the Wnt/ß-catenin pathway, providing a new potential mechanism of AHNAK2 in understanding the oncogenesis and progression of TC.

Long non-coding RNA TUG1 knockdown promotes autophagy and improves acute renal injury in ischemia-reperfusion-treated rats by binding to microRNA-29 to silence PTEN.

OBJECTIVE: Long noncoding RNA (lncRNA) taurine upregulated gene 1 (TUG1) is increased under the condition of ischemia. This study intended to identify the mechanism of TUG1 in renal ischemia-reperfusion (I/R). METHODS: First, a rat model of acute renal injury induced by I/R was established, followed by the measurement of blood urea nitrogen (BUN), serum creatine (SCr), methylenedioxyphetamine (MDA) and superoxide dismutase (SOD) in the serum of rats. TUG1 was knocked down in I/R rats (ko-TUG1 group). Next, histological staining was used to evaluate the pathological damage and apoptosis of rat kidney. Western blot analysis was used to detect the levels of apoptosis- and autophagy-related proteins and transmission electron microscope was used to observe autophagosomes. Autophagy and apoptosis were evaluated after inhibition of the autophagy pathway using the inhibitor 3-MA. The targeting relation among TUG1, microRNA (miR)-29 and phosphatase and tensin homolog (PTEN) were validated. Lastly, the effects of TUG1 on biological behaviors of renal tubular cells were evaluated in vitro. RESULTS: In vivo, the levels of BUN, SCr and MDA in the serum of I/R-treated rats were increased while SOD level and autophagosomes were reduced, tubule epithelial cells were necrotic, and TUG1 was upregulated in renal tissues of I/R-treated rats, which were all reversed in rats in the ko-TUG1 group. Autophagy inhibition (ko-TUG1 + 3-MA group) averted the protective effect of TUG1 knockdown on I/R-treated rats. TUG1 could competitively bind to miR-29 to promote PTEN expression. In vitro, silencing TUG1 (sh-TUG1 group) promoted viability and autophagy of renal tubular cells and inhibited apoptosis. CONCLUSIONS: LncRNA TUG can promote PTEN expression by competitively binding to miR-29 to promote autophagy and inhibited apoptosis, thus aggravating acute renal injury in I/R-treated rats.

Overexpression of serum lncRNA-ABHD11-AS1 as poor prognosis of patients with papillary thyroid carcinoma.

This paper was aimed at exploring the correlation of long non-coding RNA (lncRNA)-ABHD11 Antisense RNA1 (ABHD11-AS1) with the poor prognosis of patients with papillary thyroid carcinoma (PTC) and at investigating its effects on the survival of PTC cells. Serum was respectively collected from 64 PTC patients who were admitted to our hospital (PTC group) and from 50 healthy controls who underwent physical examinations (HC group) both from April 2011 to April 2015. The expression levels of ABHD11-AS1 in the serum were detected, and the values of it for diagnosis and prognosis (5-year follow-ups) were analyzed. The knockdown and overexpression models of ABHD11-AS1 in were constructed to explore the effects of the models on their proliferation, cycles and apoptosis. According to the data, the expression levels of serum ABHD11-AS1 in the PTC patients were remarkably higher than those in the healthy controls, and the area under the curve (AUC) for distinguishing the patients from the controls was 0.920. In the analysis of prognosis, the levels in patients with a poor prognosis were remarkably higher than those in patients with a good prognosis. According to the curves of overall survival rates (OSRs), the high levels of ABHD11-AS1 were remarkably correlated with the poor prognosis (a lower 5-year OSR). COX analysis showed that TNM staging, lymph node metastasis and ABHD11-AS1 were the independent prognostic factors of PTC patients. In the cell experiments, knocking down ABHD11-AS1 remarkably inhibited PTC cells from proliferation, arrested them in G0/G1 phase, and induced their apoptosis, negatively affecting their survival indices. Overexpressing this RNA had positive effects on the survival indices. Taken together, high levels of serum ABHD11-AS1 are related to the poor prognosis of PTC patients, and knocking down its expression can inhibit the survival of PTC cells.

Neutralizing interferon-α blocks inflammation-mediated vascular injury via PI3K and AMPK in systemic lupus erythematosus.

Plasmacytoid dendritic cells (pDCs) play a key role in the initiation and amplification of systemic lupus erythematosus (SLE)-associated vascular injury. In this study, we found that dsDNA induced dose- and time-dependent increase in IFN-α and Toll-like receptor 7 (TLR7), TLR9 and IRF7 expression in pDCs. Co-cultured circulating endothelial cells (ECs) with activated pDCs significantly decreased proliferation, tube formation and migration in ECs. The elevated level of cellular IFN-α increased cell adhesion, promoted cell apoptosis, induced cell senescence and arrested cells at G0/G1 phase of endothelial progenitor cells (EPCs). Additionally, the co-culture system activated MAPK and inactivated PI3K. Pristane was used to establish a in vivo SLE-like mouse model. Importantly, we showed that INF-α-neutralizing antibody (IFN-α-NA) rescued all the changes induced by IFN-α in vitro and prevented vascular injury in pristane-induced SLE model in vivo. In conclusion, we confirmed that activated pDCs promoted vascular damage and the dysfunction of ECs/EPCs via IFN-α production. IFN-α-neutralizing antibody may be a clinical implication for preventing vascular injury. PI3K signalling and AMPK signalling were associated with SLE-associated vascular functions.

Epidemiological investigation of a COVID-19 family cluster outbreak transmitted by a 3-month-old infant.

OBJECTIVE: To investigate the clinical characteristics, epidemiological characteristics, and transmissibility of coronavirus disease 2019 (COVID-19) in a family cluster outbreak transmitted by a 3-month-old confirmed positive infant. METHODS: Field-based epidemiological methods were used to investigate cases and their close contacts. Real-time fluorescent reverse transcription polymerase chain reaction (RT-PCR) was used to detect Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) for all collected specimens. Serum SARS-CoV-2 IgM and IgG antibodies were detected by Chemiluminescence and Gold immnnochromatography (GICA). RESULTS: The outbreak was a family cluster with an attack rate of 80% (4/5). The first case in this family was a 3-month-old infant. The transmission chain was confirmed from infant to adults (her father, mother and grandmother). Fecal tests for SARS-CoV-2 RNA remained positive for 37 days after the infant was discharged. The infant's grandmother was confirmed to be positive 2 days after the infant was discharged from hospital. Patients A (3-month-old female), B (patient A's father), C (patient A's grandmother), and D (patient A's mother) had positive serum IgG and negative IgM, but patients A's grandfather serum IgG and IgM were negative. CONCLUSION: SARS-CoV-2 has strong transmissibility within family settings and presence of viral RNA in stool raises concern for possible fecal-oral transmission. Hospital follow-up and close contact tracing are necessary for those diagnosed with COVID-19.

The individual and combined effects of hypoxia and high-fat diet feeding on nutrient composition and flesh quality in Nile tilapia (Oreochromis niloticus).

Hypoxia and high-fat diet (HFD) feeding are two factors commonly existing in aquaculture. However, their individual and combined effects on nutrient composition and flesh quality in fish have not been investigated. The present study evaluated the alterations of growth, nutrient composition and flesh quality in Nile tilapia (initially 7.0 ± 0.1 g and 5.6 ± 0.2 cm) fed with normal fat diet (5.95% fat) or HFD (11.8% fat) at two dissolved oxygen levels (1.1 ± 0.1 and 7.2 ± 0.1 mg/L) for 8 weeks. The results showed that hypoxia and HFD had similar effects in inducing lipid deposition, reducing flesh protein and amino acids content, pH values and water holding ability. Hypoxia had additional adverse effects in decreasing meat yield, flesh contents of n-3 PUFA and glycogen, increasing flesh fragmentation and causing liver damages. The combination of hypoxia and HFD significantly decreased feed intake, survival rate and muscle protein content, but didn't affect flesh quality-related parameters.