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Graves’ disease (GD) is an autoimmune disorder disease, and its prevalence continues to increase worldwide. Pyrroloquinoline quinone (PQQ) is a naturally antioxidant compound in milk, vegetables, and meat. We aim to identify the treatment efficacy of PQQ on GD and its regulatory effect on intestinal microbiota. The GD mice model was built by an adenovirus expressing autoantigen thyroid-stimulating hormone receptor (Ad-TSHR289). Fecal samples were collected for 16S rDNA sequencing after PQQ pretreatments (20, 40, or 60 mg/kg BW/day) for 4 weeks. Thyroid and intestine functions were measured. The levels of serum TSHR and T4 were significantly raised, and the thyroid gland size was typically enlarged in the GD group than in controls, reversed by PQQ therapy. After PQQ replenishment, IL6 and TNFα levels in small intestine tissues were lower than those in the GD group, with Nrf2 and HO1 levels improved. Also, the PQQ supplement could maintain the mucosal epithelial barrier impaired by GD. In microbial analyses, PQQ treatment could prompt the diversity recovery of gut microbiota and reconstruct the microbiota composition injured by GD. Lactobacillus served as the most abundant genus in all groups, and the abundance of Lactobacillus was increased in the GD group than in control and PQQ groups. Besides, Lactobacillus was highly correlative with all samples and the top 50 genera. PQQ supplementation regulates thyroid function and relieves intestine injury. PQQ changes the primary composition and abundance of GD’s intestine microbiota by moderating Lactobacillus, which may exert in the pathogenesis and progression of GD.

Background: Despite the potential radiotoxicity in differentiated thyroid cancer (DTC) patients with high-dose 131I therapy, the alterations and regulatory mechanisms dependent on intestinal microecology remain poorly understood. We aimed to identify the characteristics of the gut microbiota and metabolites in DTC patients suffering from high-dose 131I therapy and explore the radioprotective mechanisms underlying arachidonic acid (ARA) treatment. Methods: A total of 102 patients with DTC were recruited, with fecal samples collected before and after 131I therapy for microbiome and untargeted and targeted metabolomic analyses. Mice were exposed to total body irradiation with ARA replenishment and antibiotic pretreatment and were subjected to metagenomic, metabolomic, and proteomic analyses. Results: 131I therapy significantly changed the structure of gut microbiota and metabolite composition in patients with DTC. Lachnospiraceae were the most dominant bacteria after 131I treatment, and metabolites with decreased levels and pathways related to ARA and linoleic acid were observed. In an irradiation mouse model, ARA supplementation not only improved quality of life and recovered hematopoietic and gastrointestinal systems but also ameliorated oxidative stress and inflammation and preserved enteric microecology composition. Additionally, antibiotic intervention eliminated the radioprotective effects of ARA. Proteomic analysis and ursolic acid pretreatment showed that ARA therapy greatly influenced intestinal lipid metabolism in mice subjected to irradiation by upregulating the expression of hydroxy-3-methylglutaryl-coenzyme A synthase 1. Conclusion: These findings highlight that ARA, as a key metabolite, substantially contributes to radioprotection. Our study provides novel insights into the pivotal role that the microbiota-metabolite axis plays in radionuclide protection and offers effective biological targets for treating radiation-induced adverse effects. [ABSTRACT FROM AUTHOR]

Background and purpose: Epithelial-to-mesenchymal transition (EMT) is the key biological process of tumor cell metastasis. Blocking EMT inhibits tumor metastasis, therefore it is of great significance to elucidate the molecular mechanism of EMT. Tumor suppressor protein H2AX regulates apoptosis-related gene expression of tumor cells, and then produces anti-tumor effect. This study aimed to reveal the relationship between H2AX and EMT, and to explore the possible mechanism of H2AX regulating EMT in lung cancer cells. Methods: About 5% fetal bovine serum was used to induce EMT in lung cancer A549 stable cells including H2AX gene silencing, H2AX overexpression and H2AX phosphorylation site mutation. Western blot and real- time fluorescent quantitative polymerase chain reaction (RTFQ-PCR) were used to detect the expressions of E-cadherin, vimentin, vascular endothelial growth factor receptor 2 (VEGFR2) and other EMT-related proteins. Transwell experiment was used to analyze the migration and invasion of A549 cells. Results: Knockdown of H2AX in lung cancer A549 cells resulted in the downregulation of E-cadherin and the upregulation of vimentin, and enhanced the migration and invasion ability of A549 cells. Overexpression of H2AX in lung cancer A549 cells upregulated E-cadherin, downregulated vimentin, and inhibited the migration and invasion of A549 cells. Mutation of H2AX phosphorylation site eliminated the regulation of E-cadherin and vimentin by H2AX, and the inhibition of EMT by H2AX. H2AX knockdown in A549 cells stimulated the expression of VEGFR2, while overexpression of H2AX inhibited VEGFR2 expression. Mutation of H2AX phosphorylation site eliminated the VEGFR2 expression inhibition caused by H2AX. Knockdown of VEGFR2 inhibited the EMT of A549. Knockdown of H2AX stimulated the expression of EMT-related factors Slug and β-catenin, whereas overexpression of H2AX inhibited the expression of Slug and β-catenin. Reducing H2AX phosphorylation eliminated the expression inhibition of Slug and β-catenin by H2AX. Conclusion: H2AX inhibits EMT of lung cancer A549 cells by downregulating the expressions of VEGFR2, Slug and β-catenin.

Infections of the central nervous system (CNS) are potentially life-threatening and can cause serious morbidity. We evaluated the clinical value of metagenomic next-generation sequencing (mNGS) in the diagnosis of infectious encephalitis and meningitis and explored the factors affecting the results of mNGS. Patients with suspected cases of encephalitis or meningitis who presented in Northern Jiangsu People's Hospital from 1 March 2018 to 30 September 2022 were collected. Demographic, historical, and clinical information were obtained, and cerebrospinal fluid (CSF) samples were treated with mNGS. The pathogen was identified using National Center for Biotechnology Information (NCBI) GenBank sequence data. Ninety-six patients were screened and finally 90 subjects enrolled. Of the 90 enrolled cases, 67 (74.4%) were diagnosed with central nervous system infections, which included 48 cases (71.6%) of viral infection, 11 (12.2%) of bacterial infection, 5 (7.5%) of mycobacterium tuberculosis, 2 (3.0%) of fungal infection, and 1 (1.5%) of rickettsia infection. From these cases, mNGS identified 40 (44.4%) true-positive cases, 3 (3.3%) false-positive case, 22 (24.4%) true-negative cases, and 25 (27.8%) false-negative cases. The sensitivity and specificity of mNGS were 61.5% and 88%, respectively. mNGS of CSF could show a higher positive rate in patients with marked CSF abnormalities, including elevated protein concentrations and monocyte counts. mNGS of CSF is an effective method for detecting infectious encephalitis and meningitis, and the results should be analyzed combined with conventional microbiological testing results. [ABSTRACT FROM AUTHOR]

The COVID-19 pandemic is a serious threat to people's lives and mental health. As a key worker providing psychological assistance services, the purpose of this study was to explore the relationship between social support and vicarious posttraumatic growth of psychological hotline counselors during COVID-19 and its mechanism. A questionnaire survey was conducted among 241 psychological hotline counselors. Path analysis was conducted through structural equation modeling. The direct path from social support to vicarious posttraumatic growth of psychological hotline counselors was not significant, but the indirect path between them was significant. Social support can influence vicarious posttraumatic growth of psychological hotline counselors through the mediating effects of resilience and cognitive reappraisal as well as the chain mediating effects of these two factors. Social support does not directly stimulate vicarious posttraumatic growth in psychological hotline counselors, but social support can influence counselors' vicarious posttraumatic growth through the role of resilience, cognitive reappraisal, and the chain-mediated effects of psychological resilience and cognitive reappraisal. This encourages hotline counselors to be intentional about applying resources to balance the effects of trauma work on them as they face their clinical work. [ABSTRACT FROM AUTHOR]

BACKGROUND: The program of the "Free Training of Chinese Rural Order-Oriented Medical Students" is a plan to train general practitioners who can work at rural medical institutions. However, many students have been unwilling to fulfill their commitments and actually work in their assigned locations. OBJECTIVE: This study aimed to provide some explanation by exploring factors influencing the employment intentions of rural order-oriented medical students in Inner Mongolia Autonomous Region of China to provide a basis for formulating relevant supporting policies to help increase the fulfillment rate of medical students. METHODS: We conducted a cross-sectional study with a stratified cluster sampling method at four medical universities in Inner Mongolia using a survey questionnaire. Multivariate logistic regression was used to identify factors that were significantly associated with employment intentions. RESULTS: Approximately 67% of students were willing to work in rural areas, whereas 33% were not. Order-oriented medical students who were dissatisfied with, or indifferent to, training, were unclear about policy, were of Han ethnicity, or came from an urban area, had lower intentions to accept employment in rural areas. The training satisfaction in particular had the greatest predictive effect. CONCLUSION: The implementation of the program "Free Training of Chinese Rural Order-Oriented Medical Students" has been affected by the low actual employment intentions. This study may provide a useful basis on which medical educators and health policy makers can formulate relevant supporting policies and develop strategies to increase the number of order-oriented medical students who working in rural areas where they are most needed. [ABSTRACT FROM AUTHOR]

To solve the optimization problem of edge distance in titanium alloy sheet during a new aircraft development stage,a three dimensional FE model was built on ABAQUS platfom. The effect of edge distance on residual stress distribution was analysised with TC4 titanium alloy by interference-fit strengthening technique under cylic loading. The study indicates that a considerble reduction of fatigue life is found with a lower egde distance ratio（ L/D）,also,the location of fatigue damage is moving against the hole. Fatigue damage happens in the margin part with edge distance ratio（ L/D） less than 2.

Advancements in remote sensing technology and very-large-scale integrated circuit (VLSI) have significantly augmented the real-time processing capabilities of spaceborne synthetic aperture radar (SAR), thereby enhancing terrestrial observational capacities. However, the inefficiency of voluminous data storage and transfer inherent in conventional methods has emerged as a technical hindrance, curtailing real-time processing within SAR imaging systems. To address the constraints of a limited storage bandwidth and inefficient data transfer, this study introduces a three-dimensional cross-mapping approach premised on the equal subdivision of sub-matrices utilizing dual-channel DDR3. This method considerably augments storage access bandwidth and achieves equilibrium in two-dimensional data access. Concurrently, an on-chip data transfer approach predicated on a superscalar pipeline buffer is proposed, mitigating pipeline resource wastage, augmenting spatial parallelism, and enhancing data transfer efficiency. Building upon these concepts, a hardware architecture is designed for the efficient storage and transfer of SAR imaging system data, based on the superscalar pipeline. Ultimately, a data storage and transfer engine featuring register addressing access, configurable granularity, and state monitoring functionalities is realized. A comprehensive imaging processing experiment is conducted via a "CPU + FPGA" heterogeneous SAR imaging system. The empirical results reveal that the storage access bandwidth of the proposed superscalar pipeline-based SAR imaging system's data efficient storage and transfer engine can attain up to 16.6 GB/s in the range direction and 20.0 GB/s in the azimuth direction. These findings underscore that the storage exchange engine boasts superior storage access bandwidth and heightened data storage transfer efficiency. This considerable enhancement in the processing performance of the entire "CPU + FPGA" heterogeneous SAR imaging system renders it suitable for application within spaceborne SAR real-time processing systems. [ABSTRACT FROM AUTHOR]

Dermatophagoides farinae (Astigmata: Pyroglyphidae) occurs in both homes and storage environments. The species produces biochemically diverse allergens that cause allergic reactions and seriously endanger human health. Habitat diversity can lead to divergent adaptive selection and reduced gene flow, thereby increasing genetic drift; both factors contribute to genetic differentiation. However, there is a lack of research concerning the genetic diversity and differentiation of D. farinae in different habitats. In this study, the genetic diversity and differentiation of D. farinae populations in different habitats were studied using the mitochondrial cytochrome b (Cytb) gene, the cytochrome c oxidase subunit I (COI) gene, and the ribosomal internal transcribed spacer (ITS) region. Both pillow cores (ZX) and dormitory (SS) habitats had higher haplotype diversity than the flour mill (MF) habitat. The reasons for this phenomenon are likely to be food availability as well as differences in temperature and humidity among habitats. There was significant genetic differentiation (Fst > 0.05, P < 0.05) between the ZX and MF and between the MF and SS habitats, but there was no significant genetic differentiation between the ZX and SS habitats (Fst < 0.05, P > 0.05) based on both Cytb and COI genes, reflecting the difference between mitochondrial and nuclear genes. The low level of gene flow observed for ZX-MF and MF-SS and the gene flow between the ZX and SS habitats supported the above results. A haplotype network and a neighbour-joining phylogenetic tree showed that individuals from the ZX and SS habitats occurred in two clades without a clear distribution boundary, indicating that the genetic structure was not correlated with the habitat distribution. This research is the first genetic analysis of D. farinae in different habitats. The study can improve our understanding of the population genetics of D. farinae in different habitats and aid in the development of more effective management strategies. [ABSTRACT FROM AUTHOR]