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The objective of this study was to investigate the potential targets and mechanisms of UA in the treatment of PD. The efficacy of UA in PD was assessed through network pharmacology, molecular docking, and experimental methods. Common target protein-protein interaction (PPI) networks were constructed and visualized using Cytoscape. As a result, 9 key genes, namely CASP3, IL6, IL1B, PTGS2, CREB1, TNF, MAPK3, JUN, and CASP8, were selected. Molecular docking simulations were performed using Discovery Studio 2019 to validate the correlation between UA and the core targets. The results demonstrated a favorable binding affinity between UA and CASP8, IL1B, CASP3, TNF, MAPK3 and IL6. In vivo studies showed UA ameliorated motor dysfunction, and UA can significantly increase the protein expression of tyrosine hydroxylase (TH) in PD mice model. In addition, in vitro experiments confirmed that UA effectively reduced the protein expression of CASP8, CASP3 and MAPK3 in PD cell models and suppressed the gene expression of TNF-α, IL-6, and IL-1ß. These findings indicate that the therapeutic effects of UA on PD could be due to its influence on various targets within both the apoptosis and neuroinflammatory signaling pathways. Consequently, this study provides a methodological and theoretical foundation for further elucidating the pharmacological mechanism of UA.
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BACKGROUND: Persistent infection with high-risk human papillomavirus (HR-HPV) plays a key role in the onset of cervical cancer. This study was designed to examine the epidemiological trends and genotype distribution of HPV from 2014 to 2023 in the plateau region of Southwest China. METHODS: The findings could offer valuable insights for clinical screening of cervical cancer and the formulation of HPV vaccination policies. This retrospective study analyzed 66,000 women who received HPV-DNA testing at the First People's Hospital of Qujing, Yunnan, China, between 2014 and 2023. The cohort consisted of 33,512 outpatients, 3,816 inpatients, and 28,672 individuals undergoing health examinations. Cervical cells were collected for DNA extraction, and PCR amplification along with Luminex xMAP technology were used to detect 27 HPV genotypes. The data analysis was conducted using GraphPad Prism and IBM SPSS Statistics 27 software. RESULTS: The overall HPV infection rate at the First People's Hospital of Qujing declined from 24.92% in 2014 to 16.29% in 2023, averaging 16.02%. Specific infection rates were 18.50% among outpatients, 12.97% among inpatients, and 13.53% for health examination attendees. The predominant high-risk HPV genotypes identified were HPV52 (2.61%), HPV16 (2.06%), HPV58 (1.81%), HPV53 (1.55%), and HPV39 (1.09%). Meanwhile, the most frequent low-risk HPV genotypes were HPV6 (1.30%), HPV61 (1.21%), and HPV11 (0.85%). In HPV-positive cases, the distribution of single, double, triple, and quadruple or more infections were 79.90%, 15.17%, 3.59%, and 1.33%, respectively. The proportions of pure LR-HPV, pure HR-HPV, and mixed infections were 22.16%, 67.82%, and 10.02%, respectively. Age-specific analysis revealed a bimodal distribution of HPV infection, with the infection rate rapidly decreasing from 44.02% in the ≤ 19 age group to 19.55% in the 20-29 age group and 13.84% in the 30-39 age group, followed by a gradual increase to 14.64% in the 40-49 age group, 16.65% in the 50-59 age group, and 22.98% in the ≥ 60 age group. The coverage rates of the three available vaccines are all below 50%. The results of this study indicated a declining trend in HPV prevalence in the plateau region of Southwest China over the period from 2014 to 2023, especially in the reduction of genotypes targeted by vaccines. CONCLUSION: There were significant variations in the genotypes prevalent among different age groups, years, and patient sources within the same region. The underwhelming vaccination rates emphasize the critical need for developing either a multivalent vaccine or a personalized vaccine that targets the HPV genotypes common in the Chinese population. Furthermore, vaccinating adolescents to curb HPV infection and ensuring regular cervical cancer screenings for postmenopausal women are crucial steps.
Subject(s)
Genotype , Papillomaviridae , Papillomavirus Infections , Humans , Female , Papillomavirus Infections/epidemiology , Papillomavirus Infections/virology , China/epidemiology , Adult , Prevalence , Middle Aged , Retrospective Studies , Young Adult , Papillomaviridae/genetics , Papillomaviridae/classification , Papillomaviridae/isolation & purification , Adolescent , Aged , Uterine Cervical Neoplasms/virology , Uterine Cervical Neoplasms/epidemiology , DNA, Viral/genetics , Cervix Uteri/virologyABSTRACT
Gynostemma pentaphyllum has been used as an herbal tea, vegetable, and dietary supplement for hundreds of years in East Asia. The sweet variety, grown in large areas in Fujian Province, China, is an essential source of "Jiaogulan" herbal tea. However, its sweet components are unknown. To investigate the sweet constituents of Fujian "Jiaogulan" and discover new natural high-potency sweeteners, phytochemical and sensory evaluations were combined to obtain 15 saponins, of which 11 (1-11) were sweet-tasting, including 2 new ones with sweetness intensities 20-200 times higher than that of sucrose, and four (12-15) were bitter-tasting. Their structures were elucidated using spectroscopic methods (NMR, MS, IR, UV), hydrolysis, and comparison with literature data. The contents of the 15 saponins were quantitatively analyzed using UPLC-MS/MS in multiple reaction monitoring mode. The contents of 1 and 2 sweet-tasting gypenosides were 9.913 ± 1.735 and 35.852 ± 1.739 mg/kg, respectively. The content of the sweetest compound (6) was 124.969 ± 0.961 mg/kg. Additionally, compound 4 was the most abundant sweet component (422.530 ± 3.702 mg/kg). Furthermore, molecular docking results suggested interactions of sweet saponins with sweet taste receptors. In general, this study revealed the material basis of the Fujian "Jiaogulan" taste.
Subject(s)
Gynostemma , Plant Extracts , Receptors, G-Protein-Coupled , Sweetening Agents , Taste , Gynostemma/chemistry , Humans , Sweetening Agents/chemistry , Plant Extracts/chemistry , Receptors, G-Protein-Coupled/chemistry , Receptors, G-Protein-Coupled/metabolism , Molecular Structure , Tandem Mass Spectrometry , Molecular Docking Simulation , Saponins/chemistry , ChinaABSTRACT
OBJECTIVE: To explore the levels of regulatory T cells (Tregs) and cytokines IL-35, TGF-ß and IL-10 in peripheral blood of hemophilia A(HA) patients with Fâ § inhibitor and their clinical significance. METHODS: 43 HA patients admitted to the Hematology Department of the Affiliated Hospital of North China University of Science and Technology from October 2019 to December 2020 were selected, including 6 cases with Fâ § inhibitor and 37 cases without Fâ § inhibitor. In addition, 20 healthy males who underwent physical examinations were selected as healthy controls. Flow cytometry was used to detect the levels of CD4 + CD25 + CD127 - Tregs in peripheral blood of the HA patients and healthy controls, and ELISA assay was used to detect the expression levels of IL-35, TGF-ß and IL-10 in serum, and their differences between different groups were compared. RESULTS: Compared with the healthy control group, the level of Tregs in HA patients was decreased, and the level of Tregs in the Fâ § inhibitor positive group was the lowest, the difference was statistically significant (P <0.05). There was no significant difference in the expression level of Tregs in HA patients of different severity levels. The serum IL-35, TGF-ß, and IL-10 levels in both Fâ § inhibitor negative and positive groups were significantly lower than those in healthy control group, and those in Fâ § inhibitor positive group were significantly lower than those in Fâ § inhibitor negative group (all P <0.05). CONCLUSION: The decrease of Tregs, IL-35, TGF-ß, and IL-10 levels in HA patients may be related to the formation of Fâ § inhibitors.
Subject(s)
Hemophilia A , Interleukin-10 , Interleukins , T-Lymphocytes, Regulatory , Transforming Growth Factor beta , Humans , Interleukin-10/blood , Hemophilia A/blood , Transforming Growth Factor beta/blood , Interleukins/blood , Male , Case-Control Studies , Clinical RelevanceABSTRACT
OBJECTIVE: To investigate the effect of pre-treatment plasma Epstein-Barr virus (EBV) DNA copy number on the clinical features and prognosis of patients with adult secondary hemophagocytic lymphohistiocytosis(sHLH). METHODS: The clinical characteristics, survival rate, and prognostic factors of 171 patients with adult sHLH treated at Jiangsu Province Hospital from June 2017 to January 2022 were retrospectively analyzed in this study. Patients were divided into three groups, including the EBV DNA-negative group(<5.0×102 copies/ml), lower EBV-DNA loads group(5.0×102-8.51×104 copies/ml), and higher EBV-DNA loads group(ï¼8.51×104 copies/ml), according to pre-treatment plasma EBV-DNA copy number. Cox regression model was established for screening prognostic factors. Adult sHLH survival prediction model was constructed and realized through the nomogram based on EBV-DNA load after adjusted the factors affecting survival of etiology and treatment strategy.Concordance index (C-index) and calibration curves were calculated to verify model predictive and discriminatory capacity. RESULTS: Among 171 adult sHLH patients, 84 patients were not infected with EBV (EBV DNA-negative group), and 87 with EBV (EBV DNA-positive group, 48 lower EBV-DNA loads group and 39 higher EBV-DNA loads group). Consistent elevations in the levels of liver enzymes (ALT and AST), LDH, TG, ß 2-microglobulin and ferritin across the increasing of EBV-DNA load (all P <0.05), while the levels of fibrinogen decrease (P <0.001). The median follow-up time was 52 days (range 20-230 days), and 123 patients died. The overall survival (OS) rate of patients in EBV DNA-positive group was lower than that in EBV DNA-negative group (median OS: 40 days vs 118 days, P <0.001). Higher EBV-DNA loads had worse OS (median OS: 24 days vs 45 days vs 118 days, P <0.0001 for trend) compared to lower EBV-DNA loads and EBV DNA-negative group. Multivariate Cox analysis revealed that higher EBV-DNA loads (P =0.005), fibrinogen≤1.5 g/L (P ï¼0.012), ferritin (P ï¼0.041), associated lymphoma (P ï¼0.002), and anti-tumor based strategy (P ï¼0.001) were independent prognostic factors for OS. The C-indexes of 30 day, 90 days, 365 days survival rate were all greater than 0.8 of the nomogram model and calibration curves provided credibility to their predictive capability. Subgroup analysis showed that patients with higher EBV-DNA loads had a significantly worse prognosis in adult sHLH who were women, ferritinï¼5 000 µg/L, ß2-microglobulinï¼7.4 mmol/L and regardless of age, etiologies, HScore points. CONCLUSION: The EBV-DNA load is a strong and independent predictor for survival in patients with sHLH. The prognostic nomogram based on EBV-DNA loads was dependable and provides a visual tool for evaluating the survival of adult sHLH.
Subject(s)
DNA, Viral , Herpesvirus 4, Human , Lymphohistiocytosis, Hemophagocytic , Viral Load , Humans , Lymphohistiocytosis, Hemophagocytic/diagnosis , Lymphohistiocytosis, Hemophagocytic/blood , Lymphohistiocytosis, Hemophagocytic/virology , Prognosis , Retrospective Studies , DNA, Viral/blood , Adult , Epstein-Barr Virus Infections/blood , Survival Rate , Female , MaleABSTRACT
Background: Malignant pleural effusion (MPE) is a common clinical problem that requires cytological and/or histological confirmation obtained by invasive examination to establish a definitive diagnosis. Radiomics is rapidly evolving and can provide a non-invasive tool to identify MPE. Objectives: We aimed to develop a model based on radiomic features extracted from unenhanced chest computed tomography (CT) images and investigate its value in predicting MPE. Method: This retrospective study included patients with pleural effusions between January 2016 and June 2020. All patients underwent a chest CT scanning and medical thoracoscopy after artificial pneumothorax. Cases were divided into a training cohort and a test cohort for modelling and verifying respectively. The Mann-Whitney U test and the least absolute shrinkage and selection operator (LASSO) were applied to determine the optimal features. We built a radiomics model based on support vector machines (SVM) and evaluated its performance using ROC and calibration curve analysis. Results: Twenty-nine patients with MPE and fifty-two patients with non-MPE were enrolled. A total of 944 radiomic features were quantitatively extracted from each sample and reduced to 14 features for modeling after selection. The AUC of the radiomics model was 0.96 (95% CI: 0.912-0.999) and 0.86 (95% CI: 0.657~1.000) in the training and test cohorts, respectively. The calibration curves for model were in good agreement between predicted and actual data. Conclusions: The radiomics model based on unenhanced chest CT has good performance for predicting MPE and may provide a powerful tool for doctors in clinical decision-making.
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BACKGROUND: Type 2 diabetes mellitus (T2DM) and spinal degenerative disorders (SDD) are common diseases that frequently coexist. However, both traditional observational studies and recent Mendelian randomization (MR) studies have demonstrated conflicting evidence on the association between T2DM and SDD. This comparative study explored and compared the association between T2DM and SDD using observational and MR analyses. METHODS: For observational analyses, cross-sectional studies (44,972 participants with T2DM and 403,095 participants without T2DM), case-control studies (38,234 participants with SDD and 409,833 participants without SDD), and prospective studies (35,550 participants with T2DM and 392,046 participants without T2DM with follow-up information until 2022) were performed to test the relationship between T2DM and SDD using individual-level data from the U.K. Biobank from 2006 to 2022. For MR analyses, the associations between single-nucleotide polymorphisms with SDD susceptibility obtained using participant data from the U.K. Biobank, which had 407,938 participants from 2006 to 2022, and the FinnGen Consortium, which had 227,388 participants from 2017 to 2022, and genetic predisposition to T2DM obtained using summary statistics from a pooled genome-wide association study involving 1,407,282 individuals were examined. The onset and severity of T2DM are not available in the databases being used. RESULTS: Participants with T2DM were more likely to have SDD than their counterparts. Logistic regression analysis identified T2DM as an independent risk factor for SDD, which was confirmed by the Cox proportional hazard model results. However, using single-nucleotide polymorphisms as instruments, the MR analyses demonstrated no causal relationship between T2DM and SDD. The lack of such an association was robust in the sensitivity analysis, and no pleiotropy was seen. CONCLUSIONS: Our results suggest that the association between T2DM and SDD may be method-dependent. Researchers and clinicians should be cautious in interpreting the association, especially the causal association, between T2DM and SDD. Our findings provide fresh insights into the association between T2DM and SDD by various analysis methods and guide future research and clinical efforts in the effective prevention and management of T2DM and SDD. LEVEL OF EVIDENCE: Prognostic Level III. See Instructions for Authors for a complete description of levels of evidence.
Subject(s)
Diabetes Mellitus, Type 2 , Mendelian Randomization Analysis , Humans , Diabetes Mellitus, Type 2/genetics , Diabetes Mellitus, Type 2/complications , Polymorphism, Single Nucleotide , Female , Male , Case-Control Studies , Middle Aged , Genetic Predisposition to Disease , Cross-Sectional Studies , Prospective Studies , Observational Studies as Topic , Aged , Genome-Wide Association StudyABSTRACT
Superconducting materials have garnered widespread attention due to their zero-resistance characteristic and complete diamagnetism. After more than 100 years of exploration, various high-temperature superconducting materials including cuprates, nickelates, iron-based compounds, and ultra-high pressure multi-hydrides have been discovered. However, the practical application of these materials is severely hindered by their poor ductility and/or the need for high-pressure conditions to maintain structural stability. To address these challenges, we first provide a new thought to build high-temperature superconducting materials based on few-hydrogen metal-bonded hydrides under ambient pressure. We then review the related research efforts in this article. Moreover, based on the bonding type of atoms, we classify the existing important superconducting materials and propose the new concepts of pseudo-metal and quasi-metal superconductivity, which are expected to be helpful for the design of new high-temperature superconducting materials in the future.
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BACKGROUND: The limited understanding of the physiology and psychology of polar expedition explorers has prompted concern over the potential cognitive impairments caused by exposure to extreme environmental conditions. Prior research has demonstrated that such stressors can negatively impact cognitive function, sleep quality, and behavioral outcomes. Nevertheless, the impact of the polar environment on neuronal activity remains largely unknown. METHODS: In this study, we aimed to investigate spatiotemporal alterations in brain oscillations of 13 individuals (age range: 22-48 years) who participated in an Arctic expedition. We utilized electroencephalography (EEG) to record cortical activity before and during the Arctic journey, and employed standardized low resolution brain electromagnetic tomography to localize changes in alpha, beta, theta, and gamma activity. RESULTS: Our results reveal a significant increase in the power of theta oscillations in specific regions of the Arctic, which differed significantly from pre-expedition measurements. Furthermore, microstate analysis demonstrated a significant reduction in the duration of microstates (MS) D and alterations in the local synchrony of the frontoparietal network. CONCLUSION: Overall, these findings provide novel insights into the neural mechanisms underlying adaptation to extreme environments. These findings have implications for understanding the cognitive consequences of polar exploration and may inform strategies to mitigate potential neurological risks associated with such endeavors. Further research is warranted to elucidate the long-term effects of Arctic exposure on brain function.
Subject(s)
Brain Waves , Brain , Electroencephalography , Humans , Adult , Arctic Regions , Male , Female , Middle Aged , Electroencephalography/methods , Young Adult , Brain/physiology , Brain Waves/physiologyABSTRACT
Accurate and sensitive determination of human immunoglobulin G (HIgG) level is critical for diagnosis and treatment of various diseases, including rheumatoid arthritis, humoral immunodeficiencies, and infectious disease. In this study, versatile tri-signal probes were developed by preparing CdS@SiO2 nanorods that integrate photoluminescence (PL), multi-phonon resonant Raman scattering (MRRS) and infrared absorption (IRA) properties. Through the coating of multiple CdS nanoparticles as cores within SiO2 shells, the PL and MRRS properties of CdS were improved, resulting in a significantly lowered limit of detection (LOD), with the lowest LOD of 12.37 ag mL-1. Integration with the distinctive IRA property of SiO2 shells widened the detection range towards higher concentrations, establishing a final linear range of 50 ag mL-1 to 10 µg mL-1. The remarkable consistency among the three signals highlighted the robust internal verification capability for accurate detection. This approach enhances flexibility in selecting detection methodologies to suit diverse scenarios, facilitating HIgG detection. The tri-signal nanoprobes also exhibited excellent detection selectivity, specificity and repeatability. This study presents a fresh idea for developing high-performance detection strategies.
Subject(s)
Cadmium Compounds , Immunoglobulin G , Limit of Detection , Silicon Dioxide , Sulfides , Humans , Silicon Dioxide/chemistry , Cadmium Compounds/chemistry , Immunoglobulin G/analysis , Immunoglobulin G/chemistry , Immunoglobulin G/immunology , Sulfides/chemistry , Spectrum Analysis, Raman/methodsABSTRACT
Marek's disease (MD), caused by the Marek's disease virus (MDV), is a common infectious tumor disease in chickens and was the first neoplastic disease preventable by vaccination. However, the vaccine cannot completely prevent virulent MDV infections, allowing both the vaccine and virulent MDV to coexist in the same chicken for extended periods. This study aims to investigate the changes in viral load of the very virulent strain Md5 and the rHVT-IBD vaccine in different chicken tissues using a real-time PCR assay. The results showed that the rHVT-IBD vaccine significantly reduced the viral load of MDV-Md5 in different organs, while the load of rHVT-IBD was significantly increased when co-infected with Md5. Additionally, co-infection with Md5 and rHVT-IBD in chickens not only changed the original viral load of both viruses but also affected the positive rate of Md5 at 14 days post-vaccination. The positive rate decreased from 100% to 14.29% (feather tips), 0% (skin), 33.33% (liver), 16.67% (spleen), 28.57% (thymus), 33.33% (bursa), and 66.67% (PBL), respectively. This study enhances our understanding of the interactions between HVT vector vaccines and very virulent MDV in chickens and provides valuable insights for the future development of MD vaccines.
Subject(s)
Chickens , Coinfection , Marek Disease Vaccines , Marek Disease , Poultry Diseases , Viral Load , Animals , Marek Disease/virology , Marek Disease/prevention & control , Marek Disease/immunology , Chickens/virology , Coinfection/virology , Coinfection/veterinary , Poultry Diseases/virology , Poultry Diseases/prevention & control , Marek Disease Vaccines/immunology , Marek Disease Vaccines/genetics , Virulence , Herpesvirus 1, Meleagrid/immunology , Herpesvirus 1, Meleagrid/genetics , Vaccines, Synthetic/immunology , Vaccines, Synthetic/genetics , Herpesvirus 2, Gallid/genetics , Herpesvirus 2, Gallid/immunology , Herpesvirus 2, Gallid/pathogenicity , Vaccination , Genetic Vectors/geneticsABSTRACT
INTRODUCTION: Central nervous system leukemia (CNSL) remains a serious complication in patients with acute myeloid leukemia (AML) and an ambiguous prognostic factor for those receiving allo-geneic hematopoiesis stem cell transplantation (allo-HSCT). It is unknown whether using more sensitive tools, such as multiparameter flow cytometry (MFC), to detect blasts in the cerebrospinal fluid (CSF) would have an impact on outcome. METHODS: We retrospectively analyzed the clinical outcomes of 1472 AML patients with or without cytology or MFC positivity in the CSF before transplantation. Abnormal CSF (CSF+) was detected via conventional cytology and MFC in 44 patients at any time after diagnosis. A control group of 175 CSF-normal (CSF-) patients was generated via propensity score matching (PSM) analyses according to sex, age at transplant, and white blood cell count at diagnosis. RESULTS: Compared to those in the CSF-negative group, the conventional cytology positive and MFC+ groups had comparable 8-year nonrelapse mortality (NRM) (4%, 4%, and 6%, p = 0.82), higher cumulative incidence of relapse (CIR) (14%, 31%, and 32%, p = 0.007), lower leukemia-free survival (LFS) (79%, 63%, and 64%, p = 0.024), and overall survival (OS) (83%, 63%, and 68%, p = 0.021), with no significant differences between the conventional cytology positive and MFC+ groups. Furthermore, multivariate analysis confirmed that CSF involvement was an independent factor affecting OS and LFS. CONCLUSION: Our results indicate that pretransplant CSF abnormalities are adverse factors independently affecting OS and LFS after allotransplantation in AML patients.
Subject(s)
Flow Cytometry , Hematopoietic Stem Cell Transplantation , Leukemia, Myeloid, Acute , Transplantation, Homologous , Humans , Female , Male , Leukemia, Myeloid, Acute/therapy , Leukemia, Myeloid, Acute/cerebrospinal fluid , Leukemia, Myeloid, Acute/mortality , Retrospective Studies , Adult , Prognosis , Middle Aged , Follow-Up Studies , Adolescent , Hematopoietic Stem Cell Transplantation/adverse effects , Survival Rate , Young Adult , Graft vs Host Disease/etiology , Graft vs Host Disease/cerebrospinal fluid , Graft vs Host Disease/diagnosis , Graft vs Host Disease/mortality , Aged , Child , CytologyABSTRACT
Background: Parkinson's disease (PD) is marked by the loss of dopaminergic neurons in the substantia nigra pars compacta, leading to motor and cognitive dysfunctions. The molecular mechanisms underlying synaptic alterations in PD remain elusive, with a focus on the role of Itga5 in synaptic integrity and motor coordination and TAT-Itga5 was designed to suppress PTEN activity in this investigation. Methods: This study utilized MPTP-induced PD animal models to investigate the expression and role of Itga5 in the striatum. Techniques included quantitative PCR, Western blotting, immunostaining, CRISPR-CasRx-mediated knockdown, electrophysiological assays, behavioral tests, and mass spectrometry. Results: Itga5 expression was significantly reduced in MPTP-induced PD models. In these models, a marked decrease in dendritic spine density and a shift towards thinner spines in striatal GABA neurons were observed, suggesting impaired synaptic integration. Knockdown of Itga5 resulted in reduced dendritic branching, decreased mushroom spines, and increased thin spines, altering synaptic architecture. Electrophysiological analyses revealed changes in action potential and spontaneous excitatory postsynaptic currents, indicating altered synaptic transmission. Motor behavior assessments showed that Itga5 deficiency led to impairments in fine motor control and coordination. Furthermore, Itga5 was found to interact with PTEN, affecting AKT signaling crucial for synaptic development and motor coordination. Conclusion: The study demonstrates that Itga5 plays a critical role in maintaining synaptic integrity and motor coordination in PD. The Itga5-PTEN-AKT pathway represents a potential therapeutic target for addressing synaptic and motor dysfunctions in PD.
Subject(s)
PTEN Phosphohydrolase , Parkinson Disease , Signal Transduction , Animals , PTEN Phosphohydrolase/metabolism , PTEN Phosphohydrolase/genetics , Parkinson Disease/metabolism , Parkinson Disease/genetics , Male , Mice , Corpus Striatum/metabolism , Mice, Inbred C57BL , Integrin alpha5/metabolism , Integrin alpha5/genetics , Synapses/metabolism , Disease Models, AnimalABSTRACT
Objective: To develop a highly sensitive and rapid nucleic acid detection method for the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Methods: We designed, developed, and manufactured an integrated disposable device for SARS-CoV-2 nucleic acid extraction and detection. The precision of the liquid transfer and temperature control was tested. A comparison between our device and a commercial kit for SARS-Cov-2 nucleic acid extraction was performed using real-time fluorescence reverse transcription polymerase chain reaction (RT-PCR). The entire process, from SARS-CoV-2 nucleic acid extraction to amplification, was evaluated. Results: The precision of the syringe transfer volume was 19.2 ± 1.9 µL (set value was 20), 32.2 ± 1.6 (set value was 30), and 57.2 ± 3.5 (set value was 60). Temperature control in the amplification tube was measured at 60.0 ± 0.0 °C (set value was 60) and 95.1 ± 0.2 °C (set value was 95) respectively. SARS-Cov-2 nucleic acid extraction yield through the device was 7.10 × 10 6 copies/mL, while a commercial kit yielded 2.98 × 10 6 copies/mL. The mean time to complete the entire assay, from SARS-CoV-2 nucleic acid extraction to amplification detection, was 36 min and 45 s. The detection limit for SARS-CoV-2 nucleic acid was 250 copies/mL. Conclusion: The integrated disposable devices may be used for SARS-CoV-2 Point-of-Care test (POCT).
Subject(s)
COVID-19 , Disposable Equipment , RNA, Viral , SARS-CoV-2 , SARS-CoV-2/isolation & purification , COVID-19/diagnosis , COVID-19/virology , Humans , RNA, Viral/isolation & purification , RNA, Viral/analysis , COVID-19 Nucleic Acid Testing/instrumentation , COVID-19 Nucleic Acid Testing/methods , Nucleic Acid Amplification Techniques/instrumentation , Nucleic Acid Amplification Techniques/methods , Real-Time Polymerase Chain Reaction/methods , Real-Time Polymerase Chain Reaction/instrumentationABSTRACT
Palladium-catalyzed reaction of indolines with 1-acyl-2,3-dihydro-1H-pyrroles or 1-acyl-2,5-dihydro-1H-pyrroles in air produces N-alkylated indoles. A combination of Pd(CH3CN)2Cl2 and dppf effectively catalyzes the reaction of 1-acyl-2,3-dihydro-1H-pyrroles, and the combination of Pd(CH3CN)2Cl2 and dcypf is more effective for the reaction of 1-acyl-2,5-dihydro-1H-pyrroles. The method has a wide scope of substrates and shows good compatibility of functional groups.
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BACKGROUND: To date, Non-alcoholic fatty liver disease (NAFLD) is one of the most common liver disease associated with clinical complications. Dietary fatty acids have been suggested to be involved in preventing or reversing the accumulation of hepatic fat. However, contradicting roles of monounsaturated fatty acids to the liver have been implicated in various human and murine models, mainly due to the insolubility nature of fatty acids. METHODS: High pressure homogenization methods were used to fabricate oleic acid embedded lipid nanoparticles (OALNs). The in vitro and in vivo models were used to validate the physiological effect of this OALNs via various cellular and molecular approaches including cell viability essay, fluorescent staining, electron microscope, RNAseq, qPCR, Western blots, and IHC staining. RESULTS: We successfully fabricated OALNs with enhanced stability and solubility. More importantly, lipid accumulation was successfully induced in hepatocytes via the application of OALNs in a dose-dependent manner. Overload of OALNs resulted in ROS accumulation and apoptosis of hepatocytes dose-dependently. With the help of transcriptome sequencing and traditional experimental approaches, we demonstrated that the lipotoxic effect induced by OALNs was exerted via the DDIT3/BCL2/BAX/Caspases signaling. Moreover, we also verified that OALNs induced steatosis and subsequent apoptosis in the liver of mice via the activation of DDIT3 in vivo. CONCLUSIONS: In all, our results established a potential pathogenic model of NAFLD for further studies and indicated the possible involvement of DDIT3 signaling in abnormal steatosis process of the liver.
Subject(s)
Apoptosis , Hepatocytes , Nanoparticles , Non-alcoholic Fatty Liver Disease , Oleic Acid , Reactive Oxygen Species , Signal Transduction , Transcription Factor CHOP , Animals , Hepatocytes/metabolism , Hepatocytes/pathology , Hepatocytes/drug effects , Nanoparticles/chemistry , Mice , Humans , Oleic Acid/chemistry , Reactive Oxygen Species/metabolism , Non-alcoholic Fatty Liver Disease/pathology , Non-alcoholic Fatty Liver Disease/metabolism , Non-alcoholic Fatty Liver Disease/chemically induced , Apoptosis/drug effects , Signal Transduction/drug effects , Transcription Factor CHOP/metabolism , Transcription Factor CHOP/genetics , bcl-2-Associated X Protein/metabolism , bcl-2-Associated X Protein/genetics , Proto-Oncogene Proteins c-bcl-2/metabolism , Proto-Oncogene Proteins c-bcl-2/genetics , Male , Hep G2 Cells , LiposomesABSTRACT
In recent years, aerosols have been recognized as a prominent medium for the transmission of antibiotic-resistant bacteria and genes. Among these, particles with a particle size of 2 µm (PM2.5) can directly penetrate the alveoli. However, the presence of antibiotic-resistant genes in aerosols from pet hospitals and the potential risks posed by antibiotic-resistant bacteria in these aerosols to humans and animals need to be investigated. In this study, cefotaxime-resistant bacteria were collected from 5 representative pet hospitals in Changchun using a Six-Stage Andersen Cascade Impactor. The distribution of bacteria in each stage was analyzed, and bacteria from stage 5 and 6 were isolated and identified. Minimal inhibitory concentrations of isolates against 12 antimicrobials were determined using broth microdilution method. Quantitative Polymerase Chain Reaction was employed to detect resistance genes and mobile genetic elements that could facilitate resistance spread. The results indicated that ARBs were enriched in stage 5 (1.1-2.1 µm) and stage 3 (3.3-4.7 µm) of the sampler. A total of 159 isolates were collected from stage 5 and 6. Among these isolates, the genera Enterococcus spp. (51%), Staphylococcus spp. (19%), and Bacillus spp. (14%) were the most prevalent. The isolates exhibited the highest resistance to tetracycline and the lowest resistance to cefquinome. Furthermore, 56 (73%) isolates were multidrug-resistant. Quantitative PCR revealed the expression of 165 genes in these isolates, with mobile genetic elements showing the highest expression levels. In conclusion, PM2.5 from pet hospitals harbor a significant number of antibiotic-resistant bacteria and carry mobile genetic elements, posing a potential risk for alveolar infections and the dissemination of antibiotic resistance genes.
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Three Gram-stain-positive bacterial strains were isolated from traditional Chinese pickle and characterized using a polyphasic taxonomic approach. Results of 16S rRNA gene sequence analysis indicated that strain 74-4T was most closely related to the type strains of Lacticaseibacillus suibinensis and Lacticaseibacillus suilingensis, having 99.9% and 100% 16S rRNA gene sequence similarities, respectively, and that strains 419-1.2T and 262-4 were most closely related to the type strains of Companilactobacillus heilongjiangensis, Companilactobacillus nantensis, Companilactobacillus huachuanensis, and Companilactobacillus nuruki, having 98.5-99.7% 16S rRNA gene sequence similarities. The phylogenomic trees indicated that strain 74-4T was related to the type strains of L. suibinensis and L. suilingensis, and that strains 419-1.2T and 262-4 were related to the type strains of C. heilongjiangensis, C. nantensis, C. huachuanensis, and Companilactobacillus zhachilii. The ANI and dDDH values between strain 74-4T and type strains of phylogenetically related species were less than 92.7% and 49.9%, respectively. The ANI and dDDH values between strains 419-1.2T and 262-4 and type strains of phylogenetically related species were less than 93.4% and 51.7%, respectively. Based upon the data of polyphasic characterization obtained in the present study, two novel species, Lacticaseibacillus salsurivasis sp. nov. and Companilactobacillus muriivasis sp. nov., are proposed and the type strains are 74-4T (= JCM 35890T = CCTCC AB 2022414T) and 419-1.2T (= JCM 35891T = CCTCC AB 2022413T), respectively.
Subject(s)
DNA, Bacterial , Phylogeny , RNA, Ribosomal, 16S , RNA, Ribosomal, 16S/genetics , DNA, Bacterial/genetics , China , Bacterial Typing Techniques , Base Composition , Fermented Foods/microbiology , Sequence Analysis, DNA , Fatty Acids/analysis , Food Microbiology , LacticaseibacillusABSTRACT
Neuroendocrine neoplasms (NENs) are highly heterogeneous and potentially malignant tumors arising from secretory cells of the neuroendocrine system. Gastroenteropancreatic neuroendocrine neoplasms (GEP-NENs) are the most common subtype of NENs. Historically, GEP-NENs have been regarded as infrequent and slow-growing malignancies; however, recent data have demonstrated that the worldwide prevalence and incidence of GEP-NENs have increased exponentially over the last three decades. In addition, an increasing number of studies have proven that GEP-NENs result in a limited life expectancy. These findings suggested that the natural biology of GEP-NENs is more aggressive than commonly assumed. Therefore, there is an urgent need for advanced researches focusing on the diagnosis and management of patients with GEP-NENs. In this review, we have summarized the limitations and recent advancements in our comprehension of the epidemiology, clinical presentations, pathology, molecular biology, diagnosis, and treatment of GEP-NETs to identify factors contributing to delays in diagnosis and timely treatment of these patients.
Subject(s)
Neuroendocrine Tumors , Pancreatic Neoplasms , Stomach Neoplasms , Humans , Neuroendocrine Tumors/therapy , Neuroendocrine Tumors/epidemiology , Neuroendocrine Tumors/diagnosis , Pancreatic Neoplasms/therapy , Pancreatic Neoplasms/epidemiology , Pancreatic Neoplasms/diagnosis , Stomach Neoplasms/epidemiology , Stomach Neoplasms/therapy , Stomach Neoplasms/diagnosis , Intestinal Neoplasms/therapy , Intestinal Neoplasms/epidemiology , Intestinal Neoplasms/diagnosisABSTRACT
BACKGROUND: MicroRNAs (miRNAs) regulate gene expression and play a critical role in cancer physiology. However, there is still a limited understanding of the function and regulatory mechanism of miRNAs in gastric cancer (GC). AIM: To investigate the role and molecular mechanism of miRNA-145-5p (miR145-5p) in the progression of GC. METHODS: Real-time polymerase chain reaction (RT-PCR) was used to detect miRNA expression in human GC tissues and cells. The ability of cancer cells to migrate and invade was assessed using wound-healing and transwell assays, respectively. Cell proliferation was measured using cell counting kit-8 and colony formation assays, and apoptosis was evaluated using flow cytometry. Expression of the epithelial-mesenchymal transition (EMT)-associated protein was determined by Western blot. Targets of miR-145-5p were predicated using bioinformatics analysis and verified using a dual-luciferase reporter system. Serpin family E member 1 (SERPINE1) expression in GC tissues and cells was evaluated using RT-PCR and immunohistochemical staining. The correlation between SERPINE1 expression and overall patient survival was determined using Kaplan-Meier plot analysis. The association between SERPINE1 and GC progression was also tested. A rescue experiment of SERPINE1 overexpression was conducted to verify the relationship between this protein and miR-145-5p. The mechanism by which miR-145-5p influences GC progression was further explored by assessing tumor formation in nude mice. RESULTS: GC tissues and cells had reduced miR-145-5p expression and SERPINE1 was identified as a direct target of this miRNA. Overexpression of miR-145-5p was associated with decreased GC cell proliferation, invasion, migration, and EMT, and these effects were reversed by forcing SERPINE1 expression. Kaplan-Meier plot analysis revealed that patients with higher SERPINE1 expression had a shorter survival rate than those with lower SERPINE1 expression. Nude mouse tumorigenesis experiments confirmed that miR-145-5p targets SERPINE1 to regulate extracellular signal-regulated kinase-1/2 (ERK1/2). CONCLUSION: This study found that miR-145-5p inhibits tumor progression and is expressed in lower amounts in patients with GC. MiR-145-5p was found to affect GC cell proliferation, migration, and invasion by negatively regulating SERPINE1 levels and controlling the ERK1/2 pathway.