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1.
Life Sci ; 348: 122687, 2024 Jul 01.
Article in English | MEDLINE | ID: mdl-38718856

ABSTRACT

AIMS: Checkpoint blockade immunotherapy is a promising therapeutic modality that has revolutionized cancer treatment; however, the therapy is only effective on a fraction of patients due to the tumor environment. In tumor immunotherapy, the cGAS-STING pathway is a crucial intracellular immune response pathway. Therefore, this study aimed to develop an immunotherapy strategy based on the cGAS-STING pathway. MATERIALS AND METHODS: The physicochemical properties of the nanoparticles EM@REV@DOX were characterized by TEM, DLS, and WB. Subcutaneous LLC xenograft tumors were used to determine the biodistribution, antitumor efficacy, and immune response. Blood samples and tissues of interest were harvested for hematological analysis and H&E staining. SIGNIFICANCE: Overall, our designed nanovesicles provide a new perspective on tumor immunotherapy by ICD and cGAS-STING pathway, promoting DCs maturation, macrophage polarization, and activating T cells, offering a meaningful strategy for accelerating the clinical development of immunotherapy. KEY FINDINGS: EM@REV@DOX accumulated in the tumor site through EPR and homing targeting effect to release REV and DOX, resulting in DNA damage and finally activating the cGAS-STING pathway, thereby promoting DCs maturation, macrophage polarization, and activating T cells. Additionally, EM@REV@DOX increased the production of pro-inflammatory cytokines (e.g., TNF-α and IFN-ß). As a result, EM@REV@DOX was effective in treating tumor-bearing mice and prolonged their lifespans. When combined with αPD-L1, EM@REV@DOX significantly inhibited distant tumor growth, extended the survival of mice, and prevented long-term postoperative tumor metastasis, exhibiting great potential in antitumor immunotherapy.


Subject(s)
Immunotherapy , Membrane Proteins , Nanoparticles , Nucleotidyltransferases , Animals , Nucleotidyltransferases/metabolism , Mice , Membrane Proteins/metabolism , Immunotherapy/methods , Nanoparticles/chemistry , Humans , Signal Transduction , Doxorubicin/pharmacology , Doxorubicin/administration & dosage , Cell Line, Tumor , Mice, Inbred C57BL , Neoplasms/therapy , Neoplasms/immunology , Neoplasms/drug therapy , Neoplasms/pathology , Female , Xenograft Model Antitumor Assays , Immunogenic Cell Death/drug effects
2.
Front Cell Infect Microbiol ; 14: 1351607, 2024.
Article in English | MEDLINE | ID: mdl-38562965

ABSTRACT

Objective: Thrombocytopenia is commonly associated with infectious diseases and serves as an indicator of disease severity. However, reports on its manifestation in conjunction with Klebsiella pneumoniae liver abscess (KPLA) are scarce. The present study sought to elucidate the correlation between thrombocytopenia and KPLA severity and delve into the etiological factors contributing to the incidence of thrombocytopenia. Materials and methods: A retrospective analysis of the clinical data from patients with KPLA admitted between June 2012 and June 2023 was performed. Baseline characteristics, biochemical assessments, therapeutic interventions, complications, and clinical outcomes were compared between patients with and without thrombocytopenia. To investigate the potential etiologies underlying thrombocytopenia, the association between platelet count reduction and thrombophlebitis was examined, with a particular focus on platelet consumption. Furthermore, bone marrow aspiration results were evaluated to assess platelet production anomalies. Results: A total of 361 KPLA patients were included in the study, among whom 60 (17%) had concurrent thrombocytopenia. Those in the thrombocytopenia group exhibited significantly higher rates of thrombophlebitis (p = 0.042), extrahepatic metastatic infection (p = 0.01), septic shock (p = 0.024), admissions to the intensive care unit (p = 0.002), and in-hospital mortality (p = 0.045). Multivariate analysis revealed that thrombocytopenia (odds ratio, 2.125; 95% confidence interval, 1.114-4.056; p = 0.022) was independently associated with thrombophlebitis. Among the thrombocytopenic patients, eight underwent bone marrow aspiration, and six (75%) had impaired medullar platelet production. After treatment, 88.6% of thrombocytopenic patients (n = 47) demonstrated recovery in their platelet counts with a median recovery time of five days (interquartile range, 3-6 days). Conclusions: Thrombocytopenia in patients with KPLA is indicative of increased disease severity. The underlying etiologies for thrombocytopenia may include impaired platelet production within the bone marrow and augmented peripheral platelet consumption as evidenced by the presence of thrombophlebitis.


Subject(s)
Klebsiella Infections , Liver Abscess , Thrombocytopenia , Thrombophlebitis , Humans , Retrospective Studies , Klebsiella pneumoniae , Klebsiella Infections/complications , Klebsiella Infections/epidemiology , Liver Abscess/epidemiology , Thrombocytopenia/complications , Patient Acuity , Thrombophlebitis/complications
3.
ACS Omega ; 9(13): 15590-15602, 2024 Apr 02.
Article in English | MEDLINE | ID: mdl-38585091

ABSTRACT

Anaplastic thyroid cancer (ATC) is one of the most lethal malignant tumors for which there is no effective treatment. There are an increasing number of studies on herbal medicine for treating malignant tumors, and the classic botanical medicine Digitalis and its active ingredients for treating heart failure and arrhythmias have been revealed to have significant antitumor efficacy against a wide range of malignant tumors. However, the main components of Digitalis and the molecular mechanisms of its anti-ATC effects have not been extensively studied. Here, we screened the main components and core targets of Digitalis and verified the relationship between the active components and targets through network pharmacology, molecular docking, and experimental validation. These experiments showed that the active ingredients of Digitalis inhibit ATC cell activity and lead to ATC cell death through the apoptotic pathway.

4.
Cell Death Dis ; 15(2): 125, 2024 02 09.
Article in English | MEDLINE | ID: mdl-38336839

ABSTRACT

Anaplastic thyroid carcinoma (ATC) has a 100% disease-specific mortality rate. The JAK1/2-STAT3 pathway presents a promising target for treating hematologic and solid tumors. However, it is unknown whether the JAK1/2-STAT3 pathway is activated in ATC, and the anti-cancer effects and the mechanism of action of its inhibitor, ruxolitinib (Ruxo, a clinical JAK1/2 inhibitor), remain elusive. Our data indicated that the JAK1/2-STAT3 signaling pathway is significantly upregulated in ATC tumor tissues than in normal thyroid and papillary thyroid cancer tissues. Apoptosis and GSDME-pyroptosis were observed in ATC cells following the in vitro and in vivo administration of Ruxo. Mechanistically, Ruxo suppresses the phosphorylation of STAT3, resulting in the repression of DRP1 transactivation and causing mitochondrial fission deficiency. This deficiency is essential for activating caspase 9/3-dependent apoptosis and GSDME-mediated pyroptosis within ATC cells. In conclusion, our findings indicate DRP1 is directly regulated and transactivated by STAT3; this exhibits a novel and crucial aspect of JAK1/2-STAT3 on the regulation of mitochondrial dynamics. In ATC, the transcriptional inhibition of DRP1 by Ruxo hampered mitochondrial division and triggered apoptosis and GSDME-pyroptosis through caspase 9/3-dependent mechanisms. These results provide compelling evidence for the potential therapeutic effectiveness of Ruxo in treating ATC.


Subject(s)
Nitriles , Pyrazoles , Pyrimidines , Thyroid Carcinoma, Anaplastic , Thyroid Neoplasms , Humans , Thyroid Carcinoma, Anaplastic/drug therapy , Thyroid Carcinoma, Anaplastic/genetics , Thyroid Carcinoma, Anaplastic/metabolism , Thyroid Neoplasms/drug therapy , Thyroid Neoplasms/genetics , Thyroid Neoplasms/metabolism , Mitochondrial Dynamics , Pyroptosis , Caspase 9/metabolism , Cell Proliferation , Cell Line, Tumor , Apoptosis
5.
Stud Health Technol Inform ; 310: 760-764, 2024 Jan 25.
Article in English | MEDLINE | ID: mdl-38269911

ABSTRACT

The COVID-19 pandemic has highlighted the dire necessity to improve public health literacy for societal resilience. YouTube provides a vast repository of user-generated health information in a multi-media-rich format which may be easier for the public to understand and use if major concerns about content quality and accuracy are addressed. This study develops an automated solution to identify, retrieve and shortlist medically relevant and understandable YouTube videos that domain experts can subsequently review and recommend for disseminating and educating the public on the COVID-19 pandemic and similar public health outbreaks. Our approach leverages domain knowledge from human experts and machine learning and natural language processing methods to provide a scalable, replicable, and generalizable approach that can also be applied to enhance the management of many health conditions.


Subject(s)
COVID-19 , Health Literacy , Social Media , Humans , Public Health , Pandemics , Machine Learning
6.
Molecules ; 29(1)2024 Jan 03.
Article in English | MEDLINE | ID: mdl-38202835

ABSTRACT

A method utilizing high-performance liquid chromatography-fluorescence detection (HPLC-FLD) has been developed and refined for the simultaneous detection of florfenicol (FF) and its metabolite florfenicol amine (FFA) along with three fluoroquinolone (ciprofloxacin (CIP), enrofloxacin (ENR), and sarafloxacin (SAR)) residues in different parts of eggs (whole egg, egg yolk, and egg albumen). The QuEChERS ("Quick, easy, cheap, effective, rugged, and safe") procedure utilized 0.1 M disodium EDTA solution, water, and acetonitrile as extractants; sodium sulfate, sodium chloride, and trisodium citrate as dehydrating salts; and N-propylethylenediamine and C18 as adsorbents. A dual-channel FLD method was utilized to analyze the target compounds using an XBridge BEH C18 chromatographic column (4.6 mm × 150 mm, 5 µm). The mobile phase was employed isocratically using a solution of 0.01 M sodium dihydrogen phosphate, 0.005 M sodium dodecyl sulfate, and 0.1% triethylamine (pH 4.8) in combination with acetonitrile at a ratio of 65:35 (V/V). The limits of detection (LOD) and quantification (LOQ) of the analytes ranged from 0.03 to 1.5 µg/kg and from 0.1 to 5.0 µg/kg, respectively. The recoveries of the analytes in the blank egg samples ranged from 71.9% to 94.8% when reference standard concentrations of the LOQ, half of the maximum residual limit (MRL), MRL, and twice the MRL were added. The parameters of the presented protocol were validated and subsequently applied to the analysis of real samples, demonstrating the applicability and reliability of the method.


Subject(s)
Fluoroquinolones , Thiamphenicol/analogs & derivatives , Chromatography, High Pressure Liquid , Reproducibility of Results , Acetonitriles
7.
Plant Physiol Biochem ; 207: 108337, 2024 Feb.
Article in English | MEDLINE | ID: mdl-38199027

ABSTRACT

Seashore paspalum (Paspalum vaginatum O. Swartz) is an important warm-season turfgrass species with extreme salt tolerance, but investigations on its salt tolerance mechanism are limited. A salt induced PvWAK3 from halophyte seashore paspalum was identified in this study. Overexpression of PvWAK3 in Arabidopsis led to increased salt tolerance. Transgenic plants had higher levels of seed germination rate, root length, number of lateral roots, shoot weight, survival rate, Fv/Fm, ETR, and NPQ compared with the wild type (WT) under salt stress. Na+ content was increased and K+ content was decreased after salinity treatment, with lower levels of Na+ and Na+/K+ ratio but higher level of K+ in transgenic plants than in WT under salt stress. The improved maintenance of Na+ and K+ homeostasis was associated with the higher transcript levels of K + -Uptake Permease 4 (KUP4), Potassium Transport 2/3 (AKT2), Salt Overly Sensitive 1 (SOS1) and High-Affinity K + Transporter 5 (HAK5) in transgenic plants compared with WT. Superoxide dismutase (SOD), catalase (CAT) and ascorbate-peroxidase (APX) activities, proline concentration, and P5CS1 transcript were increased after salinity treatment, with higher levels in transgenic lines compared with WT, which led to reduced accumulation of O2·- and H2O2 under salt stress. It is suggested that PvWAK3 regulates salt tolerance positively, which is associated with promoted Na+ and K+ homeostasis, activated antioxidant enzymes, and proline biosynthesis under salt stress.


Subject(s)
Arabidopsis Proteins , Arabidopsis , Paspalum , Salt Tolerance/genetics , Arabidopsis/genetics , Reactive Oxygen Species , Hydrogen Peroxide , Plants, Genetically Modified/physiology , Membrane Transport Proteins , Homeostasis , Proline , Gene Expression Regulation, Plant , Potassium Channels
8.
JMIR Form Res ; 7: e47903, 2023 Oct 13.
Article in English | MEDLINE | ID: mdl-37831497

ABSTRACT

BACKGROUND: Mental health problems are common among men who have sex with men (MSM) living with HIV and may negatively affect medication adherence. Psychosocial interventions designed to address these urgent needs are scarce in China. Incorporating behavioral health theories into intervention development strengthens the effectiveness of these interventions. The absence of a robust theoretical basis for interventions may also present challenges to identify active intervention ingredients. OBJECTIVE: This study aims to systematically describe the development of a mobile health-based intervention for MSM recently diagnosed with HIV in China, including the theoretical basis for the content and the considerations for its technological delivery. METHODS: We used intervention mapping (IM) to guide overall intervention development, a behavioral intervention technology model for technological delivery design, and a human-centered design and cultural adaptation model for intervention tailoring throughout all steps of IM. RESULTS: The dialectical behavior therapy (DBT)-informed intervention, Turning to Sunshine, comprised 3 components: app-based individual skills learning, group-based skills training, and on-demand phone coaching. The theoretical basis for the intervention content is based on the DBT model of emotions, which fits our conceptualization of the intervention user's mental health needs. The intervention aims to help MSM recently diagnosed with HIV (1) survive moments of high emotional intensity and strong action urges, (2) change emotional expression to regulate emotions, and (3) reduce emotional vulnerability, as well as (4) augment community resources for mental health services. Technological delivery considerations included rationale of the medium, complexity, and esthetics of information delivery; data logs; data visualization; notifications; and passive data collection. CONCLUSIONS: This study laid out the steps for the development of a DBT-informed mobile health intervention that integrated app-based individual learning, group-based skills training, and phone coaching. This intervention, Turning to Sunshine, aims to improve mental health outcomes for MSM newly diagnosed with HIV in China. The IM framework informed by human-centered design principles and cultural adaptation considerations offered a systematic approach to develop the current intervention and tailor it to the target intervention users. The behavioral intervention technology model facilitated the translation of behavioral intervention strategies into technological delivery components. The systematic development and reporting of the current intervention can serve as a guide for similar intervention studies. The content of the current intervention could be adapted for a broader population with similar emotional struggles to improve their mental health outcomes.

9.
Am J Sports Med ; 51(11): 2842-2849, 2023 09.
Article in English | MEDLINE | ID: mdl-37551676

ABSTRACT

BACKGROUND: Microfracture at the rotator cuff insertion is an established surgical marrow-stimulation technique for enhancing rotator cuff healing. However, the effect of lateralized or medialized microfracture on the insertion is unknown. PURPOSE: To compare the biomechanical and histologic effects of microfracture at 3 different regions for rotator cuff repair in a rat model. STUDY DESIGN: Controlled laboratory study. METHODS: A total of 72 Sprague-Dawley rats with bilateral supraspinatus tendon insertion detachment were allocated into 4 groups with 4 different interventions: no microfracture at the humeral head as a control group (Con), traditional microfracture at the footprint area (MFA), and medialized microfracture to the footprint area (MMFA) on the articular surface of the humerus or lateralized microfracture to the footprint area at the greater tuberosity (LMFA). All underwent immediate repair. Tendon-to-bone healing was assessed by biomechanical and histologic tests 4 and 8 weeks postoperation. RESULTS: At 4 weeks, the LMFA group showed a significantly superior failure load compared with the other groups (all P < .05). The LMFA and MFA groups showed significantly superior stiffness compared with the Con and MMFA groups (all P < .01). At 8 weeks, superior failure load and stiffness were observed in the LMFA group compared with the control group (all P < .05). Histologic examination revealed that the LMFA group had superior collagen composition and tendon-to-bone maturation at the interface at 4 and 8 weeks compared with the Con group (all P < .05). CONCLUSION: Lateralized microfracture at the greater tuberosity improved the histologic quality of repair tissue and biomechanical strength at the tendon-to-bone insertion after rotator cuff repair in a rat model. CLINICAL RELEVANCE: Microfracture lateral to the footprint area might be a better way to enhance rotator cuff healing clinically.


Subject(s)
Rotator Cuff Injuries , Rotator Cuff , Rats , Animals , Rotator Cuff/surgery , Rotator Cuff/physiology , Rotator Cuff Injuries/surgery , Wound Healing/physiology , Rats, Sprague-Dawley , Biomechanical Phenomena , Tendons/surgery , Humerus/surgery , Humeral Head
10.
Microb Pathog ; 183: 106313, 2023 Oct.
Article in English | MEDLINE | ID: mdl-37625661

ABSTRACT

During 2021, 403 ticks including Haemaphysalis qinghaiensis, Ixodes ovatus, Ixodes acutitarsus, and Rhipicephalus microplus were collected from three sites (590, 310, and 576 km away from each other) in Sichuan Province, China. A total of nine Rickettsiales species were identified in them, including three Rickettsia spp., five Anaplasma spp., and one Ehrlichia sp. Anaplasma ovis and a novel Rickettsia sp. named "Candidatus Rickettsia liangshanensis" were characterized in I. ovatus ticks from Liangshan, with positive rates of 11.11% and 45.56%, respectively. Anaplasma capra (13.33%) and Anaplasma bovis (15.33%) were detected in H. qinghaiensis ticks from Maerkang. Phylogenetic analysis based on 16S rRNA, gltA, and groEL gene sequences indicated that the A. bovis strains were divided into two groups. Additionally, a novel Ehrlichia species named "Candidatus Ehrlichia maerkangensis" was identified. It is closely related to "Candidatus Ehrlichia zunyiensis" which was previously reported in Berylmys bowersi rats from Zunyi City, Southwest China. In R. microplus from Mianyang, "Candidatus Rickettsia jingxinensis" was detected with a high prevalence (92.99%). Notably, a variant of R. raoultii was identified in I. acutitarsus (33.33%). This may be the first Rickettsiales bacterium reported in I. acutitarsus. Our results reveal the remarkable biodiversity of Rickettsiales in this area. Some of these bacteria are human pathogens, indicating the potential exposure risk to local people.


Subject(s)
Ixodes , Rickettsiales , Humans , Animals , Rats , Phylogeny , RNA, Ribosomal, 16S/genetics , Ehrlichia/genetics , China
11.
Micromachines (Basel) ; 14(7)2023 Jul 15.
Article in English | MEDLINE | ID: mdl-37512737

ABSTRACT

Elliptical vibration-assisted cutting (EVAC), one of the advanced micromachining methods, enables results not possible with traditional ultra-precision machining. It is considered to be one of the most viable options for manufacturing micro/nanostructured surfaces. However, it is difficult to control the elliptical locus with different tilt angles; therefore, previous studies have primarily focused on fixed locus and investigated the effects of the amplitude and frequency on machining performance. In addition, tilt angle is an important factor affecting the characteristics of EVAC. To maximize the cutting performance of EVAC, the cutting characteristics of EVAC with variations in tilt angle of elliptical locus are investigated. The mathematical model of elliptical trajectory based on different tilt angles is established via geometric analysis. The effects of the different tilt angle (0-180°) on cutting forces, chip formation, defect generation and surface roughness are observed and theoretically analyzed in microgroove experiments. The experimental results show that the tilt angle has a significant effect on the cutting force, chip formation, defects and surface roughness. The best cutting performance can be obtained at the tilt angle of 30°, while the worst is recorded at 90°. The results can provide a valuable reference for further comprehensive studies to maximize the cutting performance of EVAC.

12.
Front Microbiol ; 14: 1211835, 2023.
Article in English | MEDLINE | ID: mdl-37426007

ABSTRACT

Introduction: Pyogenic liver abscess (PLA) patients combined with diabetes mellitus (DM) tend to have more severe clinical manifestations than without DM. The mechanism responsible for this phenomenon is not entirely clear. The current study therefore aimed to comprehensively analyze the microbiome composition and metabolome in pus from PLA patients with and without DM, to determine the potential reasons for these differences. Methods: Clinical data from 290 PLA patients were collected retrospectively. We analyzed the pus microbiota using 16S rDNA sequencing in 62 PLA patients. In addition, the pus metabolomes of 38 pus samples were characterized by untargeted metabolomics analysis. Correlation analyses of microbiota, metabolites and laboratory findings were performed to identify significant associations. Results: PLA patients with DM had more severe clinical manifestations than PLA patients without DM. There were 17 discriminating genera between the two groups at the genus level, among which Klebsiella was the most discriminating taxa. The ABC transporters was the most significant differential metabolic pathway predicted by PICRUSt2. Untargeted metabolomics analysis showed that concentrations of various metabolites were significantly different between the two groups and seven metabolites were enriched in the ABC transporters pathway. Phosphoric acid, taurine, and orthophosphate in the ABC transporters pathway were negatively correlated with the relative abundance of Klebsiella and the blood glucose level. Discussion: The results showed that the relative abundance of Klebsiella in the pus cavity of PLA patients with DM was higher than those without DM, accompanied by changes of various metabolites and metabolic pathways, which may be associated with more severe clinical manifestations.

13.
Molecules ; 28(9)2023 May 04.
Article in English | MEDLINE | ID: mdl-37175285

ABSTRACT

A novel precolumn derivatization-GC-MS/MS method was developed for the determination of decoquinate residues in chicken tissues (muscle, liver, and kidney). The samples were extracted and purified by liquid-liquid extraction combined with solid-phase extraction and derivatized with acetic anhydride and pyridine. The recovery rates for decoquinate were 77.38~89.65%, and the intra-day and inter-day RSDs were 1.63~5.74% and 2.27~8.06%, respectively. The technique parameters meet the necessities for veterinary drug residue detection in China, the US, and the EU. Finally, the method was applied to analyze tissues of 60 chickens bought from a neighborhood supermarket, and solely one sample of chicken muscle contained 15.6 µg/kg decoquinate residue.


Subject(s)
Decoquinate , Tandem Mass Spectrometry , Animals , Tandem Mass Spectrometry/methods , Gas Chromatography-Mass Spectrometry/methods , Chickens , Muscles , Chromatography, High Pressure Liquid/methods , Solid Phase Extraction
14.
J Infect Dis ; 228(8): 1127-1136, 2023 10 18.
Article in English | MEDLINE | ID: mdl-37208895

ABSTRACT

BACKGROUND: Klebsiella pneumoniae liver abscess (KPLA) with extrahepatic migratory infections is defined as invasive KPLA (IKPLA). The type VI secretion system (T6SS) is involved in the pathogenesis of KPLA. We hypothesized that T6SS plays a role in IKPLA. METHODS: 16S ribosomal RNA gene sequencing was performed on abscess samples. Polymerase chain reaction (PCR) and reverse-transcription PCR (RT-PCR) was used to validate the expression difference of T6SS hallmark genes. In vitro and in vivo experiments were performed to identify the pathogenic feature of T6SS. RESULTS: PICRUSt2 predicted that the T6SS-related genes were notably enriched in the IKPLA group. PCR detection of T6SS hallmark genes (hcp, vgrG, and icmF) showed that 197 (81.1%) were T6SS-positive strains. The T6SS-positive strain detection rate in the IKPLA group was higher than in the KPLA group (97.1% vs 78.4%; P < .05). RT-PCR showed that the hcp expression level was markedly increased in IKPLA isolates (P < .05). The T6SS-positive isolates showed higher survival against serum and neutrophil killing (all P < .05). The T6SS-positive K pneumoniae-infected mice had a shorter survival time, higher mortality, and an increased interleukin 6 expression in the liver and lungs (all P < .05). CONCLUSIONS: T6SS is an essential virulence factor for K pneumoniae and contributes to IKPLA.


Subject(s)
Klebsiella Infections , Liver Abscess , Type VI Secretion Systems , Animals , Mice , Type VI Secretion Systems/genetics , Type VI Secretion Systems/metabolism , Klebsiella pneumoniae/genetics , Klebsiella pneumoniae/metabolism , Virulence Factors/genetics , Virulence Factors/metabolism , Bacterial Proteins/genetics , Bacterial Proteins/metabolism
15.
Endocrine ; 81(3): 503-512, 2023 09.
Article in English | MEDLINE | ID: mdl-37020077

ABSTRACT

PURPOSE: Most differentiated thyroid cancer (DTC) patients have a good prognosis after surgery, but radioiodine refractory differentiated thyroid cancer (RAIR-DTC) patients have a significantly reduced 5-year survival rate (<60%) and a significantly increased recurrence rate (>30%). This study aimed to clarify the tescalcin (TESC) role in promoting the malignant PTC progression and providing a potential target for RAIR-DTC treatment. METHODS: We analyzed TESC expression and clinicopathological characteristics using the Cancer Genome Atlas (TCGA) and performed qRT-PCR on tissue samples. TPC-1 and IHH-4 proliferation, migration, and invasion were detected after transfection with TESC-RNAi. Using Western blot (WB), several EMT-related indicators were detected. Moreover, iodine uptake of TPC-1 and IHH-4 after transfection with TESC-RNAi was detected. Finally, NIS, ERK1/2, and p-ERK1/2 levels were determined by WB. RESULTS: TESC was significantly upregulated in DTC tissues and positively correlated with BRAF V600E mutation based on data analysis from TCGA and our center. Reduced expression of TESC in both IHH-4 (BRAF V600E mutation) and TPC-1 (BRAF V600E wild type) cells significantly inhibited cell proliferation, migration, and invasion. It downregulated the EMT pathway markers Vimentin and N-cadherin, and increased E- cadherin. Moreover, TESC knockdown significantly inhibited ERK1/2 phosphorylation and decreased NIS expression in DTC cells, with a remarkably increased iodine uptake rate. CONCLUSIONS: TESC was highly expressed in DTC tissues and may have promoted metastasis through EMT and induced iodine resistance by downregulating NIS in DTC cells.


Subject(s)
Adenocarcinoma , Iodine , Thyroid Neoplasms , Humans , Iodine Radioisotopes/therapeutic use , Proto-Oncogene Proteins B-raf/genetics , Thyroid Neoplasms/genetics , Thyroid Neoplasms/radiotherapy , Thyroid Neoplasms/metabolism
16.
Food Chem ; 421: 136168, 2023 Sep 30.
Article in English | MEDLINE | ID: mdl-37099949

ABSTRACT

Antimicrobial drugs are frequently used in a combination or shuttle way to cope with coinfection of bacteria or parasites and prevent drug resistance, thus the accurate quantification of multiple drug residues in animal-derived foods is crucial to ensure food safety. Here, a simple and efficient high-performance liquid chromatography-photodiode array (HPLC-PDA) method was established for the simultaneous quantitative screening of six common residues of antiparasitic drugs, including abamectin (ABM), ivermectin (IVM), albendazole (ABZ) and the three metabolites of ABZ in beef and chicken. The LODs and LOQs for six target compounds in beef and chicken are determined to be 3.2 to 12.5 µg/kg and 9.0 to 30.0 µg/kg, respectively. The calibration curves show good linearity (R2 ≥ 0.9990) between the peak area and concentration. The recoveries from the fortified blank samples are all above 85.10%. Finally, the applicability of the HPLC-PDA method is successfully demonstrated by the real sample analysis.


Subject(s)
Albendazole , Ivermectin , Animals , Cattle , Ivermectin/analysis , Chromatography, High Pressure Liquid/methods , Chickens
17.
J Org Chem ; 88(7): 4743-4756, 2023 Apr 07.
Article in English | MEDLINE | ID: mdl-36971723

ABSTRACT

A mild and efficient coupling method concerning the reactions of gem-bromonitroalkanes with α,α-diaryl allyl alcohol trimethylsilyl ethers was reported. A cascade consisting of visible-light-induced generation of an α-nitroalkyl radical and a subsequent neophyl-type rearrangement was key to realize the coupling reactions. Structurally diverse α-aryl-γ-nitro ketones, especially those bearing a nitrocyclobutyl structure, were prepared in moderate to high yields, which could be converted into spirocyclic nitrones and imines.

18.
Org Lett ; 25(12): 2098-2102, 2023 Mar 31.
Article in English | MEDLINE | ID: mdl-36943937

ABSTRACT

3-Oxazolin-5-ones are precursors of nitrile ylides and represent valuable 1,3-dipoles for constructing cyclic imines or pyrrole compounds. Harnessing the power of photocatalysis, we accomplished a straightforward synthesis of 3-oxazolin-5-ones from redox-active esters and secondary nitro compounds. Visible light-induced nondecarboxylative coupling of a redox-active ester, nitro aldol condensation, and subsequent visible light-induced N-oxide deoxygenation were accomplished within 2 h. The reaction mechanism was supported by experimental data and DFT calculations.

19.
Food Chem ; 409: 135294, 2023 May 30.
Article in English | MEDLINE | ID: mdl-36592604

ABSTRACT

Salmonella Enteritidis easily contaminate chicken during slaughtering, processing, transportation, and sales, which seriously endangers human health. This study aimed to identify metabolite biomarkers for Salmonella Enteritidis contamination in chicken meat. UPLC-Q-Orbitrap MS untargeted metabolomics analysis identified 441 and 240 confidently metabolites in positive and negative ion mode, respectively. Thirty metabolites were defined as potential biomarkers for Salmonella enteritidis contamination in chicken meat. UPLC-QQQ-MS based targeted metabolomics was used to quantitatively analyze candidate metabolite biomarkers in Salmonella enteritidis contaminated and fresh chicken samples. A total of 10 candidate metabolite biomarkers were confirmed in the validation set, among which acetylcholine, l-Methionine, l-Proline, l-Valine, and l-Norleucine were identified as biomarkers for Salmonella Enteritidis contamination in chicken. The combined receiver operating characteristic curve analysis of the five biomarkers achieved an AUC of 0.956, indicating their high sensitivity and specificity in predicting Salmonella Enteritidis in raw chicken. In conclusion, the present study identified five metabolite biomarkers for Salmonella enteritidis in raw chicken. These results provide a potential theoretical basis for developing Salmonella Enteritidis detection methods in raw chicken.


Subject(s)
Chickens , Salmonella enteritidis , Animals , Humans , Meat
20.
Arthroscopy ; 39(5): 1141-1149, 2023 05.
Article in English | MEDLINE | ID: mdl-36528465

ABSTRACT

PURPOSE: To compare the effects of anatomical preservation (AP) and interpositional preservation (IP) of subacromial bursa tissue on tendon-to-bone healing in a rat model of rotator cuff tear. METHODS: In this study, 48 male Sprague-Dawley rats (average weight 283 g) underwent bilateral supraspinatus tendons severed by sharp incision and repaired immediately. The subacromial bursa tissues were completely removed in 16 rats, who served as the control (CON) group. The other 32 rats were randomly divided into 2 groups AP and IP between tendon and bone. Eight rats of each group were sacrificed for bilateral shoulders at 3 and 9 weeks after the operation, including 5 rats for biomechanical tests and 3 for histologic analysis. RESULTS: No significant differences in terms of biomechanical properties were observed among the groups 3 weeks after surgery. At 9 weeks, the maximum load and stiffness of the AP (32.95 ± 6.33 N, P = .029; 12.49 ± 3.17 N/mm, P < .001; respectively) and IP (33.58 ± 8.47 N, P = .015; 11.63 ± 2.84 N/mm, P = .010, respectively) groups were significantly superior to that of the CON group (26.59 ± 4.47 N; 8.42 ± 2.33 N/mm, respectively). More organized collagen and more mature tendon insertion were observed in AP and IP groups at the interface at 9 weeks, which means better tendon-to-bone healing compared with the CON group. CONCLUSIONS: The subacromial bursa plays a positive role in tendon-bone healing. Either anatomical preservation or interpositional preservation between tendon and bone can similarly facilitate the process of healing. CLINICAL RELEVANCE: Considering the additional surgical time and surgical manipulation, preserving the subacromial bursa at the anatomical position seems to be a better way to promote rotator cuff healing.


Subject(s)
Rotator Cuff Injuries , Animals , Male , Rats , Biomechanical Phenomena , Rats, Sprague-Dawley , Rotator Cuff/surgery , Rotator Cuff Injuries/surgery , Tendons/surgery , Wound Healing , Models, Animal
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