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1.
Heliyon ; 10(7): e28861, 2024 Apr 15.
Article En | MEDLINE | ID: mdl-38601595

In the context of the increasingly diversified blockchain technology, interoperability among heterogeneous blockchains has become key to further advancing this field. Existing cross-chain technologies, while facilitating data and asset exchange between different blockchains to some extent, have exposed issues such as insufficient security, low efficiency, and inconsistent standards. Consequently, these issues give rise to significant obstacles in terms of both scalability and seamless communication among blockchains within a multi-chain framework. To address this, this paper proposes an efficient method for cross-chain interaction in a multi-chain environment. Building upon the traditional sidechain model, this method employs smart contracts and hash time-locked contracts (HTLCs) to design a cross-chain interaction scheme. This approach decentralizes the execution of locking, verifying, and unlocking stages in cross-chain transactions, effectively avoiding centralization risks associated with third-party entities in the process. It also greatly enhances the efficiency of fund transfers between the main chain and sidechains, while ensuring the security of cross-chain transactions to some extent. Additionally, this paper innovatively proposes a cross-chain data interaction strategy. Through smart contracts on the main chain, data from sidechains can be uploaded, verified, and stored on the main chain, achieving convenient and efficient cross-chain data sharing. The contribution of this paper is the development of a decentralized protocol that coordinates the execution of cross-chain interactions without the need to trust external parties, thereby reducing the risk of centralization and enhancing security. Experimental results validate the effectiveness of our solution in increasing transaction security and efficiency, with significant improvements over existing models. Our experiments emphasize the system's ability to handle a variety of transaction scenarios with improved throughput and reduced latency, highlighting the practical applicability and scalability of our approach.

2.
Gut Liver ; 2024 Apr 16.
Article En | MEDLINE | ID: mdl-38623059

Background/Aims: : Ulcerative colitis (UC) is an incurable, relapsing-remitting inflammatory disease that increases steadily. Mucosal healing has become the primary therapeutic objective for UC. Nevertheless, endoscopic assessments are invasive, expensive, time-consuming, and inconvenient. Therefore, it is crucial to develop a noninvasive predictive model to monitor endoscopic activity in patients with UC. Methods: : Clinical data of 198 adult patients with UC were collected from January 2016 to August 2022 at Huadong Hospital, China. Results: : Patients with UC were randomly divided into the training cohort (70%, n=138) and the validation cohort (30%, n=60). The receiver operating characteristic curve value for the training group was 0.858 (95% confidence interval [CI], 0.781 to 0.936), whereas it was 0.845 (95% CI, 0.731 to 0.960) for the validation group. The calibration curve employed the Hosmer-Lemeshow test (p>0.05) to demonstrate the consistency between the predicted and the actual probabilities in the nomogram of these two groups. The decision curve analysis validated that the nomogram had clinical usefulness. Conclusions: : The nomogram, which incorporated activated partial thromboplastin time, fecal occult blood test, ß2-globulin level, and fibrinogen degradation products, served as a prospective tool for evaluating UC activity in clinical practices.

3.
Cell Signal ; 119: 111184, 2024 Jul.
Article En | MEDLINE | ID: mdl-38640982

Estrogen receptor alpha (ERα) is expressed in approximately 70% of breast cancer cases and determines the sensitivity and effectiveness of endocrine therapy. 6-phosphofructo-2-kinase/fructose-2, 6-biphosphatase3 (PFKFB3) is a glycolytic enzyme that is highly expressed in a great many human tumors, and recent studies have shown that it plays a significant role in improving drug sensitivity. However, the role of PFKFB3 in regulating ERα expression and the underlying mechanism remains unclear. Here, we find by using immunohistochemistry (IHC) that PFKFB3 is elevated in ER-positive breast cancer and high expression of PFKFB3 resulted in a worse prognosis. In vitro and in vivo experiments verify that PFKFB3 promotes ER-positive breast cancer cell proliferation. The overexpression of PFKFB3 promotes the estrogen-independent ER-positive breast cancer growth. In an estrogen-free condition, RNA-sequencing data from MCF7 cells treated with siPFKFB3 showed enrichment of the estrogen signaling pathway, and a luciferase assay demonstrated that knockdown of PFKFB3 inhibited the ERα transcriptional activity. Mechanistically, down-regulation of PFKFB3 promotes STUB1 binding to ERα, which accelerates ERα degradation by K48-based ubiquitin linkage. Finally, growth of ER-positive breast cancer cells in vivo was more potently inhibited by fulvestrant combined with the PFKFB3 inhibitor PFK158 than for each drug alone. In conclusion, these data suggest that PFKFB3 is identified as an adverse prognosis factor for ER-positive breast cancer and plays a previously unrecognized role in the regulation of ERα stability and activity. Our results further explores an effective approach to improve fulvestrant sensitivity through the early combination with a PFKFB3 inhibitor.


Breast Neoplasms , Estrogen Receptor alpha , Fulvestrant , Phosphofructokinase-2 , Humans , Phosphofructokinase-2/metabolism , Phosphofructokinase-2/genetics , Estrogen Receptor alpha/metabolism , Breast Neoplasms/metabolism , Breast Neoplasms/pathology , Breast Neoplasms/drug therapy , Breast Neoplasms/genetics , Female , Fulvestrant/pharmacology , Animals , Protein Stability/drug effects , Mice , MCF-7 Cells , Cell Proliferation/drug effects , Mice, Nude , Carcinogenesis/metabolism , Carcinogenesis/drug effects , Gene Expression Regulation, Neoplastic/drug effects , Antineoplastic Agents, Hormonal/pharmacology , Cell Line, Tumor
5.
EJNMMI Res ; 14(1): 14, 2024 Feb 06.
Article En | MEDLINE | ID: mdl-38319452

BACKGROUND: Previous studies have demonstrated that delayed [68 Ga]Ga-PSMA PET/CT imaging improves lesion detection compared to early [68 Ga]Ga-PSMA PET/CT in patients with prostate cancer. However, the sole use of delayed [68 Ga]Ga-PSMA PET/CT has been limited due to the insufficient number of photons obtained with standard PET/CT scanners. The combination of early and delayed [68 Ga]Ga-PSMA standard PET/CT may be considered, and it is challenging to incorporate into a high-demand clinical setting. Long field-of-view (LFOV) PET/CT scanners have higher sensitivity compared to standard PET/CT. However, it remains unknown whether the image quality of solitary delayed [68 Ga]Ga-PSMA LFOV PET/CT imaging is adequate to satisfy clinical diagnostic requirements. Therefore, the purpose of this study was to evaluate the image quality of delayed [68 Ga]Ga-PSMA LFOV PET/CT and examine the feasibility of utilizing delayed [68 Ga]Ga-PSMA LFOV PET/CT imaging alone in patients with prostate cancer. METHODS: The study sample consisted of 56 prostate cancer patients who underwent [68 Ga]Ga-PSMA-11 LFOV PET/CT scanning between December 2020 and July 2021. All patients were subjected to early LFOV PET/CT imaging at 1-h post-injection as well as delayed LFOV PET/CT imaging at 3-h post-injection using [68 Ga]Ga-PSMA-11. The image quality and diagnostic efficiency of solitary delayed [68 Ga]Ga-PSMA-11 LFOV PET/CT imaging was analyzed. RESULTS: The results showed that delayed [68 Ga]Ga-PSMA-11 LFOV PET/CT yielded satisfactory image quality that fulfilled clinical diagnostic benchmarks. Compared to early imaging, delayed [68 Ga]Ga-PSMA-11 LFOV PET/CT demonstrated heightened lesion SUVmax values (11.0 [2.3-193.6] vs. 7.0 [2.0-124.3], P < 0.001) and superior tumor-to-background ratios (3.3 [0.5-62.2] vs. 1.7 [0.3-30.7], P < 0.001). Additionally, delayed [68 Ga]Ga-PSMA-11 LFOV PET/CT detected supplementary lesions in 14 patients (25%) compared to early imaging, resulting in modifications to disease staging and management plans. CONCLUSIONS: In summary, the findings indicate that the image quality of delayed [68 Ga]Ga-PSMA-11 LFOV PET/CT is satisfactory for meeting clinical diagnostic prerequisites. The use of solitary delayed [68 Ga]Ga-PSMA-11 LFOV PET/CT imaging in prostate cancer simplifies the examination protocol and improves patient compliance, compared to [68 Ga]Ga-PSMA-11 standard PET/CT which necessitates both early and delayed imaging.

7.
Org Lett ; 26(2): 565-570, 2024 Jan 19.
Article En | MEDLINE | ID: mdl-38175988

An aerobic oxidative cleavage of 1,3-diketones under visible light irradiation using an organic dye as a photocatalyst is disclosed. The newly developed reaction provides practical access to 1,2-diketones and (Z)-1,4-enediones in moderate to good yields with absolute regio- and stereoselectivity. Mechanistic studies of the reaction suggest that tetraketone intermediates might undergo a photocatalytic energy transfer from the excited photocatalyst to form biradical-like (n,π*) states of ketones.

8.
BMC Pulm Med ; 24(1): 1, 2024 Jan 02.
Article En | MEDLINE | ID: mdl-38166904

BACKGROUND: Lung cancer (LC) is one of the most devastating diseases worldwide, there is growing studies confirm the role of impaired lung function in LC susceptibility. Moreover, gut microbiota dysbiosis is associated with LC severity. Whether alterations in gut microbiota and metabolites are associated with long-term lung dysfunction in LC patients remain unclear. Our study aimed to analyze the risk factors in LC patients with impaired pulmonary function based on the characteristics of the gut microbiome and metabolites. METHODS: Fecal samples from 55 LC patients and 28 benign pulmonary nodules patients were collected. Pulmonary ventilation function was graded according to the American Thoracic Society/ European Respiratory Society (ATS/ERS) method. LC patients were divided into 3 groups, including 20 patients with normal lung ventilation, 23 patients with mild pulmonary ventilation dysfunction and 12 patients with moderate or above pulmonary ventilation dysfunction. The fecal samples were analyzed using 16 S rRNA gene amplicon sequencing and metabolomics. RESULTS: The gut microbiome composition between LC patients and benign pulmonary nodules patients presented clearly differences based on Partial Least Squares Discriminant Analysis (PLS-DA). Pulmonary ventilation function was positively correlated with LC tumor stage, the richness and diversity of the gut microbiota in LC patients with moderate or above pulmonary ventilation dysfunction increased significantly, characterized by increased abundance of Subdoligranulum and Romboutsia. The metabolomics analysis revealed 69 differential metabolites, which were mainly enriched in beta-Alanine metabolism, styrene degradation and pyrimidine metabolism pathway. The area under the curve (AUC) combining the gut microbiome and metabolites was 90% (95% CI: 79-100%), indicating that the two species and four metabolites might regarded as biomarkers to assess the prediction of LC patients with impaired pulmonary function. CONCLUSIONS: Our results showed that microbiome and metabolomics analyses provide important candidate to be used as clinically diagnostic biomarkers and therapeutic targets related to lung cancer with impaired pulmonary function.


Gastrointestinal Microbiome , Lung Neoplasms , Multiple Pulmonary Nodules , Humans , Metabolomics/methods , Feces , Biomarkers , RNA, Ribosomal, 16S/genetics
9.
Nucl Med Commun ; 45(3): 244-252, 2024 Mar 01.
Article En | MEDLINE | ID: mdl-38165165

PURPOSE: A small number of patients diagnosed with multiple myeloma (MM) by bone marrow aspiration reported as being disease-free on 18 F-FDG PET/CT. We aim to evaluate the diagnostic value of radiomics approach in patients with MM who were negative by visual analysis. MATERIALS AND METHODS: Thirty-three patients judged negative by visual analysis were assigned to the MM group. Contemporaneous 31 disease-free patients served as the control group. 70% of the whole data set was used as training set (23 from MM group and 22 from control group) and 30% as testing set (10 from MM group and 9 from control group). Axial skeleton volumes were automatically segmented and high-dimensional imaging features were extracted from PET and CT. The unsupervised machine learning method was used to filter and reduce the dimensions of the extracted features. Random forest was used to construct the prediction model and then validated with 10-fold cross-validation and evaluated on the independent testing set. RESULTS: One thousand seven hundred two quantitative features were extracted from PET and CT. Of those, three first-order and one high-order imaging features were uncorrelated. With the cross-validation on the training group, the sensitivity, specificity, accuracy and area under the curve of random forest were 0.850, 0.792, 0.818 and 0.894, respectively. On the independent testing set, the accuracy of the model was 0.850 and the area under the curve was 0.909. CONCLUSION: Radiomic analysis based on 18 F-FDG PET/CT using machine learning model provides a quantitative, objective and efficient mechanism for diagnosing patients with MM who were negative by visual analysis.


Fluorodeoxyglucose F18 , Multiple Myeloma , Humans , Positron Emission Tomography Computed Tomography/methods , Radiopharmaceuticals , Radiomics
10.
Clin Nucl Med ; 49(2): 188-190, 2024 Feb 01.
Article En | MEDLINE | ID: mdl-37976436

ABSTRACT: A 68-year-old man with chest tightness underwent cardiac blood perfusion imaging on total-body 13 N-NH 3 PET/CT. Incidentally, mildly increased 13 N-NH 3 activity was observed in the left side of the body of the tongue. Pathological diagnosis proved to be mucosal squamous cell carcinoma.


Carcinoma, Squamous Cell , Tongue Neoplasms , Male , Humans , Aged , Positron Emission Tomography Computed Tomography , Tongue Neoplasms/diagnostic imaging , Incidental Findings , Carcinoma, Squamous Cell/diagnostic imaging , Carcinoma, Squamous Cell/pathology
11.
Clin Case Rep ; 11(11): e8117, 2023 Nov.
Article En | MEDLINE | ID: mdl-37927984

Adult's Epstein-Barr virus-associated hemophagocytic lymphohistiocytosis is a rare and life-threatening condition characterized by atypical initial symptoms and rapid disease progression. To facilitate early diagnosis and prompt treatment, it is imperative to implement early multidisciplinary intervention and prioritize pathogen detection, as these measures significantly contribute to enhancing patient prognosis.

12.
World J Gastrointest Surg ; 15(9): 1901-1909, 2023 Sep 27.
Article En | MEDLINE | ID: mdl-37901736

BACKGROUND: Pancreatoduodenectomy (PD) is the most effective surgical procedure to remove a pancreatic tumor, but the prevalent postoperative complications, including postoperative pancreatic fistula (POPF), can be life-threatening. Thus far, there is no consensus about the prevention of POPF. AIM: To determine possible prognostic factors and investigate the clinical effects of modified duct-to-mucosa pancreaticojejunostomy (PJ) on POPF development. METHODS: We retrospectively collected and analyzed the data of 215 patients who underwent PD between January 2017 and February 2022 in our surgery center. The risk factors for POPF were analyzed by univariate analysis and multivariate logistic regression analysis. Then, we stratified patients by anastomotic technique (end-to-side invagination PJ vs modified duct-to-mucosa PJ) to conduct a comparative study. RESULTS: A total of 108 patients received traditional end-to-side invagination PJ, and 107 received modified duct-to-mucosa PJ. Overall, 58.6% of patients had various complications, and 0.9% of patients died after PD. Univariate and multivariate logistic regression analyses showed that anastomotic approaches, main pancreatic duct (MPD) diameter and pancreatic texture were significantly associated with the incidence of POPF. Additionally, the POPF incidence and operation time in patients receiving modified duct-to-mucosa PJ were 11.2% and 283.4 min, respectively, which were significantly lower than those in patients receiving traditional end-to-side invagination PJ (27.8% and 333.2 minutes). CONCLUSION: Anastomotic approach, MPD diameter and pancreatic texture are major risk factors for POPF development. Compared with traditional end-to-side invagination PJ, modified duct-to-mucosa PJ is a simpler and more efficient technique that results in a lower incidence of POPF. Further studies are needed to validate our findings and explore the clinical applicability of our technique for laparoscopic and robotic PD.

13.
Int J Ophthalmol ; 16(10): 1595-1600, 2023.
Article En | MEDLINE | ID: mdl-37854381

AIM: To report a novel splicing mutation in the RPGR gene (encoding retinitis pigmentosa GTPase regulator) in a three-generation Chinese family with X-linked retinitis pigmentosa (XLRP). METHODS: Comprehensive ophthalmic examinations including best corrected visual acuity, fundus photography, vision field, and pattern-visual evoked potential were performed to identify the disease phenotype of a six-year-old boy from the family (proband). Genomic DNA was extracted from peripheral blood of five available members of the pedigree. Whole-exome sequencing (WES), Sanger sequencing, and pSPL3-based exon trapping were used to investigate the aberrant splicing of RPGR. Human Splice Finder v3.1 and NNSPLICE v0.9 were used for in silico prediction of splice site variants. RESULTS: The proband was diagnosed as having retinitis pigmentosa (RP). He had severe symptoms with early onset. A novel splicing mutation, c.619+1G>C in RPGR was identified in the proband by WES and in four family members by Sanger sequencing. Minigene splicing assays verified that c.619+1G>C in RPGR would result in the formation of a damaging alternative transcript in which the last 91 bp of exon 6 were skipped, leading to the subsequent deletion of 623 correct amino acids (c.529_619del p.Val177Glnfs*16). CONCLUSION: We identify a novel splice donor site mutation causing aberrant splicing of RPGR. Our findings add to the catalog of pathological mutations of RPGR and further emphasize the functional importance of RPGR in RP pathogenesis and its complex clinical phenotypes.

14.
Front Pharmacol ; 14: 1230822, 2023.
Article En | MEDLINE | ID: mdl-37601042

Wnt signaling plays an important role in regulating the biological behavior of cancers, and many drugs targeting this signaling have been developed. Recently, a series of research have revealed that Wnt signaling could regulate DNA damage response (DDR) which is crucial for maintaining the genomic integrity in cells and closely related to cancer genome instability. Many drugs have been developed to target DNA damage response in cancers. Notably, different components of the Wnt and DDR pathways are involved in crosstalk, forming a complex regulatory network and providing new opportunities for cancer therapy. Here, we provide a brief overview of Wnt signaling and DDR in the field of cancer research and review the interactions between these two pathways. Finally, we also discuss the possibility of therapeutic agents targeting Wnt and DDR as potential cancer treatment strategies.

15.
Eur J Nucl Med Mol Imaging ; 50(13): 3961-3969, 2023 11.
Article En | MEDLINE | ID: mdl-37535107

BACKGROUND: [68Ga]Ga-FAPI-04 (gallium-68-labeled fibroblast activation protein inhibitor-04) PET/CT has been widely used in diagnosing malignant tumors. Total-body PET/CT has a long axial field of view and provides higher sensitivity compared to traditional PET/CT. However, whether the reduced injected dose of [68Ga]Ga-FAPI-04 could obtain qualified imaging has not been evaluated. PURPOSE: To explore the effect of half-dose [68Ga]Ga-FAPI-04 on image quality and tumor detectability in oncology patients. METHODS: A total of twenty-seven patients with tumors or clinically suspected tumors were included, and all patients were scanned with total-body PET/CT after an injected dose of 0.84-1.14 MBq/kg [68Ga]Ga-FAPI-04. All patients obtained superior image quality with 300 s original acquisition time. Images were reconstructed using 180 s, 120 s, 60 s, 40 s, 30 s, 20 s scanning duration by ordered subset expectation maximization algorithm. The subjective image quality of all patients in each time group was scored using 5-point Likert scale. Mediastinal blood pool, liver, spleen, and muscle were analyzed as background using semi-quantitative parameters maximum standardized uptake values (SUVmax), mean standardized uptake values (SUVmean), standard deviation (SD), and signal to noise ratio (SNR). The lesion detection rate, SUVmax, and tumor-to-background ratio (TBR) were calculated for tumors confirmed by pathology. RESULTS: The subjective image quality score decreased with the shortening of scanning time; however, both 180 s and 120 s images met the diagnostic requirements in terms of overall quality, lesion conspicuity, and image noise. The SUVmax of background increased with the reduction of scanning time, while the SUVmean was relatively stable. With the shortening of scanning time, the SD gradually increased, and the SNR gradually decreased, which was consistent with subjective image quality scores. In 180 s and 120 s images, all 11 primary lesions and 79 metastatic lesions were detected. The SUVmax of tumor focus showed an increasing trend as same as the background. Compared with 300 s, the TBR muscle had no statistical difference in 180 s and 120 s. CONCLUSIONS: Half-dose [68Ga]Ga-FAPI-04 in total-body PET/CT imaging can shorten the acquisition time to 120 s with acceptable subjective image quality and 100% tumor detection rate. Total-body PET/CT imaging with a half-dose [68Ga]Ga-FAPI-04 and reduced acquisition time can be used in radiation-sensitive and poor tolerant to prolong horizontal positioning and waiting time populations such as children and gravidas.


Neoplasms , Quinolines , Child , Humans , Positron Emission Tomography Computed Tomography , Feasibility Studies , Gallium Radioisotopes , Neoplasms/diagnostic imaging , Fluorodeoxyglucose F18
16.
Medicine (Baltimore) ; 102(32): e34703, 2023 Aug 11.
Article En | MEDLINE | ID: mdl-37565923

This study aimed to investigate the characteristics of intestinal flora in patients with chronic functional constipation before and after lactulose intervention. Twenty-nine patients with constipation in the treatment group received oral lactulose (15 mL/d) for a month. Twenty healthy subjects served as controls. Stool specimens were collected before and after lactulose treatment. Fecal bacteria were examined by 16SrRNA gene sequencing and bioinformatics analysis. After lactulose treatment, most bacteria in the constipation group, including Bifidobacteria, Bacillus cereus, Prevotella, Bacillus, Anaerostipes, Oribacterium, and Mogibacterium increased as compared to those in the healthy control group. Anaerotruncus declined in the healthy control group after lactulose treatment. Our study shows lactulose can increase the abundance of probiotics, optimize the intestinal microenvironment, and alleviate constipation.


Gastrointestinal Microbiome , Lactulose , Humans , Lactulose/therapeutic use , Constipation/drug therapy , Constipation/chemically induced , Feces/microbiology , Bacteria
17.
Front Psychol ; 14: 1202830, 2023.
Article En | MEDLINE | ID: mdl-37496800

In recent years, job burnout of English as a foreign language (EFL) teachers in China has become prominent in the field of education and psychology, with the related research articles generally on the rise. Using the database of Web of Science (WOS) and the sub-database of Chinese Social Sciences Citation Index (CSSCI) in China National Knowledge Infrastructure (CNKI) database, this paper comprehensively reviews the current situation of research on job burnout of EFL teachers in China between 2020 and 2023, from the aspects of research methods, research focuses and research findings. The literature research results show that on the whole, the research on job burnout of EFL teachers in China is still in its infancy, and that the research level is still relatively low. Based on the systematic reviews of the collected studies, we can conclude that although there is no unanimous conclusion between demographic variables and job burnout severity of EFL teachers in China, we can intervene at both the teacher and school levels to alleviate job burnout of EFL teachers. This review paper analyzes some main problems existing in the current research, for example, lack of theoretical construction and guidance, too much concentration on some research topics, lack of diversified and interdisciplinary research methods, lack of longitudinal research, and potential directions for future research are also discussed in the paper.

18.
Article En | MEDLINE | ID: mdl-37433343

Adipocyte browning increases energy expenditure by thermogenesis, which has been considered a potential strategy against obesity and its related metabolic diseases. Phytochemicals derived from natural products with the ability to improve adipocyte thermogenesis have aroused extensive attention. Acteoside (Act), a phenylethanoid glycoside, exists in various medicinal or edible plants and has been shown to regulate metabolic disorders. Here, the browning effect of Act was evaluated by stimulating beige cell differentiation from the stromal vascular fraction (SVF) in the inguinal white adipose tissue (iWAT) and 3T3-L1 preadipocytes, and by converting the iWAT-SVF derived mature white adipocytes. Act improves adipocyte browning by differentiation of the stem/progenitors into beige cells and by direct conversion of mature white adipocytes into beige cells. Mechanistically, Act inhibited CDK6 and mTOR, and consequently relieved phosphorylation of the transcription factor EB (TFEB) and increased its nuclear retention, leading to induction of PGC-1α, a driver of mitochondrial biogenesis, and UCP1-dependent browning. These data thus unveil a CDK6-mTORC1-TFEB pathway that regulates Act-induced adipocyte browning.


Adipose Tissue, White , Metabolic Diseases , Humans , Mechanistic Target of Rapamycin Complex 1/metabolism , Adipose Tissue, White/metabolism , Obesity/drug therapy , Obesity/metabolism , Adipocytes, White/metabolism , Metabolic Diseases/metabolism , Basic Helix-Loop-Helix Leucine Zipper Transcription Factors/metabolism , Cyclin-Dependent Kinase 6/metabolism , Cyclin-Dependent Kinase 6/pharmacology
19.
Epilepsia Open ; 8(3): 1002-1012, 2023 09.
Article En | MEDLINE | ID: mdl-37277986

OBJECTIVE: Anterior nucleus of thalamus (ANT) has been widely accepted as a potential therapeutic target for drug-resistant epilepsy. Although increased volume of the ANT was also reported in patients with absence epilepsy, the relationship between the ANT and absence epilepsy has been barely illustrated. METHODS: Using chemogenetics, we evaluated the effect of ANT parvalbumin (PV) neurons on pentylenetetrazole (PTZ)-induced absence seizures in mice. RESULTS: We found that intraperitoneal injection of PTZ (30 mg/kg) can stably induce absence-like seizures characterized by bilaterally synchronous spike-wave discharges (SWDs). Selective activation of PV neurons in the ANT by chemogenetics could aggravate the severity of absence seizures, whereas selective inhibition of that cannot reverse this condition and even promote absence seizures as well. Moreover, chemogenetic inhibition of ANT PV neurons without administration of PTZ was also sufficient to generate SWDs. Analysis of background EEG showed that chemogenetic activation or inhibition of ANT PV neurons could both significantly increase the EEG power of delta oscillation in the frontal cortex, which might mediate the pro-seizure effect of ANT PV neurons. SIGNIFICANCE: Our findings indicated that either activation or inhibition of ANT PV neurons might disturb the intrinsic delta rhythms in the cortex and worsen absence seizures, which highlighted the importance of maintaining the activity of ANT PV neurons in absence seizure.


Anterior Thalamic Nuclei , Epilepsy, Absence , Animals , Mice , Anterior Thalamic Nuclei/physiology , Neurons/physiology , Parvalbumins/pharmacology , Pentylenetetrazole/pharmacology , Seizures
20.
Appl Microbiol Biotechnol ; 107(15): 4947-4959, 2023 Aug.
Article En | MEDLINE | ID: mdl-37306707

Infectious African swine fever virus (ASFV) can cause the spread and morbidity of African swine fever, while the inactivated virus cannot. When they are not distinguished separately, the detection results will lack authenticity and cause unnecessary panic and detection cost. The detection technology based on cell culture is complex, high-cost, and time-consuming in practice, which is not conducive to the rapid detection of infectious ASFV. In this study, a propidium monoazide (PMA) qPCR detection method for rapid diagnosis of infectious ASFV was constructed. Parameters of PMA concentration, light intensity, and lighting time were under strict safety verification and comparative analysis for optimization. The results determined that the optimal condition for PMA to pretreat ASFV was the final concentration of PMA 100 µM. The light intensity was 40 W, the light duration was 20 min, the target fragment size of the optimal primer probe was 484 bp, and its detection sensitivity for infectious ASFV was 101.28 HAD50/mL. In addition, the method was innovatively applied to the rapid evaluation of disinfection effect. When ASFV concentration was less than 102.28 HAD50/mL, the method could still be effective for the evaluation of thermal inactivation effect, and the evaluation ability of chlorine-containing disinfectants was better, and the applicable concentration could reach 105.28 HAD50/mL. It is worth mentioning that this method can not only reflect whether the virus is inactivated, but also indirectly reflect the degree of damage to viral nucleic acid caused by disinfectants. In conclusion, the PMA-qPCR constructed in this study can be applied to laboratory diagnosis, disinfection effect evaluation, drug development, and other aspects of infectious ASFV and can provide new technical support for effective prevention and control of ASF. KEY POINTS: • A rapid detection method for infectious ASFV was developed • Provide a new scheme for rapid evaluation of disinfection effect of chlorine-containing disinfectants • PMA-qPCR can simultaneously show the survival status of the virus and the damage of nucleic acid.


African Swine Fever Virus , African Swine Fever , Disinfectants , Swine , Animals , African Swine Fever/prevention & control , Disinfection/methods , Chlorine/pharmacology , Disinfectants/pharmacology
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