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1.
Sensors (Basel) ; 24(11)2024 Jun 02.
Article in English | MEDLINE | ID: mdl-38894378

ABSTRACT

Bridge early warning based on structural health monitoring (SHM) system is of significant importance for ensuring bridge safe operation. The temperature-induced deflection (TID) is a sensitive indicator for performance degradation of continuous rigid frame bridges, but the time-lag effect makes it challenging to predict the TID accurately. A bridge early warning method based on nonlinear modeling for the TID is proposed in this article. Firstly, the SHM data of temperature and deflection of a continuous rigid frame bridge are analyzed to examine the temperature gradient variation patterns. Kernel principal component analysis (KPCA) is used to extract principal temperature components. Then, the TID is extracted through wavelet transform, and a nonlinear modeling method for the TID considering the temperature gradient is proposed using the support vector machine (SVM). Finally, the prediction errors of the KPCA-SVM algorithm are analyzed, and the early warning thresholds are determined based on the statistical patterns of the errors. The results show that the KPCA-SVM algorithm achieves high-precision nonlinear modeling for the TID while significantly reducing the computational load. The prediction results have coefficients of determination above 0.98 and fluctuate within a small range with clear statistical patterns. Setting the early warning thresholds based on the statistical patterns of errors enables dynamic and multi-level warnings for bridge structures.

2.
BMC Microbiol ; 22(1): 151, 2022 06 07.
Article in English | MEDLINE | ID: mdl-35672661

ABSTRACT

BACKGROUND: Leptospirosis is a significant emerging infectious disease worldwide. Rodents are considered to be the most critical hosts of Leptospira spp. Fujian Province is a region highly endemic for leptospirosis in China. However, the genetic diversity of leptospires circulating among rodents in Fujian is limited. RESULTS: The carrier status of rodents for Leptospira spp. was investigated by culture and serological detection in Fujian during 2018-2020. A total of 710 rodents, including 11 species, were trapped, with Rattus losea being the dominant trapped species (50.56%). Fourteen pathogenic Leptospira strains were obtained. Seven L. borgpetersenii serogroup Javanica strains belonging to ST143, 4 L. interrogans serogroup Icterohaemorrhagiae strains belonging to ST1 and ST17, 2 L. interrogans serogroup Bataviae strains belonging to ST96 and ST333, and 1 L. interrogans serogroup Pyrogenes strains belonging to ST332 were identified using 16S rDNA gene sequencing, microscopic agglutination test (MAT) and Multilocus sequence typing (MLST). L. borgpetersenii serogroup Javanica belonging to ST143 was the dominant type (50.00%). A total of 387 rodent serum samples were tested by MAT. Serum were considered positive for seroreactivity at a titer ≥ 1:160 against at least one serovar. A total of 90 (23.26%) serum samples tested positive, and four serogroups were identified, with Javanica being the dominant serogroup (87.78%), which was similar to the dominant serogroup isolated from rodents. This study demonstrates a high prevalence of leptospirosis in rodents and public health education among high-risk workers is highly recommended. CONCLUSIONS: R. losea was the dominant trapped rodent, and L. borgpetersenii serogroup Javanica ST143 was widely distributed among rodents in Fujian from 2018 to 2020. Despite the low number of isolates obtained from rodents, this study suggests that continuous epidemiological surveillance of the aetiological characteristics of pathogenic Leptospira in wild animal reservoirs may help reduce the possible risk of disease transmission.


Subject(s)
Leptospira , Leptospirosis , Animals , China/epidemiology , Leptospirosis/epidemiology , Leptospirosis/veterinary , Multilocus Sequence Typing , Rats , Rodentia , Serogroup
3.
BMC Musculoskelet Disord ; 23(1): 866, 2022 Sep 16.
Article in English | MEDLINE | ID: mdl-36114532

ABSTRACT

BACKGROUND: The one-stage posterior approach for treating spinal infection has recently been generally accepted. However, severe vertebral body loss caused by infection remains a major challenge in posterior surgery. This study was conducted to evaluate the clinical application and outcomes of S1 alar screws used in the one-stage posterior surgery of short-segment lumbosacral fixation and fusion after debridement for infection with severe S1 vertebral body loss. METHODS: The clinical features and treatment outcomes of 7 patients with spinal infections from August 2016 to August 2021 who were treated with one-stage posterior surgery using S1 alar screws were retrospectively analyzed. The clinical data, including patient data, visual analogue scale (VAS), Oswestry Disability Index (ODI), fusion time and complications of the patients, were recorded. RESULTS: All 7 patients were followed up for an average duration of 14.57 months (range, 12-18 months). The VAS score decreased significantly from 7.3 preoperatively (range, 6-8) to 2.6 postoperatively (range, 2-3). The ODI score demonstrated a steady and gradual increase from 73.8 preoperatively (range, 68-75) to 33.6 postoperatively (range, 30-37). Bony fusion time was observed approximately 6.8 months after surgery. Two patients in our study experienced the postoperative local pain, which could be relieved by analgesics and disappeared 3 months after the operation. There were no complications of intraoperative fracture, posterior wound infection or neurovascular injury. CONCLUSIONS: S1 alar screws are suitable for use in the operation and could be an alternative option to S1 pedicle screws for short-segment lumbosacral fixation and fusion with severe S1 vertebral body loss caused by spinal infection, which could provide satisfactory clinical outcomes.


Subject(s)
Spinal Diseases , Spinal Fusion , Humans , Lumbar Vertebrae/diagnostic imaging , Lumbar Vertebrae/injuries , Lumbar Vertebrae/surgery , Retrospective Studies , Spinal Fusion/adverse effects , Vertebral Body
4.
Zhongguo Yi Liao Qi Xie Za Zhi ; 46(6): 643-647, 2022 Nov 30.
Article in Zh | MEDLINE | ID: mdl-36597392

ABSTRACT

The diagnosis and differential diagnosis of bile duct stenosis are the foundation for personalized treatment. However, accurate diagnosis of bile duct stenosis remains a significant challenge in the era of precise medicine. In recent years, several novel diagnostic techniques of bile duct stenosis have been developed. And various biomarker detection, non-invasive imaging diagnostic techniques and invasive endoscopic diagnostic techniques have gradually become the conventional techniques for diagnosing bile duct stenosis. Here, we systematically reviewed the current status and future directions of diagnostic techniques related to bile duct stenosis.


Subject(s)
Cholestasis , Humans , Constriction, Pathologic/diagnosis , Cholestasis/diagnosis , Diagnostic Imaging , Bile Ducts/diagnostic imaging
5.
Bioinformatics ; 36(9): 2684-2689, 2020 05 01.
Article in English | MEDLINE | ID: mdl-31971562

ABSTRACT

MOTIVATION: The development of clustered regularly interspaced short palindromic repeat (CRISPR)/CRISPR-associated protein 9 (Cas9) technology has provided a simple yet powerful system for targeted genome editing. In recent years, this system has been widely used for various gene editing applications. The CRISPR editing efficacy is mainly dependent on the single guide RNA (sgRNA), which guides Cas9 for genome cleavage. While there have been multiple attempts at improving sgRNA design, there is a pressing need for greater sgRNA potency and generalizability across various experimental conditions. RESULTS: We employed a unique plasmid library expressed in human cells to quantify the potency of thousands of CRISPR/Cas9 sgRNAs. Differential sequence and structural features among the most and least potent sgRNAs were then used to train a machine learning algorithm for assay design. Comparative analysis indicates that our new algorithm outperforms existing CRISPR/Cas9 sgRNA design tools. AVAILABILITY AND IMPLEMENTATION: The new sgRNA design tool is freely accessible as a web application, http://crispr.wustl.edu. SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.


Subject(s)
Clustered Regularly Interspaced Short Palindromic Repeats , RNA, Guide, Kinetoplastida , Algorithms , CRISPR-Cas Systems/genetics , Gene Editing , Humans , RNA, Guide, Kinetoplastida/genetics
6.
J Surg Res ; 267: 485-494, 2021 11.
Article in English | MEDLINE | ID: mdl-34246842

ABSTRACT

BACKGROUND: Stage IV colorectal cancer (CRC) patients with liver metastasis undergoing potentially curative surgery represent a subgroup of patients with a relatively good prognosis. In this study, we aimed to evaluate the performance of mSEPT9 to monitor response to treatment and predict prognosis. METHODS: In total, we recruited 51 stage IV CRC patients with liver metastasis, including 20 patients who underwent simultaneous surgery and 31 patients who underwent staged surgery. We measured the blood levels of mSEPT9 and CEA prior to surgery and then seven days after surgery. RESULTS: mSEPT9 and CEA were detected prior to surgery in 92.2% (47/51) and 70.6% (36/51) of patients, respectively. Following simultaneous and staged surgery, levels of mSEPT9 fell significantly by 923-fold (P<0.001) and 11-fold (P<0.001), respectively. Levels of CEA also fell significantly by 17-fold (P<0.001) and 1.7-fold (P<0.01) following simultaneous and staged surgery, respectively. The mean percentage reduction of mSEPT9 levels after simultaneous surgery (12.3%) was significantly lower than that of staged surgery (33.8%) (P<0.001) while the mean percentage reduction of CEA levels after simultaneous surgery (35.5%) were significantly lower than that of staged surgery (64.6%) (P<0.05). The levels of mSEPT9 in the blood were quantitatively correlated with tumor burden. Survival analysis showed that patients who tested negative for mSEPT9 pre- and post-surgery had a better survival rate than those who tested positive, thus suggesting that mSEPT9 can act as a prognostic indicator. CONCLUSIONS: mSEPT9 showed good quantitative efficacy, higher applicability, and sensitivity, than CEA in assessing treatment response and prognosis prediction in patients with stage IV CRC and liver metastasis.


Subject(s)
Carcinoembryonic Antigen , Colorectal Neoplasms , Liver Neoplasms , Septins , Biomarkers, Tumor/blood , Carcinoembryonic Antigen/blood , Colorectal Neoplasms/blood , Colorectal Neoplasms/pathology , Colorectal Neoplasms/secondary , Humans , Liver Neoplasms/blood , Liver Neoplasms/secondary , Liver Neoplasms/surgery , Neoplasm Staging , Prognosis , Septins/blood , Septins/metabolism
7.
Mikrochim Acta ; 187(1): 9, 2019 12 03.
Article in English | MEDLINE | ID: mdl-31797061

ABSTRACT

The target-triggered DNA assembling probe is presented for highly selective protein detection. Target-triggered DNA assembling is used in an amplification strategy based on affinity binding for identification and determination of proteins in general. Specifically, it was applied to the platelet derived growth factor-BB (PDGF-BB). A hairpin DNA (H-DNA) probe was designed containing (a) an aptamer domain for protein recognition and (b) a blocked DNAzyme domain for DNAzyme cleavage. An assistant DNA (A-DNA) probe containing aptamer and complementary domains was also employed to recognize protein and to induce DNA assembly. Once H-DNA and A-DNA recognize the same protein, H-DNA and A-DNA are in close proximity to each other. This induces DNA assembling for protein-triggered complex (Protein-Complex) with free DNAzyme domains. The free DNAzymes trigger the circular cleavage of molecular beacons for amplified signals. The assay is performed by fluorometry at an excitation wavelength of 980 nm and by collecting fluorescence at 545 nm. The platelet derived growth factor-BB (PDGF-BB) was accurately identified and selectively determined by this assay with a 22 pM detection limit (using the 3σ criterion). The responses for PDGF-BB is nearly 6-fold higher than for PDGF-AB, and 16-fold higher than PDGF-AA. This upconversion assay avoids any interference by the autofluorescence of biological fluids. Graphical abstractSchematic representation of the principle of the target-triggered DNA assembling probes mediated amplification strategy based on affinity binding for PDGF-BB. The UCNP probe is used for the quantitation of PDGF-BB with high selectivity.


Subject(s)
Aptamers, Nucleotide/metabolism , Becaplermin/analysis , Biosensing Techniques/methods , DNA Probes/metabolism , Nanoparticles/chemistry , Aptamers, Nucleotide/chemistry , Becaplermin/blood , Becaplermin/metabolism , Becaplermin/urine , DNA Probes/chemistry , Enzyme-Linked Immunosorbent Assay , Feasibility Studies , Fluorometry , Humans
8.
Sensors (Basel) ; 19(23)2019 Nov 20.
Article in English | MEDLINE | ID: mdl-31756906

ABSTRACT

Great length, large weight and other factors may cause difficulty in measuring the profile accuracy of the double-headed screw rotor. To solve this problem, an on-machine measuring system based on a laser-displacement sensor (LDS) was designed and implemented in this paper by taking an LXK100 four-axis whirlwind milling machine as the carrier. To improve the measurement accuracy of the system, the generalized variable-structural-element morphological method, polynomial interpolation algorithm and ellipse fitting method were first combined to realize the rapid subpixel centroid extraction from a noise-containing spot image, thus improving the data acquisition accuracy of the LDS, and then the hybrid method was experimentally verified. Next, a wavelet threshold function with high-order differentiability and adaptive wavelet coefficient contractility was constructed based on the hyperbolic tangent function, so as to inhibit the disturbance from random errors and preserve real profile information, and this method was simulated and verified. Subsequently, a smoothing algorithm for point cloud data was proposed based on the Lagrange multiplier method to avoid the defect of the piecewise curve-fitting method, that is, function continuity and differentiability could not be satisfied at piecewise points. Finally, the profile accuracy was calculated in real time according to the data reconstruction result and the machining quality was judged. The measurement experiment of the double-headed screw rotor indicates that the proposed on-machine measuring system can complete the profile accuracy measurement for a screw pitch within 39.7 s with measurement accuracy reaching ±8 µm, and the measurement uncertainties of the major axis, minor axis and screw pitch are 0.72 µm, 0.69 µm and 1.24 µm, respectively. Therefore, the measurement accuracy and efficiency are both remarkably improved.

9.
Br J Cancer ; 118(1): 72-78, 2018 01.
Article in English | MEDLINE | ID: mdl-29112685

ABSTRACT

BACKGROUND: Pretreatment serum squamous cell carcinoma antigen (SCCA) is a prognostic biomarker in women with cervical cancer. SCCA has not been evaluated as an early indicator of response to chemoradiation therapy (CRT). The molecular role of the two SCCA isoforms, SCCA1 (SERPINB3) and SCCA2 (SERPINB4), in cervical cancer is unknown. We hypothesised that changes in serum SCCA during definitive CRT predicts treatment response, and that SCCA1 mediates radiation resistance. METHODS: Patients treated with definitive CRT for cervical squamous carcinoma with serum SCCA measured were included. SCCA immunohistochemistry was performed on tumour biopsies. Post-treatment FDG-PET/CT, recurrence, and overall survival were recorded. Radiation response of cervical tumour cell lines after SCCA1 expression or CRISPR/Cas9 knockout was evaluated by clonogenic survival assay. RESULTS: Persistently elevated serum SCCA during definitive CRT was an independent predictor of positive post-therapy FDG-PET/CT (P=0.043), recurrence (P=0.0046) and death (P=0.015). An SCCA1-expressing vector increased radioresistance, while SCCA knock out increased radiosensitivity of cervical tumour cell lines in vitro. CONCLUSIONS: Early response assessment with serum SCCA is a powerful prognostic tool. These findings suggest that escalation of therapy in patients with elevated or sustained serum SCCA and molecular targeting of SCCA1 should be considered.


Subject(s)
Antigens, Neoplasm/blood , Antigens, Neoplasm/metabolism , Biomarkers, Tumor/blood , Carcinoma, Squamous Cell/therapy , Chemoradiotherapy/methods , Serpins/blood , Serpins/metabolism , Uterine Cervical Neoplasms/therapy , Adult , Aged , Aged, 80 and over , Antigens, Neoplasm/genetics , Biomarkers, Tumor/genetics , Biomarkers, Tumor/metabolism , Carcinoma, Squamous Cell/blood , Carcinoma, Squamous Cell/metabolism , Cell Line, Tumor , Cisplatin/administration & dosage , Cisplatin/therapeutic use , Dose Fractionation, Radiation , Female , Gene Knockdown Techniques , Humans , Middle Aged , Serpins/genetics , Survival Analysis , Treatment Outcome , Up-Regulation , Uterine Cervical Neoplasms/blood , Uterine Cervical Neoplasms/metabolism
10.
J Cardiovasc Pharmacol ; 71(6): 380-387, 2018 06.
Article in English | MEDLINE | ID: mdl-29528873

ABSTRACT

BACKGROUND: At present, it is considered that atrial fibrillation (AF) is a risk factor for cognitive impairment and dementia. It is independent of stroke, but the relationship between anticoagulant drugs and cognitive function in patients with AF is unknown. OBJECTIVE: The purpose of this study was to complete a meta-analysis of studies and investigate the association between anticoagulant therapy and cognitive impairment in patients with AF. METHODS AND RESULTS: Two investigators systematically searched the Cochrane Library, PubMed, EMBASE databases, and Web of Science for all studies that present associations. Hazard ratios (HRs) were extracted and pooled. Finally, the 8 studies included 471,057 participants; time in therapeutic range (TTR) <25% versus TTR >75%; (HR 3.02, 95% CI 1.12-8.91; P = 0.03); TTR 25%-50% versus TTR >75% (HR 2.44, 95% CI 0.95-6.22; P = 0.06); TTR 50%-75% versus TTR >75% (HR 1.75, 95% CI 0.90-3.99; P = 0.1); oral anticoagulants (OAC) versus No OAC (HR 0.71, 95% CI 69-0.74; P < 0.00001); and new oral anticoagulants versus warfarin (HR 0.51, 95% CI 0.37-0.71; P < 0.00001). CONCLUSIONS: OACs significantly reduce the occurrence of cognitive impairment in patients with AF. Compared with warfarin, new oral anticoagulants have an efficiently protective effect on cognition. In the range of INR 2-3, with the increase of TTR, the incidence of cognitive impairment is lower.


Subject(s)
Anticoagulants/administration & dosage , Atrial Fibrillation/drug therapy , Blood Coagulation/drug effects , Cognition Disorders/prevention & control , Cognition/drug effects , Dementia/prevention & control , Administration, Oral , Aged , Aged, 80 and over , Anticoagulants/adverse effects , Atrial Fibrillation/blood , Atrial Fibrillation/diagnosis , Atrial Fibrillation/epidemiology , Cognition Disorders/diagnosis , Cognition Disorders/epidemiology , Cognition Disorders/psychology , Dementia/diagnosis , Dementia/epidemiology , Dementia/psychology , Female , Humans , Incidence , International Normalized Ratio , Male , Middle Aged , Protective Factors , Risk Factors , Treatment Outcome
12.
Sensors (Basel) ; 18(10)2018 Oct 18.
Article in English | MEDLINE | ID: mdl-30340433

ABSTRACT

Laser triangulation (LT) is widely used in many fields due to its good stability, high resolution and fast speed. However, the accuracy in these applications suffers from severe constraints on the data acquisition accuracy of LT. To solve this problem, the optical triangulation principle, the object equation of the optical path relationship and the deviation of the laser spot centroid are applied to deduce a mathematical model. Therefore, the image sensor inclination errors can be quantitatively calculated, and the collected data are compensated in real time. Further, a threshold sub-pixel gray-gravity (GG) extraction algorithm is proposed; the gradient function and Gaussian fit algorithm are used to set thresholds to remove the impact of the spot edge noise area on the center location; and polynomial interpolation is employed to enhance the data density of the traditional GG method, thus improving the data acquisition accuracy of LT. Finally, the above methods are applied to on-machine measurement of the American Petroleum Institute (API) thread and the screw rotor, respectively. The experimental results prove that the proposed method can significantly improve the measurement accuracy of free-form curved surfaces using LT and that the improved laser spot center extraction algorithm is more suitable for free-form curved surfaces with smaller curvature and more uniform curvature changes.

13.
Acta Derm Venereol ; 97(4): 472-477, 2017 Apr 06.
Article in English | MEDLINE | ID: mdl-27840887

ABSTRACT

Cutaneous tuberculosis (CTB) is probably underreported due to difficulties in detection and diagnosis. To address this issue, genotypes of Mycobacterium tuberculosis strains isolated from 30 patients with CTB were mapped at multiple loci, namely, RD105 deletions, spacer oligonucleotides, and Mycobacterial Interspersed Repetitive Unit-Variable Number Tandem Repeats (MIRU-VNTRs). Fifty-eight strains of pulmonary tuberculosis (PTB) were mapped as experimental controls. Drug resistance-associated gene mutations were determined by amplicon sequencing of target regions within 7 genes. Beijing family isolates were the most prevalent strains in CTB and PTB. MIRU-VNTR typing separated the Beijing strains from the non-Beijing strains, and the majority of CTB could be separated from PTB counterparts. Drug resistance determining regions showed only one CTB strain expressing isomazid resistance. Thus, while the CTB strains belonged to the same phylogenetic lineages and sub-lineages as the PTB strains, they differed at the level of several MIRU-VNTRs and in the proportion of drug resistance.


Subject(s)
DNA, Bacterial/genetics , Mycobacterium/genetics , Skin/microbiology , Tuberculosis, Cutaneous/microbiology , Adult , Antitubercular Agents/therapeutic use , Case-Control Studies , China/epidemiology , DNA, Bacterial/isolation & purification , Drug Resistance, Bacterial/genetics , Female , Genotype , Humans , Interspersed Repetitive Sequences , Male , Microbial Sensitivity Tests , Middle Aged , Minisatellite Repeats , Molecular Diagnostic Techniques , Mycobacterium/drug effects , Mycobacterium/isolation & purification , Phenotype , Phylogeny , Tuberculosis, Cutaneous/diagnosis , Tuberculosis, Cutaneous/drug therapy , Tuberculosis, Cutaneous/epidemiology
14.
J Am Chem Soc ; 138(49): 16120-16129, 2016 12 14.
Article in English | MEDLINE | ID: mdl-27960299

ABSTRACT

Copolymerizations of ethylene with vinyltrialkoxysilanes are reported using both a "traditional" cationic Pd(II) aryldiimine catalyst, t-1 (aryl = 2,6-diisopropylphenyl), and a "sandwich-type" aryldiimine catalyst, s-2 (aryl = 8-tolylnaphthyl). Incorporation levels of vinyltrialkoxysilanes between 0.25 and 2.0 mol % were achieved with remarkably little rate retardation relative to ethylene homopolymerizations. In the case of the traditional catalyst system, molecular weights decrease as the level of comonomer increases and only one trialkoxysilyl group is incorporated per chain. Molecular weight distributions of ca. 2 are observed. For the sandwich catalyst, higher molecular weights are observed with many more trialkoxysilyl groups incorporated per chain. Polymers with molecular weight distributions of ca. 1.2-1.4 are obtained. Detailed NMR mechanistic studies have revealed the formation of intermediate π-complexes of the type (diimine)Pd(alkyl)(vinyltrialkoxysilane)+. 1,2-Migratory insertions of these complexes occur with rates similar to ethylene insertion and result in formation of observable five-membered chelate intermediates. These chelates are rapidly opened with ethylene forming alkyl ethylene complexes, a requirement for chain growth. An unusual ß-silyl elimination mechanism was shown to be responsible for chain transfer and formation of low molecular weight copolymers in the traditional catalyst system, t-1. This chain transfer process is retarded in the sandwich system. Relative binding affinities of ethylene and vinyltrialkoxysilanes to the cationic palladium center have been determined. The quantitative mechanistic studies reported fully explain the features of the bulk polymerization results.

15.
J Biol Chem ; 289(47): 32639-55, 2014 Nov 21.
Article in English | MEDLINE | ID: mdl-25271158

ABSTRACT

Patients with chronic hepatitis B usually exhibit a low response to treatment with interferon α (IFN-α). An alternative approach to increase the response rate of IFN-α might be to immunologically stimulate the host with glucocorticoids (GCs) before treatment with IFN-α, but the underlying mechanism remains unclear. We hypothesized that the GCs enhance IFN signaling by inducing S-adenosylmethionine (AdoMet) when hepatitis B virus (HBV) replication was effectively suppressed by IFN-α. Here, we investigated the effect of GCs and IFN-α on AdoMet production and methionine adenosyltransferase 1A (MAT1A) expression in vitro. Furthermore, we determined whether post-transcriptional regulation is involved in HBV-repressed MAT1A expression and AdoMet production induced by dexamethasone (Dex). We found that AdoMet homeostasis was disrupted by Dex and that Dex directly regulated MAT1A expression by enhancing the binding of the glucocorticoid receptor (GR) to the glucocorticoid-response element (GRE) of the MAT1A promoter. HBV reduced AdoMet production by increasing methylation at GRE sites within the MAT1A promoter. The X protein of hepatitis B virus led to hypermethylation in the MAT1A promoter by recruiting DNA methyltransferase 1, and it inhibited GR binding to the GRE in the MAT1A promoter. Dex could increase an antiviral effect by inducing AdoMet production via a positive feedback loop when HBV is effectively suppressed by IFN-α, and the mechanism that involves Dex-induced AdoMet could increase STAT1 methylation rather than STAT1 phosphorylation. These findings provide a possible mechanism by which GC-induced AdoMet enhances the antiviral activity of IFN-α by restoring STAT1 methylation in HBV-infected cells.


Subject(s)
Glucocorticoids/pharmacology , Hepatitis B virus/drug effects , Interferon-alpha/pharmacology , S-Adenosylmethionine/metabolism , STAT1 Transcription Factor/metabolism , Antiviral Agents/pharmacology , Cell Line , Cell Line, Tumor , DNA (Cytosine-5-)-Methyltransferase 1 , DNA (Cytosine-5-)-Methyltransferases/genetics , DNA (Cytosine-5-)-Methyltransferases/metabolism , DNA Methylation/drug effects , Dexamethasone/pharmacology , Gene Expression/drug effects , Hep G2 Cells , Hepatitis B virus/physiology , Humans , Immunoblotting , Methionine Adenosyltransferase/genetics , Methionine Adenosyltransferase/metabolism , Methylation/drug effects , Promoter Regions, Genetic/genetics , Protein Binding/drug effects , Receptors, Glucocorticoid/metabolism , Response Elements/genetics , Reverse Transcriptase Polymerase Chain Reaction , Signal Transduction/drug effects
16.
RNA ; 19(12): 1745-54, 2013 Dec.
Article in English | MEDLINE | ID: mdl-24145823

ABSTRACT

MicroRNAs (miRNAs) are involved in a variety of human diseases by simultaneously suppressing many gene targets. Thus, the therapeutic value of miRNAs has been intensely studied. However, there are potential limitations with miRNA-based therapeutics such as a relatively moderate impact on gene target regulation and cellular phenotypic control. To address these issues, we proposed to design new chimeric small RNAs (aiRNAs) by incorporating sequences from both miRNAs and siRNAs. These aiRNAs not only inherited functions from natural miRNAs, but also gained new functions of gene knockdown in an siRNA-like fashion. The improved efficacy of multifunctional aiRNAs was demonstrated in our study by design and testing of an aiRNA that inherited the functions of both miR-200a and an AKT1-targeting siRNA for simultaneous suppression of cancer cell motility and proliferation. The general principles of aiRNA design were further validated by engineering new aiRNAs mimicking another miRNA, miR-9. By regulating multiple cellular functions, aiRNAs could be used as an improved tool over miRNAs to target disease-related genes, thus alleviating our dependency on a limited number of miRNAs for the development of RNAi-based therapeutics.


Subject(s)
Gene Knockdown Techniques/methods , MicroRNAs/genetics , RNA Interference , RNA, Small Interfering/genetics , Base Sequence , Cell Death , Cell Movement , Cell Proliferation , Cloning, Molecular , Gene Expression Regulation, Neoplastic , HCT116 Cells , HeLa Cells , Humans , Proto-Oncogene Proteins c-akt/genetics , Proto-Oncogene Proteins c-akt/metabolism , Transcriptome , Tumor Suppressor Protein p53/genetics , Tumor Suppressor Protein p53/metabolism
17.
Acta Derm Venereol ; 95(8): 985-9, 2015 Nov.
Article in English | MEDLINE | ID: mdl-25809023

ABSTRACT

Skin and soft tissue infections caused by rapidly growing non-tuberculous mycobacteria (RG-NTM) have become a growing clinical concern over the past decades. These RG-NTM are ubiquitous environmental organisms and most are resistant to traditional antituberculous agents. In this report, we describe 3 cutaneous infections caused by RG-NTM, namely, Mycobacterium abscessus, M. chelonae, and M. conceptionense, and present the clinical and laboratory characteristics of these infections.


Subject(s)
Mycobacterium Infections, Nontuberculous/microbiology , Mycobacterium chelonae/isolation & purification , Skin Diseases, Bacterial/microbiology , Adult , Aged , Anti-Bacterial Agents/therapeutic use , Female , Humans , Middle Aged , Mycobacterium Infections, Nontuberculous/drug therapy , Mycobacterium chelonae/genetics , Polymerase Chain Reaction , Polymorphism, Restriction Fragment Length , Skin Diseases, Bacterial/drug therapy
18.
EMBO J ; 29(10): 1726-37, 2010 May 19.
Article in English | MEDLINE | ID: mdl-20424596

ABSTRACT

Recent studies have shown a critical function for the ubiquitin-proteasome system (UPS) in regulating the signalling network for DNA damage responses and DNA repair. To search for new UPS targets in the DNA damage signalling pathway, we have carried out a non-biased assay to identify fast-turnover proteins induced by various types of genotoxic stress. This endeavour led to the identification of Rad17 as a protein exhibiting a distinctive pattern of upregulation followed by subsequent degradation after exposure to UV radiation in human primary cells. Our characterization showed that UV-induced Rad17 oscillation is mediated by Cdh1/APC, a ubiquitin-protein ligase. Studies using a degradation-resistant Rad17 mutant demonstrated that Rad17 stabilization prevents the termination of checkpoint signalling, which in turn attenuates the cellular re-entry into cell-cycle progression. The findings provide an insight into how the proteolysis of Rad17 by Cdh1/APC regulates the termination of checkpoint signalling and the recovery from genotoxic stress.


Subject(s)
Cadherins/metabolism , Cell Cycle Proteins/metabolism , Fibroblasts/metabolism , Antigens, CD , Ataxia Telangiectasia Mutated Proteins , Cell Cycle , DNA Damage , DNA-Binding Proteins/metabolism , Humans , Models, Biological , Mutation , Oscillometry/methods , Phosphatidylinositol 3-Kinases/metabolism , Protein Serine-Threonine Kinases/metabolism , Signal Transduction , Time Factors , Tumor Suppressor Proteins/metabolism
19.
Drug Dev Ind Pharm ; 40(12): 1670-6, 2014 Dec.
Article in English | MEDLINE | ID: mdl-24102615

ABSTRACT

The objective of this study was to develop and validate the in vitro-in vivo correlations (IVIVCs) of three commercially available immediate-release solid dosage forms of indapamide using drug dissolution/absorption simulating system (DDASS). The in vitro dissolution profiles of three brands of immediate-release tablets were obtained using the USP I basket method and DDASS. A single-dose, three-way, crossover pharmacokinetic study for the tablets was carried out in six beagle dogs. Correlation models were developed for each immediate release formulation using cumulative percentage dissolved/eluted (Fd) versus cumulative percentage absorbed (Fa) and cumulative percentage permeated (Fp) versus cumulative percentage absorbed (Fa). Prediction errors were estimated for the Cmax and AUC to determine the validity of the correlation. Level A IVIVCs were established for the three brands between in vitro (dissolution and permeation) data from DDASS and in vivo data from dogs. Predicted plasma concentrations of each commercial brand were obtained from the dissolution and permeation profile data using the correlation models. A percent prediction error of <15% for the Cmax and AUC was found for all of the formulations, which validates the internal predictability of the IVIVC models obtained. However, the IVIVC models from the permeation data failed to predict the AUC. The results support the use of in vitro dissolution and permeation data as a surrogate for bioequivalent study and suggest that DDASS can be applied as an in vitro system for the validated-IVIVC development of BCS II solid drug formulations.


Subject(s)
Chemistry, Pharmaceutical/methods , Indapamide/blood , Indapamide/chemistry , Animals , Dogs , Indapamide/administration & dosage , Male , Rats , Rats, Wistar , Solubility , Tablets
20.
Heliyon ; 10(8): e29581, 2024 Apr 30.
Article in English | MEDLINE | ID: mdl-38681608

ABSTRACT

The outbreak of the COVID-10 variant Omicron epidemic in Shanghai in 2022 had a huge impact on residents' food security. This study examines the roles, challenges, and sustainability of online community group food purchasing by analyzing survey data collected from 1168 households in Shanghai between March and May 2022, in the aftermath of COVID-19. This study demonstrates that online community group food purchasing played a crucial role in ensuring residents' food access and food security during the pandemic. However, this study also reveals that residents expressed concerns about the risk of epidemic transmission, food safety, increased prices, and difficulty in safeguarding rights. Only 21.5 % of residents are willing to continue using online community group purchasing. Based on the above conclusions, this study offers some suggestions.

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