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1.
Cell Chem Biol ; 2021 Aug 30.
Artigo em Inglês | MEDLINE | ID: mdl-34474009

RESUMO

Mechercharmycin A (MCM-A) is a marine natural product belonging to a family of polyazole cyclopeptides with remarkable bioactivities and unique structures. Identification, heterologous expression, and genetic characterizations of the MCM biosynthetic gene cluster in Bacillus subtilis revealed that it is a ribosomally synthesized and post-translationally modified peptide (RiPP) possessing complex with distinctive modifications. Based on this heterologous expression system, two MCM analogs with comparable antitumor activity are generated by engineering the biosynthetic pathway. Combinatorial co-production of a precursor peptide with different modifying enzymes in Escherichia coli identifies a different timing of modifications, showing that a tRNAGlu-dependent highly regioselective dehydration is the first modification step, followed by polyazole formation through heterocyclization and dehydrogenation in an N- to C-terminal direction. Therefore, a rational biosynthetic pathway of MCMs is proposed, which unveils a subfamily of azol(in)e-containing RiPPs and sets the stage for further investigations of the enzymatic mechanism and synthetic biology.

2.
Hum Mol Genet ; 2021 Sep 02.
Artigo em Inglês | MEDLINE | ID: mdl-34476477

RESUMO

The etiology of renal artery stenosis (RAS) and abdominal aortic coarctation (AAC) causing the midaortic syndrome (MAS), often resulting in renovascular hypertension (RVH), remains ill-defined. Neurofibromatosis type 1 (NF-1) is frequently observed in children with RVH. Consecutive pediatric patients (N = 102) presenting with RVH secondary to RAS with and without concurrent AAC were prospectively enrolled in a clinical data base, and blood, saliva, and operative tissue when available, were collected. Among the 102 children were 13 having a concurrent clinical diagnosis of NF-1 (12.5%). Whole exome sequencing was performed for germline variant detection and RNASeq analysis of NF1, MAPK pathway genes, and MCP1 levels were undertaken in five NF-1 stenotic renal arteries, as well as control renal and mesenteric arteries from children with no known vasculopathy or NF-1. In 11 unrelated children with sequencing data, 11 NF1 genetic variants were identified, of which 10 had not been reported in gnomAD. Histologic analysis of NF-1 RAS specimens consistently revealed intimal thickening, disruption of the internal elastic lamina, and medial thinning. Analysis of transcript expression in arterial lesions documented an approximately 5-fold reduction in NF1 expression, confirming heterozygosity, MAPK pathway activation, and increased MCP1 expression. In summary, NF-1 related RVH in children is rare but often severe and progressive and as such, important to recognize. It is associated with histologic and molecular features consistent with an aggressive adverse vascular remodeling process. Further research is necessary to define the mechanisms underlying these findings.

4.
Mater Sci Eng C Mater Biol Appl ; 128: 112292, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-34474843

RESUMO

The ever-growing threat of drug-resistant pathogens and their biofilms based persistent, chronic infections has created an urgent call for new strategies to deal with multidrug resistant bacteria (MDR). Near-infrared (NIR) laser-induced photothermal treatment (PTT) of gold nanorods (AuNRs) disinfects microbes by local heating with low possibility to develop resistant. However, PTT disinfection strategy of AuNRs alone shows less efficiency in killing multidrug resistant strains (i.e. Methicillin-resistant Staphylococcus aureus, MRSA) and their matured biofilms. Herein, a novel synergistic chemo-photothermal integrated antimicrobial platform (P(Cip-b-CB)-AuNRs) was fabricated which show enhanced killing efficiency against MRSA in both planktonic and biofilm phenotypes. Polymethacrylate copolymers with pendant ciprofloxacin (Cip) and the carboxyl betaine groups (P(Cip-b-CB)) were synthesized using reversible addition-fragmentation chain transfer (RAFT) polymerization. P(Cip-b-CB) was decorated onto AuNRs via gold-thiol bond which resulted in AuNRs with acidic-induced surface charge-switchable activities and lipase triggered Cip release properties (P(Cip-b-CB)-AuNRs). The lower pH value and overexpress of lipase are characteristics for microenvironment of microbial infections and their biofilms, which ensure the targeting on, penetration into and on-demand release of Cip from the nanocomposites in bacterial infection sites and their biofilms. The bacterial cell membrane was disrupt by photothermal therapy which could improve its permeability and sensitivity to antibiotics, meanwhile lipase-triggered release of Cip ensures a high concentration of antibiotics at the site of bacterial infection. Besides their NIR induced PTT disinfection activities, the increased local temperature generated by NIR light irradiation accelerated Cip release which further enhanced the antibacterial efficiency, leading to synergistic antibacterial activities of chemo-photothermal therapy. Taken together, the designed synergistic chemo-photothermal integrated antimicrobial platform is a promising antibacterial agent for fighting MDR bacterial infections and their biofilms.


Assuntos
Staphylococcus aureus Resistente à Meticilina , Nanotubos , Preparações Farmacêuticas , Antibacterianos/farmacologia , Antibacterianos/uso terapêutico , Biofilmes , Ciprofloxacina/farmacologia , Ouro , Concentração de Íons de Hidrogênio
5.
Bioresour Technol ; 341: 125806, 2021 Aug 19.
Artigo em Inglês | MEDLINE | ID: mdl-34481298

RESUMO

Anaerobic digestion (AD) of antibiotic fermentation dreg is effective because of its satisfactory methanogenic performance and antibiotic removal rate. Thermophilic AD, an important branch, has not been studied. This study explored the effects of mesophilic and thermophilic AD on tylosin fermentation dreg (TFD) alone-digestion and co-digestion with food waste. The methane production (245-420 mL/g-VS) of mesophilic AD was 20.7%-28.6% higher than thermophilic AD, but the maximum methane production rate (RM), lag period (λ), and hydrolysis rate constant (kh) of thermophilic AD were 1.81, 0.236 and 3.16 times higher than those of mesophilic AD, respectively. However, the residual tylosin in mesophilic AD was always higher than that in thermophilic AD. The addition of food waste increased the methane production rate and yield under both temperature conditions. Therefore, due to the higher rate and yield of methane production, mesophilic AD, especially co-digestion, is more suitable for the treatment of TFD.

6.
Hypertension ; : HYPERTENSIONAHA12117597, 2021 Sep 07.
Artigo em Inglês | MEDLINE | ID: mdl-34488438

RESUMO

While exogenous administration of recombinant erythropoietin has been associated with increased risk of hypertension, coronary artery disease, and mortality, it is not known if endogenous circulating erythropoietin level is associated with coronary artery disease and its risk factors. We measured and analyzed epidemiological and genetic associations of circulating plasma erythropoietin levels in 2 population cohorts, from China (N=4329) and the United States (N=3671). In vitro smooth muscle cell responses and in vivo murine studies of erythropoietin exposure were performed. Erythropoietin levels were positively and linearly associated with blood pressure traits and inversely associated with cholesterol levels and red cell indices. Higher erythropoietin level was associated with higher prevalence of hypertension (odds ratio, 1.20 [95% CI, 1.12-1.29], P=4.41×10-7) and coronary artery disease (odds ratio, 1.16 [95% CI, 1.00-1.34], P=0.046). In a discovery stage genetic association study of erythropoietin level, we identified a previously reported locus on chromosome 6 (rs7776054 near HBS1L-MYB, P=4.86×10-25) and a new locus on chromosome 4 (rs172629 near PDGFRA-KIT, P=2.1×10-8), which was independently replicated. Meta-analysis of discovery and replication genetic association results identified a locus on chromosome 22 (rs855791 near TMPRSS6, P=3.60×10-9). Erythropoietin administration, within a physiological range of hematocrit achieved, induced hypertension in vivo and increased contraction of vascular smooth muscle cells in vitro. In conclusion, endogenous circulating erythropoietin level is influenced by common genetic variation and is associated with blood pressure traits, hypertension, and coronary artery disease. Vascular effects of erythropoietin demonstrated in vitro and in vivo support a newly discovered mechanism of hypertension and cardiovascular risk with potential implications for erythropoietic support in the clinic.

7.
Artigo em Inglês | MEDLINE | ID: mdl-34482587

RESUMO

AIM: To evaluate the efficacy and safety of autologous platelet-rich fibrin (PRF) for the treatment of infertility with intrauterine adhesions. METHODS: Forty patients who suffered from infertility with intrauterine adhesions (IUAs) were enrolled in this prospective trial from October 2018 to December 2019. They were randomly divided into a PRF group and a control group. Both groups underwent transcervical resection of adhesions (TCRA) during the follicular phase. PRF group: PRF prepared from autologous venous blood was placed in the uterine cavity after TCRA and after the first menstrual re-fluid; control group: no PRF insertion. After the second menstrual re-fluid, both groups underwent hysteroscopy to reevaluate adhesion severity. Pregnancy rate, intrauterine adhesion score, menstrual volume and duration, and endometrial thickness were assessed and adverse events were recorded. RESULTS: (1) PRF group pregnancy rate was significantly higher than the control group (55.0% vs. 20.0%). Mean follow-up time was (17.63 ± 2.33) months. All patients fell pregnant naturally. Four (PRF) and one (control) patients delivered live births without placental complications. (2) Intrauterine adhesion scores decreased compared with treatment-before. (3) In the pictorial blood loss assessment chart, score and menstrual duration during the 3rd menstrual cycle showed significant improvements for both groups. (4) Endometrial thickness also showed an increasing trend, and subendometrial bloodflow improved. (5) No treatment-related serious adverse events were noted. CONCLUSION: Placing PRF into the uterine cavity of infertility patients with IUAs following TCRA is a safe and effective therapeutic method.

10.
PLoS One ; 16(9): e0254627, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34492027

RESUMO

We used fresh leaves of Sophora japonica L. variety 'Qingyun 1' (A0) and 10 superior clones of the same species (A1-A10) to explore leaf morphological characteristics and total particle retention per unit leaf area under natural and artificial simulated dust deposition treatments. Our objectives were to explore the relationship between the two methods and to assess particle size distribution, X-ray fluorescence (XRF) heavy metal content, and scanning electron and atomic force microscopy (SEM and AFM) characteristics of leaf surface microstructure. Using the membership function method, we evaluated the dust retention capacity of each clone based on the mean degree of membership of its dust retention index. Using correlation analysis, we selected leaf morphological and SEM and AFM indices related significantly to dust retention capacity. Sophora japonica showed excellent overall dust retention capacity, although this capacity differed among clones. A5 had the strongest overall retention capacity, A2 had the strongest retention capacity for PM2.5, A9 had the strongest retention capacity for PM2.5-10, A0 had the strongest retention capacity for PM>10, and A2 had the strongest specific surface area (SSA) and heavy metal adsorption capacity. Overall, A1 had the strongest comprehensive dust retention ability, A5 was intermediate, and A7 had the weakest capacity. Certain leaf morphological and SEM and AFM characteristic indices correlated significantly with the dust retention capacity.

11.
Artigo em Inglês | MEDLINE | ID: mdl-34505241

RESUMO

Bibliometric analysis was used in this study for the quantitative evaluation of current research trends on composting. The research articles indexed from the Science Citation Index-Expanded in Web of Science database published from 2000 to 2019 were investigated. The USA, China and Spain were the top three countries considering the number of papers. Amongst the research institutes, CSIC of Spain, Chinese Academy of Sciences and Agriculture & Agri-Food Canada ranked the top three in total publication amount. Journals that published a significant number of literature regarding topics of composting included Environmental Sciences & Ecology, Agriculture and Engineering. In terms of research content, keywords such as heavy metal, heavy metal and biodegradation appeared frequently. In addition, the analysis of keywords revealed the following research hotspots in future studies: investigation of heavy metal passivator, optimisation of composting conditioner, development of all kinds of microorganisms, rational management of the composting process and improvement of solid waste life cycle assessment. To some extent, it helps to understand the current global status and trends of the related research.

12.
Neuro Endocrinol Lett ; 42(5): 312-320, 2021 Sep 10.
Artigo em Inglês | MEDLINE | ID: mdl-34506095

RESUMO

OBJECTIVE: To investigate the negative feedback regulation from rat hippocampus on hypothalamic-pituitary-adrenal (HPA) axis under high temperature and high humidity stress. METHODS: Thirty (30) SD male rats were randomly divided into three groups: control group, high temperature and high humidity group, drug intervention group. The rats in control group were kept in the environment with temperature of 24 ± 1°C and humidity of 50 ± 5%, without any stimulation. The rats in the other groups were exposed to high temperature and high humidity environment for 4 h each day, with temperature of 35±1 °C and humidity of 85±5%. The rats in drug intervention group were intragastrically administered with the glucocorticoid receptor antagonist mifepristone. The administration was continued for 3 weeks. After 3 weeks, the serum levels of corticotropin releasing hormone (CRH), adrenocorticotropic hormone (ACTH) and corticosterone (CORT) were detected by ELISA.The protein and mRNA levels of corticosteroid receptors (MR), glucocorticoid receptors (GR) and inducible nitric oxide synthase (iNOS), transient receptor potential vanilloid 1 (TRPV1) and 11ß-hydroxysteroid dehydrogenase 1 (11ß-HSD1) in hippocampus were determined by immunohistochemistry and in situ hybridization, respectively. The apoptosis of hippocampal cells was examined with TUNEL apoptosis staining. RESULTS: After stimulation with high temperature and high humidity stress for 3 weeks, the serum levels of CRH, ACTH and CORT in the high temperature and high humidity group were significantly increased compared to that of control group; the levels of these indicators in drug intervention group were decreased compared to that of high temperature and high humidity group (P<0.05). In high temperature and high humidity group, the protein and mRNA levels of MR, GR, iNOS in hippocampus of rats were significantly increased compared with that of control group (p<0.05); and the levels of these indicators in drug intervention group were lower than that of high temperature and high humidity group (p<0.05). In addition, compared with the control group, the TRPV1 protein level in hippocampus of rats in high temperature and high humidity group was not significantly changed (p>0.05), while the TRPV1 mRNA level was significantly increased (p<0.05). Neither the protein nor mRNA levels of 11ß-HSD1 showed significant difference compared to control group (p>0.05). The apoptosis of hippocampus cells in the high temperature and high humidity group was significantly increased compared with that of control group (p<0.05); and it was lower in the drug intervention group than that of in high temperature and high humidity group while the result was not significant (p>0.05). CONCLUSION: High temperature and high humidity stress may up-regulate the local expression of iNOS in hippocampus and decrease the activity of glucocorticoids (GC) receptor, then the effective binding of GR-GC would be decreased and the negative feedback regulation of hippocampus on HPA axis would be inhibited. The glucocorticoid receptor antagonist can improve the negative feedback regulation of hippocampus on HPA axis in rat.

13.
ACS Appl Mater Interfaces ; 13(32): 38647-38655, 2021 Aug 18.
Artigo em Inglês | MEDLINE | ID: mdl-34347427

RESUMO

As a new type of nanomaterial, DNA-templated silver nanoclusters (DNA-AgNCs) have been widely studied because of their fluorescence and antibacterial properties. In this study, we combined the DNA-AgNCs with aptamers of bacteria to achieve a novel approach for the visual detection and effective elimination of bacteria. The aptamers of Staphylococcus aureus (S. aureus) were linked to G-rich sequences to achieve fluorescence enhancement when approaching the DNA-AgNCs. The capture of aptamers not only realized the visual monitoring of bacteria but also promoted the antibacterial effects. Additionally, a fluorescent nanofilm with excellent selectivity and antibacterial activity in the detection and elimination of S. aureus was developed based on the DNA-AgNCs. These aptamer-functionalized DNA-AgNCs show significant potential for many applications in food packaging and biomedical engineering.

14.
BMJ Open ; 11(8): e045031, 2021 08 09.
Artigo em Inglês | MEDLINE | ID: mdl-34373293

RESUMO

OBJECTIVES: To conduct a systematic review and meta-analysis of the efficacy and safety of abdominal paracentesis drainage (APD) in patients with acute pancreatitis (AP) when compared with conventional 'step-up' strategy based on percutaneous catheter drainage (PCD). DESIGN: Systematic review and meta-analysis. METHODS: PubMed, EMBASE, Cochrane Library, MEDLINE (OVID), China National Knowledge Infrastructure and Wanfang Database were electronically searched to collect cohort studies and randomised controlled trials (RCTs) from inception to 25 July 2020. Studies related to comparing APD with conventional 'step-up' strategy based on PCD were included. OUTCOMES: The primary outcome was all-cause mortality. The secondary outcomes were the rate of organ dysfunction, infectious complications, hospitalisation expenses and length of hospital stay. RESULTS: Five cohort studies and three RCTs were included in the analysis. Compared with the conventional 'step-up' method, pooled results suggested APD significantly decreased all-cause mortality during hospitalisation (cohort studies: OR 0.48, 95% CI 0.26 to 0.89 and p=0.02), length of hospital stay (cohort studies: standard mean difference (SMD) -0.31, 95% CI -0.53 to -0.10 and p=0.005; RCTs: SMD -0.45, 95% CI -0.64 to -0.26 and p<0.001) and hospitalisation expenses (cohort studies: SMD -2.49, 95% CI -4.46 to -0.51 and p<0.001; RCTs: SMD -0.67, 95% CI -0.89 to -0.44 and p<0.001). There was no evidence to prove that APD was associated with a higher incidence of infectious complications. However, the incidence of organ dysfunction between cohort studies and RCTs subgroup slightly differed (cohort studies: OR 0.66, 95% CI 0.34 to 1.28 and p=0.22; RCTs: OR 0.58, 95% CI 0.35 to 0.98 and p=0.04). CONCLUSIONS: The findings suggest that early application of APD in patients with AP is associated with reduced all-cause mortality, expenses during hospitalisation and the length of stay compared with the 'step-up' strategy without significantly increasing the risk of infectious complications. These results must be interpreted with caution because of the limited number of included studies as well as a larger dependence on observational trials. PROSPERO REGISTRATION NUMBER: CRD42020168537.


Assuntos
Pancreatite , Paracentese , Drenagem , Hospitalização , Humanos , Tempo de Internação , Pancreatite/terapia , Paracentese/efeitos adversos
15.
J Gynecol Oncol ; 2021 Jul 16.
Artigo em Inglês | MEDLINE | ID: mdl-34431256

RESUMO

OBJECTIVE: External beam radiation therapy (EBRT) with concurrent chemotherapy followed by intracavitary brachytherapy is the standard treatment in locally advanced cervical cancer. This study examined the brachytherapy utilization rate and evaluated the effect of brachytherapy on survival in cervical cancer patients in Korea. METHODS: In this study, data from the Korea Central Cancer Registry and Korean National Health Insurance Service and data on mortality from Statistics Korea were linked and used. Patients with other cancers, distant metastasis at diagnosis, or unknown stage or who underwent hysterectomy were excluded. A total of 12,721 cervical cancer patients were analyzed in this study. RESULTS: The brachytherapy utilization rate (%) was calculated as the proportion of patients who received brachytherapy among those who received curative EBRT. The brachytherapy utilization rate decreased from 84% in 2005 to 78% in 2013 (p<0.001). Brachytherapy utilization rates varied by region, ranging from 72% to 100% except for in Jeju Island, where the rate was 56%. The brachytherapy utilization rate was lower in patients older than 80 years; patients with localized disease, non-squamous cell carcinoma, or Charlson comorbidity index 3 or more; patients diagnosed after 2010; patients from certain regions; patients receiving medical aid; and patients who underwent gynecologic procedures. Multivariable Cox regression analysis showed that brachytherapy when added to curative EBRT was independently associated with better cancer-specific survival (CSS) and overall survival (OS) than curative EBRT only. CONCLUSION: The brachytherapy utilization rate decreased from 2005 to 2013 and varied by region in Korea. Brachytherapy use is independently associated with significantly higher CSS and OS in cervical cancer.

16.
Eur J Dermatol ; 2021 Aug 26.
Artigo em Inglês | MEDLINE | ID: mdl-34463275

RESUMO

BACKGROUND: Psoriatic arthritis (PsA) is an inflammatory form of arthritis that appears approximately 7-10 years after psoriasis and remains undiagnosed in most of patients. Currently, only a few quantitative and succinct PsA-risk prediction models are available. OBJECTIVES: The aim of this study was to establish and validate a prediction model for quantitatively assessing the risk of PsA in moderate and severe plaque psoriasis patients. MATERIALS & METHODS: A non-interventional and cross-sectional study was conducted. Demographic, clinical, and laboratory records were collected and blindly reviewed. Logistic regression was used to develop this prediction model. With C-index and calibration curve, internal validation was performed. Five-fold cross validation, external validation and decision curve analysis (DCA) were also applied to assess this model. RESULTS: Among 405 patients, 111 patients had PsA. Arthralgia (OR = 39.346; 95% CI: 20.139-82.579), C-reactive protein (OR = 2.008; 95% CI: 1.051-3.838), lymphocyte level (OR = 0.341; 95% CI: 0.177-0.621), hypertension (OR = 0.235; 95% CI: 0.077-0.660) and disease duration (OR = 1.033; 95% CI: 0.998-1.071) were identified as potential predictors affecting the risk of transition from moderate and severe PsO to PsA. C-index for the prediction nomogram was 0.911 (95% CI: 0.879-0.943), and was confirmed to be 0.905 through 1000-time bootstrapping internal validation. Cross validation and external validation were preformed and proved the accuracy and generalizability of this prediction model. CONCLUSION: This study establishes a quantitative predictive nomogram with good predictive power for assessing the risk of PsA in patients with moderate and severe PsO.

17.
IEEE Trans Cybern ; PP2021 Aug 31.
Artigo em Inglês | MEDLINE | ID: mdl-34464284

RESUMO

In this article, being different from conventional time-discretization (simply called discretization) formulas, explicit linear left-and-right 5-step (ELLR5S) formulas with sixth-order precision are proposed. The general sixth-order ELLR5S formula with four variable parameters is developed first, and constraints of these four parameters are displayed to guarantee the zero stability, consistence, and convergence of the formula. Then, by choosing specific parameter values within constraints, eight specific sixth-order ELLR5S formulas are developed. The general sixth-order ELLR5S formula is further utilized to generate discrete zeroing neural network (DZNN) models for solving time-varying linear and nonlinear systems. For comparison, three conventional discretization formulas are also utilized. Theoretical analyses are presented to show the performance of ELLR5S formulas and DZNN models. Furthermore, abundant experiments, including three practical applications, that is, angle-of-arrival (AoA) localization and two redundant manipulators (PUMA560 manipulator and Kinova manipulator) control, are conducted. The synthesized results substantiate the efficacy and superiority of sixth-order ELLR5S formulas as well as the corresponding DZNN models.

18.
Artigo em Inglês | MEDLINE | ID: mdl-34389952

RESUMO

The prevalence and interactions with biofilm and disinfectant of opportunistic pathogens in drinking water supply systems (DWSSs) have been extensively interpreted. In contrast, the large geographical distribution and in situ removal of opportunistic pathogens are overlooked aspects. Here, paired source and tap water samples of 36 parallel DWSSs across China were collected, with five common waterborne pathogens characterized by qPCR. From source to tap, the removal of bacterial biomass (16S rRNA gene copy number) was 1.10 log, and gene marker removal of five opportunistic pathogens ranged from 0.66 log to 2.27 log, with the order of Escherichia coli > Mycobacterium spp. > Clostridium perfringens > Bacillus cereus > Aeromonas hydrophila. Different with bacterial community, geographical location and source water types (river or reservoir) were not key contributor to variation of opportunistic pathogens. Gene marker removal efficacies of E. coli, Mycobacterium spp., and C. perfringens from source to tap were restricted to removal efficacy of overall bacterial biomass, while abundance of B. cereus in tap water linked to the input of B. cereus from source water. Although culture-dependent approach is important for pathogen enumeration in drinking water, qPCR-based molecular survey shows advantages of quantifiable high-throughput and easy operation, providing abundant and timely information on pathogen occurrence in water. This study provides the in situ, molecular-level evidence toward differential propagation features of multiple opportunistic pathogens in DWSSs and suggests the source protection and early warning of treatment-resistant pathogens.

19.
ACS Chem Biol ; 16(8): 1318-1324, 2021 08 20.
Artigo em Inglês | MEDLINE | ID: mdl-34374518

RESUMO

As enzymes that mediate the attachment of long-chain fatty acids to cysteine residues, ZDHHC proteins have been reported to be promising therapeutic targets for treating cancer and autoimmune diseases. Yet, due to the lack of potent selective inhibitors, scrutiny of the biological functions of ZDHHCs has been limited. The main hindrance for developing ZDHHC inhibitors is the lack of a facile high-throughput assay. Here, we developed a ZDHHC3/7/20 high-throughput assay based on the acylation-coupled lipophilic induction of polarization (Acyl-cLIP) method and screened several potential ZDHHC inhibitors. Furthermore, we demonstrated that in vitro results from the Acyl-cLIP assay are supported by the results from cell-based assays. We envision that this new ZDHHC3/7/20 Acyl-cLIP assay will accelerate the high-throughput screening of large compound libraries for improved ZDHHC inhibitors and provide therapeutic benefits for cancer and autoimmune diseases.

20.
Biosens Bioelectron ; 193: 113554, 2021 Aug 09.
Artigo em Inglês | MEDLINE | ID: mdl-34391177

RESUMO

Cardiac troponin I (cTnI) is an efficient and specific biomarker for the accurate diagnosis of acute myocardial infarction (AMI), one of the diseases with the highest mortality worldwide. Due to the short course and high fatality of this disease, a rapid, accurate and portable device for quantitative detection is urgently needed for early diagnosis and treatment. In this work, we designed a handheld device based on a dual-gate ion-sensitive field-effect transistor (ISFET) for early and accurate warning of AMI through cTnI detection. A one-step enzyme-linked immunosorbent assay strategy was proposed for use in this device to recognize trace cTnI in serum, converting the cTnI concentration to a drain-source current generated by an ultrasensitive ISFET. This portable device exhibited an ultrahigh sensitivity of 132 pA pg-1·mL-1, a wide linear range from 1 to 1000 pg/mL that enabled coverage far exceeding the threshold level (280 pg/mL), and a low detection limit of 0.3 pg/mL for the cTnI assay, which was much lower than the current diagnostic cut-off for a healthy control level for AMI (40 pg/mL). In addition, this handheld device showed satisfactory selectivity and reliable results in the analysis of real serum within 20 min, indicating its potential applications in early screening and diagnosis for the clinical evaluation of AMI.

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