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1.
Methods Mol Biol ; 2186: 77-94, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-32918731

RESUMO

Nanopore sensing is a powerful lab-on-a-chip technique that allows for the analysis of biomarkers present in small sample sizes. In general, nanopore clogging and low detection accuracy arise when the sample becomes more and more complex such as in blood or lysate. To address this, we developed an OmpG nanopore that distinguishes among not only different proteins in a mixture but also protein homologs. Here, we describe this OmpG-based nanopore system that specifically analyzes targets biomarkers in complex mixtures.

2.
Methods Mol Biol ; 2186: 115-133, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-32918733

RESUMO

Many enzymatic activity assays are based on either (1) identifying and quantifying the enzyme with methods such as western blot or enzyme-linked substrate assay (ELISA) or (2) quantifying the enzymatic reaction by monitoring the changing levels of either product or substrate. We have generated an outer membrane protein G (OmpG)-based nanopore approach to distinguish enzyme identity as well as analyze the enzyme's catalytic activity. Here, we engineered an OmpG nanopore with a peptide cut site inserted into one of its loops to detect proteolytic behavior. In addition, we generated an OmpG nanopore with a single-stranded DNA attached to a loop for analyzing nucleolytic cleavage. This OmpG nanopore approach may be highly useful in analyzing specific enzymes in complex biological samples, or in directly determining kinetics of enzyme-substrate complex association and dissociation.

3.
Methods Mol Biol ; 2186: 159-169, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-32918736

RESUMO

Bacterial porins often exhibit ion conductance and gating behavior which can be modulated by pH. However, the underlying control mechanism of gating is often complex, and direct inspection of the protein structure is generally insufficient for full mechanistic understanding. Here we describe Pretzel, a computational framework that can effectively model loop-based gating events in membrane proteins. Our method combines Monte Carlo conformational sampling, structure clustering, ensemble energy evaluation, and a topological gating criterion to model the equilibrium gating state under the pH environment of interest. We discuss details of applying Pretzel to the porin outer membrane protein G (OmpG).

4.
Methods Mol Biol ; 2186: 213-225, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-32918740

RESUMO

Reconstituted model membrane systems are powerful platforms to tackle interesting problems existing in membrane biology. One of the barriers to efficient drug delivery, as therapeutics to disease, is the physical membrane barrier of the cell. Small molecule can typically diffuse through the membrane; however, biomolecules such as proteins or nucleic acids cannot passively diffuse the bilayer and thus much research has been geared to engineering protein and/or nucleic acids delivery methods. One delivery method uses cell penetrating peptides (CPPs). In this chapter, we introduce the model "membrane army" arranged in dimple chip to study the delivery of ß-galactosidase by a CPP known as Pep-1. This method uses droplet interface bilayer technology (DIB). It accelerates the speed to screen through the working conditions in CPP-assisted protein translocations because each chip provides dimples that can accommodate 36 pairs of droplets or 18 model bilayers. We will use one of the successful translocation conditions of ß-galactosidase delivery as the example to illustrate how the model "membrane army" is built and utilized.

5.
Artigo em Inglês | MEDLINE | ID: mdl-33041225

RESUMO

BACKGROUND: Despite the increasing incidence rate of colorectal neuroendocrine carcinoma (CR-NEC), there are still few sequencing data to depict the genomic characteristics of CR-NEC. PATIENTS AND METHODS: Next-generation sequencing data of CR-NEC, colorectal adenocarcinoma (COREAD), lung neuroendocrine carcinoma (lung NEC), and gastrointestinal neuroendocrine tumor (GI-NET) were retrieved from the American Association of Cancer Research Project Genomics, Evidence, Neoplasia, Information, Exchange (GENIE) database platform. Overall survival data of patients were obtained from cBioPortal. RESULTS: The median tumor mutation burden (TMB) was 5.18 per megabase. TP53 (65.5%), APC (59.5%), KRAS (36.9%), BRAF (20.2%), and RB1 (16.7%) were the most common genes harboring somatic mutations. Nearly all of the BRAF mutations (88.2%) caused V600E. The most common copy number alterations were gain of MYC (12.3%), loss of RB1 (10.7%), and loss of PTEN (5.4%). Compared to lung NEC and GI-NET, the genetic characteristics of CR-NEC were more similar to that of COREAD. CR-NEC had a higher rate of potentially targetable gene alterations compared to lung NEC and GI-NET, and BRAFV600E might be a promising treatment target. Survival analysis indicated that patients with high TMB had significantly worse survival than patients with low TMB (P < .001). In addition, KRAS and RB1 alteration were found to be correlated with worse survival (both P = .023). CONCLUSION: CR-NEC has genetic alterations that are more similar to COREAD than other entities. A substantial group of CR-NEC harboring potentially targetable alterations (BRAFV600E) deserves to be tested in clinical practice.

6.
Artigo em Inglês | MEDLINE | ID: mdl-33044052

RESUMO

AIMS: Interleukin-35 (IL-35), a novel anti-inflammatory cytokine, has recently been implicated in tumor development, progression, and survival. However, the relationship between serum IL-35 levels and gastric cancer (GC) is inconclusive. Here, we performed this study to clarify the role of serum level of IL-35 in GC patients. METHODS: We enrolled 180 GC patients and 170 healthy controls and used enzyme-linked immunosorbent assay to detect serum IL-35 levels. The clinical relevance between IL-35 and clinical pathology parameters was assessed. Univariate and multivariate logistic regressions were used to determine the feasibility of IL-35 as a clinical biomarker. RESULTS: We observed that serum IL-35 levels were significantly higher in GC patients (17.559 ± 13.266 pg/mL) than in healthy controls (8.077 ± 3.801 pg/mL, P < .001). High serum IL-35 levels were significantly associated with clinical stage (P = .048) and Helicobacter pylori (HP) infection (P < .001). The Kaplan-Meier survival analysis indicated that patients in the high-IL-35 group had poor overall survival (OS) and progression-free survival (PFS) (median OS: 26.0 vs 36.0 months, P < .001; median PFS: 18.0 vs.26.0 months, P = .044). Multivariate analyses demonstrated that serum IL-35 was an independent prognostic factor for GC (OS: hazard ratio [HR] = 1.031 [95% CI, 1.017-1.045], P < .001; PFS: HR = 1.029 [95% CI, 1.015-1.043], P < .001). CONCLUSIONS: High serum IL-35 levels are associated with poor disease prognosis in GC patients, and it may be become a new and promising biomarker for prognosis of gastric cancer.

7.
Environ Model Softw ; : 104885, 2020 Oct 06.
Artigo em Inglês | MEDLINE | ID: mdl-33041631

RESUMO

System-of-systems approaches for integrated assessments have become prevalent in recent years. Such approaches integrate a variety of models from different disciplines and modeling paradigms to represent a socio-environmental (or social-ecological) system aiming to holistically inform policy and decision-making processes. Central to the system-of-systems approaches is the representation of systems in a multi-tier framework with nested scales. Current modeling paradigms, however, have disciplinary-specific lineage, leading to inconsistencies in the conceptualization and integration of socio-environmental systems. In this paper, a multidisciplinary team of researchers, from engineering, natural and social sciences, have come together to detail socio-technical practices and challenges that arise in the consideration of scale throughout the socio-environmental modeling process. We identify key paths forward, focused on explicit consideration of scale and uncertainty, strengthening interdisciplinary communication, and improvement of the documentation process. We call for a grand vision (and commensurate funding) for holistic system-of-systems research that engages researchers, stakeholders, and policy makers in a multi-tiered process for co-creation of knowledge and solutions to major socio-environmental problems.

8.
J Int Med Res ; 48(10): 300060520961684, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-33045897

RESUMO

Autoimmune polyglandular syndrome (APS) is a rare disease that is characterized by autoimmune reactions to multiple endocrine and non-endocrine organs, which can be divided into four main types. The principal manifestations of APS-3 are autoimmune thyroid disease and other autoimmune diseases, such as type 1 diabetes, atrophic gastritis, pernicious anemia, vitiligo, alopecia, and myasthenia gravis, but not Addison's disease or hypoparathyroidism. Here we report a case demonstrating the rare coexistence of growth hormone deficiency and hyperthyroidism with sexual dysgenesis, secondary amenorrhea, cardiomegaly, splenomegaly, hypoproteinemia, pleural effusion, seroperitoneum, pericardial effusion, anasarca, osteoporosis, vitamin D deficiency, iron-deficiency anemia, poor blood coagulation, leucocytopenia, peripheral neuropathy, hyperuricemia, ichthyosis, tinea cruris, and onychomycosis.

9.
Zhongguo Yi Liao Qi Xie Za Zhi ; 44(5): 443-447, 2020 Oct 08.
Artigo em Chinês | MEDLINE | ID: mdl-33047571

RESUMO

At present, the most commonly used sterilization method for medical devices is ethylene oxide sterilization. The residue after sterilization is closely related to the health of the people who contacted with the medical devices. The study team analyzed the possible residues of medical devices after sterilization with ethyleneoxide. It is suggested that ethylene oxide, 2-chloroethanol and ethylene glycol should be evaluated comprehensively through the analysis of factors such as production links of medical devices, production process of ethylene oxide, sterilization process, sterilization environment and detection method.

10.
Zhongguo Shi Yan Xue Ye Xue Za Zhi ; 28(5): 1787-1790, 2020 Oct.
Artigo em Chinês | MEDLINE | ID: mdl-33067991

RESUMO

The process of thrombus formation in vivo is complex, which is affected by the platelets, clotting system, and vessels, as well as blood flow. The previous research ways, which were either static or shear stress-mimicking ex vivo, could not reflect the condition in vivo completely. In recent years, The high resolution confocal microscope combined with bioluminescence system was developed which can be used to observe the animal thrombus formation in real time in vivo. By using this system, scientists have gotten a novel knowledge about the thrombus formation. In this review, the operating steps of this system, the hierarchical structure of thrombs revealed by this system and the related mechanism are sammrized briefly.


Assuntos
Trombose , Animais , Coagulação Sanguínea , Plaquetas , Microscopia
11.
NPJ Genom Med ; 5: 31, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33083009

RESUMO

Recent advances in Bionano optical mapping (BOM) provide a great insight into the determination of structural variants (SVs), but its utility in identification of clinical likely pathogenic variants needs to be further demonstrated and proved. In a family with two consecutive pregnancies affected with ventriculomegaly, a splicing likely pathogenic variant at the LAMA1 locus (NM_005559: c. 4663 + 1 G > C) inherited from the father was identified in the proband by whole-exome sequencing, and no other pathogenic variant associated with the clinical phenotypes was detected. SV analysis by BOM revealed an ~48 kb duplication at the LAMA1 locus in the maternal sample. Real-time quantitative PCR and Sanger sequencing further confirmed the duplication as c.859-153_4806 + 910dup. Based on these variants, we hypothesize that the fetuses have Poretti-Boltshauser syndrome (PBS) presenting with ventriculomegaly. With the ability to determine single nucleotide variants and SVs, the strategy adopted here might be useful to detect cases missed by current routine screening methods. In addition, our study may broaden the phenotypic spectrum of fetuses with PBS.

12.
Plant Signal Behav ; : 1836884, 2020 Oct 21.
Artigo em Inglês | MEDLINE | ID: mdl-33084518

RESUMO

Heavy metal pollution is a major environmental stress affecting plant growth and development. The heavy metal cadmium inhibits various physiological processes in plants, including seed germination and seedling growth, photosynthesis, and antioxidation. Extensive research has been conducted on the toxic effects of Cd2+ on plants and the mechanisms of Cd2+ tolerance. Here, we review recent advancements in our understanding of the absorption, transport, and accumulation of Cd2+ in plants and the mechanisms of Cd2+ tolerance.

13.
J Colloid Interface Sci ; 583: 166-177, 2020 Sep 17.
Artigo em Inglês | MEDLINE | ID: mdl-33002689

RESUMO

Photodynamic therapy (PDT) is a minimally invasive treatment strategy that uses photosensitizers and light in combination with oxygen to generate cytotoxic singlet oxygen (1O2) to kill cancer cells by necrosis or apoptosis. However, the treatment effects are still not satisfactory because of the tumor hypoxia and the PDT-induced oxygen consumption. Here, we have successfully synthesized dendritic mesoporous organosilica nanoparticles (MONs) with large center-radial pore structure that can be used to simultaneously encapsulate indocyanine green (ICG, <1 nm) and macromolecule catalase (CAT, 2.0 nm × 6.0 nm × 9.0 nm) to overcome the tumor hypoxia. Upon 808 nm laser irradiation, ICG as the organic NIR dye can generate highly cytotoxic singlet oxygen (1O2) and other reactive oxygen species (ROS) to kill cancer cells and realize photoacoustic (PA) imaging. The catalase can decompose the endogenous H2O2 in malignant cancerous cells into O2 bubble to simultaneously intensify the ultrasound (US) imaging signal and enhance PDT efficacy. These results indicate that the ICG-CAT@MONs holds great promise in multimodal photoacoustic / ultrasound image-guided tumor PDT therapy.

15.
Sci Total Environ ; 755(Pt 2): 142617, 2020 Sep 30.
Artigo em Inglês | MEDLINE | ID: mdl-33045602

RESUMO

Although benzothiazole and its derivatives (BTHs) are considered emerging contaminants in diverse environments and organisms, little information is available about their contamination profiles and health impact in ambient particles. In this study, an optimized method of ultrasound-assisted extraction coupled with the selected reaction monitoring (SRM) mode of GC-EI-MS/MS was applied to characterize and analyze PM2.5-bound BTHs from three cities of China (Guangzhou, Shanghai, and Taiyuan) during the winter of 2018. The total BTH concentration (ΣBTHs) in PM2.5 samples from the three cities decreased in the order of Guangzhou > Shanghai > Taiyuan, independently of the PM2.5 concentration. Despite the large variation in concentration of ΣBTHs in PM2.5, 2-hydroxybenzothiazole (OTH) was always the predominant compound among the PM2.5-bound BTHs and accounted for 50-80% of total BTHs in the three regions. Results from human exposure assessment and toxicity screening indicated that the outdoor exposure risk of PM2.5-bound BTHs in toddlers was much higher than in adults, especially for OTH. The developmental and reproduction toxicity of OTH was further explored in vivo and in vitro. Exposure of mouse embryonic stem cells (mESCs) to OTH for 48 h significantly increased the intracellular reactive oxygen species (ROS) and induced DNA damage and apoptosis via the functionally activating p53 expression. In addition, the growth and development of zebrafish embryos were found to be severely affected after OTH treatment. An overall metabolomics study was conducted on the exposed zebrafish larvae. The results indicated that exposure to OTH inhibited the phenylalanine hydroxylation reaction, which further increased the accumulation of toxic phenylpyruvate and acetylphenylalanine in zebrafish. These findings provide important insights into the contamination profiles of PM2.5-bound BTHs and emphasize the health risk of OTH.

16.
PLoS Negl Trop Dis ; 14(10): e0008772, 2020 Oct 15.
Artigo em Inglês | MEDLINE | ID: mdl-33057334

RESUMO

Tsutsugamushi disease (TD) is an acute infectious disease caused by Orientia tsutsugamushi. This study aimed to analyze the epidemiological features of TD, investigate chigger mites and their hosts, and investigate the meteorological factors affecting TD incidence and the host of O. tsutsugamushi in Xiamen city, China. Data on reported TD cases were collected from 2006 to 2018. Spearman's correlation test were used for identifying the relationship between meteorological factors and TD incidence and whether meteorological factors affect the host of O. tsutsugamushi. The incidence of reported TD increased gradually from 2006, reached a peak of 4.59 per 100,000 persons in 2014, and then decreased gradually. The TD incidence was seasonal, with epidemic periods occurred mainly in summer and autumn. Patients aged 40-60 years had the highest proportion of cases, accounting for 44.44% of the total cases. Farmers had the largest number of cases among all occupational groups. Rattus Norvegicus was the most common host, accounting for the largest proportion of cases (73.00%), and the highest rat density was observed in March and October every year. There were significant positive correlations between the number of reported cases and average temperature, sunshine duration, and rainfall as well as between rat density and average temperature. On phylogenetic analysis, 7 sequences of hosts and human TD cases obtained from health records demonstrated the highest similarities to the Kato, Karp, and Gilliam strains. No correlations were observed between rat density, and sunshine duration and rainfall. The transmission of TD in Xiamen city, China, was seasonal, and its incidence was affected by several meteorological factors including average temperature, sunshine duration, and rainfall. However, the host of O. tsutsugamushi was only affected by average temperature.

17.
Biochim Biophys Acta Biomembr ; : 183485, 2020 Oct 12.
Artigo em Inglês | MEDLINE | ID: mdl-33058855

RESUMO

Membrane protein pores have emerged as powerful nanopore sensors for single-molecule detection. OmpG, a monomeric nanopore, is comprised of fourteen ß-strands connected by seven flexible extracellular loops. The OmpG nanopore exhibits pH-dependent gating as revealed by planar lipid bilayer studies. Current evidence strongly suggests that the dynamic movement of loop 6 is responsible for the gating mechanism. In this work, we have shown that enhancing the electrostatic repulsion forces between extracellular loops suppressed the pH-dependent gating. Our mutant containing additional negative charges in loop 6 and loop 1 exhibited minimal spontaneous gating and reduced sensitivity to pH changes compared to the wild type OmpG. These results provide new evidence to support the mechanism of OmpG gating controlled by the complex electrostatic network around the gating loop 6. The pH-independent quiet OmpG pores could potentially be used as a sensing platform that operates at a broad range of pH conditions.

18.
Zhongguo Dang Dai Er Ke Za Zhi ; 22(10): 1114-1118, 2020 Oct.
Artigo em Chinês | MEDLINE | ID: mdl-33059810

RESUMO

This article reports the clinical and genetic features of a case of Tatton-Brown-Rahman syndrome (TBRS) caused by DNMT3A gene mutation. A girl, aged 8 months and 14 days, had the clinical manifestations of psychomotor retardation, hypotonia, ventricular enlargement, and tonsillar hernia malformation. Gene analysis identified a novel heterozygous mutation, c.134C>T(p.A45V), in the DNMT3A gene, and the wild type was observed at this locus in her parents. This mutation was determined as a possible pathogenic mutation according to the guidelines of American College of Medical Genetics and Genomics, which had not been reported in previous studies and conformed to autosomal dominant inheritance. This child was diagnosed with TBRS. TBRS often has a good prognosis, with overgrowth and mental retardation as the most common clinical manifestations, and behavioral and psychiatric problems, scoliosis, and afebrile seizures are possible complications of TBRS. The possibility of TBRS should be considered for children with overgrowth and mental retardation, and genetic diagnosis should be conducted when necessary.

19.
J Immunol Res ; 2020: 2847316, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33062719

RESUMO

Objectives: The COVID-19 epidemic triggered by coronavirus SARS-CoV-2 is rapidly spreading around the globe. This study is aimed at finding out the suspected or confirmed SARS-CoV-2 infection in patients with inflammatory bowel disease (IBD) in Hubei province, China. We also investigated symptoms, medications, life quality, and psychological issues of IBD patients under the ongoing pandemic. Methods: We conducted a self-reported questionnaire survey via an online survey platform. SARS-CoV-2 infection-related data was collected from IBD patients. The status quo of medications and symptoms of the subjects were investigated. Life quality, depression, and anxiety were measured by clinical questionnaires and rated on scoring systems. Results: A total of 204 IBD patients from Hubei province were included in this study. No suspected or confirmed SARS-CoV-2 infection case was found in this study. As a result of city shutdown, two-thirds of the patients (138/204) in our series reported difficulty in accessing medicines and nearly half of them (73/138) had to discontinue medications. Apart from gastrointestinal symptoms, systemic symptoms were common while respiratory symptoms were rare in the cohort. Though their quality of life was not significantly lowered, depression and anxiety were problems that seriously affected them during the COVID-19 epidemic. Conclusions: Inaccessibility to medications is a serious problem for IBD patients after city shutdown. Efforts have to be made to address the problems of drug withdrawal and psychological issues that IBD patients suffer from during the COVID-19 outbreak.

20.
Acta Otolaryngol ; : 1-7, 2020 Oct 16.
Artigo em Inglês | MEDLINE | ID: mdl-33063574

RESUMO

BACKGROUND: Developmental evaluation of deaf children before cochlear implantation (CI) has not been given enough attention. OBJECTIVES: This study was designed to evaluate the comprehensive developmental performance of deaf children who are CI candidates. MATERIALS AND METHODS: The medical records of pediatric candidates for CI were reviewed. Five hundred children (287 boys; median age: 21.00 months; range: 6-72 months) with a diagnosis of severe-to-profound hearing loss were included. Preoperative developmental evaluation, including gross motor, fine motor, adaptability, language and social skill were retrieved. Comprehensive developmental performances including verbal and nonverbal skill were assessed. Multivariate linear regression analysis was used to analyze the related developmental factors. RESULTS: Compared with normal developmental metrics, deaf children had developmental delay (p < .001), which occurred in not only the verbal but also nonverbal skill (all p < .05). Of the 500 deaf children, 50 (10%) had normal performance; the majority (51.6%) had mild neurological dysfunction. Of all the sub-developments, language developed worst (normal rate: 4.2%) and gross motor developed best (normal rate: 42%). Age of intervention was a risk factor for the developmental level of deaf children (ß = -0.340, p < .05). CONCLUSIONS: Pediatric candidates for CI had both verbal and nonverbal developmental delay. Age of intervention was a risk factor for the developmental level. SIGNIFICANCE: Comprehensive developmental evaluation of deaf children before cochlear implantation (CI) should be paid enough attention. Early intervention for improving hearing was of significance.

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