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1.
Gastroenterology ; 164(7): 1189-1201.e13, 2023 06.
Artigo em Inglês | MEDLINE | ID: mdl-36898551

RESUMO

BACKGROUND & AIMS: Inflammatory bowel disease (IBD) is a widespread gastrointestinal inflammatory disorder with globally increasing incidence. Clostridioides difficile infection (CDI) often occurs in patients with intestinal dysbiosis, such as after antibiotic therapy. Patients with IBD have increased incidence of CDI and the clinical outcome of IBD is reportedly worsened by CDI. However, the underlying reasons remain poorly understood. METHODS: We performed a retrospective single-center and a prospective multicenter analysis of CDI in patients with IBD, including genetic typing of C difficile isolates. Furthermore, we performed a CDI mouse model to analyze the role of the sorbitol metabolization locus that we found distinguished the main IBD- and non-IBD-associated sequence types (STs). Moreover, we analyzed sorbitol concentration in the feces of patients with IBD and healthy individuals. RESULTS: We detected a significant association of specific lineages with IBD, particularly increased abundance of ST54. We found that in contrast to the otherwise clinically predominant ST81, ST54 harbors a sorbitol metabolization locus and was able to metabolize sorbitol in vitro and in vivo. Notably, in the mouse model, ST54 pathogenesis was dependent on intestinal inflammation-induced conditions and the presence of sorbitol. Furthermore, we detected significantly increased sorbitol concentrations in the feces of patients with active IBD vs patients in remission or healthy controls. CONCLUSIONS: Sorbitol and sorbitol utilization in the infecting C difficile strain play major roles for the pathogenesis and epidemiology of CDI in patients with IBD. CDI in patients with IBD may thus be avoided or improved by elimination of dietary sorbitol or suppression of host-derived sorbitol production.


Assuntos
Clostridioides difficile , Infecções por Clostridium , Doenças Inflamatórias Intestinais , Animais , Camundongos , Estudos Retrospectivos , Sorbitol/uso terapêutico , Estudos Prospectivos , Doenças Inflamatórias Intestinais/terapia , Infecções por Clostridium/epidemiologia , Infecções por Clostridium/tratamento farmacológico , Bactérias/genética
2.
Inorg Chem ; 63(15): 6692-6700, 2024 Apr 15.
Artigo em Inglês | MEDLINE | ID: mdl-38573894

RESUMO

The fabrication of molecular crystalline materials with fast, multistimuli-responsive behavior and the construction of the corresponding structure-activity relationship are of extraordinary significance for the development of smart materials. In this context, three multistimuli-responsive functional metal-organic polyhedra (MOP), {[Dy2(bcbp)3(NO3)1.5(H2O)7]·Cl4.2·(NO3)0.3·H2O}n (1), {[Dy2(bcbp)4(H2O)8]Cl6}n (2), and {[Eu2(bcbp)4(H2O)10]Cl6·H2O}n (3; bcbp = 1,1'-bis(4-carboxyphenyl)-4,4'-bipyridinium), were successfully prepared and characterized. All of the compounds exhibit rapid and reversible photochromic and electrochromic dual-responsive behaviors. Furthermore, benefiting from the well-defined crystal structure and different responsive behaviors, the photoinduced electron transfer (PIET) process and structure-activity relationship were explored. In addition, considering the excellent photochromic performance, function filter paper and smart organic glass were successfully prepared and used for ink-free printing and UV light detection.

3.
Genomics ; 115(2): 110573, 2023 03.
Artigo em Inglês | MEDLINE | ID: mdl-36746218

RESUMO

Considerable studies have given convincing evidence of a forefront position for vascular aging in preventing cardiovascular disease. Various functions of Long non-coding RNAs (lncRNAs) are becoming increasingly distinct in aging-related diseases. This study aims at a better insight into the expression profile and mechanisms of lncRNAs in vascular senescence. High-throughput sequencing was used to detect the differential expression (DE) of lncRNAs and mRNAs in the aorta of 96 W and 8 W-old mice, while 1423 lncRNAs and 80 mRNAs were differentially expressed. By performing GO and KEGG enrichment analysis, we found that DE lncRNAs were mainly involved in purine metabolism and cGMP-PKG signaling pathways. In addition, a co-expression functional network of DE lncRNAs and DE mRNAs was constructed, and ENSMUST00000218874 could interact with 41 DE mRNAs, suggesting that it may play an essential role in vascular senescence. This study reveals DE lncRNAs in naturally aging vascular, which may provide new ideas and targets for aging-related cardiovascular diseases.


Assuntos
RNA Longo não Codificante , Transcriptoma , Camundongos , Animais , RNA Longo não Codificante/genética , RNA Longo não Codificante/metabolismo , Aorta/metabolismo , Transdução de Sinais , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Perfilação da Expressão Gênica , Redes Reguladoras de Genes
4.
Telemed J E Health ; 30(2): 393-403, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-37449779

RESUMO

Background: With advances in technology, teledermatology (TD) research has increased. However, an updated comprehensive quantitative analysis of TD research, especially one that identifies emerging trends of TD research in the coronavirus disease 2019 (COVID-19) era, is lacking. Objective: To conduct a scientometric analysis of TD research documents between 2002 and 2021 and explore the emerging trends. Methods: CiteSpace was used to perform scientometric analysis and yielded visualized network maps with corresponding metric values. Emerging trends were identified mainly through burst detection of keywords/terms, co-cited reference clustering analysis, and structural variability analysis (SVA). Results: A total of 932 documents, containing 27,958 cited references were identified from 2002 to 2021. Most TD research was published in journals from the "Dermatology" and "Health Care Sciences & Services" categories. American, Australian, and European researchers contributed the most research and formed close collaborations. Keywords/terms with strong burst values to date were "primary care," "historical perspective," "emerging technique," "improve access," "mobile teledermoscopy (TDS)," "access," "skin cancer," "telehealth," "recent finding," "artificial intelligence (AI)," "dermatological care," and "dermatological condition." Co-cited reference clustering analysis showed that the recently active cluster labels included "COVID-19 pandemic," "skin cancer," "deep neural network," and "underserved population." The SVA identified two reviews (Tognetti et al. and Mckoy et al.) that may be highly cited in the future. Conclusion: During and after the COVID-19 era, emerging trends in research on TD (especially mobile TDS) may be related to skin cancer and AI as well as further exploration of primary care in underserved areas.


Assuntos
COVID-19 , Neoplasias Cutâneas , Humanos , Inteligência Artificial , Austrália , Pandemias , COVID-19/epidemiologia
5.
J Environ Manage ; 358: 120886, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38648726

RESUMO

Intercropping-driven changes in nitrogen (N)-acquiring microbial genomes and functional expression regulate soil N availability and plant N uptake. However, present data seem to be limited to a specific community, obscuring the viewpoint of entire N-acquiring microbiomes and functions. Taking maize intercropped with legumes (peanut and soybean) and non-legumes (gingelly and sweet potato) as models, we studied the effects of intercropping on N transformations and N-acquiring microbiomes in rhizosphere soil across four maize growth stages. Meanwhile, we compiled promising strategies such as random forest analysis and structural equation model for the exploitation of the associations between microbe-driven N dynamics and soil-plant N trade-offs and maize productivity. Compared with monoculture, maize intercropping significantly increased the denitrification rate of rhizosphere soils across four maize growth stages, net N mineralization in the elongation and flowering stages, and the nitrification rate in the seedling and mature stages. The abundance of most N-acquiring microbial populations was influenced significantly by intercropping patterns and maize growth stages. Soil available N components (NH4+-N, NO3--N, and dissolved organic N content) showed a highly direct effect on plant N uptake, which mainly mediated by N transformations (denitrification rate) and N-acquiring populations (amoB, nirK3, and hzsB genes). Overall, the adaptation of N-acquiring microbiomes to changing rhizosphere micro-environments caused by intercropping patterns and maize development could promote soil N transformations and dynamics to meet demand of maize for N nutrient. This would offer another unique perspective to manage the benefits of the highly N-effective and production-effective intercropping ecosystems.


Assuntos
Nitrogênio , Rizosfera , Solo , Zea mays , Zea mays/crescimento & desenvolvimento , Zea mays/metabolismo , Nitrogênio/metabolismo , Solo/química , Microbiologia do Solo , Microbiota , Agricultura/métodos
6.
Biomacromolecules ; 24(3): 1111-1120, 2023 03 13.
Artigo em Inglês | MEDLINE | ID: mdl-36787188

RESUMO

Biopolymers are an attractive environmentally friendly alternative to common synthetic polymers, whereas primarily proteins and polysaccharides are the biomacromolecules that are used for making the biopolymer. Due to the breadth of side chains of such biomacromolecules capable of participating in hydrogen bonding, proteins and polysaccharide biopolymers were also used for the making of proton-conductive biopolymers. Here, we introduce a new platform for combining the merits of both proteins and polysaccharides while using a glycosylated protein for making the biopolymer. We use mucin as our starting point, whereas being a waste of the food industry, it is a highly available and low-cost glycoprotein. We show how we can use different chemical strategies to target either the glycan part or specific amino acids for both crosslinking between the different glycoproteins, thus making a free-standing biopolymer, as well as for introducing superior proton conductivity properties to the formed biopolymer. The resultant proton-conductive soft biopolymer is an appealing candidate for any soft bioelectronic application.


Assuntos
Polissacarídeos , Prótons , Biopolímeros/química , Polissacarídeos/química , Polímeros , Proteínas , Mucinas
7.
Inorg Chem ; 62(13): 5282-5291, 2023 Apr 03.
Artigo em Inglês | MEDLINE | ID: mdl-36943137

RESUMO

Searching for working refrigerant materials is the key element in the design of magnetic cooling devices. Herein, we report on the thermodynamic and magnetocaloric parameters of an X1 phase oxyorthosilicate, Gd2SiO5, by field-dependent static magnetization and specific heat measurements. An overall correlation strength of |J|S2 ≈ 3.4 K is derived via the mean-field estimate, with antiferromagnetic correlations between the ferromagnetically coupled Gd-Gd layers. The magnetic entropy change -ΔSm is quite impressive, reaches 0.40 J K-1 cm-3 (58.5 J K-1 kg-1) at T = 2.7 K, with the largest adiabatic temperature change Tad = 23.2 K for a field change of 8.9 T. At T = 20 K, the lattice entropy SL is small enough compared to the magnetic entropy Sm, Sm/SL = 21.3, which warrants its potential in 2 -20 K cryocoolers with both the Stirling and Carnot cycles. Though with relatively large exchange interactions, the layered A-type spin arrangement ultimately enhances the magnetocaloric coupling, raising the possibilities of designing magnetic refrigerants with a high ratio of cooling capacity to volume.

8.
Carcinogenesis ; 2022 Nov 28.
Artigo em Inglês | MEDLINE | ID: mdl-36437743

RESUMO

MicroRNAs (miRNAs) were involved in tumorigenesis, progression, recurrence and drug resistance of hepatocellular carcinoma (HCC). However, few miRNAs have been identified and entered clinical practice. We show here that miR-4461 expression is reduced in liver cancer stem cells (CSCs) and predicts the poor prognosis of HCC patients. Knockdown of miR-4461 enhances the self-renewal and tumorigenicity of liver CSCs. Conversely, forced miR-4461 expression inhibits liver CSCs self-renewal and tumorigenesis. Mechanically, miR-4461 directly targets sirtuin 1 (SIRT1) via binding to its 3'-UTR in liver CSCs. The correlation of miR-4461 and SIRT1 was confirmed in human HCC patients' tissues. Additionally, we found that miR-4461 overexpression hepatoma cells are more sensitive to cisplatin treatment. PDXs also showed that miR-4461 high HCC xenografts are sensitive to cisplatin treatment. Clinical cohort analysis further confirmed that HCC patients with high miR-4461 are benefited more from transcatheter arterial chemoembolization (TACE) treatment. In conclusion, our findings revealed the crucial role of the miR-4461 in liver CSCs expansion and cisplatin response, rendering miR-4461 as an optimal target for the prevention and intervention of HCC.

9.
J Antimicrob Chemother ; 77(10): 2816-2826, 2022 09 30.
Artigo em Inglês | MEDLINE | ID: mdl-35848785

RESUMO

OBJECTIVES: Fosfomycin resistance has become a clinical concern. In this study, we analysed the dynamic change of fosfomycin MIC in the epidemic Staphylococcus aureus lineages in a teaching hospital in Shanghai for 12 years and sought to elucidate the major underlying mechanisms. METHODS: MLST was conducted for 4580 S. aureus isolates recovered from 2008 to 2019. Fosfomycin MIC was determined by the agar dilution method. The genome data of 230 S. aureus epidemic lineage isolates were acquired from a next-generation sequencing (NGS) platform. Gene deletion and corresponding complementation mutants were constructed to confirm the mechanism of fosfomycin resistance. RESULTS: The predominant S. aureus lineages during the past 12 years were ST5 and ST239 (45.6%; 2090/4580). However, ST5 has been spreading clinically, while ST239 has gradually disappeared recently. Consistent with epidemic trends, fosfomycin-resistant ST5 increased from 19.5% to 67.3%. Most fosfomycin-resistant ST5 isolates (92.7%; 647/698) possessed high-level resistance (MIC > 1024 mg/L) with combined mutations mainly in glpT and uhpT. In contrast, fosfomycin-resistant ST239 isolates (76.8%; 149/194) mainly acquired low-level resistance (MIC = 64-128 mg/L) with mutation primarily in hptA. Deletion of a single resistant gene merely resulted in low-level fosfomycin resistance, while double-gene mutants ΔglpTΔuhpT, ΔglpTΔhptA and ΔglpTΔhptR acquired high-level fosfomycin resistance. CONCLUSIONS: The high-level fosfomycin resistance of S. aureus epidemic lineage ST5 is mainly due to the accumulation of mutations in the resistant genes related to membrane transporter systems, and partly contributes to its persistent prevalence under clinical antibiotic pressure.


Assuntos
Fosfomicina , Staphylococcus aureus Resistente à Meticilina , Infecções Estafilocócicas , Ágar , Antibacterianos/farmacologia , China/epidemiologia , Fosfomicina/farmacologia , Humanos , Proteínas de Membrana Transportadoras/genética , Staphylococcus aureus Resistente à Meticilina/genética , Testes de Sensibilidade Microbiana , Tipagem de Sequências Multilocus , Infecções Estafilocócicas/epidemiologia , Staphylococcus aureus/genética
10.
Int J Med Microbiol ; 312(2): 151550, 2022 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-35091347

RESUMO

BACKGROUND: The nasal carriage of Staphylococcus aureus introduces risks for subsequent infections, the rate of which is particularly high in children. The colonization mechanisms of S. aureus are not fully understood. METHODS: The epidemiological characteristics of nasal colonizing strains from pediatric patients undergoing liver transplantation and healthy pre-school children were analyzed first. Phenotypes, including biofilm formation and hemolytic activity, were tested for all the isolates. Bacterial pathogenicity indicated by a mouse skin abscess model and resistance to antimicrobial peptides (AMPs) was compared between the predominant genotypes from each group. RESULTS: The ST188 clone dominated in healthy children, whereas ST59 was prevalent for the pediatric patients. Although ST22 was the second most abundant genotype in the patient group, it was rarely found in healthy children. Interestingly, the colonizing ST59 and ST22 genotypes were more virulent, as indicated by the increased ability for hemolysis in vitro and severe subcutaneous abscesses in the mouse model, compared with ST188. We observed that the virulent ST59 and ST22 displayed higher resistance to antibiotics compared with ST188. Most of the ST59 and ST22 were methicillin-resistant S. aureus (MRSA), and all of the ST188 strains were methicillin-susceptible (MSSA). Moreover, we observed that the virulent ST59 and ST22 can resist killing by human antimicrobial peptides (AMPs). Mechanically, upon stimulation by AMPs, the virulent S. aureus can induce high expression of a phenol-soluble modulin transporter (Pmt) system. CONCLUSION: Pediatric patients can be colonized by virulent S. aureus clones, which are able to resist AMPs' killing through the Pmt system. The residence of virulent strains necessitates the continuous monitoring of potential infections, as well as annealing, to take protective decolonization measures.


Assuntos
Staphylococcus aureus Resistente à Meticilina , Infecções Estafilocócicas , Animais , Antibacterianos/farmacologia , Peptídeos Antimicrobianos , Criança , Pré-Escolar , Humanos , Camundongos , Testes de Sensibilidade Microbiana , Infecções Estafilocócicas/microbiologia , Staphylococcus aureus
11.
Inorg Chem ; 61(40): 15871-15879, 2022 Oct 10.
Artigo em Inglês | MEDLINE | ID: mdl-36174202

RESUMO

Three isostructural dl-serine covalently functionalized and multinuclear lanthanide (Ln3+)-embedded arsenotungstates, K2[{As4W44O137(OH)18(H2O)2(dl-Ser)2}{Ln2(H2O)4(dl-Ser)}2{Ln(H2O)7}2]·70H2O (Ln = Sm (1), Eu (2), and Gd (3); dl-Ser = C3H7NO3), were prepared, where the centrosymmetric [{As4W44O137(OH)18(H2O)2(dl-Ser)2}{Ln2(H2O)4(dl-Ser)}2]8- polyanion consists of two {As2W19O59(OH)8(H2O)}6- fragments, integrated with a two-dl-serine-ornamented [W6O23(OH)2(dl-Ser)2{Ln2(H2O)4}2]8- segment. In addition, the photochromic transformation of solid-state compounds 1-3 was observed from colorless to blue after a UV illumination of 4 min, and the decay process lasted as long as ∼20 h in the dark. The coloration kinetic half-life (t1/2) values of compounds 1, 2, and 3 were calculated to be 0.597, 0.920, and 0.723 min, respectively. Furthermore, the luminescent properties and energy migration from arsenotungstates and organic chromophores to Sm3+ and Eu3+ ions in 1 and 2 have been intensively investigated. Further analysis manifests that 1 possesses an effective luminescent switchable behavior, triggered by its fast-responsive photochromism effect.


Assuntos
Elementos da Série dos Lantanídeos , Luminescência , Aminoácidos , Íons , Elementos da Série dos Lantanídeos/química , Serina
12.
BMC Med Inform Decis Mak ; 22(1): 114, 2022 04 29.
Artigo em Inglês | MEDLINE | ID: mdl-35488252

RESUMO

BACKGROUND: Health providers create Electronic Health Records (EHRs) to describe the conditions and procedures used to treat their patients. Medical notes entered by medical staff in the form of free text are a particularly insightful component of EHRs. There is a great interest in applying machine learning tools on medical notes in numerous medical informatics applications. Learning vector representations, or embeddings, of terms in the notes, is an important pre-processing step in such applications. However, learning good embeddings is challenging because medical notes are rich in specialized terminology, and the number of available EHRs in practical applications is often very small. METHODS: In this paper, we propose a novel algorithm to learn embeddings of medical terms from a limited set of medical notes. The algorithm, called definition2vec, exploits external information in the form of medical term definitions. It is an extension of a skip-gram algorithm that incorporates textual definitions of medical terms provided by the Unified Medical Language System (UMLS) Metathesaurus. RESULTS: To evaluate the proposed approach, we used a publicly available Medical Information Mart for Intensive Care (MIMIC-III) EHR data set. We performed quantitative and qualitative experiments to measure the usefulness of the learned embeddings. The experimental results show that definition2vec keeps the semantically similar medical terms together in the embedding vector space even when they are rare or unobserved in the corpus. We also demonstrate that learned vector embeddings are helpful in downstream medical informatics applications. CONCLUSION: This paper shows that medical term definitions can be helpful when learning embeddings of rare or previously unseen medical terms from a small corpus of specialized documents such as medical notes.


Assuntos
Registros Eletrônicos de Saúde , Unified Medical Language System , Algoritmos , Humanos , Aprendizado de Máquina
13.
Anal Chem ; 93(18): 7086-7093, 2021 05 11.
Artigo em Inglês | MEDLINE | ID: mdl-33901400

RESUMO

Sensitive detection of low-abundance driver mutations may provide valuable information for precise clinical treatment. Compared to next-generation sequencing and droplet digital PCR methods, fluorescent probes show great flexibility in rapid detection of specific mutations with high sensitivity and easily accessible instruments. However, existing approaches with fluorescent probes need an additional step to convert duplex DNA to single-stranded DNA (ssDNA) before the detection step, which increases the time, cost, and risk of loss of low-input target strands. In this work, we attempt to integrate the ssDNA-generation step with the subsequent detection into a programable one-pot reaction by employing lambda exonuclease (λ exo), a versatile nanopore nuclease which exercises different functions on different substrates. The capability of λ exo in discrimination of mismatched bases in 5'- FAM-ended 2 nt-unpaired DNA duplexes was first demonstrated. Specific fluorescent probes were developed for EGFR exon 19 E746-A750del and PIK3CA E545K mutations with discrimination factors as high as 8470 and 884, respectively. By mixing the probes and λ exo with the PCR products of cell-free circulating DNA extracted from plasma samples, the reaction was immediately initiated, which allowed sensitive detection of the two types of mutations at an abundance as low as 0.01% within less than 2 h. Compared to existing approaches, the new method has distinct advantages in simplicity, low cost, and rapidity. It provides a convenient tool for companion diagnostic tests and other routine analysis targeting genetic mutations in clinical samples.


Assuntos
DNA , Testes Diagnósticos de Rotina , DNA/genética , DNA de Cadeia Simples/genética , Éxons , Mutação
14.
Biochemistry ; 59(35): 3235-3246, 2020 09 08.
Artigo em Inglês | MEDLINE | ID: mdl-32786408

RESUMO

The periplasmic protein SurA is the primary chaperone involved in the biogenesis of bacterial outer membrane proteins and is a potential antibacterial drug target. The three-dimensional structure of SurA can be divided into three parts, a core module formed by the N- and C-terminal regions and two peptidyl-prolyl isomerase (PPIase) domains, P1 and P2. Despite the determination of the structures of several SurA-peptide complexes, the functional mechanism of this chaperone remains elusive and the roles of the two PPIase domains are yet unclear. Herein, we characterize the conformational dynamics of SurA by using solution nuclear magnetic resonance and single-molecule fluorescence resonance energy transfer methods. We demonstrate a "closed-to-open" structural transition of the P1 domain that is correlated with both chaperone activity and peptide binding and show that the flexible P2 domain can also occupy conformations that closely contact the NC core module. Our results offer a structural basis for the counteracting roles of the two PPIase domains in regulating the SurA chaperone activity.


Assuntos
Proteínas de Transporte/química , Proteínas de Escherichia coli/química , Chaperonas Moleculares/química , Peptidilprolil Isomerase/química , Periplasma/metabolismo , Proteínas da Membrana Bacteriana Externa/química , Proteínas da Membrana Bacteriana Externa/genética , Proteínas da Membrana Bacteriana Externa/metabolismo , Proteínas de Transporte/genética , Proteínas de Transporte/metabolismo , Escherichia coli/genética , Escherichia coli/metabolismo , Escherichia coli/ultraestrutura , Proteínas de Escherichia coli/genética , Proteínas de Escherichia coli/metabolismo , Mutação com Ganho de Função , Modelos Moleculares , Chaperonas Moleculares/genética , Chaperonas Moleculares/metabolismo , Ressonância Magnética Nuclear Biomolecular , Peptidilprolil Isomerase/genética , Peptidilprolil Isomerase/metabolismo , Ligação Proteica , Conformação Proteica , Dobramento de Proteína , Domínios e Motivos de Interação entre Proteínas/genética , Domínios e Motivos de Interação entre Proteínas/fisiologia
15.
Nucleic Acids Res ; 46(4): e24, 2018 02 28.
Artigo em Inglês | MEDLINE | ID: mdl-29190359

RESUMO

Sensitive detection of the single nucleotide variants in cell-free DNA (cfDNA) may provide great opportunity for minimally invasive diagnosis and prognosis of cancer and other related diseases. Here, we demonstrate a facile new strategy for quantitative measurement of cfDNA mutations at low abundance in the cancer patients' plasma samples. The method takes advantage of a novel property of lambda exonuclease which effectively digests a 5'-fluorophore modified dsDNA with a 2-nt overhang structure and sensitively responds to the presence of mismatched base pairs in the duplex. It achieves a limit of detection as low as 0.02% (percentage of the mutant type) for BRAFV600E mutation, NRASQ61R mutation and three types of EGFR mutations (G719S, T790M and L858R). The method enabled identification of BRAFV600E and EGFRL858R mutations in the plasma of different cancer patients within only 3.5 h. Moreover, the terminal structure-dependent reaction greatly simplifies the probe design and reduces the cost, and the assay only requires a regular real-time PCR machine. This new method may serve as a practical tool for quantitative measurement of low-abundance mutations in clinical samples for providing genetic mutation information with prognostic or therapeutic implications.


Assuntos
DNA Tumoral Circulante/sangue , Análise Mutacional de DNA/métodos , Exodesoxirribonucleases , Proteínas Virais , DNA Tumoral Circulante/química , DNA/química , DNA/metabolismo , Receptores ErbB/genética , Humanos , Neoplasias/genética , Proteínas Proto-Oncogênicas B-raf/genética
16.
Nucleic Acids Res ; 46(6): 3119-3129, 2018 04 06.
Artigo em Inglês | MEDLINE | ID: mdl-29490081

RESUMO

Lambda exonuclease (λ exo) plays an important role in the resection of DNA ends for DNA repair. Currently, it is also a widely used enzymatic tool in genetic engineering, DNA-binding protein mapping, nanopore sequencing and biosensing. Herein, we disclose two noncanonical properties of this enzyme and suggest a previously undescribed hydrophobic interaction model between λ exo and DNA substrates. We demonstrate that the length of the free portion of the substrate strand in the dsDNA plays an essential role in the initiation of digestion reactions by λ exo. A dsDNA with a 5' non-phosphorylated, two-nucleotide-protruding end can be digested by λ exo with very high efficiency. Moreover, we show that when a conjugated structure is covalently attached to an internal base of the dsDNA, the presence of a single mismatched base pair at the 5' side of the modified base may significantly accelerate the process of digestion by λ exo. A detailed comparison study revealed additional π-π stacking interactions between the attached label and the amino acid residues of the enzyme. These new findings not only broaden our knowledge of the enzyme but will also be very useful for research on DNA repair and in vitro processing of nucleic acids.


Assuntos
Pareamento Incorreto de Bases , DNA/metabolismo , Exodesoxirribonucleases/metabolismo , Proteínas Virais/metabolismo , Sequência de Bases , Biocatálise , DNA/química , DNA/genética , Exodesoxirribonucleases/química , Exodesoxirribonucleases/genética , Interações Hidrofóbicas e Hidrofílicas , Modelos Moleculares , Conformação de Ácido Nucleico , Domínios Proteicos , Especificidade por Substrato , Proteínas Virais/química , Proteínas Virais/genética
17.
BMC Health Serv Res ; 20(1): 625, 2020 Jul 08.
Artigo em Inglês | MEDLINE | ID: mdl-32641049

RESUMO

BACKGROUND: World Health Organization initiated community-based rehabilitation (CBR) in 1978, and by now, it has been an essential process of medical services worldwide. China had strengthened primary health care on building more than 35,000 community health centers (CHCs) in cities, and more than 34,000 township health centers (THCs) in the rural area. Nevertheless, it remains unclear that if these primary health centers could provide optional rehabilitation services for disabilities. And this study aims at evaluating the supply capacity of rehabilitation service in primary health centers of Chengdu, a regional center city of southwest China. METHOD: We conducted a general investigation of primary health centers in Chengdu, a city located in southwest China with more than 15 million population. Our investigation covered all of Chengdu's 390 primary health centers from October to November 2016. We researched these primary health centers on basic rehabilitation services, diseases, and rehabilitation equipment quantity and quality, and traditional Chinese medicine (TCM) physiotherapy. RESULT: Rehabilitation therapy is available in 88.9% (337 of 379) of all primary health centers. Meanwhile, CHCs slightly surpass THCs with an available rate of 92.2% (106 of 115) and 87.5% (231 of 264), respectively. Traditional Chinese Medicine (TCM) physiotherapy is available in 97.1% (368 of 379) of all primary health centers, 97.3% (112 of 115) of CHCs and 97.0% (256 of 264) of THCs. Quantitative analysis showed that substantial factors which could make an impact on the number of patients per year contain: categories of rehabilitation disease (P < 0.001, 95% confidence interval (CI) [- 1.571, - 0.702]),number of rehabilitation bed (P < 0.001, 95%CI [- 1.249, - 0.290]). CONCLUSION: CBR and TCM physiotherapy has become accessible for disabilities in most basic health centers of Chengdu City, whereas, available rate of CBR in THCs is lesser than in CHCs, which suggests an imbalance in primary health service development between rural and urban area. Categories of rehabilitation diseases, and the number of rehabilitation beds constitute co-factors that make an impact on the CBR capacity of basic health centers.


Assuntos
Serviços de Saúde Comunitária/estatística & dados numéricos , Atenção Primária à Saúde/estatística & dados numéricos , Reabilitação/estatística & dados numéricos , China , Cidades , Estudos Transversais , Pesquisas sobre Atenção à Saúde , Humanos , Medicina Tradicional Chinesa/estatística & dados numéricos , Modalidades de Fisioterapia/estatística & dados numéricos
18.
Acc Chem Res ; 51(2): 404-413, 2018 02 20.
Artigo em Inglês | MEDLINE | ID: mdl-29412634

RESUMO

Magnetic nanomaterials (MNMs) have attracted significant interest in the past few decades because of their unique properties such as superparamagnetism, which results from the influence of thermal energy on a ferromagnetic nanoparticle. In the superparamagnetic size regime, the moments of nanoparticles fluctuate as a result of thermal energy. To understand the fundamental behavior of superparamagnetism and develop relevant potential applications, various preparation routes have been explored to produce MNMs with desired properties and structures. However, some challenges remain for the preparation of well-defined magnetic nanostructures, including exchange-coupled nanomagnets, which are considered as the next generation of advanced magnets. In such a case, effective synthetic methods are required to achieve control over the chemical composition, size, and structure of MNMs. For instance, liquid-phase chemical syntheses, a set of emerging approaches to prepare various magnetic nanostructures, facilitate precise control over the nucleation and specific growth processes of nanomaterials with diverse structures. Among them, the high-temperature organic-phase method is an indispensable one in which the microstructures and physical/chemical properties of MNMs can be tuned by controlling the reaction conditions such as precursor, surfactant, or solvent amounts, reaction temperature or time, reaction atmosphere, etc. In this Account, we present an overview of our progress on the chemical synthesis of various MNMs, including monocomponent nanostructures (e.g., metals, metal alloys, metal oxides/carbides) and multicomponent nanostructures (heterostructures and exchange-coupled nanomagnets). We emphasize the high-temperature organic-phase synthetic method, on which we have been focused over the past decade. Notably, multicomponent nanostructures, obtained by growing or incorporating different functional components together, not only retain the functionalities of each single component but also possess synergic properties that emerge from interfacial coupling, with improved magnetic, optical, or catalytic features. Herein, potential applications of MNMs are covered in three representative areas: biomedicine, catalysis, and environmental purification. Regarding biomedicine, MNMs can detect or target biological entities after being modified with specific biomolecules, and they can be applied to magnetic resonance imaging, imaging-guided drug delivery, and photothermal therapy. Apart from their magnetic features, the catalytic performance of some MNMs resulting from their highly specific chemical components and surface structure will be briefly introduced, highlighting its impact in the methanol oxidation reaction, the oxygen reduction reaction, the oxygen and hydrogen evolution reactions, and the Fischer-Tropsch synthesis. Finally, environmental purification, primarily for water remediation, will be highlighted with two main aspects: the effective capture of bacteria and the removal of adverse ions in wastewater. We hope that this Account will clarify the progress on the controllable preparation of MNMs with specific compositions, sizes, and structures and generate broad interest in the realms of biomedicine and catalysis as well as in environmental issues and other potential applications.

19.
Molecules ; 21(4): 511, 2016 Apr 22.
Artigo em Inglês | MEDLINE | ID: mdl-27110762

RESUMO

This study aimed to determine the influence of different emulsifiers or xanthan-emulsifier systems on the release of aroma compounds. Solid-phase microextraction (SPME) and GC-MS were used to study the effects of varying concentrations of xanthan gum, sucrose fatty acid ester, Tween 80 and soybean lecithin on the release of seven aroma compounds. The effects of the emulsifier systems supplemented with xanthan gum on aroma release were also studied in the same way. The results showed varying degrees of influence of sucrose fatty acid ester, soybean lecithin, Tween 80 and xanthan gum on the release of aroma compounds. Compared with other aroma compounds, ethyl acetate was more likely to be conserved in the solution system, while the amount of limonene released was the highest among these seven aroma compounds. In conclusion, different emulsifiers and complexes showed different surface properties that tend to interact with different aroma molecules. The present studies showed that the composition and structure of emulsifiers and specific interactions between emulsifiers and aroma molecules have significant effects on aroma release.


Assuntos
Emulsificantes/química , Aditivos Alimentares/química , Glycine max/química , Odorantes/análise , Indústria de Processamento de Alimentos , Cromatografia Gasosa-Espectrometria de Massas/métodos , Lecitinas/química , Polissacarídeos Bacterianos/química , Polissorbatos/química , Microextração em Fase Sólida/métodos , Sacarose/química , Propriedades de Superfície
20.
J Sci Food Agric ; 96(3): 954-61, 2016 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-25777262

RESUMO

BACKGROUND: In this study, (R)-(+)-limonene biotransformation using three fungal strains was compared. Penicillium digitatum DSM 62840 was distinguished for its capacity to transform limonene into α-terpineol with high regioselectivity. Growth kinetics in submerged liquid culture and the effects of growth phase and contact time on biotransformation were studied using this strain. Substrate concentration, co-solvent selection, and cultivation conditions were subsequently optimised. RESULTS: The maximum concentration of α-terpineol (833.93 mg L(-1)) was obtained when the pre-culture medium was in medium log-phase by adding 840 mg L(-1) substrate dissolved in ethanol and cultivation was performed at 24 °C, 150 rpm, and pH 6.0 for 12 h. Addition of small amounts of (R)-(+)-limonene (84 mg L(-1)) at the start of fungal log-phase growth yielded a 1.5-fold yield of α-terpineol, indicating that the enzyme was inducible. CONCLUSION: Among these three strains tested, P. digitatum DSM 62840 was proved to be an efficient biocatalyst to transform (R)-(+)-limonene to α-terpineol. Further studies revealed that the optimal growth phase for biotransformation was in the medium log phase of this strain. The biotransformation represented a wide tolerance of temperature; α-terpineol concentration underwent no significant change at 8-32 °C. The biotransformation could also be performed using resting cells.


Assuntos
Cicloexenos/metabolismo , Aditivos Alimentares/metabolismo , Monoterpenos/metabolismo , Penicillium/metabolismo , Terpenos/metabolismo , Biotransformação , Monoterpenos Cicloexânicos , Humanos , Limoneno
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