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1.
Biotechnol Appl Biochem ; 70(2): 688-696, 2023 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-35932185

RESUMO

The bacterium Caulobacter crescentus secretes an adhesive polysaccharide called holdfast, which is the known strongest underwater adhesive in nature. The deacetylase encoded by hfs (holdfast synthesis) H gene is a key factor affecting the adhesion of holdfast. Its structure and function are not yet clear, and whether other polysaccharide deacetylases exist in C. crescentus is still unknown. The screening of both HfsH and its structural analogue as well as their purification from the artificial expression products of Escherichia coli is the first step to clarify these questions. Here, we determined the conserved domains of HfsH via sequence alignment among carbohydrate esterase family 4 enzymes and screened out its structural analogue (CC_2574) in C. crescentus. The recombinant HfsH and CC_2574 were effectively expressed in E. coli. Both of them were purified by chromatography from their corresponding productions in E. coli and were then functionally analyzed. The results indicated that a high deacetylase activity (61.8 U/mg) was observed in recombinant HfsH but not in CC_2574, which suggesting that HfsH might be the irreplaceable gene mediating adhesion of holdfast in C. crescentus. Moreover, the divalent metal ions Zn2+ , Mg2+ , and Mn2+ could promote the activity of recombinant HfsH at the concentration from 0.05 to 1 mM, but inhibit its activity when the concentration exceeds 1 mM. In sum, our study first realized the artificial production of polysaccharide deacetylase HfsH and its structural analogue, and further explored their functions, both of which laid the foundation for the development of new adhesive materials.


Assuntos
Aderência Bacteriana , Caulobacter crescentus , Aderência Bacteriana/genética , Caulobacter crescentus/genética , Caulobacter crescentus/metabolismo , Escherichia coli/genética , Escherichia coli/metabolismo , Hormônio Foliculoestimulante Humano/metabolismo , Polissacarídeos/metabolismo , Proteínas de Bactérias/genética
2.
World J Microbiol Biotechnol ; 40(2): 51, 2023 Dec 26.
Artigo em Inglês | MEDLINE | ID: mdl-38146036

RESUMO

Vibrio alginolyticus (V. alginolyticus) is a common pathogen in the ocean. In addition to causing serious economic losses in aquaculture, it can also infect humans. The rapid detection of nucleic acids of V. alginolyticus with high sensitivity and specificity in the field is very important for the diagnosis and treatment of infection caused by V. alginolyticus. Here, we established a simple, fast and effective molecular method for the identification of V. alginolyticus that does not rely on expensive instruments and professionals. The method integrates recombinase polymerase amplification (RPA) technology with CRISPR system in a single PCR tube. Using this method, the results can be visualized by lateral flow dipstick (LFD) in less than 50 min, we named this method RPA-CRISPR/Cas13a-LFD. The method was confirmed to achieve high specificity for the detection of V. alginolyticus with no cross-reactivity with similar Vibrio and common clinical pathogens. This diagnostic method shows high sensitivity; the detection limit of the RPA-CRISPR/Cas13a-LFD is 10 copies/µL. We successfully identified 35 V. alginolyticus strains from a total of 55 different bacterial isolates and confirmed their identity by (Matrix-assisted laser desorption ionization time-of-flight mass spectrometry, MALDI-TOF MS). We also applied this method on infected mice blood, and the results were both easily and rapidly obtained. In conclusion, RPA-CRISPR/Cas13a-LFD offers great potential as a useful tool for reliable and rapid diagnosis of V. alginolyticus infection, especially in limited conditions.


Assuntos
Recombinases , Vibrio alginolyticus , Animais , Humanos , Camundongos , Recombinases/metabolismo , Vibrio alginolyticus/genética , Vibrio alginolyticus/metabolismo , Repetições Palindrômicas Curtas Agrupadas e Regularmente Espaçadas , Sensibilidade e Especificidade , Reação em Cadeia da Polimerase/métodos , Técnicas de Amplificação de Ácido Nucleico/métodos
3.
Small ; 17(40): e2102733, 2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-34477301

RESUMO

Oxygen detection by organic-inorganic halide perovskites (OIHPs) has demonstrated advantages in operating temperature, response time, and reversibility over traditional materials. However, OIHPs can only sense O2 in light and the unavoidable O2 exposure during detection easily induces the degradation of OIHPs. The trade-off between sensitivity and stability makes the OIHP-based oxygen sensors impractical. By replacing organic groups with Cs, the compact films of all-inorganic halide perovskites (AIHPs) that can adsorb O2 at grain boundaries in dark are developed. AIHPs show conductance increase of 1875.5% from 1 × 10-5 to 700 Torr of O2 pressure, associated with full reversibility and long-term stability. Combining experiments and modeling, this work reveals the donor-acceptor competition via halide vacancy filling leading to the modulation of carrier concentration and mobility. This work offers understandings on oxygen sensing by perovskite materials and paves the way for further optimization of AIHPs as promising oxygen sensors with high sensitivity and stability.

4.
Zhongguo Zhong Yao Za Zhi ; 45(8): 1833-1843, 2020 Apr.
Artigo em Chinês | MEDLINE | ID: mdl-32489067

RESUMO

The genus Syringa, belonging to the family Oleaceae, are distributed naturally in the European and Asian regions.This genus is composed of more than 20 species worldwide, among which about 16 species including 10 endemic ones are discovered in China.The Syringa sp.are extensively used as herbal medicine and ornamental aspects, such as the roots and stems of S. pinnatifolia, which is one of the typical Mongolian folk medicines in China for the treatment of cardiovascular and pulmonary symptoms. As a continuous research following the previous summary in 2015, the present reriew describes the phytochemical and pharmacological progress of the genus, which hopes to provide a valuable reference to its research, development and clinic application.


Assuntos
Oleaceae , Syringa , China , Medicina Tradicional da Mongólia , Compostos Fitoquímicos
5.
Sensors (Basel) ; 19(13)2019 Jul 09.
Artigo em Inglês | MEDLINE | ID: mdl-31324044

RESUMO

Herein, a peripherally clamped stretched square monolayer graphene sheet with a side length of 10 nm was demonstrated as a resonator for atomic-scale mass sensing via molecular dynamics (MD) simulation. Then, a novel method of mass determination using the first three resonant modes (mode11, mode21 and mode22) was developed to avoid the disturbance of stress fluctuation in graphene. MD simulation results indicate that improving the prestress in stretched graphene increases the sensitivity significantly. Unfortunately, it is difficult to determine the mass accurately by the stress-reliant fundamental frequency shift. However, the absorbed mass in the middle of graphene sheets decreases the resonant frequency of mode11 dramatically while having negligible effect on that of mode21 and mode22, which implies that the latter two frequency modes are appropriate for compensating the stress-induced frequency shift of mode11. Hence, the absorbed mass, with a resolution of 3.3 × 10-22 g, is found using the frequency ratio of mode11 to mode21 or mode22, despite the unstable prestress ranging from 32 GPa to 47 GPa. This stress insensitivity contributes to the applicability of the graphene-based resonant mass sensor in real applications.

6.
J Neuroinflammation ; 15(1): 16, 2018 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-29334965

RESUMO

BACKGROUND: Current options to treat clinical relapse in inflammatory central nervous system (CNS) conditions such as cerebral ischemia-reperfusion injury are limited, and agents that are more effective are required. Disruption of the blood-brain barrier is an early feature of lesion formation that correlates with clinical exacerbation and facilitates the entry of inflammatory medium and inflammatory cells. Interleukin-1 receptor antagonist (IL-1RA) is a naturally occurring anti-inflammatory antagonist of the interleukin-1 (IL-1) family. The broad-spectrum anti-inflammatory effects of IL-1RA have been investigated against various forms of neuroinflammation. However, the effect of IL-1RA on blood-brain barrier disruption following ischemia-reperfusion has not been reported. METHODS: In this study, we investigated the effects of IL-1RA and a novel protein (IL-1RA-PEP) that was fused to IL-1RA with a cell penetrating peptide, on blood-brain barrier integrity, in male rats subjected to transient middle cerebral artery occlusion. RESULTS: After intravenous administration, IL-1RA-PEP (50 mg/kg) penetrated cerebral tissues more effectively than IL-1RA. Moreover, it preserved blood-brain barrier integrity, attenuated changes in expression and localization of tight junction proteins and matrix metalloproteinases, and enhanced angiogenesis in ischemic brain tissue. Further study suggested that the effects of IL-1RA-PEP on preserving blood-brain barrier integrity might be closely correlated with the p65/NF-κB pathway, as evidenced by the effects of the inhibitor JSH-23. CONCLUSIONS: Collectively, our results demonstrated that IL-1RA-PEP could effectively penetrate the brain of rats with middle cerebral artery occlusion and ameliorate blood-brain barrier disruption. This finding might represent its novel therapeutic potential in the treatment of the cerebral ischemia-reperfusion injury.


Assuntos
Barreira Hematoencefálica/metabolismo , Isquemia Encefálica/metabolismo , Cisteamina/análogos & derivados , Proteína Antagonista do Receptor de Interleucina 1/metabolismo , Peptídeos/metabolismo , Traumatismo por Reperfusão/metabolismo , Administração Intravenosa , Animais , Barreira Hematoencefálica/efeitos dos fármacos , Isquemia Encefálica/tratamento farmacológico , Cisteamina/administração & dosagem , Cisteamina/metabolismo , Proteína Antagonista do Receptor de Interleucina 1/administração & dosagem , Masculino , Peptídeos/administração & dosagem , Distribuição Aleatória , Ratos , Ratos Sprague-Dawley , Traumatismo por Reperfusão/tratamento farmacológico
7.
Sensors (Basel) ; 19(1)2018 Dec 31.
Artigo em Inglês | MEDLINE | ID: mdl-30602674

RESUMO

With the wide application of wireless sensor networks (WSNs), secure data sharing in networks is becoming a hot research topic and attracting more and more attention. A huge challenge is securely transmitting the data from the source node to the sink node. Except for eavesdropping the information stored in the packages, the adversary may also attempt to analyze the contextual information of the network to locate the source node. In this paper, we proposed a secure data sharing approach to defend against the adversary. Specifically, we first design a secret key mechanism to guarantee the security of package delivery between a pair of nodes. Then, a light-weighted secret sharing scheme is designed to map the original message to a set of shares. Finally, the shares are delivered to the sink node independently based on a proper random routing algorithm. Simulation results illustrate that our approach can defend against the eavesdropping and tracing-back attack in an energy-efficient manner.

8.
Molecules ; 23(2)2018 Feb 11.
Artigo em Inglês | MEDLINE | ID: mdl-29439451

RESUMO

As one of the major active ingredients in Radix Scutellariae, wogonin has been shown to be associated with various pharmacological activities on cancer cell growth, apoptosis, and cell invasion and migration. Here, we demonstrated that wogonin may harbor potential anti-metastatic activities in hepatocarcinoma (HCC). The anti-metastasis potential of wogonin and its underlying mechanisms were evaluated by ligand-protein docking approach, surface plasmon resonance assay, and in vitro gelatin zymography studies. Our results showed that wogonin (100 µM, 50 µM) suppressed MHCC97L and PLC/PRF/5 cells migration and invasion in vitro. The docking approach and surface plasmon resonance assay indicated that the potential binding affinity between wogonin and matrix metalloproteinase-9 (MMP-9) may lead to inhibition of MMP-9 activity and further leads to suppression of tumor metastasis. This conclusion was further verified by Western blot results and gelatin zymography analysis. Wogonin might be a potent treatment option for disrupting the tumor metastasis that favors HCC development. The potential active targets from computational screening integrated with biomedical study may help us to explore the molecular mechanism of herbal medicines.


Assuntos
Antineoplásicos Fitogênicos/farmacologia , Flavanonas/farmacologia , Regulação Neoplásica da Expressão Gênica , Hepatócitos/efeitos dos fármacos , Metaloproteinase 9 da Matriz/genética , Scutellaria baicalensis/química , Antineoplásicos Fitogênicos/química , Sítios de Ligação , Linhagem Celular Tumoral , Ensaios de Migração Celular , Movimento Celular/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Flavanonas/química , Hepatócitos/enzimologia , Hepatócitos/patologia , Humanos , Molécula 1 de Adesão Intercelular/genética , Molécula 1 de Adesão Intercelular/metabolismo , Metaloproteinase 9 da Matriz/química , Metaloproteinase 9 da Matriz/metabolismo , Simulação de Acoplamento Molecular , Proteínas de Neoplasias/antagonistas & inibidores , Proteínas de Neoplasias/genética , Proteínas de Neoplasias/metabolismo , Ligação Proteica , Conformação Proteica em alfa-Hélice , Conformação Proteica em Folha beta , Domínios e Motivos de Interação entre Proteínas , Transdução de Sinais , Molécula 1 de Interação Estromal/antagonistas & inibidores , Molécula 1 de Interação Estromal/genética , Molécula 1 de Interação Estromal/metabolismo
9.
BMC Infect Dis ; 17(1): 164, 2017 02 21.
Artigo em Inglês | MEDLINE | ID: mdl-28222680

RESUMO

BACKGROUND: Current diagnostic methods for Schistosoma japonicum infection are insensitive for low-density infections. Therefore, a new diagnostic assay based on recombinase polymerase amplification (RPA) technology was established and assessed for field applification. METHODS: The S.japonicum RPA assay was developed to target highly repetitive retrotransposon SjR2 gene of S japonicum, and its sensitivity and specificity were assessed by serial dilution of S. japonicum genomic DNA and other related worm genomic DNA respectively. The RPA diagnostic validity was first evaluated in 60 fecal samples from healthy people and patients, and then compared with other diagnostic tests in 200 high-risk individuals living in endemic areas. RESULTS: The real time RPA assay could detect 0.9 fg S. japonicum DNA within 15 min and distinguish S. japonicum from other worms. The validity analysis of RPA for the detection of S. japonicum in stool samples from 30 S. japonicum-infected patients and 30 healthy persons indicated 100% sensitivity and specificity. When testing 200 fecal or serum samples from a high-risk population, the percentage sensitivity of RPA was 100%, whereas that of indirect hemagglutination assay (IHA) and enzyme-linked immunosorbent assay (ELISA) were 80.3% and 85.2% respectively. In addition, the RPA presented better consistency with the stool-based tests than IHA and ELISA. Overall, the RPA was superior to other detection methods with respect to detection time, sensitivity, and convenience. CONCLUSIONS: This is the first time we applied the RPA technology to the field evaluation of S. japonicum infection. And the results suggest that RPA-based assays can be used as a promising point-of-care test for the diagnosis of schistosomiasis.


Assuntos
Sistemas Automatizados de Assistência Junto ao Leito , Reação em Cadeia da Polimerase/métodos , Schistosoma japonicum/isolamento & purificação , Esquistossomose Japônica/diagnóstico , Adolescente , Adulto , Idoso , Animais , Estudos de Casos e Controles , China/epidemiologia , DNA de Helmintos/análise , Ensaio de Imunoadsorção Enzimática , Feminino , Testes de Hemaglutinação , Humanos , Masculino , Pessoa de Meia-Idade , Recombinases , Schistosoma japonicum/genética , Sensibilidade e Especificidade , Adulto Jovem
10.
Int J Mol Sci ; 18(4)2017 Apr 19.
Artigo em Inglês | MEDLINE | ID: mdl-28422048

RESUMO

SAK-HV is an anti-atherosclerosis recombinant fusion protein developed by our lab. Our study determined that SAK-HV promoted macrophage proliferation, of which the mechanism was explored by both RAW264.7 cells and primary macrophages. Mass spectrometric analysis and co-immunoprecipitation were combined to screen the SAK-HV-interacting proteins in RAW264.7 cells. Confocal microscopy was adopted to detect the localization of SAK-HV in cells. The results indicated that SAK-HV triggered macrophage proliferation via the mitogen-activated protein kinase (MAPK)/extracellular signal-regulated kinases (ERK) and c-Jun N-terminal kinases (JNK) pathways by its SAK-mutant functional domain. We screened out Uba1 as the SAK-HV-interacting protein in the RAW264.7 cells and discovered their co-localization in the cytoplasm and nucleus. Inhibiting Uba1 significantly decreased the SAK-HV-induced macrophage proliferation. Thus, we postulated an attractive model of ubiquitination, in which the interactions between Uba1 and specific E2 enzymes are blocked by its interaction with SAK-HV. Based on this model, we detected the decreased self-ubiquitination of MEKK1 after SAK-HV treatment and concluded that SAK-HV inhibits the self-ubiquitination of MEKK1 via its SAK-mutant functional domain to activate MAPK/ERK and JNK pathways, promoting macrophage proliferation. This conclusion highly supported our hypothesized model of ubiquitination at the level of Uba1, which may represent a novel paradigm to promote macrophage proliferation by using the E1 enzyme (Uba1) as a switch.


Assuntos
MAP Quinase Quinase Quinase 1/metabolismo , Sistema de Sinalização das MAP Quinases/efeitos dos fármacos , Macrófagos/efeitos dos fármacos , Macrófagos/metabolismo , Proteínas Recombinantes de Fusão/farmacologia , Animais , Linhagem Celular , Proliferação de Células/efeitos dos fármacos , Camundongos , Mutação , Fosforilação , Domínios e Motivos de Interação entre Proteínas/genética , Proteínas Serina-Treonina Quinases/química , Proteínas Serina-Treonina Quinases/genética , Proteínas Serina-Treonina Quinases/metabolismo , Ubiquitinação/efeitos dos fármacos
11.
Int J Mol Sci ; 18(7)2017 Jul 17.
Artigo em Inglês | MEDLINE | ID: mdl-28714941

RESUMO

Epidemiological and clinical studies have increasingly shown that fine particulate matter (PM2.5) is associated with cardiovascular morbidity and mortality, which share the common feature of PM2.5-induced vascular inflammation; however, the underlying mechanisms of how PM2.5 triggers increased inflammatory response in vascular endothelial cells are not well understood. After treating mouse aortic endothelial cells (MAECs) with different concentrations of PM2.5, we assessed interleukin (IL)-6 and four and a half LIM domains 2 (FHL2) expression in cell supernatant by enzyme-linked immunosorbent assay and Western blot, respectively, as well as activation of nuclear factor (NF)-κB and immune-response signaling pathways. Additionally, changes in pathway activation, IL-6 expression, and autophagy were evaluated under PM2.5 exposure, following FHL2 knockdown with small interfering RNA. Our results indicated that PM2.5 exposure induced FHL2 expression and IL-6 secretion, as well as activation of pathways associated with immune response. Additionally, following FHL2 knockdown, the activation of NF-κB-related pathways and IL-6 secretion was inhibited under PM2.5 exposure, although the Akt- and p38-signaling pathways were not affected. Furthermore, PM2.5 exposure induced autophagy, whereas autophagy inhibition eventually inhibited PM2.5-induced FHL2 expression. These findings suggested a novel link between autophagy induced FHL2 upregulation and IL-6 production in MAECs under PM2.5 exposure.


Assuntos
Aorta/citologia , Interleucina-6/metabolismo , Proteínas com Homeodomínio LIM/metabolismo , Proteínas Musculares/metabolismo , NF-kappa B/metabolismo , Material Particulado/toxicidade , Fatores de Transcrição/metabolismo , Regulação para Cima , Animais , Aorta/efeitos dos fármacos , Aorta/imunologia , Autofagia , Sobrevivência Celular/efeitos dos fármacos , Células Endoteliais/citologia , Células Endoteliais/efeitos dos fármacos , Células Endoteliais/imunologia , Técnicas de Silenciamento de Genes , Proteínas com Homeodomínio LIM/genética , Camundongos , Proteínas Musculares/genética , Transdução de Sinais , Fatores de Transcrição/genética , Ativação Transcricional
12.
Phys Chem Chem Phys ; 16(48): 26974-82, 2014 Dec 28.
Artigo em Inglês | MEDLINE | ID: mdl-25380409

RESUMO

By means of first-principles calculations, we have systematically investigated the structural, elastic, vibrational, thermal and electronic properties of the ground-state phase for the intermetallic compound U2Mo. Our results reveal that the previously synthesized I4/mmm structure of U2Mo is a metastable phase and unstable, neither thermodynamically nor vibrationally at the ground state. In combination with the evolutionary structural searches, our first-principles calculations suggest a new ground-state Pmmn phase, which has been confirmed theoretically to be stable, both thermodynamically and vibrationally. Moreover, through the DFT + D technique we have discussed the influence of van der Waals interactions on the structural, elastic and vibrational properties, revealing a weak effect in pure U and Mo solids and U2Mo alloy. The analysis of the electronic band structures evidences its electronic stabilities with the appearance of a deep valley in the density of states at the Fermi level. Moreover, we have investigated further the temperature-dependent structural, thermal expansion and elastic properties of our proposed Pmmn ground-state phase. These results are expected to stimulate further experimental investigations of the ground-state phase of U2Mo.

13.
Epigenetics Chromatin ; 17(1): 26, 2024 Aug 08.
Artigo em Inglês | MEDLINE | ID: mdl-39118189

RESUMO

Poly (ADP-ribose) polymerase 1 (PARP1) is a multifunctional nuclear enzyme that catalyzes poly-ADP ribosylation in eukaryotic cells. In addition to maintaining genomic integrity, this nuclear enzyme is also involved in transcriptional regulation. PARP1 can trigger and maintain changes in the chromatin structure and directly recruit transcription factors. PARP1 also prevents DNA methylation. However, most previous reviews on PARP1 have focused on its involvement in maintaining genome integrity, with less focus on its transcriptional regulatory function. This article comprehensively reviews the transcriptional regulatory function of PARP1 and its application in disease treatment, providing new ideas for targeting PARP1 for the treatment of diseases other than cancer.


Assuntos
Poli(ADP-Ribose) Polimerase-1 , Transcrição Gênica , Humanos , Poli(ADP-Ribose) Polimerase-1/metabolismo , Animais , Neoplasias/genética , Neoplasias/metabolismo , Regulação da Expressão Gênica , Metilação de DNA , Cromatina/metabolismo
14.
Heliyon ; 10(18): e37753, 2024 Sep 30.
Artigo em Inglês | MEDLINE | ID: mdl-39381226

RESUMO

Sensorineural hearing loss (SNHL) is the most common type of hearing loss worldwide. The primary mechanism is oxidative injury to the cochlea as a result of oxidative stress. Therefore, exploring antioxidant strategies is particularly important in addressing SNHL.Thioredoxin-interacting protein (TXNIP) is an upstream target of oxidative stress-induced damage, and the NOD-like receptor protein 3 (NLRP3) and NF-κB pathways may be the main downstream molecular pathways, but this has not been reported in SNHL. Therefore, we investigated the molecular mechanism and role of TXNIP in oxidative stress injury induced by H2O2 in the HEI-OC1 auditory cells. To induce oxidative stress, HEI-OC1 cells were treated with H2O2. The TXNIP expression was measured by western blotting and Immunofluorescence. Intracellular TXNIP was knocked down using small interfering RNAs (siRNAs). Cell viability was measured by CCK8, total intracellular reactive oxygen species (ROS) by DCFH-DA, mitochondrial ROS by Mito-SOX, NLRP3, pro-caspase-1, total p65 NF-κB, and phospho-p65 NF-κB expression were measured by western blotting. Statistical analyses were performed using one-way analysis of variance, and p < 0.05 was considered statistically significant. We found that H2O2 treatment induced oxidative stress injury in HEI-OC1 cells, as evidenced by decreased cell viability and increased total intracellular and mitochondrial ROS levels (p < 0.05). TXNIP expression was elevated, and NLRP3 and NF-κB were activated (p < 0.05). Moreover, siRNA-TXINIP co-treatment reversed these changes and protected HEI-OC1 cells from oxidative stress (p < 0.05). We concluded that H2O2-induced oxidative stress in HEI-OC1 cells was alleviated by TXNIP inhibition. The finding may provide new insight into the prevention and treatment of SNHL.

15.
Curr Dev Nutr ; 8(2): 102073, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38312433

RESUMO

Background: Inflammation can increase vitamin B6 uptake and catabolism. Higher vitamin B6 turnover [4-pyridoxic acid (4-PA)/pyridoxal 5'-phosphate (PLP) ratio], was associated with mortality risk in the general population. Objectives: We aimed to investigate the association between 4-PA/PLP and long-term mortality in patients with type 2 diabetes mellitus (T2DM), an inflammatory disease. Methods: In this prospective cohort study from the National Health and Nutrition Examination Survey (NHANES) cycles 2005-2010, the concentrations of 4-PA and PLP in plasma were measured using high-performance liquid chromatography, with mortality data updated to 31 December 2019. We included 2074 patients with T2DM aged between 20 and 85 y at baseline. Results: There were 739 deaths among 2279 patients with T2DM with a median follow-up of 11.83 y. In the age- and sex-adjusted COX model (model 1), 4-PA/PLP was positively associated with mortality in patients with T2DM [hazard ratio (HR) and 95% confidence interval (CI) highest compared with lowest quartiles: 35.55 (18.29, 69.09); P < 0.001], and in model 3, which was adjusted for demographics as well as inflammation, nutrition, and renal function, high 4-PA/PLP concentrations remained an independent risk factor for mortality in patients with T2DM [HR (95% CI) highest compared with lowest quartiles: 5.03 (2.46, 10.30); P < 0.001]. In restricted cubic spline (RCS), the link between 4-PA/PLP and all-cause mortality displays a positive correlation. Patients with died within the previous 2 y were excluded, the sensitivity analysis had no effect on the association between 4-PA/PLP and mortality in patients with T2DM. Finally, comparable results were found in subgroup analyses of specific-cause mortality. Conclusion: Higher vitamin B6 turnover is associated with long-term mortality risk in patients with T2DM. 4-PA/PLP may serve as a convenient prognostic marker in T2DM management.

16.
Infect Med (Beijing) ; 3(2): 100111, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38948389

RESUMO

Background: Swift and accurate detection of Vibrio parahaemolyticus, which is a prominent causative pathogen associated with seafood contamination, is required to effectively combat foodborne disease and wound infections. The toxR gene is relatively conserved within V. parahaemolyticus and is primarily involved in the expression and regulation of virulence genes with a notable degree of specificity. The aim of this study was to develop a rapid, simple, and constant temperature detection method for V. parahaemolyticus in clinical and nonspecialized laboratory settings. Methods: In this study, specific primers and CRISPR RNA were used to target the toxR gene to construct a reaction system that combines recombinase polymerase amplification (RPA) with CRISPR‒Cas13a. The whole-genome DNA of the sample was extracted by self-prepared sodium dodecyl sulphate (SDS) nucleic acid rapid extraction reagent, and visual interpretation of the detection results was performed by lateral flow dipsticks (LFDs). Results: The specificity of the RPA-CRISPR/Cas13a-LFD method was validated using V. parahaemolyticus strain ATCC-17802 and six other non-parahaemolytic Vibrio species. The results demonstrated a specificity of 100%. Additionally, the genomic DNA of V. parahaemolyticus was serially diluted and analysed, with a minimum detectable limit of 1 copy/µL for this method, which was greater than that of the TaqMan-qPCR method (102 copies/µL). The established methods were successfully applied to detect wild-type V. parahaemolyticus, yielding results consistent with those of TaqMan-qPCR and MALDI-TOF MS mass spectrometry identification. Finally, the established RPA-CRISPR/Cas13a-LFD method was applied to whole blood specimens from mice infected with V. parahaemolyticus, and the detection rate of V. parahaemolyticus by this method was consistent with that of the conventional PCR method. Conclusions: In this study, we describe an RPA-CRISPR/Cas13a detection method that specifically targets the toxR gene and offers advantages such as simplicity, rapidity, high specificity, and visual interpretation. This method serves as a valuable tool for the prompt detection of V. parahaemolyticus in nonspecialized laboratory settings.

17.
Artigo em Inglês | MEDLINE | ID: mdl-39396197

RESUMO

GeTe stands as a promising lead-free medium-temperature thermoelectric material that has garnered considerable attention in recent years. Suppressing carrier concentration by aliovalent doping in GeTe-based thermoelectrics is the most common optimization strategy due to the intrinsically high Ge vacancy concentration. However, it inevitably results in a significant deterioration of carrier mobility, which limits further improvement of the zT value. Thus, an effective Trojan doping strategy via CuScTe2 alloying is utilized to optimize carrier concentration without intensifying charge carrier scattering by increasing the solubility of Sc in the GeTe system. Because of the high doping efficiency of the Trojan doping strategy, optimized hole concentration and high mobility are obtained. Furthermore, CuScTe2 alloying leads to band convergence in GeTe, increasing the effective mass m* in (Ge0.84Sb0.06Te0.9)(CuScTe2)0.05 and thus significantly improving the Seebeck coefficient throughout the measured temperature range. Meanwhile, the achievement of the ultralow lattice thermal conductivity (κL ∼ 0.34 W m-1 K-1) at 623 K is attributed to dense point defects with mass/strain-field fluctuations. Ultimately, the (Ge0.84Sb0.06Te0.9)(CuScTe2)0.05 sample exhibits a desirable thermoelectric performance of zTmax ∼ 1.81 at 623 K and zTave ∼ 1.01 between 300 and 723 K. This study showcases an effective doping strategy for enhancing the thermoelectric properties of GeTe-based materials by decoupling phonon and carrier scattering.

18.
Int J Biol Macromol ; 275(Pt 2): 133720, 2024 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-38987000

RESUMO

Tick-borne encephalitis virus (TBEV), a zoonotic pathogen, can cause severe neurological complications and fatal outcomes in humans. Early diagnosis of TBEV infection is crucial for clinical practice. Although serological assays are frequently employed for detection, the lack of antibodies in the early stages of infection and the cross-reactivity of antibodies limit their efficacy. Conventional molecular diagnostic methods such as RT-qPCR can achieve early and accurate identification but require specialized instrumentation and professionals, hindering their application in resource-limited areas. Our study developed a rapid and visual TBEV molecular detection method by combining RT-recombinase-aided amplification, the CRISPR/Cas13a system, and lateral flow dipsticks. The diagnostic sensitivity of this method is 50 CFU/ml, with no cross-reactivity with a variety of viruses. The detection can be carried out within 1 h at a temperature between 37 and 42 °C, and the results can be visually determined without the need for complex instruments and professionals. Subsequently, this assay was used to analyze clinical samples from 15 patients suspected of TBEV infection and 10 healthy volunteers, and its sensitivity and specificity reached 100 %, which was consistent with the results of RT-qPCR. These results indicate that this new method can be a promising point-of-care test for the diagnosis of tick-borne encephalitis.


Assuntos
Sistemas CRISPR-Cas , Vírus da Encefalite Transmitidos por Carrapatos , Recombinases , Vírus da Encefalite Transmitidos por Carrapatos/genética , Humanos , Recombinases/metabolismo , Técnicas de Amplificação de Ácido Nucleico/métodos , Encefalite Transmitida por Carrapatos/diagnóstico , Encefalite Transmitida por Carrapatos/virologia , Encefalite Transmitida por Carrapatos/sangue , Sensibilidade e Especificidade , RNA Viral/genética , Técnicas de Diagnóstico Molecular/métodos
19.
Sci Total Environ ; 930: 172688, 2024 Jun 20.
Artigo em Inglês | MEDLINE | ID: mdl-38663627

RESUMO

With allergic rhinitis (AR) on the rise globally, there has been a growing focus on the role of environmental pollutants in the onset of AR. However, the potential mechanisms by how and which these pollutants exacerbate AR conditions remain unknown. This panel study of 49 patients diagnosed with AR over one year aimed to assess the individual and combined effects of short-term exposure to multiple ambient pollutants on oxidative stress, symptoms, and quality of life among patients with AR. All participants underwent four repeated assessments of health conditions and personal environmental exposures (PM2.5, O3, SO2, and NO2) over warm and cold seasons during 2017-2018. We evaluated two oxidative stress biomarkers (malondialdehyde [MDA], and superoxide dismutase [SOD]) via nasal lavage. We collected information on self-reported symptoms and quality of life using the Rhinitis Symptom Scale (SRS), the Visual Analog Scale (VAS), and the Rhinoconjunctivitis Quality of Life Questionnaire (RQLQ) through in-person interviews. Bayesian kernel machine regression (BKMR) was used to evaluate the joint effects of pollutant mixture and identify key contributors. The results revealed a significant association of the pollutant mixture when all four pollutants were at or above their median levels, with increased oxidative stress. This was evidenced by elevated MDA and reduced SOD. We found a joint detrimental effect of the pollutant mixture on AR symptoms with a strong association with increased SRS scores, but a non-significant positive association with VAS and RQLQ scores. PM2.5, O3, and SO2 presented as the potentially primary contributors to the adverse health effects associated with the pollutant mixture in Taiyuan city. Patients with AR exposed to short-term air pollutant mixture are more likely to have greater nasal symptoms and worse quality of life from increased oxidative stress and reduced antioxidant capacity. Further research is warranted to better elucidate the underlying mechanisms.


Assuntos
Poluentes Atmosféricos , Poluição do Ar , Estresse Oxidativo , Rinite Alérgica , Humanos , Poluição do Ar/efeitos adversos , Poluição do Ar/estatística & dados numéricos , Poluentes Atmosféricos/efeitos adversos , Masculino , Feminino , Adulto , Qualidade de Vida , Exposição Ambiental/estatística & dados numéricos , Exposição Ambiental/efeitos adversos , Pessoa de Meia-Idade , Material Particulado
20.
Ultrasound Med Biol ; 49(10): 2234-2246, 2023 10.
Artigo em Inglês | MEDLINE | ID: mdl-37544831

RESUMO

OBJECTIVE: Plane-wave imaging (PWI) is a high-frame-rate imaging technique that sacrifices image quality. Deep learning can potentially enhance plane-wave image quality, but processing complex in-phase and quadrature (IQ) data and suppressing incoherent signals pose challenges. To address these challenges, we present a complex transformer network (CTN) that integrates complex convolution and complex self-attention (CSA) modules. METHODS: The CTN operates in a four-step process: delaying complex IQ data from a 0° single-angle plane wave for each pixel as CTN input data; extracting reconstruction features with a complex convolution layer; suppressing irrelevant features derived from incoherent signals with two CSA modules; and forming output images with another complex convolution layer. The training labels are generated by minimum variance (MV). RESULTS: Simulation, phantom and in vivo experiments revealed that CTN produced comparable- or even higher-quality images than MV, but with much shorter computation time. Evaluation metrics included contrast ratio, contrast-to-noise ratio, generalized contrast-to-noise ratio and lateral and axial full width at half-maximum and were -11.59 dB, 1.16, 0.68, 278 µm and 329 µm for simulation, respectively, and 9.87 dB, 0.96, 0.62, 357 µm and 305 µm for the phantom experiment, respectively. In vivo experiments further indicated that CTN could significantly improve details that were previously vague or even invisible in DAS and MV images. And after being accelerated by GPU, the CTN runtime (76.03 ms) was comparable to that of delay-and-sum (DAS, 61.24 ms). CONCLUSION: The proposed CTN significantly improved the image contrast, resolution and some unclear details by the MV beamformer, making it an efficient tool for high-frame-rate imaging.


Assuntos
Processamento de Imagem Assistida por Computador , Microbolhas , Processamento de Imagem Assistida por Computador/métodos , Ultrassonografia/métodos , Imagens de Fantasmas , Simulação por Computador , Algoritmos
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