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1.
J Int Med Res ; 49(9): 3000605211016208, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-34510958

RESUMO

OBJECTIVE: This retrospective multicentre observational study was performed to assess the predictors of acute kidney injury (AKI) in patients with acute decompensated heart failure (ADHF) in emergency departments in China. METHODS: In total, 1743 consecutive patients with ADHF were recruited from August 2017 to January 2018. Clinical characteristics and outcomes were compared between patients with and without AKI. Predictors of AKI occurrence and underdiagnosis were assessed in multivariate regression analyses. RESULTS: Of the 1743 patients, 593 (34.0%) had AKI. AKI was partly associated with short-term all-cause mortality and cost. Cardiovascular comorbidities such as coronary heart disease, diabetes mellitus, and hypertension remained significant predictors of AKI in the univariate analysis. AKI was significantly more likely to occur in patients with a lower arterial pH, lower albumin concentration, higher creatinine concentration, and higher N-terminal pro-brain natriuretic peptide (NT-proBNP) concentration. Patients treated with inotropic agents were significantly more likely to develop AKI during their hospital stay. CONCLUSION: This study suggests that cardiovascular comorbidities, arterial pH, the albumin concentration, the creatinine concentration, the NT-proBNP concentration, and use of inotropic agents are predictors of AKI in patients with ADHF.


Assuntos
Injúria Renal Aguda , Insuficiência Cardíaca , Doença Aguda , Injúria Renal Aguda/diagnóstico , Biomarcadores , Serviço Hospitalar de Emergência , Insuficiência Cardíaca/complicações , Insuficiência Cardíaca/diagnóstico , Insuficiência Cardíaca/epidemiologia , Humanos , Peptídeo Natriurético Encefálico , Fragmentos de Peptídeos , Prognóstico , Estudos Retrospectivos
2.
Talanta ; 235: 122809, 2021 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-34517666

RESUMO

The 8-oxoguanine (8-oxoG) represents the most common DNA damage type, and it has been regarded as the oxidative stress biomarker, but the reported 8-oxoguanine assays are limited by poor specificity and low sensitivity. Herein, we demonstrate the construction of damage site-specific fluorescent biosensor for 8-oxoG assay by integrating single-molecule detection with hyperbranched signal amplification. In this assay, the 8-oxoG damages in DNA can generate free 3' OH with the assistance of formamidopyrimidine DNA glycosylase (Fpg) and polynucleotide kinase (PNK), which subsequently triggers the incorporation of abundant Cy5-labeled dUTPs via terminal deoxynucleotidyl transferase (TDT)-mediated site-specific hyperbranched nucleic acid amplification. After digestion of amplification products with nuclease treatment, abundant mononucleotide Cy5-dUTPs are produced, which will be easily monitored via single-molecule imaging and detection. The introduction of hyperbranched nucleic acid amplification and single-molecule detection can greatly improve the sensitivity to achieve a detection limit of 7.62 × 10-18 M. This biosensor is highly specific with the capability of discriminating 0.001% 8-oxoG target from the DNA mixture. Moreover, it can be applied for quantitative detection of 8-oxoG damage in genomic DNAs with a detection limit of 0.0017 ng, and even accurately quantifies the absolute number (7025 - 8506) of 8-oxoG damage base in single HeLa cell treated with 150 µM H2O2. Importantly, this biosensor can measure the 8-oxoG damage level in different cancer cell lines, facilitating the oxidative damage-associated biomedical researches and clinical diagnosis.


Assuntos
Técnicas Biossensoriais , Peróxido de Hidrogênio , Dano ao DNA , DNA-Formamidopirimidina Glicosilase , Células HeLa , Humanos
3.
Phys Rev Lett ; 127(10): 103601, 2021 Sep 03.
Artigo em Inglês | MEDLINE | ID: mdl-34533368

RESUMO

Interferometers are widely used in imaging technologies to achieve enhanced spatial resolution, but require that the incoming photons be indistinguishable. In previous work, we built and analyzed color erasure detectors, which expand the scope of intensity interferometry to accommodate sources of different colors. Here we demonstrate experimentally how color erasure detectors can achieve improved spatial resolution in an imaging task, well beyond the diffraction limit. Utilizing two 10.9-mm-aperture telescopes and a 0.8 m baseline, we measure the distance between a 1063.6 and a 1064.4 nm source separated by 4.2 mm at a distance of 1.43 km, which surpasses the diffraction limit of a single telescope by about 40 times. Moreover, chromatic intensity interferometry allows us to recover the phase of the Fourier transform of the imaged objects-a quantity that is, in the presence of modest noise, inaccessible to conventional intensity interferometry.

4.
Technol Cancer Res Treat ; 20: 15330338211039126, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34520292

RESUMO

Background: Aberrant expression and alternative splicing of oncogenes are the driving events in tumor initiation and development. But how these events are regulated in cancer cells is largely unknown. Functions of ATP5A1, an important mitochondrial ATP synthase gene, in transcriptional and posttranscriptional regulation were explored in this study. Methods: ATP5A1 was overexpressed using plasmid-transformed HeLa cells, and its influence on cell apoptosis and proliferation is evaluated. Transcriptome sequencing was then performed using RNA-seq to study the changes in gene expression and regulation of alternative splicing events. Validation of the implicated genes was achieved using RT-qPCR analysis. Results: It was found that ATP5A1 could significantly promote cellular apoptosis, but it had no influence on cell proliferation. ATP5A1 overexpression significantly increased the expression levels of genes associated with the innate immune response, angiogenesis, and collagen catabolic processes. This included enrichment of MMP2 and MMP19. It was also found that ATP5A1 could interfere with the alternative splicing of hundreds of genes associated with glucose homeostasis, HIF-1 signaling activation, and several pathways associated with cancers. Eight ATP5A1-regulated differentially expressed genes and 3 genes altered by splicing were selected and validated using RT-qPCR analysis. Conclusions: In summary, we illustrate the regulatory functions of ATP5A1 on the transcriptome of HeLa cells by exploring its influence on gene expression and alternative splicing. The results suggest that ATP5A1 may play an important regulatory role in cervical cancer cells by regulating expression and alternative splicing of cancer-associated genes. This study provides novel insights into the current understanding of the mechanisms of ATP5A1 on carcinogenesis and cancer progression.

5.
PLoS One ; 16(8): e0255975, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34424927

RESUMO

BACKGROUND: Activation of intravesical protease activated receptor 4 (PAR4) leads to release of urothelial macrophage migration inhibitory factor (MIF). MIF then binds to urothelial MIF receptors to release urothelial high mobility group box-1 (HMGB1) and elicit bladder hyperalgesia. Since MIF binds to multiple receptors, we investigated the contribution of individual urothelial MIF receptors to PAR4-induced HMGB1 release in vivo and in vitro and bladder pain in vivo. METHODOLOGY/PRINCIPAL FINDINGS: We tested the effect of intravesical pre-treatment with individual MIF or MIF receptor (CD74, CXCR4, CXCR2) antagonists on PAR4-induced HMGB1 release in vivo (female C57/BL6 mice) and in vitro (primary human urothelial cells) and on PAR4-induced bladder hyperalgesia in vivo (mice). In mice, PAR4 induced HMGB1 release and bladder hyperalgesia through activation of intravesical MIF receptors, CD74 and CXCR4. CXCR2 was not involved in these effects. In primary urothelial cells, PAR4-induced HMGB1 release through activation of CD74 receptors. Micturition parameters in mice were not changed by any of the treatments. CONCLUSIONS/SIGNIFICANCE: Urothelial MIF receptors CD74 and CXCR4 mediate bladder pain through release of urothelial HMGB1. This mechanism may set up persistent pain loops in the bladder and warrants further investigation. Urothelial CD74 and CXCR4 may provide novel targets for interrupting bladder pain.

6.
ACS Nano ; 2021 Aug 05.
Artigo em Inglês | MEDLINE | ID: mdl-34351124

RESUMO

It is still challenging to develop sulfur electrodes for Li-S batteries with high electrical conductivity and fast kinetics, as well as efficient suppression of the shuttling effect of lithium polysulfides. To address such issues, herein, polar MoTe2 with different phases (2H, 1T, and 1T') were deeply investigated by density functional theory calculations, suggesting that the 1T'-MoTe2 displays concentrated density of states (DOS) near the Fermi level with high conductivity. By optimization of the synthesis, 1T'-MoTe2 quantum dots decorated three-dimensional graphene (MTQ@3DG) was prepared to overcome these issues, and it accomplished exceptional performance in Li-S batteries. Owing to the chemisorption and high catalytic effect of 1T'-MoTe2 quantum dots, MTQ@3DG/S exhibits highly reversible discharge capacity of 1310.1 mAh g-1 at 0.2 C with 0.026% capacity fade rate per cycle over 600 cycles. The adsorption calculation demonstrates that the conversion of Li2S2 to Li2S is the rate-limiting step where the Gibbs free energies are 1.07 eV for graphene and 0.97 eV for 1T'-MoTe2, revealing the importance of 1T'-MoTe2. Furthermore, in situ Raman spectroscopy investigation proved the suppression of the shuttle effect of LiPSs in MTQ@3DG/S cells during the cycle.

7.
JAMA Oncol ; : e213428, 2021 Aug 26.
Artigo em Inglês | MEDLINE | ID: mdl-34436536

RESUMO

Importance: The effectiveness of the mammalian target of rapamycin (mTOR) inhibitor everolimus in premenopausal women with hormone receptor (HR)-positive/ERBB2-negative advanced breast cancer who experienced disease progression while receiving selective estrogen receptor modulators (SERMs) is unknown. Objective: To compare the effectiveness of everolimus plus letrozole vs letrozole alone in premenopausal women with HR-positive/ERBB2-negative advanced breast cancer who experienced disease progression while receiving SERMs. Design, Setting, and Participants: The Everolimus Trial for Advanced Premenopausal Breast Cancer (MIRACLE) was a multicenter, open-label phase 2 randomized clinical trial of everolimus plus letrozole vs letrozole alone as first-line treatment conducted from December 8, 2014, to September 26, 2018. Participants included premenopausal women with HR-positive, ERBB2-negative advanced breast cancer who experienced disease progression while receiving SERMs. Analysis was performed on an intent-to-treat basis from January 5, 2015, to December 30, 2019. Exposures: Patients were randomly assigned in a 1:1 ratio to receive everolimus (10 mg orally once daily) plus letrozole (2.5 mg orally once daily) (n = 101) or letrozole alone (2.5 mg orally once daily) (n = 98). Both groups received goserelin, 3.6 mg, subcutaneously on day 1 of each 28-day cycle. Patients in the letrozole group were permitted to cross over to receive everolimus with letrozole if disease progression occurred. Main Outcomes and Measures: The primary end point was progression-free survival (PFS), defined as the time from randomization to confirmed disease progression or death due to any cause. Results: A total of 199 women (mean [SD] age, 44.3 [6.3] years) were randomized. Patients receiving everolimus plus letrozole achieved a significantly longer median PFS compared with those receiving letrozole alone (19.4 months [95% CI, 16.3-22.0 months] vs 12.9 months [95% CI, 7.6-15.7 months]; hazard ratio, 0.64 [95% CI, 0.46-0.89]; P = .008). A total of 56 of the 98 patients in the letrozole group (57.1%) were crossed over to also receive everolimus. The median PFS after crossover was 5.5 months (95% CI, 3.8-8.2 months). Conclusions and Relevance: In this randomized clinical trial, PFS was significantly longer among premenopausal patients with HR-positive/ERBB2-negative advanced breast cancer who received everolimus plus letrozole than among those who received letrozole alone. The results revealed that everolimus was effective even among patients receiving treatment with the same endocrine agent after disease progression. Trial Registration: ClinicalTrials.gov Identifier: NCT02313051.

8.
Sci Rep ; 11(1): 16615, 2021 Aug 16.
Artigo em Inglês | MEDLINE | ID: mdl-34400738

RESUMO

This study describes a morphology-based unilateral cervical facet interlocking classification in an attempt to clarify the injury mechanism, instability, neurological deficits, radiological features, and determine optimum management strategies for these injuries. A total of 55 patients with unilateral cervical locked facet (UCLF) involving C3 to C7 were identified between January 1, 2012 and December 1, 2019. The injuries were classified into three types, and they were further divided into six subtypes using three-dimensional computed tomography. The injury mechanism, clinical features, neurological deficits, and imaging characteristics were analyzed, and the appropriate treatment strategies for UCLF were discussed. UCLFs were divided into the following six subtypes: UCLF without lateral mass-facet fracture (type I) in nine cases, with superior articular process fracture (type II A) in 22, with inferior articular process fracture (type II B) in seven, both superior and inferior articular process fractures (type II C) in four, with lateral mass splitting fracture (type III A) in three, and with lateral mass comminution fractures (type III B) in ten. A total of 22 (40.0%) of the 55 patients presented with radiculopathy, and 23 patients (41.8%) had spinal cord injuries. The subtype analyses showed high rates of radiculopathy in types II A (68.2%) and II C (75.0%), as well as significant spinal cord injury in types I (77.8%) and III (61.5%). Destruction of the facet capsule was observed in all patients, but the injury of disc, ligamentous complex, and vertebra had a significant difference among the types or subtypes. The instability parameters of the axial rotation angle, segmental kyphosis, and sagittal displacement showed significant differences in various types of UCLF. Closed reduction by preoperative and intraoperative general anesthesia traction was achieved in 27 patients (49.1%), and successful rate of closed reduction in type I (22.2%) was significantly lower than that in type II (51.5%) and type III (61.5%). A total of 35 of 55 patients underwent a single anterior fixation and fusion, 10 patients were treated with posterior pedicle and (or) lateral mass fixation, and combined surgery was performed in ten patients. Ten patients (18.2%) with a poor outcome were observed after first surgery. Among them, 3 patients treated with a single anterior surgery had persistent or aggravated radiculopathy and posterior approach surgery with ipsilateral facet resection, foramen enlargement, and pedicle and (or) lateral mass screw fixation was performed immediately, 5 patients treated with a short-segment posterior surgery showed mild late kyphosis deformity, and 2 patients with vertebral malalignment were encountered after anterior single-level fusion during the follow-up. This retrospective study indicated that UCLF is a rotationally unstable cervical spine injury. The classification proposed in this study will contribute to understanding the injury mechanism, radiological characteristics, and neurological deficits in various types of UCLF, which will help the surgeons to evaluate the preoperative closed reduction and guide the selection of surgical approach and fusion segment.

10.
J Innate Immun ; : 1-12, 2021 Jul 21.
Artigo em Inglês | MEDLINE | ID: mdl-34289483

RESUMO

Eosinophil (Eo) degranulation plays a central role in the initiations of allergic attacks. Flagellin (FGN), the major component of bacterial flagella, has immune regulatory functions. This study aims to investigate the role of FGN in alleviating the allergic reaction by stabilizing Eos. A toll-like receptor 5-knockout mouse strain was employed to test the role of FGN in stabilizing Eos. An airway allergy mouse model was developed to test the administration of FGN in alleviating the airway allergy by stabilizing Eos. The results showed that FGN was required in stabilizing Eos in the airway tissues. FGN prevented specific antigen-induced Eo activation. Oxidative stress was associated with the antigen-induced Eo activation that could be counteracted by the presence of FGN. The FGN levels were lower and chymase levels were higher in the airway tissues of mice with allergic inflammation. Negative correlation was detected between the data of FGN and chymase in the lung tissues. Chymase physically contacted FGN to speed up its degradation. The administration of FGN alleviated experimental allergic inflammation in the mouse airways by stabilized Eos in the lung tissues. In conclusion, FGN contributes to Eo stabilization. The administration of FGN alleviates the experimental airway allergy. The data suggest that FGN can be a candidate to be employed in the treatment of allergic disorders.

11.
Biosci Trends ; 2021 Jul 23.
Artigo em Inglês | MEDLINE | ID: mdl-34305102

RESUMO

Onco-cardiology is an emerging field linking cancer with cardiovascular injury. Understanding the mechanism of cardiac injury helps improve the quality of life of cancer survivors. A series of studies on adverse reactions to cancer or oncological treatments has indicated that adverse cardiovascular events related to cancer treatments may occur over a longer period of survival, and even years after therapy has concluded. Current cancer therapies, including chemotherapy, radiotherapy, targeted therapy, and immunotherapy, have been found to have latent cardiovascular toxicity. These toxic effects are often progressive and irreversible and ultimately lead to cardiovascular events such as heart failure, hypertension, coronary heart diseases, arrhythmia, and thromboembolism. Therefore, more emphasis should be placed on revealing the mechanism of cancer treatment-related cardiovascular toxicity. This would help to guide prevention, diagnosis, and treatment of CVDs in cancer survivors.

12.
Phys Chem Chem Phys ; 2021 Jul 02.
Artigo em Inglês | MEDLINE | ID: mdl-34198313

RESUMO

The applications of two-dimensional (2D) materials in electronics, optoelectronics, and spintronics are limited by the high contact resistance at the metal/semiconductor interface owing to the strong Fermi-level pinning. In this study, an interlayer insertion strategy is proposed to solve this problem, and first principles calculations are done to study the influences of inserting a SiC layer on the Schottky barrier and electronic properties of MoS2/metals (Mg, Al, In, Cu, Ag, Au, Pd, Ti, and Sc). The average charge value substantially increased (≥0.060 e) at the interface between SiC and MoS2 layers, and then no tunneling barrier appeared except for the MoS2/Au contact by inserting the SiC layer. Moreover, ΦSB,N almost decreases for the MoS2/metal contacts by inserting the SiC layer. When Ti, Cu, Au, and Pd are used as electrodes, the n-type Schottky barrier is formed with the ΦSB,N values of 0.479 eV, -0.073 eV, 0.498 eV, and 0.225 eV, respectively. However, if Al, In, Mg, and Ag are used as electrodes, the systems are transformed into Ohmic contact. These findings provide a practical guideline for depinning the Fermi level at contact interfaces and designing the high performance TMD-based nanoelectronic devices.

13.
Signal Transduct Target Ther ; 6(1): 251, 2021 Jul 07.
Artigo em Inglês | MEDLINE | ID: mdl-34230452

RESUMO

Circulating tumor DNA (ctDNA) is a potential biomarker of prognosis and therapeutic response. We conducted this study to explore the role of the molecular tumor burden index (mTBI) in ctDNA as a therapeutic response and prognostic biomarker in a larger cohort prospective phase III randomized multicenter study. We collected 291 plasma samples from 125 metastatic breast cancer patients from the CAMELLIA study (NCT01917279). Target-capture deep sequencing of 1021 genes was performed to detect somatic variants in ctDNA from the plasma samples. The pretreatment mTBI value was correlated with tumor burden (P = 0.025). Patients with high-level pretreatment mTBI had shorter overall survival than patients with low-level pretreatment mTBI, and the median overall survival was 40.9 months and 68.4 months, respectively (P = 0.011). Patients with mTBI decrease to less than 0.02% at the first tumor evaluation had longer progression-free survival and overall survival (P < 0.001 and P = 0.007, respectively). The mTBI has good sensitivity to identify complete response/partial response and progressive disease based on computed tomography scans (88.5% and 87.5%, respectively). The patients classified as molecular responders had longer progression-free survival and overall survival than the nonmolecular responders in the overall cohort (P < 0.001 and P = 0.036, respectively), as well as in the cohort in which computed tomography scans were defined as representing stable disease (P = 0.027 and P = 0.015, respectively). The mTBI in ctDNA detected in liquid biopsies is a potential biomarker of therapeutic response and prognosis in patients with metastatic breast cancer.

14.
Clin Exp Pharmacol Physiol ; 48(10): 1412-1420, 2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-34174105

RESUMO

Periodontitis, a human chronic inflammatory disease, has affected the lives of millions of individuals. Periodontal ligament stem cells (PDLSCs), derived from the periodontal ligament, exhibit tissue specificity and impaired differentiation ability and are closely associated with tissue regeneration in periodontitis. Klotho, a single-pass transmembrane protein, has been reported to positively affect H2 O2 -induced oxidative stress and inflammation in PDLSCs. The ultimate damage of oxidative stress stimulation in PDLSCs was cell apoptosis, which was also the major lesion in periodontitis. Thus, the present study aimed to figure out the effect of klotho on H2 O2 -injured PDLSCs and its underlying mechanism to provide new therapeutic targets in periodontitis. The expression of klotho and uncoupling protein 2 (UCP2) was investigated in the gingival tissues, gingival crevicular fluid (GCF), and periodontal ligament stem cells (PDLSCs) in patients with chronic periodontitis. Then, under klotho treatment, oxidative stress was evaluated by measuring SOD and GSH-PX levels. Cell apoptosis and cell necrosis were also detected by measuring the cell death-relevant proteins, including Caspase-3, BAX, Bcl, MLKL, RIP1, and RIP3. Finally, a rescue assay was performed by inhibiting the expression of UCP2. The results showed that klotho and UCP2 were downregulated in patients with chronic periodontitis. In addition, klotho upregulated the production of UCP2 in H2 O2 -treated PDLSCs. Klotho inhibited H2 O2 -induced oxidative stress and cellular loss in PDLSCs, moreover, the rescue assay suggested that UCP2 knockdown suppressed the effects of klotho on PDLSCs. In conclusion, this study showed that klotho inhibits H2 O2 -induced oxidative stress and apoptosis in PDLSCs by regulating UCP2 expression. This novel discovery might provide a potential target for chronic periodontitis treatment.

15.
Curr Alzheimer Res ; 18(3): 256-264, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34139973

RESUMO

BACKGROUND: Recent findings suggest a possible role of diet, particularly nutrient intakes and dietary patterns, in the prevalence of mild cognitive impairment (MCI); few studies, however, have been explicitly devoted to the relationship between dietary habits and MCI. OBJECTIVES: We aimed to explore the association between dietary habits, including meal timing, and MCI among older Chinese adults. METHODS: This cross-sectional study involved data collected at the baseline of the Tianjin Elderly Nutrition and Cognition Cohort (TENCC) study, in which 3,111 community-dwelling older adults (326 MCI patients and 2,785 non-MCIs) from a rural area of Tianjin, China, were recruited. In March 2018 to June 2019, all participants underwent a detailed neuropsychological evaluation that allowed for psychometric MCI classification. Information on self-reported dietary behaviors was gathered via face-to-face interviews. Crude and multivariable-adjusted odds ratios (ORs) and 95% confidence intervals (CIs) were estimated using logistic regression models. RESULTS: In the multivariable-adjusted models, eating breakfast 4 to 6 times per week (vs. ≤3 times per week, OR: 0.45; 95% CI: 0.26, 0.75), drinking water before breakfast (yes vs. no, OR: 0.64; 95% CI: 0.51, 0.82), consuming water ≥1.5L per day (vs. <1.5L per day, OR: 0.64; 95% CI: 0.51, 0.82), and having lunch after 12:00 (vs. before 12:00, OR: 0.59; 95% CI: 0.47, 0.75) were associated with decreased risk of MCI. Participants who consumed higher amounts of cooking oil were at a higher risk of MCI (moderate vs. low, OR: 1.42; 95% CI: 1.04, 1.92; high vs. low, OR: 1.40; 95% CI: 1.07-1.83). CONCLUSION: This study suggests that dietary habits, including breakfast frequency, daily water consumption, cooking oil consumption, and meal timing, may be associated with the risk of MCI. If replicated, these findings would open new possibilities of dietary interventions for MCI.

16.
Virus Res ; 302: 198481, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-34119571

RESUMO

Bacterial infections have a negative impact on both animal husbandry industry and medicine, and increasing bacterial drug resistance exacerbates this adverse impact. Phages show promise as an alternative to drugs against drug-resistant bacteria. In this study, a novel virulent bacteriophage (phage) vB_ValP_IME234 against Vibrio alginolyticus and Vibrio parahaemolyticus was isolated from freshwater in Beijing, China. Phage vB_ValP_IME234 had an isometric head (59 nm in diameter) and a short tail (10 nm long), belonging to Podoviridae family. Its complete genome is liner double-stranded DNA (dsDNA) with a GC content of 41.6% while encoding 61 putative proteins. Three transfer RNA (tRNA) and no lysogenic gene was detected. vB_ValP_IME234 had a polyvalent infectivity, a burst of 390 PFU/cell, and is stable under different temperatures (4 °C to 50 °C) and pH (6.0 to 10.0) values. Host range test showed that vB_ValP_IME234 has the ability to infect seven strains of Vibrio in total. Phylogenetic analyses based on terminase and capsid suggested that this phage had a close relationship with Vibrio phages. These results indicate that vB_ValP_IME234 could be used as a potential biocontrol agent against V. alginolyticus strains.

17.
J Phys Chem Lett ; 12(23): 5526-5533, 2021 Jun 17.
Artigo em Inglês | MEDLINE | ID: mdl-34096727

RESUMO

Despite extensive study, mysteries remain regarding the highly efficient ultrafast charge separation processes in photosynthetic reaction centers (RCs). In this work, transient Stark signals were found to be present in ultrafast two-dimensional electronic spectra recorded for purple bacterial RCs at 77 K. These arose from the electric field that is inherent to the intradimer charge-transfer intermediate of the bacteriochlorophyll pair (P), PA+PB-. By comparing three mutated RCs, a correlation was found between the efficient formation of PA+PB- and a fast charge separation rate. Importantly, the energy level of P* was changed due to the Stark shift, influencing the driving force for P* → P+BA- electron transfer and hence its rate. Furthermore, the orientation and amplitude of the inherent electric field varied in different ways upon different mutation, leading to contrasting changes in the rates. This mechanism of modulation provides a solution to a long-lasting inconsistency between experimental observations and activation energy theory.


Assuntos
Complexo de Proteínas do Centro de Reação Fotossintética/química , Rhodobacter sphaeroides/química , Cromatografia de Afinidade/métodos , Transporte de Elétrons/genética , Mutação/genética , Complexo de Proteínas do Centro de Reação Fotossintética/análise , Rhodobacter sphaeroides/genética , Análise Espectral/métodos , Fatores de Tempo
18.
Ecotoxicol Environ Saf ; 220: 112385, 2021 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-34082241

RESUMO

Sulfometuron methyl (SM) is a widely used herbicide and thus leading to accumulation in the environment. The toxicity assessments of SM in model organisms are currently rare. In the present study, zebrafish were utilized for evaluating the detrimental effects of SM in aquatic vertebrates. Zebrafish embryos were exposed to 0, 10, 20, and 40 mg/L SM from 5.5 to 72 h post-fertilization (hpf), respectively. Consequently, SM exposure resulted in increasing the mortality rate and reducing hatching rate in larval zebrafish at 10, 20, and 40 mg/L SM-treated groups. The reduced numbers of immune cells (neutrophils and macrophages) were observed after SM exposure by a dose-dependent manner. The inflammatory responses (TLR4, MYD88, IL-1ß, IL-6, IL-8, IFN-γ, IL-10, and TGF-ß) were measured to estimate immune responses. Anti-inflammatory factors (IL-10 and TGF-ß) were down-regulated in all the treated groups and significantly altered at 40 mg/L exposure group. Additionally, behavioral tests suggested that SM treatment significantly increased the total distance, average speed, and maximum acceleration of larval zebrafish during light-dark transition and subsequently enzymology test displayed the same trend to locomotor behaviors. The content significantly increased in oxidative stress, as reflected in ROS level in all the treated groups. The numbers of cell apoptosis were significantly increased at 20, and 40 mg/L and the highest concentration group induced the substantial increment (P < 0.001) of apoptosis-related genes including p53, Bax/Bcl-2, caspase-9, and caspase-3. In summary, our results demonstrated that exposure to SM caused toxicity of development, immune system, locomotor behavior, oxidative stress, and cell apoptosis at the early developmental stages of zebrafish.


Assuntos
Embrião não Mamífero/efeitos dos fármacos , Herbicidas/toxicidade , Compostos de Sulfonilureia/toxicidade , Peixe-Zebra/crescimento & desenvolvimento , Animais , Apoptose/efeitos dos fármacos , Catalase/metabolismo , Citocinas/genética , Citocinas/metabolismo , Regulação da Expressão Gênica no Desenvolvimento/efeitos dos fármacos , Larva/efeitos dos fármacos , Estresse Oxidativo/efeitos dos fármacos , Espécies Reativas de Oxigênio , Superóxido Dismutase/metabolismo , Poluentes Químicos da Água/toxicidade
19.
Dev Comp Immunol ; 124: 104183, 2021 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-34174242

RESUMO

The Toll signaling pathway is highly conserved from insects to mammals. Drosophila is a model species that is commonly used to study innate immunity. Although many studies have assessed protein-coding genes that regulate the Toll pathway, it is unclear whether long noncoding RNAs (lncRNAs) play regulatory roles in the Toll pathway. Here, we evaluated the expression of the lncRNA CR46018 in Drosophila. Our results showed that this lncRNA was significantly overexpressed after infection of Drosophila with Micrococcus luteus. A CR46018-overexpressing Drosophila strain was then constructed; we expected that CR46018 overexpression would enhance the expression of various antimicrobial peptides downstream of the Toll pathway, regardless of infection with M. luteus. RNA-seq analysis of CR46018-overexpressing Drosophila after infection with M. luteus showed that upregulated genes were mainly enriched in Toll and Imd signaling pathways. Moreover, bioinformatics predictions and RNA-immunoprecipitation experiments showed that CR46018 interacted with the transcription factors Dif and Dorsal to enhance the Toll pathway. During gram-positive bacterial infection, flies overexpressing CR46018 showed favorable survival compared with flies in the control group. Overall, our current work not only reveals a new immune regulatory factor, lncRNA-CR46018, and explores its potential regulatory model, but also provides a new perspective for the effect of immune disorders on the survival of Drosophila melanogaster.

20.
Eur J Neurol ; 28(9): 2907-2912, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-34075662

RESUMO

BACKGROUND AND PURPOSE: Cardiovascular risk burden in midlife has been linked to cognitive decline in later life, but whether this association still exists in older cohorts is unclear. METHODS: The association between the cardiovascular risk score and cognitive function was investigated using 9-year follow-up data. The risk score algorithms were from the Chinese guidelines on the prevention and treatment of dyslipidemia in adults (2016 revised), which were assessed at baseline and categorized into tertiles (low, middle and high). Full intelligence quotient (FIQ), verbal intelligence quotient (VIQ) and performance intelligence quotient (PIQ) were assessed at follow-ups with the Wechsler Adult Intelligence Scale-Chinese, revised (WAIS-RC). Data were analyzed using the linear mixed-effects model. RESULTS: A total of 924 participants (mean age 78.06 ± 7.58 years) were included in our study. In all participants, the risk score ranged from 0.02 to 0.55 (mean score 0.16 ± 0.08). Compared with the low tertile, a higher risk score was associated with lower FIQ (ß -0.094, 95% confidence interval [CI] -0.181, -0.007) and VIQ (ß -0.100; 95% CI -0.192, -0.007) at the follow-up. There is a more significant association between higher risk score and lower FIQ amongst females (ß -0.263; 95% CI -0.462, -0.065) and VIQ (ß -0.268; 95% CI -0.478, -0.057). CONCLUSIONS: A higher cardiovascular risk score was associated with lower FIQ and VIQ. Higher cardiovascular risk burden increased the risk of cognition impairment and accelerated its progression over time. This study has implications for early detection of cognition impairment.

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