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1.
J Environ Manage ; 325(Pt A): 116459, 2023 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-36244291

RESUMO

Trimethoprim (TMP), as a widely used chemotherapeutic antibiotic agent, has caused potential risks to the aquatic environment. In this study, magnetic Co-doped Fe3O4/α-FeOOH was fabricated by a facile one-step ageing method and used for activation of peroxymonosulfate (PMS) in TMP degradation. It was found that low catalyst (0.5 g/L) and PMS addition (0.2 mM) led to the high degradation efficiency of TMP (97.2%, kobs = 0.11211 min-1) over a wide range of pH. The oxidation of active radical (SO4·-) and non-radical singlet oxygen (1O2) co-acted on TMP degradation. Besides, PMS was activated through the cycles between Co(II)/Co(III) and Fe(II)/Fe(III). Fifteen degradation intermediates of TMP were identified by LC-MS, and three possible degradation pathways including hydroxylation, demethylation, and cleavage were proposed. The recovered catalysts exhibited high stability and reusability, maintaining 80% TMP removal efficiency with inappreciable metal leaching (0.012 mg/L of Co, 0.113 mg/L of Fe) after six cycles. Besides, the Co-Fe3O4/α-FeOOH/PMS system was highly tolerant to inorganic anions and actual water bodies (river water, lake water, tap water, and sewage plant effluent). Overall, this work provided a promising way to the potential application of Fe-based binary metal oxide for PMS activation.


Assuntos
Compostos Férricos , Trimetoprima , Peróxidos , Água
2.
J Environ Manage ; 325(Pt B): 116638, 2023 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-36335698

RESUMO

Feces in livestock farms is a reservoir of antibiotic resistance genes (ARGs), which can disseminate into surrounding soil and air, bringing risks to human health. In this study, seasonal dissemination of ARGs in a livestock farm and implications for human exposure was explored. The experimental results showed that ARGs abundance basically ranked as feces > soil > air, and significant seasonal dependence was observed. The total ARGs in pig feces was relatively higher in autumn (109.7 copies g-1) and winter (1010.0 copies g-1), and lower in summer (105.0 copies g-1). Similarly, the lowest total ARGs in soil and air were also observed in summer. There were correlations among ARGs, integron intI1, and bacterial community. Total organic carbon was an important factor affecting ARGs distribution in the feces, and pH and moisture content significantly affected soil ARGs. The daily intakes of integron intI1 and ARGs from air were 10°.5 copies h-1 and 102.3 copies h-1 for human exposure, respectively. Pseudomonas was a potential pathogenic host of blaTEM-1 in feces, Pseudomonas and Acinetobacter were potential pathogenic hosts of multiple ARGs in soil, while ARGs in air did not migrate into pathogens.


Assuntos
Antibacterianos , Gado , Humanos , Suínos , Animais , Fazendas , Solo , Genes Bacterianos , Estações do Ano , Bactérias/genética
3.
Lancet Reg Health West Pac ; 30: 100618, 2023 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-36276987

RESUMO

Background: With the outbreak of the coronavirus disease 2019 (COVID-19), nurses have won well-deserved recognition for their indispensable roles in providing humane and professional healthcare for patients. However, by the nature of their role working at the forefront of patient care, nurses are prone to experiencing mental health consequences. Therefore, we pay attention to measuring the magnitude of psychological symptoms and identifying associated factors among nurses in China. Methods: We launched a nationwide, cross-sectional survey of nurses who worked in secondary or tertiary hospitals and public or private hospitals from 30 provinces in China. The prevalence and severity of symptoms of burnout, depression, and anxiety were investigated, respectively. Multivariable logistic regression analyses were performed to identify factors associated with each psychological symptom. Findings: A total of 138 279 respondents who worked in 243 hospitals completed this survey. A substantial proportion of nurses reported symptoms of burnout (34%), depression (55·5%), and anxiety (41·8%). In line with the disproportionality of economic development, we noted that the middle or western region was an independent risk factor for depression and anxiety. Compared with those working in the secondary hospital, nurses who worked in tertiary hospitals were associated with a higher likelihood of burnout and depression. Interpretation: Nurses are experiencing emotional, physical, and mental exhaustion during the COVID-19 epidemic. Governments and health policymakers need to draw attention to reinforcing prevention and ameliorating countermeasures to safeguard nurses' health. Funding: The strategic consulting project of the Chinese Academy of Engineering [2021-32-5]. Advanced Institute of Infomation Technology, Peking University, Zhejiang Province [2020-Z-17].

4.
Front Public Health ; 10: 1028920, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36339188

RESUMO

Background: Central nervous system (CNS) infection is one of the most serious complications after neurosurgery. Traditional clinical methods are difficult to diagnose the pathogen of intracranial infection. Due to recent advances in genomic approaches, especially sequencing technologies, metagenomic next-generation sequencing (mNGS) has been applied in many research and clinical settings. Case presentation: Here, we report a case of CNS infection with Acinetobacter baumannii in a 15-year-old woman, who previously underwent surgery for recurrence of ependymoma in the fourth ventricle. On the eleventh postoperative day, the patient had a high fever and leukocytosis in the cerebrospinal fluid (CSF). mNGS using CSF rapidly and accurately identified the causative pathogen as A. baumannii with carbapenem resistance genes blaOXA-23 and blaOXA-51, which were confirmed by subsequent culture and susceptibility tests within 5 days. During the disease, mNGS, culture, and drug susceptibility testing were continued to monitor changes in pathogenic bacteria and adjust medication. At present, there are no case reports on to the use of mNGS for detecting pathogens in postoperative infection with ependymoma and guide medication. Conclusion: mNGS has great advantages in pathogen identification and even pathogen resistance prediction. Multiple mNGS examinations during the course of the disease play an important role in the dynamic monitoring of pathogens.


Assuntos
Acinetobacter baumannii , Infecções do Sistema Nervoso Central , Ependimoma , Mycobacterium tuberculosis , Neurocirurgia , Feminino , Humanos , Adolescente , Acinetobacter baumannii/genética , Testes de Sensibilidade Microbiana , Sequenciamento de Nucleotídeos em Larga Escala/métodos
5.
J Med Chem ; 2022 Nov 17.
Artigo em Inglês | MEDLINE | ID: mdl-36394224

RESUMO

Using a convergent synthetic route to enable multiple points of diversity, a series of glucocorticoid receptor modulators (GRM) were profiled for potency, selectivity, and drug-like properties in vitro. Despite covering a large range of diversity, profiling the nonconjugated small molecule was suboptimal and they were conjugated to a mouse antitumor necrosis factor (TNF) antibody using the MP-Ala-Ala linker. Screening of the resulting antibody drug conjugates (ADCs) provided a better assessment of efficacy and physical properties, reinforcing the need to conduct structure-activity relationship studies on the complete ADC. DAR4 ADCs were screened in an acute mouse contact hypersensitivity model measuring biomarkers to ensure a sufficient therapeutic window. In a chronic mouse arthritis model, mouse anti-TNF GRM ADCs were efficacious after a single dose of 10 mg/kg i.p. for over 30 days. Data on the unconjugated payloads and mouse surrogate anti-TNF ADCs identified payload 17 which was conjugated to a human anti-TNF antibody and advanced to the clinic as ABBV-3373.

6.
Gland Surg ; 11(10): 1673-1682, 2022 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-36353580

RESUMO

Background: Breast cancers characterized by triple-negative status tend to be more malignant and have a poorer prognosis. A risk model for predicting breast cancer risk should be developed. Methods: We obtained gene expression and clinical characteristics data using the Clinical Proteomic Tumor Analysis Consortium (CPTAC) and The Cancer Genome Atlas (TCGA) database. Differential gene screening between patients with triple-negative breast cancer (TNBC) and non-triple-negative breast cancers (NTNBC) was performed according to the "edgeR" filter criteria. Univariate and multivariate Cox regression analyses were used to construct a risk model and identify prognosis-related genes. XCELL, TIMER, EPIC, QUANTISEQ, MCPCOUNTER, EPIC, CIBERSORT-ABS, and CIBERSORT software programs were used to determine the extent of tumor immune cell infiltration. To evaluate the clinical responses to breast cancer treatment, the half maximal inhibitory concentration (IC50s) of common chemotherapeutics were calculated using "pRRophetic" and "ggplot2". Cell proliferation was assayed using cell counting kit-8 (CCK8) and 5-Ethynyl-2'-deoxyuridine (EdU) Cell Proliferation Kit. A dual-luciferase reporter assay confirmed the gene regulatory relationship of sex determining region Y-box 10 (SOX10). Results: An assessment model was established for Keratin23 (KRT23) and non-specific cytotoxic cell receptor 1 (NCCRP1) using the univariate and multivariate Cox regression analyses. In addition, high expression levels of KRT23 and NCCRP1 indicated high proliferation and poor prognosis. We also found that the gene expression patterns of multiple genes were significantly more predictive of risks and have a higher level of consistency when assessing risk. In vitro experiments showed that the expressions of KRT23 and NCCRP1 were increased in TNBCs and promoted cell proliferation. Mechanically, the dual-luciferase reporter assay confirmed that SOX10 regulated the expressions of KRT23 and NCCRP1. The risk score model revealed a close relationship between the expressions of KRT23 and NCCRP1, the tumor immune microenvironment, and chemotherapeutics. Conclusions: In conclusion, we constructed a risk assessment model to predict the risk of TNBC patients, which acted as a potential predictor for chemosensitivity.

7.
Gland Surg ; 11(10): 1697-1711, 2022 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-36353587

RESUMO

Background: Pancreatic cancer (PC) is a highly malignant tumor associated with low survival rates. It is challenging to predict the survival of surgically resected patients with PC. A prognostic staging tool could be beneficial to guide treatments and also aid post-treatment surveillance. This study aimed to identify tissue-based DNA methylation risk-score model to predict the prognosis of surgically resected pancreatic cancer patients. Methods: We performed a monocentric, retrospective study that included 50 patients with stage I-II PC from The First Affiliated Hospital of Soochow University (SU cohort). Both tumor and adjacent normal tissues were obtained from each patient and subjected to capture-based targeted methylation profiling. Results: In total, 1,162 DNA methylation blocks (DMBs) were differentially methylated in tumor tissues compared with adjacent long-distance tissues (P<0.05). Least Absolute Shrinkage and Selection Operator (LASSO) and stepwise regression analyses revealed a significant correlation between the methylation signature (risk score) and overall survival (OS). Patients in the high-risk group showed significantly poorer OS than those in the low-risk group in the survival analysis [P≤0.001; area under curve (AUC) at 1 year, 0.789; AUC at 2 years, 0.852]. The risk score was also validated using clinical and methylation data of 166 PC patients from The Cancer Genome Atlas pancreatic ductal adenocarcinoma (TCGA-PDAC) dataset. Patients in the high-risk group showed significantly poorer OS than those in the low-risk group (P=0.004; AUC at 1 years, 0.677; AUC at 3 years, 0.611). When clinical parameters were considered, the risk score was the only independent prognostic parameter (P<0.001) in the Cox regression analysis. Furthermore, low-risk patients had higher levels of immune infiltration, anti-tumor immune activation, and increased sensitivity to gemcitabine and paclitaxel. In contrast, high-risk patients had lower KRAS mutation rates and benefited more from cisplatin. Conclusions: In our study, we constructed and validated a tissue-based DNA methylation risk-score model to predict prognosis and identify PC patients with a high mortality risk at the time of surgery. This model might provide a tissue-based prognostic assessment tool for clinicians to aid their treatment decision-making.

8.
World J Pediatr ; 2022 Nov 10.
Artigo em Inglês | MEDLINE | ID: mdl-36357648

RESUMO

BACKGROUND: Bronchopulmonary dysplasia (BPD) is a common chronic lung disease in extremely preterm neonates. The outcome and clinical burden vary dramatically according to severity. Although some prediction tools for BPD exist, they seldom pay attention to disease severity and are based on populations in developed countries. This study aimed to develop machine learning prediction models for BPD severity based on selected clinical factors in a Chinese population. METHODS: In this retrospective, single-center study, we included patients with a gestational age < 32 weeks who were diagnosed with BPD in our neonatal intensive care unit from 2016 to 2020. We collected their clinical information during the maternal, birth and early postnatal periods. Risk factors were selected through univariable and ordinal logistic regression analyses. Prediction models based on logistic regression (LR), gradient boosting decision tree, XGBoost (XGB) and random forest (RF) models were implemented and assessed by the area under the receiver operating characteristic curve (AUC). RESULTS: We ultimately included 471 patients (279 mild, 147 moderate, and 45 severe cases). On ordinal logistic regression, gestational diabetes mellitus, initial fraction of inspiration O2 value, invasive ventilation, acidosis, hypochloremia, C-reactive protein level, patent ductus arteriosus and Gram-negative respiratory culture were independent risk factors for BPD severity. All the XGB, LR and RF models (AUC = 0.85, 0.86 and 0.84, respectively) all had good performance. CONCLUSIONS: We found risk factors for BPD severity in our population and developed machine learning models based on them. The models have good performance and can be used to aid in predicting BPD severity in the Chinese population.

9.
Front Cardiovasc Med ; 9: 1044797, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36386351

RESUMO

Background: Cardiac sympathetic nerve system (SNS) might play an important role in arrhythmogenesis of arrhythmogenic cardiomyopathy (ACM). This study aims to assess the activity of cardiac SNS in ACM patients by heart rate variability (HRV), and to investigate its predictive value for sustained ventricular tachycardia (sVT). Methods: A total of 88 ACM patients and 65 sex- and age- matched healthy participants were enrolled. The time domain measures were used to evaluate the activity of cardiac SNS. An independent cohort with 48 ACM patients was as the validation cohort. Results: ACM patients had lower levels of standard deviation of all NN intervals (SDNN) [118.0 (90.3, 136.8) vs. 152.0 (132.5, 174.5) ms, p < 0.001] compared with healthy participants. Further analysis showed ACM patients with sVT had lower levels of SDNN than those without sVT (105.0 ± 28.1 vs. 131.8 ± 33.1 ms, p < 0.001). Multivariate logistic regression analysis showed SDNN was independently associated with sVT in ACM patients [odds ratio (OR) 0.59, 95% confidence interval (CI) (0.45-0.78), p < 0.001]. Receiver operating characteristics curve demonstrated SDNN had clinical values in predicting sVT in ACM patients [area under the curve (AUC) = 0.73, 95% CI (0.63-0.84), p < 0.001], which was verified in the validation cohort. Conclusion: The present study suggests that HRV is impaired in patients with ACM, and the SDNN level has a moderate value in risk stratification for sVT in ACM patients. In addition, the finding might provide new target for the further management of ACM with integrated traditional Chinese and western medicine.

10.
Ann Transl Med ; 10(20): 1091, 2022 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-36388794

RESUMO

Background: Lenvatinib is one of the first-line treatments for unresectable hepatocellular carcinoma (HCC). However, data are lacking on lenvatinib in the postoperative setting. Methods: This retrospective analysis enrolled 242 patients with HCC who underwent liver transplantation (LTx). Eligible patients were divided into 2 groups according to their use of adjuvant lenvatinib following LTx (lenvatinib, n=42; control, n=200). The primary outcome measures were overall survival (OS), time to recurrence (TTR), and safety. Kaplan-Meier analysis was applied to calculate the OS, while a competing risk model was used to estimate the cumulative incidence of recurrence. Results: The lenvatinib group showed more advanced tumors and a higher proportion of HCC beyond the Milan criteria (P<0.001) than the control group. There were no significant differences in both the OS and TTR between the 2 groups. After focusing on the patients with HCC beyond the Milan criteria, baseline characteristics were similar in the lenvatinib group (n=38) and the control group (n=102). Competing risk analysis showed lenvatinib significantly prolonged TTR after LTx versus the control group [sub-hazard ratio (sHR), 0.40; 95% confidence interval (CI): 0.17 to 0.93; P=0.031]. In the multivariate competing risk model, adjuvant lenvatinib was an independent protective factor for tumor recurrence after LTx in patients with HCC beyond the Milan criteria (sHR, 0.33; 95% CI: 0.13 to 0.83; P=0.018). The rate of early recurrence within t2 years after LTx was also significantly decreased in the lenvatinib group (15.8% vs. 33.3%, P=0.041). However, the lenvatinib group exhibited comparable OS with the control group in patients with HCC beyond the Milan criteria. Treatment-related adverse events (TRAEs) and Grade ≥3 TRAEs occurred in 40 (95.2%) and 13 (31%) patients who received adjuvant lenvatinib, respectively. No treatment-related death was reported. Conclusions: Postoperative lenvatinib administration may provide clinical benefits and is well tolerated in patients with HCC beyond the Milan criteria who undergo LTx.

11.
Nat Prod Res ; : 1-8, 2022 Nov 09.
Artigo em Inglês | MEDLINE | ID: mdl-36352349

RESUMO

The establishment of structure activity relationship (SAR) for rakicidin derivatives is pretty vital to develop rakicidins as a new type of anti-cancer agents. Herein, two novel rakicidin derivatives, compounds B1-1 (1) and B1-2 (2), a cyclic depsipeptide and a chain lipopeptide, respectively, were isolated from culture broth of Micromonospora chalcea FIM-R160609, and their structures were elucidated clearly by extensive NMR and HR-ESI-MS analyses. Following, their cytotoxic activities were evaluated against HCT-8 and PANC-1 human cancer cell lines under hypoxic and normoxic conditions. Their activities were significantly decreased when compared with that of rakicidin B1. These results demonstrated that the double bond located on the position 9 and 10 of conjugated diene unit and cycle-type structure plays an important role in keeping the biological activity of rakicidins. Furthermore, the positive effect of double bond and cycle form on the anti-bacterial activities were also confirmed by testing their inhibitory activities against gram positive bacteria. This work will definitely diversify the SAR of rakicidins and provide the guidance for the design of new potent rakicidin analogues.

12.
BMJ Open ; 12(11): e064064, 2022 11 09.
Artigo em Inglês | MEDLINE | ID: mdl-36351728

RESUMO

INTRODUCTION: Spontaneous hyperventilation (SHV) is common in aneurysmal subarachnoid haemorrhage (aSAH). The reduction in arterial partial pressure of carbon dioxide (PaCO2) may change the brain physiology, such as haemodynamics, oxygenation, metabolism and may lead to secondary brain injury. However, how to correct SHV safely and effectively in patients with aSAH has not been well investigated. The aim of this study is to investigate the efficacy and safety of remifentanil dose titration to correct hyperventilation in aSAH, as well as the effect of changes in PaCO2 on cerebral blood flow (CBF). METHODS AND ANALYSIS: This study is a prospective, single-centre, physiological study in patients with aSAH. The patients who were mechanically ventilated and who meet with SHV (tachypnoea combined with PaCO2 <35 mm Hg and pH >7.45) will be enrolled. The remifentanil will be titrated to correct the SHV. The predetermined initial dose of remifentanil is 0.02 µg/kg/min and will be maintained for 30 min, and PaCO2 and CBF will be measured. After that, the dose of remifentanil will be sequentially increased to 0.04, 0.06, and 0.08 µg/kg/min, and the measurements for PaCO2 and CBF will be repeated 30 min after each dose adjustment and will be compared with their baseline values. ETHICS AND DISSEMINATION: This study has been approved by the Institutional Review Board of Beijing Tiantan Hospital, Capital Medical University (KY 2021-006-02) and has been registered at ClinicalTrials.gov. The results of this study will be disseminated through peer-reviewed publications and conference presentations. TRIAL REGISTRATION NUMBER: NCT04940273.


Assuntos
Hemorragia Subaracnóidea , Humanos , Dióxido de Carbono , Circulação Cerebrovascular/fisiologia , Hiperventilação , Estudos Prospectivos , Remifentanil , Hemorragia Subaracnóidea/complicações
13.
BMC Neurol ; 22(1): 430, 2022 Nov 15.
Artigo em Inglês | MEDLINE | ID: mdl-36380277

RESUMO

BACKGROUND: The aim of the study was to determine whether the combination of Glasgow Coma Scale (GCS) and Pupil responses score (GCSP) with arterial lactate level would be an index to predict the short term prognosis in patients with traumatic brain injury (TBI). METHODS: A retrospective study was performed enrolling all TBI patients admitted to intensive care unit (ICU) from 2019 to 2020. The demographics, clinical characteristics, and arterial lactate concentration were recorded. The GCSP and arterial blood analysis (ABG) with lactate was tested as soon as the patient was admitted to ICU. The Glasgow Outcome Scale (GOS) after discharge was regarded as the clinical outcome. A new index named GCSP-L was the combination of GCSP and lactate concentration. GCSP-L was the GCSP score (range 1-15) plus the lactate score (range 0-2). The lactate score was defined based on different lactate concentrations. If lactate was below 2 mmol/L, lactate score was 0, which above 5 mmol/L was 2 and between 2 and 5 mmol/L, the score was 1. As the range of GCSP was 1-15, the range of the GCSP-L was 1 to 17. The area under receiver operating characteristic curve (AUC) was calculated to evaluate the predictive ability of GCSP, lactate and GCSP-L. Statistical significance was set when p value < 0.05. RESULTS: A total of 192 TBI patients were included in the study. Based on GCSP, mild, moderate, and severe TBI were 13.02, 14.06 and 72.92%, respectively. There were 103 (53.65%) patients with the lactate concentration below 2 mmol/L (1.23 ± 0.37 mmol/l), 63 (32.81%) of the range from 2 to 5 (3.04 ± 2.43 mmol/l) and 26 (13.54%) were above 5 mmol/l (7.70 ± 2.43 mmol/l). The AUC was 0.866 (95% CI 0.827-0.904) for GCSP-L, 0.812 (95% CI 0.765-0.858) for GCSP and 0.629 (95% CI 0.570-0.0.688) for lactate. The AUC of GCSP-L was higher than the other two, GCSP and lactate alone. CONCLUSIONS: The combination of GCSP and lactate concentration can be used to predict the short term prognosis in TBI patients.


Assuntos
Lesões Encefálicas Traumáticas , Humanos , Escala de Coma de Glasgow , Estudos Retrospectivos , Lesões Encefálicas Traumáticas/diagnóstico , Prognóstico , Ácido Láctico
14.
Org Lett ; 24(45): 8364-8369, 2022 Nov 18.
Artigo em Inglês | MEDLINE | ID: mdl-36318643

RESUMO

An unprecedented tandem trifluoromethylsilylation/intramolecular SN2 substitution sequence was realized by using bifunctional reagent Me2(CH2Cl)SiCF3, allowing efficient construction of valuable trifluoromethylated oxasilacyclohexanes that are difficult to access by known methods. Initial attempts into developing asymmetric variant reveal that using cinchonine-derived dimeric PTC catalyst could afford chiral oxasilacyclohexanes in up to 92% enantiomeric excess.

15.
Opt Express ; 30(23): 42541-42552, 2022 Nov 07.
Artigo em Inglês | MEDLINE | ID: mdl-36366706

RESUMO

Longwave infrared spectral imaging (LWIR-SI) has potential in many important civilian and military fields. However, conventional LWIR-SI systems based on traditional dispersion elements always suffer the problems of high cost, large volume and complicated system structure. Micro-electro-mechanical systems Fabry-Perot filtering chips (MEMS-FPFC) give a feasible way for realizing miniaturized, low cost and customizable LWIR-SI systems. The LWIR MEMS-FPFC ever reported can't meet the demands of the next-generation LWIR-SI systems, due to the limitation of small aperture size and nonlinear actuation. In this work, we propose a large-aperture, widely and linearly tunable electromagnetically actuated MEMS-FPFC for LWIR-SI. A multi-field coupling simulation model is built and the wafer-scale bulk-micromachining process is applied to realize the design and fabrication of the proposed MEMS-FPFC. Finally, with the rational structural design and fabrication process, the filtering chip after packaging has an aperture size of 10 mm, which is the largest aperture size of LWIR MEMS-FPFC ever reported. The fabricated electromagnetically actuated MEMS-FPFC can be tuned continuously across the entire LWIR range of 8.39-12.95 µm under ±100 mA driving current with a pretty good linear response of better than 98%. The developed electromagnetically actuated MEMS-FPFC can be directly used for constructing miniaturized LWIR-SI systems, aiming for such applications as military surveillance, gas sensing, and industry monitoring.

17.
Gene Expr Patterns ; 46: 119286, 2022 Oct 29.
Artigo em Inglês | MEDLINE | ID: mdl-36341978

RESUMO

Foxl2 plays conserved central function in ovarian differentiation and maintenance in several fish species. However, its expression pattern and function in fish embryogenesis are still largely unknown. In this study, we first presented a sequential expression pattern of zebrafish foxl2a and foxl2b during embryo development. They were predominantly expressed in the cranial paraxial mesoderm (CPM) and cranial venous vasculature (CVV) during somitogenesis and subsequently expressed in the pharyngeal arches after 48 h post-fertilization (hpf). Then, we compared the brain structures among zebrafish wildtype (WT) and three homozygous foxl2 mutants (foxl2a-/-, foxl2b-/- and foxl2a-/-;foxl2b-/-) and found the reduction of the fourth ventricle in the three foxl2 mutants, especially in foxl2a-/-;foxl2b-/- mutant. Finally, we detected several key transcription factors involved in the gene regulatory network of midbrain-hindbrain boundary (MHB) patterning, such as wnt1, en1b and pax2a. Their expression levels were obviously downregulated in MHB of foxl2a-/- and foxl2a-/-;foxl2b-/- mutants. Thus, we suggest that Foxl2a and Foxl2b are involved in MHB and the fourth ventricle development in zebrafish. The current study provides insights into the molecular mechanism underlying development of brain ventricular system.

18.
J Adv Res ; 41: 169-177, 2022 11.
Artigo em Inglês | MEDLINE | ID: mdl-36328746

RESUMO

INTRODUCTION: Performing genomic large segmentation experiments will promote the annotation of complex genomic functions and contribute to the synthesis of designed genomes. It is challenging to obtain and manipulate large or complex DNA sequences with high efficiency. OBJECTIVES: This study aims to develop an effective method for direct cloning of target genome sequences from different species. METHODS: The TelN/tos system and a linear plasmid vector were first used to directly clone the large genomic segments in E. coli. For the in vitro cloning reaction, two telomeric sites were developed using TelN protelomerase at the end of the linear plasmid vector. The target DNA sequence can be easily hooked with the homology arms and maintained as a linear artificial chromosome with arbitrary restriction sites in a specific E. coli strain. RESULTS: Using the linear cloning strategy, we successfully cloned the bacterial DNA fragment of 156 kb, a yeast genomic fragment of 124 kb and mammalian mitochondrial fragment of 16 kb. The results showed a considerable improvement in cloning efficiency and demonstrated the important role of vector ratio in the cloning process. CONCLUSION: Due to the high efficiency and stability, TAPE is an effective technique for DNA cloning and fundamental molecular biotechnology method in synthetic biology.


Assuntos
Cromossomos , Escherichia coli , Animais , Escherichia coli/genética , Clonagem Molecular , DNA Bacteriano/genética , Sequência de Bases , Mamíferos/genética
19.
J Am Heart Assoc ; : e027339, 2022 Nov 23.
Artigo em Inglês | MEDLINE | ID: mdl-36416154

RESUMO

Background Eosinophil count (EOS) has been proposed to provide prognostic information in multiple cardiovascular disorders. However, few researchers have investigated the predictive value of EOS for patients with type B aortic dissection who had thoracic endovascular repair. Methods and Results The authors reviewed the records of 912 patients with type B aortic dissection who were treated with thoracic endovascular repair in Changhai Hospital, Shanghai. By using receiver operating characteristic curve analysis, patients were divided into 2 groups based on the admission EOS cutoff value (<7.4×106/L [n=505] and ≥7.4×106/L [n=407]). To reduce selection bias, propensity score matching was applied. Multivariable regression analysis and Kaplan-Meier curves were performed to assess the association between EOS and long-term outcomes. Furthermore, we investigated nonlinear correlations between EOS and outcomes using general additive models with restricted cubic splines. In the matched population, lower EOS was associated with significantly higher 30-day mortality (4.1% vs 0%, P=0.007). There was no statistically difference in 30-day adverse events between the 2 groups (all P>0.05). Kaplan-Meier analysis revealed that patients with an EOS <7.4×106/L had a higher incidence of 1-year all-cause death (7.95% vs. 2.34%, P=0.008) and aortic-related death (5.98% vs 1.81%, P=0.023) than those with higher EOS. Multivariable Cox analysis showed that continuous EOS was independently associated with 1-year mortality (hazard ratio, 3.23 [95% CI, 1.20-8.33], P=0.019). In addition, we discovered a nonlinear association between EOS and 1-year outcomes. Conclusions Lower admission EOS values predict higher short- and long-term mortality after thoracic endovascular repair.

20.
ASN Neuro ; 14: 17590914221136662, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36383501

RESUMO

Depression is a common psychiatric comorbidity in patients with epilepsy, especially those with temporal lobe epilepsy (TLE). The aim of this study was to assess changes in high mobility group box protein 1 (HMGB1) expression in epileptic patients with and without comorbid depression. Sixty patients with drug-resistant TLE who underwent anterior temporal lobectomy were enrolled. Anterior hippocampal samples were collected after surgery and analyzed by immunofluorescence (n = 7/group). We also evaluated the expression of HMGB1 in TLE patients with hippocampal sclerosis and measured the level of plasma HMGB1 by enzyme-linked immunosorbent assay. The results showed that 28.3% of the patients (17/60) had comorbid depression. HMGB1 was ubiquitously expressed in all subregions of the anterior hippocampus. The ratio of HMGB1-immunoreactive neurons and astrocytes was significantly increased in both TLE patients with hippocampal sclerosis and TLE patients with comorbid depression compared to patients with TLE only. The ratio of cytoplasmic to nuclear HMGB1-positive neurons in the hippocampus was higher in depressed patients with TLE than in nondepressed patients, which suggested that more HMGB1 translocated from the nucleus to the cytoplasm in the depressed group. There was no significant difference in the plasma level of HMGB1 among patients with TLE alone, TLE with hippocampal sclerosis, and TLE with comorbid depression. The results of the study revealed that the translocation of HMGB1 from the nucleus to the cytoplasm in hippocampal neurons may play a previously unrecognized role in the initiation and amplification of epilepsy and comorbid depression. The direct targeting of neural HMGB1 is a promising approach for anti-inflammatory therapy.


Assuntos
Epilepsia do Lobo Temporal , Epilepsia , Proteína HMGB1 , Humanos , Esclerose/metabolismo , Esclerose/patologia , Proteína HMGB1/metabolismo , Epilepsia do Lobo Temporal/cirurgia , Epilepsia do Lobo Temporal/metabolismo , Epilepsia do Lobo Temporal/patologia , Hipocampo/patologia , Epilepsia/cirurgia , Epilepsia/metabolismo , Gliose/patologia , Citoplasma/metabolismo
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