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1.
Materials (Basel) ; 17(2)2024 Jan 18.
Artigo em Inglês | MEDLINE | ID: mdl-38255625

RESUMO

An important method that coal-fired power plants use to realise low-cost zero discharge of desulfurisation wastewater (FGD wastewater) is to utilise wet slag removal systems. However, the high Cl- content of FGD wastewater in wet slag removal systems causes environmental damage. In this study, the corrosion behaviour of the inner guide wheel material, 20CrMnTi, was studied using dynamic weight loss and electrochemical methods. X-ray diffraction, scanning electron microscopy, and energy spectroscopy were used to analyse the organisational and phase changes on the surfaces and cross sections of the samples at different Cl- concentrations. The corrosion rate increased with the Cl- concentration up to 20 g/L, but it decreased slightly when the Cl- concentration exceeded 20 g/L. In all the cases, the corrosion rate exceeded 0.8 mm/a. The corrosion product film density initially increased and then decreased as the Cl- concentration increased. The corrosion products comprised mainly α-FeOOH, γ-FeOOH, ß-FeOOH, Fe3O4, and γ-Fe2O3.

2.
J Vasc Surg Venous Lymphat Disord ; 12(2): 101678, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-37708938

RESUMO

OBJECTIVE: This study aimed to compare the efficacy of customized graduated elastic compression stockings (c-GECSs) based on lower leg parameter models with standard GECSs (s-GECSs) in patients with chronic venous disease (CVD). METHODS: In this randomized, single-blind, controlled trial, 79 patients with stage C2 or C3 CVD were assigned to one of two groups: c-GECSs or s-GECSs. The primary outcome was change to Venous Insufficiency Epidemiological and Economic Study Quality of Life (VEINES-QOL) scores at months 1, 3, and 6 as compared with baseline. Secondary outcomes included compliance with wearing ECSs, interface pressure at the smallest circumference of the ankle (point B) and the largest circumference of the calf (point C), and calf volume (CV). RESULTS: There were 13 pairs of s-GECS and 2 pairs of c-GECS that showed pressure values higher than the standard at either point B or C. The c-GECSs were significantly superior to s-GECSs in terms of score improvement at all three time points (month 1, 8.47 [95% confidence interval (CI), 7.47-9.45] vs 5.89 [95% CI, 5.00-6.78]; month 3, 9.60 [95% CI, 8.47-10.72] vs 6.72 [95% CI, 5.62-7.83]; month 6, 7.09 [95% CI, 5.93-8.24] vs 3.92 [95% CI, 2.67-5.18]; P < .0001). Besides, at month 1, the mean daily use time of the c-GECS and s-GECS groups was 10.7 and 9.5 hours, respectively (P < .05). Correlation analysis indicated a negative relationship between local high pressure and daily duration in the s-GECS group (rpb = -0.388; n = 38; P < .05). Variances in pressure were greater in the s-GECSs group. The c-GECSs showed advantage in maintaining pressure. Both c-GECSs and s-GECSs effectively reduced CV (mL), with no significant differences between groups (month 1, 90.0 [95% CI, 71.4-108.5] vs 85.0 [95% CI, 65.6-104.2]; month 3, 93.8 [95% CI, 69.7-117.8] vs 85.9 [95% CI, 65.5-106.2]; month 6, 70.8 [95% CI, 46.5-95.2]) vs 60.8 [95% CI, 44.1-77.5]). CONCLUSIONS: The c-GECSs based on individual leg parameter models significantly improved VEINES-QOL scores and provided stable and enduring pressure as compared with s-GECSs for patients with stage C2 or C3 CVD. Although both c-GECSs and s-GECSs effectively reduced CV, the superior fit and comfort of c-GECSs improved patient compliance. Hence, c-GECSs are a viable alternative for patients who have difficulty tolerating s-GECSs.


Assuntos
Meias de Compressão , Insuficiência Venosa , Humanos , Qualidade de Vida , Método Simples-Cego , Veias , Insuficiência Venosa/terapia , Doença Crônica
3.
J Endovasc Ther ; : 15266028231197602, 2023 Sep 07.
Artigo em Inglês | MEDLINE | ID: mdl-37675790

RESUMO

PURPOSE: The objective was to determine the effectiveness and safety of paclitaxel-coated balloon angioplasty in hemodialysis patients with diabetic nephropathy (DN). MATERIALS AND METHODS: The outcomes of end-stage renal disease (ESRD) patients with peripheral artery disease (PAD) and treated with drug-coated balloon (DCB) angioplasty were retrospectively evaluated. The effectiveness outcomes were clinical improvement of the Rutherford classification and target lesion revascularization (TLR). Safety outcomes were all-cause mortality and amputation. RESULTS: Ninety-seven patients were treated with DCB angioplasty between December 2018 and December 2020. 87 (63.8±10.1 years) achieved technical success. Most patients had a Rutherford classification of at least grade 4. The mean lesion length was 169.8±73.8 mm, almost all had arterial calcification, and 31.0% had annular calcification. Wounds were present in 73.6% of the target limbs. The mean follow-up in this cohort was 13.4±7.4 months. The wound healing rate was 61.5% at the 12-month follow-up. All-cause mortality during 12 months of follow-up was 35.6%, amputation-free survival was 58.6%, and TLR was observed in 13 (15.3%) patients. At 3 and 12 months of follow-up, the Rutherford grade significantly improved (p<0.001). The Cox proportional hazards model revealed that wounds (hazard ratio [HR]=1.404, p=0.023) and annular calcification (HR=2.076, p=0.031) were independent predictors of amputation-free survival. CONCLUSIONS: Drug-coated balloon angioplasty in ESRD patients was effective and safe over the medium term. Wounds and annular calcification were independent predictors of amputation-free survival. CLINICAL IMPACT: The effectiveness of DCB angioplasty in ESRD patients and the factors affecting major outcome prognosis in this population remain limited. This study contributes valuable insights into the effectiveness and safety of paclitaxel-coated balloon angioplasty for PAD in hemodialysis patients. Medical professionals can now regard DCB angioplasty as a viable treatment. Identifying wound presence and annular calcification as predictors of amputation-free survival equips medical practitioners with a more tailored approach to patient management, potentially resulting in enhanced outcomes and more precise treatment strategies.

4.
Materials (Basel) ; 16(15)2023 Jul 27.
Artigo em Inglês | MEDLINE | ID: mdl-37569973

RESUMO

An effective strategy for achieving cost-effective and environmentally friendly desulfurization wastewater in coal-fired power plants involves the incorporation of desulfurization wastewater into the slag water system. The objective of this study was to analyze the corrosion behavior of Q235-A slag-picker shell material upon the introduction of FGD wastewater into the slag water system. The dynamic weight loss method, electrochemical testing method and microscopic phase characterization were employed to investigate the impact of varying chloride ion concentrations (ranging from 1000 mg/L to 30,000 mg/L) of flue gas desulfurization wastewater (FGD wastewater) on the corrosion of Q235-A slag-picker shell material. The test results indicate that as the concentration of chloride ions increases, the corrosion rate increases from 1.1487 mm/a to 1.5590 mm/a when the concentration is less than 10,000 mg/L. However, when the concentration exceeds 10,000 mg/L, the corrosion rate decreases from 1.559 mm/a to 1.0393 mm/a. The corrosion rate is above 1 mm/a at all concentrations. As the Cl- concentration, the quality of the corrosion product film initially increases and then decreases. The primary components of the corrosion product are α- FeOOH, γ-FeOOH, ß-FeOOH, Fe3O4 and γ-Fe2O3.

5.
Sci Rep ; 13(1): 14153, 2023 08 29.
Artigo em Inglês | MEDLINE | ID: mdl-37644056

RESUMO

Atherosclerosis is a chronic lipid-driven inflammatory response of the innate and adaptive immune systems, and it is responsible for several cardiovascular ischemic events. The present study aimed to determine immune infiltration-related biomarkers in carotid atherosclerotic plaques (CAPs). Gene expression profiles of CAPs were extracted from the Gene Expression Omnibus database. Differentially expressed genes (DEGs) between the CAPs and control groups were screened by the "limma" package in R software. Immune cell infiltration between the CAPs and control groups was evaluated by the single sample gene set enrichment analysis. Key infiltrating immune cells in the CAPs group were screened by the Wilcoxon test and least absolute shrinkage and selection operator regression. The weighted gene co-expression network analysis was used to identify immune cell-related genes. Hub genes were identified by the protein-protein interaction (PPI) network. Receiver operating characteristic curve analysis was performed to assess the gene's ability to differentiate between the CAPs and control groups. Finally, we constructed a miRNA-gene-transcription factor network of hub genes by using the ENCODE database. Eleven different types of immune infiltration-related cells were identified between the CAPs and control groups. A total of 1,586 differentially expressed immunity-related genes were obtained through intersection between DEGs and immune-related genes. Twenty hub genes were screened through the PPI network. Eventually, 7 genes (BTK, LYN, PTPN11, CD163, CD4, ITGAL, and ITGB7) were identified as the hub genes of CAPs, and these genes may serve as the estimable drug targets for patients with CAPs.


Assuntos
Aterosclerose , MicroRNAs , Placa Aterosclerótica , Humanos , Placa Aterosclerótica/genética , Bases de Dados Factuais , Perfilação da Expressão Gênica
6.
Phlebology ; 38(9): 605-612, 2023 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-37651292

RESUMO

OBJECTIVE: Compression therapy with the use of graduated compression stockings (GCSs) is a common treatment strategy for chronic venous disease (CVD). However, there is no uniform and objective standard to assess adherence to the use of GCSs. The aim of this study is to develop and validate a GCS Compliance Scale (GCSAS) to fill gaps in internationally recognized comprehensive scales and provide a useful tool for future research. METHODS: The items included in the GCSAS were based on a review of the literature and open-ended interviews with experts, who screened the initial items using an item-level content validity index. Then, pilot tests were conducted three times with 50 participants. After exclusion of redundant and cross-loading items by exploratory factor analysis, 290 subjects were recruited to evaluate the reliability and validity of the proposed GCSAS. Analyses included internal consistency, test-retest reliability, split-half reliability, construct validity, criterion validity, convergent validity, and discriminant validity. RESULTS: The final GCSAS consisted of 17 items and 5 dimensions. The results of the exploratory factor analysis indicated that the variances of each factor explained were 22.03%, 14.85%, 14.74%, 14.16%, and 13.35%, and all 5 factors explained 79.13% of the variance among the 17 items. The factor loadings of all items were >0.7. Confirmatory factor analysis indicated that the indices were adequate. A significant positive correlation was found between the GCSAS and the Venous Insufficiency Epidemiological and Economic Study - Quality of Life questionnaire scores (r = 0.76, p < 0.001). The Cronbach's alpha coefficient was 0.90, test-retest reliability was 0.81, and split-half reliability was 0.92. CONCLUSIONS: The GCSAS showed good validity and reliability to assess compliance with the use of GCSs among patients with CVD.


Assuntos
Doenças Cardiovasculares , Qualidade de Vida , Humanos , Reprodutibilidade dos Testes , Meias de Compressão , Psicometria/métodos , Inquéritos e Questionários , Doença Crônica
7.
Sci Rep ; 13(1): 6936, 2023 04 28.
Artigo em Inglês | MEDLINE | ID: mdl-37117396

RESUMO

To assess the safety and efficacy of endovascular embolization techniques, we compared the short- to medium-term prognosis of coil embolization for symptomatic visceral aneurysms (SVAA) and asymptomatic visceral aneurysms (ASVAA) to identify risk factors associated with 30-day mortality. Explore the symptom profile and intrinsic associations of SVAA. A retrospective study of 66 consecutive patients at two tertiary care hospitals from 2010 to 2020 compared the short- to mid-term outcomes of 22 symptomatic VAAs and 44 asymptomatic VAAs treated with coil embolization. Univariate and log-rank tests were used to analyze the prognostic impact of SVAA and ASVAA. SVAA group had significantly higher 30-day mortality than ASVAA group (2(9.1%) vs 0, P = 0.042), both patients who died had symptomatic pseudoaneurysms. Perioperative complications such as end-organ ischemia (P = 0.293) and reintervention (P = 1) were similar in both groups. No difference in event-free survival was identified between the two groups (P = 0.900), but we found that the majority of pseudoaneurysms were SVAA (4/5) and that they had a much higher event rate than true aneurysms. In addition, dyslipidemia may be an influential factor in the development of VAA (P = 0.010). Coil embolization is a safe and effective method of treatment for VAA. Most pseudoaneurysms have symptoms such as abdominal pain and bleeding, and in view of their risk, more attention should be paid to symptomatic patients and the nature of the aneurysm should be determined as soon as possible to determine the next stage of treatment.


Assuntos
Falso Aneurisma , Aneurisma , Embolização Terapêutica , Procedimentos Endovasculares , Humanos , Falso Aneurisma/terapia , Estudos Retrospectivos , Resultado do Tratamento , Aneurisma/terapia , Aneurisma/diagnóstico , Embolização Terapêutica/efeitos adversos , Embolização Terapêutica/métodos , Procedimentos Endovasculares/métodos , Artérias/cirurgia , Vísceras/irrigação sanguínea
8.
J Vasc Surg Venous Lymphat Disord ; 11(1): 127-135, 2023 01.
Artigo em Inglês | MEDLINE | ID: mdl-35940450

RESUMO

OBJECTIVE: Measurement of lower limb volume in patients with chronic venous disease (CVD) is necessary for assessing severity at the time of diagnosis and evaluating response to therapy administered. Existing methods have some limitations in clinical application and accuracy. The study aimed to investigate the reliability and validity of a three-dimensional laser scanner (3DLS) in measuring the lower limb volume of patients with CVD. METHODS: A total of 30 patients with CVD (mean age, 55.6 ± 8.07 years; mean body mass index, 24.61 ± 1.87) were recruited in a vascular surgery clinic. The lower limb volumes of all participants were measured using the 3DLS and circumferential method (CM). Statistical analysis was conducted to compare the 3DLS and CM. RESULTS: There was a strong correlation between the CM and 3DLS method (r2 = 0.9065). The 3DLS had a high intraoperator and interoperator reliability. A Bland-Altman plot showed satisfactory agreement between the two methods. The 3DLS demonstrated greater bilateral limb differences than CM. CONCLUSIONS: There was satisfactory agreement between the two investigated methods. The 3DLS method was confirmed to be accurate, repeatable, and rapid in measuring the lower limb volume in patients with CVD and is, therefore, suitable for clinical use.


Assuntos
Doenças Cardiovasculares , Extremidade Inferior , Humanos , Pessoa de Meia-Idade , Reprodutibilidade dos Testes , Lasers , Veias
9.
Nat Genet ; 54(12): 1972-1982, 2022 12.
Artigo em Inglês | MEDLINE | ID: mdl-36471073

RESUMO

Preharvest sprouting (PHS) due to lack of seed dormancy seriously threatens crop production worldwide. As a complex quantitative trait, breeding of crop cultivars with suitable seed dormancy is hindered by limited useful regulatory genes. Here by repeatable phenotypic characterization of fixed recombinant individuals, we report a quantitative genetic locus, Seed Dormancy 6 (SD6), from aus-type rice, encoding a basic helix-loop-helix (bHLH) transcription factor, which underlies the natural variation of seed dormancy. SD6 and another bHLH factor inducer of C-repeat binding factors expression 2 (ICE2) function antagonistically in controlling seed dormancy by directly regulating the ABA catabolism gene ABA8OX3, and indirectly regulating the ABA biosynthesis gene NCED2 via OsbHLH048, in a temperature-dependent manner. The weak-dormancy allele of SD6 is common in cultivated rice but undergoes negative selection in wild rice. Notably, by genome editing SD6 and its wheat homologs, we demonstrated that SD6 is a useful breeding target for alleviating PHS in cereals under field conditions.


Assuntos
Oryza , Dormência de Plantas , Fatores de Transcrição Hélice-Alça-Hélice Básicos/genética , Oryza/genética , Dormência de Plantas/genética
10.
Front Cardiovasc Med ; 9: 1018694, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36505376

RESUMO

Intramuscular ganglion cyst (IMGC) is a very rare lesion with an unidentified pathogeny that originates within the muscle. We encountered a case of 49-year-old man who complained of intermittent claudication in the right lower limb for 2 months. An intramuscular ganglion cyst in the biceps femoris muscle was diagnosed and located by Computed tomography angiography (CTA) and magnetic resonance imaging (MRI), which compressed the popliteal artery and resulted in ischemia in the right lower limb. Six months after surgical resection, there was no recurrence of the cyst and the popliteal artery was patency. We describe this case with a review of the relevant literature.

11.
ACS Appl Mater Interfaces ; 14(45): 51351-51360, 2022 Nov 16.
Artigo em Inglês | MEDLINE | ID: mdl-36332077

RESUMO

Daytime radiative cooling technology can release heat into outer space without consuming any electricity during the day while reflecting as much solar radiation as possible. This characteristic gives radiative cooling materials considerable application potential in the fields of energy-saving buildings, fabrics, and photovoltaic cells. The radiative cooling coating (RC coating) applied to a building should cover a large area of the building surface, so a RC coating was prepared by spraying. The RC coating consisted of highly near-infrared reflective yttrium oxide (Y2O3), titanium dioxide (TiO2), and polydimethylsiloxane (PDMS). The RC coating could reach a high solar reflectance of 92.2% and a high atmospheric window emissivity of 94.9%. The complementary reflectivity of TiO2 and Y2O3 was the key to obtaining high reflectivity for RC coatings. The results of field tests showed that the cavity where the RC coating is cooled was 7.7 °C lower than the ambient temperature under direct sunlight. Moreover, the average radiative cooling power of the RC coating was 72.5 W/m2 on a hot summer day. In addition, the RC coating has good stability and thus can be used in various conditions, such as on outdoor buildings.

12.
Mol Ther ; 30(9): 2933-2941, 2022 09 07.
Artigo em Inglês | MEDLINE | ID: mdl-35821638

RESUMO

Adenine base editors (ABEs) are novel genome-editing tools, and their activity has been greatly enhanced by eight additional mutations, thus named ABE8e. However, elevated catalytic activity was concomitant with frequent generation of bystander mutations. This bystander effect precludes its safe applications required in human gene therapy. To develop next-generation ABEs that are both catalytically efficient and positionally precise, we performed combinatorial engineering of NG-ABE8e. We identify a novel variant (NG-ABE9e), which harbors nine mutations. NG-ABE9e exhibits robust and precise base-editing activity in human cells, with more than 7-fold bystander editing reduction at some sites, compared with NG-ABE8e. To demonstrate its practical utility, we used NG-ABE9e to correct the frequent T17M mutation in Rhodopsin for autosomal dominant retinitis pigmentosa. It reduces bystander editing by ∼4-fold while maintaining comparable efficiency. NG-ABE9e possesses substantially higher activity than NG-ABEmax and significantly lower bystander editing than NG-ABE8e in rice. Therefore, this study provides a versatile and improved adenine base editor for genome editing.


Assuntos
Adenina , Edição de Genes , Sistemas CRISPR-Cas , Humanos , Mutação
13.
Life Sci ; 279: 119481, 2021 Aug 15.
Artigo em Inglês | MEDLINE | ID: mdl-33857573

RESUMO

AIMS: Muscle and adipose tissue-derived mesenchymal stem cells presented high osteogenic potentials, which modulate osteoblast function through releasing extracellular vesicles (EVs) containing miRNAs. Herein, this study evaluated the function of bone marrow mesenchymal stem cell-derived extracellular vesicles (BMSC-EVs) delivering miR-497-5p in ossification of the posterior longitudinal ligament (OPLL). MAIN METHODS: The expression level of miR-497-5p was validated in ossified posterior longitudinal ligament (PLL) tissues and BMSC-EVs. The uptake of BMSC-EVs by ligament fibroblasts was observed by immunofluorescence. miR-497-5p was overexpressed or downregulated to assess its role in osteogenic differentiation of ligament fibroblasts. Further, an OPLL rat model was established to substantiate the effect of BMSC-EVs enriched with miR-497-5p on OPLL. KEY FINDINGS: Ossified PLL tissues presented with high miR-497-5p expression. PLL fibroblasts were identified to endocytose BMSC-EVs. BMSC-EVs could upregulate miR-497-5p and shuttle it to ligament fibroblasts to accelerate the osteogenic differentiation. miR-497-5p targeted and inversely regulated RSPO2. Then, RSPO2 overexpression activated Wnt/ß-catenin pathway and repressed the osteogenic differentiation of ligament fibroblasts. In vivo experiments further showed that miR-497-5p-containing BMSC-EVs enhanced OPLL through diminishing RSPO2 and inactivating Wnt/ß-catenin pathway. SIGNIFICANCE: BMSC-EVs could deliver miR-497-5p to ligament fibroblasts and modulate RSPO2-mediated Wnt/ß-catenin pathway, thereby accelerating OPLL.


Assuntos
Diferenciação Celular , Vesículas Extracelulares/patologia , Regulação da Expressão Gênica , Células-Tronco Mesenquimais/patologia , MicroRNAs/genética , Ossificação do Ligamento Longitudinal Posterior/patologia , Trombospondinas/antagonistas & inibidores , Animais , Vesículas Extracelulares/metabolismo , Humanos , Células-Tronco Mesenquimais/metabolismo , Ossificação do Ligamento Longitudinal Posterior/genética , Ossificação do Ligamento Longitudinal Posterior/metabolismo , Ratos , Ratos Wistar , Trombospondinas/genética , Trombospondinas/metabolismo
14.
Clin Neurol Neurosurg ; 197: 106174, 2020 10.
Artigo em Inglês | MEDLINE | ID: mdl-32889324

RESUMO

OBJECTIVE: To predict the 5-year overall survival (OS) rate in patients with conventional chordoma of the spine PATIENTS AND METHODS: The Surveillance, Epidemiology, and End Results (SEER) Registry was used to identify patients with conventional chordoma of the spine from 1994 to 2013. The entire cohort(n = 294) was randomly divided into training (n = 147) and validation (n = 147) cohorts to construct a nomogram. We used the univariate Log-rank test and multivariate Cox model to examine the independent prognostic factors associated with OS. These prognostic factors were integrated to construct a nomogram through R studio. The predictive and validating capacity of the nomogram was calculated by Harrell's concordance index (C-index) and calibration curves. RESULTS: A total of 294 patients were identified with conventional chordoma of the spine. The patients' age at diagnosis, tumor size, EOD (extent of disease), and treatment were independent prognostic factors and associated with OS. These prognostic factors were incorporated to construct a nomogram. The concordance index for the nomogram was 0.771 and 0.732 in the training cohort and validation cohort, respectively. Internal and external calibration curves for 5-year OS showed excellent matching between nomogram prediction and observed outcomes. CONCLUSIONS: The findings of this study provide population-based estimates of patients with conventional chordoma of the spine. Using this nomogram, surgeons can classify patients into different risk groups and achieve individualized treatment.


Assuntos
Cordoma/diagnóstico , Cordoma/mortalidade , Nomogramas , Neoplasias da Coluna Vertebral/diagnóstico , Neoplasias da Coluna Vertebral/mortalidade , Adulto , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Fatores de Risco , Taxa de Sobrevida
15.
Nat Biotechnol ; 38(12): 1460-1465, 2020 12.
Artigo em Inglês | MEDLINE | ID: mdl-32601432

RESUMO

Short insertions and deletions can be produced in plant genomes using CRISPR-Cas editors, but reliable production of larger deletions in specific target sites has proven difficult to achieve. We report the development of a series of APOBEC-Cas9 fusion-induced deletion systems (AFIDs) that combine Cas9 with human APOBEC3A (A3A), uracil DNA-glucosidase and apurinic or apyrimidinic site lyase. In rice and wheat, AFID-3 generated deletions from 5'-deaminated C bases to the Cas9-cleavage site. Approximately one-third of deletions produced using AFID-3 in rice and wheat protoplasts (30.2%) and regenerated plants (34.8%) were predictable. We show that eAFID-3, in which the A3A in AFID-3 is replaced with truncated APOBEC3B (A3Bctd), produced more uniform deletions from the preferred TC motif to the double-strand break. AFIDs could be applied to study regulatory regions and protein domains to improve crop plants.


Assuntos
Proteína 9 Associada à CRISPR/metabolismo , Citidina Desaminase/metabolismo , Oryza/genética , Proteínas/metabolismo , Deleção de Sequência , Triticum/genética , Desaminação , Edição de Genes , Humanos , Oryza/microbiologia , Doenças das Plantas/microbiologia , Protoplastos/metabolismo , Regeneração
16.
Nat Biotechnol ; 38(5): 582-585, 2020 05.
Artigo em Inglês | MEDLINE | ID: mdl-32393904

RESUMO

Prime editors, which are CRISPR-Cas9 nickase (H840A)-reverse transcriptase fusions programmed with prime editing guide RNAs (pegRNAs), can edit bases in mammalian cells without donor DNA or double-strand breaks. We adapted prime editors for use in plants through codon, promoter, and editing-condition optimization. The resulting suite of plant prime editors enable point mutations, insertions and deletions in rice and wheat protoplasts. Regenerated prime-edited rice plants were obtained at frequencies of up to 21.8%.


Assuntos
Edição de Genes/métodos , Oryza/crescimento & desenvolvimento , Triticum/crescimento & desenvolvimento , Sistemas CRISPR-Cas , Desoxirribonuclease I/metabolismo , Genoma de Planta , Oryza/genética , Triticum/genética
17.
Int J Oncol ; 57(1): 249-263, 2020 07.
Artigo em Inglês | MEDLINE | ID: mdl-32319605

RESUMO

Spinal metastasis occurs in 50­75% of bone metastases caused by hepatocellular carcinoma (HCC), and HCC­derived spinal metastasis can lead to a less favorable prognosis. Recently, several studies have demonstrated that C­X3­C motif chemokine ligand 1 (CX3CL1) is closely associated with cancer metastasis, and its secretion is modulated by a disintegrin and metalloproteinase 17 (ADAM17). Bone marrow endothelial cells (BMECs) are an essential component of bone marrow. However, little is known about the roles in and effects of BMECs on HCC spinal metastasis. The present study demonstrated that CX3CL1 and C­X­C motif chemokine receptor 3 (CXCR3) expression was upregulated in HCC spinal metastases, and that CX3CL1 promoted the migration and invasion of HCC cells to the spine. Western blot analysis revealed that the Src/protein tyrosine kinase 2 (PTK2) axis participated in CX3CL1­induced HCC cell invasion and migration. CX3CL1 also increased the expression of M2 macrophage markers in THP­1 monocytes. BMECs promoted the migration and invasion of Hep3B and MHCC97H cells by secreting soluble CX3CL1, whereas the neutralization of CX3CL1 inhibited this enhancement. CX3CL1 enhanced the activation of the phosphatidylinositol­4,5­bisphosphate 3­kinase catalytic subunit alpha (PIK3CA)/AKT serine/threonine kinase 1 (AKT1) and Ras homolog family member A (RHOA)/Rho associated coiled­coil containing protein kinase 2 (ROCK2) signaling pathways through the Src/PTK2 signaling pathway. Furthermore, ADAM17 was activated by mitogen­activated protein kinase (MAPK)z14 in BMECs and significantly promoted the secretion of CX3CL1. HCC cells enhanced the recruitment and proliferation of BMECs. The overexpression of CX3CR1 facilitated the spinal metastasis of HCC in a mouse model in vivo. In addition, in vivo experiments revealed that BMECs promoted the growth of HCC in the spine. The present study demonstrated that CX3CL1 participates in HCC spinal metastasis, and that BMECs play an important role in the regulation of CX3CL1 in the spinal metastatic environment.


Assuntos
Proteína ADAM17/metabolismo , Carcinoma Hepatocelular/secundário , Quimiocina CX3CL1/metabolismo , Células Progenitoras Endoteliais/metabolismo , Neoplasias Hepáticas/patologia , Neoplasias da Coluna Vertebral/secundário , Proteína ADAM17/genética , Adulto , Idoso , Animais , Medula Óssea/patologia , Linhagem Celular Tumoral , Movimento Celular/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Proliferação de Células/genética , Quimiocina CX3CL1/antagonistas & inibidores , Quinase 1 de Adesão Focal/metabolismo , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Técnicas de Silenciamento de Genes , Humanos , Imidazóis , Masculino , Camundongos , Pessoa de Meia-Idade , Proteína Quinase 14 Ativada por Mitógeno/antagonistas & inibidores , Proteína Quinase 14 Ativada por Mitógeno/metabolismo , Piridinas , RNA Interferente Pequeno/metabolismo , Receptores CXCR3/metabolismo , Transdução de Sinais/efeitos dos fármacos , Transdução de Sinais/genética , Coluna Vertebral/patologia , Microambiente Tumoral
18.
Front Genet ; 10: 980, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31681420

RESUMO

Seed dormancy and germination are important agronomic traits in wheat (Triticum aestivum L.) because they determine pre-harvest sprouting (PHS) resistance and thus affect grain production. These processes are regulated by Gibberellic Acid-Stimulated Regulator (GASR) genes. In this study, we identified 37 GASR genes in common wheat, which were designated TaGASR1-37. Moreover, we identified 40 pairs of paralogous genes, of which only one had a Ka/Ks value greater than 1, indicating that most TaGASR genes have undergone negative selection. Chromosomal location and duplication analysis revealed 25 pairs of segmentally duplicated genes and seven pairs of tandemly duplicated genes, suggesting that large-scale duplication events may have contributed to the expansion of TaGASR gene family. Microarray analysis of the expression of 18 TaGASR genes indicated that these genes play diverse roles in different biological processes. Using wheat varieties with contrasting seed dormancy phenotypes, we investigated the expression patterns of TaGASR genes and the corresponding seed germination index phenotypes in response to water imbibition, exogenous ABA and GA treatment, and low- and high-temperature treatment. Based on these data, we identified the TaGASR34 gene as potentially associated with seed dormancy and germination. Further, we used a SNP mutation of the TaGASR34 promoter (-16) to develop the CAPS marker GS34-7B, which was then used to validate the association of TaGASR34 with seed dormancy and germination by evaluating two natural populations across environments. Notably, the frequency of the high-dormancy GS34-7Bb allele was significantly lower than that of the low-dormancy GS34-7Ba allele, implying that the favorable GS34-7Bb allele has not previously been used in wheat breeding. These results provide valuable information for further functional analysis of TaGASR genes and present a useful gene and marker combination for future improvement of PHS resistance in wheat.

19.
Theor Appl Genet ; 132(11): 2947-2963, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31324930

RESUMO

KEY MESSAGE: Three major loci for pre-harvest sprouting tolerance (PHST) were mapped on chromosomes 1AL, 3BS, and 6BL, and two CAPS and one dCAPS markers were validated. Sixteen lines with favorable alleles and increased PHST were identified. Pre-harvest sprouting (PHS) significantly affects wheat grain yield and quality. In the present study, the PHS tolerance (PHST) of 192 wheat varieties (lines) was evaluated by assessment of field sprouting, seed germination index, and period of dormancy in different environments. A high-density Illumina iSelect 90K SNP array was used to genotype the panel. A genome-wide association study (GWAS) based on single- and multi-locus mixed linear models was used to detect loci for PHST. The single-locus model identified 23 loci for PHST (P < 0.0001) and explained 6.0-18.9% of the phenotypic variance. Twenty loci were consistent with known quantitative trait loci (QTLs). Three single-nucleotide polymorphism markers closely linked with three major loci (Qphs.ahau-1A, Qphs.ahau-3B, and Qphs.ahau-6B) on chromosomes 1AL, 3BS, and 6BL, respectively, were converted to two cleaved amplified polymorphic sequences (CAPS) and one derived-CAPS markers, and validated in 374 wheat varieties (lines). The CAPS marker EX06323 for Qphs.ahau-6B co-segregated with a novel major QTL underlying PHST in a recombinant inbred line population raised from the cross Jing 411 × Wanxianbaimaizi. Linear regression showed a clear dependence of PHST on the number of favorable alleles. Sixteen varieties showing an elevated degree of PHST were identified and harbored more than 16 favorable alleles. The multi-locus model detected 39 marker-trait associations for PHST (P < 0.0001), of which five may be novel. Six loci common to the two models were identified. The combination of the two GWAS methods contributes to efficient dissection of the complex genetic mechanism of PHST.


Assuntos
Germinação/genética , Triticum/genética , Alelos , Mapeamento Cromossômico , Estudos de Associação Genética , Marcadores Genéticos , Genótipo , Desequilíbrio de Ligação , Modelos Genéticos , Fenótipo , Polimorfismo de Nucleotídeo Único , Locos de Características Quantitativas , Sementes/fisiologia , Triticum/fisiologia
20.
World Neurosurg ; 122: e1052-e1058, 2019 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-30415045

RESUMO

BACKGROUND: We evaluated the surgical outcomes of metastatic spine hepatocellular carcinoma (HCC) and determined the factors that might influence the outcomes of metastatic HCC of the spine. METHODS: From 2010 to 2017, 72 patients with HCC-derived metastatic spine tumors were treated in our department. For each patient, we recorded the pre- and postoperative visual analog scale score, Frankel grade, perioperative complications, and mortality. Univariate and multivariate analyses were used to explore a range of factors that might influence postoperative survival. RESULTS: The mean postoperative survival was 10.8 ± 5.4 months. The concordance rate between a Tokuhashi score of 0-8 and a life expectancy of <6 months was only 19.2%. The mean postoperative survival for patients undergoing excisional surgery was 14.7 ± 6.5 months, and the mean survival of those receiving palliative surgery was 8.5 ± 2.6 months. Pain had significantly improved in both patient groups (P < 0.001). Paralysis did not change significantly in the excisional surgery group (P = 0.641) or palliative surgery group (P = 0.912). Univariate analysis showed that the preoperative Frankel score, Tomita score, Tokuhashi score, blood loss, multilevel metastases, and operative type were independent prognostic factors for postoperative survival time. Multivariate analysis showed that operation type was an independent factor for prognosis, just as were the Tomita score and Tokuhashi score. CONCLUSIONS: Our results have challenged previously reported estimates of the life expectancy correlating with the Tokuhashi score. Our results showed that excisional surgery resulted in better clinical outcomes compared with palliative surgery.


Assuntos
Carcinoma Hepatocelular/mortalidade , Carcinoma Hepatocelular/cirurgia , Neoplasias Hepáticas/mortalidade , Neoplasias Hepáticas/cirurgia , Adulto , Idoso , Carcinoma Hepatocelular/diagnóstico , Feminino , Seguimentos , Humanos , Expectativa de Vida/tendências , Neoplasias Hepáticas/diagnóstico , Masculino , Pessoa de Meia-Idade , Prognóstico , Estudos Retrospectivos , Taxa de Sobrevida/tendências , Resultado do Tratamento
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