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Efficient, mild, and reversible adsorption of nucleic acids onto nanomaterials represents a promising analytical approach for medical diagnosis. However, there is a scarcity of efficient and reversible nucleic acid adsorption nanomaterials. Additionally, the lack of comprehension of the molecular mechanisms governing their interactions poses significant challenges. These issues hinder the rational design and analytical applications of the nanomaterials. Herein, we propose an ultra-efficient nucleic acid affinity nanomaterial based on programmable lanthanide metal-organic frameworks (Ln-MOFs). Through experiments and density functional theory calculations, a rational design guideline for nucleic acid affinity of Ln-MOF was proposed, and a modular and flexible preparation scheme was provided. Then, Er-TPA (terephthalic acid) MOF emerged as the optimal candidate due to its pore size-independent adsorption and desorption capabilities for nucleic acids, enabling ultra-efficient adsorption (about 150% mass ratio) within 1 min. Furthermore, we elucidate the molecular-level mechanisms underlying the Ln-MOF adsorption of single- and double-stranded DNA and G4 structures. The affinity nanomaterial based on Ln-MOF exhibits robust nucleic acid extraction capability (4-fold higher than commercial reagent kits) and enables mild and reversible CRISPR/Cas9 functional regulation. This method holds significant promise for broad application in DNA/RNA liquid biopsy and gene editing, facilitating breakthroughs in analytical chemistry, pharmacy, and medical research.
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DNA , Elementos da Série dos Lantanídeos , Estruturas Metalorgânicas , Estruturas Metalorgânicas/química , Elementos da Série dos Lantanídeos/química , Adsorção , DNA/química , DNA/isolamento & purificação , Ácidos Ftálicos/química , Nanoestruturas/química , Teoria da Densidade Funcional , HumanosRESUMO
SnTe, as a potential medium-temperature thermoelectric material, reaches a maximum power factor (PF) usually above 750 K, which is not conducive to continuous high-power output in practical applications. In this study, PF is maintained at high values between 18.5 and 25 µW cm-1 K-2 for Sn0.99In0.01Te-x wt% tourmaline samples within the temperature range of 323 to 873 K, driving the highest PFeng of 1.2 W m-1 K-1 and PFave of 22.5 µW cm-1 K-2, over 2.5 times that of pristine SnTe. Such an extraordinary PF is attributed to the synergy of resonant levels and Sn vacancy suppression. Specifically, the Seebeck coefficient increases dramatically, reaching 88 µV K-1 at room temperature. Meanwhile, by Sn vacancy suppression, carrier concentration, and mobility are optimized to ≈1019 cm-3 and 740 cm2 V-1 s-1, respectively. With the tourmaline compositing, Sn vacancies are further suppressed and the thermal conductivity simultaneously decreases, with the minimum lattice thermal conductivity of 0.9 W m-1 K-1. Finally, the zT value ≈0.8 is obtained in the Sn0.99In0.01Te sample. The peak of the power output density reaches 0.89 W cm-2 at a temperature difference of 600 K. Such SnTe alloys with high and "temperature-independent" PF will offer an option for realizing high output power in thermoelectric devices.
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PRDM16 is a transcription co-factor that plays critical roles in development of brown adipose tissue, as well as maintenance of adult hematopoietic and neural stem cells. Here we report that PRDM16 is a histone H3K4 methyltransferase on chromatin. Mutation in the N-terminal PR domain of PRDM16 abolishes the intrinsic enzymatic activity of PRDM16. We show that the methyltransferase activity of PRDM16 is required for specific suppression of MLL fusion protein-induced leukemogenesis both in vitro and in vivo. Mechanistic studies show that PRDM16 directly activates the SNAG family transcription factor Gfi1b, which in turn downregulates the HOXA gene cluster. Knockdown Gfi1b represses PRDM16-mediated tumor suppression, while Gfi1b overexpression mimics PRDM16 overexpression. In further support of the tumor suppressor function of PRDM16, silencing PRDM16 by DNA methylation is concomitant with MLL-AF9-induced leukemic transformation. Taken together, our study reveals a previously uncharacterized function of PRDM16 that depends on its PR domain activity.
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OBJECTIVE: We aimed to assess the early efficacy of anlotinib in patients with progressive radioactive iodine refractory differentiated thyroid cancer at the structural, biochemical, and metabolic levels. METHODS: Ten eligible patients were prospectively enrolled to receive anlotinib. Their responses were assessed at 6 weeks. Apart from the structural response according to Response Evaluation Criteria in Solid Tumors version 1.1, the biochemical response was assessed by serum thyroglobulin (Tg), and the metabolic response was assessed by 2-deoxy-2-[18F] fluoro-D-glucose positron emission tomography/computed tomography (18F-FDG PET/CT) according to the European Organization for Research and Treatment of Cancer criteria. A safety profile was recorded. RESULTS: Structurally controlled disease (20% partial response + 80% stable disease) was observed in all patients. The median longest diameter of target lesions shrank from 20.8 mm (IQR, 14.9-27.5) to 17.0 mm (IQR, 14.1-23.7) (P < .001), and the average shrinkage rate was -15.1 ± 14.1%. Sharp serum Tg reduction by 72.8 ± 16.4% was observed in 8 measurable patients. The 18F-FDG PET/CT-mapped glucose metabolic response was not quite comparable to the structural response, with 90% of the patients having controlled disease (30% partial metabolic response + 60% stable metabolic disease), whereas 10% presented progressive metabolic disease. The most common treatment-emergent adverse events (AEs) were hypertension (100%) and proteinuria (70%). Most AEs were grade 1 or 2, whereas grade 3 AEs occurred only in hypertension. CONCLUSION: Anlotinib is generally well tolerated and can bring early disease control within the initial 6 weeks of treatment. The sharp biochemical response suggests Tg to be an early sensitive biomarker to anlotinib, whereas the heterogeneous metabolic response might play a complementary role.
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Indóis , Radioisótopos do Iodo , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada , Quinolinas , Neoplasias da Glândula Tireoide , Humanos , Feminino , Masculino , Pessoa de Meia-Idade , Quinolinas/uso terapêutico , Quinolinas/administração & dosagem , Neoplasias da Glândula Tireoide/tratamento farmacológico , Neoplasias da Glândula Tireoide/radioterapia , Neoplasias da Glândula Tireoide/metabolismo , Neoplasias da Glândula Tireoide/patologia , Indóis/uso terapêutico , Indóis/administração & dosagem , Adulto , Radioisótopos do Iodo/uso terapêutico , Idoso , Fluordesoxiglucose F18 , Estudos Prospectivos , Tireoglobulina/sangue , Antineoplásicos/uso terapêutico , Resultado do TratamentoRESUMO
Neural tube defects (NTDs) are characterized by the failure of neural tube closure during embryogenesis and are considered the most common and severe central nervous system anomalies during early development. Recent microRNA (miRNA) expression profiling studies have revealed that the dysregulation of several miRNAs plays an important role in retinoic acid (RA)-induced NTDs. However, the molecular functions of these miRNAs in NTDs remain largely unidentified. Here, we show that miR-10a-5p is significantly upregulated in RA-induced NTDs and results in reduced cell growth due to cell cycle arrest and dysregulation of cell differentiation. Moreover, the cell adhesion molecule L1-like ( Chl1) is identified as a direct target of miR-10a-5p in neural stem cells (NSCs) in vitro, and its expression is reduced in RA-induced NTDs. siRNA-mediated knockdown of intracellular Chl1 affects cell proliferation and differentiation similar to those of miR-10a-5p overexpression, which further leads to the inhibition of the expressions of downstream ERK1/2 MAPK signaling pathway proteins. These cellular responses are abrogated by either increased expression of the direct target of miR-10a-5p ( Chl1) or an ERK agonist such as honokiol. Overall, our study demonstrates that miR-10a-5p plays a major role in the process of NSC growth and differentiation by directly targeting Chl1, which in turn induces the downregulation of the ERK1/2 cascade, suggesting that miR-10a-5p and Chl1 are critical for NTD formation in the development of embryos.
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BACKGROUND: Oblique lumbar interbody fusion (OLIF) procedures have the potential to increase the segmental lordosis by inserting lordotic cages, however, the amount of segmental lordosis (SL) changes can vary and is likely influenced by several factors, such as patient characteristics, radiographic parameters, and surgical techniques. The objective of this study was to analyze the impact of related factors on the amount of SL changes in OLIF procedures and to build up predictive model for SL changes. METHODS: This is a retrospective study involving prospectively enrolled patients. A total of 119 patients with 174 segments undergoing OLIF procedure were included and analyzed. The lordotic cages used in all cases had 6-degree angle. Radiographic parameters including preoperative and postoperative segmental disc angle (SDA, preSDA and postSDA), SDA changes on flexion-extension views (ΔSDA-FE), CageLocation and CageInclination were measured by two observers. Interobserver reliability of measurements were ensured by analysis of interclass correlation coefficient (ICC > 0.75). Pearson correlation coefficient analysis and multivariate linear regression were employed to identify factors related to SDA changes and to build up predictive model for SDA changes. RESULTS: The average change of segmental disc angle (ΔSDA, postSDA-preSDA) was 3.9° ± 4.8° (95% confidence interval [CI]: 3.1°-4.6°) with preSDA 5.3° ± 5.0°. ΔSDA was 10.8° ± 3.2° with negative preSDA (kyphotic), 5.0° ± 3.7° with preSDA ranging from 0° to 6°, and 1.0° ± 4.1° with preSDA> 6°. Correlation analysis revealed a significant negative correlation between ΔSDA and preSDA (r = - 0.713, P < 0.001), CageLocation (r = - 0.183, P = 0.016) and ΔSDA-FE (r = - 0.153, P = 0.044). In the multivariate linear regression, preSDA and CageLocation were included in the predictive model, resulting in minimal adjusted R2 change (0.017) by including CageLocation. Therefore, the recommended predictive model was ΔSDA = 7.9-0.8 × preSDA with acceptable fit. (adjusted R2 = 0.508, n = 174, P < 0.001). CONCLUSIONS: The restoration of segmental lordosis through OLIF largely depends on the preoperative segmental lordosis. The predictive model, which utilized preoperative segmental lordosis, facilitates preoperative planning for corrective surgery using the OLIF procedure.
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Lordose , Fusão Vertebral , Humanos , Estudos Retrospectivos , Lordose/diagnóstico por imagem , Lordose/cirurgia , Reprodutibilidade dos Testes , Fusão Vertebral/métodos , Vértebras Lombares/diagnóstico por imagem , Vértebras Lombares/cirurgia , Resultado do TratamentoRESUMO
OBJECTIVE: Previous observational studies have indicated associations between various immune cells and diabetic nephropathy (DN). However, the causality remains unclear. We aimed to further evaluate the causal association between immune cells and DN using bidirectional two-sample Mendelian randomization (MR) analysis. METHOD: The DN data were retrieved from the IEU OpenGWAS Project database, while the data for 731 immune cells were sourced from GWAS summary statistics by Orru Ì et al. The investigation into the causal relationship between immune cells and DN employed the inverse variance weighted (IVW), weighted median (WME), and MR-Egger methods. The stability and reliability of the findings underwent evaluation through Cochran's Q test, MR-Egger intercept's P-value, MR-PRESSO, and Leave-One-Out (LOO) method. RESULT: The IVW estimates suggested a positive causal effect of CD25 on IgD-CD38dim B cell, CD25 on naive-mature B cell, CD127 on granulocyte, SSC-A on HLA DR + Natural Killer, HLA DR on plasmacytoid Dendritic Cell, and HLA DR on Dendritic Cell on DN. Conversely, the abundance of Myeloid Dendritic Cell, CD62L- Dendritic Cell %Dendritic Cell, CD86+ myeloid Dendritic Cell %Dendritic Cell, CD14- CD16-, CX3CR1 on CD14- CD16-, and SSC-A on CD4+ T cell had negative causal effects on DN. However, after correcting the P value for significant causality results using the FDR method, it was concluded that only Myeloid Dendritic Cells had a causal relationship with DN (FDR-p = 0.041), while the other immune cells showed no significant association with DN, so their relationship was suggestive. The results were stable with no observed horizontal pleiotropy and heterogeneity. Reverse MR analysis indicated no causal relationship between DN and the increased risk of positively identified immune cells. CONCLUSION: This study provides an initial insight into the genetic perspective of the causal relationship between immune cells and DN. It establishes a crucial theoretical foundation for future endeavors in precision medicine and individualized treatment.
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Nefropatias Diabéticas , Análise da Randomização Mendeliana , Humanos , Nefropatias Diabéticas/genética , Nefropatias Diabéticas/imunologia , Estudo de Associação Genômica Ampla , Células Dendríticas/imunologia , Reprodutibilidade dos Testes , Linfócitos B/imunologia , Fatores de RiscoRESUMO
Objective: Patients with radioactive iodine-refractory differentiated thyroid cancer (RAIR-DTC) are often diagnosed with delay and constrained to limited treatment options. The correlation between RAI refractoriness and the underlying genetic characteristics has not been extensively studied. Methods: Adult patients with distant metastatic DTC were enrolled and assigned to undergo next-generation sequencing of a customized 26-gene panel (ThyroLead). Patients were classified into RAIR-DTC or non-RAIR groups to determine the differences in clinicopathological and molecular characteristics. Molecular risk stratification (MRS) was constructed based on the association between molecular alterations identified and RAI refractoriness, and the results were classified as high, intermediate or low MRS. Results: A total of 220 patients with distant metastases were included, 63.2% of whom were identified as RAIR-DTC. Genetic alterations were identified in 90% of all the patients, with BRAF (59.7% vs. 17.3%), TERT promoter (43.9% vs. 7.4%), and TP53 mutations (11.5% vs. 3.7%) being more prevalent in the RAIR-DTC group than in the non-RAIR group, except for RET fusions (15.8% vs. 39.5%), which had the opposite pattern. BRAF and TERT promoter are independent predictors of RAIR-DTC, accounting for 67.6% of patients with RAIR-DTC. MRS was strongly associated with RAI refractoriness (P<0.001), with an odds ratio (OR) of high to low MRS of 7.52 [95% confidence interval (95% CI), 3.96-14.28; P<0.001] and an OR of intermediate to low MRS of 3.20 (95% CI, 1.01-10.14; P=0.041). Conclusions: Molecular alterations were associated with RAI refractoriness, with BRAF and TERT promoter mutations being the predominant contributors, followed by TP53 and DICER1 mutations. MRS might serve as a valuable tool for both prognosticating clinical outcomes and directing precision-based therapeutic interventions.
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Three-dimensional (3D) cages in the mesopore regime (2-50 nm) assembled from molecular building blocks are highly desirable in biological applications; however, their synthesis in crystalline form is quite challenging, as well as their structure characterization. Here, we report the synthesis of extremely large 3D cages in MOF crystals, with internal cage sizes of 6.9, and 8.5 nm in MOF-929; 9.3 and 11.4 nm in MOF-939, in cubic unit cells, a = 17.4 and 22.8 nm, respectively. These cages are constructed from relatively short organic linkers with the lengths of 0.85 and 1.3 nm, where the influence from molecular motion is minimized, thus favoring their crystallization. A 0.45 nm linker length elongation leads to a maximum 2.9 nm increase in cage size, giving a supreme efficiency in cage expansion. The spatial arrangements of these 3D cages were visualized by both X-ray diffraction and transmission electron microscopy. The efforts to obtain these cages in crystals pushed forward the size boundary for the construction of 3D cages from molecules and also exploited the limit of the area in space possibly supported per chemical bond, where the expansion efficiencies of the cages were found to play a critical role. These extremely large 3D cages in MOFs were useful in the complete extraction of long nucleic acid, such as total RNA and plasmid from aqueous solution.
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Although the widespread use of antiretroviral therapy (ART) has prolonged the life span of people living with HIV (PLWH), the incidence of HIV-associated neurocognitive disorders (HAND) in PLWH is also gradually increasing, seriously affecting the quality of life for PLWH. However, the pathogenesis of HAND has not been elucidated, which leaves HAND without effective treatment. HIV protein transactivator of transcription (Tat), as an important regulatory protein, is crucial in the pathogenesis of HAND, and its mechanism of HAND has received widespread attention. The blood-brain barrier (BBB) and its cellular component brain microvascular endothelial cells (BMVECs) play a necessary role in protecting the central nervous system (CNS), and their damage associated with Tat is a potential therapeutic target of HAND. In this review, we will study the Tat-mediated damage mechanism of the BBB and present multiple lines of evidence related to BMVEC damage caused by Tat.
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Infecções por HIV , HIV-1 , Humanos , Barreira Hematoencefálica/metabolismo , Células Endoteliais/metabolismo , Proteínas de Junções Íntimas/genética , Proteínas de Junções Íntimas/metabolismo , Transativadores/metabolismo , Qualidade de Vida , Produtos do Gene tat do Vírus da Imunodeficiência Humana/metabolismo , HIV-1/metabolismo , Encéfalo/metabolismo , Infecções por HIV/patologiaRESUMO
Thermal stability is one of the most important properties of enzymes, which sustains life and determines the potential for the industrial application of biocatalysts. Although traditional methods such as directed evolution and classical rational design contribute greatly to this field, the enormous sequence space of proteins implies costly and arduous experiments. The development of enzyme engineering focuses on automated and efficient strategies because of the breakthrough of high-throughput DNA sequencing and machine learning models. In this review, we propose a data-driven architecture for enzyme thermostability engineering and summarize some widely adopted datasets, as well as machine learning-driven approaches for designing the thermal stability of enzymes. In addition, we present a series of existing challenges while applying machine learning in enzyme thermostability design, such as the data dilemma, model training, and use of the proposed models. Additionally, a few promising directions for enhancing the performance of the models are discussed. We anticipate that the efficient incorporation of machine learning can provide more insights and solutions for the design of enzyme thermostability in the coming years.
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Engenharia de Proteínas , Estabilidade EnzimáticaRESUMO
Objective: Investigating postoperative infection risk factors in elderly spinal fracture patients is crucial for optimizing surgical outcomes, improving patient safety, and guiding clinical decision-making in the management of these complex cases. To investigate the risk factors for postoperative infection in elderly patients with spinal fractures, with the goal of giving clinical care guidelines. Methods: From January 2019 to January 2022, 120 elderly patients admitted to our hospital for elective spinal fracture surgery were featured as the study subjects, and the patients were divided into infected and non-infected categories according to whether they had postoperative infection or not. A mathematical prediction model was built after using logistic multiple regression to investigate the parameters influencing postoperative infection of a spinal fracture. Results: There were 20 patients in the infected category and 100 patients in the non-infected category. Univariate analysis showed that the proportion of patients in the infected category with male, age ≥65 years, multiple fractures, use of hormones or combined diabetes was notably higher than that in the non-infected category (P < .05). Male gender, age ≥65 years, multiple fractures, and certain medical conditions are independent risk factors for postoperative infection. Conclusions: Logistic regression analysis revealed that male, age ≥65 years, multiple fractures, use of hormones, or combined diabetes was an independent risk factor for postoperative infection in elderly patients with spinal fracture. Our study provides valuable insights that can guide clinical care and decision-making for elderly patients with spinal fractures. By applying these findings in practice, clinicians can refine their treatment strategies, improve patient outcomes, and enhance the overall quality of care provided to this vulnerable population.
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Due to the high affinity with water molecules, amide compounds are easily contaminated by moisture; therefore, the water interference effect cannot be totally excluded from the amide-involved reactions. Thus, the perfect solution is to use the interference effect but not shield it in a real application. In this work, we introduced different contents of sodium acrylate (AAS) to scavenge water from the monomers of N-isopropylacrylamide (NIPAm) when copolymerized with TPA-Vinyl-4CN. Herein, water molecules play a role as nucleophilic reagents to attack highly active functional groups as -C=C-CN from TPA-Vinyl-4CN, leading to a blue emissive TPA-Vinyl-2CHO. From this study, we made a deep awareness of the interactions between three reaction partners of AAS and NIPAm as well as TPA-Vinyl-4CN. Our results clearly demonstrated the fact that water can be perfectly used and controlled by the water absorbent of AAS, developing a new approach to synthesizing multiple emission-coloured polymers by using only one luminogen of TPA-Vinyl-4CN.
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Intelligent operation and maintenance technology for vessels can ensure the safety of the entire system, especially for the development of intelligent and unmanned marine technology. The material properties of metal abrasive particles in oil could demonstrate the wear areas of the marine mechanical system because different components consist of different materials. However, most sensors can only roughly separate metallic contaminants into ferromagnetic and non-ferromagnetic particles but cannot differentiate them in greater detail. A micro-three-coil sensor is designed in this paper; the device applies different excitation signals to two excitation coils to differentiate materials, based on the different effects of different material particles in the asymmetric magnetic field. Therefore, a particle's material can be judged by the shape of the induction electromotive force output signal from the induction coil, while the particle size can be judged by the amplitude of the signal. Experimental results show that the material differentiation of four different types of particles can be achieved, namely, of aluminum, iron, 304 stainless steel, and carbon steel. This newly designed sensor provides a new research prospect for the realization of an inductive detection method to distinguish non-ferrous metals and a reference for the subsequent detection of metal contaminants in oil and other liquids.
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Bacterial wilt negatively impacts the yield and quality of tomatoes. cis-Abienol, a labdane diterpenoid abundantly produced in the trichome secretion of Nicotiana spp., can induce bacterial wilt resistance in plants; however, study on its practical application and acting mechanism is very limited. This study established the application conditions of cis-abienol for inducing tomato bacterial wilt resistance by pot-inoculation experiments and investigated the underlying mechanism by determining the physio-biochemical indexes and transcriptomic changes. The results showed that applying cis-abienol to the roots was the most effective approach for inducing tomato bacterial wilt resistance. The optimal concentration was 60 µg/mL, and 2-3 consecutive applications with 3-6 days intervals were sufficient to induce the bacterial wilt resistance of tomato plants. cis-Abienol could enhance the antioxidant enzyme activity and stimulate the defensive signal transduction in tomato roots, leading to the upregulation of genes involved in the mitogen-activated protein kinase cascade. It also upregulated the expression of JAZ genes and increased the content of jasmonic acid (JA) and salicylic acid (SA), which control the expression of flavonoid biosynthetic genes and the content of phytoalexins in tomato roots. cis-Abienol-induced resistance mainly depends on the JA signalling pathway, and the SA signalling pathway is also involved in this process. This study established the feasibility of applying the plant-derived terpenoid cis-abienol to induce plant bacterial wilt resistance, which is of great value for developing eco-friendly bactericides.
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Diterpenos , Solanum lycopersicum , Nicotiana/genética , Nicotiana/metabolismo , Solanum lycopersicum/genética , Transdução de Sinais , Diterpenos/farmacologia , Ácido Salicílico/metabolismo , Doenças das Plantas/genética , Doenças das Plantas/microbiologia , Regulação da Expressão Gênica de PlantasRESUMO
Phosphate fertilizers have been excessively applied in agricultural production, bringing the risk of phosphorus (P) loss to nearby river systems and low utilization efficiency. In this study, eggshell-modified biochars prepared by pyrolysis of eggshell and corn straw or pomelo peel were applied to soil for enhancing P immobilization and utilization. The structure and properties of modified biochars before and after P adsorption were analyzed using the Brunauer-Emmett-Teller (BET) nitrogen adsorption method, Fourier transform infrared spectroscopy (FTIR), X-ray diffraction (XRD), X-ray photoelectron spectroscopy (XPS), and scanning electron microscope (SEM). The eggshell-modified biochar performed an excellent adsorption performance for P (up to 200 mg/g), which was well described by the Langmuir model (R2 > 0.969), showing monolayer chemical adsorption with homogenous surface. The Ca(OH)2 appeared on the surface of eggshell modified biochars and changed to Ca5(PO4)3(OH) and CaHPO4(H2O)2 after P adsorption. The release of immobilized P by modified biochar increased with decreased pH. In addition, pot experiments of soybean indicated that the combined application of modified biochar and P fertilizer significantly increased the content of microbial biomass P in soil, raising from 4.18 mg/kg (control group) to 51.6-61.8 mg/kg (treatment group), and plants height increased by 13.8-26.7%. Column leaching experiments showed that P concentration in the leachate decreased by 97.9% with the modified biochar application. This research provides a new perspective that the eggshell-modified biochar could serve as a potential soil amendment for enhancing P immobilization and utilization.
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Casca de Ovo , Solo , Animais , Biomassa , Fosfatos , Carvão Vegetal/química , Adsorção , Espectroscopia de Infravermelho com Transformada de Fourier , CinéticaRESUMO
Circulating tumor cells (CTC) have been represented by different phenotypes due to the epithelial-mesenchymal transition (EMT), which are epithelial CTC (E-CTC), mesenchymal CTC (M-CTC), and mixed (epithelial, mesenchymal) CTC (EM-CTC). Limited work has systematically discussed the associations of CTC number, especially proportions of E-CTC, M-CTC, and EM-CTC in total CTC, with colorectal cancer (CRC) progressions via a simple method with high performances. To achieve this goal, this paper presents the fabrication of a novel anti-nonspecific adsorption immunomagnetic platform called Fe3O4@SiO2@PTMAO@Aptamer, which was obtained by modifying polymeric trimethylamine N-oxide (PTMAO) on magnetic Fe3O4@SiO2, which was then linked with dual aptamers of an epithelial cellular adhesion molecule (EpCAM) and cell surface vimentin (CSV), targeting different CTC phenotypes. Results demonstrated that the abundant coating of PTMAO on Fe3O4@SiO2 improved the anti-nonspecific adsorption and noncell adhesion abilities of the immunomagnetic particles and could capture heterogeneous CTC with higher efficiency within 10 min. These excellent performances of Fe3O4@SiO2@PTMAO@Aptamer allowed us to inspect the correlations of numbers of E-CTC, M-CTC, EM-CTC, or proportions of them in total CTC with clinical information on CRC patients in detail. Our data innovatively and clearly revealed that the captured CTC, especially M-CTC proportion, displayed more close associations with progression, diagnosis, surgery, and chemotherapeutic effects for CRC patients. Overall, we believe that our approach will bring a new understanding of CTC-based liquid biopsy for cancer diagnosis and treatment.
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Neoplasias Colorretais , Células Neoplásicas Circulantes , Humanos , Células Neoplásicas Circulantes/patologia , Adsorção , Dióxido de Silício , Transição Epitelial-Mesenquimal/genética , Neoplasias Colorretais/diagnóstico , Neoplasias Colorretais/patologia , Biomarcadores Tumorais , Molécula de Adesão da Célula EpitelialRESUMO
A new coupled fiber optic humidity sensor based on a double-tapered fiber twisted weakly coupled structure coated with a graphene oxide/polyvinyl alcohol (GO/PVA) film has been reported for the first time, to the best of our knowledge. The sensor adopts a 2×2 coupler structure with a waist diameter of 20 µm. The GO/PVA composite film is coated in the weakly coupled area to increase the sensitivity of the sensor. The thickness of the coating layer is about 3 µm. The sensor can realize linear sensing in the relative humidity (RH) range of 45%-85%RH with a dynamic response time of 1.9 s and a recovery time of 5.7 s. The sensitivity of the sensor is up to 0.002/%RH, and the linearity of the sensor is as high as 98.65%. Moreover, the sensor has good stability, reversibility, and low-temperature crosstalk.
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Morel mushroom (Morchella spp.) is a valuable mushroom, which has extremely high nutritional and economic value. In the early March of 2022, a serious rot disease was observed on approximately 30% fruiting bodies at an M. esculenta farm of Suzhou City, Anhui province, China. A white mold-like hyphae was initially present on the pileus, which then gradually spread to the whole fruiting body, eventually resulting in softening of the fruiting body and death. This disease developed rapidly at relatively high temperature (>20°C) and humidity (>85%), resulting in approximately 80% loss of yield. Twenty infected tissues were cut into small pieces (5 × 5 mm) and placed on potato dextrose agar (PDA) and incubated at 25°C for 5 days. Fifteen morphologically similar isolates were obtained and purified using the single spore isolation technique. Colonies of these isolates were yellowish-white, and tomentose with thick aerial hyphae after 7 days at 25°C on PDA plates. Conidiophores were dimorphic: primary conidiophores were Verticillium-like, secondary conidiophores were penicillate. Primary conidiophore stipe length ranged from 68.6 to 180.5 µm, and the base width was 3.2-5.6 µm. Phialides were solitary, straight, generally slightly tapering towards the tip, each producing a small, hyaline drop of conidia. Secondary conidiophores stipe length ranged from 68.4 to 120.5 µm, the base measured 3.3-6.1µm. Phialides were straight to slightly curved, slightly flask-shaped, with widest point below the middle, slightly tapering in the upper part, without visible collarette. Conidia were colorless, smooth, slightly curved, and distally broadly rounded with an average size of 6.3 to 8.2 × 2.4 to 3.7 µm (n=30). These isolates were initially identified as Clonostachys rosea based on morphological features (Schroers et al. 1999). To confirm the identity of C. rosea, primers ITS1/ITS4 (White et al. 1990) and EF1-728F/ EF1-986R (Carbone and Kohn 1999), were used to amplify the internal transcribed spacer (ITS), and translation elongation factor 1-alpha (EF-1α) genes of the representative isolate 5-3-2. These sequences were deposited in GenBank (GenBank accession nos. ON614093 and ON630916) and had 100% and 99.45% nucleotide identity with Clonostachys rosea E5R(17) and Clonostachys rosea KGSJ26 (GenBank accession nos. MK752437 and MT462122), respectively. Single conidium were isolated and multiplied on PDA for pathogenicity testing. To fulfill Koch's postulates, pathogenicity tests were performed using the fruiting bodies. Spores of C. rosea isolates 5-3-2 were collected and diluted with sterile distilled water at a concentration of 1 × 106 conidia/ml. Five healthy fruiting bodies were inoculated with 1 ml of the spore suspension, which were maintained in an artificial climate chamber at 22°C and 85% humidity. Sterile water inoculated on other 10 healthy fruiting bodies served as control. Mycelia grew rapidly and overgrew more than half of the fruiting bodies within 3 days. The fruiting bodies died five days after inoculation. Clonostachys rosea isolates were re-isolated from symptomatic fruiting bodies and identified by the methods described above. The control group showed no symptoms. The experiment was conducted twice. To our knowledge, this is the first identification of Clonostachys rosea as the causal agent of the Morchella sextelata rot.
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BACKGROUND: To perform a comparative assessment of percutaneous transfacet screws (TFS) and percutaneous bilateral pedicle screws (BPS) in oblique lateral interbody fusion (OLIF) for the treatment of single-level degenerative lumbar spine diseases in terms of radiological examinations and clinical outcomes. METHODS: Sixty-six patients who received single-level OLIF with percutaneous supplementary fixation assisted by the robot for the treatment of degenerative lumbar spine diseases were selected. There were 16 cases of OLIF with TFS and 50 cases of OLIF with BPS. The propensity score matching method selected 11 patients in each group with matched characteristics to perform a clinical comparison. RESULTS: The estimated blood loss was 68.2 ± 25.2 ml in the OLIF with TFS group compared to 113.6 ± 39.3 ml in the OLIF with BPS group (P < 0.05). The intervertebral disc height raised from 8.6 to 12.9 mm in the TFS group and from 8.9 to 13.9 mm in the BPS group in the immediate postoperative period, and dropped to 10.8 and 12.9 mm at the twelfth month, respectively (P < 0.05). The fusion rates were 91% and 100% for TFS and BPS groups (P > 0.05). Quantitative assessments of back/leg pain of the two groups reached a healthy level in the late period of the follow-up. CONCLUSION: Both TFS and BPS techniques for the OLIF surgery relieve back pain caused by degenerative lumbar spine diseases. The TFS technique exhibits less blood loss compared with the BPS. A moderate cage subsidence is present in TFS but no complication is reported.