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1.
Blood ; 141(3): 231-237, 2023 01 19.
Artigo em Inglês | MEDLINE | ID: mdl-36322931

RESUMO

Germ line loss-of-function heterozygous mutations in the RUNX1 gene cause familial platelet disorder with associated myeloid malignancies (FPDMM) characterized by thrombocytopenia and a life-long risk of hematological malignancies. Although gene therapies are being considered as promising therapeutic options, current preclinical models do not recapitulate the human phenotype and are unable to elucidate the relative fitness of mutation-corrected and RUNX1-heterozygous mutant hematopoietic stem and progenitor cells (HSPCs) in vivo long term. We generated a rhesus macaque with an FPDMM competitive repopulation model using CRISPR/Cas9 nonhomologous end joining editing in the RUNX1 gene and the AAVS1 safe-harbor control locus. We transplanted mixed populations of edited autologous HSPCs and tracked mutated allele frequencies in blood cells. In both animals, RUNX1-edited cells expanded over time compared with AAVS1-edited cells. Platelet counts remained below the normal range in the long term. Bone marrows developed megakaryocytic dysplasia similar to human FPDMM, and CD34+ HSPCs showed impaired in vitro megakaryocytic differentiation, with a striking defect in polyploidization. In conclusion, the lack of a competitive advantage for wildtype or control-edited HSPCs over RUNX1 heterozygous-mutated HSPCs long term in our preclinical model suggests that gene correction approaches for FPDMM will be challenging, particularly to reverse myelodysplastic syndrome/ acute myeloid leukemia predisposition and thrombopoietic defects.


Assuntos
Subunidade alfa 2 de Fator de Ligação ao Core , Leucemia Mieloide Aguda , Animais , Humanos , Macaca mulatta , Subunidade alfa 2 de Fator de Ligação ao Core/genética , Leucemia Mieloide Aguda/genética , Leucemia Mieloide Aguda/terapia , Leucemia Mieloide Aguda/patologia , Trombopoese , Fenótipo
2.
Drug Resist Updat ; 76: 101115, 2024 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-39002266

RESUMO

Pancreatic ductal adenocarcinoma (PDAC) is a lethal disease, notably resistant to existing therapies. Current research indicates that PDAC patients deficient in homologous recombination (HR) benefit from platinum-based treatments and poly-ADP-ribose polymerase inhibitors (PARPi). However, the effectiveness of PARPi in HR-deficient (HRD) PDAC is suboptimal, and significant challenges remain in fully understanding the distinct characteristics and implications of HRD-associated PDAC. We analyzed 16 PDAC patient-derived tissues, categorized by their homologous recombination deficiency (HRD) scores, and performed high-plex immunofluorescence analysis to define 20 cell phenotypes, thereby generating an in-situ PDAC tumor-immune landscape. Spatial phenotypic-transcriptomic profiling guided by regions-of-interest (ROIs) identified a crucial regulatory mechanism through localized tumor-adjacent macrophages, potentially in an HRD-dependent manner. Cellular neighborhood (CN) analysis further demonstrated the existence of macrophage-associated high-ordered cellular functional units in spatial contexts. Using our multi-omics spatial profiling strategy, we uncovered a dynamic macrophage-mediated regulatory axis linking HRD status with SIGLEC10 and CD52. These findings demonstrate the potential of targeting CD52 in combination with PARPi as a therapeutic intervention for PDAC.


Assuntos
Carcinoma Ductal Pancreático , Recombinação Homóloga , Macrófagos , Neoplasias Pancreáticas , Humanos , Carcinoma Ductal Pancreático/imunologia , Carcinoma Ductal Pancreático/genética , Carcinoma Ductal Pancreático/tratamento farmacológico , Carcinoma Ductal Pancreático/patologia , Neoplasias Pancreáticas/genética , Neoplasias Pancreáticas/imunologia , Neoplasias Pancreáticas/tratamento farmacológico , Neoplasias Pancreáticas/patologia , Macrófagos/imunologia , Macrófagos/metabolismo , Inibidores de Poli(ADP-Ribose) Polimerases/farmacologia , Inibidores de Poli(ADP-Ribose) Polimerases/uso terapêutico , Microambiente Tumoral/imunologia
3.
Nano Lett ; 24(1): 331-338, 2024 Jan 10.
Artigo em Inglês | MEDLINE | ID: mdl-38108571

RESUMO

Solar-driven photothermal catalytic H2 production from lignocellulosic biomass was achieved by using 1T-2H MoS2 with tunable Lewis acidic sites as catalysts in an alkaline aqueous solution, in which the number of Lewis acidic sites derived from the exposed Mo edges of MoS2 was successfully regulated by both the formation of an edge-terminated 1T-2H phase structure and tunable layer number. Owing to the abundant Lewis acidic sites for the oxygenolysis of lignocellulosic biomass, the 1T-2H MoS2 catalyst shows high photothermal catalytic lignocellulosic biomass-to-H2 transformation performance in polar wood chips, bamboo, rice straw corncobs, and rice hull aqueous solutions, and the highest H2 generation rate and solar-to-H2 (STH) efficiency respectively achieves 3661 µmol·h-1·g-1 and 0.18% in the polar wood chip system under 300 W Xe lamp illumination. This study provides a sustainable and cost-effective method for the direct transformation of renewable lignocellulosic biomass to H2 fuel driven by solar energy.

4.
Nano Lett ; 24(38): 11968-11975, 2024 Sep 25.
Artigo em Inglês | MEDLINE | ID: mdl-39259027

RESUMO

The conversion of woody biomass to H2 through photocatalysis provides a sustainable strategy to generate renewable hydrogen fuel but was limited by the slow decomposition rate of woody biomass. Here, we fabricate ultrasmall TiO2 nanoparticles with tunable concentration of oxygen vacancy defects (VO-TiO2) as highly efficient photocatalysts for photocatalytic conversion of woody biomass to H2. Owing to the positive role of oxygen vacancy in reducing energy barrier for the generation of •OH which was the critical species to oxidize woody biomass, the obtained VO-TiO2 achieves rapid photocatalytic conversion of α-cellulose and poplar wood chip to H2 in the presence of Pt nanoclusters as the cocatalyst. As expected, the highest H2 generation rate in α-cellulose and poplar wood chip system respectively achieve 1146 and 59 µmol h-1 g-1, and an apparent quantum yield of 4.89% at 380 nm was obtained in α-cellulose aqueous solution.

5.
J Am Chem Soc ; 2024 Oct 05.
Artigo em Inglês | MEDLINE | ID: mdl-39367841

RESUMO

The origin of the unique directionality of myosin has been a problem of fundamental and practical importance. This work establishes in a conclusive way that the directionality is controlled by tuning the barrier for the rate-determining step, namely, the ADP release step. This conclusion is based on exploring the molecular origin behind the reverse directionality of myosins V and VI and the determination of the origin of the change in the barriers of the ADP release for the forward and backward motions. Our investigation is performed by combining different simulation methods such as steer molecular dynamics (SMD), umbrella sampling, renormalization method, and automated path searching method. It is found that in the case of myosin V, the ADP release from the postrigor (trailing head) state overcomes a lower barrier than the prepowerstroke (leading head) state, which is also evident from experimental observation. In the case of myosin VI, we noticed a different trend when compared to myosin V. Since the directionality of myosins V and VI follows a reverse trend, we conclude that such differences in the directionality are controlled by the free energy barrier for the ADP release. Overall, the proof that the directionality of myosin is determined by the activation barrier of the rate-determining step in the cycle, rather than by some unspecified dynamical effects, has general importance.

6.
J Am Chem Soc ; 146(20): 13875-13885, 2024 May 22.
Artigo em Inglês | MEDLINE | ID: mdl-38718165

RESUMO

Bioluminescence is a fascinating natural phenomenon, wherein organisms produce light through specific biochemical reactions. Among these organisms, Renilla luciferase (RLuc) derived from the sea pansy Renilla reniformis is notable for its blue light emission and has potential applications in bioluminescent tagging. Our study focuses on RLuc8, a variant of RLuc with eight amino acid substitutions. Recent studies have shown that the luminescent emitter coelenteramide can adopt multiple protonation states, which may be influenced by nearby residues at the enzyme's active site, demonstrating a complex interplay between protein structure and bioluminescence. Herein, using the quantum mechanical consistent force field method and the semimacroscopic protein dipole-Langevin dipole method with linear response approximation, we show that the phenolate state of coelenteramide in RLuc8 is the primary light-emitting species in agreement with experimental results. Our calculations also suggest that the proton transfer (PT) from neutral coelenteramide to Asp162 plays a crucial role in the bioluminescence process. Additionally, we reproduced the observed emission maximum for the amide anion in RLuc8-D120A and the pyrazine anion in the presence of a Na+ counterion in RLuc8-D162A, suggesting that these are the primary emitters. Furthermore, our calculations on the neutral emitter in the engineered AncFT-D160A enzyme, structurally akin to RLuc8-D162A but with a considerably blue-shifted emission peak, aligned with the observed data, possibly explaining the variance in emission peaks. Overall, this study demonstrates an effective approach to investigate chromophores' bimolecular states while incorporating the PT process in emission spectra calculations, contributing valuable insights for future studies of PT in photoproteins.


Assuntos
Pirazinas , Teoria Quântica , Pirazinas/química , Pirazinas/metabolismo , Renilla/enzimologia , Luciferases/química , Luciferases/metabolismo , Luminescência , Animais , Imidazóis/química , Benzenoacetamidas
7.
Phys Rev Lett ; 132(25): 250204, 2024 Jun 21.
Artigo em Inglês | MEDLINE | ID: mdl-38996245

RESUMO

The Hamiltonian, which determines the evolution of a quantum system, is fundamental in quantum physics. Therefore, it is crucial to implement high-precision generation and measurement of the Hamiltonian in a practical quantum system. Here, we experimentally demonstrate ultrahigh-precision Hamiltonian parameter estimation with a significant quantum advantage in a superconducting circuit via sequential control. We first observe the commutation relation for noncommuting operations determined by the system Hamiltonian, both with and without adding quantum control, verifying the commuting property of controlled noncommuting operations. Based on this control-induced commuting property, we further demonstrate Hamiltonian parameter estimation for polar and azimuth angles in superconducting circuits, achieving ultrahigh metrological gains in measurement precision exceeding the standard quantum limit by up to 16.0 and 16.1 dB at N=100, respectively.

8.
Analyst ; 149(4): 1212-1220, 2024 Feb 12.
Artigo em Inglês | MEDLINE | ID: mdl-38214602

RESUMO

A fluorometric method based on boron, bromide-codoped carbon dots (BBCNs) was developed for the first time for the highly selective detection of p-nitroaniline (PNA) in wastewater samples. It should be noted that the introduction of bromine greatly increases the molecular polarizability of the probe, which can regulate the energy level matching between the probe and PNA, resulting in the interaction between BBCNs and PNA. In the presence of PNA, the fluorescence of BBCNs is obviously quenched and accompanied by a red shift of the fluorescence band, which might be attributed to the formation of aggregates caused by the polar adsorption of BBCNs and PNA. It is beneficial for constructing a highly selective sensing platform for PNA determination compared to its isomers (o-nitroaniline and m-nitroaniline) through atomic bromine-mediated polarization of the BBCNs. With the help of this mechanism, an excellent linear range of 0.5-300 µM with a low detection limit of 0.24 µM toward PNA was obtained. This work further confirms that there is a significant relationship between the nature of doping elements and the optical and physicochemical properties of fluorescent materials.

9.
Phytopathology ; 2024 Sep 08.
Artigo em Inglês | MEDLINE | ID: mdl-39244657

RESUMO

The commercialized genetically modified (GM) papaya cultivars have protected papaya from the devastating disease caused by papaya ringspot virus (PRSV). However, papaya leaf distortion mosaic virus (PLDMV), which causes similar infection symptoms but is serologically distinct from PRSV, was found as a competitive threat to the papaya industry. Our study surveyed the occurrence of PRSV and PLDMV as well as the transgenic markers of the 35S promoter from cauliflower mosaic virus (CaMV 35S) and the neomycin phosphotransferase II (NPT II) gene in feral papaya plants, which were found frequently growing outside of cultivated papaya fields on Hainan Island. In total, 123 feral papayas, comprising 62 (50.4%) GM plants and 61 (49.6%) non-GM ones, were sampled. Among them, 23 (18.7%) were positive for PRSV, 49 (39.8%) were positive for PLDMV, including 5 plants co-infected by PRSV and PLDMV, and 56 (45.5%) plants were free of either virus. In traditional papaya growing regions, we detected fewer PRSV-infected plants (2 in 33, 6%) than in other regions (21 in 90, 23%). But overall, whether transgenic or not made no significance in PRSV incidence (P=0.230), with 9 PRSV-infected plants among 62 GM papayas and 14 among 61 non-GM papayas. Phylogenetic and genetic differentiation analysis showed a clear correlation between PRSV and PLDMV populations and their geographical origins. Negative selection was estimated for the selected gene regions of both viruses. Notably, PLDMV has deviated from neutral evolution and experienced population expansion, exhibiting increased genetic diversity and is becoming the predominant threat to papaya in Hainan.

10.
BMC Musculoskelet Disord ; 25(1): 185, 2024 Feb 29.
Artigo em Inglês | MEDLINE | ID: mdl-38424582

RESUMO

BACKGROUND: Osteoporosis is a serious global public health issue. Currently, there are few studies that explore the use of multiparametric MRI radiomics for osteoporosis detection. The purpose of this study was to compare the performance of radiomics features from multiple MRI sequences (T1WI, T2WI and T1WI combined with T2WI) for detecting osteoporosis in patients. METHODS: A retrospective analysis was performed on 160 patients who had undergone dual-energy X-ray absorptiometry(DXA) and lumbar magnetic resonance imaging (MRI) at our hospital. Among them, 86 patients were diagnosed with abnormal bone mass (osteoporosis or low bone mass), and 74 patients were diagnosed with normal bone mass based on the DXA results. Sagittal T1-and T2-weighted images of all patients were imported into the uAI Research Portal (United Imaging Intelligence) for image delineation and radiomics analysis, where a series of radiomic features were obtained. A radiomic model that included T1WI, T2WI, and T1WI+T2WI was established using features selected by LASSO regression. We used ROC curve analysis to evaluate the predictive efficacy of each model for identifying bone abnormalities and conducted decision curve analysis (DCA) to evaluate the net benefit of each model. Finally, we validated the model in a sample of 35 patients from different health care institution. RESULTS: The T1WI + T2WI radiomics model showed better screening performance for patients with abnormal bone mass. In the training group, the sensitivity was 0.758, the specificity was 0.78, and the accuracy was 0.768 (AUC =0.839, 95% CI=0.757-0.901). In the validation group, the sensitivity was 0.792, the specificity was 0.875, and the accuracy was 0.833 (AUC =0.86, 95% CI=0.73-0.943).The DCA also showed that the combined model had better net benefits. In the external validation group, the sensitivity was 0.764, the specificity was 0.833, and the accuracy was 0.8 (AUC =0.824, 95% CI 0.678-0.969). CONCLUSIONS: Radiomics-based multiparametric MRI can be used for the quantitative analysis of lumbar MRI and for accurately screening patients with abnormal bone mass.


Assuntos
Imageamento por Ressonância Magnética Multiparamétrica , Osteoporose , Humanos , Radiômica , Estudos Retrospectivos , Osteoporose/diagnóstico por imagem , Densidade Óssea , Imageamento por Ressonância Magnética
11.
BMC Musculoskelet Disord ; 25(1): 484, 2024 Jun 20.
Artigo em Inglês | MEDLINE | ID: mdl-38898448

RESUMO

BACKGROUND: Spinal fractures in patients with ankylosing spondylitis (AS) mainly present as instability, involving all three columns of the spine, and surgical intervention is often considered necessary. However, in AS patients, the significant alterations in bony structure and anatomy result in a lack of identifiable landmarks, which increases the difficulty of pedicle screw implantation. Therefore, we present the clinical outcomes of robotic-assisted percutaneous fixation for thoracolumbar fractures in patients with AS. METHODS: A retrospective review was conducted on a series of 12 patients diagnosed with AS. All patients sustained thoracolumbar fractures between October 2018 and October 2022 and underwent posterior robotic-assisted percutaneous fixation procedures. Outcomes of interest included operative time, intra-operative blood loss, complications, duration of hospital stay and fracture union. The clinical outcomes were assessed using the visual analogue scale (VAS) and Oswestry Disability Index (ODI). To investigate the achieved operative correction, pre- and postoperative radiographs in the lateral plane were analyzed by measuring the Cobb angle. RESULTS: The 12 patients had a mean age of 62.8 ± 13.0 years and a mean follow-up duration of 32.7 ± 18.9 months. Mean hospital stay duration was 15 ± 8.0 days. The mean operative time was 119.6 ± 32.2 min, and the median blood loss was 50 (50, 250) ml. The VAS value improved from 6.8 ± 0.9 preoperatively to 1.3 ± 1.0 at the final follow-up (P < 0.05). The ODI value improved from 83.6 ± 6.1% preoperatively to 11.8 ± 6.6% at the latest follow-up (P < 0.05). The average Cobb angle changed from 15.2 ± 11.0 pre-operatively to 8.3 ± 7.1 at final follow-up (P < 0.05). Bone healing was consistently achieved, with an average healing time of 6 (5.3, 7.0) months. Of the 108 screws implanted, 2 (1.9%) were improperly positioned. One patient experienced delayed nerve injury after the operation, but the nerve function returned to normal upon discharge. CONCLUSION: Posterior robotic-assisted percutaneous internal fixation can be used as an ideal surgical treatment for thoracolumbar fractures in AS patients. However, while robot-assisted pedicle screw placement can enhance the accuracy of pedicle screw insertion, it should not be relied upon solely.


Assuntos
Fixação Interna de Fraturas , Vértebras Lombares , Procedimentos Cirúrgicos Robóticos , Fraturas da Coluna Vertebral , Espondilite Anquilosante , Vértebras Torácicas , Humanos , Fraturas da Coluna Vertebral/cirurgia , Fraturas da Coluna Vertebral/diagnóstico por imagem , Fraturas da Coluna Vertebral/etiologia , Masculino , Pessoa de Meia-Idade , Vértebras Torácicas/cirurgia , Vértebras Torácicas/lesões , Vértebras Torácicas/diagnóstico por imagem , Feminino , Estudos Retrospectivos , Espondilite Anquilosante/cirurgia , Espondilite Anquilosante/complicações , Vértebras Lombares/cirurgia , Vértebras Lombares/lesões , Vértebras Lombares/diagnóstico por imagem , Procedimentos Cirúrgicos Robóticos/métodos , Fixação Interna de Fraturas/métodos , Fixação Interna de Fraturas/instrumentação , Resultado do Tratamento , Idoso , Duração da Cirurgia , Tempo de Internação , Parafusos Pediculares , Adulto , Perda Sanguínea Cirúrgica/estatística & dados numéricos , Seguimentos
12.
Eur Radiol ; 2023 Nov 08.
Artigo em Inglês | MEDLINE | ID: mdl-37938384

RESUMO

OBJECTIVES: Aimed to develop a nomogram model based on deep learning features and radiomics features for the prediction of early hematoma expansion. METHODS: A total of 561 cases of spontaneous intracerebral hemorrhage (sICH) with baseline Noncontrast Computed Tomography (NCCT) were included. The metrics of hematoma detection were evaluated by Intersection over Union (IoU), Dice coefficient (Dice), and accuracy (ACC). The semantic features of sICH were judged by EfficientNet-B0 classification model. Radiomics analysis was performed based on the region of interest which was automatically segmented by deep learning. A combined model was constructed in order to predict the early expansion of hematoma using multivariate binary logistic regression, and a nomogram and calibration curve were drawn to verify its predictive efficacy by ROC analysis. RESULTS: The accuracy of hematoma detection by segmentation model was 98.2% for IoU greater than 0.6 and 76.5% for IoU greater than 0.8 in the training cohort. In the validation cohort, the accuracy was 86.6% for IoU greater than 0.6 and 70.0% for IoU greater than 0.8. The AUCs of the deep learning model to judge semantic features were 0.95 to 0.99 in the training cohort, while in the validation cohort, the values were 0.71 to 0.83. The deep learning radiomics model showed a better performance with higher AUC in training cohort (0.87), internal validation cohort (0.83), and external validation cohort (0.82) than either semantic features or Radscore. CONCLUSION: The combined model based on deep learning features and radiomics features has certain efficiency for judging the risk grade of hematoma. CLINICAL RELEVANCE STATEMENT: Our study revealed that the deep learning model can significantly improve the work efficiency of segmentation and semantic feature classification of spontaneous intracerebral hemorrhage. The combined model has a good prediction efficiency for early hematoma expansion. KEY POINTS: • We employ a deep learning algorithm to perform segmentation and semantic feature classification of spontaneous intracerebral hemorrhage and construct a prediction model for early hematoma expansion. • The deep learning radiomics model shows a favorable performance for the prediction of early hematoma expansion. • The combined model holds the potential to be used as a tool in judging the risk grade of hematoma.

13.
Inorg Chem ; 62(13): 5200-5206, 2023 Apr 03.
Artigo em Inglês | MEDLINE | ID: mdl-36959113

RESUMO

In the field of recycling CO2, the photocatalytic CO2 reduction reaction (CO2RR) is a typical example, and researchers have designed a variety of photocatalysts to improve the conversion rate of CO2 over the years. In this paper, two metal-oxygen clusters are designed and formulated as [Co3Zn(OH)6(SO4)]·4H2O (1) and [Ni3Zn(OH)6(SO4)]·4H2O (2). As for compound 1, the main structure is composed of {CoO6} octahedra connected by edge-sharing to form a two-dimensional layer, on which {ZnO4} and {SO4} tetrahedra are supported. More interestingly, compound 1 has outstanding photocatalytic activity, which is mainly attributed to the open-framework structure and the cobalt ions as active sites. Upon catalysis for eight hours, its maximum CO generation rate is 9982.13 µmol g-1 h-1, with a selectivity of 81.8%. Additionally, compound 1 takes on weak antiferromagnetic coupling due to Co(II) ions.

14.
Artigo em Inglês | MEDLINE | ID: mdl-37072569

RESUMO

Emergence delirium (ED) is a common mental complication during recovery from anesthesia. However, studies on the effects of esketamine, an intravenous anesthetic for pediatrics, on ED are still lacking. This study aimed to investigate the effects of a single-dose of esketamine during anesthesia induction on ED after minor surgery in preschool children. A total of 230 children (aged 2-7 years) completed the study. The exposed group (0.46 mg kg-1: average dose of esketamine) was associated with an increased incidence of ED and a higher maximum Pediatric Anesthesia Emergence Delirium score than the non-exposed group. The length of post-anesthesia care unit stay was longer in the exposed group than the non-exposed group. In contrast, extubation time, face, legs, activity, cry, and consolability (FLACC) scores, and the proportions of rescue analgesics were comparable between the two groups. Furthermore, five factors, including preoperative anxiety scores, sevoflurane and propofol compared with sevoflurane alone for anesthesia maintenance, dezocine for postoperative analgesia, FLACC scores, and esketamine exposure, were associated with ED. In conclusion, a near-anesthetic single-dose of esketamine for anesthesia induction may increase the incidence of ED in preschool children after minor surgery. The use of esketamine in preschool children for minor surgery should be noticed during clinical practice.

15.
J Sep Sci ; 46(19): e2200793, 2023 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-37528471

RESUMO

Lingyang Qingfei pills (LQP), the renowned traditional Chinese medicine recipe, have been extensively utilized for the therapy of xerostomia, sore throat, bronchiolitis, and pneumonia in clinics. However, its phytochemicals remain equivocal, which severely limits the development of quality control and activity mechanisms. In the current research, a trusted method founded on ultra-high performance liquid chromatography with Quadrupole-Exactive Orbitrap mass spectrometry technique was proposed for the comprehensive screening of in vitro and in vivo chemical compositions of LQP. As a consequence, 239 constituents were preliminarily characterized, 37 of which were accurately confirmed by reference standards. In addition, a total of 208 xenobiotics, containing 71 absorbed prototypes and 137 metabolites, were revealed in rat plasma, bile, urine, and feces, respectively. The metabolic reaction of hydrolysis, hydroxylation, methylation, glycosylation, sulfation, and mixed-mode was detected in the biotransformations of flavonoids, terpenoids, alkaloids, anthraquinones, organic acids, phenylpropanoids, and so forth. And 12 of the metabolites were new compounds. This experiment acted as the first reference for chemical substances and metabolites of LQP, which could provide valuable chemical information for further clarifying pharmacodynamic substances and pharmacokinetic studies.

16.
Ren Fail ; 45(1): 2162417, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-36632830

RESUMO

OBJECTIVES: To construct a valid and reliable Nutritional Literacy Scale for patients with end-stage kidney disease (ESKD) receiving dialysis and evaluate associations between nutrition literacy and quality of life. METHODS: A total of 208 ESKD patients receiving dialysis were selected for this study. Nutrition literacy evaluation items were drafted based on dietary guidelines for chronic kidney disease (CKD), Literature reviews and expert consultation. Scale reliability and validity were then assessed. Factors influencing nutrition literacy and the associations among nutrition literacy, nutritional status, and quality of life were evaluated. RESULTS: The scale consists of 28 items with a scale-level content validity index of 0.91 and item-level content validity indices ranging from 0.83 to 1.00. Factor analysis identified 4 common factors (dimensions) named nutrition knowledge, cognitive attitude, behavioral practice, and information acquisition ability that collectively explained 56.31% of literacy score variation. The overall Cronbach's α coefficient of the scale was 0.83, the dimensional Cronbach's α coefficients ranged from 0.79 to 0.87, and the retest reliability was r = 0.73 (p < 0.05). Age, education level, residence (urban vs. Rural) , occupational status and dialysis modalities were significant factors influencing nutrition literacy. Nutrition literacy score was negatively correlated with SGA score and positively correlated with serum albumin and prealbumin concen- trations, and with SF-36 quality of life score (all p < 0.05). CONCLUSIONS: This new Nutrition Literacy Scale demonstrates high reliability and validity for Chinese ESKD patients undergoing dialysis. The nutrition literacy is influenced by age, education level, residence, occupational status and dialysis modalities, associated not only with nutritional status but also with quality of life.


Assuntos
Dieta Saudável , Falência Renal Crônica , Avaliação Nutricional , Estado Nutricional , Diálise Renal , Humanos , Falência Renal Crônica/terapia , Qualidade de Vida , Reprodutibilidade dos Testes , Inquéritos e Questionários
17.
J Asian Nat Prod Res ; 25(8): 810-817, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36394297

RESUMO

Investigation on the chemical components of Valeriana jatamansi Jones (Caprifoliaceae), a new lignan with pyran-ring, dipsalignan G (1), along with eight known compounds (2-9) were isolated. Their structures were elucidated by extensive analysis of 1D, 2D NMR and HR-ESI-MS spectroscopic data. Additionally, possible biosynthetic pathway of 1 was proposed. Finally, biological evaluation results showed that 8 had significant scavenging ability to ABTS and DPPH free radicals, with IC50 values of 1.35 ± 0.01 and 2.94 ± 0.01 µg/ml, respectively.

18.
Int Orthop ; 47(10): 2497-2505, 2023 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-37386277

RESUMO

PURPOSE: To construct and validate a nomogram model that integrated deep learning radiomic features based on multiparametric MRI and clinical features for risk stratification of meniscus injury. METHODS: A total of 167 knee MR images were collected from two institutions. All patients were classified into two groups based on the MR diagnostic criteria proposed by Stoller et al. The automatic meniscus segmentation model was constructed through V-net. LASSO regression was performed to extract the optimal features correlated to risk stratification. A nomogram model was constructed by combining the Radscore and clinical features. The performance of the models was evaluated by ROC analysis and calibration curve. Subsequently, the model was simulated by junior doctors in order to test its practical application effect. RESULTS: The Dice similarity coefficients of automatic meniscus segmentation models were all over 0.8. Eight optimal features, identified by LASSO regression, were employed to calculate the Radscore. The combined model showed a better performance in both the training cohort (AUC = 0.90, 95%CI: 0.84-0.95) and the validation cohort (AUC = 0.84, 95%CI: 0.72-0.93). The calibration curve indicated a better accuracy of the combined model than either the Radscore or clinical model alone. The simulation results showed that the diagnostic accuracy of junior doctors increased from 74.9 to 86.2% after using the model. CONCLUSION: Deep learning V-net demonstrated great performance in automatic meniscus segmentation of the knee joint. It was reliable for stratifying the risk of meniscus injury of the knee by nomogram which integrated the Radscores and clinical features.

19.
Zhongguo Zhong Yao Za Zhi ; 48(1): 226-233, 2023 Jan.
Artigo em Zh | MEDLINE | ID: mdl-36725275

RESUMO

The aim of this study was to explore the effects of Huangqin Tang(HQT) on the NLRP3/Caspase-1 signaling pathway in mice with DSS-induced ulcerative colitis(UC). C57BL/6J mice were randomly divided into a blank group, a model group(DSS group), and low-, medium-and high-dose HQT groups(HQT-L, HQT-M, and HQT-H), and western medicine mesalazine group(western medicine group). The UC model was induced in mice. Subsequently, the mice in the HQT-L, HQT-M, HQT-H groups, and the western medicine group were given low-, medium-, high-dose HQT, and mesalazine suspension by gavage, respectively, while those in the blank and DSS groups were given an equal volume of distilled water by gavage. After 10 days of administration, the body weight, DAI scores, and colonic histopathological score of mice in each group were determined. The levels of IL-6, IL-10, IL-1ß, and TNF-α in serum were determined by ELISA. The mRNA expression of NLRP3 and Caspase-1 in colon tissues was determined by RT-qPCR. The protein expression of NLRP3 and Caspase-1 in colon tissues was detected by immunohistochemistry. The results showed that compared with the blank group, the DSS group showed decreased body weight of mice and increased DAI scores and intestinal histopathological score. Compared with the DSS group, the HQT groups and the western medicine group showed improved DAI scores, especially in the HQT-M, HQT-H, and the western medicine groups(P<0.05). The intestinal histopathological scores of the HQT groups and the western medicine group significantly decreased, especially in the HQT-M, HQT-H, and the western medicine groups(P<0.05). In addition, compared with the blank group, the DSS group showed elevated expression of NLRP3 and Caspase-1 in colon tissues, increased serum levels of IL-6, IL-1ß, and TNF-α, and decreased IL-10 level. Compared with the DSS group, the HQT groups and the western medicine group displayed decreased expression of NLRP3 and Caspase-1 in colon tissues, reduced serum levels of IL-6, IL-1ß, and TNF-α, and increased IL-10 level. The improvement was the most significant in the HQT-H group and the western medicine group(P<0.01). In conclusion, HQT may reduce the expression of NLRP3 and Caspase-1 in colon tissues, reduce the se-rum levels of IL-6, IL-1ß, and TNF-α, and increase the expression of IL-10 by regulating the classic pyroptosis pathway of NLRP3/Caspase-1, thereby improving the symptoms of intestinal injury and inflammatory infiltration of intestinal mucosa in DSS mice to achieve its therapeutic effect.


Assuntos
Colite Ulcerativa , Medicamentos de Ervas Chinesas , Animais , Camundongos , Caspase 1/genética , Colite Ulcerativa/induzido quimicamente , Colite Ulcerativa/tratamento farmacológico , Colite Ulcerativa/genética , Colo , Sulfato de Dextrana/efeitos adversos , Modelos Animais de Doenças , Interleucina-10/genética , Interleucina-6/genética , Mesalamina/farmacologia , Camundongos Endogâmicos C57BL , Proteína 3 que Contém Domínio de Pirina da Família NLR/genética , Scutellaria baicalensis/química , Fator de Necrose Tumoral alfa/metabolismo , Medicamentos de Ervas Chinesas/farmacologia
20.
Blood ; 136(21): 2373-2385, 2020 11 19.
Artigo em Inglês | MEDLINE | ID: mdl-32929473

RESUMO

Inversion of chromosome 16 is a consistent finding in patients with acute myeloid leukemia subtype M4 with eosinophilia, which generates a CBFB-MYH11 fusion gene. It is generally considered that CBFß-SMMHC, the fusion protein encoded by CBFB-MYH11, is a dominant negative repressor of RUNX1. However, recent findings challenge the RUNX1-repression model for CBFß-SMMHC-mediated leukemogenesis. To definitively address the role of Runx1 in CBFB-MYH11-induced leukemia, we crossed conditional Runx1 knockout mice (Runx1f/f) with conditional Cbfb-MYH11 knockin mice (Cbfb+/56M). On Mx1-Cre activation in hematopoietic cells induced by poly (I:C) injection, all Mx1-CreCbfb+/56M mice developed leukemia in 5 months, whereas no leukemia developed in Runx1f/fMx1-CreCbfb+/56M mice, and this effect was cell autonomous. Importantly, the abnormal myeloid progenitors (AMPs), a leukemia-initiating cell population induced by Cbfb-MYH11 in the bone marrow, decreased and disappeared in Runx1f/fMx1-CreCbfb+/56M mice. RNA-seq analysis of AMP cells showed that genes associated with proliferation, differentiation blockage, and leukemia initiation were differentially expressed between Mx1-CreCbfb+/56M and Runx1f/fMx1-CreCbfb+/56M mice. In addition, with the chromatin immunocleavage sequencing assay, we observed a significant enrichment of RUNX1/CBFß-SMMHC target genes in Runx1f/fMx1-CreCbfb+/56M cells, especially among downregulated genes, suggesting that RUNX1 and CBFß-SMMHC mainly function together as activators of gene expression through direct target gene binding. These data indicate that Runx1 is indispensable for Cbfb-MYH11-induced leukemogenesis by working together with CBFß-SMMHC to regulate critical genes associated with the generation of a functional AMP population.


Assuntos
Transformação Celular Neoplásica/genética , Subunidade alfa 2 de Fator de Ligação ao Core/fisiologia , Regulação Leucêmica da Expressão Gênica , Leucemia Experimental/genética , Células Mieloides/metabolismo , Proteínas de Neoplasias/fisiologia , Células-Tronco Neoplásicas/metabolismo , Proteínas de Fusão Oncogênica/fisiologia , Ativação Transcricional , Animais , Subunidade alfa 2 de Fator de Ligação ao Core/deficiência , Subunidade alfa 2 de Fator de Ligação ao Core/genética , Regulação Leucêmica da Expressão Gênica/efeitos dos fármacos , Técnicas de Introdução de Genes , Humanos , Leucemia Experimental/etiologia , Camundongos da Linhagem 129 , Camundongos Endogâmicos C57BL , Camundongos Knockout , Células Mieloides/citologia , Células-Tronco Neoplásicas/citologia , Proteínas de Fusão Oncogênica/genética , Poli I-C/farmacologia , RNA Mensageiro/biossíntese , RNA Mensageiro/genética , RNA Neoplásico/biossíntese , RNA Neoplásico/genética , RNA-Seq , Análise de Célula Única
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