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1.
J Control Release ; 373: 265-276, 2024 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-39019087

RESUMO

Curcumin potentiates the stabilization of atherosclerotic plaques by polarizing macrophages, but its non-specific targeting hinders its clinical application. We aim to harness multifunctional lipid nanoparticles (MLNPs) to facilitate the imaging and targeted delivery of curcumin specifically to inflammatory macrophages, counteracting vulnerable plaques and mitigating the risk of ischemic events. Cholesteryl-9-carboxynonanoate-(125I­iron oxide nanoparticle/Curcumin)-lipid-coated nanoparticles [9-CCN-(125I-ION/Cur)-LNPs], namely MLNPs, are designed to carry hybrid imaging agents. These agents combine 125I-ION with lipids containing phagocytic 'eat-me' signals, inducing macrophages to engulf the MLNPs. Our research demonstrates that the designed MLNPs accurately accumulate at unstable plaques and are precisely visualized and highlighted by both SPECT and MRI. Furthermore, MLNPs achieve high efficiency in delivering 125I-ION and curcumin to macrophages, ultimately leading to significant M1-to-M2 macrophage polarization. These real-time imaging and polarization capabilities of plaques have immediate clinical applicability and may pave the way for novel therapies to stabilize unstable atherosclerotic plaques.


Assuntos
Curcumina , Macrófagos , Nanopartículas , Placa Aterosclerótica , Curcumina/administração & dosagem , Curcumina/química , Animais , Placa Aterosclerótica/diagnóstico por imagem , Placa Aterosclerótica/tratamento farmacológico , Nanopartículas/química , Nanopartículas/administração & dosagem , Macrófagos/efeitos dos fármacos , Camundongos , Fagocitose/efeitos dos fármacos , Imageamento por Ressonância Magnética/métodos , Masculino , Radioisótopos do Iodo/administração & dosagem , Células RAW 264.7 , Camundongos Endogâmicos C57BL , Tomografia Computadorizada de Emissão de Fóton Único/métodos , Lipídeos/química , Lipossomos
2.
Radiology ; 311(2): e232178, 2024 05.
Artigo em Inglês | MEDLINE | ID: mdl-38742970

RESUMO

Background Accurate characterization of suspicious small renal masses is crucial for optimized management. Deep learning (DL) algorithms may assist with this effort. Purpose To develop and validate a DL algorithm for identifying benign small renal masses at contrast-enhanced multiphase CT. Materials and Methods Surgically resected renal masses measuring 3 cm or less in diameter at contrast-enhanced CT were included. The DL algorithm was developed by using retrospective data from one hospital between 2009 and 2021, with patients randomly allocated in a training and internal test set ratio of 8:2. Between 2013 and 2021, external testing was performed on data from five independent hospitals. A prospective test set was obtained between 2021 and 2022 from one hospital. Algorithm performance was evaluated by using the area under the receiver operating characteristic curve (AUC) and compared with the results of seven clinicians using the DeLong test. Results A total of 1703 patients (mean age, 56 years ± 12 [SD]; 619 female) with a single renal mass per patient were evaluated. The retrospective data set included 1063 lesions (874 in training set, 189 internal test set); the multicenter external test set included 537 lesions (12.3%, 66 benign) with 89 subcentimeter (≤1 cm) lesions (16.6%); and the prospective test set included 103 lesions (13.6%, 14 benign) with 20 (19.4%) subcentimeter lesions. The DL algorithm performance was comparable with that of urological radiologists: for the external test set, AUC was 0.80 (95% CI: 0.75, 0.85) versus 0.84 (95% CI: 0.78, 0.88) (P = .61); for the prospective test set, AUC was 0.87 (95% CI: 0.79, 0.93) versus 0.92 (95% CI: 0.86, 0.96) (P = .70). For subcentimeter lesions in the external test set, the algorithm and urological radiologists had similar AUC of 0.74 (95% CI: 0.63, 0.83) and 0.81 (95% CI: 0.68, 0.92) (P = .78), respectively. Conclusion The multiphase CT-based DL algorithm showed comparable performance with that of radiologists for identifying benign small renal masses, including lesions of 1 cm or less. Published under a CC BY 4.0 license. Supplemental material is available for this article.


Assuntos
Meios de Contraste , Aprendizado Profundo , Neoplasias Renais , Tomografia Computadorizada por Raios X , Humanos , Feminino , Masculino , Pessoa de Meia-Idade , Neoplasias Renais/diagnóstico por imagem , Neoplasias Renais/patologia , Estudos Retrospectivos , Tomografia Computadorizada por Raios X/métodos , Estudos Prospectivos , Interpretação de Imagem Radiográfica Assistida por Computador/métodos , Idoso , Algoritmos , Rim/diagnóstico por imagem , Adulto
3.
Sci Adv ; 9(49): eadk2407, 2023 Dec 08.
Artigo em Inglês | MEDLINE | ID: mdl-38064555

RESUMO

Current chemical recycling of bulk synthetic plastic, polyethylene (PE), operates at high temperature/pressure and yields a complex mixture of products. PE conversion under mild conditions and with good selectivity toward value-added chemicals remains a practical challenge. Here, we demonstrate an atomic engineering strategy to modify a TiO2 photocatalyst with reversible Pd species for the selective conversion of PE to ethylene (C2H4) and propionic acid via dicarboxylic acid intermediates under moderate conditions. TiO2-supported atomically dispersed Pd species exhibits C2H4 evolution of 531.2 µmol gcat-1 hour-1, 408 times that of pristine TiO2. The liquid product is a valuable chemical propanoic acid with 98.8% selectivity. Plastic conversion with a C2 hydrocarbon yield of 0.9% and a propionic acid yield of 6.3% was achieved in oxidation coupled with 3 hours of photoreaction. In situ spectroscopic studies confirm a dual role of atomic Pd species: an electron acceptor to boost charge separation/transfer for efficient photoredox, and a mediator to stabilize reaction intermediates for selective decarboxylation.

4.
Nat Commun ; 14(1): 5842, 2023 Sep 20.
Artigo em Inglês | MEDLINE | ID: mdl-37730706

RESUMO

Renewable energy-based electrocatalytic oxidation of organic nucleophiles (e.g.methanol, urea, and amine) are more thermodynamically favourable and, economically attractive to replace conventional pure water electrooxidation in electrolyser to produce hydrogen. However, it is challenging due to the competitive oxygen evolution reaction under a high current density (e.g., >300 mA cm-2), which reduces the anode electrocatalyst's activity and stability. Herein, taking lower energy cost urea electrooxidation reaction as the model reaction, we developed oxyanion-engineered Nickel catalysts to inhibit competing oxygen evolution reaction during urea oxidation reaction, achieving an ultrahigh 323.4 mA cm-2 current density at 1.65 V with 99.3 ± 0.4% selectivity of N-products. In situ spectra studies reveal that such in situ generated oxyanions not only inhibit OH- adsorption and guarantee high coverage of urea reactant on active sites to avoid oxygen evolution reaction, but also accelerate urea's C - N bond cleavage to form CNO - intermediates for facilitating urea oxidation reaction. Accordingly, a comprehensive mechanism for competitive adsorption behaviour between OH- and urea to boost urea electrooxidation and dynamic change of Ni active sites during urea oxidation reaction was proposed. This work presents a feasible route for high-efficiency urea electrooxidation reaction and even various electrooxidation reactions in practical applications.

5.
J Hepatocell Carcinoma ; 10: 1143-1156, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37492267

RESUMO

Objective: To determine the preoperative clinicoradiological factors to predict microvascular invasion (MVI) in patients with resectable multinodular hepatocellular carcinoma (mHCC), and further to establish and validate a stratified risk scoring system. Methods: Two hundred and seventy-three patients with pathologically confirmed mHCC (≥2 lesions) without major vascular invasion and biliary tract tumor thrombosis, who underwent preoperative contrast-enhanced MRI and hepatectomy, were consecutively enrolled (training/validation cohort=193/80). Preoperative clinicoradiological variables were collected and analyzed. The multivariable logistic regression was performed to determine the independent predictors of MVI and create a risk score system. The C-index, calibration curve and decision curve were used to evaluate the performance of the risk score. A risk score-based prognostic stratification system was performed in mHCC patients. The risk score system was further verified in the validation cohort. Results: AFP > 400 ng/mL, presence of satellite nodule, mosaic architecture and increased total tumor diameter were independent predictors of MVI while fat in mass was an independent protective factor of MVI. The risk score yielded satisfactory C-index values (training/validation cohort: 0.777/0.758) and fitted well in calibration curves. Decision curve analysis further confirmed its clinical utility. Based on the risk score, mHCC patients were stratified into high-/low-MVI-risk subgroups with significantly different recurrence-free survival (both P < 0.001). Conclusion: The presented risk score incorporating clinicoradiological parameters could stratify mHCC patients into high-risk and low-risk subgroups and predict prognosis in patients with resectable mHCC.

6.
J Am Chem Soc ; 145(28): 15565-15571, 2023 Jul 19.
Artigo em Inglês | MEDLINE | ID: mdl-37395649

RESUMO

Ethylene oxidation to oxygenates via electrocatalysis is practically promising because of less energy input and CO2 output compared with traditional thermal catalysis. However, current ethylene electrooxidation reaction (EOR) is limited to alkaline and neutral electrolytes to produce acetaldehyde and ethylene glycol, significantly limiting cell energy efficiency. Here, we report for the first time an EOR to 2-chloroethanol product in a strongly acidic environment with natural seawater as an electrolyte. We demonstrate a 2-chloroethanol Faradaic efficiency (FE) of ∼70% with a low electrical energy consumption of ∼1.52 × 10-3 kWh g-1 over a commercial Pd catalyst. We establish a mechanism to evidence that 2-chloroethanol is produced at low potentials via direct interaction of adsorbed chloride anions (*Cl) with ethylene reactant because of the high coverage of *Cl during reaction. Importantly, this differs from the accepted multiple step mechanism of subsequent chlorine oxidation and ethylene chlorination reactions at high potentials. With highly active Cl- participation, the production rate for 2-chloroethanol in acidic seawater is a high 26.3 g m-2 h-1 at 1.6 V operation. Significantly, we show that this is 223 times greater than that for ethylene glycol generation in acidic freshwater. We demonstrate chloride-participated EOR in a proton exchange membrane electrolyzer that exhibits a 68% FE for 2-chloroethanol at 2.2 V operation in acidic seawater. This new understanding can be used for designing selective anode oxidation reactions in seawater under mild conditions.

7.
J Hepatocell Carcinoma ; 10: 169-180, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36789251

RESUMO

Objective: To compare the pathologic diagnosis and survival of patients with subcentimeter and 1-2 cm nodules that present with diagnostic hallmarks of hepatocellular carcinoma (HCC). Methods: Diagnostic hallmarks of HCC were defined as hyperintensity on T2 weighted imaging, restricted diffusion, arterial phase hyperenhancement, washout on portal venous phase, and hypointensity on hepatobiliary phase. We retrospectively included 139 patients undergoing curative resection with single nodules ≤2 cm that present imaging features described above on gadoxetic acid-enhanced MRI. The final diagnosis was confirmed by histopathological assessment. Recurrence-free survival (RFS) was compared using Kaplan-Meier analysis with the Log-rank test. Factors associated with overall and early recurrence were identified using Cox regression analysis. Results: Among 139 nodules (49 nodules <1 cm), there was no significant difference in the percentage of HCC between subcentimeter and 1-2 cm nodules (94.0% vs 94.4%, P > 0.999). Microvascular invasion (MVI) was less common in subcentimeter HCC (4.3% vs 17.6%, P = 0.032). There were 27 recurrences during a median follow-up time of 46.7 months. Patients with subcentimeter HCC achieved less recurrence, with a 5-year RFS rate of 87.3%. The MVI-positive patients had more early and overall recurrence. A tumor size <1 cm was associated with lower overall recurrence (HR, 0.336; P = 0.047). No factors were independently associated with early recurrence. Conclusion: Subcentimeter nodules with diagnostic hallmarks of HCC are highly associated with HCC diagnosis and achieve less tumor recurrence after resection. Early diagnosis and treatment of subcentimeter HCC may be more appropriate.

8.
Orthop Surg ; 14(7): 1378-1384, 2022 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-35656705

RESUMO

OBJECTIVE: To establish a digital model of the ankle joint through 3D imaging technology and explore the preoperative placement of ankle replacement prostheses. METHODS: Computed tomography images of intact ankle joints from 54 cases in the outpatient and inpatient departments of our hospital were collected; according to the INBONE® total ankle system surgery process, the surgery model and surgical osteotomy were finished using MIMICS based on computer simulation method. The shortest distance was measured between the center point and the anterior, posterior, medial, and lateral, respectively, to ensure the precise position of the ankle replacement prosthesis by digital simulation surgery. The relationship between the two variables was analyzed by bivariate correlation analysis. RESULTS: The dataset of this study included 48 cases of the sub-data set (26 males and 22 females) and included 27 cases of left ankle and 21 cases of right ankle. The average medial malleolar angle was 18.67°± 2.87°, the average amount of bone resection was 12.13 ± 1.86 cm3 , the mid-anterior distance was 1.72 ± 0.19 cm, the mid-posterior distance was 2.00 ± 0.19 cm, the ratio of mid-anterior to mid-posterior was 0.87, the mid-medial distance was 1.26 ± 0.17 cm, the mid-lateral distance was 1.19 ± 0.16 cm, and the ratio of mid-medial to mid-lateral was 1.06. After osteotomy, the anteroposterior diameter was 3.73 ± 0.32 cm, the transverse diameter was 2.46 ± 0.27 cm, and the ratio of anteroposterior diameter to transverse diameter was 1.53. In the bottom view, the shape after osteotomy is rectangular. The mid-anterior distance was strongly negatively correlated with age, the mid-anterior distance and the amount of bone resection, the mid-medial distance and the amount of bone resection, the mid-lateral distance and the amount of bone resection, the mid-lateral distance and the anteroposterior diameter, the anteroposterior diameter and the transverse diameter were all strongly positively correlated. CONCLUSION: The projection point of the lower tibia centerline on the tibial horizontal osteotomy surface is located at a position slightly anterior to the midpoint of the transverse diameter after ankle arthroplasty. The rational positioning of the total ankle replacement is located at both a position slightly anterior to the midpoint of the transverse diameter and midpoint of the anteroposterior diameter, which can be used as a reference method before total ankle arthroplasty surgery.


Assuntos
Artroplastia de Substituição do Tornozelo , Articulação do Tornozelo/diagnóstico por imagem , Articulação do Tornozelo/cirurgia , Artroplastia de Substituição do Tornozelo/métodos , Simulação por Computador , Feminino , Humanos , Masculino , Osteotomia/métodos , Tíbia/cirurgia
9.
Drug Deliv ; 29(1): 1312-1325, 2022 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-35475384

RESUMO

Photothermal therapy (PTT) has become one of the most promising therapies in cancer treatment as its noninvasiveness, high selectivity, and favorable compliance in clinic. However, tumor thermotolerance and distal metastasis reduce its efficacy, becoming the bottleneck of applying PTT in clinic. In this study, a chidamide-loaded magnetic polypyrrole nanocomposite (CMPP) has been fabricated as a visualized cancer photothermal agent (PTA) to counter tumor thermotolerance and metastasis. The efficacy of CMPP was characterized by in vitro and in vivo assays. As a result, this kind of magnetic polypyrrole nanocomposites were black spherical nanoparticles, possessing a favorable photothermal effect and the suitable particle size of 176.97 ± 1.45 nm with a chidamide loading rate of 12.92 ± 0.45%. Besides, comparing with PTT, CMPP exhibited significantly higher cytotoxicity and cellular apoptosis rate in two tumor cell lines (B16-F10 and HepG2). In vivo study, the mice showed obvious near-infrared (NIR) and magnetic resonance imaging (MRI) dual-modal imaging at tumor sites and sentinel lymph nodes (SLNs); on the other hand, magnetic targeting guided CMPP achieved a cure level on melanoma-bearing mice through preventing metastasis and thermotolerance. Overall, with high loading efficiency of chidamide and strong magnetic targeting to tumor sites and SLNs, CMPP could significantly raise efficiency of PTT by targeting tumor thermotolerance and metastasis, and this strategy may be exploited therapeutically to upgrade PTT with MPP as one of appropriate carriers for histone deacetylase inhibitors (HDACis).


Assuntos
Neoplasias , Termotolerância , Aminopiridinas , Animais , Benzamidas , Imageamento por Ressonância Magnética/métodos , Camundongos , Neoplasias/tratamento farmacológico , Fototerapia , Terapia Fototérmica , Polímeros/química , Pirróis
10.
Front Bioeng Biotechnol ; 10: 839756, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35237584

RESUMO

Programmed cell death protein 1 (PD-1) expression is considered a prognostic marker of tumor response to the immuno-blocking therapy. In this study, nivolumab was conjugated with diethylenetriamine pentaacetate (DTPA) via condensation reaction between amidogen and p-SCN-Bn-DTPA, which provided labeling sites for 99mTc4+ or Gd3+ ions. SPECT and magnetic resonance T1 weighted imaging (T1WI) analyses were performed on mouse models of colorectal carcinoma expressing humanized PD-1 antigen. Furthermore, PD-1 expression in intestinal tracks was assessed by immunohistochemistry, and then compared with the imageological findings. Nivolumab-DTPA was synthesized with varying molar ratios and was labeled with Gd or 99mTc with a chemical purity of 96.28 ± 1.16% and good stability. In SPECT images, lesions with high 99mTc-DTPA-nivolumab uptake and relatively clear background were shown at 6 h. Thereafter, the suspected intestinal thickening in Gd-free T1WI was observed at 2 h after the addition of Gd-DTPA-nivolumab. Notably, the results of both SPECT and T1WI analyses were consistent with the postmortem examination and immunohistochemistry results (for linear correlation with target to non-target ratios, R 2 = 0.8038, p < 0.05). In conclusion, nivolumab-DTPA could act as a probe precursor for identifying PD-1-positive lesions, not only through integrating the advantages of immunohistochemistry and molecular imaging but also by providing a noninvasive method for monitoring systemic changes.

11.
J Magn Reson Imaging ; 56(4): 1009-1017, 2022 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-35119776

RESUMO

BACKGROUND: Recently, a prototype 5.0 T whole-body MRI scanner was developed. A 5.0 T diffusion-weighted imaging (DWI) may help overcome the issues that limit 3.0 T DWI. PURPOSE: To evaluate the feasibility of 5.0 T high-field DWI in the upper abdomen and assess the agreement of the apparent diffusion coefficient (ADC) with that from 3.0 T abdominal DWI. STUDY TYPE: Prospective proof of concept. POPULATION: Nine volunteers (mean ± SD age: 37.3 ± 7.0 years, 8 M), eight healthy and one with liver and kidney cysts. FIELD STRENGTH/SEQUENCE: 3.0 T and 5.0 T; respiratory-triggered spin-echo echo-planar-imaging (SE-EPI)-based DWI sequence. ASSESSMENT: Subjective image quality scores. The ADC values in abdominal organs (liver, pancreas, spleen, and kidney) were measured by two observers for evaluating the interobserver and interfield agreement. STATISTICAL TESTS: Wilcoxon-rank sum test, Bland-Altman analysis, intraclass correlation coefficients (ICCs), and coefficients of variation (CVs). RESULTS: The 5.0 T DWI displayed an increase in subjective image quality score compared to 3.0 T DWI without the significant difference (3.0 T DWI: 3.50 ± 0.47, 5.0 T DWI: 3.72 ± 0.42, P = 0.157). Both the interfield and interobserver agreements of ADC values were substantial to excellent (ICCs = 0.640-0.902). For all four upper abdominal organs, there were no significant differences between the ADC values measured by two observers and between the ADC values of 3.0 T and 5.0 T DWI (P = 0.134-1.000). The CVs of ADC measurements from 3.0 T and 5.0 T DWI were all less than 15.0% (6.7%-14.2%). DATA CONCLUSION: The substantial to excellent agreements between the ADC values measured with 3.0 T and 5.0 T DWI for liver, pancreas, spleen, and kidney suggested that 5.0 T DWI can be applied for abdominal imaging. The ADC values from 5.0 T abdominal DWI hold the potential to serve as the quantitative markers for clinical investigations. EVIDENCE LEVEL: 2 TECHNICAL EFFICACY: Stage 1.


Assuntos
Imagem de Difusão por Ressonância Magnética , Imagem Ecoplanar , Abdome/diagnóstico por imagem , Adulto , Imagem de Difusão por Ressonância Magnética/métodos , Imagem Ecoplanar/métodos , Humanos , Imageamento por Ressonância Magnética , Estudos Prospectivos , Reprodutibilidade dos Testes
12.
J Int Med Res ; 49(10): 3000605211050781, 2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-34666530

RESUMO

OBJECTIVE: Kashin-Beck disease (KBD) is an endemic degenerative joint disease with a high disability rate. We retrospectively evaluated the 18-year clinical follow-up outcomes of adult patients with KBD who underwent arthroscopic debridement for knee osteoarthritis. METHODS: Thirty-one patients with KBD (31 knees) underwent arthroscopy for knee osteoarthritis. The visual analog scale (VAS) score, walking distance, knee mobility, and patients' self-evaluated improvement in clinical symptoms were retrospectively evaluated before and 18 years after the operation. RESULTS: The patients' self-evaluated clinical symptoms showed considerable improvement at 2, 6, and 8 years after surgery but deteriorated at 10 and 18 years after surgery. Knee mobility was greater after than before arthroscopy but decreased from 6 to 18 years postoperatively. The VAS score for knee pain was high before the operation, decreased at 2 years postoperatively, increased at 6 years postoperatively, and was significantly lower at 18 years postoperatively than before surgery. The walking distance was significantly longer at 2, 6, and 8 years postoperatively than preoperatively. CONCLUSIONS: Arthroscopic treatment may be an effective therapy for adult patients with KBD who develop knee osteoarthritis. In this study, arthroscopy had a long-term effect on patients with KBD who had Kellgren-Lawrence grade

Assuntos
Doença de Kashin-Bek , Osteoartrite do Joelho , Adulto , Artroscopia , Desbridamento , Seguimentos , Humanos , Doença de Kashin-Bek/cirurgia , Osteoartrite do Joelho/cirurgia , Estudos Retrospectivos , Resultado do Tratamento
14.
J Cell Mol Med ; 25(18): 8775-8788, 2021 09.
Artigo em Inglês | MEDLINE | ID: mdl-34337860

RESUMO

Artesunate is a widely used derivative of artemisinin for malaria. Recent researches have shown that artesunate has a significant anti-inflammatory effect on many diseases. However, its effect on acute kidney injury with a significant inflammatory response is not clear. In this study, we established a cisplatin-induced AKI mouse model and a co-culture system of BMDM and tubular epithelial cells (mTEC) to verify the renoprotective and anti-inflammatory effects of artesunate on AKI, and explored the underlying mechanism. We found that artesunate strongly down-regulated the serum creatinine and BUN levels in AKI mice, reduced the necroptosis of tubular cells and down-regulated the expression of the tubular injury molecule Tim-1. On the other hand, artesunate strongly inhibited the mRNA expression of inflammatory cytokines (IL-1ß, IL-6 and TNF-α), protein levels of inflammatory signals (iNOS and NF-κB) and necroptosis signals (RIPK1, RIPK3 and MLKL) in kidney of AKI mouse. Notably, the co-culture system proved that Mincle in macrophage can aggravate the inflammation and necroptosis of mTEC induced by LPS, and artesunate suppressed the expression of Mincle in macrophage of kidney in AKI mouse. Overexpression of Mincle in BMDM restored the damage and necroptosis inhibited by artesunate in mTEC, indicating Mincle in macrophage is the target of artesunate to protect tubule cells in AKI. Our findings demonstrated that artesunate can significantly improve renal function in AKI, which may be related to the inhibition of Mincle-mediated macrophage inflammation, thereby reducing the damage and necroptosis to tubular cells that provide new option for the treatment of AKI.


Assuntos
Injúria Renal Aguda/tratamento farmacológico , Anti-Inflamatórios/farmacologia , Artesunato/farmacologia , Inflamação/tratamento farmacológico , Necroptose/efeitos dos fármacos , Animais , Macrófagos , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Cultura Primária de Células
15.
Front Oncol ; 11: 671333, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34094971

RESUMO

OBJECTIVES: This study constructed and validated a machine learning model to predict CD8+ tumor-infiltrating lymphocyte expression levels in patients with pancreatic ductal adenocarcinoma (PDAC) using computed tomography (CT) radiomic features. MATERIALS AND METHODS: In this retrospective study, 184 PDAC patients were randomly assigned to a training dataset (n =137) and validation dataset (n =47). All patients were divided into CD8+ T-high and -low groups using X-tile plots. A total of 1409 radiomics features were extracted from the segmentation of regions of interest, based on preoperative CT images of each patient. The LASSO algorithm was applied to reduce the dimensionality of the data and select features. The extreme gradient boosting classifier (XGBoost) was developed using a training set consisting of 137 consecutive patients admitted between January 2017 and December 2017. The model was validated in 47 consecutive patients admitted between January 2018 and April 2018. The performance of the XGBoost classifier was determined by its discriminative ability, calibration, and clinical usefulness. RESULTS: The cut-off value of the CD8+ T-cell level was 18.69%, as determined by the X-tile program. A Kaplan-Meier analysis indicated a correlation between higher CD8+ T-cell levels and better overall survival (p = 0.001). The XGBoost classifier showed good discrimination in the training set (area under curve [AUC], 0.75; 95% confidence interval [CI]: 0.67-0.83) and validation set (AUC, 0.67; 95% CI: 0.51-0.83). Moreover, it showed a good calibration. The sensitivity, specificity, accuracy, positive and negative predictive values were 80.65%, 60.00%, 0.69, 0.63, and 0.79, respectively, for the training set, and 80.95%, 57.69%, 0.68, 0.61, and 0.79, respectively, for the validation set. CONCLUSIONS: We developed a CT-based XGBoost classifier to extrapolate the infiltration levels of CD8+ T-cells in patients with PDAC. This method could be useful in identifying potential patients who can benefit from immunotherapies.

16.
Angew Chem Int Ed Engl ; 60(35): 19079-19084, 2021 Aug 23.
Artigo em Inglês | MEDLINE | ID: mdl-34187100

RESUMO

Controlling the chemo- and regioselectivity of transition-metal-catalyzed C-C activation remains a great challenge. The transformations of benzocyclobutenones (BCBs) usually involve the cleavage of C1-C2 bond. In this work, an unprecedented highly selective cleavage of C1-C8 bond with the insertion of alkynes is achieved by using blocking strategy via Ni catalysis, providing an efficient method for synthesis of 1,8-disubstituted naphthalenes. Notably, the blocking group could be readily removed after the transformation.

17.
Adv Mater ; 33(13): e2007508, 2021 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-33624901

RESUMO

Electrocatalytic production of hydrogen from seawater provides a route to low-cost and clean energy conversion. However, the hydrogen evolution reaction (HER) using seawater is greatly hindered by the lack of active and stable catalysts. Herein, an unsaturated nickel surface nitride (Ni-SN@C) catalyst that is active and stable for the HER in alkaline seawater is prepared. It achieves a low overpotential of 23 mV at a current density of 10 mA cm-2 in alkaline seawater electrolyte, which is superior to Pt/C. Compared to conventional transition metal nitrides or metal/metal nitride heterostructures, the Ni-SN@C has no detectable bulk nickel nitride phase. Instead, unsaturated NiN bonding on the surface is present. In situ Raman measurements show that the Ni-SN@C performs like Pt with the ability to generate hydronium ions in a high-pH electrolyte. The catalyst operation is then demonstrated in a two-electrode electrolyzer system, coupling with hydrazine oxidation at the anode. Using this system, a cell voltage of only 0.7 V is required to achieve a current density of 1 A cm-2 .

18.
Chin Med J (Engl) ; 133(22): 2653-2659, 2020 Nov 20.
Artigo em Inglês | MEDLINE | ID: mdl-33009025

RESUMO

BACKGROUND: Liver fibrosis (LF) continues to develop and eventually progresses to cirrhosis. However, LF and early-stage cirrhosis (ESC) can be reversed in some cases, while advanced cirrhosis is almost impossible to cure. Advances in quantitative imaging techniques have made it possible to replace the gold standard biopsy method with non-invasive imaging, such as radiomics. Therefore, the purpose of this study is to develop a radiomics model to identify LF and ESC. METHODS: Patients with LF (n = 108) and ESC (n = 116) were enrolled in this study. As a control, patients with healthy livers were involved in the study (n = 145). Diffusion-weighted imaging (DWI) data sets with three b-values (0, 400, and 800 s/mm) of enrolled cases were collected in this study. Then, radiomics features were extracted from manually delineated volumes of interest. Two modeling strategies were performed after univariate analysis and feature selection. Finally, an optimal model was determined by the receiver operating characteristic area under the curve (AUC). RESULTS: The optimal models were built in plan 1. For model 1 in plan 1, the AUCs of the training and validation cohorts were 0.973 (95% confidence interval [CI] 0.946-1.000) and 0.948 (95% CI 0.903-0.993), respectively. For model 2 in plan 1, the AUCs of the training and validation cohorts were 0.944, 95% CI 0.905 to 0.983, and 0.968, 95% CI 0.940 to 0.996, respectively. CONCLUSIONS: Radiomics analysis of DWI images allows for accurate identification of LF and ESC, and the non-invasive biomarkers extracted from the functional DWI images can serve as a better alternative to biopsy.


Assuntos
Cirrose Hepática , Aprendizado de Máquina , Imagem de Difusão por Ressonância Magnética , Humanos , Cirrose Hepática/diagnóstico por imagem , Curva ROC , Estudos Retrospectivos
19.
Chem Commun (Camb) ; 56(76): 11275-11278, 2020 Sep 24.
Artigo em Inglês | MEDLINE | ID: mdl-32832952

RESUMO

Highly selective CO2 electroreduction to CO (∼90% faradaic efficiency) was achieved on NiCu0.25 bimetallic nanoparticle catalysts. By combining Synchrotron based X-ray absorption and in situ Raman spectroscopy studies, we found that there is a negative correlation between the Cu content in NiCux and CO selectivity due to redistribution of the 3d electrons.

20.
Med Eng Phys ; 81: 30-38, 2020 07.
Artigo em Inglês | MEDLINE | ID: mdl-32505662

RESUMO

There is a large gap between the elastic modulus of the existing femoral stem and the host bone. This gap can lead to long-term complications, such as aseptic loosening and, eventually, a need for revision surgery. The porous metallic biomimetic femoral stem can effectively reduce stress shielding and provide firm implant fixation through bone ingrowth. The purpose of this research is to investigate the application of different porous femoral stems in relieving bone resorption and promoting osseointegration by finite element analysis. We present an intuitive visualization method based on a diamond lattice structure to understand the relationship between pore size, porosity, bone ingrowth criteria and additive manufacturing constraints. We further obtain an admissible design space of diamond lattice structure for porosity selection. We evaluate the relative micromotion of bone-implant interface and bone volume with density loss for three femoral stems with diamond lattice-based homogenous porous structures in admissible design space. We also evaluate porous femoral stems with four different grading orientations along the axial and radial directions of the femoral stem. These include an axial graded femoral stem with a porosity increased distally (DAGS), an axial graded femoral stem with a porosity increased proximally (PAGS), a radial graded femoral stem with a porosity increased inwardly (IRGS), and a radial graded femoral stem with a porosity increased externally (ERGS). The results indicate that: (i) homogenous porous femoral stems with 40% porosity, (ii) DAGS and (iii) IRGS can maintain the relative micromotion of the bone-implant interface in the safety range for bone ingrowth. The calculated volumes of bone with density loss in the cases of DAGS and IRGS are 3.6% and 3.3%, respectively, which are nearly 74% lower than that of fully dense stems. Therefore, DAGS and IRGS have an evident advantage in promoting osseointegration and relieving bone resorption. Thus, the graded femoral stem is more promising than the homogeneous porous stem.


Assuntos
Módulo de Elasticidade , Fêmur , Desenho de Prótese , Artroplastia de Quadril , Fêmur/cirurgia , Prótese de Quadril , Humanos , Movimento (Física) , Osseointegração , Porosidade
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