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1.
Abdom Radiol (NY) ; 2021 Oct 12.
Artigo em Inglês | MEDLINE | ID: mdl-34636931

RESUMO

BACKGROUND: At present, numerous challenges exist in the diagnosis of pancreatic SCNs and MCNs. After the emergence of artificial intelligence (AI), many radiomics research methods have been applied to the identification of pancreatic SCNs and MCNs. PURPOSE: A deep neural network (DNN) model termed Multi-channel-Multiclassifier-Random Forest-ResNet (MMRF-ResNet) was constructed to provide an objective CT imaging basis for differential diagnosis between pancreatic serous cystic neoplasms (SCNs) and mucinous cystic neoplasms (MCNs). MATERIALS AND METHODS: This study is a retrospective analysis of pancreatic unenhanced and enhanced CT images in 63 patients with pancreatic SCNs and 47 patients with MCNs (3 of which were mucinous cystadenocarcinoma) confirmed by pathology from December 2010 to August 2016. Different image segmented methods (single-channel manual outline ROI image and multi-channel image), feature extraction methods (wavelet, LBP, HOG, GLCM, Gabor, ResNet, and AlexNet) and classifiers (KNN, Softmax, Bayes, random forest classifier, and Majority Voting rule method) are used to classify the nature of the lesion in each CT image (SCNs/MCNs). Then, the comparisons of classification results were made based on sensitivity, specificity, precision, accuracy, F1 score, and area under the receiver operating characteristic curve (AUC), with pathological results serving as the gold standard. RESULTS: Multi-channel-ResNet (AUC 0.98) was superior to Manual-ResNet (AUC 0.91).CT image characteristics of lesions extracted by ResNet are more representative than wavelet, LBP, HOG, GLCM, Gabor, and AlexNet. Compared to the use of three classifiers alone and Majority Voting rule method, the use of the MMRF-ResNet model exhibits a better evaluation effect (AUC 0.96) for the classification of the pancreatic SCNs and MCNs. CONCLUSION: The CT image classification model MMRF-ResNet is an effective method to distinguish between pancreatic SCNs and MCNs.

2.
J Pharm Sci ; 2021 Sep 03.
Artigo em Inglês | MEDLINE | ID: mdl-34487745

RESUMO

The commercially available Polysorbate 80 (PS-80) is a highly heterogeneous product. It is a complex and structurally diverse mixture consisting of polymeric species containing polyoxyethylenes (POEs), fatty acid esters, with/or without a carbohydrate core. The core is primarily sorbitan, with some isosorbide and sorbitol. Depending on the sources of fatty acids and the degrees of esterification, multiple combinations of fatty acid esters are commonly observed. A number of POE intermediates, such as polyoxyethylene glycols, POE-sorbitans, POE-isosorbides, and an array of fatty acid esters from these intermediates remain in the raw material as well. The complex composition of PS-80 is difficult to control and poses a significant characterization challenge for its use in the pharmaceutical industry. Here, we present a novel solution for PS-80 characterization using ultra high-performance liquid chromatography coupled with charge-reduction high resolution mass spectrometry. Post column co-infusion of triethylamine focused the signal into mainly singly charged molecular ions and reduced the extent of in-source fragmentation, resulting in a simpler ion map and enhanced measurement of PS-80 species. The data processing workflow is designed to programmatically identify PS-80 component classes and reduce the burden of manually analyzing complex MS data. The 2-dimensional graphical representation of the data helps visualize these features. Together, these innovative methodologies enabled us to analyze components in PS-80 with unprecedented detail and shall be a useful tool to study formulation and stability of pharmaceutical preparations. The power of this approach was demonstrated by comparing the composition of PS-80 obtained from different vendors.

3.
Artigo em Inglês | MEDLINE | ID: mdl-34491920

RESUMO

BACKGROUND: The Skeletal Oncology Research Group machine-learning algorithms (SORG-MLAs) estimate 90-day and 1-year survival in patients with long-bone metastases undergoing surgical treatment and have demonstrated good discriminatory ability on internal validation. However, the performance of a prediction model could potentially vary by race or region, and the SORG-MLA must be externally validated in an Asian cohort. Furthermore, the authors of the original developmental study did not consider the Eastern Cooperative Oncology Group (ECOG) performance status, a survival prognosticator repeatedly validated in other studies, in their algorithms because of missing data. QUESTIONS/PURPOSES: (1) Is the SORG-MLA generalizable to Taiwanese patients for predicting 90-day and 1-year mortality? (2) Is the ECOG score an independent factor associated with 90-day and 1-year mortality while controlling for SORG-MLA predictions? METHODS: All 356 patients who underwent surgery for long-bone metastases between 2014 and 2019 at one tertiary care center in Taiwan were included. Ninety-eight percent (349 of 356) of patients were of Han Chinese descent. The median (range) patient age was 61 years (25 to 95), 52% (184 of 356) were women, and the median BMI was 23 kg/m2 (13 to 39 kg/m2). The most common primary tumors were lung cancer (33% [116 of 356]) and breast cancer (16% [58 of 356]). Fifty-five percent (195 of 356) of patients presented with a complete pathologic fracture. Intramedullary nailing was the most commonly performed type of surgery (59% [210 of 356]), followed by plate screw fixation (23% [81 of 356]) and endoprosthetic reconstruction (18% [65 of 356]). Six patients were lost to follow-up within 90 days; 30 were lost to follow-up within 1 year. Eighty-five percent (301 of 356) of patients were followed until death or for at least 2 years. Survival was 82% (287 of 350) at 90 days and 49% (159 of 326) at 1 year. The model's performance metrics included discrimination (concordance index [c-index]), calibration (intercept and slope), and Brier score. In general, a c-index of 0.5 indicates random guess and a c-index of 0.8 denotes excellent discrimination. Calibration refers to the agreement between the predicted outcomes and the actual outcomes, with a perfect calibration having an intercept of 0 and a slope of 1. The Brier score of a prediction model must be compared with and ideally should be smaller than the score of the null model. A decision curve analysis was then performed for the 90-day and 1-year prediction models to evaluate their net benefit across a range of different threshold probabilities. A multivariate logistic regression analysis was used to evaluate whether the ECOG score was an independent prognosticator while controlling for the SORG-MLA's predictions. We did not perform retraining/recalibration because we were not trying to update the SORG-MLA algorithm in this study. RESULTS: The SORG-MLA had good discriminatory ability at both timepoints, with a c-index of 0.80 (95% confidence interval 0.74 to 0.86) for 90-day survival prediction and a c-index of 0.84 (95% CI 0.80 to 0.89) for 1-year survival prediction. However, the calibration analysis showed that the SORG-MLAs tended to underestimate Taiwanese patients' survival (90-day survival prediction: calibration intercept 0.78 [95% CI 0.46 to 1.10], calibration slope 0.74 [95% CI 0.53 to 0.96]; 1-year survival prediction: calibration intercept 0.75 [95% CI 0.49 to 1.00], calibration slope 1.22 [95% CI 0.95 to 1.49]). The Brier score of the 90-day and 1-year SORG-MLA prediction models was lower than their respective null model (0.12 versus 0.16 for 90-day prediction; 0.16 versus 0.25 for 1-year prediction), indicating good overall performance of SORG-MLAs at these two timepoints. Decision curve analysis showed SORG-MLAs provided net benefits when threshold probabilities ranged from 0.40 to 0.95 for 90-day survival prediction and from 0.15 to 1.0 for 1-year prediction. The ECOG score was an independent factor associated with 90-day mortality (odds ratio 1.94 [95% CI 1.01 to 3.73]) but not 1-year mortality (OR 1.07 [95% CI 0.53 to 2.17]) after controlling for SORG-MLA predictions for 90-day and 1-year survival, respectively. CONCLUSION: SORG-MLAs retained good discriminatory ability in Taiwanese patients with long-bone metastases, although their actual survival time was slightly underestimated. More international validation and incremental value studies that address factors such as the ECOG score are warranted to refine the algorithms, which can be freely accessed online at https://sorg-apps.shinyapps.io/extremitymetssurvival/. LEVEL OF EVIDENCE: Level III, therapeutic study.

4.
PLoS One ; 16(9): e0257816, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34555101

RESUMO

BACKGROUND: Inadvertent intraoperative hypothermia is frequent during open surgeries; however, few studies on hypothermia during laparoscopic abdominal surgery have been reported. We aimed to investigate the incidence and risk factors for hypothermia in patients undergoing laparoscopic abdominal surgery. METHODS: This single-center prospective cohort observational study involved patients undergoing laparoscopic surgery between October 2018 and June 2019. Data on core body temperature and potential variables were collected. A multivariate logistic regression analysis was performed to identify the risk factors associated with hypothermia. A Cox regression analysis was used to verify the sensitivity of the results. RESULTS: In total, 690 patients were included in the analysis, of whom 200 (29.0%, 95% CI: 26%-32%) had a core temperature < 36°C. The core temperature decreased over time, and the incident hypothermia increased gradually. In the multivariate logistic regression analysis, age (OR = 1.017, 95% CI: 1.000-1.034, P = 0.050), BMI (OR = 0.938, 95% CI: 0.880-1.000; P = 0.049), baseline body temperature (OR = 0.025, 95% CI: 0.010-0.060; P < 0.001), volume of irrigation fluids (OR = 1.001, 95% CI: 1.000-1.001, P = 0.001), volume of urine (OR = 1.001, 95% CI: 1.000-1.003, P = 0.070), and duration of surgery (OR = 1.010, 95% CI: 1.006-1.015, P < 0.001) were significantly associated with hypothermia. In the Cox analysis, variables in the final model were age, BMI, baseline body temperature, volume of irrigation fluids, blood loss, and duration of surgery. CONCLUSIONS: Inadvertent intraoperative hypothermia is evident in patients undergoing laparoscopic surgeries. Age, BMI, baseline body temperature, volume of irrigation fluids, and duration of surgery are significantly associated with intraoperative hypothermia.

5.
J Hematol Oncol ; 14(1): 152, 2021 Sep 23.
Artigo em Inglês | MEDLINE | ID: mdl-34556152

RESUMO

Chimeric antigen receptor T-cell (CAR-T) therapy has shown tremendous success in eradicating hematologic malignancies. However, this success has not yet been extrapolated to solid tumors due to the limited infiltration and persistence of CAR-T cells in the tumor microenvironment (TME). In this study, we screened a novel anti-CD70 scFv and generated CD70 CAR-T cells that showed effective antitumor functions against CD70+ renal carcinoma cells (RCCs) both in vitro and in vivo. We further evaluated the effect and explored the molecular mechanism of a PARP inhibitor (PARPi) in CAR-T cell immunotherapy by administering the PARPi to mouse xenografts model derived from human RCC cells. Treatment with the PARPi promoted CAR-T cell infiltration by stimulating a chemokine milieu that promoted CAR-T cell recruitment and the modulation of immunosuppression in the TME. Moreover, our data demonstrate that PARPi modulates the TME by activating the cGAS-STING pathway, thereby altering the balance of immunostimulatory signaling and enabling low-dose CAR-T cell treatment to induce effective tumor regression. These data demonstrate the application of CD70 CAR-T cell therapeutic strategies for RCC and the cross-talk between targeting DNA damage responses and antitumor CAR-T cell therapy. These findings provide insight into the mechanisms of PARPis in CAR-T cell therapy for RCC and suggest a promising adjuvant therapeutic strategy for CAR-T cell therapy in solid tumors.

6.
Carbohydr Polym ; 273: 118607, 2021 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-34561006

RESUMO

Injectable hydrogels have shown therapeutic effects on wound repair, but most of them exhibit poor mechanical strength. The impacts of stiff injectable hydrogels on cell behavior and wound healing remain unclear. Herein, an injectable hydrogel was developed based on thiolated poly(γ-glutamic acid) (γ-PGA-SH) and glycidyl methacrylate-conjuated oxidized hyaluronic acid (OHA-GMA). Thiol-methacrylate Michael chemistry-mediated post-stabilization and increase of polymer concentration were found to improve the mechanical strength of γ-PGA-SH/OHA-GMA hydrogel. Moreover, in vitro studies confirmed its biodegradability, biocompatibility, and self-healing property. Using the mechanically-tunable hydrogel, it further showed that fibroblasts migrated faster on the surface of stiffer hydrogel, but infiltrated slowly inside it compared with softer hydrogel. In animal experiments, the injectable hydrogel could promote wound healing by increasing collagen deposition and vascularization. In summary, γ-PGA-SH/OHA-GMA hydrogel is able to regulate migration and infiltration of fibroblasts by altering stiffness and offers effective in situ forming scaffolds towards skin tissue regeneration.

7.
World J Gastroenterol ; 27(32): 5404-5423, 2021 Aug 28.
Artigo em Inglês | MEDLINE | ID: mdl-34539141

RESUMO

BACKGROUND: Intestinal barrier breakdown, a frequent complication of intestinal ischemia-reperfusion (I/R) including dysfunction and the structure changes of the intestine, is characterized by a loss of tight junction and enhanced permeability of the intestinal barrier and increased mortality. To develop effective and novel therapeutics is important for the improvement of outcome of patients with intestinal barrier deterioration. Recombinant human angiopoietin-like protein 4 (rhANGPTL4) is reported to protect the blood-brain barrier when administered exogenously, and endogenous ANGPTL4 deficiency deteriorates radiation-induced intestinal injury. AIM: To identify whether rhANGPTL4 may protect intestinal barrier breakdown induced by I/R. METHODS: Intestinal I/R injury was elicited through clamping the superior mesenteric artery for 60 min followed by 240 min reperfusion. Intestinal epithelial (Caco-2) cells and human umbilical vein endothelial cells were challenged by hypoxia/ reoxygenation to mimic I/R in vitro. RESULTS: Indicators including fluorescein isothiocyanate-conjugated dextran (4 kilodaltons; FD-4) clearance, ratio of phosphorylated myosin light chain/total myosin light chain, myosin light chain kinase and loss of zonula occludens-1, claudin-2 and VE-cadherin were significantly increased after intestinal I/R or cell hypoxia/reoxygenation. rhANGPTL4 treatment significantly reversed these indicators, which were associated with inhibiting the inflammatory and oxidative cascade, excessive activation of cellular autophagy and apoptosis and improvement of survival rate. Similar results were observed in vitro when cells were challenged by hypoxia/reoxygenation, whereas rhANGPTL4 reversed the indicators close to normal level in Caco-2 cells and human umbilical vein endothelial cells significantly. CONCLUSION: rhANGPTL4 can function as a protective agent against intestinal injury induced by intestinal I/R and improve survival via maintenance of intestinal barrier structure and functions.


Assuntos
Proteína 4 Semelhante a Angiopoietina/farmacologia , Intestinos , Traumatismo por Reperfusão , Células CACO-2 , Células Endoteliais da Veia Umbilical Humana , Humanos , Mucosa Intestinal , Proteínas Recombinantes/farmacologia , Traumatismo por Reperfusão/prevenção & controle
8.
J Am Chem Soc ; 2021 Sep 23.
Artigo em Inglês | MEDLINE | ID: mdl-34553913

RESUMO

Understanding the chemical behavior of actinide elements is essential for the effective management and use of actinide materials. In this study, we report an unprecedented η2 (side-on) coordination of U by a cyanide in a UCN cluster, which was stabilized inside a C82 fullerene cage. UCN@Cs(6)-C82 was successfully synthesized and fully characterized by mass spectrometry, single crystal X-ray crystallography, cyclic voltammetry, spectroscopy, and theoretical calculations. The bonding analysis demonstrates significant donation bonding between CN- and uranium, and covalent interactions between uranium and the carbon cage. These effects correlate with an observed elongated cyanide C-N bond, resulting in a rare case where the oxidation state of uranium shows ambiguity between U(III) and U(I). The discovery of this unprecedented triangular configuration of the uranium cyanide cluster provides a new insight in coordination chemistry and highlights the large variety of bonding situations that uranium can have.

9.
J Am Chem Soc ; 143(37): 15309-15318, 2021 Sep 22.
Artigo em Inglês | MEDLINE | ID: mdl-34516733

RESUMO

Endohedral mono-metallofullerenes are the prototypes to understand the fundamental nature and the unique interactions between the encapsulated metals and the fullerene cages. Herein, we report the crystallographic characterizations of four new U-based mono-metallofullerenes, namely, U@Cs(6)-C82, U@C2(8)-C84, U@Cs(15)-C84, and U@C1(12)-C86, among which the chiral cages C2(8)-C84 and C1(12)-C86 have never been previously reported for either endohedral or empty fullerenes. Symmetrical patterns, such as indacene, sumanene, and phenalene, and charge transfer are found to determine the metal positions inside the fullerene cages. In addition, a new finding concerning the metal positions inside the cages reveals that the encapsulated metal ions are always located on symmetry planes of the fullerene cages, as long as the fullerene cages possess mirror planes. DFT calculations show that the metal-fullerene motif interaction determines the stability of the metal position. In fullerenes containing symmetry planes, the metal prefers to occupy a symmetrical arrangement with respect to the interacting motifs, which share one of their symmetry planes with the fullerene. In all computationally analyzed fullerenes containing at least one symmetry plane, the actinide was found to be located on the mirror plane. This finding provides new insights into the nature of metal-cage interactions and gives new guidelines for structural determinations using crystallographic and theoretical methods.

10.
J Invest Dermatol ; 141(10): 2313-2319.e1, 2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-34560913

RESUMO

Circular RNAs (circRNAs) are a unique class of covalently closed, single-stranded RNAs. High-throughput sequencing has uncovered the abundance and complexity of circRNAs. Changes in levels of circRNAs correlate with diverse disease states, including many skin diseases. CircRNAs can function as microRNA inhibitors, protein interactors, or mRNAs. Although circRNAs do have unique topological features, they share many similarities, including primary sequence, with their linear orthologs, so carefully controlled experiments are required to detect and study them. Here, we summarize some protocols used in the identification, validation, and characterization of circRNAs. We also discuss ways to repress and overexpress specific circRNAs to assess potential unique functions for these molecules. These techniques may be useful in exploring how circRNAs contribute to skin disease.

11.
J Int Med Res ; 49(9): 3000605211045540, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-34590915

RESUMO

OBJECTIVE: Esophagectomy is a high-risk surgical procedure with significant postoperative morbidity and mortality. This study aimed to investigate the risk factors of cervical anastomotic leakage and postoperative mortality. METHODS: In this retrospective, observational study, we recruited 1010 patients with esophageal cancer. Cox regression analysis was performed to identify factors affecting anastomotic leakage and postoperative mortality. After propensity score matching, the Kaplan-Meier curve was used to evaluate the effect of leakage on postoperative mortality. RESULTS: The number of patients with cervical anastomotic leakage, in-hospital mortality, 30-day postoperative mortality, and 60-day postoperative mortality was 194 (19.2%), 13 (1.3%), 12 (1.2%), and 16 (1.6%), respectively. The total length of hospital stay and hospital stay postoperatively were 29.7 ± 21.1 and 21.3 ± 20.3 days, respectively. Diabetes, stage IV, and an upper thoracic tumor were significant risk factors for leakage. Leakage and diabetes were significant risk factors for postoperative mortality. After propensity score matching, leakage also significantly affected postoperative mortality. CONCLUSIONS: Patients with tumors in the upper thoracic segment of the esophagus may be more prone to developing anastomotic leakage compared with those with tumors in the middle or lower thoracic segment. Anastomotic leakage may prolong the length of hospital stay and increase postoperative mortality.


Assuntos
Fístula Anastomótica , Neoplasias Esofágicas , Fístula Anastomótica/etiologia , Neoplasias Esofágicas/cirurgia , Esofagectomia/efeitos adversos , Humanos , Estudos Retrospectivos
12.
Anal Chem ; 93(39): 13334-13341, 2021 10 05.
Artigo em Inglês | MEDLINE | ID: mdl-34553919

RESUMO

Herein, a versatile ECL biosensor was fabricated for ultrasensitive detection of microRNA-21 (miRNA-21) from cancer cells based on a novel H2O2-free electrochemiluminescence (ECL) system (luminol/dissolved oxygen/Fe@Fe2O3 nanowires). Compared with the previously reported coreaction accelerator that needed a negative potential to produce reactive oxygen species (ROS), these newly discovered Fe@Fe2O3 nanowires could generate ROS in the detection solution immediately without the application of voltage, which narrowed down the detection potential range to avoid side reactions, favoring their practical application in biological systems. Especially, the Fe@Fe2O3 nanowires could produce H• for activating dissolved oxygen into ROS to improve the ECL intensity dramatically, which initiates a novel pathway to promote the generation of ROS for the ECL system. In addition, an original strand displacement amplification coupled with strand displacement reaction (SDA-SDR) was developed to improve the conversion efficiency of the target for sensitive detection of miRNA-21. By virtue of the SDR, a quadruple quenching effect was achieved through each output DNA strand of SDA; hence, the nucleic acid signal amplification efficiency was effectively enhanced. As expected, on account of the superb activation performance of Fe@Fe2O3 nanowires and the outstanding amplification efficiency of the SDR-SDA strategy, the fabricated ECL biosensor realized ultrasensitive detection of miRNA-21 with a detection limit down to 52.5 aM. The established ECL sensing platform ushered a new route for H2O2-free detection and a promising biomarker assay method for clinical diagnosis.


Assuntos
MicroRNAs , Nanofios , Luminol , Oxigênio
13.
Diagn Interv Radiol ; 27(5): 587-594, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-34559047

RESUMO

PURPOSE: The present work aims to evaluate whether dynamic contrast-enhanced magnetic resonance Imaging (DCE-MRI) can monitor non-invasively the blocking effect on microvessels of the Combretastatin-A4-phosphate (CA4P) and assess the therapeutic efficacy. METHODS: Forty rabbits were implanted the VX2 tumors specimens. Two weeks later, serial MRI (T1 weighted image, T2 weighted image and DCE) were performed at 0 h, 4 h, 24 h, 3 d and 7 d after CA4P (10 mg/kg) or saline treatment. The parameters of DCE (Ktrans, Kep, Ve and iAUC60) of enhancement tumor portions were measured. Then all the tumor samples were stained to count microvessel density (MVD). At last, two-way repeated measures ANOVA was used to analyze the difference between and within groups. The correlation between the Ktrans, Kep, Ve, iAUC60 and MVD was analyzed by using the Pearson correlation analysis and Spearman's rank correlation. RESULTS: The Ktrans and iAUC60 in the CA4P group were lower than the values of the control group at 4 h after treatment, which have significant differences (D-value: -0.133 min-1, 95%CI: -0.169~-0.097 min-1,F = 59.109, p < 0.001 for Ktrans; D-value: -10.533 mmol/sec, 95%CI: -17.147~-3.919 mmol/sec,F = 11.110, and p = 0.003 for iAUC60). In the CA4P group, the Ktrans and iAUC60 reached the minimum values at 4 h. There were significant differences between 4 h and other different time points of the Ktrans and iAUC60 in the treatment group (all p < 0.01). The parameters Ktrans (r = 0.532, P = 0.016 and r = 0.681, P = 0.001, respectively) and iAUC60 (r = 0.580, P = 0.007 and r = 0.568, P = 0.009, respectively) of 7 days showed correlation with MVD in both groups, while Kep and Ve did not show correlation with MVD (P > 0.05). CONCLUSION: The blocking effect of microvessels after CA4P treatment can be evaluated by DCE-MRI, and the parameters of quantitative Ktrans and semi- quantitative iAUC60 can assess the change of the tumor angiogenesis noninvasively.


Assuntos
Meios de Contraste , Neoplasias Hepáticas , Animais , Imageamento por Ressonância Magnética , Microvasos/diagnóstico por imagem , Neovascularização Patológica , Coelhos
14.
Inorg Chem ; 60(19): 14810-14819, 2021 Oct 04.
Artigo em Inglês | MEDLINE | ID: mdl-34546744

RESUMO

Three tris-heteroleptic mononuclear Ru(II) complexes with dual fluorescence and phosphorescence-[Ru(dpma)(bpy)(phen)]2+ (12+), [Ru(dpma)(bpy)(dppz)]2+ (22+), and [Ru(dpma)(phen)(dppz)]2+ (32+)-have been designed and used as ratiometric light-response probes for DNA, where dpma is di(pyrid-2-yl)(methyl)-amine, bpy is 2,2'-bipyridine, phen is 1,10-phenanthroline, and dppz is dipyridophenazine, respectively. Single crystals of complex 2(PF6)2 have been obtained and studied by X-ray analysis. The interactions of these complexes with different DNAs are investigated by means of spectroscopic methods, viscosity measurements, and molecular modeling. In the presence of calf thymus DNA, complexes 2(PF6)2 and 3(PF6)2 show the emergence of a new lower-energy phosphorescence emission band; meanwhile, the higher-energy fluorescence emission band is essentially unchanged, functioning as an intrinsic internal reference. These two complexes exhibit stronger preference for calf thymus DNA over single-strand DNA (d(A)16 and d(C)16). In contrast, no binding interaction between 1(PF6)2 and calf thymus DNA is observed. The intrinsic binding constants (Kb) of 2(PF6)2 and 3(PF6)2 with calf thymus DNA are determined to be (1.4 ± 0.4) × 105 and (9.5 ± 0.15) × 104 M-1, respectively. In addition, these spectroscopic results are compared with those of the prototype complex [Ru(bpy)2(dppz)]2+ (42+), and density functional theory and time-dependent density functional theory calculations are employed to elucidate these experimental findings.


Assuntos
Complexos de Coordenação/química , DNA/química , Rutênio/química , Animais , Bovinos , Estrutura Molecular
15.
Sci China Mater ; : 1-9, 2021 Aug 12.
Artigo em Inglês | MEDLINE | ID: mdl-34413988

RESUMO

Although conventional suturing techniques are commonly used in assisting wound closure, they do pose limited conduciveness and may lead to secondary injury to wound tissues. Inspired by marine organism mussels, we designed and manufactured a bio-inspired hydrogel-based bandage with tough wet tissue adhesion to substitute traditional surgical suture, accelerate wound healing and avoid infection. Poly(γ-glutamic acid) was modified with 3,4-dihydroxyphenylalanine and glycidyl methacylate, then introduced into the acrylic acid-co-acrylamide hydrogel matrix with robust mechanical properties. The hydrogel bandage showed strong chemical linkage adhesion (70 ± 2.1 kPa), which is 2.8 times that of commercial tissue adhesive fibrin glue (25 ± 2.2 kPa). The hydrogel bandage can not only maintain the self-stability, but is also capable of self-tuning adhesive strength in the range of 14-70 kPa to achieve different adhesion effects by tuning constituent ratio. The bandage has desirable compression properties (0.7 ± 0.11 MPa) and tensile elongation (about 25 times), which ensures its resistance to damages, especially in joint spaces. Secondly, the bandage was endowed with antioxidant and endogenous broad-spectrum antibacterial properties with its catechol structure. Results also demonstrated excellent cell compatibility and blood compatibility, certifying its eligible biological safety profile. In a rat full-thickness cutaneous deficiency model, we can clearly observe that the bandage possesses the ability to promote wound healing (only need 6 days). Above all, this research provides a new strategy for the emergency treatment of liver hemostasis and myocardial repair during disaster rescue. Supplementary information: Experimental details and supporting data are available in the online version of the paper10.1007/s40843-021-1724-8.

16.
Carbohydr Polym ; 270: 118330, 2021 Oct 15.
Artigo em Inglês | MEDLINE | ID: mdl-34364592

RESUMO

Based on the gradient distribution of structure and composition in biological cartilage tissue, we designed a gradient hydrogel scaffold by the moving photomask, using chondroitin sulfate and poly (γ-glutamic acid) as crude materials. The hydrogel scaffold had a gradient distribution of cross-linking density, which can be verified from the results of SEM and swelling behavior. Besides, the hydrogel exhibited great viscoelastic, toughness (70% strain), and strength properties (600 kPa). Additionally, the gradient hydrogel's superior cell compatibility was proved through the MTT, live/dead staining assays, and 3D cell culture experiments. Remarkably, the results of in vitro stem cell differentiation experiments showed that the duration of light directly affected the differentiation extent of stem cells, demonstrating that the gradient hydrogel scaffold can better simulate the function of natural cartilage than the homogeneous one. Due to these outstanding characteristics, this gradient hydrogel is a potential scaffold for cartilage tissue engineering.

17.
Medicine (Baltimore) ; 100(33): e27007, 2021 Aug 20.
Artigo em Inglês | MEDLINE | ID: mdl-34414992

RESUMO

ABSTRACT: The objective of this report was to introduce a new suture augmentation of coracoclavicular (CC) and acromioclavicular ligament reconstruction for acute Rockwood grade III to V acromioclavicular dislocations.From January 2015 to January 2019, 43 patients with Rockwood III to VI acute acromioclavicular dislocations were retrospectively reviewed. For comparison, another series of 28 patients treated with double Endobutton technique from January 2011 to December 2014 were reviewed. A P < .05 was considered statistical significance.The mean follow-up period of the 2 series were 39.69 ±â€Š7.42 months (range, 24-54 months) and 37.86 ±â€Š8.23 months (range, 26-48 months) (P > .05), respectively. There were significant differences regarding CC space (11.62 ±â€Š2.54 mm vs 16.78 ±â€Š5.53 mm; P < .05), CC reduction loss (5.56 ±â€Š4.73 mm vs 26.25 ±â€Š4.42 mm; P < .05), and acromioclavicular space (6.89 ±â€Š1.87 mm vs 7.95 ±â€Š2.37 mm; P < .05). There were significant differences regarding the disabilities of the arm, shoulder, and hand questionnaire (3.3 ±â€Š2.8 vs 5.32 ±â€Š4.37; P < .05) and University of California-Los Angeles shoulder rating scale (31.19 ±â€Š2.48 vs 29.24 ±â€Š2.48; P < .05). The excellent to good percentages were 100% (n = 32) and 85% (n = 23), respectively.In conclusion, the suture augmentation of acromioclavicular and CC ligament reconstruction is a reliable technique for acute acromioclavicular dislocation with minimal complications.Type of study/level of evidence: Therapeutic IIa.


Assuntos
Articulação Acromioclavicular/cirurgia , Ligamentos/cirurgia , Suturas/normas , Articulação Acromioclavicular/fisiopatologia , Adulto , Feminino , Humanos , Ligamentos/fisiopatologia , Masculino , Pessoa de Meia-Idade , Procedimentos Ortopédicos/métodos , Estudos Retrospectivos , Luxação do Ombro/cirurgia , Suturas/efeitos adversos , Resultado do Tratamento
18.
Stem Cell Res Ther ; 12(1): 453, 2021 08 11.
Artigo em Inglês | MEDLINE | ID: mdl-34380571

RESUMO

Hair follicle stem cells (HFSCs) are among the most widely available resources and most frequently approved model systems used for studying adult stem cells. HFSCs are particularly useful because of their self-renewal and differentiation properties. Additionally, the cyclic growth of hair follicles is driven by HFSCs. There are high expectations for the use of HFSCs as favourable systems for studying the molecular mechanisms that contribute to HFSC identification and can be applied to hair loss therapy, such as the activation or regeneration of hair follicles, and to the generation of hair using a tissue-engineering strategy. A variety of molecules are involved in the networks that critically regulate the fate of HFSCs, such as factors in hair follicle growth and development (in the Wnt pathway, Sonic hedgehog pathway, Notch pathway, and BMP pathway), and that suppress apoptotic cues (the apoptosis pathway). Here, we review the life cycle, biomarkers and functions of HFSCs, concluding with a summary of the signalling pathways involved in HFSC fate for promoting better understanding of the pathophysiological changes in the HFSC niche. Importantly, we highlight the potential mechanisms underlying the therapeutic targets involved in pathways associated with the treatment of hair loss and other disorders of skin and hair, including alopecia, skin cancer, skin inflammation, and skin wound healing.


Assuntos
Folículo Piloso , Células-Tronco , Cabelo , Proteínas Hedgehog , Via de Sinalização Wnt
19.
Nat Mater ; 2021 Aug 05.
Artigo em Inglês | MEDLINE | ID: mdl-34354215

RESUMO

Two-dimensional heterostructures are excellent platforms to realize twist-angle-independent ultra-low friction due to their weak interlayer van der Waals interactions and natural lattice mismatch. However, for finite-size interfaces, the effect of domain edges on the friction process remains unclear. Here we report the superlubricity phenomenon and the edge-pinning effect at MoS2/graphite and MoS2/hexagonal boron nitride van der Waals heterostructure interfaces. We found that the friction coefficients of these heterostructures are below 10-6. Molecular dynamics simulations corroborate the experiments, which highlights the contribution of edges and interface steps to friction forces. Our experiments and simulations provide more information on the sliding mechanism of finite low-dimensional structures, which is vital to understand the friction process of laminar solid lubricants.

20.
Int J Mol Sci ; 22(16)2021 Aug 15.
Artigo em Inglês | MEDLINE | ID: mdl-34445455

RESUMO

Glycerol is used in many skin care products because it improves skin function. Anecdotal reports by patients on the National Psoriasis Foundation website also suggest that glycerol may be helpful for the treatment of psoriasis, although to date no experimental data confirm this idea. Glycerol entry into epidermal keratinocytes is facilitated by aquaglyceroporins like aquaporin-3 (AQP3), and its conversion to phosphatidylglycerol, a lipid messenger that promotes keratinocyte differentiation, requires the lipid-metabolizing enzyme phospholipase-D2 (PLD2). To evaluate whether glycerol inhibits inflammation and psoriasiform lesion development in the imiquimod (IMQ)-induced mouse model of psoriasis, glycerol's effect on psoriasiform skin lesions was determined in IMQ-treated wild-type and PLD2 knockout mice, with glycerol provided either in drinking water or applied topically. Psoriasis area and severity index, ear thickness and ear biopsy weight, epidermal thickness, and inflammatory markers were quantified. Topical and oral glycerol ameliorated psoriasiform lesion development in wild-type mice. Topical glycerol appeared to act as an emollient to induce beneficial effects, since even in PLD2 knockout mice topical glycerol application improved skin lesions. In contrast, the beneficial effects of oral glycerol required PLD2, with no improvement in psoriasiform lesions observed in PLD2 knockout mice. Our findings suggest that the ability of oral glycerol to improve psoriasiform lesions requires its PLD2-mediated conversion to phosphatidylglycerol, consistent with our previous report that phosphatidylglycerol itself improves psoriasiform lesions in this model. Our data also support anecdotal evidence that glycerol can ameliorate psoriasis symptoms and therefore might be a useful therapy alone or in conjunction with other treatments.


Assuntos
Glicerol/farmacologia , Imiquimode/efeitos adversos , Psoríase/tratamento farmacológico , Pele/metabolismo , Animais , Aquaporina 3/genética , Aquaporina 3/metabolismo , Modelos Animais de Doenças , Humanos , Imiquimode/farmacologia , Camundongos , Camundongos Knockout , Fosfolipase D/deficiência , Fosfolipase D/metabolismo , Psoríase/induzido quimicamente , Psoríase/genética , Psoríase/metabolismo
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