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1.
Asian J Pharm Sci ; 19(2): 100901, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38645467

RESUMO

Postoperative tumor recurrence remains a predominant cause of treatment failure. In this study, we developed an in situ injectable hydrogel, termed MPB-NO@DOX + ATRA gel, which was locally formed within the tumor resection cavity. The MPB-NO@DOX + ATRA gel was fabricated by mixing a thrombin solution, a fibrinogen solution containing all-trans retinoic acid (ATRA), and a Mn/NO-based immune nano-activator termed MPB-NO@DOX. ATRA promoted the differentiation of cancer stem cells, inhibited cancer cell migration, and affected the polarization of tumor-associated macrophages. The outer MnO2 shell disintegrated due to its reaction with glutathione and hydrogen peroxide in the cytoplasm to release Mn2+ and produce O2, resulting in the release of doxorubicin (DOX). The released DOX entered the nucleus and destroyed DNA, and the fragmented DNA cooperated with Mn2+ to activate the cGAS-STING pathway and stimulate an anti-tumor immune response. In addition, when MPB-NO@DOX was exposed to 808 nm laser irradiation, the Fe-NO bond was broken to release NO, which downregulated the expression of PD-L1 on the surface of tumor cells and reversed the immunosuppressive tumor microenvironment. In conclusion, the MPB-NO@DOX + ATRA gel exhibited excellent anti-tumor efficacy. The results of this study demonstrated the great potential of in situ injectable hydrogels in preventing postoperative tumor recurrence.

2.
Front Med (Lausanne) ; 11: 1362588, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38523908

RESUMO

Background: Accurately differentiating between ovarian endometrioma and ovarian dermoid cyst is of clinical significance. However, the ultrasound appearance of these two diseases is variable, occasionally causing confusion and overlap with each other. This study aimed to develop a diagnostic classification model based on ultrasound radiomics to intelligently distinguish and diagnose the two diseases. Methods: We collected ovarian ultrasound images from participants diagnosed as patients with ovarian endometrioma or ovarian dermoid cyst. Feature extraction and selection were performed using the Mann-Whitney U-test, Spearman correlation analysis, and the least absolute shrinkage and selection operator (LASSO) regression. We then input the final features into the machine learning classifiers for model construction. A nomogram was established by combining the radiomic signature and clinical signature. Results: A total of 407 participants with 407 lesions were included and categorized into the ovarian endometriomas group (n = 200) and the dermoid cyst group (n = 207). In the test cohort, Logistic Regression (LR) achieved the highest area under curve (AUC) value (0.981, 95% CI: 0.963-1.000), the highest accuracy (94.8%), and the highest sensitivity (95.5%), while LightGBM achieved the highest specificity (97.1%). A nomogram incorporating both clinical features and radiomic features achieved the highest level of performance (AUC: 0.987, 95% CI: 0.967-1.000, accuracy: 95.1%, sensitivity: 88.0%, specificity: 100.0%, PPV: 100.0%, NPV: 88.0%, precision: 93.6%). No statistical difference in diagnostic performance was observed between the radiomic model and the nomogram (P > 0.05). The diagnostic indexes of radiomic model were comparable to that of senior radiologists and superior to that of junior radiologist. The diagnostic performance of junior radiologists significantly improved with the assistance of the model. Conclusion: This ultrasound radiomics-based model demonstrated superior diagnostic performance compared to those of junior radiologists and comparable diagnostic performance to those of senior radiologists, and it has the potential to enhance the diagnostic performance of junior radiologists.

3.
Environ Sci Pollut Res Int ; 29(23): 35338-35349, 2022 May.
Artigo em Inglês | MEDLINE | ID: mdl-35050471

RESUMO

Biogas production in the cold regions of China is hindered by low temperatures, which led to slow lignocellulose biotransformation. Cold-adapted lignocellulose degrading microbial complex community LTF-27 was used to investigate the influence of hydrolysis on biogas production. After 5 days of hydrolysis at 15 ± 1 °C, the hydrolysis conversion rate of the corn straw went up to 22.64%, and the concentration of acetic acid increased to 2596.56 mg/L. The methane production rates of total solids (TS) inoculated by LTF-27 reached 204.72 mL/g, which was higher than the biogas (161.34 mL/g), and the control group (CK) inoculated with cultural solution (121.19 mL/g), the methane production rate of volatile solids (VS) increased by 26.88% and 68.92%, respectively. Parabacteroides, Lysinibacillus, and Citrobacter were the main organisms that were responsible for hydrolysis. While numerous other bacteria genera in the gas-producing phase, Macellibacteroides were the most commonly occurring one. Methanosarcina and Methanobacteriaceae contributed 86.25% and 11.80% of the total Archaea abundance during this phase. This study proves the psychrotrophic LTF-27's applicability in hydrolysis and biomass gas production in low temperatures.


Assuntos
Biocombustíveis , Microbiota , Anaerobiose , Reatores Biológicos/microbiologia , Metano/metabolismo , Temperatura
4.
Front Mol Biosci ; 8: 670241, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34095224

RESUMO

Hepatocellular carcinoma (HCC) has been recognized as the third leading cause of cancer-related deaths worldwide. There is increasing evidence that the abnormal expression of autophagy-related genes plays an important role in the occurrence and development of HCC. Therefore, the study of autophagy-related genes can further elucidate the genetic drivers of cancer and provide valuable therapeutic targets for clinical treatment. In this study, we used 232 autophagy-related genes extracted from the Human Autophagy Database (HADb) and Molecular Signatures Database (MSigDB) to construct 1884 autophagy-related gene pairs. On this basis, we developed a prognostic model based on autophagy-related gene pairs using least absolute shrinkage and selection operator (LASSO) Cox regression to evaluate the prognosis of patients after liver cancer resection. We then used 845 liver cancer samples from three different databases to test the reliability of the risk signature through survival analysis, receiver operating characteristic (ROC) curve analysis, univariate and multivariate analysis. To further explore the underlying biological mechanisms, we conducted an enrichment analysis of autophagy-related genes. Finally, we combined the signature with independent prognostic factors to construct a nomogram. Based on the autophagy-related gene pair (ARGP) signature, we can divide patients into high- or low-risk groups. Survival analysis and ROC curve analysis verified the validity of the signature (AUC: 0.786-0.828). Multivariate Cox regression showed that the risk score can be used as an independent predictor of the clinical outcomes of liver cancer patients. Notably, this model has a more accurate predictive effect than most prognostic models for hepatocellular carcinoma. Moreover, our model is a powerful supplement to the HCC staging indicator, and a nomogram comprising both indicators can provide a better prognostic effect. Based on pairs of multiple autophagy-related genes, we proposed a prognostic model for predicting the overall survival rate of HCC patients after surgery, which is a promising prognostic indicator. This study confirms the importance of autophagy in the occurrence and development of HCC, and also provides potential biomarkers for targeted treatments.

5.
Medicine (Baltimore) ; 100(4): e24326, 2021 Jan 29.
Artigo em Inglês | MEDLINE | ID: mdl-33530224

RESUMO

ABSTRACT: The spleen plays an important role in tumor progression and the curative effects of splenectomy before hepatectomy for hypersplenism and hepatocellular carcinoma (HCC) are not clear. We investigated whether splenectomy before hepatectomy increases survival rate among patients with HCC and hypersplenism compared with that of patients who underwent synchronous hepatectomy and splenectomy or hepatectomy alone.Between January 2011 and December 2016, 266 patients who underwent hepatectomy as a result of HCC and portal hypertension secondary to hepatitis were retrospectively analyzed. Their perioperative complications and survival outcome were evaluated.Patients underwent synchronous hepatectomy and splenectomy (H-S group) and underwent splenectomy before hepatectomy (H-preS group) exhibited significantly higher disease-free survival (DFS) rates than those of patients underwent hepatectomy alone (H-O group). The DFS rates for patients in the H-S group, H-preS group, and H-O group were 74.6%, 48.4%, 39.8%, and 80.1%, 54.2%, 40.1%, and 60.5%, 30.3%, 13.3%, at 1, 3, and 5 years after surgery, respectively. Tumor size, tumors number, and levels of alpha fetoprotein (AFP) were independent risk factors for DFS. Gender and tumor size were independent prognostic factor for overall survival (OS). The preoperative white blood cell (WBC) and platelet (PLT) counts were significantly higher in the H-preS group than in those of the H-S group and the H-O group. After operation, the WBC and PLT counts in the H-S group and H-preS groups were significantly higher compared to those of the H-O group.No matter splenectomy before hepatectomy or synchronous hepatectomy and splenectomy, hepatectomy with splenectomy may improve DFS rates in patients with HCC and hypersplenism, and splenectomy before hepatectomy alleviates hypersplenism without an increased surgical risk.


Assuntos
Carcinoma Hepatocelular/cirurgia , Hepatectomia/mortalidade , Hiperesplenismo/cirurgia , Neoplasias Hepáticas/cirurgia , Esplenectomia/mortalidade , Adulto , Biomarcadores/sangue , Carcinoma Hepatocelular/complicações , Carcinoma Hepatocelular/mortalidade , Terapia Combinada , Intervalo Livre de Doença , Feminino , Hepatectomia/métodos , Humanos , Hiperesplenismo/complicações , Hiperesplenismo/mortalidade , Contagem de Leucócitos , Neoplasias Hepáticas/complicações , Neoplasias Hepáticas/mortalidade , Masculino , Pessoa de Meia-Idade , Contagem de Plaquetas , Prognóstico , Estudos Retrospectivos , Esplenectomia/métodos , Taxa de Sobrevida , Fatores de Tempo , Resultado do Tratamento , alfa-Fetoproteínas/análise
6.
World J Gastrointest Oncol ; 13(12): 2190-2202, 2021 Dec 15.
Artigo em Inglês | MEDLINE | ID: mdl-35070051

RESUMO

BACKGROUND: The long-term effect of anatomic resection (AR) is better than that of non-anatomic resection (NAR). At present, there is no study on microvascular invasion (MVI) and liver resection types. AIM: To explore whether AR improves long-term survival in patients with hepatocellular carcinoma (HCC) by removing the peritumoral MVI. METHODS: A total of 217 patients diagnosed with HCC were enrolled in the study. The surgical margin was routinely measured. According to the stratification of different tumor diameters, patients were divided into the following groups: ≤ 2 cm group, 2-5 cm group, and > 5 cm group. RESULTS: In the 2-5 cm diameter group, the overall survival (OS) of MVI positive patients was significantly better than that of MVI negative patients (P = 0.031). For the MVI positive patients, there was a statistically significant difference between AR and NAR (P = 0.027). AR leads to a wider surgical margin than NAR (2.0 ± 2.3 cm vs 0.7 ± 0.5 cm, P < 0.001). In the groups with tumor diameters < 2 cm, both AR and NAR can obtain a wide surgical margin, and the surgical margins of AR are wider than that of NAR (3.5 ± 5.8 cm vs 1.6 ± 0.5 cm, P = 0.048). In the groups with tumor diameters > 5 cm, both AR and NAR fail to obtain wide surgical margin (0.6 ± 1.0 cm vs 0.7 ± 0.4 cm, P = 0.491). CONCLUSION: For patients with a tumor diameter of 2-5 cm, AR can achieve the removal of peritumoral MVI by obtaining a wide incision margin, reduce postoperative recurrence, and improve prognosis.

7.
ACS Omega ; 6(51): 35810-35820, 2021 Dec 28.
Artigo em Inglês | MEDLINE | ID: mdl-34984310

RESUMO

Source rocks of the Mohe Basin, Northeast China are gas-prone and the organic matter has advanced to late oil-generation stages, producing condensate and natural gas. This provides suitable conditions for the Mohe Basin to become one of the most prolific terrestrial natural gas hydrate (NGH)-bearing areas in China. Knowing this, here we predict the depth and thickness of pure methane hydrate stability zones (HSZs) and gas hydrate stability zones (GHSZs) via simulating the hydrate-phase equilibrium and other formation P-T conditions. Furthermore, factors that have a major impact on the occurrence of HSZs are discussed. Results showed that the composition of gas (guest) molecules and the geothermal gradient are the two most controlling factors on HSZs. Moreover, it was found that a pure methane HSZ with a thickness of about 255 m can form in areas with a geothermal gradient of <1.5 °C/100 m, with top and bottom depth limits less than 493 m and greater than 748 m, respectively. In contrast, pure methane hydrates have difficulty forming, while hydrates from wet gas can form where there is a geothermal gradient of >1.6 °C/100 m. Furthermore, a wet gas HSZ with a thickness of at least 735 m can be expected when the geothermal gradient reaches 2.3 °C/100 m, with top and bottom depth limits at 115 and 850 m, respectively. Ultimately, a pure methane HSZ can still form in the abnormally high-pressured areas when the geothermal gradient is up to 2.0 °C/100 m. Overall, HSZs can occur due to the combined effect of formation temperature, pressure, and gas composition. Finally, based on the results from this study and drilling data, future successful hydrate drilling schemes can be implemented in the Mohe Basin and similar terrestrial areas.

8.
BMC Cancer ; 20(1): 1047, 2020 Oct 31.
Artigo em Inglês | MEDLINE | ID: mdl-33129301

RESUMO

BACKGROUND: This study explored the diagnostic power of preoperative circulating tumor cells (CTCs) for the presence of microvascular invasion (MVI) and the relationship between dynamic changes in postoperative CTCs and prognosis. METHODS: A total of 137 patients were recruited for the study. Preoperative blood samples were collected from all patients to detect CTCs. The time points for blood collection were before the operation, during the operation, and at 1 week, 1 month, 2 months, 3 months, 6 months, and 1 year after surgery. The predictive power of CTC count for the presence of MVI was analyzed by receiver operating characteristic (ROC) curve analysis. According to recurrence status, 137 patients were divided into three groups: no recurrence, early recurrence, and non-early recurrence groups. RESULTS: A threshold CTC count of 5 showed the most significant power for predicting the existence of MVI. In multivariate analysis, the parameters of preoperative CTC count, alpha-fetoprotein (AFP) and tumor diameter were independent predictors of MVI (P <  0.05). A CTC count greater than or equal to 5 had better predictive value than AFP > 400 µg/L and tumor diameter > 5 cm. The number of intraoperative CTCs in the three groups did not increase compared to that before surgery (P > 0.05). The number of CTCs in the nonrecurrence group and the non-early recurrence group decreased significantly 1 week after surgery compared with the intraoperative values (P <  0.001), although there was no significant difference in the early recurrence group (P = 0.95). Patients with mean CTC count ≥5 had significantly worse long-term outcomes than those with mean CTC count < 5 (P <  0.001). CONCLUSION: The preoperative CTC counts in the peripheral blood of patients with HCC are closely correlated with MVI. The intraoperative manipulation of the lesion by the surgeon does not increase the number of CTCs in peripheral blood. Surgical removal of the tumor decreases the number of CTCs. The persistence of CTCs at a high level (≥ 5) after surgery suggests a risk of early recurrence. CLINICAL TRIAL REGISTRATION: Registration number is ChiCTR-OOC-16010183 , date of registration is 2016-12-18.


Assuntos
Carcinoma Hepatocelular/patologia , Hepatectomia/métodos , Neoplasias Hepáticas/patologia , Microvasos/patologia , Recidiva Local de Neoplasia/patologia , Células Neoplásicas Circulantes/patologia , Adulto , Idoso , Carcinoma Hepatocelular/cirurgia , Feminino , Seguimentos , Humanos , Neoplasias Hepáticas/cirurgia , Masculino , Pessoa de Meia-Idade , Invasividade Neoplásica , Recidiva Local de Neoplasia/cirurgia , Prognóstico , Fatores de Risco , Taxa de Sobrevida , Adulto Jovem
9.
J Card Surg ; 35(1): 89-99, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31765025

RESUMO

OBJECTIVE: Prediction of acute renal failure (ARF) and paraplegia after thoracoabdominal aortic aneurysm repair (TAAAR) is helpful for decision-making during the postoperative phase. To find a more efficient method for making a prediction, we performed tests on the efficacy of different machine learning predicting models. METHODS: Perioperative TAAAR data were retrospectively collected from Beijing Anzhen Hospital and Shanghai DeltaHealth Hospital. Operations were conducted under normothermia using a four-branched graft. Four commonly used machine learning classification models (ie, logistic regression, linear and Gaussian kernel support vector machine, and random forest) were chosen to predict ARF and paraplegia separately. The efficacy of the models was validated by five-fold cross-validation. RESULTS: From 2009 to 2017, 212 TAAARs were performed. ARF was identified in 27 patients, and paraplegia was found in 18 patients. Five-fold cross-validation showed that among the four classification models, random forest was the most precise model for predicting ARF, with an average area under the curve (AUC) of 0.89 ± 0.08. Linear support vector machine was the most precise model for predicting paraplegia, with an average AUC of 0.89 ± 0.18. The prediction program has been uploaded to GitHub for open access. CONCLUSION: Machine learning models can precisely predict ARF and paraplegia during early stages after surgery. This program allows cardiac surgeons to address complications earlier and may help improve the clinical outcomes of TAAAR.


Assuntos
Injúria Renal Aguda , Aneurisma da Aorta Abdominal/cirurgia , Aneurisma da Aorta Torácica/cirurgia , Aprendizado de Máquina , Paraplegia , Complicações Pós-Operatórias , Adulto , Idoso , Feminino , Previsões , Humanos , Masculino
10.
ACS Omega ; 4(7): 12817-12826, 2019 Jul 31.
Artigo em Inglês | MEDLINE | ID: mdl-31460406

RESUMO

Dry coal beneficiation has played a vital role during the initial stage of coal cleaning in recent years. Successful utilization of a gas-solid fluidized bed for >6 mm coal cleaning motivates scholars to explore the possibility of fine coal cleaning using dry beneficiation methods. In this study, pulsed flow was introduced into a fluidized bed to optimize bubble behavior, thus improving the density stability. The equation of minimum fluidization velocity (U mfp) in a gas-vibro fluidized bed for coal preparation was investigated theoretically. An equation has been proposed for predicting U mfp while considering changes in the friction coefficient (C f) in the gas-vibro fluidized bed. Based on two-phase theory, the correlation of bed density was determined by analyzing the bubble behavior in the gas-vibro fluidized bed. The theoretical bed density was then compared with experimental data of the bed density and separation density. The predicted bed density in monodisperse and binary dense medium systems was found to be consistent with the experimental results. Overall, the equation of bed density is suitable for estimating the separation density in the gas-vibro fluidized bed.

11.
Chemosphere ; 211: 44-49, 2018 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-30071435

RESUMO

The low-low temperature electrostatic precipitator (LLT-ESP) is one of the most used devices for pollutant control in ultra-low emission coal-fired power plants. This study investigated the influence of the LLT-ESP on polycyclic aromatic hydrocarbons (PAHs) distributions in flue gas from an ultra-low emission coal-fired power plant. The total gas-phase PAH concentration was reduced from 27.52 µg/m3 to 3.38 µg/m3. The total particulate-phase PAH concentration decreased from 14.36 µg/m3 to 0.34 µg/m3. The removal efficiency of the LLT-ESP for gas-phase and particulate phase carcinogenic higher molecular weight (HMW) PAHs was 85% and 99%, respectively. The total concentration of 16 selected PAHs in feed coal was 98.16 µg/g. The fly ash particle size successively decreased from Electric Field 1 (F1) to Electric Field 4 (F4). The total PAH concentration decreased from F1 to F2 but increased again from F3 to F4. The flue gas cooling process significantly contributed to the elimination of both gas- and particulate-phase PAHs in the flue gas. Presumably, most of the condensed PAHs were adhered to or absorbed in the fly ash and were scavenged in Field 1. Both gas- and particulate-phase 5- and 6-ring PAHs in the flue gas were completely removed in Field 1. The discharge process in the electric fields may promote the formation of several 4- or 5-ring PAHs. In this study, benzo[k]fluoranthene (BKF) and benzo[a]pyrene (BaP) were regenerated in the particles rather than in the flue gas during the discharge process in the electric fields.


Assuntos
Hidrocarbonetos Policíclicos Aromáticos/química , Centrais Elétricas/estatística & dados numéricos , Eletricidade Estática , Hidrocarbonetos Policíclicos Aromáticos/análise , Temperatura
12.
PLoS One ; 11(1): e0147157, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-26784960

RESUMO

Developing drugs that can effectively block STAT3 activation may serve as one of the most promising strategy for cancer treatment. Currently, there is no putative STAT3 inhibitor that can be safely and effectively used in clinic. In the present study, we investigated the potential of dihydroartemisinin (DHA) as a putative STAT3 inhibitor and its antitumor activities in head and neck squamous cell carcinoma (HNSCC). The inhibitory effects of DHA on STAT3 activation along with its underlying mechanisms were studied in HNSCC cells. The antitumor effects of DHA against HNSCC cells were explored both in vitro and in vivo. An investigation on cooperative effects of DHA with cisplatin in killing HNSCC cells was also implemented. DHA exhibited remarkable and specific inhibitory effects on STAT3 activation via selectively blocking Jak2/STAT3 signaling. Besides, DHA significantly inhibited HNSCC growth both in vitro and in vivo possibly through induction of apoptosis and attenuation of cell migration. DHA also synergized with cisplatin in tumor inhibition in HNSCC cells. Our findings demonstrate that DHA is a putative STAT3 inhibitor that may represent a new and effective drug for cancer treatment and therapeutic sensitization in HNSCC patients.


Assuntos
Artemisininas/farmacologia , Carcinoma de Células Escamosas/tratamento farmacológico , Neoplasias de Cabeça e Pescoço/tratamento farmacológico , Janus Quinase 2/metabolismo , Fator de Transcrição STAT3/metabolismo , Transdução de Sinais/efeitos dos fármacos , Animais , Apoptose/efeitos dos fármacos , Western Blotting , Carcinoma de Células Escamosas/metabolismo , Carcinoma de Células Escamosas/patologia , Proliferação de Células/efeitos dos fármacos , Citometria de Fluxo , Neoplasias de Cabeça e Pescoço/metabolismo , Neoplasias de Cabeça e Pescoço/patologia , Humanos , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Fosforilação/efeitos dos fármacos , Fator de Transcrição STAT3/antagonistas & inibidores , Células Tumorais Cultivadas , Cicatrização , Ensaios Antitumorais Modelo de Xenoenxerto
13.
J Chem Theory Comput ; 11(11): 5473-80, 2015 Nov 10.
Artigo em Inglês | MEDLINE | ID: mdl-26574335

RESUMO

To test whether our recently developed residue-specific force field RSFF2 can reproduce the mutational effect on the thermal stability of Trp-cage mini-protein and decipher its detailed folding mechanism, we carried out long-time replica-exchange molecular dynamics (REMD) simulations on five Trp-cage variants, including TC5b and TC10b. Initiated from their unfolded structures, the simulations not only well-reproduce their experimental structures but also their melting temperatures and folding enthalpies reasonably well. For each Trp-cage variant, the overall folding free energy landscape is apparently two-state, but some intermediate states can be observed when projected on more detailed coordinates. We also found different variants have the same major folding pathway, including the well formed PII-helix in the unfolded state, the formation of W6-P12/P18/P19 contacts and the α-helix before the transition state, the following formation of most native contacts, and the final native loop formation. The folding mechanism derived here is consistent with many previous simulations and experiments.


Assuntos
Simulação de Dinâmica Molecular , Peptídeos/química , Termodinâmica , Cinética , Modelos Moleculares , Dobramento de Proteína , Estabilidade Proteica
14.
J Phys Chem B ; 119(3): 1035-47, 2015 Jan 22.
Artigo em Inglês | MEDLINE | ID: mdl-25358113

RESUMO

Recently, we developed a residue-specific force field (RSFF1) based on conformational free-energy distributions of the 20 amino acid residues from a protein coil library. Most parameters in RSFF1 were adopted from the OPLS-AA/L force field, but some van der Waals and torsional parameters that effectively affect local conformational preferences were introduced specifically for individual residues to fit the coil library distributions. Here a similar strategy has been applied to modify the Amber ff99SB force field, and a new force field named RSFF2 is developed. It can successfully fold α-helical structures such as polyalanine peptides, Trp-cage miniprotein, and villin headpiece subdomain and ß-sheet structures such as Trpzip-2, GB1 ß-hairpins, and the WW domain, simultaneously. The properties of various popular force fields in balancing between α-helix and ß-sheet are analyzed based on their descriptions of local conformational features of various residues, and the analysis reveals the importance of accurate local free-energy distributions. Unlike the RSFF1, which overestimates the stability of both α-helix and ß-sheet, RSFF2 gives melting curves of α-helical peptides and Trp-cage in good agreement with experimental data. Fitting to the two-state model, RSFF2 gives folding enthalpies and entropies in reasonably good agreement with available experimental results.


Assuntos
Simulação de Dinâmica Molecular , Proteínas/química , Dipeptídeos/química , Entropia , Peptídeos/química , Desnaturação Proteica , Estrutura Secundária de Proteína , Temperatura de Transição
15.
J Phys Chem B ; 118(25): 6983-98, 2014 Jun 26.
Artigo em Inglês | MEDLINE | ID: mdl-24815738

RESUMO

Traditional protein force fields use one set of parameters for most of the 20 amino acids (AAs), allowing transferability of the parameters. However, a significant shortcoming is the difficulty to fit the Ramachandran plots of all AA residues simultaneously, affecting the accuracy of the force field. In this Feature Article, we report a new strategy for protein force field parametrization. Backbone and side-chain conformational distributions of all 20 AA residues obtained from protein coil library were used as the target data. The dihedral angle (torsion) potentials and some local nonbonded (1-4/1-5/1-6) interactions in OPLS-AA/L force field were modified such that the target data can be excellently reproduced by molecular dynamics simulations of dipeptides (blocked AAs) in explicit water, resulting in a new force field with AA-specific parameters, RSFF1. An efficient free energy decomposition approach was developed to separate the corrections on ϕ and ψ from the two-dimensional Ramachandran plots. RSFF1 is shown to reproduce the experimental NMR (3)J-coupling constants of AA dipeptides better than other force fields. It has a good balance between α-helical and ß-sheet secondary structures. It can successfully fold a set of α-helix proteins (Trp-cage and Homeodomain) and ß-hairpins (Trpzip-2, GB1 hairpin), which cannot be consistently stabilized by other state-of-the-art force fields. Interestingly, the RSFF1 force field systematically overestimates the melting temperature (and the stability of native state) of these peptides/proteins. It has a potential application in the simulation of protein folding and protein structure refinement.


Assuntos
Proteínas de Bactérias/química , Dipeptídeos/química , Proteínas de Homeodomínio/química , Simulação de Dinâmica Molecular , Peptídeos/química , Proteínas/química , Espectroscopia de Ressonância Magnética , Modelos Teóricos , Dobramento de Proteína , Estrutura Secundária de Proteína , Eletricidade Estática , Água/química
16.
Zhonghua Yi Xue Za Zhi ; 92(24): 1660-4, 2012 Jun 26.
Artigo em Chinês | MEDLINE | ID: mdl-22944153

RESUMO

OBJECTIVE: To retrospectively analyze the curative efficacy of umbilical cord blood transplantation (UCBT) with improved myeloablative conditioning regimen (total body irradiation (TBI)/cytosine arabinoside (Ara-c)/cyclophosphamide (CY) without antithymocyte globulin (ATG)) in adult patients with hematological malignancies. METHODS: Forty consecutive adult patients with hematological malignancies received improved myeloablative unrelated CBT at a single center from September 2006 to May 2011. Their average age was (23 ± 6) years and the average weight (58 ± 9) kg. Thirty-five (87.5%) patients were high-risk and 15 (37.5%) at the advanced disease status at pre-transplantation. They received 1 (n = 23) or 2 (n = 17) cord blood units. Seventy-five percent of them were transplanted with 1/2-human leukocyte antigen mismatched unit. The conditioning regimen consisted of 12 Gy TBI, granulocyte colony-stimulating factor (G-CSF) plus Ara-c and CY without ATG. All patients received a combination of cyclosporine (CsA) and mycophenolate mofetil (MMF) for the prophylaxis of graft-versus-host disease (GVHD). RESULTS: For the entire group of patients, the average cell doses infused were (4.1 ± 1.1)×107 total nucleated cells/kg and (2.4 ± 1.0)×105 CD34(+) cells/kg. All patients acquired engraftment with an implantation rate of 100%. The average time of absolute neutrophil count (ANC) ≥ 0.5×109/L was (20 ± 5) days and the average time of platelet ≥ 20×109/L was(38 ± 12) days. Acute GVHD occurred in 23 patients (57.5%) and 4 (10.0%) were of grade III-IV. Chronic GVHD occurred in 22.9% (8/35) evaluable patients. Relapse occurred in 12.5% (5/40) patients. During a median follow-up period of 19.8 (range 4.6 - 55.0) months, the transplantation-related mortality was 15.0% (6/40) within 100 days and 35.0% (14/40) within 1 year. The main causes of mortality were pneumonia and severe acute GVHD. Two-year overall survival (OS) or disease-free survival was 58.8% and 58.8%, respectively. Two-year OS for patients with advanced or complete remission disease was 48.6% and 63.8%, respectively. CONCLUSIONS: The TBI/Ara-c/CY myeloablative conditioning regimen is well-tolerated and capable of establishing sustained donor cell engraftment and decreasing the risks of transplant-related death in adults with hematologic malignancies. For the high-risk and advanced patients, it may reduce the occurrences of relapse and chronic GVHD.


Assuntos
Transplante de Células-Tronco de Sangue do Cordão Umbilical/métodos , Neoplasias Hematológicas/cirurgia , Condicionamento Pré-Transplante/métodos , Adolescente , Adulto , Feminino , Doença Enxerto-Hospedeiro/prevenção & controle , Humanos , Leucemia/cirurgia , Masculino , Irradiação Corporal Total , Adulto Jovem
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