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1.
Front Immunol ; 13: 992611, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36119072

RESUMO

Anti-PD-1/PD-L1 therapy has shown significant benefits in the treatment of a variety of malignancies. However, not all cancer patients can benefit from this strategy due to drug resistance. Therefore, there is an urgent need for methods that can effectively improve the efficacy of anti-PD-1/PD-L1 therapy. Combining anti-PD-1/PD-L1 therapy with regorafenib has been demonstrated as an effective method to enhance its therapeutic effect in several clinical studies. In this review, we describe common mechanisms of resistance to anti-PD-1/PD-L1 therapy, including lack of tumor immunogenicity, T cell dysfunction, and abnormal expression of PD-L1. Then, we illustrate the role of regorafenib in modifying the tumor microenvironment (TME) from multiple aspects, which is different from other tyrosine kinase inhibitors. Regorafenib not only has immunomodulatory effects on various immune cells, but can also regulate PD-L1 and MHC-I on tumor cells and promote normalization of abnormal blood vessels. Therefore, studies on the synergetic mechanism of the combination therapy may usher in a new era for cancer treatment and help us identify the most appropriate individuals for more precise treatment.


Assuntos
Antígeno B7-H1 , Neoplasias , Antígeno B7-H1/metabolismo , Humanos , Neoplasias/tratamento farmacológico , Compostos de Fenilureia/uso terapêutico , Receptor de Morte Celular Programada 1 , Inibidores de Proteínas Quinases/farmacologia , Inibidores de Proteínas Quinases/uso terapêutico , Piridinas , Microambiente Tumoral
2.
J Neurosci ; 2022 Sep 12.
Artigo em Inglês | MEDLINE | ID: mdl-36100398

RESUMO

Aquaporin-4 (AQP4) is characterized by the formation of orthogonal arrays of particles (OAPs) comprising its M1 and M23 isoforms in the plasma membrane. However, the biological importance of OAP formation is obscure. Here, we developed an OAP depolymerization male mouse model by transgenic knock-in of an AQP4-A25Q mutation. Analyses of the mutant brain tissue using blue native polyacrylamide gel electrophoresis, super-resolution imaging and immunogold electron microscopy (IEM) revealed remarkably reduced OAP structures and glial endfeet localization of the AQP4-A25Q mutant protein without effects on its overall mRNA and protein expression. AQP4A25Q/A25Q mice showed better survival and neurological deficit scores (NDSs) when cerebral edema was induced by water intoxication or middle cerebral artery occlusion/reperfusion (MCAO/R). The brain water content and swelling of pericapillary astrocytic endfeet processes in AQP4A25Q/A25Q mice were significantly reduced, functionally supporting decreased AQP4 protein expression at the blood-brain barrier (BBB). The infarct volume and neuronal damage were also reduced in AQP4A25Q/A25Q mice in the MCAO/R model. Astrocyte activation in the brain was alleviated in AQP4A25Q/A25Q mice, which may be associated with decreased cell swelling. We conclude that the OAP structure of AQP4 plays a key role in its polarized expression in astrocytic endfeet processes at the BBB. Therefore, our study provided new insights into intervention of cerebral cellular edema caused by stroke and traumatic brain injury through regulating AQP4 OAP formation.SIGNIFICANCE STATEMENT:Aquaporin-4 (AQP4) is characterized by orthogonal arrays of particles (OAPs) comprising the M1 and M23 isoforms in the membrane. Here, an OAP depolymerization male mouse model induced by AQP4-A25Q mutation was firstly established and the functions of OAP depolymerization in cerebral edema has been studied. The results revealed that AQP4 lost its OAP structure without affecting AQP4 mRNA and protein levels in AQP4-A25Q mice. AQP4-A25Q mutation mice has neuroprotective effects on cerebral edema induced by water intoxication and middle cerebral artery occlusion/reperfusion through relieving the activation of astrocytes and suppressed microglia-mediated neuroinflammation. We concluded that the OAP structure of AQP4 plays a key role in its polarized expression in astrocytic endfeet processes at BBB. Therefore, our study provided new insights into intervention of cerebral cellular edema caused by stroke and traumatic brain injury through regulating AQP4 OAP formation.

3.
Front Oncol ; 12: 980736, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36059669

RESUMO

Background: The efficacies of anatomical resection (AR) and non-anatomical resection (NAR) in the treatment of combined hepatocellular-cholangiocarcinoma (cHCC-CCA) remain unclear. This study aimed to compare the prognostic outcomes of AR with those of NAR for cHCC-CCA. Method: Patients diagnosed with pathology-confirmed cHCC-CCA, and who underwent curative resection at Tongji hospital between January 2010 and December 2019 were included in this retrospective study. A one-to-one propensity score matching (PSM) analysis was used to compare the long-term outcomes of AR to those of NAR. Results: A total of 105 patients were analyzed, of whom 48 (45.7%) and 57 (54.3%) underwent AR and NAR, respectively. There were no significant differences in short-term outcomes between the two groups, including duration of postoperative hospital stay, the incidence of perioperative complications, and incidence of 30-day mortality. However, both, the 5-year overall survival (OS) and recurrence-free survival (RFS) rates of AR were significantly better than those of NAR (40.5% vs. 22.4%, P=0.002; and 37.3% vs. 14.4%, P=0.002, respectively). Multivariate analysis showed that NAR, multiple tumors, larger-sized tumors (>5 cm), cirrhosis, lymph node metastasis, and vascular invasion were independent risk factors for poor prognoses. Stratified analysis demonstrated similar outcomes following AR versus NAR for patients with tumors > 5cm in diameter, while AR had better survival than NAR in patients with tumors ≤5 cm in diameter. After PSM, when 34 patients from each group were matched, the 5-year OS and RFS rates of AR were still better than those of NAR. Conclusion: Patients with cHCC-CCA who underwent AR had better long-term surgical outcomes than those who underwent NAR, especially for those with tumors ≤5 cm in diameter. However, no differences in the risk of surgical complications were detected between the two groups.

4.
Artigo em Inglês | MEDLINE | ID: mdl-36030891

RESUMO

OBJECTIVES: We systematically reviewed published clinical trials to evaluate the effectiveness of virtual reality (VR) technology on functional improvement, pain relief, and reduction of mental distress among burn patients undergoing rehabilitation. DATA SOURCES: Systematic searches were conducted in 4 databases, including PubMed, the Cochrane Library, Embase, and Web of Science, from inception to August 2021. STUDY SELECTION: Randomized controlled trials (RCTs) evaluating any type of VR for the rehabilitation in burn patients with dysfunction were included. DATA EXTRACTION: Two reviewers evaluated the eligibility, and another 2 reviewers used the Cochrane risk of bias assessment tool to assess the risk of bias. The extracted data included the main results of rehabilitation evaluation (quality of life [QOL], work performance, range of motion [ROM] of joints, hand grip and pinch strength, pain, fun, anxiety), the application performance of VR (realness and presence), adverse effects (fatigue and nausea), and characteristics of the included studies. Heterogeneity was evaluated using the chi-square tests and I2 statistics. Random- or fixed-effects models were conducted to pool the effect sizes expressed as standardized mean differences (SMDs). DATA SYNTHESIS: Sixteen RCTs with 535 burn patients were included. VR-based interventions were superior to usual rehabilitation in QOL and work performance of burn patients and produced positive effect on the average gain of ROM (SMD=0.72) as well. VR was not associated with improved hand grip and pinch strength (SMD=0.50, 1.22, respectively) but was associated with reduced intensity, affective, and cognitive components of pain (SMD=-1.26, -0.71, -1.01, respectively) compared with control conditions. Ratings of fun in rehabilitation therapy were higher (SMD=2.38), and anxiety scores were lower (SMD=-0.73) than in control conditions. CONCLUSIONS: VR-based burn rehabilitation significantly improves the QOL and work performance of burn patients, increases the ROM gain in the joints, reduces the intensity and unpleasantness of pain and the time spent thinking about pain, increases the fun in the rehabilitation therapy, reduces the anxiety caused by the treatment, and has no obvious adverse effects. However, it did not significantly improve hand grip or pinch strength.

5.
NPJ Sci Food ; 6(1): 38, 2022 Aug 27.
Artigo em Inglês | MEDLINE | ID: mdl-36030278

RESUMO

Stigmasterol (ST) has been shown to improve both lipid and bile acid (BA) metabolism. However, the mechanism(s) by which ST prevents dyslipidemia via BA metabolism, and the potential involvement of other regulatory mechanisms, remains unclear. Here, we found that ST treatment effectively alleviates lipid metabolism disorder induced by a high-fat diet (HFD). Moreover, we also show that fecal microbiota transplantation from ST-treated rats displays similar protective effects in rats fed on an HFD. Our data confirm that the gut microbiota plays a key role in attenuating HFD-induced fat deposition and metabolic disorders. In particular, ST reverses HFD-induced gut microbiota dysbiosis in rats by reducing the relative abundance of Erysipelotrichaceae and Allobaculum bacteria in the gut. In addition, ST treatment also modifies the serum and fecal BA metabolome profiles in rats, especially in CYP7A1 mediated BA metabolic pathways. Furthermore, chenodeoxycholic acid combined with ST improves the therapeutic effects in HFD-induced dyslipidemia and hepatic steatosis. In addition, this treatment strategy also alters BA metabolism profiles via the CYP7A1 pathway and gut microbiota. Taken together, ST exerts beneficial effects against HFD-induced hyperlipidemia and obesity with the underlying mechanism being partially related to both the reprogramming of the intestinal microbiota and metabolism of BAs in enterohepatic circulation. This study provides a theoretical basis for further study of the anti-obesity effects of ST and consideration of the gut microbiota as a potential target for the treatment of HFD-induced dyslipidemia.

6.
Hepatology ; 2022 Aug 03.
Artigo em Inglês | MEDLINE | ID: mdl-35921500

RESUMO

BACKGROUND & AIMS: Gain-of-function (GOF) mutations of CTNNB1 and loss-of-function (LOF) mutations of AXIN1 are recurrent genetic alterations in hepatocellular carcinoma (HCC). We aim to investigate the functional contribution of Hippo/YAP/TAZ in GOF CTNNB1 or LOF AXIN1 mutant HCCs. APPROACH & RESULTS: The requirement of YAP/TAZ in c-Met/ß-Catenin and c-Met/sgAxin1 driven HCC was analyzed using conditional Yap, Taz, and Yap;Taz knockout (KO) mice. Mechanisms of AXIN1 in regulating YAP/TAZ were investigated using AXIN1 mutated HCC cells. Hepatocyte-specific inducible TTR-CreERT2 KO system was applied to evaluate the role of Yap;Taz during tumor progression. Cabozantinib and G007-LK combinational treatment were tested in vitro and in vivo. Nuclear YAP/TAZ was strongly induced in c-Met/sgAxin1 mouse HCC cells. Activation of Hippo via overexpression of Lats2 or concomitant deletion of Yap and Taz significantly inhibited c-Met/sgAxin1 driven HCC development, whereas the same approaches had mild effects in c-Met/ß-Catenin HCCs. YAP is the major Hippo effector in c-Met/ß-Catenin HCCs, and both YAP and TAZ are required for c-Met/sgAxin1 dependent hepatocarcinogenesis. Mechanistically, AXIN1 binds to YAP/TAZ in human HCC cells and regulates YAP/TAZ stability. Genetic deletion of YAP/TAZ suppresses already formed c-Met/sgAxin1 liver tumors, supporting the requirement of YAP/TAZ during tumor progression. Importantly, tankyrase inhibitor G007-LK, which targets Hippo and Wnt pathways, synergizes with cabozantinib, a c-MET inhibitor, leading to tumor regression in the c-Met/sgAxin1 HCC model. CONCLUSIONS: Our studies demonstrate that YAP/TAZ are major signaling molecules downstream of LOF AXIN1 mutant HCCs, and targeting YAP/TAZ as an effective treatment against AXIN1 mutant human HCCs.

7.
Biopreserv Biobank ; : 1-10, 2022 Aug 23.
Artigo em Inglês | MEDLINE | ID: mdl-36001824

RESUMO

Cryopreservation of human T lymphocytes has become a key strategy for supporting cell-based immunotherapy. However, the effects of ice seeding on the cryopreservation of cells under relatively slow cooling have not been well researched. The cryopreservation strategy with a nontoxic, single-ingredient, and injectable cryoprotective solution remains to be developed. We conducted ice seeding for the cells in a solution of normal saline with 1% (v/v) dimethyl sulfoxide (Me2SO), 0.1 M trehalose, and 4% (w/v) human serum albumin (HSA) under different slow cooling rates. With the positive results, we further applied seeding in the solution of 0.2 M trehalose and 4% (w/v) HSA under the same cooling rates. The optimal concentration of trehalose in the Me2SO-free solutions was then investigated under the optimized cooling rate with seeding, with control groups without seeding, and in a freezing container. In vitro toxicity of the cryoprotective solutions to the cells was also tested. We found that the relative viability of cells (1% [v/v] Me2SO, 0.1 M trehalose and 4% [w/v] HSA) was improved significantly from 88.6% to 94.1% with ice seeding, compared with that without seeding (p < 0.05). The relative viability of cells (0.2 M trehalose and 4% [w/v] HSA) with seeding was significantly higher than that without seeding, 96.3% and 92.0%, respectively (p < 0.05). With no significant difference in relative viability between the solutions of 0.2 M trehalose or 0.3 M trehalose with 4% (w/v) HSA (92.4% and 94.6%, respectively, p > 0.05), the solution of 0.2 M trehalose and 4% (w/v) HSA was selected as the optimized Me2SO-free solution. This strategy could cryopreserve human T lymphocytes without any toxic cryoprotectant and boost the application of cell products in humans by intravenous injection, with the osmolality of the low-concentration cryoprotective solution close to that of human plasma.

8.
Micromachines (Basel) ; 13(8)2022 Aug 05.
Artigo em Inglês | MEDLINE | ID: mdl-36014183

RESUMO

Compliant bipedal robots demonstrate a potential for impact resistance and high energy efficiency through the introduction of compliant elements. However, it also adds to the difficulty of stable control of the robot. To motivate the control strategies of compliant bipedal robots, this work presents an improved control strategy for the stable and fast planar jumping of a compliant one-legged robot designed by the authors, which utilizes the concept of the virtual pendulum. The robot was modeled as an extended spring-loaded inverted pendulum (SLIP) model with non-negligible torso inertia, leg inertia, and leg damping. To enable the robot to jump forward stably, a foot placement method was adopted, where due to the asymmetric feature of the extended SLIP model, a variable time coefficient and an integral term with respect to the forward speed tracking error were introduced to the method to accurately track a given forward speed. An energy-based leg rest length regulation method was used to compensate for the energy dissipation due to leg damping, where an integral term, regarding jumping height tracking error, was introduced to accurately track a given jumping height. Numerical simulations were conducted to validate the effectiveness of the proposed control strategy. Results show that stable and fast jumping of compliant one-legged robots could be achieved, and the desired forward speed and jumping height could also be accurately tracked. In addition to that, using the proposed control strategy, the robust jumping performance of the robot could be observed in the presence of disturbances from state variables or uneven terrain.

9.
Onco Targets Ther ; 15: 703-716, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35791424

RESUMO

Background: Scalp and skull metastasis of hepatocellular carcinoma (HCC) is extremely rare. Modalities for the treatment of this disease include craniotomy, radiotherapy and chemotherapy, which are unsatisfactory. We report a case of HCC with scalp and skull metastasis and review similar cases from the literature to accumulate experience for better management of this type of HCC metastasis. Case Presentation: A 54-year-old female was diagnosed with advanced HCC with posterior portal vein tumor thrombus (PVTT) at admission. She received laparoscopic microwave therapy for a large tumor in Segment 6, which was then followed by sorafenib therapy. One year later, sorafenib resistance developed, metastasis occurred in the scalp and skull, left sacroiliac joint, and lung; PVTT extended into the main portal vein and alpha-feta protein (AFP) levels exceeded 65,000 ng/mL. Systemic therapy was then substituted by regorafenib combined with sintilimab. Three months later, AFP decreased to 2005 ng/mL; meanwhile, skull and lung metastatic lesions shrank significantly. Furthermore, both lump and limp disappeared. One year after the combination of regorafenib and sintilimab, skull and lung metastasis, and PVTT were completely relieved. Moreover, primary liver lesions showed no sign of activity. With comprehensive therapy, the patient has survived for 5 years and 7 months. Conclusion: Sorafenib-regorafenib sequential treatment combined with sintilimab is safe and effective when used to treat HCC skull metastasis, for which high-level evidence is needed to support this treatment strategy.

10.
RSC Adv ; 12(28): 18215-18223, 2022 Jun 14.
Artigo em Inglês | MEDLINE | ID: mdl-35800299

RESUMO

A thiourea modified low molecular weight polyamide (TLMPA) as a room temperature curing agent was synthesized by a two-step method. Firstly, a low molecular weight polyamide curing agent (LMPA) with low viscosity and high amine value was synthesized by amidation of sebacic acid with tetraethylenepentamine, then the synthesized curing agent was modified with thiourea to increase its reactivity at room temperature. The optimal reaction conditions were studied by L9(33) orthogonal experiments. The structure of the prepared curing agent was analyzed by Fourier transform infrared spectroscopy (FT-IR). The kinetics of TLMPA curing of E-51 epoxy resin was analyzed using the Kissinger method with non-isothermal differential scanning calorimetry (DSC). The activation energy of TLMPA/E-51 calculated by the Kissinger method and FWO method was 38.79 kJ mol-1 and 42.73 kJ mol-1. The nano-SiO2 filler was compounded with E-51 epoxy resin, TLMPA, allyl glycidyl ether diluent, and KH-560 coupling agent to prepare the room temperature curing epoxy resin (EP) system. L9(34) orthogonal experiments were carried out to study the effect of various factors on the mechanical properties of the cured resin systems. The best formulation of the system is that the content of nano-SiO2, curing agent, diluent, and coupling agent is 3, 35, 15, 1 wt%, respectively. With the optimal formulation, the tensile and shear strength, tensile strength, impact strength, and bending strength of the cured EP system was 13.19 MPa, 53.8 MPa, 52.16 kJ m-2, and 94.95 MPa, respectively.

11.
Neurosci Lett ; 785: 136787, 2022 08 10.
Artigo em Inglês | MEDLINE | ID: mdl-35820551

RESUMO

The NLRP3-mediated pyroptosis, which could affect inflammation response, plays a key role in the development of depression. Acupuncture has been shown to be an effective treatment for depression. In this study, we aimed to determine whether acupuncture could confer antidepressant activity via decreasing NLRP3-mediated pyroptosis by reducing inflammation. Here, depression model of rats was induced by chronic unpredictable mild stress (CUMS) for 4 weeks. Acupuncture group was subjected to acupuncture at the Shangxing (GV23) and Fengfu (GV16) acupoints for 20 min every other day (a total of 14 times). Fluoxetine group was administered with fluoxetine (2.1 mg/kg with the concentration of 0.21 mg/mL) by oral gavage (1 mL/100 g) once a day for 28 days. Rats' depression-like phenotypes were reflected with behavioral tests and biological detection methods. Results showed that acupuncture significantly improved the depression-like behavior of CUMS rat, suppressed the expressions of NLRP3, ASC, caspase-1, GSDMD, IL-1ß, IL-18, HMGB1, IFN-γ, IL-6 and TNF-α in the serum and hippocampus, restored the %area of microglia, astrocytes and neuronal cells in the hippocampus. These indicate that acupuncture can prevent CUMS-induced depression-like behaviors by reducing NLRP3-mediated pyroptosis and inflammation.


Assuntos
Terapia por Acupuntura , Proteína 3 que Contém Domínio de Pirina da Família NLR , Animais , Depressão/metabolismo , Depressão/terapia , Fluoxetina/farmacologia , Fluoxetina/uso terapêutico , Inflamassomos/metabolismo , Inflamação , Proteína 3 que Contém Domínio de Pirina da Família NLR/metabolismo , Piroptose , Ratos , Ratos Sprague-Dawley , Estresse Psicológico/terapia
12.
Microorganisms ; 10(5)2022 May 17.
Artigo em Inglês | MEDLINE | ID: mdl-35630484

RESUMO

Trichoderma longibrachiatum sp. are free-living filamentous fungi which are common in agro-ecosystems. However, few studies thus far have examined the interaction between Trichoderma longibrachiatum and arbuscular mycorrhizal (AM) fungi in saline soil and their potential for improving plant stress tolerance. Here, single, dual-inoculated (T. longibrachiatum MF, AM fungal community or Glomus sp.), and non-inoculated maize (Zea may L.) were subjected to different salinity levels (0, 75, 150, and 225 mM NaCl) to test the synergistic effects of dual inoculants on maize plants in different salt stress conditions. Plant performance and metabolic profiles were compared to find the molecular mechanisms underlying plant protection against salt stress. The first experiment revealed that dual inoculation of an AM fungal community and T. longibrachiatum MF improved the biomass and K+/Na+ ratio in maize under non-saline conditions, and generally enhanced AM fungal growth in root and soil under all but the 225 mM NaCl conditions. However, MF inoculant did not influence the structure of AM fungal communities in maize roots. In the second experiment, dual inoculation of Glomus sp. and T. longibrachiatum MF increased maize plant biomass, K+/Na+ ratio, and AM fungal growth in root and soil significantly at both 0 and 75 mM NaCl conditions. We identified metabolic compounds differentially accumulated in dual-inoculated maize that may underline their enhanced maize plant tolerance to increasing soil salinity. Our data suggested that the combination of Glomus sp. and T. longibrachiatum leads to interactions, which may play a potential role in alleviating the stress and improve crop productivity in salt-affected soils.

13.
Sensors (Basel) ; 22(10)2022 May 11.
Artigo em Inglês | MEDLINE | ID: mdl-35632073

RESUMO

Dealing with low-light images is a challenging problem in the image processing field. A mature low-light enhancement technology will not only be conductive to human visual perception but also lay a solid foundation for the subsequent high-level tasks, such as target detection and image classification. In order to balance the visual effect of the image and the contribution of the subsequent task, this paper proposes utilizing shallow Convolutional Neural Networks (CNNs) as the priori image processing to restore the necessary image feature information, which is followed by super-pixel image segmentation to obtain image regions with similar colors and brightness and, finally, the Attentive Neural Processes (ANPs) network to find its local enhancement function on each super-pixel to further restore features and details. Through extensive experiments on the synthesized low-light image and the real low-light image, the experimental results of our algorithm reach 23.402, 0.920, and 2.2490 for Peak Signal to Noise Ratio (PSNR), Structural Similarity (SSIM), and Natural Image Quality Evaluator (NIQE), respectively. As demonstrated by the experiments on image Scale-Invariant Feature Transform (SIFT) feature detection and subsequent target detection, the results of our approach achieve excellent results in visual effect and image features.


Assuntos
Aumento da Imagem , Processamento de Imagem Assistida por Computador , Algoritmos , Humanos , Aumento da Imagem/métodos , Processamento de Imagem Assistida por Computador/métodos , Redes Neurais de Computação , Razão Sinal-Ruído
14.
J Oncol ; 2022: 7031674, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35637856

RESUMO

Background: Cirrhotic severity scoring (CSS) is a noninvasive method that can predict histological severity of cirrhosis. This study is aimed at assessing the predictive value of CSS on long-term outcomes after curative hepatectomy for patients with hepatitis B virus- (HBV-) related hepatocellular carcinoma (HCC) and Child-Pugh grade A liver function and further developing novel nomograms to preoperatively predict posthepatectomy recurrence and survival. Methods: Consecutive patients who underwent curative hepatectomy for HCC between 2008 and 2014 were retrospectively studied. According to the CSS, patients were subclassified into 3 groups: no/mild, moderate, and severe cirrhosis. The impact of CSS on recurrence-free survival (RFS) and overall survival (OS) was assessed. Furthermore, RFS and OS nomograms were developed. Results: The 5-year RFS and OS rates were 36.1% and 62.8% in the no/mild cirrhosis group, compared with 28.4% and 56.2% in the moderate cirrhosis group, and 16.2% and 33.0% in the severe cirrhosis group. Long-term survival outcomes were significantly worse with the increment of cirrhotic severity. CSS, alpha-fetoprotein level, tumor size, tumor number, and macrovascular invasion were identified as independent predictors of both RFS and OS. Besides, albumin-bilirubin grade was an independent risk factor of OS not RFS. RFS- and OS-predictive nomograms based on these preoperative variables were built. For these 2 nomograms, the C-indexes were 0.696 and 0.732, respectively. Calibration curves exhibited good agreement between actual observation and nomogram prediction. Conclusions: CSS was a predictor for long-term outcomes in HCC patients after curative hepatectomy. The novel nomograms exhibited accurate preoperative prediction of posthepatectomy recurrence and OS.

15.
ACS Omega ; 7(17): 14527-14534, 2022 May 03.
Artigo em Inglês | MEDLINE | ID: mdl-35557659

RESUMO

In order to shorten the ignition delay of 2-azido-N,N-dimethylethanamine (DMAZ) and dinitrogen tetroxide (NTO), four amines [tert-butylamine, pyrrole, N,N,N',N'-tetramethyl ethylenediamine (TMEDA), and diethylenetriamine (DABH)] with a mass fraction of 5% were added to DMAZ, and the potential energy change and the product change during the reaction of the mixture of an additive and DMAZ with NTO were analyzed by Reactive molecular dynamics (ReaxFF MD) calculation. Then, the ignition delay of the mixture of the additive and DMAZ as well as pure DMAZ with NTO was measured by a drop experiment with a photoelectric sensor and high-speed camera. The results show that the addition of pyrrole greatly reduced the time to reach the maximum system energy and greatly increased the rate of HNO2 formation. The dripping of the fuel was approximately a uniform linear motion, and the expression was y = 43.13 + 7.16x. The ignition delay time recorded by the camera was in good agreement with that of the optical signal. The measured ignition delay time for DMAZ with NTO was 261.5 ms. The mixture of pyrrole and DMAZ with NTO had the shortest ignition delay time of 100 ms, and the proportion of shortening the ignition delay time was the largest. The results of the droplet experiment were consistent with those of ReaxFF MD simulation, indicating that HNO2 plays an important role in the ignition delay, that is, the formation rate of HNO2 is positively correlated with the ignition delay.

16.
J Mater Chem B ; 10(35): 6752-6757, 2022 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-35403657

RESUMO

ß-Lactoglobulin (ß-Lg), a food allergen, can easily cause allergic reactions in infants and young children. Therefore, it is necessary to develop a rapid, sensitive, and selective detection method to protect individuals prone to allergies. In this paper, a fluorescence assay based on WS2 nanosheets and a fluorescent dye (FAM)-labeled ß-Lg aptamer was designed to detect ß-Lg rapidly with high sensitivity. In the sensing platform, the ß-Lg aptamer is adsorbed on the WS2 nanosheet surface by van der Waals forces, which trigger the phenomenon of fluorescence resonance energy transfer (FRET) and suppress the fluorescence signal in the system. When ß-Lg is present, the conformation of the aptamer specifically bound to ß-Lg changes. Therefore, the aptamer is separated from the WS2 nanosheet surface, and the fluorescence signal is recovered. This method combines the high quenching efficiency of WS2 nanosheets and good specificity of the ß-Lg aptamer. The detection range of this method for ß-Lg is 0.1-100 µg mL-1. The detection limit is 20.4 ng mL-1. This method exhibits high sensitivity, selectivity and good reproducibility, and it can be used for ß-Lg detection in actual samples.


Assuntos
Lactoglobulinas , Leite , Alérgenos , Animais , Criança , Pré-Escolar , Corantes Fluorescentes , Humanos , Limite de Detecção , Reprodutibilidade dos Testes
17.
Hepatobiliary Surg Nutr ; 11(2): 227-252, 2022 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-35464283

RESUMO

Recent advances in systemic and locoregional treatments for patients with unresectable or advanced hepatocellular carcinoma (HCC) have resulted in improved response rates. This has provided an opportunity for selected patients with initially unresectable HCC to achieve adequate tumor downstaging to undergo surgical resection, a 'conversion therapy' strategy. However, conversion therapy is a new approach to the treatment of HCC and its practice and treatment protocols are still being developed. Review the evidence for conversion therapy in HCC and develop consensus statements to guide clinical practice. Evidence review: Many research centers in China have accumulated significant experience implementing HCC conversion therapy. Preliminary findings and data have shown that conversion therapy represents an important strategy to maximize the survival of selected patients with intermediate stage to advanced HCC; however, there are still many urgent clinical and scientific challenges for this therapeutic strategy and its related fields. In order to summarize and learn from past experience and review current challenges, the Chinese Expert Consensus on Conversion Therapy for Hepatocellular Carcinoma (2021 Edition) was developed based on a review of preliminary experience and clinical data from Chinese and non-Chinese studies in this field and combined with recommendations for clinical practice. Sixteen consensus statements on the implementation of conversion therapy for HCC were developed. The statements generated in this review are based on a review of clinical evidence and real clinical experience and will help guide future progress in conversion therapy for patients with HCC.

18.
Mar Drugs ; 20(3)2022 Mar 04.
Artigo em Inglês | MEDLINE | ID: mdl-35323490

RESUMO

Oxidative stress has been implicated in the etiology of Parkinson's disease (PD). Molecules non-covalently binding to the Keap1-Nrf2 complex could be a promising therapeutic approach for PD. Herein, two novel prenylated indole alkaloids asperpenazine (1), and asperpendoline (2) with a scarce skeleton of pyrimido[1,6-a]indole were discovered from the co-cultivated fungi of Aspergillus ochraceus MCCC 3A00521 and Penicillium sp. HUBU 0120. Compound 2 exhibited potential neuroprotective activity on SH-SY5Y cells against oxidative stress. Molecular mechanism research demonstrated that 2 inhibited Keap1 expression, resulting in the translocation of Nrf2 from the cytoplasm to the nucleus, activating the downstream genes expression of HO-1 and NQO1, leading to the reduction in reactive oxygen species (ROS) and the augment of glutathione. Molecular docking and dynamic simulation analyses manifested that 2 interacted with Keap1 (PDB ID: 1X2R) via forming typical hydrogen and hydrophobic bonds with residues and presented less fluctuation of RMSD and RMSF during a natural physiological condition.


Assuntos
Alcaloides Indólicos/farmacologia , Proteína 1 Associada a ECH Semelhante a Kelch/metabolismo , Fator 2 Relacionado a NF-E2/metabolismo , Fármacos Neuroprotetores/farmacologia , Aspergillus ochraceus/química , Aspergillus ochraceus/metabolismo , Linhagem Celular Tumoral , Glutationa/metabolismo , Humanos , Alcaloides Indólicos/química , Alcaloides Indólicos/metabolismo , Simulação de Acoplamento Molecular , Simulação de Dinâmica Molecular , Estrutura Molecular , Neuroproteção/efeitos dos fármacos , Fármacos Neuroprotetores/química , Fármacos Neuroprotetores/metabolismo , Estresse Oxidativo/efeitos dos fármacos , Penicillium/química , Penicillium/metabolismo , Prenilação
19.
Luminescence ; 37(6): 944-952, 2022 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-35338676

RESUMO

Inorganic-organic hybrid nanoparticles formed by lanthanide-doped nanostructures and organic ligands have been intensively studied, which could greatly increase their photoluminescence performance as a result of the energy transfer process from organic ligands to Ln3+ ions. However, the photoluminescence intensity and excitation spectral width are still quite limited on coordinating with a single type of organic ligand. In this work, Eu3+ -doped LaF3 (LaF3 :Eu3+ ) nanoparticles were prepared using a hydrothermal method, and were then hybridized with benzoic acid and thenoyltrifluoroacetone to form the hybrid nanostructures. After that, the hybrid nanostructures were mixed with 2,2'-azobisisobutyronitrile and methyl methacrylate to prepare the composites. The sample obtained by hybridization and composite doping with 5% Eu3+ exhibited the best photoluminescence performance. The excitation peak width and luminescence intensity of the hybrid nanostructures were significantly increased. The excitation spectral width of the inorganic-organic mixed hybrid nanostructures was particularly enhanced, and covered the whole ultraviolet band region of solar light on Earth. The prepared composites exhibited good optical properties.

20.
J Environ Manage ; 310: 114752, 2022 May 15.
Artigo em Inglês | MEDLINE | ID: mdl-35231691

RESUMO

Aeration system is the main energy consumer in a wastewater treatment process. In this paper, the Naive Bayes classification (NBC) algorithm and response surface method (RSM) were firstly used to establish a methodology to improve the aeration efficiency and estimate effluent quality. Lab-scale experiments were conducted to verify the model. The errors between experimental values and predicted values were 3.36, -0.67 and -3.78% at operating temperatures of 20, 30 and 35 °C, indicating the applicability. To further elucidate the biological mechanisms of the experimental results, the microbial community composition was investigated under various operating conditions, the results shows that aerobic heterotrophic bacteria (HET) activity and COD removal efficiency were promoted at 30 °C. AOB and NOB activity and NH4+-N removal efficiency were promoted at 30-35 °C. These findings together suggest that operating temperature is crucial for activated sludge treatment, which should be considered when regulating DO content or aeration rate in practical application.


Assuntos
Microbiota , Purificação da Água , Teorema de Bayes , Reatores Biológicos/microbiologia , Nitrogênio , Esgotos , Eliminação de Resíduos Líquidos/métodos , Águas Residuárias
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