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1.
ACS Nano ; 2020 Mar 26.
Artigo em Inglês | MEDLINE | ID: mdl-32203665

RESUMO

Systemic lupus erythematosus (SLE), a common lethal autoimmune disease, is characterized by effector/regulatory T cells imbalance. Current therapies are either inefficient or have severe side effects. MicroRNA-125a (miR-125a) can stabilize Treg-mediated self-tolerance by targeting effector programs, but it is significantly downregulated in peripheral T cells of patients with SLE. Therefore, overexpression of miR-125a may have therapeutic potential to treat SLE. Considering the stability and targeted delivery of miRNA remains a major challenge in vivo, we constructed a monomethoxy (polyethylene glycol)-poly(d,l-lactide-co-glycolide)-poly(l-lysine) (mPEG-PLGA-PLL) nanodelivery system to deliver miR-125a into splenic T cells. Results demonstrate that miR-125a-loaded mPEG-PLGA-PLL (PEALmiR-125a) nanoparticles (NPs) exhibit good biocompatibility and protect miR-125a from degradation, thereby prolonging the circulatory time of miRNA in vivo. In addition, PEALmiR-125a NPs are preferentially enriched in a pathological spleen and efficiently deliver miR-125a into the splenic T cells in SLE mice models. The PEALmiR-125a NPs treatment significantly alleviates SLE disease progression by reversing the imbalance of effector/regulatory T cells. Collectively, the PEALmiR-125a NPs show excellent therapeutic efficacy and safety, which may provide an effective treatment for SLE.

2.
Chemistry ; 2020 Mar 24.
Artigo em Inglês | MEDLINE | ID: mdl-32212175

RESUMO

In this work, we successfully prepared Pb-doped titanium-oxo clusters with core structures as isolated perovskite PbTiO3 species. In the obtained highly symmetric Pb8Ti7-oxo cluster, the central TiO6 octahedra are orthogonally extended to adjacent ones in corner-sharing way and the doped 8 Pb ions form a cubic arrangement, making it the first molecular model of perovskite PbTiO3. Moreover, they show high solution stability confirmed by MALDI-TOF-MS measurements. Based on such solution processability, they can be easily spin-coated into homogeneous films, which were further applied as electron transport materials in perovskite solar cells to give the average PCE of ~15 % and improved device stability. The developed bottom-up cluster assembly method opens an efficient way for the construction of atomically precise models of perovskite metal oxides, and provides potential molecular tools to extend their applications.

3.
ACS Sens ; 2020 Mar 25.
Artigo em Inglês | MEDLINE | ID: mdl-32208610

RESUMO

Accurate and efficient gas monitoring is still in challenge because the existing sensing techniques mostly lack the specific identification of gases or hardly meet the requirement of real-time readout. Herein, we present a strategy of conductometric response-triggered surface enhanced Raman spectroscopy (SERS) for such gas monitoring, via designing and using ultrathin oxide-wrapped plasmonic metal nanoparticles (NPs). The oxide wrapping layer can interact with and capture target gaseous molecules, and produce the conductometric response, while the plasmonic metal NPs possess strong SERS activity. In this strategy, the conductometric gas sensing is performed throughout the whole monitoring process, and once a conductometric response is generated, it will trigger the SERS measurements which can accurately recognize molecules and hence realize gas monitoring. The feasibility of this strategy has been demonstrated via using ultrathin SnO2 layer-wrapped Au NPs' film to monitor gaseous 2-phenylethanethiol molecules. It has been shown that the monitoring is rapid, accurate and quantifiable. There exist the optimal values of working temperature and SnO2 layer's thickness, which are about 100 oC and 2.5 nm, respectively, for monitoring gaseous 2-phenylethanethiol. The monitoring signal intensity has a linear relation with the gas concentration in the range from 1 ppm to 100 ppm in logarithmic scale. Further, the monitoring limits are at ppm level for some typical gases, such as 2-phenylethanethiol, cyclohexanethiol, 1-dodecanethiol and toluene. This study establishes the conductometric response-triggered SERS, which enables the accurate gas recognition and real-time monitoring.

4.
Opt Express ; 28(1): 314-324, 2020 Jan 06.
Artigo em Inglês | MEDLINE | ID: mdl-32118960

RESUMO

Hyperspectral imaging provides rich spatial-spectral-temporal information with wide applications. However, most of the existing hyperspectral imaging systems require light splitting/filtering devices for spectral modulation, making the system complex and expensive, and sacrifice spatial or temporal resolution. In this paper, we report an end-to-end deep learning method to reconstruct hyperspectral images directly from a raw mosaic image. It saves the separate demosaicing process required by other methods, which reconstructs the full-resolution RGB data from the raw mosaic image. This reduces computational complexity and accumulative error. Three different networks were designed based on the state-of-the-art models in literature, including the residual network, the multiscale network and the parallel-multiscale network. They were trained and tested on public hyperspectral image datasets. Benefiting from the parallel propagation and information fusion of different-resolution feature maps, the parallel-multiscale network performs best among the three networks, with the average peak signal-to-noise ratio achieving 46.83dB. The reported method can be directly integrated to boost an RGB camera for hyperspectral imaging.

5.
Int J Biometeorol ; 2020 Mar 04.
Artigo em Inglês | MEDLINE | ID: mdl-32130524

RESUMO

Since systolic pulmonary arterial pressure (SPAP) is an important diagnostic indicator for various cardiovascular diseases, it is of great significance to determine scientific SPAP reference value in clinical application. However, the SPAP reference values currently have not been applied under a unified standard, and its formulation does not consider the impacts from geographical environment which has proved to be closely associated with SPAP. This study aims to quantify the impacts of geographical factors on SPAP and formulate scientific SPAP reference values, thereby providing support for more accurate diagnosis. Measured SPAP values of 4550 healthy adults were collected from 88 cities across China, and 11 geographical factors were selected. Four geographical factors with significant impacts on SPAP were determined via correlation analysis, including two positive factors (altitude, soil organic matter) and two negative ones (longitude, annual average temperature). Then partial least-squares regression analysis (PLSR) and trend surface analysis were applied to establish predictive models. Through model test using both collected and simulated SPAP data of control points, the PLSR model was determined to have better prediction accuracy and was selected as optimal model to calculate the SPAP reference values of 2322 cities in China. The predictive results ranged from 22.09 to 31.77 mmHg. Finally, hotspot analysis and kriging interpolation method were applied to explore the spatial distribution of SPAP reference values. The result of spatial analysis shows that SPAP reference values of Chinese adults decreased gradually from the West to East in China. This study indicated the significant impacts of geographical environment on SPAP and established predictive model for determining SPAP reference values, which is expected to help enhance clinical diagnostic accuracy.

6.
Nanoscale ; 2020 Mar 04.
Artigo em Inglês | MEDLINE | ID: mdl-32129398

RESUMO

Multinary copper-based chalcogenide nanocrystals (NCs) as light-driven photocatalysts have attracted extensive research interest due to their great potential for generating sustainable energy without causing environmental concerns. However, systematic studies on the growth mechanism and related photocatalytic activities involving different valent metal ions (either M2+ or N3+) as foreign cations and monoclinic Cu1.94S NCs as the 'parent lattice' have rarely been carried out. In this work, we report an effective seed-mediated method for the synthesis of heterostructured Cu1.94S-MS NCs (M = Zn, Cd and Mn) and alloyed CuNS2 NCs (N = In and Ga). A typical cation exchange process took place prior to the growth of heterostructured NCs, while further inter-cation diffusion occurred only for the alloyed NCs. When compared with Cu1.94S NCs, all the heterostructured Cu1.94S-MS NCs and CuGaS2 NCs showed enhanced photocatalytic activities toward hydrogen production by water splitting, owing to their tailored optical band gaps and energy level alignments. Although optically favored, CuInS2 ANCs were not comparable to others due to their low conduction band minimum for the reduction of H2O to H2.

7.
J Mater Chem B ; 8(10): 2115-2122, 2020 Mar 11.
Artigo em Inglês | MEDLINE | ID: mdl-32073099

RESUMO

Finding out how to overcome multistage biological barriers for nanocarriers in cancer therapy to obtain highly precise drug delivery is still a challenge. Herein, we prepared a multistage and cascaded switchable polymeric nanovehicle, self-assembled from polyethylene glycol grafted amphiphilic copolymer containing hydrophobic poly(ortho ester) and hydrophilic ethylenediamine-modified poly(glycidyl methacrylate) (PEG-g-p(GEDA-co-DMDEA)) for imaging-guided chemo-photothermal combination anticancer therapy. Notably, a novel ATRP initiator containing cyanine dye was designed and attached to the polymer, providing the nanovehicle with NIR-light induced photothermal and fluorescent properties. The PEG shell displayed tumor-microenvironment-induced detachment, resulting in the surface charge change of the nanovehicle from neutral to positive and thus enhancing cellular uptake. Subsequently, the hydrophobic pDMDEA hydrolyzed into a hydrophilic segment in the acidic lysosome, leading to sufficient drug release. Finally, with the aid of the photothermal property, the therapeutic drug DOX successfully escaped from the lysosome to exert chemotherapy. This well-defined polymeric nanoplatform promoted the development of designing novel theranostic polymeric nanovehicles for precise cancer therapy.

8.
Nanoscale Horiz ; 5(4): 739-746, 2020 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-32073017

RESUMO

Detection of trace harmful small gaseous molecules (h-SGMs), based on surface enhanced Raman spectroscopy (SERS), has been expected to be a useful strategy but is challenging due to the extremely small Raman cross section (RCS) and weak metal affinity of the h-SGMs. Here, a new strategy, ultrathin layer solid transformation-enabled (ULSTE)-SERS, is proposed. It uses the chemical reaction between the target h-SGM and an ultrathin layer of solid sensing matter coated on a plasmonic metal SERS substrate. This reaction in situ produces a new solid matter with large RCS, which ensures the detection of trace h-SGMs via SERS. The validity of this strategy has been demonstrated by detecting trace H2S gas with an ultrathin CuO layer wrapped around Au nanoparticles. Furthermore, this strategy allows fast and ultrasensitive detection. The detection limit can be down to ppb (even ppt) levels with 10 min preprocessing. Importantly, this strategy has good universality for various other h-SGMs, such as SO2, CS2, CH3SH, and HCl, etc., using appropriate sensing matter. Additionally, the ULSTE-SERS is also suitable for unstable molecules and fast portable detection due to the stable solid layer. This work provides highly efficient SERS-based detection of trace h-SGMs, which is easily applied in practical situations.

9.
Curr Med Chem ; 2020 Jan 27.
Artigo em Inglês | MEDLINE | ID: mdl-32003658

RESUMO

Breast cancer is the most common cancer in women worldwide. Due to the heterogeneous nature of breast cancer, the optimal treatment and expected response for each patient may not necessarily be universal. Molecular imaging techniques could play an important role in the early detection and targeted therapy evaluation of breast cancer. This review focuses on the development of peptides labeled with SPECT and PET radionuclides for breast cancer imaging. We summarized the current status of radiolabeled peptides for different receptors in breast cancer. The characteristics of radionuclides and major techniques for peptide labeling are also briefly discussed.

10.
Bioinformatics ; 2020 Feb 19.
Artigo em Inglês | MEDLINE | ID: mdl-32073624

RESUMO

MOTIVATION: For the diagnosis of cancer, manually counting nuclei on massive histopathological images is tedious and the counting results might vary due to the subjective nature of the operation. RESULTS: This paper presents a new segmentation and counting method for nuclei, which can automatically provide nucleus counting results. This method segments nuclei with detected nuclei seed markers through a modified simple one-pass superpixel segmentation method. Rather than using a single pixel as a seed, we created a superseed for each nucleus to involve more information for improved segmentation results. Nucleus pixels are extracted by a newly proposed fusing method to reduce stain variations and preserve nucleus contour information. By evaluating segmentation results, the proposed method was compared to five existing methods on a dataset with 52 immunohistochemically (IHC) stained images. Our proposed method produced the highest mean F1-score of 0.668. By evaluating the counting results, another dataset with more than 30,000 IHC stained nuclei in 88 images were prepared. The correlation between automatically generated nucleus counting results and manual nucleus counting results was up to R2 = 0.901 (p < 0.001). By evaluating segmentation results of proposed method-based tool, we tested on a 2018 Data Science Bowl (DSB) competition dataset, three users obtained DSB score of 0.331 ± 0.006. AVAILABILITY: The proposed method has been implemented as a plugin tool in ImageJ and the source code can be freely downloaded. SUPPLEMENTARY INFORMATION: Supplementary data are available at https://www.dropbox.com/sh/e7oz4nhp3gekvk4/AAC-xuqg5DUx0H5JdqPApbWTa?dl=0s online.

11.
ACS Sens ; 5(2): 571-579, 2020 Feb 28.
Artigo em Inglês | MEDLINE | ID: mdl-32013398

RESUMO

During the detection of industrial toxic gases, such as triethylamine (TEA), poor selectivity and negative humidity impact are still challenging issues. A frequently reported strategy is to employ molecular sieves or metal-organic framework (MOF) membranes so that interference derived from surrounding gases or water vapor can be blocked. Nevertheless, the decline in the response signal was also observed after coating these membranes. Herein, an alternative strategy that is based on a hydrophobic, TEA adsorption-selective p-n conjunction core-shell heterostructure is proposed and is speculated to simultaneously enhance selectivity, sensitivity, and humidity resistance. To verify the practicability of the proposed strategy, a thickness-tunable nitrogen-doped carbon (N-C) shell-coated α-Fe2O3 nano-olive (N-C@α-Fe2O3 NO)-based core-shell heterostructure that is obtained via a unique all-vapor-phase processing method is selected as the research example. After forming the core-shell heterostructure, a relatively hydrophobic and TEA adsorption-selective N-C@α-Fe2O3 NO surface was experimentally confirmed. Particularly, a chemiresistive sensor that comprises N-C@α-Fe2O3 NOs exhibits satisfactory selectivity and response magnitude to TEA when compared with the sensor using α-Fe2O3 NOs. The detection limit can even reduce to be 400 ppb at 250 °C. Furthermore, the sensor based on N-C@α-Fe2O3 NOs shows desirable humidity resistance within the relative humidity (RH) range of 30-90%. For practical usage, a sensing prototype based on the N-C@α-Fe2O3 NO probe is fabricated, and its satisfactory sensing performance further confirms the potential for future applications in industrial organic amine detection. These promising results show a bright future in enhancing the humidity resistance and selectivity as well as sensitivity of chemiresistive sensors by simply designing a hydrophobic and target gas adsorption (e.g., TEA) preferred p-n junction core-shell heterostructure.

12.
Mol Brain ; 13(1): 22, 2020 Feb 18.
Artigo em Inglês | MEDLINE | ID: mdl-32070382

RESUMO

The anterior cingulate cortex (ACC) serves as a critical hub for the anxiety and pain perception. The large-conductance Ca2+-activated potassium channels, or BKCa channels, are ubiquitously expressed throughout the central nervous system including the cingulate cortex. However, what changes of cortical BKCa channels undergo in the ACC remains unknown in pain-related anxiety. In the present study, a significant upregulation of synaptic and non-synaptic BKCa channel accessory ß4 subunits in the ACC was accompanied with pain-associated anxiety-like behaviors in the chronic compression of multiple dorsal root ganglia (mCCD) of the rat. NS1619, an opener of BKCa channels, significantly rescued the alteration of fAHP and AP duration of ACC pyramidal neurons in mCCD rats. The mRNA expression of BKCa ß4 subunits was extremely upregulated in the ACC after mCCD with the increased amount of both synaptic and non-synaptic BKCa ß4 subunit protein. Meanwhile, NS1619 reversed the enhanced AMPA receptor-mediated spontaneous excitatory postsynaptic current (sEPSC) frequency and the attenuated PPR of ACC neurons in mCCD rats. Local activation of BKCa channels in the ACC reversed mechanical allodynia and anxiety-like behaviors. These results suggest that the upregulation of postsynaptic and presynaptic BKCa ß4 subunit may contribute to neuronal hyperexcitability and the enhanced synaptic transmission in the ACC in neuropathic pain state, and then may result in anxiety-like behavior induced by neuropathic pain.

13.
Nanoscale ; 2020 Feb 04.
Artigo em Inglês | MEDLINE | ID: mdl-32016256

RESUMO

Blackening (or enhancing the optical absorption in the visible region) of nano-sized white semiconducting oxides (N-WSOs) is of significant importance for solar utilization. Here, we present a novel Mars-van-Krevelen mechanism-based method for blackening the N-WSOs via facile one-step heating of the N-WSOs with alcohols. Taking n-butanol-induced blackening of TiO2 (anatase) as an example, the pristine TiO2 NP powders can be successfully blackened to form black TiO2 (B-TiO2) via heating with n-butanol at 300 °C for 20 min. Technical analyses demonstrate that the B-TiO2 nanocrystals are wrapped with a 2 nm thick disordered layer, which is rich in oxygen vacancies, Ti3+ and hydroxyl groups. Both theoretical and experimental results show that B-TiO2 has much stronger optical absorption in the visible region than pristine TiO2. Furthermore, the influence factors (including heating temperatures and alcohol types) and good universality of this blackening method are also demonstrated. A blackening principle based on Mars-van-Krevelen mechanism-induced oxygen vacancy generation and hydroxylation-anchoring of oxygen vacancies has been proposed, and the mechanism can well explain all the phenomena observed in experiments. Importantly, such B-TiO2 shows hugely enhanced activity in solar photodegradation of dye pollutants. Under simulated solar irradiation, the degradation rate constant achieved by the B-TiO2 catalyst is 2.3 times that of the pristine TiO2, showing an obvious enhancement. Further experiments reveal that the improved degradation activity is mainly attributed to the enhanced optical absorption in the visible region and the synergistic photothermal and photocatalytic effect. This study demonstrates a new and facile approach to blacken the N-WSOs for enhanced solar utilization.

14.
J Environ Radioact ; 213: 106136, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-31983445

RESUMO

Beibu Gulf is a highly dynamic and complex coastal environment that is currently experiencing one of the largest rates of development and urbanization in west China. Little is known about the effects of this increased human activity on coastal sedimentation processes and on the rates of sediment accumulation and the variation of organic materials to the coast. In this study, four sediment cores were collected and applied the 210Pb dating method to reconstruct sedimentation rates and historical changes of materials to the northern Beibu Gulf over the past century. Depth profiles of excess 210Pb (210Pbex) showed highest activity values at the surface (28.4-104.0 Bq kg-1) followed by a linear or exponential decay with depth for all but one study site. 137Cs activity ranged between 0.236 and 2.034 Bq kg-1, and a distinct peak activity - representing the 1963 fallout maximum - was observed at all but one site. Sediment chronologies were determined using the Constant Rate of Supply (CRS) model. Calculated accumulation rates in the studied sites were the lowest in the late 1920s and early 1930s (mass accumulation rate (MAR): 0.06 ± 0.01 g cm-2 y-1; sediment accumulation rate (SAR): 0.08 ± 0.01 cm y-1) and increased gradually until reaching maximum values in the 2010s (MAR: 0.22 ± 0.09 g cm-2 y-1; SAR: 0.46 ± 0.32 cm y-1). Current accumulation rates are up to 800% higher than rates observed in the 1920s, with most of the increase happening after 1970, coinciding with the increasing rate of urbanization and development in the region. The highest increase in SAR over the last century (+877%) was observed in Sanniang Bay, with the lowest rate of increase (+283%) observed in Lianzhou Bay. TOC content in these sediments has also increased over the last 100 years. Current values (0.98-1.28%) are about 170% higher than historical concentrations (before 1970). The positive correlations between TOC and population density and GDP growth in major cities surrounding the gulf, provide further indication that human activities have significantly altered the sedimentary environment in recent decades along the northern Beibu Gulf coast.


Assuntos
Sedimentos Geológicos , Monitoramento de Radiação , Césio , China , Monitoramento Ambiental , Humanos , Chumbo , Poluentes Químicos da Água
15.
Chem Commun (Camb) ; 56(14): 2103-2106, 2020 Feb 18.
Artigo em Inglês | MEDLINE | ID: mdl-31970353

RESUMO

Porous organic polymers (POPs) have received much attention, due to their multiple potential applications and flexibility in chemical structure design. Creation of a novel chemical structure has been the central task in the research of POPs, which are usually constructed by direct coupling polymerizations. The fascinating rearrangement/tautomerization could lead to some novel structures, which are hard to access by conventional direct coupling polymerizations. Herein, the tautomerization from tris(ß-hydroxyl-azo)benzene to the tris(ß-keto-hydrozo)cyclohexane structure has been proved unambiguously based on an advanced 2D NMR technique such as 15N-1H-HSQC and 1H-1H-NOESY. The crucial tautomerization was used to synthesize TKH-POPs for the first time. The as-synthesized TKH-POP-1 was found to have an adsorption capacity as high as 66.3 mmol g-1 (at 273 K and P/P0 = 0.98) towards acetonitrile vapor, which was the highest among all the reported materials. The general and flexible strategy to make functional POPs with tunable pores such as ultramicropores, micropores and mesopores will help develop interesting functional POPs in the near future.

16.
Epidemiol Infect ; 148: e4, 2020 Jan 10.
Artigo em Inglês | MEDLINE | ID: mdl-31918780

RESUMO

Lassa fever (LF) is increasingly recognised as an important rodent-borne viral haemorrhagic fever presenting a severe public health threat to sub-Saharan West Africa. In 2017-18, LF caused an unprecedented epidemic in Nigeria and the situation was worsening in 2018-19. This work aims to study the epidemiological features of epidemics in different Nigerian regions and quantify the association between reproduction number (R) and state rainfall. We quantify the infectivity of LF by the reproduction numbers estimated from four different growth models: the Richards, three-parameter logistic, Gompertz and Weibull growth models. LF surveillance data are used to fit the growth models and estimate the Rs and epidemic turning points (τ) in different regions at different time periods. Cochran's Q test is further applied to test the spatial heterogeneity of the LF epidemics. A linear random-effect regression model is adopted to quantify the association between R and state rainfall with various lag terms. Our estimated Rs for 2017-18 (1.33 with 95% CI 1.29-1.37) was significantly higher than those for 2016-17 (1.23 with 95% CI: (1.22, 1.24)) and 2018-19 (ranged from 1.08 to 1.36). We report spatial heterogeneity in the Rs for epidemics in different Nigerian regions. We find that a one-unit (mm) increase in average monthly rainfall over the past 7 months could cause a 0.62% (95% CI 0.20%-1.05%)) rise in R. There is significant spatial heterogeneity in the LF epidemics in different Nigerian regions. We report clear evidence of rainfall impacts on LF epidemics in Nigeria and quantify the impact.

17.
Oncologist ; 2020 Jan 20.
Artigo em Inglês | MEDLINE | ID: mdl-31957916

RESUMO

BACKGROUND: Because beneficial response and progression-free survival (PFS) were achieved by well-designed clinical trials with tyrosine kinase inhibitors (TKIs) in patients with progressive radioiodine-refractory differentiated thyroid cancer (RR-DTC), the overall survival (OS) and improvement of therapeutic outcomes in the real world have been anticipated. SUBJECTS, MATERIALS, AND METHODS: This prospective, single-center, real-world study assessed the predictive significance of clinicopathological features on disease control rate (DCR), objective response rate (ORR), PFS, and OS in a cohort of 72 patients with progressive RR-DTC treated with sorafenib at an initial dose of 200 mg twice daily. RESULTS: Disease control, objective response, and biochemical effectiveness were achieved in 73.3%, 21.7%, and 77.9% of patients, respectively. The median PFS and OS were 17.6 and 28.9 months, respectively. Multivariate analyses showed that hand-foot syndrome (HFS) was an independent predictor for better DCR and ORR, and 131 I-avidity for higher ORR. In univariate analyses, longer PFS and OS were observed in patients with Eastern Cooperative Oncology Group performance status (ECOG PS) ≤2, pathologically well DTC, lung-only metastasis, absence of bone metastasis, biochemically nonineffective response, HFS, or radiological disease control. In multivariate analyses, only well DTC and ECOG PS ≤2 remained as independent prognostic factors for more favorable PFS and OS, respectively, whereas the absence of bone metastasis and biochemically nonineffective response independently predicted superior PFS and OS. CONCLUSION: This study demonstrated that clinicopathological features might play a vital role in predicting therapeutic outcomes in patients with progressive RR-DTC treated with sorafenib, warranting further optimization of candidates for TKIs. IMPLICATIONS FOR PRACTICE: This prospective, single-center, real-world study was designed to investigate the significance of clinicopathological features in predicting response, progression-free survival, and overall survival in patients with progressive radioiodine-refractory differentiated thyroid cancer (DTC) treated with sorafenib. Multivariate analyses showed that hand-foot syndrome was an independent predictor for better response. Meanwhile, well DTC, Eastern Cooperative Oncology Group performance status ≤2, biochemically nonineffective response, and the absence of bone metastasis were independent prognostic factors for more favorable survival. This study demonstrated that clinicopathological features might play a vital role in predicting outcomes in sorafenib-treated patients with radioiodine-refractory DTC, warranting optimization of indications.

18.
J Cell Mol Med ; 24(6): 3336-3345, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-31970877

RESUMO

Clinical efficacy of differentiation therapy with mitogen-activated protein kinase inhibitors (MAPKi) for lethal radioiodine-refractory papillary thyroid cancer (RR-PTC) urgently needs to be improved and the aberrant trimethylation of histone H3 lysine 27 (H3K27) plays a vital role in BRAFV600E -MAPK-induced cancer dedifferentiation and drug resistance. Therefore, dual inhibition of MAPK and histone methyltransferase (EZH2) may produce more favourable treatment effects. In this study, BRAFV600E -mutant (BCPAP and K1) and BRAF-wild-type (TPC-1) PTC cells were treated with MAPKi (dabrafenib or selumetinib) or EZH2 inhibitor (tazemetostat), or in combination, and the expression of iodine-metabolizing genes, radioiodine uptake, and toxicity were tested. We found that tazemetostat alone slightly increased iodine-metabolizing gene expression and promoted radioiodine uptake and toxicity, irrespective of the BRAF status. However, MAPKi induced these effects preferentially in BRAFV600E mutant cells, which was robustly strengthened by tazemetostat incorporation. Mechanically, MAPKi-induced decrease of trimethylation of H3K27 was evidently intensified by tazemetostat in BRAFV600E -mutant cells. In conclusion, tazemetostat combined with MAPKi enhances differentiation of PTC cells harbouring BRAFV600E through synergistically decreasing global trimethylation of H3K27, representing a novel differentiation strategy.

19.
Spectrochim Acta A Mol Biomol Spectrosc ; 226: 117589, 2020 Feb 05.
Artigo em Inglês | MEDLINE | ID: mdl-31634714

RESUMO

Cornu Caprae Hircus (goat horn, GH) is one of the frequently used medicinal animal horns in traditional Chinese medicine (TCM). Hydrolysis is one of the key steps for GH pretreatment in pharmaceutical manufacturing. However, the physicochemical complexity of the hydrolysis samples imposes a challenge for hydrolysis process analysis and monitoring. In this study, convolutional neural networks (CNNs), one of the most popular deep learning methods, were used to develop quantitative calibration models based on on-line Raman spectroscopy for monitoring the GH hydrolysis process. Partial least squares (PLS) calibration models were also developed for model performance comparison. For CNN modeling, raw Raman spectra were used as inputs and hyperparameters in the CNN structure were optimized. Results show for four of the seven analytes, the optimized CNN models using raw spectra as inputs outperform the optimized PLS models developed with preprocessed spectra. Therefore, compared with the commonly used PLS algorithm, CNN modeling is also a practicable regression method and can be employed for the analytical purpose of this study. Models with better performance are expected to be obtained by improving the CNN model structure and using more effective hyperparameter optimization approaches in further studies. To the best of our knowledge, this is the first reported case study of combining CNNs and on-line Raman spectroscopy for a regression task.

20.
J Sep Sci ; 43(3): 663-670, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31674130

RESUMO

The chromatographic elution process is a key step in the production of notoginseng total saponins. Due to quality variability of loading samples and resin capacity decreasing over cycle time, saponins, especially the five main saponins of notoginseng total saponins, need to be monitored in real time during the elution process. In this study, convolutional neural networks, one of the most popular deep learning methods, were used to develop quantitative calibration models based on in-line near-infrared spectroscopy for notoginsenoside R1 , ginsenosides Rg1 , Re, Rb1 and Rd, and their sum concentration, with root mean square error of prediction values of 0.87, 2.76, 0.60, 1.57, 0.28, and 4.99 mg/mL, respectively. Partial least squares calibration models were also developed for model performance comparison. Results show predicted concentration profiles outputted by both the convolutional neural network models and partial least squares models show agreements with the real trends defined by reference measurements, and can be used for elution process monitoring and endpoint determination. To the best of our knowledge, this is the first reported case study of combining convolutional neural networks and in-line near-infrared spectroscopy for monitoring of the chromatographic elution process in commercial production of botanical drug products.

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