Synergistic Antitumor Effect of Dichloroacetate in Combination with 5-Fluorouracil in Colorectal Cancer

Dichloroacetate (DCA), an inhibitor of pyruvate dehydrogenase kinase (PDK), has been recently demonstrated as a promising nontoxic antineoplastic agent that promotes apoptosis of cancer cells. In the present study, we aimed to investigate the antitumor effect of DCA combined with 5-Fluorouracil (5-FU) on colorectal cancer (CRC) cells. Four human CRC cell lines were treated with DCA or 5-FU, or a combination of DCA and 5-FU. The cell viability was determined by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay. The interaction between DCA and 5-FU was evaluated by the median effect principle. Immunocytochemistry with bromodeoxyuridine (BrdU) was carried out to determine the proliferation of CRC cells. Cell cycle and apoptosis were measured by flow cytometry, and the expression of apoptosis-related molecules was assessed by western blot. Our results demonstrated that DCA inhibited the viability of CRC cells and had synergistic antiproliferation in combination with 5-FU. Moreover, compared with 5-FU alone, the apoptosis of CRC cells treated with DCA and 5-FU was enhanced and demonstrated with the changes of Bcl-2, Bax, and caspase-3 proteins. Our results suggest that DCA has a synergistic antitumor effect with 5-FU on CRC cell lines in vitro

Continuous Wave Single-longitudinal-mode 1342 nm Lasers: Modelling and Experiments

A model suitable to the continuous wave single longitudinal mode1342 nm solid state laser with energy transfer upconversion and excited state absorption taken into account is established. The critical condition for robust mode hop free operation and the methods for power scaling are proposed via iteration method. The theory agrees well with the experiment

Effects of Charge Transport Materials on Blue Fluorescent Organic Light-Emitting Diodes with a Host-Dopant System

High efficiency blue fluorescent organic light-emitting diodes (OLEDs), based on 1,3-bis(carbazol-9-yl)benzene (mCP) doped with 4,4’-bis(9-ethyl-3-carbazovinylene)-1,1’-biphenyl (BCzVBi), were fabricated using four different hole transport layers (HTLs) and two different electron transport layers (ETLs). Fixing the electron transport material TPBi, four hole transport materials, including 1,1-Bis[(di-4-tolylamino)phenyl]cyclohexane (TAPC), N,N’-Di(1-naphthyl)-N,N’-diphenyl-(1,1’-biphenyl)-4’-diamine(NPB), 4,4’-Bis(N-carbazolyl)-1,1,-biphenyl (CBP) and molybdenum trioxide (MoO3), were selected to be HTLs, and the blue OLED with TAPC HTL exhibited a maximum luminance of 2955 cd/m2 and current efficiency (CE) of 5.75 cd/A at 50 mA/cm2, which are 68% and 62% higher, respectively, than those of the minimum values found in the device with MoO3 HTL. Fixing the hole transport material TAPC, the replacement of TPBi ETL with Bphen ETL can further improve the performance of the device, in which the maximum luminance can reach 3640 cd/m2 at 50 mA/cm2, which is 23% higher than that of the TPBi device. Furthermore, the lifetime of the device is also optimized by the change of ETL. These results indicate that the carrier mobility of transport materials and energy level alignment of different functional layers play important roles in the performance of the blue OLEDs. The findings suggest that selecting well-matched electron and hole transport materials is essential and beneficial for the device engineering of high-efficiency blue OLEDs

Improved Efficiency of Perovskite Light-Emitting Diodes Using a Three-Step Spin-Coated CH3NH3PbBr3 Emitter and a PEDOT:PSS/MoO3-Ammonia Composite Hole Transport Layer

High efficiency perovskite light-emitting diodes (PeLEDs) using PEDOT:PSS/MoO3-ammonia composite hole transport layers (HTLs) with different MoO3-ammonia ratios were prepared and characterized. For PeLEDs with one-step spin-coated CH3NH3PbBr3 emitter, an optimal MoO3-ammonia volume ratio (0.02) in PEDOT:PSS/MoO3-ammonia composite HTL presented a maximum luminance of 1082 cd/m2 and maximum current efficiency of 0.7 cd/A, which are 82% and 94% higher than those of the control device using pure PEDOT:PSS HTL respectively. It can be explained by that the optimized amount of MoO3-ammonia in the composite HTLs cannot only facilitate hole injection into CH3NH3PbBr3 through reducing the contact barrier, but also suppress the exciton quenching at the HTL/CH3NH3PbBr3 interface. Three-step spin coating method was further used to obtain uniform and dense CH3NH3PbBr3 films, which lead to a maximum luminance of 5044 cd/m2 and maximum current efficiency of 3.12 cd/A, showing enhancement of 750% and 767% compared with the control device respectively. The significantly improved efficiency of PeLEDs using three-step spin-coated CH3NH3PbBr3 film and an optimum PEDOT:PSS/MoO3-ammonia composite HTL can be explained by the enhanced carrier recombination through better hole injection and film morphology optimization, as well as the reduced exciton quenching at HTL/CH3NH3PbBr3 interface. These results present a promising strategy for the device engineering of high efficiency PeLEDs

MicroRNA-275 and its target vitellogenin-2 are crucial in ovary development and blood digestion of Haemaphysalis longicornis

Background: The hard tick Haemaphysalis longicornis is widely distributed in eastern Asia, New Zealand and Australia and is considered the major vector of Theileria and Babesia, harmful parasites to humans and animals. Female ticks need successful blood meals to complete the life-cycle. Therefore, elucidation of the underlying molecular mechanisms of H. longicornis development and reproduction is considered important for developing control strategies against the tick and tick-borne pathogens. Methods: Luciferase assays were used to identify the targets of micro RNA miR-275 in vitro. RNAi of Vitellogenin (Vg) was used in phenotype rescue experiments of ticks with miR-275 inhibition, and these analyses were used to identify the authentic target of miR-275 in vivo. The expression of miR-275 in different tissues and developmental stages of ticks was assessed by real-time PCR. To elucidate the functions of miR-275 in female ticks, we injected a miR-275 antagomir into female ticks and observed the phenotypic changes. Statistical analyses were performed with GraphPad5 using Student’s t-test. Results: In this study, we identified Vg-2 as an authentic target of miR-275 both in vitro and in vivo by luciferase assays and phenotype rescue experiments. miR-275 plays the regulatory role in a tissue-specific manner and differentially in developmental stages. Silencing of miR-275 resulted in blood digestion problems, substantially impaired ovary development and significantly reduced egg mass (P < 0.0001). Furthermore, RNAi silencing of Vg-2 not only impacted the blood meal uptake (P < 0.05) but also the egg mass (P < 0.05). Significant rescue was observed in miR-275 knockout ticks when RNAi was applied to Vg-2. Conclusion: To our knowledge, this study is the first demonstration that miR-275 targets Vg-2 in H. longicornis and regulates the functions of blood digestion and ovary development. These findings improve the molecular understanding of tick development and reproduction

The Protective Antibodies Induced by a Novel Epitope of Human TNF-α Could Suppress the Development of Collagen-Induced Arthritis

Tumor necrosis factor alpha (TNF-α) is a major inflammatory mediator that exhibits actions leading to tissue destruction and hampering recovery from damage. At present, two antibodies against human TNF-α (hTNF-α) are available, which are widely used for the clinic treatment of certain inflammatory diseases. This work was undertaken to identify a novel functional epitope of hTNF-α. We performed screening peptide library against anti-hTNF-α antibodies, ELISA and competitive ELISA to obtain the epitope of hTNF-α. The key residues of the epitope were identified by means of combinatorial alanine scanning and site-specific mutagenesis. The N terminus (80–91 aa) of hTNF-α proved to be a novel epitope (YG1). The two amino acids of YG1, proline and valine, were identified as the key residues, which were important for hTNF-α biological function. Furthermore, the function of the epitope was addressed on an animal model of collagen-induced arthritis (CIA). CIA could be suppressed in an animal model by prevaccination with the derivative peptides of YG1. The antibodies of YG1 could also inhibit the cytotoxicity of hTNF-α. These results demonstrate that YG1 is a novel epitope associated with the biological function of hTNF-α and the antibodies against YG1 can inhibit the development of CIA in animal model, so it would be a potential target of new therapeutic antibodies

Plasmonic-Enhanced Organic Light-Emitting Diodes Based on a Graphene Oxide/Au Nanoparticles Composite Hole Injection Layer

Organic light-emitting diodes (OLEDs) have drawn a great deal of attention due to their broad applications in lighting and displaying. With the development of nanotechnology, surface plasmas have been widely used in photonics, microscopes, solar cells and biosensors. In this paper, by inserting graphene oxide (GO), Au nanoparticles (Au NPs) and GO/Au NP composite structures between the hole transport layer (NPB) and indium tin oxide (ITO) anode, respectively, the electroluminescent performance of Alq3-based OLEDs was significantly enhanced. Compared to the reference devices, the devices with the composite inserting layer containing 10% GO/Au NP doping have the best electroluminescent performance, which improved 47.9% in maximum luminance, 49.2% in maximum current efficiency and 45.3% in maximum external quantum efficiency (EQE). Such substantial enhancement of photoelectric performance can be attributed to the combined effects of LSPR coupling and the better hole transport property by introducing Au NPs and a graphene oxide-doped layer

Multi-view radiomics and deep learning modeling for prostate cancer detection based on multi-parametric MRI

IntroductionThis study aims to develop an imaging model based on multi-parametric MR images for distinguishing between prostate cancer (PCa) and prostate hyperplasia.MethodsA total of 236 subjects were enrolled and divided into training and test sets for model construction. Firstly, a multi-view radiomics modeling strategy was designed in which different combinations of radiomics feature categories (original, LoG, and wavelet) were compared to obtain the optimal input feature sets. Minimum-redundancy maximum-relevance (mRMR) selection and least absolute shrinkage selection operator (LASSO) were used for feature reduction, and the next logistic regression method was used for model construction. Then, a Swin Transformer architecture was designed and trained using transfer learning techniques to construct the deep learning models (DL). Finally, the constructed multi-view radiomics and DL models were combined and compared for model selection and nomogram construction. The prediction accuracy, consistency, and clinical benefit were comprehensively evaluated in the model comparison.ResultsThe optimal input feature set was found when LoG and wavelet features were combined, while 22 and 17 radiomic features in this set were selected to construct the ADC and T2 multi-view radiomic models, respectively. ADC and T2 DL models were built by transferring learning from a large number of natural images to a relatively small sample of prostate images. All individual and combined models showed good predictive accuracy, consistency, and clinical benefit. Compared with using only an ADC-based model, adding a T2-based model to the combined model would reduce the model’s predictive performance. The ADCCombinedScore model showed the best predictive performance among all and was transformed into a nomogram for better use in clinics.DiscussionThe constructed models in our study can be used as a predictor in differentiating PCa and BPH, thus helping clinicians make better clinical treatment decisions and reducing unnecessary prostate biopsies

Enhanced photocatalysis by coupling of anatase TiO2 film to triangular Ag nanoparticle island

In order to overcome the low utilization ratio of solar light and high electron-hole pair recombination rate of TiO(2), the triangular Ag nanoparticle island is covered on the surface of the TiO(2) thin film. Enhancement of the photocatalytic activity of the Ag/TiO(2) nanocomposite system is observed. The increase of electron-hole pair generation is caused by the enhanced near-field amplitudes of localized surface plasmon of the Ag nanoparticles. The efficiently suppressed recombination of electron-hole pair caused by the metal-semiconductor contact can also enhance the photocatalytic activity of the TiO(2) film

Structure-Based Peptide Inhibitor Design of Amyloid-β Aggregation

Many human neurodegenerative diseases are associated with amyloid fibril formation. Inhibition of amyloid formation is of importance for therapeutics of the related diseases. However, the development of selective potent amyloid inhibitors remains challenging. Here based on the structures of amyloid β (Aβ) fibrils and their amyloid-forming segments, we designed a series of peptide inhibitors using RosettaDesign. We further utilized a chemical scaffold to constrain the designed peptides into β-strand conformation, which significantly improves the potency of the inhibitors against Aβ aggregation and toxicity. Furthermore, we show that by targeting different Aβ segments, the designed peptide inhibitors can selectively recognize different species of Aβ. Our study developed an approach that combines the structure-based rational design with chemical modification for the development of amyloid inhibitors, which could be applied to the development of therapeutics for different amyloid-related diseases