Multi-modal features-based human-herpesvirus protein-protein interaction prediction by using LightGBM.

The identification of human-herpesvirus protein-protein interactions (PPIs) is an essential and important entry point to understand the mechanisms of viral infection, especially in malignant tumor patients with common herpesvirus infection. While natural language processing (NLP)-based embedding techniques have emerged as powerful approaches, the application of multi-modal embedding feature fusion to predict human-herpesvirus PPIs is still limited. Here, we established a multi-modal embedding feature fusion-based LightGBM method to predict human-herpesvirus PPIs. In particular, we applied document and graph embedding approaches to represent sequence, network and function modal features of human and herpesviral proteins. Training our LightGBM models through our compiled non-rigorous and rigorous benchmarking datasets, we obtained significantly better performance compared to individual-modal features. Furthermore, our model outperformed traditional feature encodings-based machine learning methods and state-of-the-art deep learning-based methods using various benchmarking datasets. In a transfer learning step, we show that our model that was trained on human-herpesvirus PPI dataset without cytomegalovirus data can reliably predict human-cytomegalovirus PPIs, indicating that our method can comprehensively capture multi-modal fusion features of protein interactions across various herpesvirus subtypes. The implementation of our method is available at https://github.com/XiaodiYangpku/MultimodalPPI/.

The Effects of NAA on the Tuberous Root Yield and Quality of Rehmannia glutinosa and Its Regulatory Mechanism by Transcriptome and Metabolome Profiling.

Naphthylacetic acid (NAA) was used to increase the tuberous root yield of Rehmannia glutinosa, but the differences between its NAA-treated and control tuberous roots (NT and CG) and the regulatory mechanism of NAA effect remain unclear. In order to investigate them, NTs and CGs were used as materials, and both yield-related indices were measured; the metabolomics and transcriptomics were used to capture differentially accumulated metabolites (DAM) and to validate them via mining differentially expressed genes (DEGs), respectively. The effects of NAA treatment: increased NT mass per plant by 21.14%, through increasing the number of roots and increasing the mean root diameter; increased catalpol content by 1.2234% (p < 0.05); up-regulated 11DAMs and 596DEGs; and down-regulated 18 DAMs and 517DEGs. In particular, we discovered that NAA regulated its DAMs and biomass via 10 common metabolic pathways, and that the number of NAA-down-regulated DAMs was more than that of NAA-up-regulated DAMs in its tuberous root. Furthermore, HPLC validated the changes of several DAMs and 15 DEGs (4CL, ARF, CCoAOMT, ARGOS, etc.) associated with the yield increase and DAMs were verified by RT-qPCR. This study provided some valuable resources, such as tuberous root indices, key genes, and DAMs of Rehmannia glutinosa in response to NAA for distinguishing the CGs from NTs, and novel insights into the regulatory mechanism of NAA effects on both at the transcriptomic and metabolomic levels, so it will lay a theoretical foundation for NAA-regulated plant yield and quality, and provide references for prohibiting the uses of NAA as a swelling agent in medicinal tuber plants in China.

New Strategy for Optimizing the Properties of Copper Halide Organic-Inorganic Hybrid Lighting-emitting Materials.

Copper(I) halide organic-inorganic hybrid luminescent materials have many advantages, such as diverse structure, facile synthesis, high luminescent efficiency, tunable optical performance, etc., and show a broad application prospect in energy-saving lighting, display and other fields. However, compared with commercial rare-earth-metal-based phosphors, the reported hybrids generally suffer from poor stability and low luminescent efficiency, which are the bottleneck problem of their practical application. With the aim of developing high-performance organic-inorganic hybrid luminescent materials, a new synthesis strategy has been reported. This strategy can systematically design and synthesis copper(I) halide ionic hybrid structures by combining the covalent bonding and ionic bonding between inorganic and organic components into one structure, and use their synergistic effect to optimizing their properties. This design method is expected to develop high-performance organic-inorganic hybrid luminescent materials, promote the in-depth understanding of this field, and provide new ideas for the optimization of other types of hybrid materials.

Relationship between periodontal disease and male infertility: A case-control study.

OBJECTIVES: To compare the prevalence of chronic periodontitis between men who had semen abnormalities and those who had normozoospermia through a case-control study. MATERIALS AND METHODS: Male patients who visited the assisted reproduction clinic of a large general hospital and were diagnosed with semen abnormalities were included in the case group. The control group was composed of patients of the same clinic with normozoospermia. The semen analysis included sperm concentration, count and progressive and total motility, which were measured in the laboratory. A questionnaire and clinical periodontal examination were conducted for all participants. Logistic regression was performed to explore the relationship between chronic periodontitis and male infertility. RESULTS: A total of 192 participants were included: 63 participants (32.8%) had some type of semen abnormality (case group), while 129 participants (67.2%) had normozoospermia (control group). The case group had a significantly higher prevalence of moderate/severe periodontitis than the control group (33.3% vs. 17.8%, p = .012). The logistic regression showed that participants who had moderate/severe periodontitis had a greater chance of having semen abnormalities after adjusting for other confounding factors (OR = 3.377, p = .005). CONCLUSIONS: Periodontitis is associated with semen abnormalities and sperm motility in men.

A novel prognostic model based on epithelial-mesenchymal transition-related genes predicts patient survival in gastric cancer.

BACKGROUND: Gastric cancer (GC) represents a major malignancy and is the third deathliest cancer globally. Several lines of evidence indicate that the epithelial-mesenchymal transition (EMT) has a critical function in the development of gastric cancer. Although plentiful molecular biomarkers have been identified, a precise risk model is still necessary to help doctors determine patient prognosis in GC. METHODS: Gene expression data and clinical information for GC were acquired from The Cancer Genome Atlas (TCGA) database and 200 EMT-related genes (ERGs) from the Molecular Signatures Database (MSigDB). Then, ERGs correlated with patient prognosis in GC were assessed by univariable and multivariable Cox regression analyses. Next, a risk score formula was established for evaluating patient outcome in GC and validated by survival and ROC curves. In addition, Kaplan-Meier curves were generated to assess the associations of the clinicopathological data with prognosis. And a cohort from the Gene Expression Omnibus (GEO) database was used for validation. RESULTS: Six EMT-related genes, including CDH6, COL5A2, ITGAV, MATN3, PLOD2, and POSTN, were identified. Based on the risk model, GC patients were assigned to the high- and low-risk groups. The results revealed that the model had good performance in predicting patient prognosis in GC. CONCLUSIONS: We constructed a prognosis risk model for GC. Then, we verified the performance of the model, which may help doctors predict patient prognosis.

Fully endoscopic versus microscopic vascular decompression for hemifacial spasm: a retrospective cohort study.

INTRODUCTION: Microvascular decompression (MVD) is the preferred surgical method for hemifacial spasm (HFS). The purpose of this study was to analyze the effectiveness and safety of fully endoscopic MVD for HFS relative to microscopic MVD. MATERIAL AND METHODS: The retrospective study was conducted on HFS patients who underwent microscopic or fully endoscopic MVD from January 2018 to March 2019. All patients were treated at a single institution and by a single surgeon. Patients were divided into two groups based on the surgical method, and clinical data were then compared between groups. RESULTS: A total of 116 patients, including 54 cases who received fully endoscopic MVD (E group) and 62 cases who received microscopic MVD (M group), were included in this study. Follow-up efficacy did not differ significantly between groups, with total effective rates of 88.9% in the E group and 90.3% in the M group. When postoperative complications were compared individually, there were no statistically significant differences between the two groups; however, the E group had a higher total incidence of complications than the M group (48.1% vs. 29.0%, P = 0.034). CONCLUSION: Although both fully endoscopic and microscopic MVD for HFS achieved good efficacy, the former method had a higher total incidence of complications. Based on the results of this study, there is no evidence that a microscope can be replaced by a full endoscope in MVD for HFS.

Targeting BAX ubiquitin-binding sites reveals that BAX activation is essential for its ubiquitin-dependent degradation.

BAX is an important proapoptotic protein of the BCL-2 family, and its stability is essential for the regulation of the mitochondrial apoptotic pathway. A previous study revealed that BAX could undergo degradation through the ubiquitin-proteasome pathway. In this study, we identified two lysine sites, K21 and K123, that were critical ubiquitin-binding sites in BAX. Mutation of these two sites prolonged the half-life of BAX and also affected its proapoptotic ability. Intriguingly, we found that ABT-737, a BCL-2 inhibitor, significantly enhanced TRAIL-induced BAX degradation in HCT116 cells and increased TRAIL-induced apoptosis in the HCT116 only with the BAX K21R/K123R mutant, not other BAX mutants. In addition, overexpression of PARKIN, an E3 ubiquitin ligase targeting BAX, dramatically decreased BAX protein level when only treated with ABT-737 in HCT116 cells. Therefore, we speculated that BAX activation is essential for its ubiquitin-dependent degradation.

Interleukin-35 promotes progression of prostate cancer and inhibits anti-tumour immunity.

BACKGROUND: Interleukin-35 (IL-35) has been reported to play an important role in the progression of cancers. The role of IL-35 in prostate cancer (PCA) is not well understood. In this study, we investigated the effects of IL-35 on PCA and its immunoregulatory effect on PCA. METHODS: The protein and mRNA expression of IL-35 in PCA cells was detected by western blot and RT-PCR. The invasion and migration of cells were detected using transwell and wound-healing assays. A CCK-8 assay was conducted to observe cell proliferation. In vivo, IL-35 plasma concentration was test by enzyme-linked immunosorbent assay. The role of IL-35 in tumour cell proliferation and angiogenesis of mice was detected by immunohistochemical stains. The mouse survival and tumour volumes were calculated, and lung metastasis rate was detected by HE staining. The modulatory effects of IL-35 on myeloid-derived inhibitory cells (MDSCs), regulatory T cells (Tregs), CD4+ T cells and CD8+ T cells from PCA mice were investigated by immunohistochemical stains and flow cytometry. RESULTS: High levels of IL-35 significantly promoted the migration, invasion and cell proliferation of PCA cells in vitro. IL-35 was associated with tumour growth, metastasis and poor prognosis in PCA mice. Additionally, high levels of IL-35 significantly increased the proportions of MDSCs and Tregs and decreased the proportions of CD4+ and CD8+ T cells in the spleen, blood and tumour microenvironment. The IL-35 neutralizing antibody played the opposite role. CONCLUSIONS: IL-35 contributed to the progression of PCA through promoting cell proliferation and tumour angiogenesis. IL-35 might limit the anti-tumour immune response by upregulating the proportions of Tregs and MDSCs and by reducing the proportions of CD4+ and CD8+ T cells. IL-35 might serve as a novel therapeutic target for PCA.

Growth mechanism and photoelectric properties of a silver nanowire network prepared by solid state ionics method.

A macroscopic silver nanowire (AgNW) network is grown by solid state ionics method. The ion flow during growth of the AgNW network is controlled by maintaining a current in the order of 10-7 A. Scanning electron microscopy (SEM) analysis reveals that the growth direction of AgNWs in the network is irregular and spread evenly in all directions and the nanowires are 40-160 nm in diameter. The microcosmic mechanism of silver nanostructures grown by the solid state ionics method is established by real time and in situ SEM analysis of the growth process of the AgNW networks. To study the photoelectric properties of the network, a self-supported AgNW network sample (∼1 mm wide and 8 mm long) is irradiated with lasers of different wavelengths of 375, 405, 532, 633, 808, and 1064 nm and 10.6 µm, and changes in the current between the two ends of the sample are recorded. The network displays negative photoconductance effect, and the maximum light responsivity is 43 mA W-1. The network displays light responsivity in the ultraviolet light-to-mid-infrared light region, with response times of tens of milliseconds. These findings indicate that the AgNW network has broad application prospect in ultra-wide spectrum photoelectric detection.

Facile fabrication of eutectic gallium-indium alloy nanostructure and application in photodetection.

Eutectic gallium-indium (EGaIn) alloy is a kind of liquid metal and has attracted much attention due to good properties. In order to satisfy the trend of miniaturization and realize more practical applications, the exploration for preparation method and properties of EGaIn at nanoscale are very important. Here, facile vacuum thermal evaporation method is developed to fabricate EGaIn nanostructures. The EGaIn nanoparticle and nanofilm with naturally formed 5 nm thick oxide layers are well prepared. The oxide film formed on the EGaIn surface is an important factor, making the properties of the nanostructure different from the properties of the bulk. Compared with ignorance of oxide layer in bulk materials, the proportion of oxide layer increases evidently in nanostructures, which produce obvious influence on the electric and optical properties. The rectifying characteristic and optoelectronic performance are experimentally observed. The EGaIn nanostructures can generate evident photocurrent responses with good responsivities (∼1 mA W-1) and response speed (∼1 s) under irradiation of 206 nm, 405 nm, 532 nm, 635 nm, 808 nm, 1064 nm and 10.6 µm lasers. These properties are completely different from the metallic properties of EGaIn bulk material.

Visual Interpretability in Computer-Assisted Diagnosis of Thyroid Nodules Using Ultrasound Images.

BACKGROUND The number of studies on deep learning in artificial intelligence (AI)-assisted diagnosis of thyroid nodules is increasing. However, it is difficult to explain what the models actually learn in artificial intelligence-assisted medical research. Our aim is to investigate the visual interpretability of the computer-assisted diagnosis of malignant and benign thyroid nodules using ultrasound images. MATERIAL AND METHODS We designed and implemented 2 experiments to test whether our proposed model learned to interpret the ultrasound features used by ultrasound experts to diagnose thyroid nodules. First, in an anteroposterior/transverse (A/T) ratio experiment, multiple models were trained by changing the A/T ratio of the original nodules, and their classification, accuracy, sensitivity, and specificity were tested. Second, in a visualization experiment, class activation mapping used global average pooling and a fully connected layer to visualize the neural network to show the most important features. We also examined the importance of data preprocessing. RESULTS The A/T ratio experiment showed that after changing the A/T ratio of the nodules, the accuracy of the neural network model was reduced by 9.24-30.45%, indicating that our neural network model learned the A/T ratio information of the nodules. The visual experiment results showed that the nodule margins had a strong influence on the prediction of the neural network. CONCLUSIONS This study was an active exploration of interpretability in the deep learning classification of thyroid nodules. It demonstrated the neural network-visualized model focused on irregular nodule margins and the A/T ratio to classify thyroid nodules.

Ensemble Deep Learning Model for Multicenter Classification of Thyroid Nodules on Ultrasound Images.

BACKGROUND Thyroid nodules are extremely common and typically diagnosed with ultrasound whether benign or malignant. Imaging diagnosis assisted by Artificial Intelligence has attracted much attention in recent years. The aim of our study was to build an ensemble deep learning classification model to accurately differentiate benign and malignant thyroid nodules. MATERIAL AND METHODS Based on current advanced methods of image segmentation and classification algorithms, we proposed an ensemble deep learning classification model for thyroid nodules (EDLC-TN) after precise localization. We compared diagnostic performance with four other state-of-the-art deep learning algorithms and three ultrasound radiologists according to ACR TI-RADS criteria. Finally, we demonstrated the general applicability of EDLC-TN for diagnosing thyroid cancer using ultrasound images from multi medical centers. RESULTS The method proposed in this paper has been trained and tested on a thyroid ultrasound image dataset containing 26 541 images and the accuracy of this method could reach 98.51%. EDLC-TN demonstrated the highest value for area under the curve, sensitivity, specificity, and accuracy among five state-of-the-art algorithms. Combining EDLC-TN with models and radiologists could improve diagnostic accuracy. EDLC-TN achieved excellent diagnostic performance when applied to ultrasound images from another independent hospital. CONCLUSIONS Based on ensemble deep learning, the proposed approach in this paper is superior to other similar existing methods of thyroid classification, as well as ultrasound radiologists. Moreover, our network represents a generalized platform that potentially can be applied to medical images from multiple medical centers.

Knockdown of circ-ABCB10 promotes sensitivity of lung cancer cells to cisplatin via miR-556-3p/AK4 axis.

BACKGROUND: Due to the acquired drug resistance, the potency of cisplatin-based chemotherapy is limited in lung cancer, which is a big obstacle in clinical treatment of lung cancer. Abundant evidence has revealed that circular RNAs (circRNAs) exerted facilitating or suppressive function on the tumorigenesis of multiple cancers. The oncogenic role of circ-ABCB10 in breast cancer and clear cell renal cell carcinoma has been validated in recent researches. However, the regulatory mechanism of circ-ABCB10 and its relation to cellular sensitivity to cisplatin in lung cancer is poorly understood. METHODS: The expression and characteristic of circ-ABCB10 were analyzed by RT-qPCR and nucleic acid electrophoresis. CCK-8, colony formation, TUNEL and transwell assays were applied to probe the role of FOXD3-AS1 in lung cancer. The interactions of miR-556-3p with circ-ABCB10 and AK4 were testified by luciferase reporter and RIP assays. RESULTS: Circ-ABCB10 was markedly upregulated and featured with loop structure in lung cancer. Circ-ABCB10 depletion suppresses lung cancer progression and sensitizes lung cancer cells to cisplatin. Molecular mechanism assays manifested that circ-ABCB10 bound with miR-556-3p and negatively modulated miR-556-3p expression. Additionally, AK4 was testified to be the downstream target of miR-556-3p. More importantly, rescue assays clarified that upregulation of AK4 could reverse the cisplatin-sensitizing and tumor-suppressing effect of circ-ABCB10 knockdown on lung cancer cells. CONCLUSIONS: Circ-ABCB10 knockdown enhances sensitivity of lung cancer cells to cisplatin by targeting miR-556-3p/AK4 axis.

Mild hypertension protects the elderly from cognitive impairment: a 7-year retrospective cohort study.

AIM: People with mild cognitive impairment have a high risk of converting to dementia. Previous studies have suggested that hypertension is implicated in the development of mild cognitive impairment, but such effect in people much older than 70 years may be quite different. The aim of the study was to reveal the relationship between hypertension and mild cognitive impairment risk in this age group. METHODS: A total of 985 subjects were retrospectively enrolled from Tianjin Medical University General Hospital, and all of them were cognitively normal 7 years earlier. During these years, 134 subjects were diagnosed with mild cognitive impairment according to the Mini-Mental State Examination. Research data of all the subjects were collected from medical records. RESULTS: Multivariate Cox regression analysis revealed that compared with the subjects without hypertension, the subjects with grade 1 hypertension or duration <10 years showed a decreased risk of mild cognitive impairment (hazards ratio (HR): 0.54, 95%CI: 0.32-0.87; HR: 0.65, 95%CI: 0.40-0.99), and the subjects with grade 2-3 hypertension or duration ≥10 years had an increased risk of the disease (HR: 1.75, 95%CI: 1.25-2.42; HR: 1.52, 95%CI: 1.08-2.15). In addition, compared with the patients without hypertension, the patients taking angiotensin II receptor antagonists / angiotensin converting enzyme inhibitors had an increased risk of the disease (HR: 1.91, 95%CI: 1.29-2.83). CONCLUSION: In subjects over 70 years old, short-term and mild hypertension might be a protective factor for mild cognitive impairment and prevent them from such a disease.

Increases in miR-124-3p in Microglial Exosomes Confer Neuroprotective Effects by Targeting FIP200-Mediated Neuronal Autophagy Following Traumatic Brain Injury.

In our recent study, we observed consistent increases in miR-124-3p levels in exosomes derived from cultured BV2 microglia which was treated with repetitive traumatic brain injury (rTBI) mouse model brain extracts. To clarify the mechanisms underlying increases in microglia-derived exosomal miR-124-3p and their role in regulating neuronal autophagy after TBI, we investigated the impact of exosomal miR-124-3p on neuronal autophagy in scratch-injured HT22 neurons and rTBI mice. We harvested injured brain extracts from rTBI mice at 3 to 21 days post injury (DPI) for the treatment of cultured BV2 microglia in vitro. We observed significant induction of autophagy following TBI in vitro, and that inhibition of activated neuronal autophagy could protect against trauma-induced injury. Our results indicated that co-culture of injured HT22 neurons with miR-124-3p overexpressing BV2 microglia exerted a protective effect by inhibiting neuronal autophagy in scratch-injured neurons. Further research revealed that these effects were achieved mainly via upregulation of exosomal miR-124-3p, and that Focal adhesion kinase family-interacting protein of 200 kDa (FIP200) plays a key role in trauma-induced autophagy. Injection of exosomes into the vena caudalis in in vivo experiments revealed that exosomal miR-124-3p was associated with decreases in the modified neurological severity score (mNSS) and improvements in Morris water maze (MWM) test results in rTBI mice. Altogether, our results indicate that increased miR-124-3p in microglial exosomes following TBI may inhibit neuronal autophagy and protect against nerve injury via their transfer into neurons. Thus, treatment with microglial exosomes enriched with miR-124-3p may represent a novel therapeutic strategy for the treatment of nerve injury after TBI.

Self-assembled gold micro/nanostructure arrays based on superionic conductor RbAg4I5 films.

Herein, we propose a new strategy to fabricate gold (Au) micro/nanostructure arrays by photocatalytic solid-state electrochemical reaction between superionic conductor RbAg4I5 and Au films. The Au and RbAg4I5 films were successively deposited on a clean quartz substrate by vacuum thermal deposition method. A copper microgrid possessing periodic holes 100 µm in diameter was put above the RbAg4I5 film as a mask plate, whereupon irradiation from a 405 nm wavelength laser was used to diffuse gold ions (Au+ ions) into vacant silver sites of RbAg4I5 and transfer Au+ through ion passageways in the RbAg4I5 film. When the laser was turned off, the Au+ ions were easily reduced due to low activity compared to the silver (Ag+) ions. After multiple on/off cycles of the 405 nm laser, the irradiated area of uniform Au film exhibited a periodic structural unit array whose period was the same as that of the mask plate hole array. Atomic force microscope and scanning electron microscope images revealed that a self-assembled needle-like nanostructure array grew perpendicular to the substrate surface inside each circle's structural unit. The height of the grown nanostructure array increased with laser power density. Raman enhancement of the gold nanostructure array as substrate was detected using Rhodamine 6G (R6G) ethanol solutions as probe molecules. The enhancement effect increased with the height of the grown nanostructure array, and could increase by two orders of magnitude greater than that of unirradiated Au film. This strategy offers a new method for the micro/nanostructure processing of gold and provides microscale-array-mediated surface-enhancement Raman-scattering (SERS) substrates comprising Au nanostructures for application in high-sensitivity spectrum analysis.

Exosomes from MiR-21-5p-Increased Neurons Play a Role in Neuroprotection by Suppressing Rab11a-Mediated Neuronal Autophagy In Vitro After Traumatic Brain Injury.

BACKGROUND Traumatic brain injury (TBI) produces a series of pathological processes. Recent studies have indicated that autophagy pathway is persistently activated after TBI, which may lead to deterioration of nerve injury. Our preliminary work found miR-21-5p was upregulated in both in vivo and in vitro TBI models. MicroRNAs (miRNAs) could be loaded into exosomes to perform cell-to-cell interactions. This research aimed to evaluate the therapeutic effect of neuron-derived exosomes enriched with miR-21-5p on the TBI in vitro and to further explore the possible mechanisms. MATERIAL AND METHODS Brain extracts harvested from an rTBI mouse model were added to cultured HT-22 neurons to imitate the microenvironment of injured brain on in vitro cultured cells. Ultracentrifugation was performed to isolate exosomes. Transmission electron microscopy and Nano sight technology were used to examine exosomes. An in vitro model of TBI was established to study the effect of exosomal miR-21-5p on nerve injury and on neuronal autophagy regulation. RESULTS The expression of miR-21-5p was increased in exosomes derived from HT-22 neurons after treatment with rTBI mouse brain extracts. Autophagy was activated in HT-22 neurons after scratch injury. Exosomal miR-21-5p produced a protective effect by suppressing autophagy in a TBI model in vitro. MiR-21-5p could directly target the Rab11a 3'UTR region to reduce its translation and further suppressed Rab11a-mediated neuronal autophagy. CONCLUSIONS The levels of miR-21-5p in neuronal exosomes increased from the acute to the chronic phase of TBI. Neuronal exosomes enriched with miR-21-5p can inhibit the activity of neuronal autophagy by targeting Rab11a, thus attenuating trauma-induced, autophagy-mediated nerve injury in vitro.

Efficacy of the MEK Inhibitor Cobimetinib and its Potential Application to Colorectal Cancer Cells.

BACKGROUND/AIMS: Mutations in the Ras/Raf/MEK/ERK pathway are detected in 50% of colorectal cancer cases and play a crucial role in cancer development and progression. Cobimetinib is a MEK inhibitor approved for the treatment of advanced melanoma and inhibits the cell viability of other types of cancer cells. METHODS: HCT116 colorectal cancer cells were treated with cobimetinib, and MTT assay, colony formation assay, and flow cytometry were used to evaluate cell viability, cell cycle, and apoptosis, respectively. The expression of genes associated with the cell cycle and apoptosis were evaluated by quantitative real-time PCR and western blotting. To explore use of cobimetinib in colorectal cancer treatment and further understand its mechanisms, RNA-seq technology was used to identify differentially expressed genes (DEGs) between cobimetinib-treated and untreated HCT116 cells. Furthermore, we compared these DEGs with Gene Expression Omnibus data from colorectal cancer tissues and normal colonic epithelial tissues. RESULTS: We found that cobimetinib not only inhibited cell proliferation but also induced G1 phase arrest and apoptosis in HCT116 colorectal cancer cells, suggesting that cobimetinib may useful in colorectal cancer therapy. After cobimetinib treatment, 3,495 DEGs were obtained, including 2,089 upregulated genes and 1,406 downregulated genes, and most of these DEGs were enriched in the cell cycle, DNA replication, and DNA damage repair pathways. Our results revealed that some genes with high expression in colorectal cancer tissues were downregulated by cobimetinib in HCT116 cells, including CCND1, E2F1, CDC25C, CCNE2, MYC, and PCNA. These genes have vital roles in DNA replication and the cell cycle. Furthermore, genes with low expression in colorectal cancer tissues were upregulated by cobimetinib, including PRKCA, PI3K, RTK, and PKC. Based on our results, the PKC and PI3K pathways were activated after cobimetinib treatment, and inhibition of these two pathways can increase the cytotoxicity of cobimetinib in HCT116 cells. Notably, cobimetinib appeared to enhance the efficacy of 5-fluorouracil (5-FU) by decreasing TYMS expression, high expression of which is responsible for 5-FU resistance in colorectal cancer. CONCLUSIONS: Our results suggest the potential use of cobimetinib in colorectal cancer therapy.

Terahertz photodetector based on double-walled carbon nanotube macrobundle-metal contacts.

We report on the characterization of a terahertz (THz) photodetector with an extremely simple structure consisting of only a macroscopic bundle of double-walled carbon nanotubes (DWCNTs) suspended between two metal electrodes. Polarization-sensitive, broadband, and significant photoresponse occurring at the DWCNT-metal contacts under THz illumination are observed with room-temperature photocurrent and photovoltage responsivities up to ∼16 mA/W and ∼0.2 V/W at 2.52 THz, respectively. Scanning photocurrent measurements provide evidence that the photothermoelectric mechanism dominates the detector response. The simple geometry and compact nature of our device make it suitable for integration and show promising applications for THz detection.

Photocurrent response of carbon nanotube-metal heterojunctions in the terahertz range.

We investigate the optoelectronic properties of a carbon nanotube (CNT)-metal heterostructure in the terahertz range. On the basis of terahertz time-domain spectroscopy characterization of a double-walled CNT (DWNT) film, we present and analyze the photocurrent measurement for a DWNT-nickel heterojunction illuminated by continuous-wave terahertz radiation. A significant current across the junction directly induced by terahertz excitation is observed and a negative photoconductivity behavior is found to occur in the device. The photocurrent shows a linear response to the bias voltage and the illumination power within the examined range. These phenomena support the feasibility of using CNT-metal heterojunctions as novel terahertz detectors.