A Targeted Quantitative Proteomic Method Revealed a Substantial Reprogramming of Kinome during Melanoma Metastasis.

Kinases are involved in numerous critical cell signaling processes, and dysregulation in kinase signaling is implicated in many types of human cancers. In this study, we applied a parallel-reaction monitoring (PRM)-based targeted proteomic method to assess kinome reprogramming during melanoma metastasis in three pairs of matched primary/metastatic human melanoma cell lines. Around 300 kinases were detected in each pair of cell lines, and the results showed that Janus kinase 3 (JAK3) was with reduced expression in the metastatic lines of all three pairs of melanoma cells. Interrogation of The Cancer Genome Atlas (TCGA) data showed that reduced expression of JAK3 is correlated with poorer prognosis in melanoma patients. Additionally, metastatic human melanoma cells/tissues exhibited diminished levels of JAK3 mRNA relative to primary melanoma cells/tissues. Moreover, JAK3 suppresses the migration and invasion of cultured melanoma cells by modulating the activities of matrix metalloproteinases 2 and 9 (MMP-2 and MMP-9). In summary, our targeted kinome profiling method provided by far the most comprehensive dataset for kinome reprogramming associated with melanoma progression, which builds a solid foundation for examining the functions of other kinases in melanoma metastasis. Moreover, our results reveal a role of JAK3 as a potential suppressor for melanoma metastasis

Cataract Surgery in Microphthalmic Eyes

Microphthalmos is a congenital ocular abnormality that mainly manifests as a significant reduction in the size of the eye and is often associated with cataracts and other eye diseases. Due to its special anatomical features, cataract surgery in microphthalmos has a higher risk of intraoperative and postoperative complications and impaired visual prognosis and is associated with reduced intraocular lens (IOL) calculation accuracy. This chapter describes the characteristics of microphthalmic cataract surgery, the incidence of complications, classic and additional surgical procedures (e.g., phacoemulsification combined with prophylactic anterior lamellar sclerostomy, laser peripheral iridotomy, anterior segment vitrectomy, piggyback IOLs), and selection of IOL calculation formula

Sugarcane bagasse dietary fiber as an adjuvant therapy for stable chronic obstructive pulmonary disease: a four-center, randomized, double-blind, placebo-controlled study

AbstractObjectiveTo evaluate the efficacy and safety of sugarcane bagasse dietary fiber as an adjuvant therapy for improving quality of life in patients with stable chronic obstructive pulmonary disease (COPD).MethodsThis was a multicenter, randomized, double-blind, placebo-controlled trial. A total of 196 participants were randomized into a trial group (treated with 6 g/day sugarcane bagasse plus conventional treatment, n = 98) and a control group (treated with placebo plus conventional treatment, n = 98). All efficacy analyses were performed according to the intention-to-treat (ITT) principle. A per-protocol analysis set (PPS) was used to analyze the cases that completed the clinical trial with good compliance. The trial period was 30 days, with a 6-month follow-up. Pre- and post-treatment pulmonary symptom scores (cough, sputum, wheezing, and dyspnea) were recorded for both groups. The St. George's Respiratory Questionnaire (SGRQ) and the modified Medical Research Council (mMRC) dyspnea scale were assessed before treatment and at the end of the 6-month follow-up.ResultsThe ITT population was 178 and the PPS population was 166. Post-treatment pulmonary clinical symptoms and severity of dyspnea (mMRC and SGRQ evaluation) were significantly improved in both the trial group and the control group (ITT and PPS: P < 0.05). However, there was no statistical difference between the two groups in post-treatment pulmonary symptoms and mMRC. There was a greater reduction in the SGRQ subscales of activity, effect and total score in the trial group compared with the control group (ITT and PPS: P < 0.01). There was no statistical difference in pre- and post-treatment safety variables in either group.ConclusionSugarcane bagasse combined with conventional treatment improved quality of life in patients with stable COPD. Sugarcane bagasse appears to be a safe herbal medicine with potential for treating patients with stable COPD when taken orally as an adjuvant therapy

Selective oxidation of methane to C2+ products over Au-CeO2 by photon-phonon co-driven catalysis.

Direct methane conversion to high-value chemicals under mild conditions is attractive yet challenging due to the inertness of methane and the high reactivity of valuable products. This work presents an efficient and selective strategy to achieve direct methane conversion through the oxidative coupling of methane over a visible-responsive Au-loaded CeO2 by photon-phonon co-driven catalysis. A record-high ethane yield of 755 μmol h−1 (15,100 μmol g−1 h−1) and selectivity of 93% are achieved under optimised reaction conditions, corresponding to an apparent quantum efficiency of 12% at 365 nm. Moreover, the high activity of the photocatalyst can be maintained for at least 120 h without noticeable decay. The pre-treatment of the catalyst at relatively high temperatures introduces oxygen vacancies, which improves oxygen adsorption and activation. Furthermore, Au, serving as a hole acceptor, facilitates charge separation, inhibits overoxidation and promotes the C-C coupling reaction. All these enhance photon efficiency and product yield

M2 macrophage inhibits the antitumor effects of Lenvatinib on intrahepatic cholangiocarcinoma

Background and objectivesThe relationship between the tumor microenvironment and the network of key signaling pathways in cancer plays a key role in the occurrence and development of tumors. Tumor-associated macrophages (TAMs) are important inflammatory cells in the tumor microenvironment and play an important role in tumorigenesis and progression. Macrophages in malignant tumors, mainly the M2 subtype, promote tumor progression by producing cytokines and down-regulating anti-inflammatory immune responses. Several articles have investigated the effect of macrophages on the sensitivity of cancer chemotherapeutic agents, but few such articles have been reported in cholangiocarcinoma, so we investigated the effect of M2 macrophage on the sensitivity of cholangiocarcinoma cells to Lenvatinib compared to M1.MethodsTHP-1 monocytes were polarized to M0 macrophage by phorbol 12-myristate 13-acetate (PMA) and then induced to differentiate into M1 and M2 macrophages by LPS, IFN-γ and IL-4 and IL-13, respectively. Macrophages and cholangiocarcinoma cells were co-cultured prior to 24 hours of Lenvatinib administration, cancer cell apoptosis was detected by western-blot, FACS analysis of Annexin V and PI staining. Furthermore, we use xCELLigence RTCA SP Instrument (ACEA Bio-sciences) to monitor cell viability of Lenvatinib administration in co-culture of cholangiocarcinoma cells and macrophages. After tumorigenesis in immunodeficient mice, Lenvatinib was administered, and the effects of M2 on biological characteristics of cholangiocarcinoma cells were investigated by immuno-histochemistry.ResultsmRNA and protein expression of M1 and M2 markers confirmed the polarization of THP-1 derived macrophages, which provided a successful and efficient model of monocyte polarization to TAMs. Lenvatinib-induced apoptosis of cholangiocarcinoma cells was significantly reduced when co-cultured with M2 macrophage, whereas apoptosis of cholangiocarcinoma cells co-cultured with M1 macrophage was increased. In the CDX model, Lenvatinib-induced cancer cell apoptosis was markedly reduced, and proliferative cells increased in the presence of M2 macrophages. Angiogenesis related factors was significantly increased in cholangiocarcinoma cells co-cultured with M2.ConclusionCompared with M1, M2 macrophages can inhibit the anti-tumor effect of Lenvatinib on cholangiocarcinoma through immune regulation, which may be related to the tumor angiogenesis factor effect of M2 macrophage

Targeted Profiling of Epitranscriptomic Reader, Writer, and Eraser Proteins Accompanied with Radioresistance in Breast Cancer Cells.

Epitranscriptomic reader, writer, and eraser (RWE) proteins recognize, install, and remove modified nucleosides in RNA, which are known to play crucial roles in RNA processing, splicing, and stability. Here, we established a liquid chromatography-parallel-reaction monitoring (LC-PRM) method for high-throughput profiling of a total of 152 epitranscriptomic RWE proteins. We also applied the LC-PRM method, in conjunction with stable isotope labeling by amino acids in cell culture (SILAC), to quantify these proteins in two pairs of matched parental/radioresistant breast cancer cells (i.e., MDA-MB-231 and MCF-7 cells and their corresponding radioresistant C5 and C6 clones), with the goal of assessing the roles of these proteins in radioresistance. We found that eight epitranscriptomic RWE proteins were commonly altered by over 1.5-fold in the two pairs of breast cancer cells. Among them, TRMT1 (an m2,2G writer) may play a role in promoting breast cancer radioresistance due to its clinical relevance and its correlation with DNA repair gene sets. To our knowledge, this is the first report of a targeted proteomic method for comprehensive quantifications of epitranscriptomic RWE proteins. We envision that the LC-PRM method is applicable for studying the roles of these proteins in the metastatic transformation of cancer and therapeutic resistance of other types of cancer in the future

Design and analysis of an InGaAs/InGaAsP quantum well microlaser with longitudinal periodical strain distribution for single-mode lasing

Single-mode lasing for small size semiconductor laser is significantly important in the on-chip optical signal processing, data storage, and dense optical integrated systems. This paper presents new, to the best of our knowledge, single-mode quantum well microlasers by distributing periodical strain along the longitudinal laser cavity. The quantum transmission line modeling (Q-TLM) method is employed to establish the model for strained microlasers. The dynamic output of quantum well microlasers with longitudinal periodical strain (LPS) distribution is analyzed in the time and frequency domains, and it is found that the introduction of LPS significantly improves the single-mode output of quantum well microlasers by increasing the side mode suppression ratio (SMSR) from 8.44 to 28.29 dB. The study results confirm that well-controlled periodical strain along the longitudinal laser cavity provides an alternative routine for realizing single-mode lasing by strain engineering

Research on Digital Twin Dynamic Modeling Method for Transmission Line Deicing System

A digital twin is recognized as a pivotal technology in a new type of power system monitoring as it provides an effective method for monitoring the vibration caused by ice shedding in overhead transmission lines. The digital twin model differs from traditional models in that it has the characteristics of precise mapping and real-time simulation. These emerging characteristics lead to urgent updating of the existing modeling approaches. Therefore, the current study proposes a dynamic digital twin modeling method for transmission line ice-shedding systems. In this approach, an analytical solution for conductor deicing oscillation is proposed to describe the span and tension unchanged in any time period and then segmented and iteratively corrected with measured time-varying parameters to implement real-time simulation functionality. A dynamic geometric model for transmission lines is proposed based on the Unity3D platform. In addition, a human-computer interaction visualization platform is proposed to display twin data, with the objective of realizing precise mapping of real transmission lines. Finally, an application of this systematic approach to continuous three-span wire demonstrates the feasibility and effectiveness of the proposed approach

A New Blockchain-Based Multi-Level Location Secure Sharing Scheme

Currently, users’ location information is collected to provide better services or research. Using a central server to collect, store and share location information has inevitable defects in terms of security and efficiency. Using the point-to-point sharing method will result in high computation overhead and communication overhead for users, and the data are hard to be verified. To resolve these issues, we propose a new blockchain-based multi-level location secure sharing scheme. In our proposed scheme, the location data are set hierarchically and shared with the requester according to the user’s policy, while the received data can be verified. For this, we design a smart contract to implement attribute-based access control and establish an incentive and punishment mechanism. We evaluate the computation overhead and the experimental results show that the computation overhead of our proposed scheme is much lower than that of the existing scheme. Finally, we analyze the performances of our proposed scheme and demonstrate that our proposed scheme is, overall, better than existing schemes