This study aimed to investigate the roles of COP9 signalosome subunit 8 (COPS8) and its underlying mechanism in cutaneous melanoma. Bioinformatics tools were utilized to analyze the expression of ...COPS8 in cutaneous melanoma, while Kaplan-Meier analysis was employed to assess the correlation between COPS8 and patients' overall survival. The proliferation, migration, and invasion of cells were estimated by CCK8, colony formation, and Transwell assays. Western blot was used to check the expression of epithelial-mesenchymal transition (EMT)-related proteins. Results showed that COPS8 was up-regulated and predicted a poor clinical outcome for cutaneous melanoma patients. Knockdown of COPS8 inhibited cutaneous melanoma cell proliferation, migration and invasion, whereas overexpression of COPS8 resulted in the opposite outcomes. The up-regulation of E-cadherin and down-regulation of N-cadherin, vimentin, and snail were caused by silencing COPS8 while their expression showed contrary trends in cells with overexpressed COPS8. Collectively, COPS8 is up-regulated and promotes cutaneous melanoma progression via regulating EMT.
Compared with fluorescence imaging utilizing fluorophores whose lifetimes are in the order of nanoseconds, time-resolved fluorescence microscopy has more advantages in monitoring target fluorescence. ...In this work, compound DCF-MPYM, which is based on a fluorescein derivative, showed long-lived luminescence (22.11 μs in deaerated ethanol) and was used in time-resolved fluorescence imaging in living cells. Both nanosecond time-resolved transient difference absorption spectra and time-correlated single-photon counting (TCSPC) were employed to explain the long lifetime of the compound, which is rare in pure organic fluorophores without rare earth metals and heavy atoms. A mechanism of thermally activated delayed fluorescence (TADF) that considers the long wavelength fluorescence, large Stokes shift, and long-lived triplet state of DCF-MPYM was proposed. The energy gap (ΔE ST) of DCF-MPYM between the singlet and triplet state was determined to be 28.36 meV by the decay rate of DF as a function of temperature. The ΔE ST was small enough to allow efficient intersystem crossing (ISC) and reverse ISC, leading to efficient TADF at room temperature. The straightforward synthesis of DCF-MPYM and wide availability of its starting materials contribute to the excellent potential of the compound to replace luminescent lanthanide complexes in future time-resolved imaging technologies.
This paper studies the operations of a telemedicine service system consisting of independent hospitals general hospital (GH) and telemedicine firm (TF). Through the healthcare alliance, the GH and ...the TF collaborate in capacity decisions and revenue sharing, and establish a green channel to refer patients. We adopt a two-stage game model to study a revenue sharing scheme of the telemedicine healthcare alliance. In the first-stage the game, the GH and the TF negotiate a revenue-sharing ratio to distribute the revenue of the referred patients. In the second stage game, given the profit-sharing ratio, GH makes capacity allocation decisions, and TF determines its own price to maximize its own revenue. Results show that the revenue sharing scheme can increase profits and promote collaboration between GH and TF. When a large number of mild patients arrive at the GH, the GH tends to participate in the alliance. For the TF, high prices do not always yield high profit under the comprehensive influence of the alliance.
Mass spectrometry (MS)-based top-down proteomics (TDP) requires high-resolution separation of proteoforms before electrospray ionization (ESI)-MS and tandem mass spectrometry (MS/MS). Capillary ...isoelectric focusing (cIEF)-ESI-MS and MS/MS could be an ideal method for TDP because cIEF can enable separation of proteoforms based on their isoelectric points (pIs) with ultra-high resolution. cIEF-ESI-MS has been well-recognized for protein characterization since 1990s. However, the widespread adoption of cIEF-MS for the characterization of proteoforms had been impeded by several technical challenges, including the lack of highly sensitive and robust ESI interface for coupling cIEF to MS, ESI suppression of analytes from ampholytes, and the requirement of manual operations. In this mini review, we summarize the technical improvements of cIEF-ESI-MS for characterizing proteoforms and highlight some recent applications to hydrophobic proteins, urinary albumin variants, charge variants of monoclonal antibodies, and large-scale TDP of complex proteomes.
The shading-type BIPV claddings can act as power generators as well as external shading devices and insulation panels. There is little available information about the impacts of orientations and ...inclinations on the combined energy effects of the shading-type BIPV claddings, including the power output of PV modules, the cooling load reduction of windows and concrete walls. It is worth studying the effects of different shading-type BIPV cladding designs on the total energy saving in order to maximize the system’s energy performance. By considering the meteorological conditions in Hong Kong, the energy effect of the shading-type BIPV claddings with different surface azimuth angles, in terms of electricity generation and cooling energy consumption reduction is analyzed in this paper. Based on the investigations, the optimum design of the shading-type BIPV claddings for different orientations can be achieved.
Treatment of severe Coronavirus Disease 2019 (COVID-19) is challenging. We performed a phase 2 trial to assess the efficacy and safety of human umbilical cord-mesenchymal stem cells (UC-MSCs) to ...treat severe COVID-19 patients with lung damage, based on our phase 1 data. In this randomized, double-blind, and placebo-controlled trial, we recruited 101 severe COVID-19 patients with lung damage. They were randomly assigned at a 2:1 ratio to receive either UC-MSCs (4 × 10
cells per infusion) or placebo on day 0, 3, and 6. The primary endpoint was an altered proportion of whole lung lesion volumes from baseline to day 28. Other imaging outcomes, 6-minute walk test (6-MWT), maximum vital capacity, diffusing capacity, and adverse events were recorded and analyzed. In all, 100 COVID-19 patients were finally received either UC-MSCs (n = 65) or placebo (n = 35). UC-MSCs administration exerted numerical improvement in whole lung lesion volume from baseline to day 28 compared with the placebo (the median difference was -13.31%, 95% CI -29.14%, 2.13%, P = 0.080). UC-MSCs significantly reduced the proportions of solid component lesion volume compared with the placebo (median difference: -15.45%; 95% CI -30.82%, -0.39%; P = 0.043). The 6-MWT showed an increased distance in patients treated with UC-MSCs (difference: 27.00 m; 95% CI 0.00, 57.00; P = 0.057). The incidence of adverse events was similar in the two groups. These results suggest that UC-MSCs treatment is a safe and potentially effective therapeutic approach for COVID-19 patients with lung damage. A phase 3 trial is required to evaluate effects on reducing mortality and preventing long-term pulmonary disability. (Funded by The National Key R&D Program of China and others. ClinicalTrials.gov number, NCT04288102.
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•Perfluorobutane sulfonate has higher environmental safety in plants.•Perfluorobutane sulfonate inhibits primary root growth and photosynthesis.•Perfluorobutane sulfonate disrupts ...phytohormone signaling pathways.•Photosynthesis is a common target of organic pollutants inhibiting plant growth.
Perfluorobutane sulfonate (PFBS) has oily and hydrophobic characteristics similar to those of perfluorooctane sulfonic acid (PFOS), which is an environmental organic pollutant and has gradually become the main substitute for PFOS in industry. Several studies have revealed the potential toxicity of PFBS in animals. PFBS can be taken up and accumulate in plants; however, whether and how PFBS affects plant growth remain largely unclear. A low concentration of PFBS did not affect plant growth, indicating that it had higher environmental safety than other perfluorinated compounds; however, a high concentration of PFBS (>1 mM) markedly inhibited primary root growth in Arabidopsis thaliana. Subsequently, we investigated the molecular mechanisms underlying plant growth mediated by high concentrations of PFBS. First, a genome-wide transcriptomic analysis revealed that PFBS altered the expression of genes associated with phytohormone signaling pathways. Combining physio-biochemical and genetic analyses, we next demonstrated that PFBS reduced the contents of indole-3-acetic acid (IAA) and abscisic acid (ABA), and disrupted the two signaling pathways in plants, finally inhibiting root growth. Moreover, a high concentration of PFBS also inhibited photosynthesis by comprehensively repressing the expression of genes related to the Calvin cycle and the photosynthetic apparatus. Such an understanding is helpful for elucidating the phytotoxicity of PFBS and provides a new strategy for toxicology research on organic pollutants in plants.
Small satellites in low Earth orbit (LEO) are typically organized as a satellite constellation. The satellite number of a LEO satellite constellation would be several hundred or even tens of ...thousands to realize a fully global coverage. This imposes a big challenge on ground station for satellite ordinary management and control operation. Phased array antennas are considered as attractive candidates for future satellite ground station. The primary reason is that phased array antennas can produce numbers of beams by the beamforming network thus support multiple satellites simultaneously. This paper aims to provide a tutorial-like review on phased array antennas as satellite ground station. The advantages of phased array antennas for this application are summarized by comparing them with traditional reflector antennas. Several array geometries for realizing the hemispherical coverage required for satellite tracking are presented. System architecture are given, and some considerations for engineering practice about phased array antenna based satellite ground station are also discussed.
The multi-mode tracking control of robot manipulators with unknown dynamics is investigated in this paper. In view of varying loads, robot manipulators are modeled as multi-mode switched systems. ...Adaptive PID (proportion–integration–differentiation)–like switched controllers are designed via the error transformation and multiple Lyapunov function method, which can make the error system practical stability within prescribed time under a class of switching signals satisfying average dwell time. Furthermore, two cases under the healthy actuator and faulty actuator are discussed. For the case of the partial failure of the actuator, the fault-tolerant adaptive PID-like controller is presented, which consists of two parts. Finally, a simulation example is given to demonstrate the effectiveness of the proposed method.
Femtogram proteomics: An ultrasensitive capillary zone electrophoresis–mass spectrometry system that is based on an improved nanospray interface has been developed. This system is used for the ...analysis of picogram to femtogram amounts of E. coli digests; for example, over 100 proteins were identified from 16 pg digests by tandem mass spectrometry. AMTs=accurate mass and time tags.
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