STAT3 Contributes To Oncolytic Newcastle Disease Virus-Induced Immunogenic Cell Death in Melanoma Cells

Background: Oncolytic viruses (OVs) are emerging as potent inducers of immunogenic cell death (ICD), releasing danger-associated molecular patterns (DAMPs) that induce potent anticancer immunity. Oncolytic Newcastle disease virus (NDV) has been shown to educe ICD in both glioma and lung cancer cells. The objective of this study is to investigate whether oncolytic NDV induces ICD in melanoma cells and how it is regulated.Methods: Various time points were actuated to check the expression and release of ICD markers induced by NDV strain, NDV/FMW in melanoma cell lines. The expression and release of ICD markers induced by oncolytic NDV strain, NDV/FMW, in melanoma cell lines at various time points were determined. Surface-exposed calreticulin (CRT) was inspected by confocal imaging. The supernatants of NDV/FMW infected cells were collected and concentrated for the determination of ATP secretion by ELISA, HMGB1, and HSP70/90 expression by immunoblot (IB) analysis. Pharmacological inhibition of apoptosis, autophagy, necroptosis, ER Stress, and STAT3 (signal transducer and activator of transcription 3) was achieved by treatment with small molecule inhibitors. Melanoma cell lines stably depleted of STAT3 were established with lentiviral constructs. Supernatants from NDV-infected cells were intratumorally injected to mice bearing melanoma cells-derived tumors.Results: Oncolytic NDV induced CRT exposure, the release of HMGB1 and HSP70/90 as well as secretion of ATP in melanoma cells. Inhibition of apoptosis, autophagy, necroptosis or ER stress attenuated NDV/FMW-induced release of HMGB1 and HSP70/90. Moreover, NDV/FMW-induced ICD markers in melanoma cells were also suppressed by either treatment with a STAT3 inhibitor or shRNA-mediated depletion of STAT3. Of translational importance, treatment of mice bearing melanoma cells-derived tumors with supernatants from NDV/FMW-infected cells significantly inhibited tumor growth.Conclusions: Our data authenticate that oncolytic NDV/FMW might be a potent inducer of ICD in melanoma cells, which is amalgamated with several forms of cell death. We also show that STAT3 plays a role in NDV/FMW-induced ICD in melanoma cells. Together, our data highlight oncolytic NDV as propitious for cancer therapeutics by stimulatingan anti-melanoma immune response

Measurements of Higgs boson production cross sections and couplings in the diphoton decay channel at root s=13 TeV

Measurements of Higgs boson production cross sections and couplings in events where the Higgs boson decays into a pair of photons are reported. Events are selected from a sample of proton-proton collisions at root s = 13TeV collected by the CMS detector at the LHC from 2016 to 2018, corresponding to an integrated luminosity of 137 fb(-1). Analysis categories enriched in Higgs boson events produced via gluon fusion, vector boson fusion, vector boson associated production, and production associated with top quarks are constructed. The total Higgs boson signal strength, relative to the standard model (SM) prediction, is measured to be 1.12 +/- 0.09. Other properties of the Higgs boson are measured, including SM signal strength modifiers, production cross sections, and its couplings to other particles. These include the most precise measurements of gluon fusion and vector boson fusion Higgs boson production in several different kinematic regions, the first measurement of Higgs boson production in association with a top quark pair in five regions of the Higgs boson transverse momentum, and an upper limit on the rate of Higgs boson production in association with a single top quark. All results are found to be in agreement with the SM expectations.Peer reviewe

Search for lepton-flavor violating decays of the Higgs boson in the mu tau and e tau final states in proton-proton collisions at root s=13 TeV

A search is presented for lepton-flavor violating decays of the Higgs boson to mu t and et. The dataset corresponds to an integrated luminosity of 137 fb(-1) collected at the LHC in proton-proton collisions at a center-of-mass energy of 13 TeV. No significant excess has been found, and the results are interpreted in terms of upper limits on lepton-flavor violating branching fractions of the Higgs boson. The observed (expected) upper limits on the branching fractions are, respectively, B(H -> mu t) e tau) < 0.22(0.16)% at 95% confidence level.Peer reviewe

Horizontal-Vertical-Rocking Coupled Response Analysis of Vertical Seismic Isolated Structure under Near-Fault Earthquakes

For vertical isolated structures with excessive vertical eccentricity for mass and vertical stiffness, horizontal-vertical-rocking response needs to be better understood for vertical isolated structures located in near-fault areas, where long-period velocity pulse can be produced. In this study, a seismic isolation system including quasizero stiffness (QZS) and vertical damper (VD) is used to control near-fault (NF) vertical earthquakes. The responses of horizontal-vertical-rocking coupling base-isolated structure including quasizero stiffness (QZS) and vertical damper (VD) subjected to NF horizontal and vertical ground motions are investigated. Nonlinear dynamic analyses are conducted to study the effects of essential parameters such as isolation system eccentricity, static equilibrium position, vertical isolation period, and vertical damping ratio on seismic responses of vertical isolated structure. It is found that increasing vertical period and damping ratio causes the vertical isolated structures to behave well in reducing rocking responses of structure. The effect of horizontal-vertical-rocking coupling on vertical seismic isolation efficiency is insignificant. The vertical seismic isolation remains effective as compared to the system supported on rubber bearings. The vertical damping can significantly control the vertical displacement and rocking moment

The Routing Problem for Electric Truck with Partial Nonlinear Charging and Battery Swapping

The maritime industry has introduced the concept of “green ports” as a means to achieve sustainable development by reducing carbon emissions. Within ports, trucks play a crucial role in transportation operations. However, there is limited comprehensive research on the electric truck routing problem containing practical constraints such as charging options and charging processes. This study presents a more realistic routing problem for electric trucks, with a specific focus on multiple charging options within green ports. To address this challenge, we formulate a mixed-integer programming model designed to minimize overall operational costs associated with the transportation of trucks over the planning horizon. In order to solve this problem effectively, we devise an Adaptive Large Neighborhood Search (ALNS) algorithm, embedded with several customized operators. Through a series of numerical experiments, the effectiveness of the proposed algorithm is verified. The experimental results provide compelling evidence of the superior performance of the proposed algorithm compared to the original ALNS algorithm. Furthermore, sensitivity analysis is conducted, leading to valuable managerial insights

Hybrid Network-on-Chip: An Application-Aware Framework for Big Data

Burst growing IoT and cloud computing demand exascale computing systems with high performance and low power consumption to process massive amounts of data. Modern system platforms based on fundamental requirements encounter a performance gap in chasing exponential growth in data speed and amount. To narrow the gap, a heterogamous design gives us a hint. A network-on-chip (NoC) introduces a packet-switched fabric for on-chip communication and becomes the de facto many-core interconnection mechanism; it refers to a vital shared resource for multifarious applications which will notably affect system energy efficiency. Among all the challenges in NoC, unaware application behaviors bring about considerable congestion, which wastes huge amounts of bandwidth and power consumption on the chip. In this paper, we propose a hybrid NoC framework, combining buffered and bufferless NoCs, to make the NoC framework aware of applications’ performance demands. An optimized congestion control scheme is also devised to satisfy the requirement in energy efficiency and the fairness of big data applications. We use a trace-driven simulator to model big data applications. Compared with the classical buffered NoC, the proposed hybrid NoC is able to significantly improve the performance of mixed applications by 17% on average and 24% at the most, decrease the power consumption by 38%, and improve the fairness by 13.3%

Effects of traditional Chinese mind-body exercise-Baduanjin for type 2 diabetes on psychological well-being: A systematic review and meta-analysis

BackgroundType 2 diabetes is considered one of the most psychologically demanding chronic conditions. Patients suffering from this disease often have poor psychological well-being due to emotional stress. Baduanjin exercises, a traditional Chinese mind-body exercise, are used in the management of type 2 diabetes, especially for mental health. However, the effect of Baduanjin exercises on psychological well-being of patients with type 2 diabetes maintains controversial. Therefore, this systematic review was conducted to evaluate the effects on psychological well-being of Baduanjin exercises for type 2 diabetes.MethodsSix electronic databases were searched from their inception to March 2022 for randomized controlled trials of Baduanjin exercises for type 2 diabetes. Two reviewers independently extracted data and assessed methodological quality based on PEDro scale. The subgroup analysis was conducted based on different control interventions. The Cochran Q statistic and I2 were applied to assess the heterogeneity.ResultsTwenty-seven studies between 2005 and 2019 were included in our review. Most of them exceeded the cutoff score 6 based on the PEDro scale. In psychological well-being, the aggregated results indicated that Baduanjin exercises showed positive effects in psychological well-being (SMD, 0.96; 95% CI, 0.57 to 1.36; p &lt; 0.00001), depression (SMD, 1.03; 95% CI, 0.08 to 1.97; p = 0.03), anxiety (SMD, 0.88; 95% CI, 0.30 to 1.46; p = 0.003), and mental health (SMD, 0.72; 95% CI, 0.42 to 1.02; p &lt; 0.00001). In glycemic control, Baduanjin exercises showed better improvements in FBG (SMD, 0.53; 95% CI, 0.34 to 0.72; p &lt; 0.00001), HbA1c (SMD, 0.58; 95% CI, 0.41 to 0.75; p &lt; 0.00001), and 2-hPBG (SMD, 0.56; 95% CI, 0.08 to 1.03; p = 0.02) compared with usual care/education. However, Baduanjin exercises only showed better improvements in HbA1c when compared with other exercises.ConclusionsThe traditional Chinese mind-body exercise-Baduanjin is a beneficial comprehensive therapy for type 2 diabetes, especially in promoting psychological well-being.Systematic review registrationhttps://www.crd.york.ac.uk/PROSPERO/display_record.php?RecordID=110034