In these proceedings, we present the measurements of nuclear modification factors for electrons from open charm (
c→e
) and bottom hadron decays (
b→e
) at mid-rapidity region in Au+Au collisions at ...√
S
NN
= 200 GeV. The significance of the difference in nuclear modification factors between
b→e
and
c→e
is ≥ 3σ. We also present the measurements of the elliptic flow (
v
2
) of inclusive heavy-flavor hadron decayed electrons (HFE) in Au+Au collisions at √
S
NN
= 27 and 54.4 GeV. The results show non-zero HFE
v
2
in 54.4 GeV Au+Au collisions and a hint of smaller HFE
v
2
in 27 GeV Au+Au collisions than those at 54.4 and 200 GeV.
Critically ill patients diagnosed with COVID-19 may develop a pro-thrombotic state that places them at a dramatically increased lethal risk. Although platelet activation is critical for thrombosis ...and is responsible for the thrombotic events and cardiovascular complications, the role of platelets in the pathogenesis of COVID-19 remains unclear.
Using platelets from healthy volunteers, non-COVID-19 and COVID-19 patients, as well as wild-type and hACE2 transgenic mice, we evaluated the changes in platelet and coagulation parameters in COVID-19 patients. We investigated ACE2 expression and direct effect of SARS-CoV-2 virus on platelets by RT-PCR, flow cytometry, Western blot, immunofluorescence, and platelet functional studies in vitro, FeCl
-induced thrombus formation in vivo, and thrombus formation under flow conditions ex vivo.
We demonstrated that COVID-19 patients present with increased mean platelet volume (MPV) and platelet hyperactivity, which correlated with a decrease in overall platelet count. Detectable SARS-CoV-2 RNA in the blood stream was associated with platelet hyperactivity in critically ill patients. Platelets expressed ACE2, a host cell receptor for SARS-CoV-2, and TMPRSS2, a serine protease for Spike protein priming. SARS-CoV-2 and its Spike protein directly enhanced platelet activation such as platelet aggregation, PAC-1 binding, CD62P expression, α granule secretion, dense granule release, platelet spreading, and clot retraction in vitro, and thereby Spike protein enhanced thrombosis formation in wild-type mice transfused with hACE2 transgenic platelets, but this was not observed in animals transfused with wild-type platelets in vivo. Further, we provided evidence suggesting that the MAPK pathway, downstream of ACE2, mediates the potentiating role of SARS-CoV-2 on platelet activation, and that platelet ACE2 expression decreases following SARS-COV-2 stimulation. SARS-CoV-2 and its Spike protein directly stimulated platelets to facilitate the release of coagulation factors, the secretion of inflammatory factors, and the formation of leukocyte-platelet aggregates. Recombinant human ACE2 protein and anti-Spike monoclonal antibody could inhibit SARS-CoV-2 Spike protein-induced platelet activation.
Our findings uncovered a novel function of SARS-CoV-2 on platelet activation via binding of Spike to ACE2. SARS-CoV-2-induced platelet activation may participate in thrombus formation and inflammatory responses in COVID-19 patients.
High-slope and rock mass joint development are the factors for predicting and controlling blasting vibrations under open pit mining. Blasting vibration adversely affects the stability of jointed rock ...slopes, thus studying the characteristics of blasting vibration frequency bands in jointed rock masses slope is an important task to ensure the safety of blasting operations. In the present study, vibratory ground motions were measured during blasting excavation in open-pit mining, and the blasting vibration frequency band characteristics of jointed rock masses and high slope were studied through the wavelet transform and response spectrum method. The results demonstrated that the amplification effects of the peak particle velocity (PPV) and energy between different frequency bands exhibited distinguishing characteristics. It was found that, with the increase in elevation, the PPV and energy amplification effects were the most obvious in the 0–16 Hz band, while they were attenuated in the 32–64 Hz band. Furthermore, the distribution of dominant frequency bands of vibration signals observed to be low and narrow, and the average frequency had been reduced. In the development of joints in rock masses, the PPV and energy in each frequency band were attenuated, and the distribution of the dominant frequency bands of vibration signals was high and wide. Also, the average frequency had been increased and the multi-modal characteristics of the responses to blasting vibrations were more obvious. The rock mass structures had displayed different amplification effects on the frequency components of the blasting seismic waves. Finally, as the effects of jointed rock masses on the blasting load responses could not be simply considered as reducing vibrations, they must be analyzed using vibration theory and actual situations.
Heavy quarks, produced at early stages of heavy-ion collisions, are an excellent probe of the Quark-Gluon Plasma (QGP) also created in these collisions. Electrons from open heavy-flavor hadron decays ...(HFE) are good proxies for heavy quarks, and have been measured extensively in the last two decades to study QGP properties. These measurements are traditionally carried out by subtracting all known background sources from the inclusive electron sample. More recently, a significant enhancement of
e
+
e
-
pair production at very low transverse momenta was observed in peripheral heavy-ion collisions. The production characteristics is consistent with coherent photon–photon interactions, which should also constitute a background source to the HFE measurements. In this article, we provide theoretical predictions for the contribution of coherent electron production to HFEs as a function of transverse momentum, centrality and collision energy in Au+Au and Pb+Pb collisions.
Intratumoral accumulation of CD4
CD25
Foxp3
regulatory T (Treg) cells occurs in acute myeloid leukemia (AML), but little is known about the role of tumor cells themselves in this process. Here, we ...showed that an immune checkpoint PD-L1 expressed by AML cells promoted the conversion and expansion of Treg cells sustaining high expression of Foxp3 and PD-1 as well as a suppressive function. Furthermore, an AML cell line HEL overexpressed PD-L1 promoted the conversion and expansion of Treg cells and CD4
PD-1
Foxp3
T (PD-1
Treg) cells from the conventional CD4
T cells. CD4
CD25
PD-1
T cells secreted more IL-10 production than CD4
CD25
PD-1
T cells. IL-35, another cytokine secreted by Treg cells, promoted the proliferation of HL-60 cells and enhanced chemoresistance to cytarabine. Blockade of PD-1 signaling using anti-PD-L1 antibody dramatically impaired the generation of Treg cells and sharply retarded the progression of a murine AML model injected with C1498 cells. The frequency of intratumoral PD-1
Treg cells was capable of predicting patient survival in patients with AML. In conclusion, our data suggest that PD-L1 expression by AML cells may directly drive Treg cell expansion as a mechanism of immune evasion and the frequency of PD-1
Treg cells is a potential prognostic predictor in patients with AML.
Chemotherapy was conventionally applied to kill cancer cells, but regrettably, they also induce damage to normal cells with high-proliferative capacity resulting in cardiotoxicity, nephrotoxicity, ...peripheral nerve toxicity, and ovarian toxicity. Of these, chemotherapy-induced ovarian damages mainly include but are not limited to decreased ovarian reserve, infertility, and ovarian atrophy. Therefore, exploring the underlying mechanism of chemotherapeutic drug-induced ovarian damage will pave the way to develop fertility-protective adjuvants for female patients during conventional cancer treatment. Herein, we firstly confirmed the abnormal gonadal hormone levels in patients who received chemotherapy and further found that conventional chemotherapeutic drugs (cyclophosphamide, CTX; paclitaxel, Tax; doxorubicin, Dox and cisplatin, Cis) treatment significantly decreased both the ovarian volume of mice and the number of primordial and antral follicles and accompanied with the ovarian fibrosis and reduced ovarian reserve in animal models. Subsequently, Tax, Dox, and Cis treatment can induce the apoptosis of ovarian granulosa cells (GCs), likely resulting from excessive reactive oxygen species (ROS) production-induced oxidative damage and impaired cellular anti-oxidative capacity. Thirdly, the following experiments demonstrated that Cis treatment could induce mitochondrial dysfunction through overproducing superoxide in GCs and trigger lipid peroxidation leading to ferroptosis, first reported in chemotherapy-induced ovarian damage. In addition, N-acetylcysteine (NAC) treatment could alleviate the Cis-induced toxicity in GCs by downregulating cellular ROS levels and enhancing the anti-oxidative capacity (promoting the expression of glutathione peroxidase, GPX4; nuclear factor erythroid 2-related factor 2, Nrf2 and heme oxygenase-1, HO-1). Our study confirmed the chemotherapy-induced chaotic hormonal state and ovarian damage in preclinical and clinical examination and indicated that chemotherapeutic drugs initiated ferroptosis in ovarian cells through excessive ROS-induced lipid peroxidation and mitochondrial dysfunction, leading to ovarian cell death. Consequently, developing fertility protectants from the chemotherapy-induced oxidative stress and ferroptosis perspective will ameliorate ovarian damage and further improve the life quality of cancer patients.
Advanced civil aero-engines tend to adopt lean burn combustors to meet emission requirements. The exit of a lean burn combustor experiences highly non-uniformities in both temperature (Hot Streak, ...HS) and flow (swirl). This paper presents a numerical investigation on the behaviors of a High-Pressure (HP) turbine under a combined effect of swirl and hot streak. The investigation was conducted on a GE-E3 HP turbine with unsteady numerical simulations, which considered the realistic clocking position of the HP Nozzle Guide Vane (NGV) relative to the combustor. The influences of swirl orientations on the HS migration and thermal performances on the blade surface were examined. Results indicate that, inside the NGV passage, the swirl’s induced incidence angle effect dominates the HS radial migration. The transversal movement of HS follows the cross flow and thus makes itself approach the Suction Side (SS) and keep away from the Pressure Side (PS) as passing through the NGV, so that HS near the SS is more influenced by the incidence angle effect than that near the PS. As for the heat transfer, swirl affects the Heat Transfer Coefficient (HTC) on the NGV’s PS and SS mainly through the incidence angle effect. Different from the NGV, the inlet swirl and HS have limited effect on the HTC on the rotor blade’s PS, while on the rotor blade’s SS, the original vortex system dominates; therefore, the inlet non-uniformities merely enhance the HTC on the SS rather than alter its distribution characteristics.
Large-scale personalization is becoming a reality. To ensure market competitiveness and economic benefits, enterprises require rapid response capability and flexible manufacturing operations. ...However, variant design and production line reconfiguration are complicated because it involves the commissioning, replacement, and adaptive integration of equipment and remodification of control systems. Herein, a digital twin-driven production line variant design is presented. As a new technology, the digital twin can realize the parallel control from the physical world to the digital world and accelerate the design process of the production line through a virtual-real linkage. Simultaneously, the actual production line can be simulated to verify the rationality of the design scheme and avoid cost wastage. Four key technologies are described in detail, and a production line variant design platform based on digital twin is built to support rapid production line variant design. Finally, experiments using a smartphone assembly line as an example are performed; the results demonstrate that the proposed method can realize production line variant design and increase production efficiency.
Acute myeloid leukemia (AML) is a hematological malignancy characterized by a rapid increase in the number of immature myeloid cells in bone marrow. Despite recent advances in the treatment, AML ...remains an incurable disease. Matrine, a major component extracted from Sophora flavescens Ait, has been demonstrated to exert anticancer effects on various cancer cell lines. However, the effects of matrine on AML remain largely unknown. Here we investigated its anticancer effects and underlying mechanisms on human AML cells in vitro and in vivo. The results showed that matrine inhibited cell viability and induced cell apoptosis in AML cell lines as well as primary AML cells from patients with AML in a dose- and time-dependent manner. Matrine induced apoptosis by collapsing the mitochondrial membrane potential, inducing cytochrome c release from mitochondria, reducing the ratio of Bcl-2/Bax, increasing activation of caspase-3, and decreasing the levels of p-Akt and p-ERK1/2. The apoptotic effects of matrine on AML cells were partially blocked by a caspase-3 inhibitor Z-DEVD-FMK and a PI3K/Akt activator IGF-1, respectively. Matrine potently inhibited in vivo tumor growth following subcutaneous inoculation of HL-60 cells in SCID mice. These findings indicate that matrine can inhibit cell proliferation and induce apoptosis of AML cells and may be a novel effective candidate as chemotherapeutic agent against AML.
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