Abstract Previous data demonstrate that traumatic brain injury (TBI) activates autophagy, and increases microtubule-associated protein 1 light chain 3 (LC3) immunostaining mainly in neurons. However, ...the role of autophagy in traumatic brain damage remains elusive. The aim of the present study was to investigate the autophagic mechanisms participating in traumatic brain injury. The autophagy inhibitors 3-methyladenine (3-MA) and bafliomycin A1 (BFA) were administered with a single i.c.v. injection before TBI. We first examined the protein levels of Beclin-1 and LC3 II, which have been found to promote autophagy previously. Immunoblotting analysis showed that 3-MA pretreatment reduced post-TBI Beclin-1 and LC3-II levels, and maintained p62/SQSTM1 (p62) levels. In addition, double immunolabeling showed that the increased punctate LC3-II dots colocalizing with Propidium Iodide (PI)-stained nuclei at 24 h after injury, were partially inhibited by 3-MA pretreatment. Furthermore, inhibition of autophagy could reduce TBI-induced cell injury assessed with i.p. injection of PI and lesion volume, and attenuate behavioral outcome evaluated by motor test and Morris water maze. The neuroprotective effects were associated with an inhibition on TBI-induced up-regulation of LC3, Beclin-1, cathepsin B, caspase-3 and the Beclin-1/Bcl-2 ratio. Taken together, these data imply that the autophagy pathway is involved in the pathophysiologic responses after TBI, and inhibition of this pathway may help attenuate traumatic damage and functional outcome deficits.
High tumor mutational burden (TMB-H) is correlated with enhanced objective response rate (ORR) and progression-free survival (PFS) for certain cancers receiving immunotherapy. This study aimed to ...investigate the safety and efficacy of toripalimab, a humanized programmed death-1 (PD-1) antibody, in advanced gastric cancer (AGC), and the predictive survival benefit of TMB and PD-L1.
We reported on the AGC cohort of phase Ib/II trial evaluating the safety and activity of toripalimab in patients with AGC, oesophageal squamous cell carcinoma, nasopharyngeal carcinoma and head and neck squamous cell carcinoma. In cohort 1, 58 chemo-refractory AGC patients received toripalimab (3 mg/kg d1, Q2W) as a monotherapy. In cohort 2, 18 chemotherapy-naive AGC patients received toripalimab (360 mg d1, Q3W) with oxaliplatin 130 mg/m2 qd, d1, capecitabine 1000 mg/m2 b.i.d., d1–d14, Q3W as first-line treatment. Primary end point was ORR. Biomarkers such as PD-L1 and TMB were evaluated for correlation with clinical efficacy.
In cohort 1, the ORR was 12.1% and the disease control rate (DCR) was 39.7%. Median PFS was 1.9 months and median OS was 4.8 months. The TMB-H group showed significant superior OS than the TMB-L group 14.6 versus 4.0 months, HR = 0.48 (96% CI 0.24–0.96), P = 0.038, while PD-L1 overexpression did not correlate with significant survival benefit. A 77.6% of patients experienced at least one treatment-related adverse event (TRAE), and 22.4% of patients experienced a grade 3 or higher TRAE. In cohort 2, the ORR was 66.7% and the DCR was 88.9%. A 94.4% of patients experienced at least one TRAE and 38.9% of patients experienced grade 3 or higher TRAEs.
Toripalimab has demonstrated a manageable safety profile and promising antitumor activity in AGC patients, especially in combination with XELOX. High TMB may be a predictive marker for OS of AGC patients receiving toripalimab as a single agent.
ClinicalTrials.gov NCT02915432.
The cross section for the process e^{+}e^{-}→π^{+}π^{-}J/ψ is measured precisely at center-of-mass energies from 3.77 to 4.60 GeV using 9 fb^{-1} of data collected with the BESIII detector operating ...at the BEPCII storage ring. Two resonant structures are observed in a fit to the cross section. The first resonance has a mass of (4222.0±3.1±1.4) MeV/c^{2} and a width of (44.1±4.3±2.0) MeV, while the second one has a mass of (4320.0±10.4±7.0) MeV/c^{2} and a width of (101.4_{-19.7}^{+25.3}±10.2) MeV, where the first errors are statistical and second ones are systematic. The first resonance agrees with the Y(4260) resonance reported by previous experiments. The precision of its resonant parameters is improved significantly. The second resonance is observed in e^{+}e^{-}→π^{+}π^{-}J/ψ for the first time. The statistical significance of this resonance is estimated to be larger than 7.6σ. The mass and width of the second resonance agree with the Y(4360) resonance reported by the BABAR and Belle experiments within errors. Finally, the Y(4008) resonance previously observed by the Belle experiment is not confirmed in the description of the BESIII data.
The power battery thermal management problem in EV (electric vehicle) and HEV (hybrid electric vehicle) has been widely discussed, and EIS (electrochemical impedance spectroscopy) is an effective ...experimental method to test and estimate the status of the battery. Firstly, an electrochemical-based impedance matrix analysis for lithium-ion battery is developed to describe the impedance response of electrochemical impedance spectroscopy. Then a method, based on electrochemical impedance spectroscopy measurement, has been proposed to estimate the internal temperature of power lithium-ion battery by analyzing the phase shift and magnitude of impedance at different ambient temperatures. Respectively, the SoC (state of charge) and temperature have different effects on the impedance characteristics of battery at various frequency ranges in the electrochemical impedance spectroscopy experimental study. Also the impedance spectrum affected by SoH (state of health) is discussed in the paper preliminary. Therefore, the excitation frequency selected to estimate the inner temperature is in the frequency range which is significantly influenced by temperature without the SoC and SoH. The intrinsic relationship between the phase shift and temperature is established under the chosen excitation frequency. And the magnitude of impedance related to temperature is studied in the paper. In practical applications, through obtaining the phase shift and magnitude of impedance, the inner temperature estimation could be achieved. Then the verification experiments are conduced to validate the estimate method. Finally, an estimate strategy and an on-line estimation system implementation scheme utilizing battery management system are presented to describe the engineering value.
We report a study of the processes of e^{+}e^{-}→K^{+}D_{s}^{-}D^{*0} and K^{+}D_{s}^{*-}D^{0} based on e^{+}e^{-} annihilation samples collected with the BESIII detector operating at BEPCII at five ...center-of-mass energies ranging from 4.628 to 4.698 GeV with a total integrated luminosity of 3.7 fb^{-1}. An excess of events over the known contributions of the conventional charmed mesons is observed near the D_{s}^{-}D^{*0} and D_{s}^{*-}D^{0} mass thresholds in the K^{+} recoil-mass spectrum for events collected at sqrts=4.681 GeV. The structure matches a mass-dependent-width Breit-Wigner line shape, whose pole mass and width are determined as (3982.5_{-2.6}^{+1.8}±2.1) MeV/c^{2} and (12.8_{-4.4}^{+5.3}±3.0) MeV, respectively. The first uncertainties are statistical and the second are systematic. The significance of the resonance hypothesis is estimated to be 5.3 σ over the contributions only from the conventional charmed mesons. This is the first candidate for a charged hidden-charm tetraquark with strangeness, decaying into D_{s}^{-}D^{*0} and D_{s}^{*-}D^{0}. However, the properties of the excess need further exploration with more statistics.
Using a low background data sample of 9.7×10^{5} J/ψ→γη^{'}, η^{'}→γπ^{+}π^{-} events, which are 2 orders of magnitude larger than those from the previous experiments, recorded with the BESIII ...detector at BEPCII, the decay dynamics of η^{'}→γπ^{+}π^{-} are studied with both model-dependent and model-independent approaches. The contributions of ω and the ρ(770)-ω interference are observed for the first time in the decays η^{'}→γπ^{+}π^{-} in both approaches. Additionally, a contribution from the box anomaly or the ρ(1450) resonance is required in the model-dependent approach, while the process specific part of the decay amplitude is determined in the model-independent approach.
The cross sections of e^{+}e^{-}→π^{+}π^{-}h_{c} at center-of-mass energies from 3.896 to 4.600 GeV are measured using data samples collected with the BESIII detector operating at the Beijing ...Electron Positron Collider. The cross sections are found to be of the same order of magnitude as those of e^{+}e^{-}→π^{+}π^{-}J/ψ and e^{+}e^{-}→π^{+}π^{-}ψ(2S), but the line shape is inconsistent with the Y states observed in the latter two modes. Two structures are observed in the e^{+}e^{-}→π^{+}π^{-}h_{c} cross sections around 4.22 and 4.39 GeV/c^{2}, which we call Y(4220) and Y(4390), respectively. A fit with a coherent sum of two Breit-Wigner functions results in a mass of (4218.4_{-4.5}^{+5.5}±0.9) MeV/c^{2} and a width of (66.0_{-8.3}^{+12.3}±0.4) MeV for the Y(4220), and a mass of (4391.5_{-6.8}^{+6.3}±1.0) MeV/c^{2} and a width of (139.5_{-20.6}^{+16.2}±0.6) MeV for the Y(4390), where the first uncertainties are statistical and the second ones systematic. The statistical significance of Y(4220) and Y(4390) is 10σ over one structure assumption.
We study the e^{+}e^{-}→γωJ/ψ process using 11.6 fb^{-1} e^{+}e^{-} annihilation data taken at center-of-mass energies from sqrts=4.008 GeV to 4.600 GeV with the BESIII detector at the BEPCII ...storage ring. The X(3872) resonance is observed for the first time in the ωJ/ψ system with a significance of more than 5σ. The relative decay ratio of X(3872)→ωJ/ψ and π^{+}π^{-}J/ψ is measured to be R=1.6_{-0.3}^{+0.4}±0.2, where the first uncertainty is statistical and the second systematic (the same hereafter). The sqrts-dependent cross section of e^{+}e^{-}→γX(3872) is also measured and investigated, and it can be described by a single Breit-Wigner resonance, referred to as the Y(4200), with a mass of 4200.6_{-13.3}^{+7.9}±3.0 MeV/c^{2} and a width of 115_{-26}^{+38}±12 MeV. In addition, to describe the ωJ/ψ mass distribution above 3.9 GeV/c^{2}, we need at least one additional Breit-Wigner resonance, labeled as X(3915), in the fit. The mass and width of the X(3915) are determined. The resonant parameters of the X(3915) agree with those of the Y(3940) in B→KωJ/ψ and of the X(3915) in γγ→ωJ/ψ observed by the Belle and BABAR experiments within errors.
Wind energy development in built environment is important for the future sustainable cities. The effects of corner modifications (benchmark, recessed, chamfered, and rounded roofs) and wind angles ...(θ = 0°, 22.5°, and 45°) over the flat rooftops of tall buildings were investigated through computational fluid dynamics (CFD) simulations. The velocity, turbulence intensity, skew angle, wind energy, and installation of wind turbines over roofs were also examined. The vertical wind profiles over the rooftops showed similar patterns at various corner modifications. The rounded and chamfered roofs showed higher velocities and lower turbulence intensities than the benchmark and recessed roofs, which can be attributed to the smooth flow separation from leading edges and the flow reattachment over the rounded and chamfered roofs. The hub heights were significantly lower at θ = 45° than those at 0° and 22.5°, due to the thinner boundary layer over roofs at θ = 45°. The highest wind energy amplification factor of 2.0 occurred over the rounded roof. The rounded roof was found to be ideal for the installation of wind turbines, due to the high velocity (more energy), low turbulence (small fatigue loads of wind turbines), and low installation height (low cost).
•Flow features and energy over roofs of tall buildings are investigated by CFD.•Effect of corner modification (sharp, recess, chamfer, and round) is examined.•larger wind angles induce larger zones of higher velocity and lower hub height.•Rounded roofs have a great potential for high energy yield and are idea for turbines.•Smooth flow separation and reattachment occur on rounded and chamfered roofs.
PDF
