Autophagy regulation in heme-induced neutrophil activation is associated with microRNA expression on transfusion-related acute lung injury

AbstractTransfusion-related acute lung injury (TRALI) is the leading cause of death after transfusion therapy. The pathogenesis of TRALI is associated with neutrophil activation in the lungs, causing endothelial damage and capillary leakage, and thus neutrophil extravasation. Heme-related molecules derived from the hemolysis of red blood cell components have been recognized as a stimulator, inducing neutrophil activation at TRALI. To investigate post-transcriptional changes of the neutrophil at TRALI, we performed heme-related molecules induced reactive oxygen species production in the neutrophil as a model. Neutrophils were isolated from heparinized peripheral blood and stimulated with heme-related molecules. After stimulation, reactive oxygen species production, degranulation, phagocytosis activity, and miRNA expression profile of neutrophil were analyzed by luminol assay, flow cytometry, and real-time polymerase chain reaction. The expression of miRNA targeting NADPH oxidase and autophagy in the neutrophil activation of TRALI was explored. The expression profile of miRNAs will be a useful predictor of disease severity and for the grading of patients for transfusion

Functional building blocks for scalable multipartite entanglement in optical lattices

Featuring excellent coherence and operated parallelly, ultracold atoms in optical lattices form a competitive candidate for quantum computation. For this, a massive number of parallel entangled atom pairs have been realized in superlattices. However, the more formidable challenge is to scale-up and detect multipartite entanglement due to the lack of manipulations over local atomic spins in retro-reflected bichromatic superlattices. Here we developed a new architecture based on a cross-angle spin-dependent superlattice for implementing layers of quantum gates over moderately-separated atoms incorporated with a quantum gas microscope for single-atom manipulation. We created and verified functional building blocks for scalable multipartite entanglement by connecting Bell pairs to one-dimensional 10-atom chains and two-dimensional plaquettes of $2\times4$ atoms. This offers a new platform towards scalable quantum computation and simulation

Efficacy, Safety, and Immunogenicity of an Escherichia coliProduced Bivalent Human Papillomavirus Vaccine: An Interim Analysis of a Randomized Clinical Trial

HPV是一种常见的生殖道感染病毒，高危型HPV持续性感染能够导致几乎所有的宫颈癌，其中HPV 16型和18型危害最大，可导致约70%的宫颈癌。预防性HPV疫苗有望减少甚至最终消灭由疫苗型别导致的宫颈癌，降低HPV相关的疾病负担。该研究是在全国4个中心5个现场的18-45岁健康女性中进行的多中心、随机、双盲、对照（戊肝疫苗）的三期临床试验，该研究结果证实我校自主研发的双价人乳头瘤病毒疫苗（大肠杆菌）具有良好的安全性、免疫原性和免疫持久性，可有效地预防HPV 16型和/或18型相关的宫颈高度癌前病变及持续性感染。 该论文报告了我校和厦门万泰沧海生物技术有限公司自主研发的双价人乳头瘤病毒疫苗（大肠杆菌）三期临床试验的期中分析结果。这是第一个进入临床试验并提交药品注册申请的国产人乳头瘤病毒疫苗（HPV疫苗），有望成为世界上第四个上市的HPV疫苗，受到世界卫生组织和盖茨基金会等国际组织的高度关注。 中国医学科学院肿瘤医院乔友林教授、我校吴婷教授、广西壮族自治区疾病预防控制中心李荣成主任医师、江苏省疾病预防控制中心胡月梅主任医师、北京大学人民医院魏丽惠教授、中国食品药品检定研究院李长贵研究员、中国医学科学院肿瘤医院陈汶教授为该论文的共同第一作者，我校张军教授、夏宁邵教授和中国医学科学院肿瘤医院乔友林教授为该论文的共同通讯作者。【Abstract】Background The high cost and insufficient supply of human papillomavirus (HPV) vaccines have slowed the pace of controlling cervical cancer. A phase 3 clinical trial was conducted to evaluate the efficacy, safety and immunogenicity of a novel Escherichia coli-produced bivalent HPV-16/18 vaccine. Methods A multi-centre, randomized, double-blind trial started on November 22, 2012, in China. In total, 7372 eligible women aged 18-45 years were age-stratified and randomly assigned to receiving 3 doses of the test or control (hepatitis E) vaccine at months 0, 1 and 6. Co-primary endpoints included high-grade genital lesions and persistent infection (over 6 months) associated with HPV-16/18. The primary analysis was performed on a per-protocol susceptible population of individuals who were negative for relevant HPV type-specific neutralizing antibodies (at day 0) and DNA (at day 0 through month 7) and who received 3 doses of the vaccine. This report presents data from a pre-specified interim analysis used for regulatory submission. Results In the per-protocol cohort, the efficacies against high-grade genital lesions and persistent infection were 100.0% (95% confidence interval [CI] = 55.6% to 100.0%, 0/3306 in the vaccine group vs. 10/3296 in the control group) and 97.8% (95% CI = 87.1% to 99.9%, 1/3240 vs. 45/3246), respectively. The side effects were mild. No vaccine-related serious adverse events were noted. Robust antibody responses for both types were induced and persisted for at least 42 months. Conclusions The Escherichia coli-produced HPV-16/18 vaccine is well tolerated and highly efficacious against HPV-16/18 associated high-grade genital lesions and persistent infection in women.This work was supported by grants from the Chinese National High-tech R&D Program (863 program, 2012AA02A408), the Chinese National Major Scientific and Technological Special Project for “Significant New Drug Development” (2018ZX09308010 and 2012ZX09101316), the National Natural Science Foundation of China (81673240 and U1705283), the Fujian Provincial Major Scientific and Technological Project (2015YZ0002), the Chinese Academy of Medical Sciences Innovation Fund for Medical Sciences (CIFMS, 2017-I2M-B&R-03, and 2016-I2M-1-019) and Xiamen Innovax. 该研究获得了国家高技术研究发展计划（863计划）、新药创制国家科技重大专项、国家自然科学基金、福建省科技重大专项、中国医学科学院医学与健康科技创新工程基金以及厦门万泰沧海生物技术有限公司的资助

Search for hidden-charm tetraquark with strangeness in e+e−→K+Ds∗−D∗0+c.c.e^{+}e^{-}\rightarrow K^+ D_{s}^{*-} D^{*0}+c.c.

We report a search for a heavier partner of the recently observed $Z_{cs}(3985)^{-}$ state, denoted as $Z_{cs}^{\prime -}$, in the process $e^{+} e^{-}\rightarrow K^{+}D_{s}^{*-}D^{* 0}+c.c.$, based on $e^+e^-$ collision data collected at the center-of-mass energies of $\sqrt{s}=4.661$, 4.682 and 4.699 GeV with the BESIII detector. The $Z_{cs}^{\prime -}$ is of interest as it is expected to be a candidate for a hidden-charm and open-strange tetraquark. A partial-reconstruction technique is used to isolate $K^+$ recoil-mass spectra, which are probed for a potential contribution from $Z_{cs}^{\prime -}\to D_{s}^{*-}D^{* 0}$ ($c.c.$). We find an excess of $Z_{cs}^{\prime -}\rightarrow D_{s}^{*-}D^{*0}$ ($c.c.$) candidates with a significance of $2.9\sigma$, after considering systematic uncertainties, at a mass of $(4123.5 \pm 0.7_{\mathrm{stat.}} \pm 1.1_{\mathrm{syst.}}) \mathrm{MeV}/c^{2}$. As the data set is limited in size, the upper limits are evaluated at the 90% confidence level on the product of the Born cross section and the branching fraction of $Z_{cs}^{\prime-}\rightarrow D_{s}^{*-}D^{* 0}$, $\sigma^{\rm Born}\cdot\mathcal{B}$ at the three energy points, under different assumptions of the $Z_{cs}^{\prime -}$ mass from 4.120 to 4.140 MeV and of the width from 10 to 50 MeV. Under various mass and width assumptions, the upper limits of $\sigma^{\rm Born}\cdot\mathcal{B}$ are found to lie in the range of $2\sim6$, $3\sim7$ and $3\sim6$ pb at $\sqrt{s}=4.661$, 4.682 and 4.699 GeV, respectively. The larger data samples that will be collected in the coming years will allow a clearer picture to emerge concerning the existence and nature of the $Z_{cs}^{\prime -}$ state.Comment: 17 pages, 7 figure

Precise Measurements of Decay Parameters and CPCP Asymmetry with Entangled Λ−Λˉ\Lambda-\bar{\Lambda} Pairs

Based on 10 billion $J/\psi$ events collected at the BESIII experiment, a search for $CP$ violation in $\Lambda$ decay is performed in the difference between $CP$-odd decay parameters $\alpha_{-}$ for $\Lambda \rightarrow p\pi^-$ and $\alpha_{+}$ for $\bar\Lambda \rightarrow \bar{p}\pi^+$ by using the process $e^+e^- \to J/\psi \rightarrow \Lambda \bar\Lambda$. With a five-dimensional fit to the full angular distributions of the daughter baryon, the most precise values for the decay parameters are determined to be $\alpha_{-} = 0.7519 \pm 0.0036 \pm 0.0024$ and $\alpha_{+} = -0.7559 \pm 0.0036 \pm 0.0030$, respectively. The $\Lambda$ and $\bar{\Lambda}$ averaged value of the decay parameter is extracted to be $\alpha_{\rm{avg}} = 0.7542 \pm 0.0010 \pm 0.0024$ with unprecedented accuracy. The $CP$ asymmetry $A_{CP}=(\alpha_{-}+\alpha_{+})/(\alpha_{-}-\alpha_{+})$ is determined to be $-0.0025 \pm 0.0046 \pm 0.0012$, which is one of the most precise measurements in the baryon sector. The reported results for the decay parameter will play an important role in the studies of the polarizations and $CP$ violations for the strange, charmed and beauty baryons

Study of η(1405)/η(1475)\eta(1405)/\eta(1475) in J/ψ→γKS0KS0π0J/\psi\to\gamma K^{0}_{S} K^{0}_{S}\pi^{0} decay

Using a sample of $(10.09\pm0.04)\times10^{9}$ $J/\psi$ decays collected with the BESIII detector, partial wave analyses of the decay $J/\psi\to\gamma K^{0}_{S} K^{0}_{S}\pi^{0}$ are performed within the $K^{0}_{S} K^{0}_{S}\pi^{0}$ invariant mass region below 1.6 ${\textrm{GeV}/c^2}$. The covariant tensor amplitude method is used in both mass independent and mass dependent approaches. Both analysis approaches exhibit dominant pseudoscalar and axial vector components, and show good consistency for the other individual components. Furthermore, the mass dependent analysis reveals that the $K^{0}_{S} K^{0}_{S}\pi^{0}$ invariant mass spectrum for the pseudoscalar component can be well described with two isoscalar resonant states, ${\it i.e.}$, the $\eta(1405)$ with a mass of $1391.7\pm0.7_{-0.3}^{+11.3}$ $\textrm{MeV}/c^2$ and a width of $60.8\pm1.2_{-12.0}^{+5.5}$ $\textrm{MeV}$, and the $\eta(1475)$ with a mass of $1507.6\pm1.6_{-32.2}^{+15.5}$ $\textrm{MeV}/c^2$ and a width of $115.8\pm2.4_{-10.9}^{+14.8}$ $\textrm{MeV}$. The first and second uncertainties are statistical and systematic, respectively. Alternate models for the pseudoscalar component are also tested, but the description of the $K^{0}_{S} K^{0}_{S}\pi^{0}$ invariant mass spectrum deteriorates significantly.Comment: 20 pages, 6 figures, 6 table

Observation of the Y(4230)Y(4230) and evidence for a new vector charmonium-like state Y(4710)Y(4710) in e+e−→KS0KS0J/ψe^{+}e^{-}\to K_{S}^{0} K_{S}^{0} J/\psi

Cross sections for the process $e^{+} e^{-} \to K_{S}^{0} K_{S}^{0} J/\psi$ at center-of-mass energies from $4.128$ to $4.950$ GeV are measured using data samples with a total integrated luminosity of 21.2 fb$^{-1}$ collected by the BESIII detector operating at the BEPCII storage ring. The $Y(4230)$ state is observed in the energy dependence of the $e^{+} e^{-} \to K_{S}^{0} K_{S}^{0} J/\psi$ cross section for the first time with a statistical significance of 26.0$\sigma$. In addition, an enhancement around $4.710$ GeV, called the $Y(4710)$, is seen with a statistical significance of 4.2$\sigma$. There is no clear structure around $4.484$ GeV. Using a fit with a coherent sum of three Breit-Wigner functions, we determine the mass and width of the $Y(4230)$ state to be $4226.9 \pm 6.6 \pm 21.9$ MeV/$c^{2}$ and $71.7 \pm 16.2 \pm 31.4$ MeV, respectively, and the mass and width of the $Y(4710)$ state to be $4704.0 \pm 52.3 \pm 69.5$ MeV/$c^{2}$ and $183.2 \pm 114.0 \pm 90.8$ MeV, respectively, where the first uncertainties are statistical and the second are systematic. In addition, the average Born cross section ratio of $e^{+} e^{-} \to K_{S}^{0} K_{S}^{0} J/\psi$ to $e^{+} e^{-} \to K^{+} K^{-} J/\psi$ is measured to be $0.388_{-0.028}^{+0.035}\pm0.016$, or $0.426_{-0.031}^{+0.038}\pm0.018$ if three-body phase space is considered.Comment: Update draft based the comments from PRD refere