职业健康安全管理体系认证与企业创新

本文以我国2011-2015年沪市、深市A股上市公司数据为样本，实证研究职业健康安全管理体系认证对企业创新能力的影响，并考察了上述影响效应在企业有无政治关联和认证覆盖人数占企业总人数比例高低时的差异。研究表明：企业通过职业健康安全管理体系认证能够有效促进创新投入和创新产出，进一步分析企业创新动机和认证实施效果发现，职业健康安全管理体系认证对创新效率的激励在无政治关联的企业和认证覆盖人数占总人数比例高的企业更为显著。

Diagnostic Accuracy of Transthoracic Echocardiography to Predict Fluid Responsiveness by Passive Leg Raising in the Critically Ill: A Meta-Analysis

Background: Hemodynamic instability is common in critical patients and not all patients respond to fluid challenge, so we need accurate and rapid hemodynamic techniques to help the clinicians to guide fluid treatment. Numerous hemodynamic techniques have been used to predict fluid responsiveness till now. Transthoracic echocardiography (TTE) appears to have the ability to predict fluid responsiveness, but there is no consensus on whether it can be used by passive leg raising (PLR). Methods: We performed a literature search using MEDLINE (source PubMed, from 1947), EMBASE (from 1974) and the Cochrane Database of Systematic Reviews for prospective studies with no restrictions. Pooled effect estimates were obtained by using random-effects meta-analysis. Results: 7 prospective studies involving 261 patients and 285 boluses were identified. The pooled sensitivity and specificity of TTE are 86% (79% - 91%) and 90% (83% - 94%), respectively. The summary receiver operating characteristic (sROC) curve shows an optimum joint sensitivity and specificity of 0.88, with area under the sROC curve (AUC) of 0.94. The result of diagnostic odds ratio (DOR) is 50.62 (95% confidence interval [CI]: 23.70 - 108.12). The results of positive likelihood ratio (+LR) and negative likelihood ratio (?LR) are 7.07 (95% CI: 4.39 - 11.38) and 0.19 (95% CI: 0.13 - 0.28), which indicated strong diagnostic evidence. Conclusions: TTE is a repeatable and reliable noninvasive tool to predict fluid responsiveness in the critically ill during PLR with good test performance. This meta-analysis brings evidence to employ well-trained clinician-echocardiographers to assess patients’ volume statue via TTE to benefit daily work in intensive care units (ICUs).

Meta-Analysis of Invasive versus Non-Invasive Techniques to Predict Fluid Responsiveness by Passive Leg Raising in the Critically Ill

Objective: To analyze the accuracy and specificity of recent studies to compare the ability of predicting fluid responsiveness with Passive Leg Raising (PLR) by using invasive or non-invasive techniques during passive leg raising. Data Sources: MEDLINE, EMBASE and the Cochrane Database of Systematic Reviews were systematically searched. Study Selection: Clinical trials that reported the sensitivity, specificity and area under the receiver operating characteristic curve (AUC) between the responder and non-responder induced by passive leg raising and Volume Expansion (VE) in critical ill patients were selected. 246 studies were screened, 14 studies were included for data extraction, which met our inclusion criteria. Data Extraction: Data were abstracted on study characteristics, patient population, type and amount of VE, time of VE, definition of responders, position, techniques used for measuring hemodynamic change, number and percentage of responders, the correlation coefficient, sensitivity, specificity, best threshold and area under the ROC curve (AUC). Meta-analytic techniques were used to summarize the data. Data Synthesis: A total of 524 critical ill patients from 14 studies were analyzed. Data are reported as point estimate (95% confidence intervals). The pooled sensitivity and specificity of invasive techniques were 80% (73% - 85%) and 89% (84% - 93%) respectively with the area under the sROC of 0.94. While, the pooled sensitivity and specificity of non-invasive techniques were 88% (84% - 92%) and 91% (86% - 94%) respectively with the area under the sROC of 0.95. The pooled DOR of invasive techniques was 32.2 (13.6 - 76.8), which was much lower than that of non-invasive techniques with the value of 64.3 (33.9 - 121.7). Conclusions: The hemodynamic indexes changes induced by PLR could reliably predict fluid responsiveness. Non-invasive hemodynamic techniques with their accuracy and safety can benefit the daily work in ICUs. Because the number of patients included in the present trials was small, further studies should be undertaken to confirm these findings.

One-step fabrication superhydrophobic sand filter for capillary-driven separation of water-in-oil emulsions

The efficient separation of water-in-oil emulsion is of significance in environment and energy filed,and it has become a world-wide challenge.Herein,we have presented a one-step,facile and low-cost approach to prepare superhydrophobic sands for efficient separation of water-in-oil emulsion.The as-prepared sand layers possessed a water contact angle higher than 151°,demonstrating their superior superhydrophobic property.Besides,the as-prepared sand layers could separate water-in-emulsions with separation efficiency up to 99.7%,which is superior to both traditional and superwettable filtration membranes.The effect of thickness of sand layer on separation performance was also investigated.The results showed that the filtration flux decreased with the increased of filtration thickness while the separation efficiency increased.The as-prepared sand layer proposed by this study is a processing candidate for separating water-in-oil emulsion in practical industry.Additionally,the as-prepared superhydrophobic sand fabrication method also provides an alternative for desert water storage.

Rapid qualitative and quantitative analysis of strong aroma base liquor based on SPME-MS combined with chemometrics

To objectively classify and evaluate the strong aroma base liquors(SABLs)of different grades,solid-phase microextraction-mass spectrometry(SPME-MS)combined with chemometrics were used.Results showed that SPME-MS combined with a back-propagation artificial neural network(BPANN)method yielded almost the same recognition performance compared to linear discriminant analysis(LDA)in distinguishing different grades of SABL,with 84%recognition rate for the test set.Partial least squares(PLS),successive projection algorithm partial least squares(SPA-PLS)model,and competitive adaptive reweighed samplingpartial least squares(CARS-PLS)were established for the prediction of the four esters in the SABL.CARS-PLS model showed a greater advantage in the quantitative analysis of ethyl acetate,ethyl butyrate,ethyl caproate,and ethyl lactate.These results corroborated the hypothesis that SPME-MS combined with chemometrics can effectively achieve an accurate determination of different grades of SABL and prediction performance of esters.

Quantifying the impact of mineralogical heterogeneity on reactive transport modeling of CO_(2)+O_(2) in-situ leaching of uranium

CO_(2)+O_(2) in-situ leaching(ISL)of sandstonetype uranium ore represents the third generation of solution mining in China.In this study,reactive transport modeling of the interaction between hydrodynamic and geochemical reactions is performed to enable better prediction and regulation of the CO_(2)+O_(2) in-situ leaching process of uranium.Geochemical reactions between mining solutions and rock,and the kinetic uranium dissolution controlled by O_(2)(aq)and bicarbonate(HCO_(3)-)are considered in the CO_(2)+O_(2) ISL reactive transport model of a typical sandstone-hosted uranium ore deposit in northern China.The reactive leaching of uranium is most sensitive to the spatial distribution of the mineralogical properties of the uranium deposit.Stochastic geostatistical models are used to represent the uncertainty on the spatial distribution of mineral grades.A Monte Carlo analysis was also performed to simulate the uranium production variability over an entire set of geostatistical realizations.The ISL stochastic simulation performed with the selected geostatistical realizations approximates the uranium production variability well.The simulation results of the ISL reactive transport model show that the extent of the uranium plume is highly dependent on mineralogical heterogeneity.The uncertainty analysis suggests the effect of uranium grade heterogeneity was found to be important to improve the accurate capture of the uncertainty.This study provides guidance for the accurate simulation and dynamic regulation of the CO_(2)+O_(2) leaching process of uranium at the scale of large mining areas.

The sequence-dependent morphology of self-assembly peptides after binding with organophosphorus nerve agent VX

VX is a highly toxic organophosphorus nerve agent that the Chemical Weapons Convention classifies as a Schedule 1. In our previous study, we developed a method for detecting organophosphorus compounds using peptide self-assembly. Nevertheless, the self-assembly mechanisms of peptides that bind organophosphorus and the roles of each peptide residue remain elusive, restricting the design and application of peptide materials. Here, we use a multi-scale computational combined with experimental approach to illustrate the self-assembly mechanism of peptide-bound VX and the roles played by residues in different peptide sequences. We calculated that the self-assembly of peptides was accelerated after adding VX, and the final size of assembled nanofibers was larger than the original one, aligning with experimental findings. The atomic scale details offered by our approach enabled us to clarify the connection between the peptide sequences and nanostructures formation, as well as the contribution of various residues in binding VX and assembly process. Our investigation revealed a tight correlation between the number of Tyrosine residues and morphology of the assembly. These results indicate a self-assembly mechanism of peptide and VX, which can be used to design functional peptides for binding and hydrolyzing other organophosphorus nerve agents for detoxification and biomedical applications.

COVID-19 risk prediction scores for mortality:A validation study from the National Registry of COVID-19 in China

To the Editor:Coronavirus disease 2019(COVID-19)has evolved into a global pandemic,with over 700 million confirmed cases worldwide and still mounting.^([1])The clinical impact of this pandemic is immense,given the wide spectrum of disease manifestation,ranging from mild respiratory symptoms to severe pulmonary infections.Identifying high-risk individuals,especially during their initial encounters in clinics and hospital emergency services,is crucial to provide timely effective treatment.Therefore,the timely risk stratification of COVID-19 patients in the emergency room can greatly benefit both infected individuals and healthcare professionals.^([2])This study aims to identify features of serious COVID-19 infection at presentation that may lead to mortality of the patients.

Bypassing PELO-mediated ATPase activation of the NLR is a common pathogenic cause of NLR-associated autoinflammatory diseases

Nucleotide-binding and oligomerization domain(NOD)-like receptors(NLRs)are evolutionarily conserved intracellular pattern recognition receptors(PRRs)that sense microbial and danger signals,trigger immediate host defenses,and prime the adaptive immune response for long-lasting protection[1].In humans,22 known NLRs exist,and mutations in NLR family genes are associated with a wide range of inflammatory and autoimmune conditions,including hereditary periodic fever syndromes,Crohn’s disease,Blau’s syndrome,infantile enterocolitis,multiple sclerosis,and asthma[2,3].

Phase-separated nucleocapsid protein of SARS-CoV-2 suppresses cGAS-DNA recognition by disrupting cGAS-G3BP1 complex

Currently,the incidence and fatality rate of SARS-CoV-2 remain continually high worldwide.COVID-19 patients infected with SARS-CoV-2 exhibited decreased type I interferon(IFN-I)signal,along with limited activation of antiviral immune responses as well as enhanced viral infectivity.Dramatic progresses have been made in revealing the multiple strategies employed by SARS-CoV-2 in impairing canonical RNA sensing pathways.However,it remains to be determined about the SARS-CoV-2 antagonism of cGAS-mediated activation of IFN responses during infection.In the current study,we figure out that SARS-CoV-2 infection leads to the accumulation of released mitochondria DNA(mtDNA),which in turn triggers cGAS to activate IFN-I signaling.As countermeasures,SARS-CoV-2 nucleocapsid(N)protein restricts the DNA recognition capacity of cGAS to impair cGAS-induced IFN-I signaling.Mechanically,N protein disrupts the assembly of cGAS with its co-factor G3BP1 by undergoing DNA-induced liquid-liquid phase separation(LLPS),subsequently impairs the double-strand DNA(dsDNA)detection ability of cGAS.Taken together,our findings unravel a novel antagonistic strategy by which SARS-CoV-2 reduces DNA-triggered IFN-I pathway through interfering with cGAS-DNA phase separation.

The nearest neutron star candidate in a binary revealed by optical time-domain surveys

The near-Earth(within~100 pc)supernova explosions in the past several million years can cause the global deposition of radioactive elements(e.g.,60Fe)on Earth.The remnants of such supernovae are too old to be easily identified.It is therefore of great interest to search for million-year-old near-Earth neutron stars or black holes,the products of supernovae.However,neutron stars and black holes are challenging to find even in our Solar neighbourhood if they are not radio pulsars or X-ray/γ-ray emitters.Here we report the discovery of one of the nearest(127.7±0.3 pc)neutron star candidates in a detached single-lined spectroscopic binary LAMOST J235456.73+335625.9(hereafter J2354).Utilizing the time-resolved ground-based spectroscopy and space photometry,we find that J2354 hosts an unseen compact object with M_(inv)being 1.4-1.6 M_(⊙).The follow-up Swift ultraviolet(UV)and X-ray observations suggest that the UV and X-ray emission is produced by the visible star rather than the compact object.Hence,J2354 probably harbours a neutron star rather than a hot ultramassive white dwarf.Two-hour exceptionally sensitive radio follow-up observations with Five-hundred-meter Aperture Spherical radio Telescope fail to reveal any pulsating radio signals at the 6σflux upper limit of 12.5μJy.Therefore,the neutron star candidate in J2354 can only be revealed via our time-resolved observations.Interestingly,the distance between J2354 and our Earth can be as close as~50 pc around 2.5 million years(Myrs)ago,as revealed by the Gaia kinematics.Our discovery demonstrates a promising way to unveil the hidden near-Earth neutron stars in binaries by exploring the optical time domain,thereby facilitating understanding of the metal-enrichment history in our Solar neighbourhood.

基于网络药理学和生物信息学探讨龙胆泻肝汤治疗葡萄膜炎的分子机制

目的:探讨龙胆泻肝汤治疗葡萄膜炎的药效学研究和分子机制分析。方法:实验研究。在体实验验证龙胆泻肝汤治疗葡萄膜炎的疗效,利用中药网络药理学数据和分析平台查询并筛选复方龙胆泻肝汤的入血有效成分,并进行网络拓扑分析其可能的治疗靶点。通过查询多种已知疾病靶点数据库,筛选葡萄膜炎的治疗靶点,并与有效成分治疗靶点构建出有效成分-疾病治疗靶点网络,并筛选出关键节点;拓扑分析关键节点参与的信号通路并进行富集分析,筛选出中药复方龙胆泻肝汤治疗葡萄膜炎的可能信号通路。结果:在体实验结果证实龙胆泻肝汤能够减轻大鼠结膜充血、虹膜粘连,减轻前房、睫状体和视网膜炎症细胞浸润,具有治疗葡萄膜炎的的作用;网络药理学分析显示龙胆泻肝汤治疗葡萄膜炎主要通过MAPK信号通路、促性腺激素信号通路和雌激素信号通路,减少炎症因子的产生和细胞浸润,调节机体免疫状况,调控葡萄膜炎的发生发展。结论:龙胆泻肝汤治疗葡萄膜炎可能主要是通过MAPK信号通路、促性腺激素信号通路和雌激素信号通路,调控炎症细胞和炎症因子、自身免疫等来实现。

Comparison of dilution effects of R134a and nitrogen on flammable hydrofluorocarbons

An experimental apparatus has been built to measure the flammability limits of combustible gases based on Chinesenational standard GB/T 12474-90. The flammability limits of four binary mixtures of R161/R134a,R152a/R134a, R161/N2 and R152a/N2 were measured with this apparatus at atmospheric pressure and ambienttemperature. The fuel inertization points (FIP) of these mixtures can be found from the envelopes. Comparisonswere made with the literature data; good agreement for most measurements was obtained. R134a was found tohave a better dilution effect than nitrogen in reducing the flammability of hydrofluorocarbons.

Nucleate Pool Boiling Heat Transfer of Pure Refrigerants and Binary Mixtures

Heat transfer coefficients in nucleate boiling on a smooth flat surface were measured for pure fluids of R-134a, propane, isobutane and their binary mixtures at different pressure from 0.1 to 0.6 MPa. Series of experiments with different heat flux and mixture concentrations were carried out. The influences of pressure and heat flux on the heat transfer coefficient for different pure fluids were studied. Isobutane and propane were used to make up binary mixtures. Compared to the pure components, binary mixtures show lower heat transfer coefficients. This reduction was more pronounced as the heat flux increasing. Several heat transfer correlations are obtained for different pure refrigerants and their binary mixtures.

Emergence of photoluminescence on bulk MoS2 by laser thinning and gold particle decoration

We demonstrate a facile and effective approach to significantly improve the photoluminescence of bulk MoS2 via laser thinning followed by gold particle decoration. Upon laser thinning of exfoliated bulk MoSz photoluminescence emerges from the laser-thinned region. After further treatment with an AuCl3 solution, gold particles self-assemble on the laser-thinned region and thick edges, further increasing the fluorescence of bulk MoS2 28 times and the Raman response 3 times. Such fluorescence enhancement can be attributed to both surface plasmon resonance and p-type doping induced by gold particles. The combination of laser thinning and AuCl3 treatment enables the functionalization of bulk MoS2 for optoelectronic applications. It can also provide a viable strategy for mask-free and area-selective p-type doping on single MoS2 flakes.

SAMD4 family members suppress human hepatitis B virus by directly binding to the Smaug recognition region of viral RNA

HBV infection initiates hepatitis B and promotes liver cirrhosis and hepatocellular carcinoma.IFN-α is commonly used in hepatitis B therapy,but how it inhibits HBV is not fully understood.We screened 285 human interferon-stimulated genes(ISGs)for anti-HBV activity using a cell-based assay,which revealed several anti-HBV ISGs.Among these ISGs,SAMD4A was the strongest suppressor of HBV replication.We found the binding site of SAMD4A in HBV RNA,which was a previously unidentified Smaug recognition region(SRE)sequence conserved in HBV variants.SAMD4A binds to the SRE site in viral RNA to trigger its degradation.The SAM domain in SAMD4A is critical for RNA binding and the C-terminal domain of SAMD4A is required for SAMD4A anti-HBV function.Human SAMD4B is a homolog of human SAMD4A but is not an ISG,and the murine genome encodes SAMD4.All these SAMD4 proteins suppressed HBV replication when overexpressed in vitro and in vivo.We also showed that knocking out the Samd4 gene in hepatocytes led to a higher level of HBV replication in mice and AAV-delivered SAMD4A expression reduced the virus titer in HBVproducing transgenic mice.In addition,a database analysis revealed a negative correlation between the levels of SAMD4A/B and HBV in patients.Our data suggest that SAMD4A is an important anti-HBV ISG for use in IFN therapy of hepatitis B and that the levels of SAMD4A/B expression are related to HBV sensitivity in humans.

p38α has an important role in antigen cross-presentation by dendritic cells

The role of the p38 signaling pathway in the innate and adaptive immune responses has been well documented,especially in inflammatory cytokine production by dendritic cells(DCs).However,whether the p38 signaling pathway affects the important antigen(Ag)presentation function of DCs remains largely unknown.In this study,we reported that the deletion of p38αresulted in an impaired cross-presentation ability of CD8^(+) conventional DCs(cDCs)and a reduction in the direct presentation ability of CD8−cDCs ex vivo.Further study revealed that p38αhad a crucial role in Ag processing by CD8^(+) cDCs but did not affect the Ag uptake or co-stimulation of T cells.Moreover,p38αdeficiency led to reduced cross-priming of T cells in vivo.The production of the IL-12p40 and IL-12p70 cytokines by p38α-deficient cDCs was also significantly reduced.Our study identified a new role for p38αin modulating the important antigen cross-presentation function of DCs.

Identification of serum metabolites enhancing inflammatory responses in COVID-19

Coronavirus disease 2019(COVID-19),caused by severe acute respiratory syndrome coronavirus 2(SARS-CoV-2),is characterized by a strong production of inflammatory cytokines such as TNF and IL-6,which underlie the severity of the disease.However,the molecular mechanisms responsible for such a strong immune response remains unclear.Here,utilizing targeted tandem mass spectrometry to analyze serum metabolome and lipidome in COVID-19 patients at different temporal stages,we identified that 611 metabolites(of 1,039)were significantly altered in COVID-19 patients.Among them,two metabolites,agmatine and putrescine,were prominently elevated in the serum of patients;and 2-quinolinecarboxylate was changed in a biphasic manner,elevated during early COVID-19 infection but levelled off.When tested in mouse embryonic fibroblasts(MEFs)and macrophages,these 3 metabolites were found to activate the NF-κB pathway that plays a pivotal role in governing cytokine production.Importantly,these metabolites were each able to cause strong increase of TNF and IL-6 levels when administered to wildtype mice,but not in the mice lacking NF-κB.Intriguingly,these metabolites have little effects on the activation of interferon regulatory factors(IRFs)for the production of type I interferons(IFNs)for antiviral defenses.These data suggest that circulating metabolites resulting from COVID-19 infection may act as effectors to elicit the peculiar systemic inflammatory responses,exhibiting severely strong proinflammatory cytokine production with limited induction of the interferons.Our study may provide a rationale for development of drugs to alleviate inflammation in COVID-19 patients.

牛樟芝免疫调节蛋白的过量表达及活性分析

【目的】用大肠杆菌高效表达牛樟芝免疫调节蛋白(Antrodia camphorata immunomodulatory protein,ACA)。【方法】借助DNAworks3.2.4设计引物合成大肠杆菌密码子偏好性的ACA基因,构建于pET-32a和pGEX-4t-2,转化大肠杆菌,测序后分别命名为pET-32a-ACA/BL21和pGEX-4t-2-ACA/BL21;探索密码子偏好性、载体、培养基种类和诱导条件对ACA表达的影响并使用响应面法优化蛋白表达。纯化重组ACA(recombinant ACA,rACA)并干预小鼠巨噬细胞RAW264.7,通过测定rACA对巨噬细胞增殖能力、吞噬能力、细胞形态及产NO、肿瘤坏死因子α(tumor necrosis factor-α,TNFα)、白介素lβ(interleukin-1β,IL-1β)等细胞因子能力的影响来评估rACA的活性。【结果】pET-32a-ACA/BL21更适合ACA表达;在优化的SOB(酵母粉8.92 g/L)中培养pET-32a-ACA/BL21,添加0.42 mmol/L IPTG 25℃诱导7 h时rACA以可溶性表达为主,产量达187.122μg/mL,是目前大肠杆菌表达真菌免疫调节蛋白的最高报道。纯化的rACA能显著促进小鼠巨噬细胞增殖、提高细胞的吞噬活性和改变细胞形态,显著诱导巨噬细胞分泌NO、TNF-α和IL-1β。【结论】rACA的高效可溶性表达及类似天然ACA的活性使它可以替代天然ACA作为制药行业的食品添加剂或者免疫调节剂,甚至可以用于药物研究。

CO_2 solubility in aqueous solutions of N-methyldiethanolamine+piperazine by electrolyte NRTL model

Accurate modeling of the solubility behavior of CO_2 in the aqueous alkanolamine solutions is important to design and optimization of equipment and process. In this work, the thermodynamics of CO_2 in aqueous solution of N-methyldiethanolamine(MDEA) and piperazine(PZ) is studied by the electrolyte non-random two liquids(NRTL) model. The chemical equilibrium constants are calculated from the free Gibbs energy of formation, and the Henry's constants of CO_2 in MDEA and PZ are regressed to revise the value in the pure water. New experimental data from literatures are added to the regression process. Therefore, this model should provide a comprehensive thermodynamic representation for the quaternary system with broader ranges and more accurate predictions than previous work. Model results are compared to the experimental vapor-liquid equilibrium(VLE), speciation and heat of absorption data, which show that the model can predict the experimental data with reasonable accuracy.