Fluorescence Properties and Chemical Composition of Fine Particles in the Background Atmosphere of North China

To understand the aerosol characteristics in a regional background environment,fine-particle(PM_(2.5),n=228)samples were collected over a one-year period at the Shangdianzi(SDZ)station,which is a Global Atmospheric Watch regional background station in North China.The chemical and optical characteristics of PM_(2.5)were analyzed,including organic carbon,elemental carbon,water-soluble organic carbon,water-soluble inorganic ions,and fluorescent components of watersoluble organic matter.The source factors of major aerosol components are apportioned,and the sources of the fluorescent chromophores are further analyzed.The major chemical components of PM_(2.5)at SDZ were NO_(3)^(-),organic matter,SO_(4)^(2-),and NH_(4)^(+).Annually,water-soluble organic carbon contributed 48%±15%to the total organic carbon.Secondary formation(52%)and fossil fuel combustion(63%)are the largest sources of water-soluble organic matter and water-insoluble organic matter,respectively.In addition,three humic-like and one protein-like matter were identified via parallel factor analysis for excitation–emission matrices.The fluorescence intensities of the components were highest in winter and lowest in summer,indicating the main impact of burning sources.This study contributes to understanding the chemical and optical characteristics of ambient aerosols in the background atmosphere.

Seabuckthorn juice alleviates allergic symptoms in shrimp-induced food allergy mice

Tropomyosin(TM)in shrimp is one of the predominant causes of food allergy around the world.In the present study,the effect of seabuckthorn juice against TM-induced shrimp allergy was investigated in BALB/c mice.Allergic symptoms,spleen index,intestinal section and diarrhea were measured in shrimp allergy mice.As the results,seabuckthorn juice suppressed the lesions in jejunum tissue,diarrhea and allergic symptoms in shrimp allergy mice.Seabuckthorn juice also reduced serum concentrations of tumor necrosis factor-a(TNF-α)as well as immunoglobulin E(IgE)and stimulated the secretion of interleukin-10(IL-10)in mice with shrimp allergy.Taken together,our findings suggest that increased IL-10 by seabuckthorn juice inhibits Th2 cytokine production to suppress shrimp allergic symptoms.Furthermore,seabuckthorn juice also regulates shrimp allergy by reducing jejunum lesions,inhibiting levels of TNF-αand IgE.

基于TorchMD的粗粒化分子动力模拟研究

粗粒化模型通过简化原子性质以及原子间的相互作用实现生物大分子长时间尺度的分子动力学模拟.深度学习通过模拟人类的认知过程实现海量数据的准确分类和回归过程.本论文将这两种技术进行融合,利用基于深度学习的粗粒化分子动力学模拟技术研究分子在不同状态之间的变化过程,并提出基于TorchMD的分子动力学模拟的分析框架.在本工作中,MFDP聚类算法被用于在三维的CV变量空间中进行聚类,并确定分子的若干主要状态,在完成聚类的同时,给出各类中的代表分子构象,并给出类之间的分子构象.这为后续利用String算法分析分子在不同状态间的转换路径打下基础.通过String算法,迭代搜索得到分子在不同状态之间的变化路径以及对应的势能变化曲线.通过与已有文献的结果进行对比,验证了基于TorchMD的粗粒化分子动力学模拟的理论框架可以在相对较短的时间尺度里研究分子的变化过程.

Analysis of variabilities of serum proteomic spectra in patients with gastric cancer before and after operation

瞄准：为了在手术前后与胃的癌症在病人学习浆液 proteomic 系列的可变性以便检测特定的蛋白质标记，那能被用于胃的癌症的快诊断。方法：从有在操作前后的胃的癌症的病人的 46 件浆液样品的 Proteomic 系列并且 40 被 IMAC-Cu 蛋白质薄片和飞行团分光术的提高表面的激光 desorption/ 电离时间从正常个人产生。结果：十四差别在浆液表示了蛋白质被外科手术前的病人和正常个人的 proteomic 系列的分析屏蔽。我们获得了 4 蛋白质(热吃惊蛋白质 27，调整葡萄糖的蛋白质，禁止在，蛋白质二硫化物异构酶 A3 ) 完成对班有能力的标记模式耐心队、正常队。这些标记模式分别地产出 95.7% 敏感和 92.5% 特性。在外科手术前的病人的浆液过去表示的蛋白质显然是下面调整的。结论：胃的癌症的特定的蛋白质标记能被用于胃的癌症的快诊断和预后的判断。SELDI-TOF-MS 是为在浆液的新蛋白质标记的察觉和鉴定的一个有用工具。

分子构象聚类中的K-means密度峰值搜索算法

分子构象的聚类是搜索分子动力学模拟轨迹中代表构象的主要方法。它是分析复杂构象改变或分子间相互作用机制的关键步骤.作为一种基于密度的聚类算法,密度峰值搜索算法因其聚类的准确度而被应用于分子聚类过程中.但随着模拟时长的增长,密度峰值搜索算法较低的计算效率限制了其应用的可能.本文提出K-means密度峰值搜索算法的聚类算法,它是密度峰值搜索算法在计算效率方面的一个扩展版本,用于解决密度峰值搜索算法中巨大的资源消耗问题.在K-means密度峰值搜索算法中,首先,通过高效的聚类算法(例如K-means)进行初始聚类,得到的聚类中心被定义为具有权重的典型点.然后,对加权的典型点通过密度峰值搜索算法实现二次聚类,并细化点为核心点、边界点、加细光晕点.在与密度峰值搜索算法具有相似的精度的同时,计算复杂度由O(n^(2))降至O(n).通过二面角,二级结构,关联图描述的分子构象,将KFDP用于多个模拟轨迹的聚类过程中.并通过与K-means聚类算法,DBSCAN聚类算法的比较结果,验证了K-means密度峰值搜索算法的优势.

基于深度张量神经网络预测有机分子的相互作用能

分子的相互作用在分子动力学模拟过程中起着关键的作用.受限于计算资源,大分子的长时间尺度的相互作用能无法通过量化计算实现.本文采用一种深度学习框架-深度张量神经网络来预测三个有机分子相关体系中量化精度的相互作用能.其中,分子的几何结构和原子类型作为网络的输入用于预测相互作用能.通过分层生成的数据集合实现了网络中隐层参数的优化和训练.相互作用能的预测结果显示,深度张量神经网络可以在较短的时间内,在1kcal/mol的平均绝对误差的范围内准确预测分子间的相互作用能.这一过程提高了计算效率,并为计算相互作用能提供了可靠的计算框架.

Replication of hepatitis B virus in primary duck hepatocytes transfected with linear viral DNA

AIM: To explore the expression and replication of hepatitis B virus (HBV) DNA in primary duck hepatocytes (PDHs).METHODS: Complete HBV genome was transfected into PDHs by electroporation (transfected group, 1.19×1012copies of linear HBV DNA/1×107 PDHs). After 1-5 d of transfection, HBsAg and HBeAg in the supernatant and lysate of PDHs were measured with the IMX System.Meanwhile, replicative intermediates of HBV DNA were analyzed by Southern blotting and Dot blotting. PDHs electroporated were used as control group.RESULTS: HBsAg in the hepatocyte lysates of transfected group was 15.24 (1 d), 14.55 (3 d) and 5.13 (5 d; P/N values, positive≥2.1) respectively. HBeAg was negative (＜2.1). Both HBsAg and HBeAg were negative in the supernatant of transfected group. Dot blotting revealed that HBV DNA was strongly positive in the transfected group and negative in the control group. Southern blot analysis of intracellular total DNA indicated that there were relaxed circular (rc DNA), covalently closed circular (ccc DNA), and single-stranded (ss DNA) HBV DNA replicative intermediates in the transfected group, there was no integrated HBV DNA in the cellular genome. These parameters were negative in control group.CONCLUSION: Expression and replication of HBV genes can occur in hepatocytes from non-mammalian species.HBV replication has no critical species-specificity, and yet hepatic-specific regulating factors in hepatocytes may be essential for viral replication.

The natural history of chronic hepatitis B:a retrospective study

OBJECTIVE: To clarify the natural history, of chronic hepatitis B so as to evaluate its long-term therapeutic outcome of the patients and the efficacy of antiviral drugs. METHODS: A cohort of 183 biopsy-proven chronic hepatitis B patients (mean age of 31.75±8.03 years, male/female ratio: 152:31) and 247 controls were followed up retrospectively for 11.81±4.08 years. This study was focused on long-term clinical outcome including the rates of liver cirrhosis, hepatocellular carcinoma and death, apart from the long-term effect of antiviral drugs and prognostic factors. RESULTS: In the 183 chronic hepatitis B patients, 22 (12.02%) developed liver cirrhosis, 12 (6.56%) developed hepatocellular carcinoma, and 20 (10.93%) died. The 5-, 10- and 15-year survival rates were 97. 27%, 91.62%, and 84.47%, respectively. The 5-, 10- and 15-year incidence rates of HCC were O, 3.19%, and 11.56%, respectively. In the 247 controls, 6 (2.43%) died; none of them developed cirrhosis or HCC. The rates of death, liver cirrhosis, and HCC in the hepatitis B patients were markedly different (P<0. 005) compared with the controls. The overall mortality of hepatitis B patients was 4.5-fold higher than the general population. Cox multiple regression analysis showed that old age, severe histological injury, and positive HBeAg were closely related to liver cirrhosis; old age, severe histological injury, and male were major factors leading to death. The independent variable of predicted HCC was not found. CONCLUSION: The long-term outcome of hepatitis B patients is poor and the efficacy of antiviral drugs needs further study.

Microstructure formation mechanism of catalyst layer and its effect on fuel cell performance:Effect of dispersion medium composition

The design of the catalyst layer(CL)offers a feasible way to realize the commercialization of proton exchange membrane fuel cells(PEMFCs).An in-depth understanding of catalyst inks is critical to achieving the optimal CL structure and cell performance.In this work,the effects of the solvent evaporation process during ink drying on the formation of the CL microstructure are particularly considered to reveal the structure-property correlations among the catalyst ink,drying process,CL microstructure and fuel cell performance.An increase in the alcohol content of the catalyst ink increases the amount of free ionomers while allowing the ionomer backbone to be more stretched in the dispersion medium.The higher alcohol content contributes to rapid solvent evaporation and thus inhibits the formation of coffee rings;as a result,a more developed ionomer network with a denser pore structure is obtained.Therefore,the alcohol-rich electrode exhibits better proton conduction capability,but higher oxygen transport resistance.For complex fuel cell operating conditions,a catalyst ink formulation with 50 wt%alcohol content is preferred due to its proper ionomer and pore size distribution,providing satisfactory fuel cell performance.

SI of Interaction energy prediction of organic molecules using Deep Tensor Neural Network

The support informations of DTNN architecture and prediction results of six testing cases in K-fold are listed here.

Mahuang Xixin Fuzi decoction protects against ovalbumin-induced allergic rhinitis by inhibiting type 2 innate lymphoid cells in mice

Objective:As a traditional herbal formula,Mahuang Xixin Fuzi decoction(MXFD)has been used to treat allergic rhinitis(AR).It regulates the transcription factor GATA3 in T cells,blocks Th2 skewing and rebalances the Th1/Th2 immunity.Type 2 innate lymphoid cells(ILC2s)are closely associated with GATA3.However,it remains unknown whether ILC2s could be one mechanism through which MXFD acts.We sought to elucidate the efficacy and mechanism of action of this decoction in AR treatment.Methods:Forty C57BL/6J female mice were equally divided into control,model,loratadine-and MXFDtreated groups in random.AR was induced by ovalbumin(OVA),and then treatment with loratadine or MXFD was administered.AR scores were evaluated and compared before and after treatment.Pathological changes in the nasal mucosa and lung were observed using hematoxylin-eosin staining of tissue samples.Activation of ILC2 in nasal mucosa was assessed by immunofluorescence and quantitative polymerase chain reaction analysis.ILC2 cell count in lungs was measured by flow cytometry and levels of interleukin-(IL)4,IL-5 and IL-13 in serum were detected by ELISA.Results:The decoction alleviated the symptoms of AR in mice,improved vascular congestion and expansion,glandular hyperplasia and inflammatory cell infiltration in mouse nasal mucosa and slowly improved the interstitial pneumonia and lesions.Meanwhile,MXFD reduced the number and percentage of ILC2s in the nasal mucosa and lungs,downregulated the expression of GATA3 mRNA and RORa mRNA,and reduced the related inflammatory cytokine levels,including IL-4,IL-5 and IL-13.Conclusion:These data suggest that inhibition of ILC2s by MXFD may be an important means by which to treat AR.

Using network pharmacology and molecular docking to explore the mechanism of action of Huajiao against colon cancer

Background:The mechanism of Huajiao(Zanthoxylum bungeanum Maxim.),as a commonly used herbal medicine,has been suggested as a potential agent for colon cancer.This study aims to use network pharmacology and molecular docking to identify the bioactive constituents of Huajiao and the underlying mechanisms of cancer prevention.Methods:Putative components of Huajiao and their relevant targets were identified from the Traditional Chinese Medicine Systematic Pharmacology and Swiss target prediction database.Subsequently,targets interacting with colon cancer were collected using the databases of GeneCards,OMIM and Drugbank.Kyoto Encyclopedia of Genes and Genomes pathway and Gene Ontology enrichment analyses were performed to explore the therapeutic signalling pathways related to Huajiao for carcinoma.P rotein-protein interaction and compound-target networks were constructed using Cytoscape 3.8.2.Finally,Discovery studio software was accustomed to identifying key genes and active components of Huajiao.Results:Seventeen potentially active compounds,197 interacting targets and 1,636 disease-related targets were collected,of which 111 cross-targets were obtained.A complete of twenty-two key targets were identified by PPI network analysis,including AKT1,TP53,TNF,JUN,IL6 and HSP90AA1.These key targets are significantly involved in biological processes and pathways,such as those involved in phosphatidylinositol 3-kinase signalling,promoting maturation,structural maintenance and proper regulation of specific target proteins,and regulating tumor cell growth arrest and apoptosis.KEGG enrichment showed that three signalling pathways were closely related to the cancer prevention,endocrine resistance and viral hepatitis pathways in carcinoma.AKT1,TP53,TNF,JUN,IL6 and HSP90AA1 were identified as the most vital genes and were validated by molecular docking simulations.Conclusion:The present study demonstrates that Huajiao produces preventive effects against colon cancer by modulating multiple components of multiple targets and pathways.Moreover,these data provide new insights into developing Huajiao compounds as new anti-colon cancer drugs.

燃烧源氨排放对灰霾期间北京大气铵的重要贡献

Aerosol ammonium(NH_(4)^(+)),mainly produced from the reactions of ammonia(NH_(3))with acids in the atmosphere,has significant impacts on air pollution,radiative forcing,and human health.Understanding the source and formation mechanism of NH_(4)^(+)can provide scientific insights into air quality improvements.However,the sources of NH_(3)in urban areas are not well understood,and few studies focus on NH_(3)/NH_(4)^(+)at different heights within the atmospheric boundary layer,which hinders a comprehensive understanding of aerosol NH_(4)^(+).In this study,we perform both field observation and modeling studies(the Community Multiscale Air Quality,CMAQ)to investigate regional NH_(3)emission sources and vertically resolved NH_(4)^(+)formation mechanisms during the winter in Beijing.Both stable nitrogen isotope analyses and CMAQ model suggest that combustion-related NH_(3)emissions,including fossil fuel sources,NH_(3)slip,and biomass burning,are important sources of aerosol NH_(4)^(+)with more than 60%contribution occurring on heavily polluted days.In contrast,volatilization-related NH_(3)sources(livestock breeding,N-fertilizer application,and human waste)are dominant on clean days.Combustion-related NH_(3)is mostly local from Beijing,and biomass burning is likely an important NH_(3)source(~15%–20%)that was previously overlooked.More effective control strategies such as the two-product(e.g.,reducing both SO_(2)and NH_(3))control policy should be considered to improve air quality.

Weakened humoral and cellular immune response to the inactivated COVID-19 vaccines in Chinese individuals with obesity/overweight

Inactivated COVID-19 vaccines have been widely used to vaccinate the Chinese population.However,limited literature exists to explore the effect of obesity on the humoral and cellular immune response to these vaccines.In this study,132 high BMI(Body mass index)(obesity and overweight,BMI≥24 kg/m^(2))and 82 normal BMI(BMI<24 kg/m^(2))participants were enrolled.Adverse events(AEs),Spike receptor-binding domain IgG antibody(anti-RBD-IgG),neutralizing antibodies(NAbs),and specific B-cell and T-cell responses were evaluated 21–105 days after full-course inactivated COVID-19 vaccination.The overall incidence of AEs was similar in individuals with and without obesity/overweight.No serious vaccine-related AEs occurred.Individuals with obesity/overweight had a reduced seropositivity rate of NAbs compared to those with normal BMI.Anti-RBD-IgG and NAbs titers in the high BMI group were significantly lower than those in the normal BMI group.The frequencies of RBD-specific memory B cells(MBCs)and the numbers of spike-specific TNF-α+spot-forming cells(SFCs)in individuals with obesity/overweight were reduced compared with those noted in individuals without obesity/overweight.A similar trend of weakened humoral responses was also observed in individuals with central obesity.Our study results suggested that inactivated COVID-19 vaccines were safe and well tolerated but induced poor humoral and cellular immune responses in Chinese individuals with obesity/overweight.

Weakened humoral immune responses of inactivated SARS-CoV-2 vaccines in patients with solid tumors

Dear Editor Coronavirus disease 19(COVID-19),caused by severe acute respiratory syndrome coronavirus 2(SARS-CoV-2),remains a pandemic.Cancer patients have a higher risk of poor outcomes for SARS-CoV-2 infection than the general population[1].Vaccines were shown to effectively prevent SARS-CoV-2 infection,severe disease progression,and mortality.Inactivated SARS-CoV-2 vaccines(BBIBPCorV and CoronaVac)have been approved and widely used in China,with the former shown to be more effective than the latter[2].Hence,there is an urgent need to investigate the safety and humoral immune responses of inactivated vaccines in cancer patients.

TDF Promotes Glycolysis and Mitochondrial Dysfunction to Accelerate Lactate Accumulation by Downregulating PGC1α in Mice

Tenofovir disoproxil fumarate(TDF),is a product of tenofovir and has been recommended for long-term use by guidelines1 because of its favorable efficacy in the treatment of human immunodeficiency virus(HIV)and hepatitis B virus(HBV)infection.Hence,a better understanding of the safety profiles of long-term TDF use is extremely important.Lactic acidosis,as a rare but fatal adverse event of TDF,were reported both in HIV-infected patients,2-4 and in CHB patients.5-7 Hyperlactatemia occurred in 15.6%HIV-infected patients using TDF in a Cameroon cohort study8 and was 3%in another South Africa cohort study.9 Therefore,TDF increases the risk of abnormal serum lactate,but the mechanism is unclear.

HBsAg Loss with Peg-interferon Alfa-2a in Hepatitis B Patients with Partial Response to Nucleos(t)ide Analog:New Switch Study

Background and Aims:Hepatitis B surface antigen(HBsAg)loss is seldom achieved with nucleos(t)ide analog(NA)therapy in chronic hepatitis B patients but may be enhanced by switching to finite pegylated-interferon(Peg-IFN)alfa-2a.We assessed HBsAg loss with 48-and 96-week Peg-IFN alfa-2a in chronic hepatitis B patients with partial response to a previous NA.Methods:Hepatitis B e antigen(HBeAg)-positive patients who achieved HBeAg loss and hepatitis B virus DNA<200 IU/mL with previous adefovir,lamivudine or entecavir treatment were randomized 1:1 to receive Peg-IFN alfa-2a for 48(n=153)or 96 weeks(n=150).The primary endpoint of this study was HBsAg loss at end of treatment.The ClinicalTrials.gov identifier is NCT01464281.Results:At the end of 48 and 96 weeks'treatment,14.4%(22/153)and 20.7%(31/150)of patients,respectively,who switched from NA to Peg-IFN alfa-2a cleared HBsAg.Rates were similar irrespective of prior NA or baseline HBeAg seroconversion.Among those who cleared HBsAg by the end of 48 and 96 weeks'treatment,77.8%(14/18)and 71.4%(20/28),respectively,sustained HBsAg loss for a further 48 weeks.Baseline HBsAg<1500 IU/mL and week 24 HBsAg<200 IU/mL were associated with the highest rates of HBsAg loss at the end of both 48-and 96-week treatment(51.4%and 58.7%,respectively).Importantly,extending treatment from 48 to 96 weeks enabled 48.3%(14/29)more patients to achieve HBsAg loss.Conclusions:Patients on long-term NA who are unlikely to meet therapeutic goals can achieve high rates of HBsAg loss by switching to Peg-IFN alfa-2a.HBsAg loss rates may be improved for some patients by extending treatment from 48 to 96 weeks,although the differences in our study cohort were not statistically significant.Baseline and on-treatment HBsAg may predict HBsAg loss with Peg-IFN alfa-2a.

Chronic Hepatitis B Infection with Low Level Viremia Correlates with the Progression of the Liver Disease

Background and Aims:Currently,insufficient clinical data are available to address whether low-level viremia(LLV)observed during antiviral treatment will adversely affect the clinical outcome or whether treatment strategies should be altered if LLV occurs.This study compared the clinical out-comes of patients with a maintained virological response(MVR)and patients who experienced LLV and their treatment strategies.Methods:A retrospective cohort of 674 patients with chronic hepatitis B virus(HBV)infection who received antiviral treatment for more than 12 months was analyzed for the development of end-stage liver disease and treatment strategies during the follow-up period.End-stage liver disease included decompensated liver cirrhosis and hepatocellular carcinoma(HCC).Results:During a median 42-month follow-up,end-stage liver disease developed more frequently in patients who experienced LLV than in those who experienced MVR(7.73%and 15.85%vs.0.77%and 5.52%at 5 and 10 years,respectively;p=0.000).The trend was consistent after propensity score matching.In the high-risk group of four HCC risk models,LLV patients had a higher risk of HCC development(p<0.05).By Cox proportional hazard model analysis,LLV was an independent risk factor for end-stage liver disease and HCC(hazard ratio[HR]=6.280,confidence interval[CI]=2.081-18.951,p=0.001;HR=5.108,CI=1.392-18.737,respectively;p=0.014).Patients achieved a lower rate of end-stage liver disease by adjusting treatment compared to continuing the original treatment once LLV occurred(p<0.05).Conclusions:LLV is an independent risk factor for end-stage liver disease and HCC,and treatment adjustments can be considered.

Liver-infiltrating CD11b−CD27− NK subsets account for NK-cell dysfunction in patients with hepatocellular carcinoma and are associated with tumor progression

Natural killer(NK)cells have a vital role in killing hepatocellular carcinoma(HCC)cells;however,the mechanism underlying tumor-infiltrating NK(TINK)-cell dysfunction remains poorly understood.Using flow cytometry staining,we precisely characterized the frequency,phenotype and function of NK subsets distinguished by CD27 and CD11b in 30 patients with HCC in comparison to 30 healthy controls.Interestingly,we found a substantial proportion of liver-infiltrating CD11b?CD27?(DN)NK subsets in tumor tissue from HCC patients.Remarkably,these relatively expanded DN NK subsets exhibited an inactive and immature phenotype.By detecting the expression of CD107a and interferon-gamma(IFN-γ)on NK subsets and NK cells,we demonstrated that DN NK subsets exhibited a poor cytotoxic capacity and deficient potential to produce IFN-γin comparison to the other three subsets,which contributed to the dysfunction of TINK cells in HCC patients.In addition,we found that the presence of DN NK cells was closely associated with the clinical outcomes of HCC patients,as the frequency of DN NK cells among TINK cells was positively correlated with tumor stage and size.A large percentage of DN NK cells among TINK cells was an independent prognostic factor for lower survival in the 60-month follow-up period.In conclusion,a substantial proportion of CD11b?CD27?NK subsets among TINK cells accounts for NK-cell dysfunction in patients with HCC and is associated with tumor progression.Our study may provide a novel therapeutic target for the treatment of patients with HCC.