A new radical way to N,N-dimethylaniline hydroperoxide (DMAHP) and its application in organic synthesis

N,N-Dimethylaniline hydroperoxide was obtained when treating N,N-dimethylaniline with NHPI/Co（OAc）2/O2 via a radical reaction mechanism. This intermediate has potential application in the synthesis of some important chemical scaffolds.

Gunn器件中畴的静止-渡越-静止模式的实验观察和计算机模拟

本文讨论在GaAs n^+-n-n^+夹层结构的Cunn器件中畴的静止-渡越-静止模式,进行了实验观察和计算机模拟,指出在超过阈值的偏置电压下,当畴的耗尽层进入阳极附近的高掺杂区后,会逐渐停止下来形成准静态畴,这时畴外电场达到最大值.如果这时阴极凹口仍不能形成新畴,则准静态畴将进一步调整成为真正的静止畴,而畴外电场也将由最大值下降到一个与偏压无关的固定值.经过理论分析,得到了静止畴所固有的与外加偏压无关的畴外电场与有源区掺杂浓度的关系式,并和计算机模拟的结果相比较,得到很好的符合.如果偏压的增加使准静态畴所对应的畴外电场最大值已经足够使阴极凹口形成新的畴,则静止畴将转变为渡越畴.如果偏压继续增加,使积累层尾部覆盖了阴极凹口,则畴会再次静止下来,直到偏压增加到畴发生雪崩为止.计算和实验表明,后一个静止区的电压变化范围要比前一个大得多.本文还讨论了两个转变电压和温度的关系及扩散系数对静止畴的影响.

Kinetic Spectrophotometric Determination of Trace Iron (III) with p-Amino-N,N-Dimethylaniline Dihydrochloride and Hydrogen Peroxide

A new, simple and highly sensitive kinetic method for the determination oftrace iron (III) has been developed based on the catalytic effect of iron (III) on colorreaction of p-amino-N, N-dimethylaniline dihydrochloride (p-DMA) oxidated by hydrogenperoxide. The reaction is followed spectrophotometrically by measuring the absorbanceat 510 nm. The detection limit is 4.47×10-11 g/ml, and the calibration curve is linear inthe range of 0-0.10μg Fe(III) /25 ml with a relative standard deviation of ±3.25%. Themethod has been applied to the determination of iron in tap-water, chemical reagents andhuman hair.

Optical properties for N,N’-bis (lnaphyhly)N,N’-diphenyl-1,1’-biphenyl-4,4’-diamine and tris (8-hydroxyquinolinato) aluminum in organic light emitting devices

The optical properties of N,N’-bis (Inaphthyl)N,N’-diphenyl-1,1’-biphenyl-4,4’-diamine (NPB) and tris (8-hydroxyquinolinato) aluminum (Alq3) organic materials used as hole transport and electron transport layers in organic light-emitting devices (OLED) have been investigated. The NPB and Alq3 layers were prepared using thermal evaporation method. The results show that the energy band gap of Alq3 is thickness independence while the energy band gap of NPB decreases with the increasing of sample thickness. For the case of photoluminescence the Alq3 with thickness of 84 nm shows the highest relative intensity peak at 510 nm.

Model of Universe as Described by Dynamic Universe Model

In this paper we will see the model of Universe according to Dynamic Universe Model of Cosmology by visualizing various processes that are happening in the Universe as per experimental evidences. For simplifying the matter here, we will see in part 1: about the Galaxy life cycle, where the birth and death of Galaxies discussed. Probably Universe gives guidance for the movement of Galaxies. We call this Part 1: Thinking and Reproducing Universe or Mindless Universe? (Galaxy life cycle). We see every day Sun, Stars, Galaxies etc., dissipating enormous energy in the form of radiation by the way of fusion of Hydrogen to helium. So after sometime all the Hydrogen is spent and Universe will die, is it not? … Dynamic Universe Model says that the energy in the form of electromagnetic radiation passing grazingly near any gravitating mass changes in frequency and finally will convert into neutrinos (mass). Hence Dynamic Universe Model proposes another process where energy will be converted back into matter and the cycle energy to mass to energy continues, sustaining the Universe to maintain this present status for ever in this form something like a Steady state model without any expansion. This we will see in Part 2: Energy - Mass - Energy Cycle. After converting energy into mass “how various elements are formed and where they are formed?” will be next logical question. Dynamic Universe Model says that these various particles change into higher massive particles or may get bombarded into stars or planets and various elements are formed. Here we bifurcate the formation of elements into 6 processes. They are for Elementary particles and elements generated in frequency changing process, By Cosmic rays, By Small stars, By Large Stars, By Super Novae and Manmade elements By Neutron Stars. This we will discuss in Part 3: Nucleosynthesis.

Important role of lymphovascular and perineural invasion in prognosis of colorectal cancer patients with N1c disease

BACKGROUND Lymphovascular invasion(LVI)and perineural invasion(PNI)are associated with decreased survival in colorectal cancer(CRC),but its significance in N1c stage remains to be clearly defined.AIM We retrospectively identified 107 consecutive patients who had CRC with N1c disease radically resected at our hospital.Tumors were reviewed for LVI and PNI by one pathologist blinded to the patients’outcomes.Disease-free survival(DFS),overall survival(OS)and cancer-specific survival(CSS)were determined using the Kaplan-Meier method,with LVI and PNI prognosis differences determined by multivariate analysis using the Cox multiple hazards model.Results were compared using log-rank test.The receiver operating characteristic(ROC)curve was used to evaluate the prognostic predictive ability.RESULTS The median follow-up time was 63.17(45.33-81.37)months for DFS,with 33.64%(36/107)of patients experiencing recurrence;21.5%of tumors were found to be LVI positive and 44.9%PNI positive.The 5-year DFS rate was greater for patients with LVI-negative tumors compared with LVI-positive tumors(74.0%vs 35.6%),and PNI was similar(82.5%vs 45.1%).On multivariate analysis,LVI[hazard ratio(HR)=3.368,95%confidence interval(CI):1.628-6.966,P=0.001]and PNI(HR=3.055,95%CI:1.478-6.313,P=0.002)were independent prognostic factors for DFS.All patients could be divided into three groups of patients with different prognosis according to LVI and PNI.The 5-year ROC curve for LVI,PNI and their combination prediction of DFS was 0.646,0.709 and 0.759,respectively.Similar results were seen for OS and CSS.CONCLUSION LVI and PNI could serve as independent prognostic factors of outcomes in N1c CRC patients.Patients with LVI or PNI should be given more attention during treatment.

N6-methyladenosine methyltransferase Wilms tumor 1-associated protein impedes diabetic wound healing through epigenetically activating DNA methyltransferase 1

BACKGROUND Diabetic wound injury is a significant and common complication in individuals with diabetes.N6-methyladenosine(m6A)-related epigenetic regulation is widely involved in the pathogenesis of diabetes complications.However,the function of m6A methyltransferase Wilms tumor 1-associated protein(WTAP)in diabetic wound healing remains elusive.AIM To investigate the potential epigenetic regulatory mechanism of WTAP during diabetic wound healing.METHODS Human umbilical vein endothelial cells(HUVECs)were induced with high glucose(HG)to establish in vitro cell model.Male BALB/c mice were intraperitoneally injected with streptozotocin to mimic diabetes,and full-thickness excision was made to mimic diabetic wound healing.HG-induced HUVECs and mouse models were treated with WTAP siRNAs and DNA methyltransferase 1(DNMT1)overexpression vectors.Cell viability and migration ability were detected by cell counting kit-8 and Transwell assays.In vitro angiogenesis was measured using a tube formation experiment.The images of wounds were captured,and re-epithelialization and collagen deposition of skin tissues were analyzed using hematoxylin and eosin staining and Masson’s trichrome staining.RESULTS The expression of several m6A methyltransferases,including METTL3,METTL14,METTL16,KIAA1429,WTAP,and RBM15,were measured.WTAP exhibited the most significant elevation in HG-induced HUVECs compared with the normal control.WTAP depletion notably restored cell viability and enhanced tube formation ability and migration of HUVECs suppressed by HG.The unclosed wound area of mice was smaller in WTAP knockdowntreated mice than in control mice at nine days post-wounding,along with enhanced re-epithelialization rate and collagen deposition.The m6A levels on DNMT1 mRNA in HUVECs were repressed by WTAP knockdown in HUVECs.The mRNA levels and expression of DNMT1 were inhibited by WTAP depletion in HUVECs.Overexpression of DNMT1 in HUVECs notably reversed the effects of WTAP depletion on HG-induced HUVECs.CONCLUSION WTAP expression is elevated in HG-induced HUVECs and epigenetically regulates the m6A modification of DNMT1 to impair diabetic wound healing.

Pattern of disharmony between the heart and kidney: Theoretical basis, identification and treatment

'Harmony between the heart and kidney' refers to the physiological relationship between these two zang organs in Chinese medicine,while 'disharmony between the heart and kidney' (also called disharmony between fire and water) refers to the pathological state.The pattern of disharmony between the heart and kidney is widely observed in patients with insomnia,anxiety disorder and menopausal syndrome,etc..In order to gain a full and systematical understanding of this pattern,from the perspective of ancient Chinese philosophy and zang-fu theory in Chinese medicine,we systematically reviewed and discussed the functions and physiological characteristics of the heart and kidney,the origin and development of theories relating to heart-kidney relationship,the pathogenesis and identification of the pattern,as well as the commonly used classical formulas for its treatment,including Coptis and DonkeyHide Gelatin Decoction (Huánglián (E)jiāo Tāng) and Grand Communication Pill (Jiāotài Wán).Two examples of clinical modifications of these formulas in the treatment of insomnia and menopausal syndrome are provided in this article.It should be noted that in clinical practice,these formulas should be used flexibly,and modified in accordance to the condition of the patient.

SMAD specific E3 ubiquitin protein ligase 1 accelerates diabetic macular edema progression by WNT inhibitory factor 1

BACKGROUND Diabetic macular edema(DME)is the most common cause of vision loss in people with diabetes.Tight junction disruption of the retinal pigment epithelium(RPE)cells has been reported to induce DME development.SMAD-specific E3 ubiquitin protein ligase(SMURF)1 was associated with the tight junctions of cells.However,the mechanism of SMURF1 in the DME process remains unclear.AIM To investigate the role of SMURF1 in RPE cell tight junction during DME.METHODS ARPE-19 cells treated with high glucose(HG)and desferrioxamine mesylate(DFX)for establishment of the DME cell model.DME mice models were constructed by streptozotocin induction.The trans-epithelial electrical resistance and permeability of RPE cells were analyzed.The expressions of tight junction-related and autophagy-related proteins were determined.The interaction between insulin like growth factor 2 mRNA binding protein 2(IGF2BP2)and SMURF1 mRNA was verified by RNA immunoprecipitation(RIP).SMURF1 N6-methyladenosine(m6A)level was detected by methylated RIP.RESULTS SMURF1 and vascular endothelial growth factor(VEGF)were upregulated in DME.SMURF1 knockdown reduced HG/DFX-induced autophagy,which protected RPE cell tight junctions and ameliorated retinal damage in DME mice.SMURF1 activated the Wnt/β-catenin-VEGF signaling pathway by promoting WNT inhibitory factor(WIF)1 ubiquitination and degradation.IGF2BP2 upregulated SMURF1 expression in an m6A modification-dependent manner.CONCLUSION M6A-modified SMURF1 promoted WIF1 ubiquitination and degradation,which activated autophagy to inhibit RPE cell tight junctions,ultimately promoting DME progression.

Optimizing crop yields while minimizing environmental impact through deep placement of nitrogen fertilizer

Nitrogen(N)serves as an essential nutrient for yield formation across diverse crop types.However,agricultural production encounters numerous challenges,notably high N fertilizer rates coupled with low N use efficiency and serious environmental pollution.Deep placement of nitrogen fertilizer(DPNF)is an agronomic measure that shows promise in addressing these issues.This review aims to offer a comprehensive understanding of DPNF,beginning with a succinct overview of its development and methodologies for implementation.Subsequently,the optimal fertilization depth and influencing factors for different crops are analyzed and discussed.Additionally,it investigates the regulation and mechanism underlying the DPNF on crop development,yield,N use efficiency and greenhouse gas emissions.Finally,the review delineates the limitations and challenges of this technology and provides suggestions for its improvement and application.This review provides valuable insight and reference for the promotion and adoption of DPNF in agricultural practice.

Synergistically S/N self-doped biochar as a green bifunctional cathode catalyst in electrochemical degradation of organic pollutant

Biomass-derived heteroatom self-doped cathode catalysts has attracted considerable interest for electrochemical advanced oxidation processes(EAOPs)due to its high performance and sustainable synthesis.Herein,we illustrated the morphological fates of waste leaf-derived graphitic carbon(WLGC)produced from waste ginkgo leaves via pyrolysis temperature regulation and used as bifunctional cathode catalyst for simultaneous H_(2)O_(2) electrochemical generation and organic pollutant degradation,discovering S/N-self-doping shown to facilitate a synergistic effect on reactive oxygen species(ROS)generation.Under the optimum temperature of 800℃,the WLGC exhibited a H_(2)O_(2) selectivity of 94.2%and tetracycline removal of 99.3%within 60 min.Density functional theory calculations and in-situ Fourier transformed infrared spectroscopy verified that graphitic N was the critical site for H_(2)O_(2) generation.While pyridinic N and thiophene S were the main active sites responsible for OH generation,N vacancies were the active sites to produce ^(1)O_(2) from O_(2).The performance of the novel cathode for tetracycline degradation remains well under a wide pH range(3–11),maintaining excellent stability in 10 cycles.It is also industrially applicable,achieving satisfactory performance treating in real water matrices.This system facilitates both radical and non-radical degradation,offering valuable advances in the preparation of cost-effective and sustainable electrocatalysts and hold strong potentials in metal-free EAOPs for organic pollutant degradation.

Relationship between high dietary fat intake and Parkinson’s disease risk: a meta-analysis

OBJECTIVE: To assess whether dietary fat intake influences Parkinson’s disease risk. DATA SOURCES: We systematically surveyed the Embase and PubMed databases, reviewing manuscripts published prior to October 2018. The following terms were used:(“Paralysis agitans” OR “Parkinson disease” OR “Parkinson” OR “Parkinson’s” OR “Parkinson’s disease”) AND (“fat” OR “dietary fat” OR “dietary fat intake”). DATA SELECTION: Included studies were those with both dietary fat intake and Parkinson’s disease risk as exposure factors. The Newcastle-Ottawa Scale was adapted to investigate the quality of included studies. Stata V12.0 software was used for statistical analysis. OUTCOME MEASURES: The primary outcomes included the relationship between high total energy intake, high total fat intake, and Parkinson’s disease risk. The secondary outcomes included the relationship between different kinds of fatty acids and Parkinson’s disease risk. RESULTS: Nine articles met the inclusion criteria and were incorporated into this meta-analysis. Four studies scored 7 and the other five studies scored 9 on the Newcastle-Ottawa Scale, meaning that all studies were of high quality. Meta-analysis results showed that high total energy intake was associated with an increased risk of Parkinson’s disease (P = 0.000, odds ratio (OR)= 1.49, 95% confidence interval (CI): 1.26–1.75);in contrast, high total fat intake was not associated with Parkinson’s disease risk (P = 0.123, OR = 1.07, 95% CI: 0.91–1.25). Subgroup analysis revealed that polyunsaturated fatty acid intake (P = 0.010, OR = 1.03, 95% CI: 0.88–1.20) reduced the risk of Parkinson’s disease, while arachidonic acid (P = 0.026, OR = 1.15, 95% CI: 0.97–1.37) and cholesterol (P = 0.002, OR = 1.09, 95% CI: 0.92–1.29) both increased the risk of Parkinson’s disease. Subgroup analysis also demonstrated that, although the results were not significant, consumption of n-3 polyunsaturated fatty acids (P = 0.071, OR = 0.88, 95% CI: 0.73–1.05),α-linolenic acid (P = 0.06, OR = 0.86, 95% CI: 0.72–1.02), and the n-3 to n-6 ratio (P = 0.458, OR = 0.89, 95% CI: 0.75–1.06) were all linked with a trend toward reduced Parkinson’s disease risk. Monounsaturated fatty acid (P = 0.450, OR = 1.06, 95% CI: 0.91–1.23), n-6 polyunsaturated fatty acids (P = 0.100, OR = 1.15, 95% CI: 0.96–1.36) and linoleic acid (P = 0.053, OR = 1.11, 95% CI: 0.94–1.32) intakes were associated with a non-significant trend toward higher PD risk. Saturated fatty acid (P = 0.619, OR = 1.01, 95% CI: 0.87–1.18) intake was not associated with Parkinson’s disease. CONCLUSION: Dietary fat intake affects Parkinson’s disease risk, although this depends on the fatty acid subtype. Higher intake of polyunsaturated fatty acids may reduce the risk of Parkinson’s disease, while higher cholesterol and arachidonic acid intakes may elevate Parkinson’s disease risk. However, further studies and evidence are needed to validate any link between dietary fat intake and Parkinson’s disease.

Transfer of Paralytic Shellfish Toxins via Marine Food Chains:A Simulated Experiment

Objective To study the transfer of paralytic shellfish toxins （PST） using four simulated marine food chains： dinoflagellate Alexandrium tamarense→Artemia Artemia salina→Mysid shrimp Neomysis awatschensis; A. tamarense→N. awatschensis; A. tamarense→A, salina→Perch Lateolabrax japonicus; and A. tamarense→L, japonicus. Methods The ingestion of A. tamarense, a producer of PST, by L. japonicus, N. awatschensis, and A. salina was first confirmed by microscopic observation of A. tamarense cells in the intestine samples of the three different organisms, and by the analysis of Chl.a levels in the samples. Toxin accumulation in L. japonicus and N. awatschensis directly from the feeding on A. tamarense or indirectly through the vector of A. salina was then studied, The toxicity of samples was measured using the AOAC mouse bioassay method, and the toxin content and profile of A. tamarense were analyzed by the HPLC method. Results Both A. salina and N. awatschensis could ingest A. tamarense cells. However, the ingestion capability of A. salina exceeded that of N. awatschensis. After the exposure to the culture of A. tamarense （2 000 cells·mL^-1） for 70 minutes, the content of Chl.a in A. salina and N. awatschensis reached 0.87 and 0.024 μg.mg^-1, respectively. Besides, A. tamarense cells existed in the intestines of L. japonicus, N. awatschensis and A. salina by microscopic observation. Therefore, the three organisms could ingest A. tamarense cells directly. A. salina could accumulate high content of PST, and the toxicity of A. salina in samples collected on days 1, 4, and 5 of the experiment was 2.18, 2.6, and 2.1 MU.g^-1, respectively. All extracts from the samples could lead to death of tested mice within 7 minutes, and the toxin content in anemia sample collected on the 1st day was estimated to be 1.65×10 ^5 μg STX equal/individual. Toxin accumulation in L japonicus and N. awatschensis directly from the feeding on A. tamarense or indirectly from the vector ofA. salina was also studied. The mice injected with extracts from L japonicus and N. awatschensis samples that accumulated PST either directly or indirectly showed PST intoxication symptoms, indicating that low levels of PST existed in these samples. Conclusion Paralytic shellfish toxins can be transferred to L. japonicus, N. awatschensis, and A. salina from A. tamarense directly or indirectly via the food chains.

Exploring the effect of aggregation-induced emission on the excited state intramolecular proton transfer for a bis-imine derivative by quantum mechanics and our own n-layered integrated molecular orbital and molecular mechanics calculations

We theoretically investigate the excited state intramolecular proton transfer(ESIPT) behavior of the novel fluorophore bis-imine derivative molecule HNP which was designed based on the intersection of 1-(hydrazonomethyl)-naphthalene-2-ol and 1-pyrenecarboxaldehyde. Especially, the density functional theory(DFT) and time-dependent density functional theory(TDDFT) methods for HNP monomer are introduced. Moreover, the "our own n-layered integrated molecular orbital and molecular mechanics"(ONIOM) method(TDDFT:universal force field(UFF)) is used to reveal the aggregation-induced emission(AIE) effect on the ESIPT process for HNP in crystal. Our results confirm that the ESIPT process happens upon the photoexcitation for the HNP monomer and HNP in crystal, which is distinctly monitored by the optimized geometric structures and the potential energy curves. In addition, the results of potential energy curves reveal that the ESIPT process in HNP will be promoted by the AIE effect. Furthermore, the highest occupied molecular orbital(HOMO) and lowest unoccupied molecular orbital(LUMO) for the HNP monomer and HNP in crystal have been calculated. The calculation demonstrates that the electron density decrease of proton donor caused by excitation promotes the ESIPT process. In addition, we find that the variation of atomic dipole moment corrected Hirshfeld population(ADCH) charge for proton acceptor induced by the AIE effect facilitates the ESIPT process. The results will be expected to deepen the understanding of ESIPT dynamics for luminophore under the AIE effect and provide insight into future design of high-efficient AIE compounds.

Assessing Lysine Requirement of Growing Chicken by Direct Comparison between Supplementation Technique and “Goettingen Approach”

Validated procedures play an important role to obtain accurate information about individual amino acid requirement data. The aim of the present study was to assess lysine (Lys) requirement of growing chicken both by classical supplementation technique and principles of diet dilution technique as applied with “Goettingen approach”. During the starter period (1 - 21 d), a growth study with male meat type chicken (Ross 308) was conducted making use of five graded dietary Lys-levels (3 repetition boxes with 3 birds/box). L-Lys×HCl was gradually added to a diet based on wheat, soybean protein concentrate, wheat gluten and fishmeal to yield 80%, 87.5%, 95%, 102.5% and 110% of the expected requirement level (13 g Lys/kg as fed). Diets were iso-energetic (12.8 MJME/kg) and iso-nitrogenous (21.65% crude protein). Birds were fed on free choice level also to assess the feed intake (FI) effects as important factor on traditional response criteria. Analyzed body composition at start and end of the growth study yielded N deposition (ND) data for further data assessment using exponential approximations depending on dietary Lys content or observed Lys intake. The results indicated significant differences (p < 0.05) in response on body weight gain (BWG) and observed dietary protein quality with unexpected consequences for the derived Lys requirement data. According to the independent variable (Lys in % of diet versus daily Lys intake) and aimed level of daily ND, the needed in-feed content of Lys varied between 1.24% and 1.46%. Application of the exponential modelling by “Goettingen approach” overcame these misleading conclusions by modelling the relationship between required Lys intake and observed response data (BWG, ND) taking also into account the expected real feed intake to formulate the needed in-feed concentration.

Estrogen affects neuropathic pain through upregulating N-methyl-D-aspartate acid receptor 1 expression in the dorsal root ganglion of rats

Estrogen affects the generation and transmission of neuropathic pain,but the specific regulatory mechanism is still unclear.Activation of the N-methyl-D-aspartate acid receptor 1（NMDAR1） plays an important role in the production and maintenance of hyperalgesia and allodynia.The present study was conducted to determine whether a relationship exists between estrogen and NMDAR1 in peripheral nerve pain.A chronic sciatic nerve constriction injury model of chronic neuropathic pain was established in rats.These rats were then subcutaneously injected with 17β-estradiol,the NMDAR1 antagonist D（-）-2-amino-5-phosphonopentanoic acid（AP-5）,or both once daily for 15 days.Compared with injured drug na？ve rats,rats with chronic sciatic nerve injury that were administered estradiol showed a lower paw withdrawal mechanical threshold and a shorter paw withdrawal thermal latency,indicating increased sensitivity to mechanical and thermal pain.Estrogen administration was also associated with increased expression of NMDAR1 immunoreactivity（as assessed by immunohistochemistry） and protein（as determined by western blot assay） in spinal dorsal root ganglia.This 17β-estradiol-induced increase in NMDAR1 expression was blocked by co-administration with AP-5,whereas AP-5 alone did not affect NMDAR1 expression.These results suggest that 17β-estradiol administration significantly reduced mechanical and thermal pain thresholds in rats with chronic constriction of the sciatic nerve,and that the mechanism for this increased sensitivity may be related to the upregulation of NMDAR1 expression in dorsal root ganglia.

Boundary Control Problem of Infinite Order Distributed Hyperbolic Systems Involving Time Lags

Various optimal boundary control problems for linear infinite order distributed hyperbolic systems involving constant time lags are considered. Constraints on controls are imposed. Necessary and sufficient optimality conditions for the Neumann problem with the quadratic performance functional are derived.

Nonalcoholic fatty liver disease:A comprehensive review of a growing epidemic

Nonalcoholic fatty liver disease(NAFLD)is quickly becoming one of the most prominent causes of liver disease worldwide.The increasing incidence of NAFLD is tied to the obesity epidemic and the subsequent metabolic derangements brought along with it.Current efforts to elucidate the mechanism and causes of the disease have answered some questions,but much remains unknown about NAFLD.The aim of this article is to discuss the current knowledge regarding the pathogenesis of the disease,as well as the current and future diagnostic,preventative,and therapeutic options available to clinicians for the management of NAFLD.

Antibodies elicited by Newcastle disease virus-vectored H7N9 avian influenza vaccine are functional in activating the complement system

H7N9 subtype avian influenza virus poses a great challenge for poultry industry.Newcastle disease virus(NDV)-vectored H7N9 avian influenza vaccines(NDV_(vec)H7N9)are effective in disease control because they are protective and allow mass administration.Of note,these vaccines elicit undetectable H7N9-specific hemagglutination-inhibition(HI)but high IgG antibodies in chickens.However,the molecular basis and protective mechanism underlying this particular antibody immunity remain unclear.Herein,immunization with an NDV_(vec)H7N9 induced low anti-H7N9 HI and virus neutralization titers but high levels of hemagglutinin(HA)-binding IgG antibodies in chickens.Three residues(S150,G151 and S152)in HA of H7N9 virus were identified as the dominant epitopes recognized by the NDV_(vec)H7N9 immune serum.Passively transferred NDV_(vec)H7N9 immune serum conferred complete protection against H7N9 virus infection in chickens.The NDV_(vec)H7N9 immune serum can mediate a potent lysis of HA-expressing and H7N9 virus-infected cells and significantly suppress H7N9 virus infectivity.These activities of the serum were significantly impaired after heat-inactivation or treatment with complement inhibitor,suggesting the engagement of the complement system.Moreover,mutations in the 150-SGS-152 sites in HA resulted in significant reductions in cell lysis and virus neutralization mediated by the NDV_(vec)H7N9 immune serum,indicating the requirement of antibody-antigen binding for complement activity.Therefore,antibodies induced by the NDV_(vec)H7N9 can activate antibody-dependent complement-mediated lysis of H7N9 virus-infected cells and complement-mediated neutralization of H7N9 virus.Our findings unveiled a novel role of the complement in protection conferred by the NDV_(vec)H7N9,highlighting a potential benefit of engaging the complement system in H7N9 vaccine design.

Seismic displacement demand prediction in non-linear domain: Optimization of the N2 method

In Europe, computation of displacement demand for seismic assessment of existing buildings is essentially based on a simplified formulation of the N2 method as prescribed by Eurocode 8(EC8). However, a lack of accuracy of the N2 method in certain conditions has been pointed out by several studies. This paper addresses the assessment of effectiveness of the N2 method in seismic displacement demand determination in non-linear domain. The objective of this work is to investigate the accuracy of the N2 method through comparison with displacement demands computed using non-linear timehistory analysis(NLTHA). Results show that the original N2 method may lead to overestimation or underestimation of displacement demand predictions. This may affect results of mechanical model-based assessment of seismic vulnerability at an urban scale. Hence, the second part of this paper addresses an improvement of the N2 method formula by empirical evaluation of NLTHA results based on EC8 ground-classes. This task is formulated as a mathematical programming problem in which coefficients are obtained by minimizing the overall discrepancy between NLTHA and modified formula results. Various settings of the mathematical programming problem have been solved using a global optimization metaheuristic. An extensive comparison between the original N2 method formulation and optimized formulae highlights benefits of the strategy.