Neuroprotective effect of the Chinese medicine Tiantai No.1 and its molecular mechanism in the senescence-accelerated mouse prone 8

Tiantai No.1, a Chinese medicine predominantly composed of powdered Rhizoma Gastrodiae, Radix Ginseng, and Ginkgo leaf at a ratio of 2：1：2 and dissolved in pure water, is neuroprotective in animal models of various cognitive disorders, but its molecular mechanism remains unclear. We administered Tiantai No.1 intragastrically to senescence-accelerated mouse prone 8（SAMP8） mice（a model of Alzheimer＇s disease） at doses of 50, 100 or 150 mg/kg per day for 8 weeks and evaluated their behavior in the Morris water maze and expression of Alzheimer＇s disease-related proteins in the brain. Tiantai No.1 shortened the escape latency in the water maze training trials, and increased swimming time in the target quadrant during the spatial probe test, indicating that Tiantai No.1 improved learning and memory in SAMP8 mice. Immunohistochemistry revealed that Tiantai No.1 restored the proliferation potential of Ki67-positive cells in the hippocampus. In addition, mice that had received Tiantai No.1 had fewer astrocytes, and less accumulation of amyloid-beta and phosphorylated tau. These results suggest that Tiantai No.1 is neuroprotective in the SAMP8 mouse model of Alzheimer＇s disease and acts by restoring neuronal number and proliferation potential in the hippocampus, decreasing astrocyte infiltration, and reducing the accumulation of amyloid-beta and phosphorylated tau.

Prevention of malignant digestive system tumors should focus on the control of chronic inflammation

Chronic inflammation,through a variety of mechanisms,plays a key role in the occurrence and development of digestive system malignant tumors(DSMTs).In this study,we feature and provide a comprehensive understanding of DSMT prevention strategies based on preventing or controlling chronic inflammation.The development and evaluation of cancer prevention strategies is a longstanding process.Cancer prevention,especially in the early stage of life,should be emphasized throughout the whole life course.Issues such as the time interval for colon cancer screening,the development of direct-acting antiviral drugs for liver cancer,and the Helicobacter pylori vaccine all need to be explored in long-term,large-scale experiments in the future.

帕博利珠单抗治疗后应用阿莫西林致斑丘疹1例

1例64岁男性右肺腺癌患者行化疗联合帕博利珠单抗治疗2周期后发生4级免疫介导肝损伤而住院治疗,期间服用阿莫西林胶囊0.5 g,q8h治疗肺部感染,用药约10 h后躯干部出现斑丘疹型药疹,未行处理。第2天早上皮疹遍布躯干部及双上肢,颜色加深。停用可疑药物阿莫西林胶囊,给予苯海拉明20 mg,im,盐酸西替利嗪10 mg,po,qd。第3天患者双上肢皮疹消失,躯干部皮疹部分消退,皮疹颜色变浅。第6天皮疹全部消失。患者既往多次服用阿莫西林,均未发生过敏反应,考虑本次出现阿莫西林致斑丘疹型药疹与帕博利珠单抗使用后引起的免疫状态过度激活有关。

Identification of propranolol and derivatives that are chemical inhibitors of phosphatidate phosphatase as potential broad-spectrum fungicides

Plant diseases cause enormous economic losses in agriculture and threaten global food security,and application of agrochemicals is an important method of crop disease control.Exploration of disease-resis-tance mechanisms and synthesis of highly bioactive agrochemicals are thus important research objectives.Here,we show that propranolol,a phosphatidate phosphatase(Pah)inhibitor,effectively suppresses fungal growth,sporulation,sexual reproduction,and infection of diverse plants.The MoPah1 enzyme activity of the rice blast fungus Magnaporthe oryzae is inhibited by propranolol.Alterations in lipid metabolism are associated with inhibited hyphal growth and appressorium formation caused by propranolol in M.oryzae.Propranolol inhibits a broad spectrum of 12 plant pathogens,effectively inhibiting infection of barley,wheat,maize,tomato,and pear.To improve antifungal capacity,we synthesized a series of propranolol derivatives,one of which shows a 16-fold increase in antifungal ability and binds directly to MoPah1.Propranolol and its derivatives can also reduce the severity of rice blast and Fusarium head blight of wheat in thefield.Taken together,our results demonstrate that propranolol suppresses fungal development and infection through mechanisms involved in lipid metabolism.Propranolol and its derivatives may therefore be promising candidates for fungicide development.

Synthesis, Characterization, and Catalytic Ethylene Oligomerization of Pyridine-imine Palladium Complexes

Two neutral five-membered pyridine-imine palladium complexes with the bulky dibenzhydryl（CH（Ph）2） substituted aniline were synthesized and fully characterized by nuclear magnetic resonance（NMR） and X-ray crystal diffraction. Well-defined cationic palladium complexes were further obtained by treatment of chloromethylpalladium complexes with sodium tetrakis（3,5-bis（trifluoromethyl）phenyl）borate（NaBArF） in CH3CN. Cationic palladium complexes were capable of catalyzing ethylene oligomerization without any cocatalysts. The influences of catalyst structure, reaction temperature, and ethylene pressure on ethylene oligomerization were studied in detail. The introduction of bulky benzhydryl（CH（Ph）2） on the ortho position of the aniline moiety enhanced catalytic activity, thermal stability of the catalyst, and molecular weight of the obtained products. Highly branched oligomers with molecular weights of 600-800 g/mol and narrow polydispersities（1.03-1.12） were produced.

An On-line Finite Element Temperature Field Model for Plate Ultra Fast Cooling Process

Taking the element specific-heat interpolation function into account, a one-dimensional （l-D） finite ele- ment temperature field model for the on-line control of the ultra fast cooling process was developed based on the heat transfer theory. This 1-D model was successfully implemented in one 4 300 mm plate production line. To improve the calculation accuracy of this model, the temperature-dependent material properties inside an element were considered during the modeling process. Furthermore, in order to satisfy the real-time requirements of the on-line model, the variable bandwidth storage method and the Cholesky decomposition method were used in the programming to storage the data and carry out the numerical solution. The on-line application of the proposed model indicated that the devia- tion between the calculated cooling stop temperature and the measured one was less than ± 15 ℃.

Rainbow k-connectivity of Random Bipartite Graphs

A path in an edge-colored graph G is called a rainbow path if no two edges of the path are colored the same color.The minimum number of colors required to color the edges of G such that every pair of vertices are connec ted by at least k internally ver tex-disjoint rainbow paths is called the rainbow k-connectivity of the graph G,denoted by rck(G).For the random graph G(n,p),He and Liang got a sharp threshold function for the property rck(G(n,p))≤d.For the random equi-bipartite graph G(n,n,p),Fujita et.al.got a sharp threshold function for the property rck(G(n,n,p))≤3.They also posed the following problem:For d≥2,determine a sharp threshold function for the property rck(G)≤d,where G is another random graph model.This paper is to give a solution to their problem in the general random bipartite graph model G(m,n,p).

Inhibition of Zinc Corrosion by Fucoidan in Natural Sea water

Research on corrosion behaviour of zinc in natural sea water without and with fucoidan was carried out by potentiodynamic polarisation test and electrochemical impedance spectroscopy （EIS）. The results revealed that fucoidan serves as a good inhibitor for zinc in sea water. Polarisation curves suggested that corrosion potential values shifted to the positive ones after adding inhibitor and fucoidan retards anodic reaction more. Thus, fucoidan can be acted as anodic inhibitor. EIS results showed two phenomena including a charge transfer and an adsorption film. The corrosion inhibition of fucoidan was further confirmed by the scanning electron microscope （SEM） and atomic force microscope （AFM） analysis. Langmuir＇s adsorption isotherm was found the appropriate adsorption model.

Regression Analysis for the Additive Hazards Model with General Biased Survival Data

In survival analysis,data are frequently collected by some complex sampling schemes,e.g.,length biased sampling,case-cohort sampling and so on.In this paper,we consider the additive hazards model for the general biased survival data.A simple and unified estimating equation method is developed to estimate the regression parameters and baseline hazard function.The asymptotic properties of the resulting estimators are also derived.Furthermore,to check the adequacy of the fitted model with general biased survival data,we present a test statistic based on the cumulative sum of the martingale-type residuals.Simulation studies are conducted to evaluate the performance of proposed methods,and applications to the shrub and Welsh Nickel Refiners datasets are given to illustrate the methodology.

Partially Time-varying Coefficient Linear Rate Model for the Recurrent Event Data

In [13], Schaubel et al. proposed a semiparametric partially linear rate model for the statistical analysis of recurrent event data. But they only considered the model with time-independent covariate effects. In this paper, rate function of the recurrent event is modeled by a semipaxametric partially linear function which can include the time-varying effects. We propose the method of generalized estimating equations to make inferences about both the time-varying effects and time-independent effects. The large sample properties are established, while extensive simulation studies are carried out to examine the proposed procedures. At last, we apply the procedures to the well-known bladder cancer study.

Mallows Model Averaging Estimation for Linear Regression Model with Right Censored Data

This paper is concerned with an optimal model averaging estimation for linear regression model with right censored data. The weights for model averaging are picked up via minimizing the Mallows criterion. Under some mild conditions, it is shown that the identified weights possess the property of asymptotic optimality, that is,the model averaging estimator corresponding to these weights achieves the lowest squared error asymptotically.Some numerical studies are conducted to evaluate the finite-sample performance of our method and make comparisons with its intuitive competitors, while an application to the PBC dataset is provided to serve as an illustration.

Cerebral ischemia at early postoperative period of direct revascularization for moyamoya disease: a case report and literature review

Hypoperfusion and hyperperfusion could be causes of early postoperative complications that lead to neurological deterioration in patients with moyamoya diseases (MMD) after superficial temporal artery (STA) and middle cerebral artery (MCA) anastomosis. Here, the authors described a case of child-onset bilateral MMD that manifested transient cerebral ischemia in the contralateral hemisphere after left STA-MCA bypass in young adulthood. A new onset of cerebral ischemia in the contralateral hemisphere and transient neurological deterioration suggested the fragile hemodynamics of MMD during early perioperative period. Serial evaluation of postoperative cerebral hemodynamics and perfusion might facilitate targeted management in patients with unstable or advanced MMD.

A lipid droplet-associated protein Nem1 regulates appressorium function for infection of Magnaporthe oryzae

Lipid droplets are important storages in fungal conidia and can be used by plant pathogenic fungi for infection.However,the regulatory mechanism of lipid droplets formation and the utilization during fungal development and infection are largely unknown.Here,in Magnaporthe oryzae,we identified a lipid droplet-associated protein Nem1 that played a key role in lipid droplets biogenesis and utilization.Nem1 was highly expressed in conidia,but lowly expressed in appressoria,and its encoded protein was localized to lipid droplets.Deletion of NEM1 resulted in reduced numbers of lipid droplets and decreased content of diacylglycerol(DAG)or triacylglycerol(TAG).NEM1 was required for asexual development especially conidia production.TheΔnem1 mutant was nearly loss of virulence to host plants due to defects in appressorial penetration and invasive growth.Remarkably,Nem1 was regulated by the TOR signaling pathway and involved in the autophagy process.The Ser303 residue of Nem1 could be phosphorylated by the cAMP-PKA signaling pathway and was important for biological function of Nem1.Together,our study revealed a regulatory mechanism of lipid biogenesis and metabolism during the conidium and appressorium formation of the rice blast fungus.