反应树(Reaction Tree)--归纳总结法在“药物合成反应”教学中的应用

针对“药物合成反应”这一课程有机反应多、化合物结构复杂的特点,设计用一种“反应树”式的归纳总结方法对教材每个章节的有机反应进行总结。反应树可以清晰地展示同一章节里不同有机反应之间的区别与联系,使看上去无规律的有机反应更加系统化、条理化,从而帮助提高教学效果。

浅谈制药工程专业有机化学实验教学的心得和体会——以三苯甲醇的制备和重结晶实验为例

有机化学实验是制药工程专业的一门必修课,旨在训练学生有机合成基本实验技能。本文以三苯甲醇的制备和重结晶实验为例,讲述了笔者在多年教学中获得的一点感悟和经验:1)将实验步骤分解成片断讲解可以使学生更好地理解和记忆实验过程和操作目的;2)重要的基本操作应反复练习,即“学习、复习、提高”,通过三次重复练习来实现巩固和熟练掌握该操作的目的。

Multi-scale modeling of hemodynamics in the cardiovascular system

The human cardiovascular system is a closed- loop and complex vascular network with multi-scaled het- erogeneous hemodynamic phenomena. Here, we give a selective review of recent progress in macro-hemodynamic modeling, with a focus on geometrical multi-scale model- ing of the vascular network, micro-hemodynamic modeling of microcirculation, as well as blood cellular, subcellular, endothelial biomechanics, and their interaction with arter- ial vessel mechanics. We describe in detail the methodology of hemodynamic modeling and its potential applications in cardiovascular research and clinical practice. In addition, we present major topics for future study： recent progress of patient-specific hemodynamic modeling in clinical applica- tions, micro-hemodynamic modeling in capillaries and blood cells, and the importance and potential of the multi-scale hemodynarnic modeling.

Highly active binuclear Cu(Ⅱ) catalyst bearing an unsymmetrical bipyridine-pyrazole-amine ligand for the azide-alkyne cycloaddition reaction

Ligands containing NH groups often show special characteristics.In this paper,a well-defined dinuclear Cu（II） complex bearing an unsymmetrical bipyridine-pyrazole-amine ligand was synthesized by the condensation of N–H to release H2O.Using sodium L-ascorbate as a reductant,the binuclear complex showed excellent activity in 1,3-dipolar cycloaddition reactions between alkynes and azides to obtain 1,4-disubstituted triazoles in 95%–99% isolated yields.

Impact Dynamics of a Dragonfly Wing

The lift force was reported not to be high enough to support the dragonfly’s weight during flight in some conventional investigations,and higher lift force is required for its takeoff.In this study,by employing a thin plate model,impact effect is investigated for the wing deformation in dragonfly flapping during takeoff.The static displacement is formulated to compare with the dynamical displacement caused by impact.The governing equation of motion for the impact dynamics of a dragonfly wing is derived based on Newton’s second law.Separation of variables technique and assumed modes method are introduced to solve the resulting equations.Further,lift force is presented for the cases of considering and without considering the impact on the wing flapping which indicates that the impact has prominent effects for the dragonfly’s aerodynamic performance.Numerical simulations demonstrate that considering the impact effect on the wing flapping can increase the wing deformation,which results in the rise of the lift force.The enhanced lift force is of critical importance for the dragonfly’s takeoff.

Expression of MMP-2 and MMP-13 in Bullous Pemphigoid

Objective:To investigate the expression and significance of matrix metalloproteinase-2(MMP-2)and matrix metalloproteinase-13(MMP-13)in bullous pemphigoid(BP)skin lesions.Methods:Immunohistochemical SP method was used to detect the expression of MMP-2 and MMP-13 in 32 BP skin lesions,and compared with 15 normal skin tissues.Results:The expression of MMP-2 in the case group was significantly increased(38.56±10.06)compared to the normal control group(21.20±5.98);the expression of MMP-13 in the case group was significantly augmented(18.62±5.90)compared to the normal control group(11.47±8.484).The expressions of MMP-2 and MMP-13 in the skin lesions of patients with bullous pemphigoid were statistically different from those of normal people(both P<0.05).Compared with the expression of MMP-2 and MMP-13 in bullous pemphigoid,the expression of MMP-2 and MMP-13 was moderately correlated(correlation coefficient was 0.523).Conclusion:The expression of MMP-2 and MMP-13 is significantly increased in bullous pemphigoid skin lesions,suggesting that they may play an important role in the pathogenesis of BP.There is a certain correlation between the expression of MMP-2 and MMP-13,suggesting that the high expression of MMP-13 may play a role in the mechanism that further leads to the high expression of MMP-2.

Simulating potential outbreaks of Delta and Omicron variants based on contact-tracing data:A modelling study in Fujian Province,China

Although studies have compared the relative severity of Omicron and Delta variants by assessing the relative risks,there are still gaps in the knowledge of the potential COVID-19 burden these variations may cause.And the contact patterns in Fujian Province,China,have not been described.We identified 8969 transmission pairs in Fujian,China,by analyzing a contact-tracing database that recorded a SARS-CoV-2 outbreak in September 2021.We estimated the waning vaccine effectiveness against Delta variant infection,contact patterns,and epidemiology distributions,then simulated potential outbreaks of Delta and Omicron variants using a multi-group mathematical model.For instance,in the contact setting without stringent lockdowns,we estimated that in a potential Omicron wave,only 4.7%of infections would occur in Fujian Province among individuals aged>60 years.In comparison,58.75%of the death toll would occur in unvaccinated individuals aged>60 years.Compared with no strict lockdowns,combining school or factory closure alone reduced cumulative deaths of Delta and Omicron by 28.5%and 6.1%,respectively.In conclusion,this study validates the need for continuous mass immunization,especially among elderly aged over 60 years old.And it confirms that the effect of lockdowns alone in reducing infections or deaths is minimal.However,these measurements will still contribute to lowering peak daily incidence and delaying the epidemic,easing the healthcare system's burden.

A Common Functional Variant at the Enhancer of the Rheumatoid Arthritis Risk Gene ORMDL3 Regulates its Expression Through Allele-Specific JunD Binding

Genome-wide association studies(GWASs)have identified over 100 loci associated with rheumatoid arthritis(RA);how-ever,the functionally affected genes and the underlying molecular mechanisms contributing to these associations are often unknown.In this study,we conducted an integrative genomic analysis incorporating multiple“omics”data and identified a functional regulatory DNA variant,rs56199421,and a plausible mechanism by which it regulates the expression of a puta-tive RA risk gene,ORMDL Sphingolipid Biosynthesis Regulator 3(ORMDL3).The T allele of rs56199421,located in the enhancer region of ORMDL3,exhibited stronger direct binding ability than the other C allele of rs56199421 did in vitro with the transcription factor JunD and demonstrated higher transcriptional activity.Moreover,the T allele of rs56199421 is associated with elevated RA risk,and ORMDL3 expression is increased in RA patients.Thus,these findings suggest that the T allele of rs56199421 enhances JunD transcription factor binding,increases enhancer activity,and elevates the expression of the RA risk gene ORMDL3.

Modelling the Emerging COVID-19 Epidemic and Estimating Intervention Effectiveness—Taiwan,China,2021

Introduction:The coronavirus disease 2019(COVID-19)pandemic recently affected Taiwan,China.This study aimed to calculate the transmissibility of COVID-19 to predict trends and evaluate the effects of interventions.Methods:The data of reported COVID-19 cases was collected from April 20 to May 26,2021,which included daily reported data(Scenario I)and reported data after adjustment(Scenario II).A susceptibleexposed-symptomatic-asymptomatic-recovered model was developed to fit the data.The effective reproductive number(Reff)was used to estimate the transmissibility of COVID-19.Results:A total of 4,854 cases were collected for the modelling.In Scenario I,the intervention has already taken some effects from May 17 to May 26(the Reff reduced to 2.1).When the Reff was set as 0.1,the epidemic was projected to end on July 4,and a total of 1,997 cases and 855 asymptomatic individuals would have been reported.In Scenario II,the interventions were projected as having been effective from May 24 to May 26(the Reff reduced to 0.4).When the Reff was set as 0.1,the epidemic was projected to end on July 1,and a total of 1,482 cases and 635 asymptomatic individuals would have been reported.Conclusion:The epidemic of COVID-19 was projected to end after at least one month,even if the most effective interventions were applied in Taiwan,China.Although there were some positive effects of intervention in Taiwan,China.

Clinical correlations with disease-associated auto-antibodies in a Chinese cohort with systemic sclerosis

To the Editor:Systemic sclerosis(SSc)is an autoimmune disease characterized by,progressive skin and visceral fibrosis,microvasculopathy,and autoimmunity.Circulating auto-antibodies(AAbs)are detectable in 90%to 95%of patients with SSc.

Salicylic acid sensitizes cervical cancer cells to radiotherapy by activating AMPK/TSC2/mTOR pathway

Objective:To investigate the radio-sensitizing effect of salicylic acid(SA)on human cervical cancer cells and its potential molecular mechanism.Methods:Cervical cancer cells were treated with SA and ionizing radiation.The expression ofγ-H2AX was evaluated by immunofluorescence(IF)assay.Cell cycle and apoptosis were analyzed by flow cytometry.Western blot was performed to detect the protein level of AMPK/TSC2/mTOR pathway.Results:SA inhibited basal proliferation of cervical cancer cells in a dose and time dependent manner.In addition,SA increased radiation-induced DNA damage,promoted apoptosis,triggered a redistribution of cell cycle from G2-M phase to G1-S phase of cervical cancer cells,and hence increased cell sensitivity to radiation.Moreover,SA treatment elevated the expression levels of p-AMPKα(t=3.996,P<0.05)and p-TSC2(t=5.308,P<0.05),whereas the level of p-mTOR(t=10.160,P<0.05)was significantly decreased.Conclusion:SA enhances the radiosensitivity of cervical cancer cells by targeting AMPK/TSC2/mTOR signaling pathway,and might serve as a promising therapeutic strategy to improve the efficacy of radiotherapy for cervical cancer.

An Efficient Hybrid DSMC/MD Algorithm for Accurate Modeling of Micro Gas Flows

Aiming at simulating micro gas flows with accurate boundary conditions,an efficient hybrid algorithm is developed by combining the molecular dynamics(MD)method with the direct simulation Monte Carlo(DSMC)method.The efficiency comes from the fact that the MD method is applied only within the gas-wall interaction layer,characterized by the cut-off distance of the gas-solid interaction potential,to resolve accurately the gas-wall interaction process,while the DSMC method is employed in the remaining portion of the flow field to efficiently simulate rarefied gas transport outside the gas-wall interaction layer.A unique feature about the present scheme is that the coupling between the two methods is realized by matching the molecular velocity distribution function at the DSMC/MD interface,hence there is no need for one-toone mapping between a MD gas molecule and a DSMC simulation particle.Further improvement in efficiency is achieved by taking advantage of gas rarefaction inside the gas-wall interaction layer and by employing the“smart-wall model”proposed by Barisik et al.The developed hybrid algorithm is validated on two classical benchmarks namely 1-D Fourier thermal problem and Couette shear flow problem.Both the accuracy and efficiency of the hybrid algorithm are discussed.As an application,the hybrid algorithm is employed to simulate thermal transpiration coefficient in the free-molecule regime for a system with atomically smooth surface.Result is utilized to validate the coefficients calculated from the pure DSMC simulation with Maxwell and Cercignani-Lampis gas-wall interaction models.