Multi-dimensional visualization for the morphology of lubricant stearic acid particles and their distribution in tablets

The shapes of particles and their distribution in tablets, controlled by pretreatment and tableting process, determine the pharmaceutical performance of excipient like lubricant. This study aims to provide deeper insights to the relationship of the morphology and spatial distribution of stearic acid(SA) with the lubrication efficiency, as well as the resulting tablet property. Unmodified SA particles as flat sheet-like particles were firstly reprocessed by emulsification in hot water to obtain the reprocessed SA particles with spherical morphology. The three-dimensional(3 D) information of SA particles in tablets was detected by a quantitative and non-invasive 3 D structure elucidation technique, namely, synchrotron radiation X-ray micro-computed tomography(SR-μCT). SA particles in glipizide tablets prepared by using unmodified SA(GUT), reprocessed SA(GRT), as well as reference listed drug(RLD) of glipizide tablets were analyzed by SR-μCT. The results showed that the reprocessed SA with better flowability contributed to similarity of breaking forces between that of GRT and RLD. SA particles in GRT were very similar to those in RLD with uniform morphology and particle size, while SA particles in GUT were not evenly distributed. These findings not only demonstrated the feasibility of SR-μCT as a new method in revealing the morphology and spatial distribution of excipient in drug delivery system, but also deepened insights of solid dosage form design into a new scale by powder engineering.

The Influence of Two Natural Reinforcement Fibers on the Hygrothermal Properties of Earthen Plasters in Mogao Grottoes of China

Murals in Mogao Grottoes consist of three parts:support layer,earthen plasters and paint layer.The earthen plasters play a key role in the preservation of murals.It is a mixture of Dengban soil,sand,and plant fiber.Two different natural fibers,hemp fiber and cotton fiber,were reinforced to earthen plasters in the same percentage to evaluate the influence on hygrothermal performance.The two types of earthen plasters were studied:one containing hemp fiber in the fine plaster(HFP)and the other containing cotton fiber in the fine plaster(CFP).Specific heat capacity,dry thermal conductivity,water vapor permeability,and sorption isotherms were investigated.The results showed that the difference between two natural fibers has much more impact on the hygric properties(water vapor permeability and sorption isotherms)of earthen plasters than on their thermal performance(specific heat capacity and dry thermal conductivity).The CFP with higher density has higher thermal conductivity than the HFP with lower density.But no significant differences of specific heat capacity were observed.Compared with HFP,CFP used in murals can reduce the rate of water transfer and prevent salt from transferring water to the mural surface.The overall findings highlight that all these features of CFP are beneficial to the long-term preservation of murals.The study of the earthen plasters in Mogao Grottoes is of general significance,and the measured properties can be used to obtain coupled heat and moisture analysis of the earthen plasters and to dissect the degradation mechanism of murals.

Determination and Analysis on Heat of Trapezoidal Soil Wall in Solar Greenhouse

Solar greenhouse with trapezoidal soil wall is widely used due to its good heat retaining property and cost efficiency.In this study, solar irradiance, heat flux and the temperature 0.05 and 0.3 m from the inner surface of the wall at the upper,middle and lower measured positions were determined to study the thermal condition of the trapezoidal soil wall in solar greenhouse. The results showed: first, both the solar irradiance and the temperature increased from the upper to the lower measured position. Second, the heat absorption also increased from the upper to the lower measured position. In clear day, the heat absorption at the three measured positions accounted for 31.4%, 32.6% and 36.0% of the total amount of heat absorption of the whole wall. In cloudy day, the heat absorption at the three measured positions were 0.249, 0.370 and 0.440 MJ/m^2, which accounted for 23.5%, 35.0% and 41.4% of the total amount of heat absorption of the whole wall. When P<0.05, the heat fluxes were strikingly different between the upper and lower measured positions. But when P<0.01, the heat flux had no big difference among the three measured positions. Third, in clear day, the heat emission was the biggest at the middle measured position and smallest at the upper measured position. The heat emission at the three measured positions accounted for 27.5%, 36.7%and 35.8% of the total amount of heat emission of the whole wall. And the heat emission between the middle and lower measured position was not strikingly different. In cloudy day, the heat emission was the biggest at the lower measured position and smallest at the upper measured position. The average heat emission at the three measured positions accounted for 26.1%,36.4% and 37.4% of the total amount of heat emission of the whole wall. Fourthly, correlativity, the solar irradiance directly influenced the heat absorption and had close relation with heat emission. And heat emission again had close relation with the temperature in the greenhouse. Solar irradiance directly influences the thermal condition of a solar green house. It is hoped that this study can be referred to optimize trapezoidal structure and to improve the thermal conditions of the solar greenhouse.

Disciplinary development of global health academic degree programs in China

This study aims to provide a brief overview of the history and development of global health education(GHE)as academic degree programs worldwide,and to identify GHE’s development opportunities and obstacles in China.This is a state-of-the-art review of published and unpublished information that described and evaluated disciplinary development of global health degree programs worldwide,written in English,and published or shared between 1990 and 2020.Data were derived from official websites of leading global health institutions,like“Google Scholar”,“PubMed”,and unpublished information such as presentation files and unpublished manuscripts collected from knowledgeable leaders in the field.We retrieved and reviewed a total of 35 articles and a large amount of unpublished information or sources on the internet.Global Health emerged as a new discipline around the end of the last millennium and proliferated in the last two decades in developed nations,especially the United States and the United Kingdom.The development of China’s GHE programs was built on China’s increasing engagement in global health affairs and research.In 2012,Wuhan University established the first official global health department in China.Several universities such as Peking University and Duke Kunshan University subsequently set up departments or programs to offer undergraduate and postgraduate majors and degrees.The first school-level global health unit was established in Shanghai in 2019.The Consortium of Chinese Universities for Global Health(CCUGH)grew from 10 founding members in 2013 to 25 in 2020.Major desirable attributes“unique”to students majoring in global health include global-mindedness,health interests,compassion,intercultural sensitivity,and adventurous spirit.Graduates from GHE programs have a diverse set of career choices spanning research,government,not-for-profit,and private sector occupations.We identified a number of strengths,weaknesses,opportunities,and threats to the future development of GHE in China.To ensure sustainable future growth,we advocate addressing the following key aspects:(1)clearer disciplinary distinctions;(2)multidisciplinary collaborations;(3)public-sector investments;and(4)non-public sectors participation.Amidst China’s increasing engagement in health affairs globally and the proliferation of GHE programs in developed nations,China has experienced fast growth in GHE degree programs since 2012 while a number of challenges remain for its future development.

Current Situation and Countermeasures of Platycodon grandiflorus Industry Development in Shandong Province

In order to promote the green,healthy and sustainable development of Platycodon grandiflorus industry,the current situations of P.grandiflorus industry development in Shandong Province were analyzed.That is,an advantageous area has been gradually formed;product processing is diversified;industrialization development pattern is gradually emerging.Three problems in the development of P.grandiflorus industry were deeply analyzed.That is,it is difficult to control product quality;the problem of soil obstacles to continuous cropping is serious;the problem of talent shortage is prominent.Four countermeasures for the next development were put forward as follows:increasing government support,strengthening the construction of talent team,implementing crop rotation or intercropping,and increasing technology promotion.

Cretaceous integrative stratigraphy,biotas,and paleogeographical evolution of the Qinghai-Tibetan Plateau and its surrounding areas

The Cretaceous Period is a vital time interval in deciphering the evolutionary history of the Neo-Tethys Ocean and the convergence of different plates and blocks across the Qinghai-Tibetan Plateau.A detailed stratigraphic framework and paleogeographic patterns are the basis for understanding the evolution of the Neo-Tethys Ocean and the formation of the QinghaiTibetan Plateau.Here,the Cretaceous stratigraphy,biota,paleogeography,and major geological events in the Qinghai-Tibetan Plateau are analyzed to establish an integrative stratigraphic framework,reconstruct the paleogeography during the Cretaceous Period,and decode the history of the major geological events.The Cretaceous rocks of the Qinghai-Tibetan Plateau and its surrounding area are predominantly marine deposits,with a small amount of interbedded marine-terrestrial and terrestrial conponents.The Indus-Yarlung Tsangpo Suture Zone was responsible for the deposition of deep marine sediments dominated by ophiolite suites and radiolarian silicalite.To the south,the Tethys Himalayas and Indus Basin received marine sediments of varying depths and lithology;to the north,the Xigaze and Ladakh forearc basins are also filled with marine sediments.The Lhasa Block,Karakorum Block,western Tarim Basin,and West Burma block consist of shallow marine,interbedded marine-terrestrial,and terrestrial sediments.The Qiangtang Basin and other areas are dominated by terrestrial sedimentation.The Cretaceous strata of the Qinghai-Tibetan Plateau and its surrounding areas are widely distributed and diversified,with abundant foraminifera,calcareous nannofossils,radiolarians,ammonites,bivalves,and palynomorphs.On the basis of integrated lithostratigraphic,biostratigraphic,geochronologic,and chemostratigraphic analyses,we proposed herein a comprehensive stratigraphic framework for the Cretaceous Period of the eastern Neo-Tethys.By analyzing the Cretaceous biota of different biogeographic zones from eastern Neo-Tethys and its surrounding areas,we reconstructed the paleobiogeography of different periods of eastern NeoTethys.The Cretaceous paleogeographic evolution of the Qinghai-Tibetan Plateau and its surrounding areas can be divided into three phases:(1)gradual breakup of the Indian Plate from the Australia-Antarctica continent and the early collision phase of the Lhasa-Qiangtang blocks(145-125 Ma);(2)northward drift of the Indian Plate and the collision phase of the Lhasa-Qiangtang blocks(125-100 Ma);(3)rapid northward drift of the Indian Plate,formation of the Tarim-Tajik-Karakorum Bay,and early uplift of the Gangdise Mountains(100-66 Ma).The Indus-Tethys Himalayan biota underwent a transition from the cold-water type in the high latitudes of the southern hemisphere to the warm-water type near the equator from the Early Cretaceous to the MidCretaceous.The biodiversity and abundance of the eastern Neo-Tethys Ocean increased gradually in the Early Cretaceous,peaking in the Mid-Cretaceous,and decreased sharply during the late Late Cretaceous(late Maastrichtian).Along with the northward drift of the Indian Plate and subduction of the Neo-Tethys,the eastern Neo-Tethys and its surrounding areas experienced a series of major geological events,including the formation of the large igneous province,oceanic anoxia events,and mass extinction,etc.

Visualization of nasal powder distribution using biomimetic human nasal cavity model

Nasal drug delivery efficiency is highly dependent on the position in which the drug is deposited in the nasal cavity.However,no reliable method is currently available to assess its impact on delivery performance.In this study,a biomimetic nasal model based on three-dimensional(3D)reconstruction and three-dimensional printing(3DP)technology was developed for visualizing the deposition of drug powders in the nasal cavity.The results showed significant differences in cavity area and volume and powder distribution in the anterior part of the biomimetic nasal model of Chinese males and females.The nasal cavity model was modified with dimethicone and validated to be suitable for the deposition test.The experimental device produced the most satisfactory results with five spray times.Furthermore,particle sizes and spray angles were found to significantly affect the experimental device’s performance and alter drug distribution,respectively.Additionally,mometasone furoate(MF)nasal spray(NS)distribution patterns were investigated in a goat nasal cavity model and three male goat noses,confirming the in vitro and in vivo correlation.In conclusion,the developed human nasal structure biomimetic device has the potential to be a valuable tool for assessing nasal drug delivery system deposition and distribution.

A multi-parameter-induced activation of gas therapeutic platform to remarkably amplify photodynamic therapy efficacy

Gas therapy(GT)combined with photodynamic therapy(PDT)is an effective strategy to compensate for the PDT limitation caused by the hypoxic tumor microenvironment,which can greatly improve PDT efficacy.The uncontrolled leakage of gas molecules during delivery seriously hinders its practical biological application.Herein,we report a multifunction nanomedicine that enables precise gas therapy(including carbon monoxide(CO)release and H_(2)S depletion)using a multi-parameter-induced activation gas release strategy,enlarging the PDT efficacy.This nanomedicine uses a disulfide bond to covalently link a photosensitizer with the CO donor 3-hydroxyflavone(3-HF).The disulfide bond can be specifically consumed in H_(2)S-rich tumor areas,releasing the CO donor(3-HF),and also depleting H_(2)S.More importantly,the photo-controlled production of^(1)O_(2)can induce 3-HF precise release of CO in the tumor location.Such H_(2)S,light,and^(1)O_(2)multi-parameter-induced activation of gas release strategy ensures the accuracy of GT to amplify PDT efficiency.As expected,in vitro and in vivo investigations show that GT makes up for the PDT limitation,exhibiting the highest tumor therapeutic effect.This multi-parameter-activated design strategy provides a new way to improve the precision and efficacy of multimodal synergistic therapy of tumors.

Hantzsch Ester Modified Asymmetric BODIPY Probe with Ultra-high Sensitivity for Ultra-fast Detection of Endogenous Hypochlorite in Living Cells

Hypochlorite(ClO^(-))is an important reactive oxygen species produced by the immune system to fight off invading pathogens,but its over-expression can interfere with normal physiological process and induce serious diseases.Although a variety of molecular probes have been reported for detecting ClO^(-),the development of advanced fluorescent tools with faster response and higher sensitivity to precisely monitor ClO^(-)remains a challenge.In this work,two Hantzsch ester(a derivative of 1,4-dihydropyridine)derived fluorescent probes MeDHP-BCl and MeDHP-PhBCl were constructed based on asymmetric BODIPY-matrix.These probes exhibit significant fluorescence turn-on in the ultra-sensitive(detection limit<1 nmol/L)and ultra-fast response(≤5 s)to ClO^(-).The reaction has been determined to be a highly selective N-chlorination of Hantzsch ester which cannot be activated by various common bioactive species,including nitric oxide(NO)that could oxidize Hantzsch ester under aerobic physiological conditions in most reports.MeDHP-PhBCl possessed a relatively longer fluorescence emission wavelength and higher quantum yield after activation,while more notably,MeDHP-BCl displayed lower cytotoxicity and more remarkable fluorescence increment in the response to ClO^(-),enabling selective and precise visualization of endogenous ClO^(-)over-expression in living RAW264.7 cells.

A dual-modality hydrogen sulfide-specific probe integrating chemiluminescence with NIR fluorescence for targeted cancer imaging

Taking apart in numerous physiological and pathological activities,hydrogen sulfide(H_(2)S)has been selected as an excellent target spot for the early diagnosis of cancer.So far,there are many mature probes that apply single optical imaging to monitor endogenous H_(2)S.Nevertheless,a single modality is not an ideal method to afford accurate diagnostic information in comprehensive biological organisms.Herein,we developed a dual-modal imaging probe BWS.This designed probe showed a specific response to H_(2)S with both chemiluminescence and NIR fluorescence light-up.The concurrence of fluorescence and chemiluminescence signal provided“double insurances”for highly accurate monitoring of H_(2)S.Satisfactorily,this dual-modal imaging probe performed precise visualization of endogenous H_(2)S in living cells and in vivo.We envisaged that this chemiluminescence/fluorescence real-time dual-modality strategy for H_(2)S detection will expand and optimize the multimodal imaging methods for efficient diagnosis and treatment of cancer.

Deformation-induced interfacial-twin-boundary ω-phase in an Fe_(48)Mn_(37)Al_(15) body-centered cubic metastable alloy

Omega(ω)phase has a trigonal or hexagonal crystal structure and was first discovered inβ-type Ti-Cr alloys[1].Since then,theω-phase has been widely reported in numerous group IV transition metal(Ti,Ta,Hf,and Zr)based alloys[2–9].The morphologies ofω-phase could be particle-like(athermalω-phase)[10],ellipsoidal or cuboidal after aging(isothermalω-phase)[11],and plate-like after deformation(stress-relatedω-phase)[12].Amongst,the stressrelatedω-phase is usually located at the twinning boundary,thus also called interfacial-twin-boundary-ω(ITB-ω)phase.The formation of the ITB-ωphase is considered to be related to the formation of{112}bcc<111>mechanical twin(i.e.,{112}bcc twin)in bodycentered cubic(BCC)metals and alloys[13].

A new perspective of triptolide-associated hepatotoxicity:the relevance of NF-κB and NF-κB-mediated cellular FLICE-inhibitory protein

Previously,we proposed a new perspective of triptolide(TP)-associated hepatotoxicity:liver hypersensitivity upon lipopolysaccharide(LPS)stimulation.However,the mechanisms for TP/LPSinduced hepatotoxicity remained elusive.The present study aimed to clarify the role of LPS in TP/LPS-induced hepatotoxicity and the mechanism by which TP induces liver hypersensitivity upon LPS stimulation.TSF-αinhibitor,etanercept,was injected intraperitoneally into mice to investigate whether induction of TNF-αby LPS participated in the liver injury induced by TP/LPS co-treatment.Mice and hepatocytes pretreated with TP were stimulated with recombinant TNF-αto assess the function of TNF-αin TP/LPS co-treatment.Additionally,time-dependent MF-κB activation and NF-κB-mediated pro-survival signals were measured in vivo and in vitro.Finally,overexpression of cellular FLICEinhibitory protein(FLIP),the most potent NF-κB-mediated pro-survival protein,was measured in vivo and in vitro to assess its function in TP/LPS-induced hepatotoxicity.Etanercept counteracted the toxic reactions induced by TP/LPS.TP-treatment sensitized mice and hepatocytes to TNF-α,revealing the role of TNF-αin TP/LPS-induced hepatotoxicity.Mechanistic studies revealed that TP inhibited NF-κB dependent pro-survival signals,especially FLIP,induced by LPS/TNF-α.Moreover,overexpression of FLIP alleviated TP/LPS-induced hepatotoxicity in vivo and TP/TNF-α-induced apoptosis in vitro.Mice and hepatocytes treated with TP were sensitive to TNF-α,which was released from LPS-stimulated immune cells.These and other results show that the TP-induced inhibition of NF-κB-dependent transcriptional activity and FLIP production are responsible for liver hypersensitivity.

On-the-fly active learning of interpretable Bayesian force fields for atomistic rare events

Machine learned force fields typically require manual construction of training sets consisting of thousands of first principles calculations,which can result in low training efficiency and unpredictable errors when applied to structures not represented in the training set of the model.This severely limits the practical application of these models in systems with dynamics governed by important rare events,such as chemical reactions and diffusion.We present an adaptive Bayesian inference method for automating the training of interpretable,low-dimensional,and multi-element interatomic force fields using structures drawn on the fly from molecular dynamics simulations.Within an active learning framework,the internal uncertainty of a Gaussian process regression model is used to decide whether to accept the model prediction or to perform a first principles calculation to augment the training set of the model.The method is applied to a range of single-and multi-element systems and shown to achieve a favorable balance of accuracy and computational efficiency,while requiring a minimal amount of ab initio training data.We provide a fully opensource implementation of our method,as well as a procedure to map trained models to computationally efficient tabulated force fields.

DeST 3.0:A new-generation building performance simulation platform

Buildings contribute to almost 30%of total energy consumption worldwide.Developing building energy modeling programs is of great significance for lifecycle building performance assessment and optimization.Advances in novel building technologies,the requirements of high-performance computation,and the demands for multi-objective models have brought new challenges for building energy modeling software and platforms.To meet the increasing simulation demands,DeST 3.0,a new-generation building performance simulation platform,was developed and released.The structure of DeST 3.0 incorporates four simulation engines,including building analysis and simulation(BAS)engine,HVAC system engine,combined plant simulation(CPS)engine,and energy system(ES)engine,connected by air loop and water loop balancing iterations.DeST 3.0 offers numerous new simulation features,such as advanced simulation modules for building envelopes,occupant behavior and energy systems,cross-platform and compatible simulation kernel,FMI/FMU-based co-simulation functionalities,and high-performance parallel simulation architecture.DeST 3.0 has been thoroughly evaluated and validated using code verification,inter-program comparison,and case-study calibration.DeST 3.0 has been applied in various aspects throughout the building lifecycle,supporting building design,operation,retrofit analysis,code appliance,technology adaptability evaluation as well as research and education.The new generation building simulation platform DeST 3.0 provides an efficient tool and comprehensive simulation platform for lifecycle building performance analysis and optimization.

Four Methods to Estimate Minimum Miscibility Pressure of CO2-Oil Based on Machine Learning

Summary of main observation and conclusion CO2 flooding accounts for a considerable proportion in gas flooding.Using CO2 as a gas displacement agent is benefit for enhanced oil recovery(EOR),and the alleviation of the greenhouse effect by the permanent storage of CO2 in the crust.Minimum miscibility pressure(MMP)of CO2-oil is a key factor affecting EOR,which determines the yield and economic benefit of crude oil recovery.Therefore,it is of great importance to use fast,accurate and cheap prediction methods for MMP estimation.In the present study,to evaluate the reliability of four recently developed prediction models based on machine learning(i.e.,neural network analysis(NNA),genetic function approximation(GFA),multiple linear regression(MLR),partial least squares(PLS)),136 sets of data are selected for calculation via outlier analysis from 147 sets of data.Afterwards,we compared the four models with existing prediction models from the literature.The analysis of correlation coefficients and multiple error functions shows that the four models can solve the MMP prediction problem well,and the model using intelligent algorithm has a higher prediction accuracy than the simple linear model.Besides,intelligent methods based on similarity algorithm have little difference from each other.Finally,a sensitivity analysis was conducted.

Discussion on the relationship between the Yanshanian Movement and cratonic destruction in North China

The relationship between the Yanshanian Movement, destruction of the North China Craton(NCC), and subduction of the western Pacific plate is crucial to reconstructing the middle-late Mesozoic tectonic evolution of the eastern Asian continent and margin. The Yanshanian Movement was a globally important change in crustal tectonics during the Middle-Late Jurassic.Previous research has systematically studied the formation and evolution of the Yanshanian Movement, focusing on the timing and location of tectonic movements, and the sedimentary and volcanic strata. However, the question of whether the tectonic activity occurred globally, and the characteristics of the Yanshanian Movement remain debated. The main argument is that if a tectonic movement can only be characterized by a regional or local disconformity, and if the tectonic movement occurred in an intracontinental setting, with extensive deformation but with no disconformity despite volcanic eruptions and magmatic intrusions, accompanied by changes in crustal structure and composition, should it be defined as a tectonic event or process? This question requires further analysis. The main aim of this study is to distinguish whether the Yanshanian Movement is a local feature of the eastern Asian continent, or a global tectonic event related to subduction of the Pacific Plate. In this paper, based on previous research, we discuss the spatial and temporal evolution of the Yanshanian Movement, the controlling tectonic mechanisms, and its relationship to the reactivation and destruction of the NCC and the subduction of the western Paleo-Pacific slab.We emphasize that the Yanshanian Movement in the Middle-Late Jurassic is distinct from the lithospheric thinning responsible for Early Cretaceous extension and magmatism related to the destruction of the NCC. The various tectonic stages were constrained by different dynamics and tectonic settings, or by different tectonic events and processes. Therefore, it is possible that the deformation and reactivation of the NCC contributed to its destruction, in addition to lithospheric thinning. Finally, we discuss whether the Yanshanian Movement was associated with the destruction of the NCC.

Targeted metabolic analysis of nucleotides and identification of biomarkers associated with cancer in cultured cell models

Cancer,like other diseases accompanied by metabolic changes,shows characteristic DNA/RNA modifications and activities of modifying enzymes,resulting in fluctuations in nucleoside levels.In this study,we undertook targeted metabolomic analyses of nucleotides in different cancer cell culture models using a sensitive and reproducible ion-pair HPLC method.The experimental data were analyzed by principal component analysis(PCA)to identify potential biomarkers in cancer cells,and statistical significance was determined by one-way analysis of variance.As a result,a clear differentiation of normal and tumor cells into two clusters was shown,indicating abnormal metabolism of nucleotides in tumor cells.Six variables(AMP,UDP,CTP levels with a significance of Po0.05;ATP,UTP and GMP levels with a significance of Po0.01)were considered as potential biomarkers;the content of AMP,UTP,GMP and ATP was significantly higher in cancer cells.The receiver operating characteristic(ROC)curve analysis allowed us to discriminate normal cells from tumor cells based on area under the curve(AUC).The sequence of their AUC values were:ATP(0.979)4UTP(0.938)4CTP¼GMP(0.896)4AMP(0.812)4UDP(0.792),so we conclude that ATP and UTP are the best potential biomarkers in tumor cells.This study may provide a valuable tool for studying minute alterations of intracellular nucleotide pools induced by anticancer/antiviral drugs,diseases or environmental factors.

Bayesian force fields from active learning for simulation of inter-dimensional transformation of stanene

We present a way to dramatically accelerate Gaussian process models for interatomic force fields based on many-body kernels by mapping both forces and uncertainties onto functions of low-dimensional features.This allows for automated active learning of models combining near-quantum accuracy,built-in uncertainty,and constant cost of evaluation that is comparable to classical analytical models,capable of simulating millions of atoms.Using this approach,we perform large-scale molecular dynamics simulations of the stability of the stanene monolayer.We discover an unusual phase transformation mechanism of 2D stanene,where ripples lead to nucleation of bilayer defects,densification into a disordered multilayer structure,followed by formation of bulk liquid at high temperature or nucleation and growth of the 3D bcc crystal at low temperature.The presented method opens possibilities for rapid development of fast accurate uncertainty-aware models for simulating long-time large-scale dynamics of complex materials.

Effects of antibiotic antitumor drugs on nucleotide levels in cultured tumor cells:an exploratory method to distinguish the mechanisms of antitumor drug action based on targeted metabolomics

Nucleotide pools in mammalian cells change due to the influence of antitumor drugs,which may help in evaluating the drug effect and understanding the mechanism of drug action.In this study,an ion-pair RP-HPLC method was used for a simple,sensitive and simultaneous determination of the levels of 12 nucleotides in mammalian cells treated with antibiotic antitumor drugs(daunorubicin,epirubicin and dactinomycin D).Through the use of this targeted metabolomics approach to find potential biomarkers,UTP and ATP were verified to be the most appropriate biomarkers.Moreover,a holistic statistical approach was put forward to develop a model which could distinguish 4 categories of drugs with different mechanisms of action.This model can be further validated by evaluating drugs with different mechanismsof action.This targeted metabolomics study may provide a novel approach to predict the mechanism of action of antitumor drugs.

Aldehyde Dehydrogenase 1 making molecular inroads into the differential vulnerability of nigrostriatal dopaminergic neuron subtypes in Parkinson’s disease

A preferential dysfunction/loss of dopaminergic(DA)neurons in the substantia nigra pars compacta(SNpc)accounts for the main motor symptoms of Parkinson’s disease(PD),the most common degenerative movement disorder.However,the neuronal loss is not stochastic,but rather displays regionally selectivity,indicating the existence of different DA subpopulations in the SNpc.To identify the underlying molecular determinants is thereby instrumental in understanding the pathophysiological mechanisms of PD-related neuron dysfunction/loss and offering new therapeutic targets.Recently,we have demonstrated that aldehyde dehydrogenase 1(ALDH1A1)is one such molecular determinant that defines and protects an SNpc DA neuron subpopulation preferentially affected in PD.In this review,we provide further analysis and discussion on the roles of ALDH1A1 in the function and survival of SNpc DA neurons in both rodent and human brains.We also explore the feasibility of ALDH1A1 as a potential biomarker and therapeutic target for PD.