肿瘤力学生物学

肿瘤是指机体在各种致瘤因子作用下局部细胞增生所形成的新生物。按照危害性,肿瘤可大致分为良性肿瘤和恶性肿瘤(癌症)两大类。按照组织形态,癌症可分为固体恶性肿瘤和血液癌症(简称血癌)两大类,本文主要关注前者。癌症一般发生侵袭性生长,易转移到其它组织中,严重威胁人类健康,是死亡率非常高的一种疾病~[1]。超过85%的癌症死亡是由于固体肿瘤导致的~[2]。

Coarse grained molecular dynamics and theoretical studies of carbon nanotubes entering cell membrane

Motivated by recent experimental observations that carbon nanotubes （CNT） can enter animal cells, here we conduct coarse grained molecular dynamics and theoretical studies of the intrinsic interaction mechanisms between CNT＇s and lipid bilayer. The results indicate that CNT-cell interaction is dominated by van der Waals and hydrophobic forces, and that CNT＇s with sufficiently small radii can directly pierce through cell membrane while larger tubes tend to enter cell via a wrapping mechanism. Theoretical models are proposed to explain the observed size effect in transition of entry mechanisms.

Molecular dynamics simulation of peeling a DNA molecule on substrate

Molecular dynamics （MD） simulations are performed to study adhesion and peeling of a short fragment of single strand DNA （ssDNA） molecule from a graphite surface. The critical peel-off force is found to depend on both the peeling angle and the elasticity of ssDNA. For the short ssDNA strand under investigation, we show that the simulation results can be explained by a continuum model of an adhesive elastic band on substrate. The analysis suggests that it is often the peak value, rather than the mean value, of adhesion energy which determines the peeling of a nanoscale material.

Molecular simulation of diffusion of rigidity-tuned nanoparticles in biological hydrogels

The penetration capability of the drug nano-carriers (NCs) in biological hydrogels, such as mucus and tumor interstitial matrix, would typically influence the efficiency of drug delivery. Understanding the effect of the physicochemical property of the drug carriers on their diffusion capability in biological hydrogel becomes important for designing and optimizing the nano-carriers. Here, using a coarse-grained molecular dynamics model, we studied how the rigidity of NCs affected their diffusivity in biological hydrogel. The results showed that semi-elastic NCs have higher diffusivity than the hard and the soft NCs. Furthermore, the affinity between the NCs and biological hydrogels and the size ratio between the hydrogel meshes and NCs have also affected the diffusivity of the NCs. Further analysis revealed the mechanism that the deformation of the NCs dominates their diffusivity. These findings demonstrated that the rigidity of NCs is a key parameter in designing efficient NCs for deep penetration into the biological hydrogels.

The Mechanics of Target Drug Delivery

The rapid development of nanotechnology enables the successful application of target drug delivery,which provides new hope for the clinical examination and treatment.In the whole process of drug delivery,we foundcouple of mechanics problems existed,including the transportation of nanocarriers,the molecular level target and the cellular uptake of nanoparticles.In recent years,we focused on the investigation of diffusion of drug delivery systems in mucus of gastrointestinal(GI)tract and tumor intestinal.We studied the stiffness effect and geometric effect of nanoparticles in cell internalization,and found that the shape,stiffness and adhesion of nanoparticle-based drug carriers affect their transportation in biological tissues.We revealed the internal mechanism with a theoretical model for the diffusion of nanoparticles in an adhesive/nonadhesive polymer network.These findings shed new light on the design of NP-based drug delivery systems targeted to mucosal and tumor sites that possess a fibrous structure/porous medium.

Energy barrier for configurational transformation of graphene nanoribbon on nanotube

A graphene nanoribbon （GNR） has two basic configurations when winding on the outer surface of a carbon nanotube （CNT）： helix and scroll. Here the transformation between the two configurations is studied utilizing molecular dynamics simulations. The energy barrier during the transformation as well as its relationship with the interfacial energy and the radius of CNT are investigated. Our work offers further insights into the formation of desirable helix/scroll of GNR winding on nanotubes or nanowires, and thus can enable novel design of potential graphene-based electronics.

Study on the Theoretical Limitation of the Mid-Infrared PbSe N⁺-P Junction Detectors at High Operating Temperature

This paper provides a theoretical study and calculation of the specific detectivity-D* limit of photovoltaic (PV) mid-wave infrared (MWIR) PbSe n+-p junction detectors operating at both room temperature and TE-cooled temperature. For a typical PbSe p-type doping concentration of 2 × 1017 cm-3 and with high quantum efficiency, the D* limits of a photovoltaic PbSe n+-p junction detector are shown to be 2.8 × 1010 HZ1/2/W and 3.7 × 1010 HZ1/2/W at 300 K and 240 K, with cut-off wavelength of 4.5 μm and 5.0 μm, respectively. It is almost one magnitude higher than the current practical MWIR PV detector. Above 244 K, the detector is Johnson noise limited, and below 191 K the detector reaches background limited infrared photodetector (BLIP) D*. With optimization of carrier concentration, D* and BLIP temperature could be further increased.

Enhanced sampling in molecular dynamics simulations and their latest applications--A review

Molecular dynamics(MD)simulations are capable of reproducing dynamic evolution at the molecular scale,but are limited by temporal scales.Enhanced sampling has emerged as a powerful tool to improve sampling efficiency,thereby extending the simulation timescales of a range of simulation studies in materials,chemistry,biology,nanoscience,and related fields.Here,we provide a systematic overview of established enhanced sampling methods and clarify the principles and interconnections between these methods.Furthermore,we categorically elaborate on the state-of-the-art applications of enhanced sampling in the last five years.Through these exemplified applications,we discuss the unique advantages of this technique,showing the prospects and challenges for its future development.This review could help researchers in different fields gain a comprehensive understanding of the enhanced sampling technique,and jointly facilitate its application and advancement.

Full reaction mechanism of hydrogen peroxide catalyzed by reductive CoP nanoparticles:the enzyme-like activity

The hydrogen peroxide(H2O2)catalyzed by nanoparticles(NPs)demonstrates potential broad applications in the field of biomedicine and environmental protection.However,a systematic understanding of the catalytic mechanism severely limited the rational design of NPs with better enzyme-like activity and selectivity.Here,compared with the widely concerned Fe3O4NPs,the decomposition process of H_(2)O_(2) on reductive Co P NPs and p H-regulated peroxidase-and catalase-like activities with 3,3′,5,5′-tetramethylbenzidine(TMB)as reductive substrates were explored.All results show that OH·radical intermediates generated from the decomposition of H2O2*/OOH*at acidic conditions and complexed with TMB via H-bonds(complexed OH·)are the principal oxidant of TMB rather than free OH·as reported.Besides,the produced O*/OH*on Co P NPs shows negligible oxidation activity due to the strong reducibility of catalysts.The high coverage of O*/OH*from the dissociation of H2O2(H2O)at neutral(alkaline)p H conditions on Co P NPs enhances the dehydrogenation of H_(2)O_(2) to O2,leading to the transition between peroxidase-and catalase-like activities.

Regulation of the cellular uptake of nanopartides by the orientation of helical polypeptides

Controlling the cellular interactio n and internal izatio n of polymer-modified nan oparticles (NPs) is of central importa nee to the developme nt of promisi ng nano medici nes. Here, we describe the use of synthetic polypeptides for NP surface coati ng and regulati on of their cellular uptake behaviors by simply switching the conformation and anchoring orientation. Our results show that gold NPs (AuNPs) coated with a helical poly(Y-(2-(2-(2-methoxyethoxy)ethoxy)ethoxy)esteryl「glutamate)(L-P(EG3Glu)5o) from the C-terminus ((L-C)-AuNPs) exhibit greater zeta potential and more cellular uptake (2.0-5.5 fold higher) than those coated with the same polypeptide but anchored from the N-terminus ((L-N)-AuNPs), or from both the C- and N-terminus at a 1/1 molar ratio ((L-C/L-N)-AuNPs). A similar orientation-regulated cellular internalization pattern is observed in D-P(EG3Glu)50 but not the unstructured DL-P(EG3Glu)5o-rnodified AuNPs, suggesting an important and universal role of the helix-derived macrodipole in cellular uptake. Moreover, this orientation-governed internalization is successfully reproduced in P(EG3Glu)50-coated gold nano rods (AuNRs), and applied to the desig n of doxorubici reloaded polypeptide micelles. Simulation study offers time-resolved in sights regarding the NP-membrane in teracti ons and membrane remodeling. Thus, our study provides a delicate way of regulating the surface chemistry of NPs and the subsequent NP-cell interactions. Moreover, the results highlight the uniqueness of polypeptides in NP surface engineering, and urge a more careful consideration on the polymer orientation effect.

The electrochemical performance of super P carbon black in reversible Li/Na ion uptake

Super P carbon black (SPCB) has been widely used as a conducting additive in Li/Na ion batteries to improve the electronic conductivity. However, there has not yet been a comprehensive study on its structure and electrochemical properties for Li/Na ion uptake, though it is important to characterize its contribution in any study of active materials that uses this additive in non-negligible amounts. In this article the structure of SPCB has been characterized and a comprehensive study on the electrochemical Li/Na ion uptake capability and reaction mechanisms are reported. SPCB exhibits a considerable lithiation capacity (up to 310 mAh g^(–1)) from the Li ion intercalation in the graphite structure. Sodiation in SPCB undergoes two stages: Na ion intercalation into the layers between the graphene sheets and the Na plating in the pores between the nano-graphitic domains, and a sodiation capacity up to 145 mAh g^(–1) has been achieved. Moreover, the influence of the type and content of binders on the lithiation and sodiation properties has been investigated. The cycling stability is much enhanced with sodium carboxymethyl cellulose (NaCMC) binder in the electrode and fluoroethylene carbonate (FEC) in the electrolyte; and a higher content of binder improves the Coulombic efficiency during dis-/charge.

Effect of defects on the electronic structure of a PbI2/MoS2 van der Waals heterostructure: A first-principles study

PbI2/MoS2,as a typical van der Waals(vdW)heterostructure,has attracted intensive attention owing to its remarkable electronic and optoelectronic properties.In this work,the effect of defects on the electronic structures of a PbI2/MoS2 heterointerface has been systematically investigated.The manner in which the defects modulate the band structure of PbI2/MoS2,including the band gap,band edge,band alignment,and defect energy-level density within the band gap is discussed herein.It is shown that sulfur defects tune the band gaps,iodine defects shift the positions of the band edge and Fermi level,and lead defects realize the conversions between the straddling-gap band alignment and valence-band-aligned gap,thus enhancing the light-absorption ability of the material.

Identifying MicroRNA and Gene Expression Networks Using Graph Communities

Integrative network analysis is powerful in helping understand the underlying mechanisms of genetic and epigenetic perturbations for disease studies. Although it becomes clear that microRNAs, one type of epigenetic factors, have direct effect on target genes, it is unclear how microRNAs perturb downstream genetic neighborhood. Hence, we propose a network community approach to integrate microRNA and gene expression profiles, to construct an integrative genetic network perturbed by microRNAs. We apply this approach to an ovarian cancer dataset from The Cancer Genome Atlas project to identify the fluctuation of microRNA expression and its effects on gene expression. First, we perform expression quantitative loci analysis between microRNA and gene expression profiles via both a classical regression framework and a sparse learning model. Then, we apply the spin glass community detection algorithm to find genetic neighborhoods of the microRNAs and their associated genes. Finally, we construct an integrated network between microRNA and gene expression based on their community structure. Various disease related microRNAs and genes, particularly related to ovarian cancer, are identified in this network. Such an integrative network allows us to investigate the genetic neighborhood affected by microRNA expression that may lead to disease manifestation and progression.

Single site catalyst with enzyme-mimic micro-environment for electroreduction of CO_(2)

Single site catalysts provide a unique platform for mimicking natural enzyme due to their tunable interaction between metal center and coordinated ligand.However,most works have focused on preparing structural and functional models of nature enzyme,with less reports also taking the local chemical environment,i.e.,functional/catalytic residues around the active site which is an essential feature of enzymes,into consideration.Herein,we report a Co-centered porphyrinic polymer containing the enzyme-mimic micro-environment,where the linker triazole over CoN4 site enables formation of hydrogen bond with the*COOH intermediate,thus promoting the electrocatalytic reduction of CO_(2).As-prepared catalyst achieves the CO_(2)-to-CO conversion of 5,788 h^(−1) turnover frequency value and near unit(~96%)faradaic efficiency at−0.61 V versus reversible hydrogen electrode.This strategy will bring new dimension of designing highly active single-site catalysts.

Molecular dynamics simulation of diffusion of nanoparticles in mucus

The rapid diffusion of nanoparticles （NPs） through mucus layer is critical for efficient transportation of NPs-loaded drug delivery system. To understand how the physical and surface properties of NPs affect their diffusion in mucus, we have developed a coarse-grained molecular dynamics model to study the diffusion of NPs in modeled mucus layer. Both steric obstruction and hydrodynamic interaction are included in the model capable of capturing the key characteristics of NPs＇ diffusion in mucus. The results show that both particle size and surface properties significantly affect the diffusivities of NPs in mucus. Furthermore, we find rodlike NPs can gain a higher diffusivity than spherical NPs with the same hydrodynamic diameter. In addition, the disturbed environment can enhance the diffusivity of NPs. Our findings can be utilized to design mucus penetrating NPs for targeted drug delivery system.

MECHANICS OF CARBON NANOSCROLLS: A REVIEW

Carbon nanoscrolls （CNSs） belong to the same class of carbon-based nanomaterials as carbon nanotubes but are much less studied in spite of their great potential for applications in nanotechnology and bioengineering. Fundamental description, understanding and regulation of such materials will ultimately lead to a new generation of integrated systems that utilize their unique properties. In this review, we describe some of the recent advances in theoretical investi- gation on structural and dynamical behavior of CNS, as well as relevant simulation techniques. Theoretically it has been found that a stable equilibrium core size of CNS can be uniquely determined or tuned from the basal graphene length, the interlayer spacing, the interaction energy between layers of CNS and the bending stiffness of graphene. Perturbations of the surface energy, which can be controlled by an electric field, will cause a CNS to undergo breathing oscillatory motion as well as translational rolling motion on a substrate. The tunable core size of CNS also enables it to serve potentially as transmembrane water channels in biological systems.

Mechanics of molecular beacons for mRNA detecting

Decoding genetic information is crucial for gene therapy and cancer diagnosis,which has attracted growing interest in the field of clinical medicine and life science.In this study,we conducted a comprehensive exploration to obtain the detection mechanism of molecular beacons from a mechanics point of view.The potential energy function of molecular beacon/target system is established firstly,based on which the profile of molecular beacons is solved by genetic algorithm optimization.The length of stem and the total energy are further calculated when the target is hybridized with loop and stem.The results show that the hybridization between target and stem is energetically favorable compared with that between target and loop,indicating a new detection strategy.These analyses may cast light on understanding the mechanism of molecular beacons detection,and further help to design novel molecular beacons with high resolution and quantification.

Methods for Population-Based eQTL Analysis in Human Genetics

Gene expression is a critical process in biological system that is influenced and modulated by many factors including genetic variation. Expression Quantitative Trait Loci（e QTL） analysis provides a powerful way to understand how genetic variants affect gene expression. For genome wide e QTL analysis, the number of genetic variants and that of genes are large and thus the search space is tremendous. Therefore, e QTL analysis brings about computational and statistical challenges. In this paper, we provide a comprehensive review of recent advances in methods for e QTL analysis in population-based studies. We first present traditional pairwise association methods, which are widely used in human genetics. To account for expression heterogeneity, we investigate the methods for correcting confounding factors. Next, we discuss newly developed statistical learning methods including Lasso-based models. In the conclusion, we provide an overview of future method development in analyzing e QTL associations. Although we focus on human genetics in this review, the methods are applicable to many other organisms.