NAMD is a molecular dynamics program designed for high-performance simulations of very large biological objects on central processing unit (CPU)-and graphics processing unit (GPU)-based architectures. NAMD offers scalable performance on petascale parallel supercomputers consisting of hundreds of thousands of cores, as well as on inexpensive commodity clusters commonly found in academic environments. It is written in C++ and leans on Charm++ parallel objects for optimal performance on low-latency architectures. NAMD is a versatile, multipurpose code that gathers state-of-the-art algorithms to carry out simulations in apt thermodynamic ensembles, using the widely popular CHARMM, AMBER, OPLS and GROMOS biomolecular force fields. Here, we review the main features of NAMD that allow both equilibrium and enhanced-sampling molecular dynamics simulations with numerical efficiency. We describe the underlying concepts utilized by NAMD and their implementation, most notably for handling long-range electrostatics, controlling the temperature, pressure and pH, applying external potentials on tailored grids, leveraging massively parallel resources in multiple-copy simulations, as well as hybrid QM/MM descriptions. We detail the variety of options offered by NAMD for enhanced-sampling simulations aimed at determining free-energy differences of either alchemical or geometrical transformations, and outline their applicability to specific problems. Last, we discuss the roadmap for the development of NAMD and our current efforts towards achieving optimal performance on GPUbased architectures, for pushing back the limitations that have prevented biologically realistic billion-atom objects to be fruitfully simulated, and for making large-scale simulations less expensive and easier to set up, run and analyze. NAMD is distributed free of charge with its source code at www.ks.uiuc.edu.

Imaging-guided site-specific photothermal therapy (PTT) of glioma and other tumors in central nervous system presents a great challenge for the current nanomaterial design. Herein, an in situ solid-state transformation method was developed for the preparation of multicolor highly crystalline carbon nanodots (HCCDs). The synthesis yields 6-8 nm-sized HCCDs containing a highly crystalline carbon nanocore and a hydrophilic surface, which therefore simultaneously provide strong photoacoustic and photothermal performances as well as tunable fluorescence emission. In vitro and in vivo results demonstrate that the novel HCCDs have high water dispersity and good biocompatibility, but potent tumor cell killing upon near-infrared irradiation. As demonstrated in U87 glioma-bearing mice, HCCDs specifically accumulate in brain tumors and facilitate dual-modal imaging-guided PTT, with therapeutic antitumoral effects without any apparent damage to normal tissues.

Bacterial determination, emerging as a critical step in the understanding of increasingly serious bacterial contaminations, remains a major challenge. Herein, a novel chemiluminescence biosensor was exploited for the ultrasensitive determination of nuclease activity and bacteria, in which, hemin, the chemiluminescent (CL) tag molecule was encapsulated into ordered mesopores of mesoporous silica nanoparticles with a specific DNA gate. The capped DNA could be specifically switched upon exposure to the DNA nuclease or bacterial lysate and allowed for an increased release of the encapsulated hemin, which therefore resulted in an obviously enhanced CL signal for the luminol−H 2 O 2 system. Attributed to this unique behavior with the linear or sigmoidal relationship between CL intensity and DNA nuclease or bacterial concentration, the as-prepared CL biosensor could detect S1 nuclease activity in the concentration range 0.01−10.0 U with a detection limit of 0.1 mU, and Escherichia coli O157:H7 (E. coli) or Staphylococcus aureus (S. aureus) in the concentration ranges 10 1 to 10 9 cfu mL −1 . The detection limit of E. coli and S. aureus was calculated to be 3.0 and 2.5 cfu mL −1 , respectively, which was comparable or even better than that of previous studies. Thus, this detection method could achieve detectable levels without cell enrichment overnight. Moreover, the proposed biosensing system could be conducted in the homogeneous solution without separation and washing, greatly improving the reaction efficiency and simplifying the procedure. As expected, the novel CL biosensor promised a great potential for simple and convenient detection of nuclease and bacteria in fields such as food bacterial contamination, pharmaceuticals, and clinical analysis.

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were obtained with an Olympus IX71 microscope. At the same time, the transendothelial electrical resistance (TEER) value (>300 Ω cm −2 ) was monitored to validate the reliability of these models. No obvious reduction in the TEER values was observed during the whole experiment, indicating that the transport of drug system did not compromise the BBB barrier properties. All animals were maintained in a pathogen-free environment and fed ad libitum. The procedures for the care and use of animals were approved by the Ethics Committee of Nantong University and all institutional and governmental regulations concerning the ethical use of animals followed.