Computational and theoretical modeling of intermediate filament networks:Structure,mechanics and disease

Intermediate filaments, in addition to microtubules and actin microfilaments, are one of the three major components of the cytoskeleton in eukaryotic cells. It was discovered during the recent decades that in most cells, intermediate filament proteins play key roles to reinforce cells subjected to large-deformation, and that they participate in signal transduction, and it was proposed that their nanome- chanical properties are critical to perform those functions. However, it is still poorly understood how the nanoscopic structure, as well as the combination of chemical composition, molecular structure and interfacial properties of these protein molecules contribute to the biomechanical properties of filaments and filament networks. Here we review recent progress in computational and theoretical studies of the intermediate filaments network at various levels in the protein＇s structure. A multiple scale method is discussed, used to couple molecular modeling with atomistic detail to larger-scale material properties of the networked material. It is shown that a finer-trains-coarser method- ology as discussed here provides a useful tool in understanding the biomechanical property and disease mechanism of intermediate filaments, coupling experiment and simulation. It further allows us to improve the understanding of associated disease mechanisms and lays the foundation for engineering the mechanical properties of biomaterials.

Three-dimensional FDEM numerical simulation of failure processes observed in Opalinus Clay laboratory samples

This study presents the first step of a research project that aims at using a three-dimensional （3D） hybridfinite-discrete element method （FDEM） to investigate the development of an excavation damaged zone（EDZ） around tunnels in a clay shale formation known as Opalinus Clay. The 3D FDEM was first calibratedagainst standard laboratory experiments, including Brazilian disc test and uniaxial compression test. Theeffect of increasing confining pressure on the mechanical response and fracture propagation of the rockwas quantified under triaxial compression tests. Polyaxial （or true triaxial） simulations highlighted theeffect of the intermediate principal stress （s2） on fracture directions in the model： as the intermediateprincipal stress increased, fractures tended to align in the direction parallel to the plane defined by themajor and intermediate principal stresses. The peak strength was also shown to vary with changing s2. 2014 Institute of Rock and Soil Mechanics, Chinese Academy of Sciences. Production and hosting byElsevier B.V. All rights reserved.

Synthesis and acaricidal activity of strobilurin-pyrimidine derivatives

Pyriminostrobin, a new acaricide, was discovered in our previous studies. Because introducing fluorine into organic compounds can increase bioactivity, pyriminostrobin was modified as a series of strobilurin-pyrimidine derivatives for biological screening. The compounds were characterized by 1H NMR, MS and elemental analysis. Preliminary bioassays demonstrated that compounds 7e and 7i exhibited significant control against Tetranychus cinnabarinus （Boisd.） at 0.625 mg L^-1, and their acaricidal potencies were higher than pyriminostrobin in a greenhouse. The relationship between structure and acaricidal activity was also studied.

Synthesis and Antifungal Activities of Novel Strobilurin Derivatives Containing Quinolin-2（1H）-one Moiety

To discover novel lead compounds with better antifungal activities, a series of novel strobilurin derivatives containing quinolin-2（1H）-one moiety was designed and synthesized via intermediate derivatization method. Their structures were characterized by means of 1H nuclear magnetic resonance（IH NMR）, 13C NMR and high reso- lution mass spectrometry（HRMS）. The biological assay results indicate that most target compounds exhibit good to excellent fungicidal activities against 10 plant pathogens. Compounds 4d, 5b and 5c possess 94.1%, 83.8% and 80.9% in vitro inhibition respectively against Rhizotonia cereals at the concentration of 50 μg/mL, which are better than that of the control agents. Especially, the inhibition activities of compound 4d against all of the tested fungi approach or exceed those of the controls. The structure-activity relationship was also discussed.

Design, synthesis, and fungicidal activity of novel 1,3,4-oxadiazole derivatives

Employing the intermediate derivatization method（IDM）, twenty novel 1,3,4-oxadiazole derivatives containing arylpyrazoloxyl moiety were designed and synthesized. The structures of the title compounds were identified by1 H NMR,13 C NMR, MS and elemental analyses, compound 4 was further identified by single-crystal X-ray diffraction. Antifungal activities against rice sheath blight（RSB） and sorghum anthracnose（SA） were evaluated by the mycelium linear growth rate method. Compounds 4, 16 and 20 displayed significant activities against RSB（EC50= 0.88 mg/L, 0.91 mg/L and 0.85 mg/L, respectively）,higher than the reference tebuconazole; While compound 3 exhibited higher activity against SA（EC50= 1.03 mg/L）, equal to commercial pyraclostrobin（EC50= 1.06 mg/L）. The study showed that compound 20 is a promising fungicide for further development.

Intrinsic chemiluminescence production from the degradation of haloaromatic pollutants during environmentally-friendly advanced oxidation processes:Mechanism,structure-activity relationship and potential applications

The ubiquitous distribution of halogenated aromatic compounds（XAr） coupled with their carcinogenicity has raised public concerns on their potential risks to both human health and the ecosystem. Recently, advanced oxidation processes（AOPs） have been considered as an＂environmentally-friendly＂ technology for the remediation and destruction of such recalcitrant and highly toxic XAr. During our study on the mechanism of metal-independent production of hydroxyl radicals（UOH） by halogenated quinones and H_2O_2, we found, unexpectedly, that an unprecedented UOH-dependent two-step intrinsic chemiluminescene（CL） can be produced by H_2O_2 and tetrachloro-p-benzoquinone, the major carcinogenic metabolite of the widely used wood preservative pentachlorophenol. Further investigations showed that, in all UOH-generating systems, CL can also be produced not only by pentachlorophenol and all other halogenated phenols, but also by all XAr tested. A systematic structure–activity relationship study for all 19 chlorophenolic congeners showed that the CL increased with an increasing number of Cl-substitution in general. More importantly, a relatively good correlation was observed between the formation of quinoid/semiquinone radical intermediates and CL generation. Based on these results, we propose that UOH-dependent formation of quinoid intermediates and electronically excited carbonyl species is responsible for this unusual CL production; and a rapid, sensitive,simple, and effective CL method was developed not only to detect and quantify trace amount of XAr, but also to provide useful information for predicting the toxicity or monitoring real-time degradation kinetics of XAr. These findings may have broad chemical, environmental and biological implications for future studies on halogenated aromatic persistent organic pollutants.

Synthesis and bioactivity of novel coumarin derivatives containing(E)-methyl 2-(methoxyimino)-2-phenylacetates

Ten coumarin derivatives containing（E）-methyl 2-（methoxyimino）-2-phenylacetate were synthesized and bioassayed.The compounds were identified by IR,~1H NMR and elemental analyses.The test results indicated that compound 5j（R^1 is methyl and R^2 is n-C_6H_（13）） was the optimal structure in this paper with good fungicidal activity against CDM（85%） at 6.25 mg/L concentration.