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This paper collected 22 cases of explosion accidents in laboratories in China in the past 10 years, analyzed the causes of the accidents, and put forward measures of preventing and mitigating the hazards of explosion accidents by identifying the explosion hazards in laboratories, assessing the explosion risks, minimizing the explosion hazards, and preparing for possible explosion accidents. Specific preventive measures are the DATS principles: keep the Distance as far as possible, use the minimum Amount of explosives, shorten the residence Time, and use appropriate Shielding. [ABSTRACT FROM AUTHOR]

A study was conducted to determine the specific sequence of the coiled-coil interfaces in the lac repressor tetramerization domain. The results provide insight into the structural specificity in antiparallel four-stranded coiled coils of side chain packing which forms the tertiary structure of a functional protein.

The design of a recombinant peptide inhibitor, C52L that induces both the C-peptide and tryptophan rich regions is described. C52L binds to a peptide mimic of the amino-terminal coiled coli and potently inhibits in vitro infection of human T cells by diverse primary HIV-1 isolates and hence it might find a practical application as a vaginal or rectal microbicide to prevent HIV-1 infection.

The 1.15 [Angstrom] X-ray crystal structure of a short [alpha]-helix in which the N-terminal i and i + 4 main chain hydrogen bond is replaced with a carbon-carbon bond is reported. The structure indicates that the hydrogen-bond surrogate (HBS) derived [alpha]-helix resembles the structure of canonical [alpha]-helices and provides support for helix nucleation strategy.

Ag/ZnO heterostructure nanocatalysts with excellent photocatalytic performance are synthesized. The presence of metallic Ag nanoparticles and oxygen vacancy on the surface of ZnO nanorods promote the separation of photogenerated electron-hole pairs and enhances the photocatalytuc activity.

Low-dimensional ZnO nanocrystals with controlled size, aspect ratio and oxygen defects are prepared by using simple solvothermal and thermal treatment methods. It is shown that the photocatalytic activity of the ZnO nanocrystals is dependent on the type and concentration of oxygen defects.

A leucine-zipper peptide is used to investigate the first (a), fourth (d) and fifth (e) packing interactions, where the nonpolar valine side chains have replaced the three charged amino acids at the e positions. The results have shown that distinct van der Waals interaction beyond the 'a' and 'd' side chains can generate a diverse set of helix-helix interfaces and three-dimensional supercoil structures.

A protein-dissection method is used to identify and determine the X-ray crystal structure of a proteolytically resistant C-terminal transmembrane fusion domain (S2) core from human coronavirus NL63 (HCoV-NL63). The HCoV-NL63 S2 core structure has served as the starting point for addressing the role of proteolytic maturation in coronavirus membrane fusion and entry.

Solvothermal method was used to synthesize uniform quasicubic alpha-Fe2O3 nanoparticles by six identical planes {110}. The shape of the nanoparticles is controlled by the experimental parameters such as reaction duration and surfactant.

We report on the synthesis of poly(diethylene oxide-alt-oxymethylene), P(2EO-MO), via cationic ring-opening polymerization of the cyclic ether monomer, 1,3,6-trioxocane. We use a combined experimental and computational approach to study ion transport in electrolytes comprising mixtures of P(2EO-MO) and lithium bis(trifluoromethanesulfonyl) imide (LiTFSI) salt. Mixtures of poly(ethylene oxide) (PEO) and LiTFSI are used as a baseline. The maximum ionic conductivities, s, of P(2EO-MO) and PEO electrolytes at 90 °C are 1.1 × 10-3 and 1.5 × 10-3 S/cm, respectively. This difference is attributed to the Tg of P(2EO-MO)/LiTFSI (-12 °C), which is significantly higher than that of PEO/LiTFSI (-44 °C) at the same salt concentration. Self-diffusion coefficients measured using pulsed-field gradient NMR (PFG-NMR) show that both Li+ and TFSI- ions diffuse more rapidly in PEO than in P(2EO-MO). However, the NMR-based cation transference number in P(2EO-MO) (0.36) is approximately twice that in PEO (0.19). The transference number measured by the steady-state current technique, t+,ss, in P(2EO-MO) (0.20) is higher than in PEO (0.08) by a similar factor. We find that the product st+,ss is greater in P(2-EO-MO) electrolytes; thus, P(2EO-MO) is expected to sustain higher steady-state currents under dc polarization, making it a more efficacious electrolyte for battery applications. Molecular-level insight into the factors that govern ion transport in our electrolytes was obtained using MD simulations. These simulations show that the solvation structures around Li+ are similar in both polymers. The same is true for TFSI-. However, the density of Li+ solvation sites in P(2EO-MO) is double that in PEO. We posit that this is responsible for the observed differences in the experimentally determined transport properties of P(2EO-MO) and PEO electrolytes. [ABSTRACT FROM AUTHOR]

Heteroanion (HA) moieties have a key role in templating of heteropolyoxometalate (HPA) architectures, but clusters templated by two different templates are rarely reported. Herein, we show how a cross-shaped HPA-based architecture can self-sort the HA templates by pairing two different guests into a divacant {XYW15O54} building block, with four of these building block units being linked together to complete the cross-shaped architecture. We exploited this observation to incorporate HA templates into well-defined positions within the clusters, leading to the isolation of a collection of mixed-HA templated cross-shaped polyanions [(XYW15O[sub 54])[sub 4](WO[sub 2])[sub 4]][sup 32-/36-] (X = H-P, Y = Se, Te, As). The template positions have been unambiguously determined by single crystal X-ray diffraction, NMR spectroscopy, and high-resolution electrospray ionization mass spectrometry; these studies demonstrated that the mixed template containing HPA clusters are the preferred products which crystallize from the solution. Theoretical studies using DFT calculations suggest that the selective self-sorting originates from the coordination of the template in solution. The cross-shaped polyoxometalate clusters are redox-active, and the ability of molecules to accept electrons is slightly modulated by the HA incorporated as shown by differential pulse voltammetry experiments. These results indicate that the cross-shaped HPAs can be used to select templates from solution, and themselves have interesting geometries, which will be useful in developing functional molecular architectures based upon HPAs with well-defined structures and electronic properties. [ABSTRACT FROM AUTHOR]

Autophagy inducers represent new promising agents for the treatment of a wide range of medical illnesses. However, safe autophagy inducers for clinical applications are lacking. Inhibition of cdc2-like kinase 1 (CLK1) was recently found to efficiently induce autophagy. Unfortunately, most of the known CLK1 inhibitors have unsatisfactory selectivity. Herein, we report the discovery of a series of new CLK1 inhibitors containing the 1H-[1,2,3]triazolo[4,5-c]quinoline scaffold. Among them, compound 25 was the most potent and selective, with an IC50 value of 2 nM against CLK1. The crystal structure of CLK1 complexed with compound 25 was solved, and the potency and kinase selectivity of compound 25 were interpreted. Compound 25 was able to induce autophagy in in vitro assays and displayed significant hepatoprotective effects in the acetaminophen (APAP)-induced liver injury mouse model. Collectively, due to its potency and selectivity, compound 25 could be used as a chemical probe or agent in future mechanism-of-action or autophagy-related disease therapy studies. [ABSTRACT FROM AUTHOR]

A formalthio [3 3]-cyclization catalyzed by a DPEN-derivedchiral thiourea has been reported for the construction ofoptically active thiopyrano-indole annulated heterocyclic compoundsin high yields with excellent enantioselectivities. The high reactivitybetween indoline-2-thione (keto-S) and 2-benzylidenemalononitrilehas also been supported by density functional theory (DFT) calculations. [ABSTRACT FROM AUTHOR]

By the reactions of MnIII Schiff-base complexes with the tricyanometalate building block, [(Tp)Cr(CN)3]- (Tp = Tris(pyrazolyl) hydroborate), two couples of enantiomerically pure chiral cyano-bridged heterobimetallic one-dimensional (1D) chain complexes, [Mn((R,R)-Salcy)Cr(Tp)(CN)3∙1/4H2O∙1/2CH2Cl2]n (1) and [Mn((S,S)-Salcy)Cr(Tp)(CN)3∙1/4H2O∙1/2CH2Cl2]n (2) (Salcy = N,N'-(1,2-cyclohexanediylethylene)bis(salicylideneiminato) dianion), [Mn((R,R)-Salphen)Cr(Tp)(CN)3]n (3) and [Mn((S,S)-Salphen)Cr(Tp)(CN)3]n (4) (Salphen = N,N'-1,2-diphenylethylene-bis(salicylideneiminato) dianion), have been successfully synthesized. Circular dichroism (CD) spectra confirm the enantiomeric nature of the optically active complexes. Structural analyses reveal the formation of neutral cyano-bridged zigzag single chains in 1 and 2, and neutral cyano-bridged zigzag double chains in 3 and 4. Magnetic studies show that antiferromagnetic couplings are operative between CrIII and MnIII centers bridged by cyanide. Complexes 1 and 2 are the rare examples of chiral ferrimagnets; while complexes 3 and 4 exhibit a coexistence of chirality and spin-glass behavior in a 1D chain. [ABSTRACT FROM AUTHOR]

Herein we report the 1.15 Å X-ray crystal structure of a short α-helix in which the N-terminal i and i + 4 main chain hydrogen bond is replaced with a carbon-carbon bond. The structure shows that the hydrogen-bond surrogate (HBS) derived α-helix truly resembles the structure of canonical a-helices and provides unequivocal support for our helix nucleation strategy. [ABSTRACT FROM AUTHOR]

Using the tricyano precursor (Bu4N)[(Tp)Cr(CN)3] (Bu4N+ = tetrabutylammonium cation; Tp = tris(pyrazolyl)hydroborate), a pentanuclear heterometallic cluster [(Tp)2Cr2(CN)6Cu3(Me3tacn)3][(Tp)Cr(CN)3](ClO4)3·5H2O (1, Me3tacn = N,N′,N′-trimethyl-1,4,7-triazacyclononane), three tetranuclear heterometallic clusters [(Tp)2Cr2(CN)6Cu2(LOEt)2]·2.5CH3CN (2, LOEt = [(Cp)Co(P(O)(OEt)2)3], Cp = cyclopentadiene), [(Tp)2Cr2(CN)6Mn2(LOEt)2]·4H2O (3), and [(Tp)2Cr2(CN)6Mn2(phen)4](ClO4)2 (4, phen = phenanthroline), and a one-dimensional (1D) chain polymer [(Tp)2Cr2(CN)6Mn(bpy)]n (5, bpy = 2,2′-bipyridine) have been synthesized and structurally characterized. Complex 1 shows a trigonal bipyramidal geometry in which [(Tp)Cr(CN)3]- units occupy the apical positions and are linked through cyanide to [Cu(Me3tacn)]2+ units situated in the equatorial plane. Complexes 2-4 show similar square structures, where CrIII and MII (M = CuII or MnII) ions are alternatively located on the rectangle corners. Complex 5 consists of a 4,2-ribbon-like bimetallic chain. Ferromagnetic interactions between CrIII and CuII ions bridged by cyanides are observed in complexes 1 and 2. Antiferromagnetic interactions are presented between CrIII and MnII ions bridged by cyanides in complexes 3-5. Complex 5 shows metamagnetic behavior with a critical field of about 22.5 kOe at 1.8 K. [ABSTRACT FROM AUTHOR]

PSPP-1 was obtained from purple sweet potato, and the effects of PSPP-1 on the immune modulation on macrophage cells were investigated for the first time. PSPP-1 promoted RAW264.7 proliferation and increased the total cell percentage in DNA synthesis and mitosis phases, and the cell morphology changed in volume and appearance. Additionally, the RAW264.7 immune functions of phagocytic activity and nitric oxide, reactive oxygen species, and cytokine production were improved by PSPP-1. The western blot experiment showed that PSPP-1 could activate toll-like receptor 2 and toll-like receptor 4-mediated pathways, and the expressions of proteins in MyD88-dependent, mitogen-activated protein kinase (MAPK)-signaling, NF-κB-signaling, AP-1 signaling, and TRIF-dependent pathways were improved markedly. Molecular docking and Biolayer Interferometry study further indicated that PSPP-1 could recognize and bind TLR2 and TLR4 by targeting the binding sites with a strong affinity. It suggested that PSPP-1 could enhance immunity via TLR2- and TLR4-mediated pathways, and it could be explored as an immunomodulatory agent.

The differences in catalytic activity between two catalyst ligands of Buchwald-Hartwig amination reaction, BrettPhos versus RuPhos, were investigated using density functional theory (DFT) calculations. The reaction process consists of three consecutive steps: (1) oxidative addition, (2) deprotonation, and (3) reductive elimination. Among them, the rate-limiting step of Pd-BrettPhos catalytic system is oxidative addition but that of Pd-RuPhos catalytic system is reductive elimination due to their differences in steric hindrance and electronic structure. It was also revealed that amines with large-size substituents or halides with electron-withdrawing groups would reduce the activation energy barriers of the reactions. The insights gained from the calculations of the Buchwald-Hartwig amination reaction would be helpful for the rational designing of new catalysts and reactions., Competing Interests: The authors declare no competing financial interest., (Copyright © 2020 American Chemical Society.)

Autophagy inducers represent new promising agents for the treatment of a wide range of medical illnesses. However, safe autophagy inducers for clinical applications are lacking. Inhibition of cdc2-like kinase 1 (CLK1) was recently found to efficiently induce autophagy. Unfortunately, most of the known CLK1 inhibitors have unsatisfactory selectivity. Herein, we report the discovery of a series of new CLK1 inhibitors containing the 1H-[1,2,3]triazolo[4,5-c]quinoline scaffold. Among them, compound 25 was the most potent and selective, with an IC 50 value of 2 nM against CLK1. The crystal structure of CLK1 complexed with compound 25 was solved, and the potency and kinase selectivity of compound 25 were interpreted. Compound 25 was able to induce autophagy in in vitro assays and displayed significant hepatoprotective effects in the acetaminophen (APAP)-induced liver injury mouse model. Collectively, due to its potency and selectivity, compound 25 could be used as a chemical probe or agent in future mechanism-of-action or autophagy-related disease therapy studies.

We describe the structural optimization of a hit compound, 1-(4-(1H-pyrazolo[3,4-d]pyrimidin-4-ylamino)phenyl)-3-(3-methoxyphenyl)urea (1), which exhibits inhibitory activity but low potency against FLT3 and VEGFR2. A series of pyrazolo[3,4-d]pyrimidine derivatives were synthesized, and structure-activity relationship analysis using cell- and transgenic-zebrafish-based assays led to the discovery of a number of compounds that exhibited both high potency against FLT3-driven human acute myeloid leukemia (AML) MV4-11 cells and a considerable antiangiogenic effect in transgenic-zebrafish-based assays. The compound 1-(4-(1H-pyrazolo[3,4-d]pyrimidin-4-yloxy)phenyl)-3-(4-chloro-3-(trifluoromethyl)phenyl)urea (33), which exhibited the highest activity in preliminary in vivo anti-AML assays, was chosen for further anti-AML studies. The results demonstrated that compound 33 is a multikinase inhibitor that potently inhibits FLT3 and VEGFR2. In an MV4-11 xenograft mouse model, a once-daily dose of compound 33 at 10 mg/kg for 18 days led to complete tumor regression without obvious toxicity. Western blot and immunohistochemical analyses were performed to determine the mechanism of action of compound 33.

Structure-activity relationship (SAR) studies of 2-(quinazolin-4-ylthio)thiazole derivatives, which are for optimizing the in vitro and in vivo antiacute myeloid leukemia (AML) activity of a previously identified FLT3 inhibitor 2-(6,7-dimethoxyquinazolin-4-ylthio)thiazole (1), are described. SAR studies centering around the head (thiazole) and tails (6- and 7-positions) of the quinazoline moiety of 1 led to the discovery of a series of compounds that exhibited significantly increased potency against FLT3-driven AML MV4-11 cells. Preliminary in vivo assays were carried out on three highly active compounds, whose results showed that 1-{5-[7-(3-morpholinopropoxy)quinazolin-4-ylthio]-[1,3,4]thiadiazol-2-yl}-3-p-tolylurea (20c) had the highest in vivo activity. Further in vitro and in vivo anti-AML studies were then performed on 20c; in an MV4-11 xenograft mouse model, a once-daily dose of 20c at 100 mg/kg for 18 days led to complete tumor regression without obvious toxicity. Western blot and immunohistochemical analysis were carried out to illustrate the mechanism of action of 20c.