Nano‐based methods for novel coronavirus 2019 (2019‐nCoV) diagnosis: A review

Today, tremendous attention has been devoted to a new coronavirus, SARS‐CoV‐2 (2019‐nCoV), due to severe effects on the global public in all over the world. Rapid and accurate diagnosis of 2019‐nCoV are important for early treatment and cutting off epidemic transmission. In this regard, laboratory detection protocols, such as polymerase chain reaction (PCR) and computed tomography (CT) examination, have been utilized broadly for 2019‐nCoV detection. Recently, nano‐based methods for 2019‐nCoV diagnoses are rapidly expanding and declaring comparable results with PCR and CT. In this review, recent advances in nano‐based techniques have been highlighted and compared briefly with PCR and CT as well‐known methods for 2019‐nCoV detection.     

Subjecting the theory of the small‐island effect to Ockham’s razor

Species–area curves from islands and other isolates often differ in shape from sample‐area curves generated from mainlands or sections of isolates (or islands), especially at finer scales. We examine two explanations for this difference: (1) the small‐island effect (SIE), which assumes the species–area curve is composed of two distinctly different curve patterns; and (2) a sigmoid or depressed isolate species–area curve with no break‐points (in arithmetic space). We argue that the application of Ockham’s razor – the principle that the simplest, most economical explanation for a hypothesis should be accepted over less parsimonious alternatives – leads to the conclusion that the latter explanation is preferable. We hold that there is no reason to assume the ecological factors or patterns that affect the shapes of isolate (or island) curves cause two distinctly different patterns. This assumption is not required for the alternative, namely that these factors cause a single (though depressed) isolate species–area curve with no break‐points. We conclude that the theory of the small‐island effect, despite its present standing as an accepted general pattern in nature, should be abandoned.     

A novel synthetic small molecule YH‐306 suppresses colorectal tumour growth and metastasis via FAK pathway

Cell migration and invasion are key processes in the metastasis of cancer, and suppression of these steps is a promising strategy for cancer therapeutics. The aim of this study was to explore small molecules for treating colorectal cancer (CRC) and to investigate their anti‐metastatic mechanisms. In this study, six CRC cell lines were used. We showed that YH‐306 significantly inhibited the migration and invasion of CRC cells in a dose‐dependent manner. In addition, YH‐306 inhibited cell adhesion and protrusion formation of HCT116 and HT‐29 CRC cells. Moreover, YH‐306 potently suppressed uninhibited proliferation in all six CRC cell lines tested and induced cell apoptosis in four cell lines. Furthermore, YH‐306 inhibited CRC colonization in vitro and suppressed CRC growth in a xenograft mouse model, as well as hepatic/pulmonary metastasis in vivo. YH‐306 suppressed the activation of focal adhesion kinase (FAK), c‐Src, paxillin, and phosphatidylinositol 3‐kinases (PI3K), Rac1 and the expression of matrix metalloproteases (MMP) 2 and MMP9. Meanwhile, YH‐306 also inhibited actin‐related protein (Arp2/3) complex‐mediated actin polymerization. Taken together, YH‐306 is a candidate drug in preventing growth and metastasis of CRC by modulating FAK signalling pathway.     

Guanidine hydrochloride denaturation of dopamine‐induced α‐synuclein oligomers: A small‐angle X‐ray scattering study

Alpha‐synuclein (α‐syn) forms the amyloid‐containing Lewy bodies found in the brain in Parkinson's disease. The neurotransmitter dopamine (DA) reacts with α‐syn to form SDS‐resistant soluble, non‐amyloid, and melanin‐containing oligomers. Their toxicity is debated, as is the nature of their structure and their relation to amyloid‐forming conformers of α‐syn. The small‐angle X‐ray scattering technique in combination with modeling by the ensemble optimization method showed that the un‐reacted native protein populated three broad classes of conformer, while reaction with DA gave a restricted ensemble range suggesting that the rigid melanin molecule played an important part in their structure. We found that 6 M guanidine hydrochloride did not dissociate α‐syn DA‐reacted dimers and trimers, suggesting covalent linkages. The pathological significance of covalent association is that if they are non‐toxic, the oligomers would act as a sink for toxic excess DA and α‐syn; if toxic, their stability could enhance their toxicity. We argue it is essential, therefore, to resolve the question of whether they are toxic or not. Proteins 2014; 82:10–21. © 2013 Wiley Periodicals, Inc.     

Inhibition of melanoma development in the Nras(Q61K)::Ink4a−/− mouse model by the small molecule BI‐69A11

To date, there are no effective therapies for tumors bearing NRAS mutations, which are present in 15–20% of human melanomas. Here we extend our earlier studies where we demonstrated that the small molecule BI‐69A11 inhibits the growth of melanoma cell lines. Gene expression analysis revealed the induction of interferon‐ and cell death‐related genes that were associated with responsiveness of melanoma cell lines to BI‐69A11. Strikingly, the administration of BI‐69A11 inhibited melanoma development in genetically modified mice bearing an inducible form of activated Nras and a deletion of the Ink4a gene (Nras^(Q61K)::Ink4a^?/?). Biweekly administration of BI‐69A11 starting at 10 weeks or as late as 24 weeks after the induction of mutant Nras expression inhibited melanoma development (100 and 36%, respectively). BI‐69A11 treatment did not inhibit the development of histiocytic sarcomas, which constitute about 50% of the tumors in this model. BI‐69A11‐resistant Nras^(Q61K)::Ink4a^?/? tumors exhibited increased CD45 expression, reflective of immune cell infiltration and upregulation of gene networks associated with the cytoskeleton, DNA damage response, and small molecule transport. The ability to attenuate the development of NRAS mutant melanomas supports further development of BI‐69A11 for clinical assessment.     

A Highly Enantioselective Access to Chiral 1‐(β‐Arylalkyl)‐1H‐1,2,4‐triazole Derivatives as Potential Agricultural Bactericides

A series of chiral 1‐(β‐arylalkyl)‐1H‐1,2,4‐triazole derivatives has been designed as potential antifungal agents. The target triazoles have been synthesized by using a chiral auxiliary as a controlling reagent. All of the compounds were obtained with high ee values, reaching up to 99%. Preliminary bioassay results have revealed that most of the synthesized compounds display significantly higher fungicidal activities against the species Fusarium oxysporium, Rhizoctonia solani, Botrytis cinereapers, Gibberella zeae, Dothiorella gregaria, and Colletotrichum gossypii than the commercial agent triadimefon. Moreover, some of the enantiomers have been found to display significant differences in activity.     

A novel molecule ‘shati’ increases dopamine uptake via the induction of tumor necrosis factor‐α in pheochromocytoma‐12 cells

The psychostimulant properties of methamphetamine (METH) are associated with an increase in extracellular dopamine (DA) levels in the brain, via facilitation of DA’s release from pre‐synaptic nerve terminals and inhibition of its reuptake through DA transporter. Recently, we have demonstrated that tumor necrosis factor‐α (TNF‐α) increases DA uptake and inhibits METH dependence. Moreover, we have clarified ‘shati’ identified in the nucleus accumbens of mice treated with METH is involved in METH dependence. In the present study, we investigated the effects of TNF‐α on DA uptake in PC12 cells and established a PC12 cell line transfected with a vector containing shati cDNA to examine the precise mechanism behind the role of shati in DA uptake. Moreover, we examined the relationship between shati and TNF‐α. TNF‐α increased DA uptake via the mitogen‐activated protein kinase kinase pathway and inhibited the METH‐induced decrease in DA uptake in PC12 cells. Transfection of the vector containing shati cDNA into PC12 cells, induced the expression of shati and TNF‐α mRNA, accelerated DA uptake, and inhibited the METH‐induced decrease in DA uptake. These results suggest that the functional roles of shati in METH‐regulated behavioral changes are mediated through inhibition of the METH‐induced decrease in DA uptake via TNF‐α.     

Diagnostic and therapeutic value of progastrin‐releasing peptide on small‐cell lung cancer: A Single‐Center Experience in China

We aimed to compare the diagnostic efficiency of proGRP and NSE on SCLC and to investigate whether the change of proGRP level would predict therapeutic response. Patients who were firstly diagnosed pathologically in Nanjing Chest Hospital and measured proGRP level consecutively were enrolled in the study. ProGRP level was detected using Elecsys ProGRP Assay. Totally 75 SCLC, 234 NSCLC and 264 benign lung diseases (BLD) were enrolled. Both proGRP and NSE levels in SCLC were significantly higher than those in NSCLC and BLD, and proGRP in extensive stage SCLC was higher than which in limited stage (P ≤ .001). The diagnostic efficiency of proGRP on SCLC was higher than that of NSE, but when the two biomarkers were bind together, the diagnostic efficiency was the best. When SCLC was differentiated from NSCLC and BLD, the cut‐off values were 114.35 pg/mL and 162.55 pg/mL respectively. For treatment responsive patients, proGRP level decreased markedly after the first cycle of therapy and kept a continued momentum of decline during treatment. But for unresponsive patients, no obvious decline was observed. ProGRP had higher diagnostic efficiency on SCLC when compared to NSE, and it could better predict therapeutic response of pulmonary target lesions on chemotherapy.     

Asymmetric Addition of Triethylaluminium to Aromatic Aldehydes Catalyzed by Titanium‐(5,5’‐Biquinoline‐6,6’‐Diol) Complexes

A novel convenient procedure for the resolution of 5,5’‐biquinoline‐6,6’‐diol (BIQOL) was achieved by separating the corresponding diastereomeric mixture of (S)‐(+)‐camphorsulfonates on a semiprepared XDB‐C8 column followed by hydrolysis. The efficient asymmetric addition of triethylaluminium to aromatic aldehydes catalyzed by Ti‐(+)/(–)BIQOL complexes under mild conditions is described. The reactions led to the formation of 1‐arylpropan‐1‐ol in up to 87.5% ee. Chirality 26:268‐271, 2014. © 2014 Wiley Periodicals, Inc.     

Tsimane’ Amazonian Panel Study (TAPS): The first 5 years (2002–2006) of socioeconomic, demographic, and anthropometric data available to the public

The Tsimane' Amazonian Panel Study (TAPS) is making available the first five years (2002-2006, inclusive) of annual socioeconomic, demographic, and anthropometric data available to the public. The information comes from a foraging-farming society of native Amazonians in Bolivia and includes 13 villages, 332 households, and 1985 people who have been tracked annually since 2002. The article provides a brief overview of the data covered and the steps needed to access the data.     

Synthesis,crystal structure and biological evaluation of spectroscopic characterization of Ni(II) and Co(II) complexes with N‐salicyloil‐N′‐maleoil‐hydrazine as anticholinergic and antidiabetic agents

[Ni(C₁₁H₉N₂O₅)₂(H₂O)₂]?3(C₃H₇NO) ( 1 ) and [Co(C₁₁H₉N₂O₅)₂(H₂O)₂]?3(C₃H₇NO) ( 2 ) are synthesized and characterized by elemental analysis, FT‐IR spectra, magnetic susceptibility, and thermal analysis. In addition, the crystal structure of Ni(II) complex is presented. Both complexes show distorted octahedral geometry. In 1 and 2, metal ions are coordinated by two oxygen atoms of salicylic residue and two nitrogen atoms of maleic amide residue from two ligands, and two oxygen atoms from two water molecules. In this paper, both compounds showed excellent inhibitory effects against human carbonic anhydrase (hCA) isoforms I, and II, α‐glycosidase, acetylcholinesterase (AChE), and butyrylcholinesterase (BChE). Compounds 1 and 2 had Ki values of 18.36 ± 4.38 and 26.61 ± 7.54 nM against hCA I and 13.81 ± 3.02 and 29.56 ± 6.52 nM against hCA II, respectively. On the other hand, their Ki values were found to be 487.45 ± 54.18 and 453.81 ± 118.61 nM against AChE and 199.21 ± 50.35 and 409.41 ± 6.86 nM against BChE, respectively.     

Posttranslational oxidative modification of (R)‐2‐(2,4‐dichlorophenoxy)propionate/α‐ketoglutarate‐dependent dioxygenases (RdpA) leads to improved degradation of 2,4‐dichlorophenoxyacetate (2,4‐D)

Microbial activities and the versatility gained through adaptation to xenobiotic compounds are the main biological forces to counteract environmental pollution. The current results present a new adaptive mechanism that is mediated through posttranslational modifications. Strains of Delftia acidovorans incapable of growing autochthonously on 2,4‐dichlorophenoxyacetate (2,4‐D) were cultivated in a chemostat on 2,4‐D in the presence of (R)‐2‐(2,4‐dichlorophenoxy)propionate. Long‐term cultivation led to enhanced 2,4‐D degradation, as demonstrated by improved values of the Michaelis–Menten constant K_m for 2,4‐D and the catalytic efficiency k_cat/K_m of the initial degradative key enzyme (R)‐2‐(2,4‐dichlorophenoxy)propionate/α‐ketoglutarate‐dependent dioxygenases (RdpA). Analyses of the rdpA gene did not reveal any mutations, indicating a nongenetic mechanism of adaptation. 2‐DE of enzyme preparations, however, showed a series of RdpA forms varying in their pI. During adaptation increased numbers of RdpA variants were observed. Subsequent immunoassays of the RdpA variants showed a specific reaction with 2,4‐dinitrophenylhydrazine (DNPH), characteristic of carbonylation modifications. Together these results indicate that posttranslational carbonylation modified the substrate specificity of RdpA. A model was implemented explaining the segregation of clones with improved degradative activity within the chemostat. The process described is capable of quickly responding to environmental conditions by reversibly adapting the degradative potential to various phenoxyalkanoate herbicides.     

Benzo[1,2‐b:4,5‐b′]Dithiophene–6,7‐Difluoroquinoxaline Small Molecule Donors with >8% BHJ Solar Cell Efficiency

Solution‐processable small molecule (SM) donors are promising alternatives to their polymer counterparts in bulk‐heterojunction (BHJ) solar cells. While SM donors with favorable spectral absorption, self‐assembly patterns, optimum thin‐film morphologies, and high carrier mobilities in optimized donor–acceptor blends are required to further BHJ device efficiencies, material structure governs each one of those attributes. As a result, the rational design of SM donors with gradually improved BHJ solar cell efficiencies must concurrently address: (i) bandgap tuning and optimization of spectral absorption (inherent to the SM main chain) and (ii) pendant‐group substitution promoting structural order and mediating morphological effects. In this paper, the rational pendant‐group substitution in benzo[1,2‐b:4,5‐b′]dithiophene–6,7‐difluoroquinoxaline SMs is shown to be an effective approach to narrowing the optical gap (E_opt) of the SM donors ( SM1 and SM2 ), without altering their propensity to order and form favorable thin‐film BHJ morphologies with PC₇₁BM. Systematic device examinations show that power conversion efficiencies >8% and open‐circuit voltages (V_OC) nearing 1 V can be achieved with the narrow‐gap SM donor analog ( SM2 , E_opt = 1.6 eV) and that charge transport in optimized BHJ solar cells proceeds with minimal, nearly trap‐free recombination. Detailed device simulations, light intensity dependence, and transient photocurrent analyses emphasize how carrier recombination impacts BHJ device performance upon optimization of active layer thickness and morphology.     

Determination of p‐Aminobenzenesulfonic acid based on the electrochemiluminescence quenching of tris (2,2’‐bipyridine)‐ ruthenium (II)

This study describes the quenching effects of p‐aminobenzenesulfonic acid (p‐ABSA) based on electrochemiluminescence (ECL) of the tris (2,2^’‐bipyridyl)‐ruthenium(II)(Ru(bpy)₃²⁺)/tri‐n‐propylamine (TPrA) system in aqueous solution. Quenching behaviours were observed with a 200‐fold excess of p‐ABSA over Ru(bpy)₃²⁺. In the presence of 0.1 M TPrA, the Stern‐Volmer constant (K_SV) of ECL quenching was as high as 1.39 × 10⁴ M^‐1 for p‐ABSA. The logarithmic plot of inhibited ECL versus concentration of p‐ABSA was linear over the range of 6.0 × 10^‐6 ‐3.0 × 10^‐4 mol/L. The corresponding limit of detection was 1.2 × 10^‐6 mol/L for p‐ABSA (S/N = 3). The mechanism of quenching is believed to involve an energy transfer from the excited‐state luminophore to a dimer of p‐ABSA and the adsorption of free radicals of p‐ABSA at the electrode surface that impeded the oxidation of the Ru(bpy)₃²⁺/TPrA system. Copyright © 2012 John Wiley & Sons, Ltd.