Local Electric Potential-Driven Nanofluidic Ion Transport for Ultrasensitive Biochemical Sensing.

Nanofluidic biosensors have been widely used for detection of analytes based on the change of system resistance before and after target-probe interactions. However, their sensitivity is limited when system resistance barely changes toward low-concentration targets. Here, we proposed a strategy to address this issue by means of target-induced change of local membrane potential under relatively unchanged system resistance. The local membrane potential originated from the directional diffusion of photogenerated carriers across nanofluidic biosensors and gated photoinduced ionic current signal before and after target-probe interactions. The sensitivity of such biosensors for the detection of biomolecules such as circulating tumor DNA (ctDNA) and lysozyme exceeds that of applying a traditional strategy by more than 3 orders of magnitude under unchanged system resistance. Such biosensors can specifically detect the small molecule biomarker in the blood sample between prostate cancer patients and healthy humans. The key advantages of such nanofluidic biosensors are therefore complementary to traditional nanofluidic biosensors, with potential applications in a point-of-care analytical tool.

Trifunctional of Phosphorus-Doped NiCo2O4 Nanowire Materials for Asymmetric Supercapacitor, Oxygen Evolution Reaction, and Hydrogen Evolution Reaction.

Nowadays, transition-metal oxides are regarded as the most potential materials for the supercapacitor and electrocatalyst. However, the poor electrical conductivity and insufficient active sites limited their development in various fields. Herein, we report the method of phosphorous-doped NiCo2O4 (named as P-NCO) prepared by the two-step strategy: the NiCo2O4 nanostructure is grown on the nickel foams by hydrothermal treatment and subsequently phosphatized in a tube furnace. Successfully, the rich oxygen vacancies and the P element introduced into the NiCo2O4 structure obviously improve the electrical conductivity, and the resulting P-NCO NWs/NF material shows an ultrahigh specific capacitance of 2747.8 F g-1 at 1 A g-1 and a prominent rate performance (maintain 50% at 100 A g-1). Furthermore, the assembled P-NCO NWs/NF//RGO asymmetric supercapacitor has an energy density of 28.2 W h kg-1 even at a high power density of 7750.35 W kg-1. After 10,000 cycles, the capacitance still also has an 88.48% retention rate. As an electrocatalyst, P-NCO NWs/NF has an excellent hydrogen evolution reaction (55 mV at 10 mA cm-2) and oxygen evolution reaction (300 mV at 10 mA cm-2) activities in 1 M KOH solution. This study provides an effective strategy to prepare multifunctional materials.

Asymmetric supercapacitors with high energy densities.

The low energy densities of supercapacitors (SCs) are generally limited by the used anodes. To develop SCs with high energy densities, Fe3+ modified V2O5@GQDs (m-V2O5@GQDs) and ZIF-67-derived nanoporous carbon loaded with Mn3O4 (C/N-Mn3O4) were synthesized. After their detailed characterization using electron microscopy, X-ray methods and electrochemical techniques, they were further utilized as the anode and the cathode, respectively, to construct asymmetric supercapacitors (ASCs). The as-synthesized m-V2O5@GQDs improve the poor conductivity of V2O5, contributing greatly to a specific capacitance of 761 F g-1 at a current density of 2 A g-1. With application of a cell voltage of 2 V, an energy density of up to 99.4 W h kg-1 is achieved at a power density of 1000 W kg-1. Such ASCs also exhibit outstanding cycling performance (95% of initial capacitance even after 10 000 charging/discharging cycles). This study thus provides a new way to design and construct ASCs with high energy densities.

Overview of Stigma against Psychiatric Illnesses and Advancements of Anti-Stigma Activities in Six Asian Societies.

Background: In psychiatry, stigma is an attitude of disapproval towards people with mental illnesses. Psychiatric disorders are common in Asia but some Asians receive inadequate treatment. Previous review found that Asians with mental illness were perceived to be dangerous and aggressive. There is a need for renewed efforts to understand stigma and strategies which can effectively reduce stigma in specific Asian societies. The objective of this systematic review was to provide an up-to-date overview of existing research and status on stigma experienced by psychiatric patients and anti-stigma campaigns in China, Hong Kong, Japan, Singapore, Korea, and Thailand. Methods: A systematic literature search was conducted in the following databases, including PubMed, PsycINFO, Embase, Web of Science, and local databases. Studies published in English and the official language of included countries/territories were considered for inclusion in the systematic review. Any article on stigma related to any form of psychiatric illness in the six Asian societies was included. Results: One hundred and twenty-three articles were included for this systematic review. This review has six major findings. Firstly, Asians with mental illnesses were considered as dangerous and aggressive, especially patients suffering from schizophrenia and bipolar disorder; second, psychiatric illnesses in Asian societies were less socially-acceptable and were viewed as being personal weaknesses; third, stigma experienced by family members was pervasive and this is known as family stigma; fourth, this systemic review reported more initiatives to handle stigma in Asian societies than a decade ago; fifth, there have been initiatives to treat psychiatric patients in the community; and sixth, the role of supernatural and religious approaches to psychiatric illness was not prevailing. Conclusion: This systematic review provides an overview of the available scientific evidence that points to areas of needed intervention to reduce and ultimately eliminate inequities in mental health in Asia.

Changes in Cuticular Wax Composition of Two Blueberry Cultivars during Fruit Ripening and Postharvest Cold Storage.

Cuticular wax plays an important role for the quality of blueberry fruits. In this study, the cuticular wax composition of two blueberry cultivars, 'Legacy' ( Vaccinium corymbosum) and 'Brightwell' ( Vaccinium ashei), was examined during fruit ripening and postharvest cold storage. The results showed that wax was gradually deposited on the epidermis of blueberry fruits and the content of major wax compounds, except that for diketones, increased significantly during fruit ripening. The total wax content was 2-fold greater in 'Brightwell' blueberries than that in 'Legacy' blueberries during fruit ripening. The total wax content of both cultivars decreased during 30 days of storage at 4 °C, and the variation of cuticular wax composition was cultivar-dependent. The content of diketones decreased significantly in 'Legacy' blueberries, while the content of triterpenoids and aliphatic compounds showed different fold changes in 'Brightwell' blueberries after 30 days of storage at 4 °C. Overall, our study provided a quantitative and qualitative overview of cuticular wax compounds of blueberry fruits during ripening and postharvest cold storage.

Effect of O2 Concentration on the Electrochromic Properties of NiOx Films.

Nickel oxide (NiOx) films were deposited onto ITO-coated glass at room temperature by DC magnetron sputtering in Ar/O2 mixing gas. The effect of O2 concentration on structure, morphology, electrochemical and electrochromic properties of NiOx films was systematically investigated. X-ray diffraction results showed NiOx films had the polycrystalline structure. NiOx films deposited at low O2 concentration had the preferred (200) peak. On the other hand, the films exhibited the strong (111) peak at high O2 concentration. Small roughness and grain size of NiOx film deposited at 15% O2 concentration were observed by atomic force microscope and scanning electron microscope results, and small crystallite size was obtained from the XRD data which leads to the good cyclic durability. The large transmittance modulation, high color efficiency and fast coloring/bleaching response time make NiOx films suitable to be applied as an anodic coloring material complemented with WO3 electrochromic window.

Electrochromic Properties of NiOx Films Deposited by DC Magnetron Sputtering.

Nickel oxide (NiOx) films were deposited onto ITO-coated glass at room temperature by DC magnetron sputtering and the electrochromic properties were investigated. The effects of film thickness on structure, morphology, electrochemical and electrochromic properties of NiOx films were systematically studied. X-ray diffraction and scanning electron microscopy results indicate NiOx films have the polycrystalline structure and the crystallinity improves with the increase of thickness. In atomic force microscopy analysis, the surface roughness of NiOx films increases as the thickness increases and large roughness is obtained in the films of more than 300 nm. The electrochemical properties were measured by using conventional three-electrode configuration in 1 M LiClO4-PC electrolyte and all the samples show good cyclic stability. A transmittance modulation of 62% between colored and bleached state at 550 nm wavelength is obtained for 500 nm thick film and the high color efficiencies of more than 62 cm2C-1 are obtained in NiOx films. However, coloring and bleaching response times increase with the increase of thickness because of the larger depth of charge insertion/extraction. The results confirm that magnetron sputtering technology provides a feasibility for electrochromic devices with excellent electrochromic performance.

Effects of cuticular wax on the postharvest quality of blueberry fruit.

The blueberry fruit has a light-blue appearance because its blue-black skin is covered with a waxy bloom. This layer is easily damaged or removed during fruit harvesting and postharvest handling. We investigated the effects of wax removal on the postharvest quality of blueberry fruit and their possible mechanisms. The removal of natural wax on the fruit was found to accelerate the postharvest water loss and decay, reduce the sensory and nutritional qualities, and shorten the shelf-life. Wax removal decreased the activities of antioxidant enzymes and contents of antioxidants, and accelerated accumulation of ROS and lipid peroxidation, especially at the later period of storage. Moreover, the organellar membrane structure was disrupted in fruit with wax removed. These results indicate that cuticular wax plays an important role in maintaining the postharvest quality and delaying fruit senescence. The results should improve our understanding for better preservation of postharvest quality of blueberry fruit.

Discovery of Novel Pyridone-Conjugated Monosulfactams as Potent and Broad-Spectrum Antibiotics for Multidrug-Resistant Gram-Negative Infections.

Conjugating a siderophore to an antibiotic is a promising strategy to overcome the permeability-mediated resistance of Gram-negative pathogens. On the basis of the structure of BAL30072, novel pyridone-conjugated monosulfactams incorporating diverse substituents into the methylene linker between the 1,3-dihydroxypyridin-4(1H)-one and the aminothiazole oxime were designed and synthesized. Structure-activity relationship studies revealed that a variety of substituents were tolerated, with isopropyl (compound 12c) and methylthiomethyl (compound 16a) showing the best efficacy against multidrug-resistant (MDR) Gram-negative pathogens. In addition, compound 12c exhibits a good free fraction rate in an in vitro human plasma protein binding test, along with a low clearance and favorable plasma exposure in vivo. In a murine systemic infection model with MDR Klebsiella pneumoniae, compound 12c shows an ED50 of 10.20 mg/kg. Taken together, the results indicate that compound 12c is a promising drug candidate for the treatment of serious infections caused by MDR Gram-negative pathogens.

Composition and morphology of cuticular wax in blueberry (Vaccinium spp.) fruits.

The chemical composition and morphology of cuticular wax in mature fruit of nine blueberry cultivars were investigated using gas chromatography-mass spectrometry (GC-MS) and scanning electron microscope (SEM). Triterpenoids and ß-diketones were the most prominent compounds, accounting for on average 64.2% and 16.4% of the total wax, respectively. Ursolic or oleanolic acid was identified as the most abundant triterpenoids differing in cultivars. Two ß-diketones, hentriacontan-10,12-dione and tritriacontan-12,14-dione, were detected in cuticular wax of blueberry fruits for the first time. Notably, hentriacontan-10,12-dione and tritriacontan-12,14-dione were only detected in highbush (V. corymbosum) and rabbiteye (V. ashei) blueberries, respectively. The results of SEM showed that a large amount of tubular wax deposited on the surface of blueberry fruits. There was no apparent difference in wax morphology among the nine cultivars.

Optical scheme for simulating post-quantum nonlocality distillation.

An optical scheme for simulating nonlocality distillation is proposed in post-quantum regime. The nonlocal boxes are simulated by measurements on appropriately pre- and post-selected polarization entangled photon pairs, i.e. post-quantum nonlocality is simulated by exploiting fair-sampling loophole in a Bell test. Mod 2 addition on the outputs of two nonlocal boxes combined with pre- and post-selection operations constitutes the key operation of simulating nonlocality distillation. This scheme provides a possible tool for the experimental study on the nonlocality in post-quantum regime and the exact physical principle precisely distinguishing physically realizable correlations from nonphysical ones.

Optical simulation of a Popescu-Rohrlich Box.

It is well known that the fair-sampling loophole in Bell test opened by the selection of the state to be measured can lead to post-quantum correlations. In this paper, we make the selection of the results after measurement, which opens the fair- sampling loophole too, and thus can lead to post-quantum correlations. This kind of result-selection loophole can be realized by pre- and post-selection processes within the "two-state vector formalism", and a physical simulation of Popescu-Rohrlich (PR) box is designed in linear optical system. The probability distribution of the PR has a maximal CHSH value 4, i.e. it can maximally violate CHSH inequality. Because the "two-state vector formalism" violates the information causality, it opens the locality loophole too, which means that this kind of results selection within "two-state vector formalism" leads to both fair- sampling loophole and locality loophole, so we call it a comprehensive loophole in Bell test. The comprehensive loophole opened by the results selection within "two-state vector formalism" may be another possible explanation of why post-quantum correlations are incompatible with quantum mechanics and seem not to exist in nature.

Design, synthesis, and structure-activity relationship studies of novel thienopyrrolidone derivatives with strong antifungal activity against Aspergillus fumigates.

In order to further enhance the anti-Aspergillus efficacy of our previously discovered antifungal lead compounds (I), two series of novel azoles featuring thieno[2,3-c]pyrrolidone and thieno[3,2-c]pyrrolidone nuclei were designed and evaluated for their in vitro activity on the basis of the binding mode of albaconazole using molecular docking, along with SARs of antifungal triazoles. Most of target compounds exhibited excellent activity against Candida and Cryptococcus spp., with MIC values in the range of 0.0625 µg/ml to 0.0156 µg/ml. The thieno[3,2-c]pyrrolidone unit was more suited for improving activity against Aspergillus spp. The most potent compound, 18a, was selected for further development due to its significant in vitro activity against Aspergillus spp. (MIC = 0.25 µg/ml), as well as its high metabolic stability in human liver microsomes.

Synthesis and structure-activity relationship studies of novel [6,6,5] tricyclic oxazolidinone derivatives as potential antibacterial agents.

In our previous Letter, we reported the discovery of a novel benzoxazinyl-oxazolidinone antibacterial candidate 2. In order to identify a potential backup compound, extensive modifications on the B/C ring and C3 side chain were undertaken. A series of novel [6,6,5] tricyclic analogues were synthesized and their in vitro antibacterial activities were tested against a panel of susceptible and resistant Gram-positive pathogens. Among of them, benzothiazinyl-oxazolidinones with acetamide or thioamide as C3 side chains exhibited moderate to good antibacterial activity, such as compounds 54, 58, 59 and 63. In vitro liver microsomal stability was further evaluated and the results manifested that compounds 54 and 58 were both metabolically stable in rat and human liver microsomes. Additionally, insights gained from this investigation should provide directions for the further research of new oxazolidinone antibiotics.

Simple synthesis and photoelectrochemical characterizations of polythiophene/Pd/TiO2 composite microspheres.

We report here a simple, effective, and low cost method to synthesize polythiophene/Pd/TiO2 (PTh/Pd/TiO2) ternary composite microspheres and apply such a composite to photoelectrochemical (PEC) sensing. TiO2 spherical aggregates of 200 nm diameter, consisting of nanoscale building blocks of TiO2, have been prepared by hydrolysis of tetrabutyl titanate in a water-in-oil emulsion system (Vwater/Vacetone=1/100). Pd species and PTh layer were decorated onto TiO2 microspherical substrates by reduction of Pd salts and polymerization of thiophene, respectively. The high surface area, effective charge transfer, and enhanced light absorption of the ternary composite could improve PEC performance under simulated sunlight. The sensitivity, selectivity, and stability of PEC sensor for detecting l-cysteine were much higher than those of the traditional electrochemical sensor. The detection limit of l-cysteine was 9.24 µM in the linear range of 0.31-5.30 mM. Moreover, the results also indicated a good anti-interference and acceptable accuracy in practical application, providing a rapid and sensitive detection method.

Design, synthesis, and structure-activity and structure-pharmacokinetic relationship studies of novel [6,6,5] tricyclic fused oxazolidinones leading to the discovery of a potent, selective, and orally bioavailable FXa inhibitor.

The blood coagulation enzyme factor Xa (FXa) is a particularly promising target for anticoagulant therapy, and identification of oral small-molecule inhibitors of FXa remains a research focus. On the basis of the X-ray crystal structure of FXa and its inhibitor rivaroxaban, we designed and synthesized a series of conformationally restricted mimics containing a novel [6,6,5] tricyclic fused oxazolidinone scaffold. Intensive structure-activity relationship (SAR) and structure-pharmacokinetic relationship (SPR) studies on this new series led to the discovery of compound 11a: a highly potent, selective, direct, and orally bioavailable FXa inhibitor with excellent in vivo antithrombotic efficacy and preferable pharmacokinetic profiles. Druggability evaluation of compound 11a was undertaken and elicited positive outcomes. All results indicate that compound 11a is a promising drug candidate for the prevention and treatment of thromboembolic diseases in venous and arterial systems.

Design, synthesis, and structure-activity relationship studies of novel thioether pleuromutilin derivatives as potent antibacterial agents.

A series of novel thioether pleuromutilin derivatives incorporating various heteroaromatic substituents into the C14 side chain have been reported. Structure-activity relationship (SAR) studies resulted in compounds 52 and 55 with the most potent in vitro antibacterial activity among the series (MIC = 0.031-0.063 µg/mL). Further optimization to overcome the poor water solubility of compound 55 resulted in compounds 87, 91, 109, and 110 possessing good in vitro antibacterial activity with increased hydrophilicity. Compound 114, the water-soluble phosphate prodrug of compound 52, was also prepared and evaluated. Among the derivatives, compound 110 showed moderate pharmacokinetic profiles and good in vivo efficacy in both MSSA and MRSA systemic infection models. Compound 110 was further evaluated in CYP450 inhibition assay and displayed intermediate in vitro inhibition of CYP3A4.

Design, synthesis, and structure-activity relationship studies of novel fused heterocycles-linked triazoles with good activity and water solubility.

Triazoles with fused-heterocycle nuclei were designed and evaluated for their in vitro activity on the basis of the binding mode of albaconazole using molecular docking, along with SAR of antifungal triazoles. Tetrahydro-[1,2,4]triazolo[1,5-a]pyrazine and tetrahydro-thiazolo[5,4-c]pyridine nuclei were preferable to the other four fused-heterocycle nuclei investigated. Potent in vitro activity, broad spectrum and better water solubility were attained when triazoles containing nitrogen aromatic heterocycles were attached to these two nuclei. The most potent compounds 27aa and 45x, with low hERG inhibition and hepatocyte toxicity, both exhibited excellent activity against Candida, Cryptococcus, and Aspergillus spp., as well as selected fluconazole-resistant strains. A high water-soluble compound 58 (the disulfate salt of 45x) displayed unsatisfactory in vivo activity because of its poor PK profiles. Mice infected with C.alb. SC5314 and C.alb. 103 (fluconazole-resistant strain) and administered with 27aa displayed significantly improved survival rates. 27aa also showed favorable pharmacokinetic (PK) profiles.

Synthesis and biological evaluation of novel benzoxazinyl-oxazolidinones as potential antibacterial agents.

A number of benzoxazinyl-oxazolidinones bearing 3-trizolylmethyl or 3-carboxamide side chain were designed and synthesized with the aim to develop antibacterial agents with improved properties. In vitro antibacterial activities of these novel compounds were evaluated against a panel of resistant and susceptible Gram-positive bacteria. Most analogues bearing 3-trizolylmethyl showed good to moderate antibacterial activities. Compound 12a exhibited a fourfold increase in activity compared with linezolid against all the tested strains, which was identified to be a promising antibacterial agent for further evaluation.