Cleavage-intermediate Lassa virus trimer elicits neutralizing responses, identifies neutralizing nanobodies, and reveals an apex-situated site-of-vulnerability.

Lassa virus (LASV) infection is expanding outside its traditionally endemic areas in West Africa, posing a pandemic biothreat. LASV-neutralizing antibodies, moreover, have proven difficult to elicit. To gain insight into LASV neutralization, here we develop a prefusion-stabilized LASV glycoprotein trimer (GPC), pan it against phage libraries comprising single-domain antibodies (nanobodies) from shark and camel, and identify one, D5, which neutralizes LASV.

Allosteric Neutralization by Human H7N9 Antibodies.

The avian influenza A virus H7N9 causes severe human infections with more than 30% fatality despite the use of neuraminidase inhibitors. Currently there is no H7N9-specific prevention or treatment for humans. From a 2013 H7N9 convalescent case occurred in Hong Kong, we isolated four H7 hemagglutinin (HA)-reactive monoclonal antibodies (mAbs) by single B cell cloning, with three mAbs directed to the HA globular head domain (HA1) and one to the HA stem region (HA2).

Multidisciplinary studies with mutated HIV-1 capsid proteins reveal structural mechanisms of lattice stabilization.

HIV-1 capsid (CA) stability is important for viral replication. E45A and P38A mutations enhance and reduce core stability, thus impairing infectivity. Second-site mutations R132T and T216I rescue infectivity.

Tryptophan-like side chain holding aptamers inhibit respiratory syncytial virus infection of lung epithelial cells.

Respiratory syncytial virus (RSV) is a leading cause of serious and even fatal acute lower respiratory tract infections in infants and in the elderly. Potent RSV neutralization has been achieved by antibodies that selectively bind the prefusion form of the viral fusion (F) protein. We hypothesised that similar potent neutralization could be achieved using F protein targeting aptamers.

Preparation, Application and Enhancement Dyeing Properties of ZnO Nanoparticles in Silk Fabrics Dyed with Natural Dyes.

In this study, ZnO nanoparticles were prepared by a hydrothermal method with varying the reaction times, material ratios and reaction temperatures. The samples were characterized by scanning electron microscopy (SEM), transmission electron microscopy (TEM), X-ray Diffraction (XRD) and Fourier infrared spectroscopy (FTIR). It was shown that the material ratio significantly affected the structure and morphology of the synthesized ZnO nanoparticles, and then the uneven nano-octahedral structure, uniform nano-octahedral structure, nano-tubular structure, and nano-sheet structure could be obtained successively.

Studies on crystal structures, optical, dyeing and biological properties of protoberberine alkaloids and their supramolecular salts.

The novel Palmatine (PLT)-based supramolecular salt palmatine-sulfosalicylic acid (PLT-SSA) was designed and synthesized, and its structures was determined by the single crystal X-ray diffraction. It is found that PLT-SSA exhibited enhancing thermodynamic stability, fluorescence intensity and emission lifetime in crystal state, which indicated that these structures and aromatic rings may give more overlap between the host-guest units and give rise to a long-lived charge-separated state. In addition, the dyeing properties and toxicity of these protoberberine alkaloid (BBC and PLTCl) and their supramolecular salts will be developed in this work used as yellow dyes for development multifunctional fabrics.

Facile Electrodeposition of NiCoO Nanosheets on Porous Carbonized Wood for Wood-Derived Asymmetric Supercapacitors.

Multichannel-porous carbon derived from wood can serve as a conductive substrate for fast charge transfer and ion diffusion, supporting the high-theory capacitance of pseudocapacitive materials. Herein, NiCoO nanosheets, which are hierarchically porous, anchored on the surface of carbonized wood via electrodeposition for free-binder high-performance supercapacitor electrode materials, were proposed. Benefiting from the effectively alleviated NiCoO nanosheets accumulation and sufficient active surface area for redox reaction, a N-doped wood-derived porous carbon-NiCoO nanosheet hybrid material (NCNS-NCW) electrode exhibited a specific electric capacity of 1730 F g at 1 A g in 1 mol L KOH and splendid electrochemical firmness with 80% capacitance retention after cycles.

Wood-Derived High-Mass-Loading MnO Composite Carbon Electrode Enabling High Energy Density and High-Rate Supercapacitor.

The simple design of a high-energy-density device with high-mass-loading electrode has attracted much attention but is challenging. Manganese oxide (MnO ) with its low cost and excellent electrochemical performance shows high potential for practical application in this regard. Hence, the high-mass-loading of the MnO electrode with wood-derived carbon (WC) as the current collector is reported through a convenient hydrothermal reaction for high-energy-density devices.

Discovery of New Small Molecule Hits as Hepatitis B Virus Capsid Assembly Modulators: Structure and Pharmacophore-Based Approaches.

Hepatitis B virus (HBV) capsid assembly modulators (CpAMs) have shown promise as potent anti-HBV agents in both preclinical and clinical studies. Herein, we report our efforts in identifying novel CpAM hits via a structure-based virtual screening against a small molecule protein-protein interaction (PPI) library, and pharmacophore-guided compound design and synthesis. Curated compounds were first assessed in a thermal shift assay (TSA), and the TSA hits were further evaluated in an antiviral assay.

Design, Synthesis and Characterization of HIV-1 CA-Targeting Small Molecules: Conformational Restriction of PF74.

Small molecules targeting the PF74 binding site of the HIV-1 capsid protein (CA) confer potent and mechanistically unique antiviral activities. Structural modifications of PF74 could further the understanding of ligand binding modes, diversify ligand chemical classes, and allow identification of new variants with balanced antiviral activity and metabolic stability. In the current work, we designed and synthesized three series of PF74-like analogs featuring conformational constraints at the aniline terminus or the phenylalanine carboxamide moiety, and characterized them using a biophysical thermal shift assay (TSA), cell-based antiviral and cytotoxicity assays, and in vitro metabolic stability assays in human and mouse liver microsomes.

Novel PF74-like small molecules targeting the HIV-1 capsid protein: Balance of potency and metabolic stability.

Of all known small molecules targeting human immunodeficiency virus (HIV) capsid protein (CA), PF74 represents by far the best characterized chemotype, due to its ability to confer antiviral phenotypes in both early and late phases of viral replication. However, the prohibitively low metabolic stability renders PF74 a poor antiviral lead. We report herein our medicinal chemistry efforts toward identifying novel and metabolically stable small molecules targeting the PF74 binding site.

Novel HIV-1 capsid-targeting small molecules of the PF74 binding site.

The PF74 binding site in HIV-1 capsid protein (CA) is a compelling antiviral drug target. Although PF74 confers mechanistically distinct antiviral phenotypes by competing against host factors for CA binding, it suffers from prohibitively low metabolic stability. Therefore, there has been increasing interest in designing novel sub-chemotypes of PF74 with similar binding mode and improved metabolic stability.

Chemical profiling of HIV-1 capsid-targeting antiviral PF74.

The capsid protein (CA) of HIV-1 plays essential roles in multiple steps of the viral replication cycle by assembling into functional capsid core, controlling the kinetics of uncoating and nuclear entry, and interacting with various host factors. Targeting CA represents an attractive yet underexplored antiviral approach. Of all known CA-targeting small molecule chemotypes, the peptidomimetic PF74 is particularly interesting because it binds to the same pocket used by a few important host factors, resulting in highly desirable antiviral phenotypes.

Toward Structurally Novel and Metabolically Stable HIV-1 Capsid-Targeting Small Molecules.

HIV-1 capsid protein (CA) plays an important role in many steps of viral replication and represents an appealing antiviral target. Several CA-targeting small molecules of various chemotypes have been studied, but the peptidomimetic has drawn particular interest due to its potent antiviral activity, well-characterized binding mode, and unique mechanism of action. Importantly, competes against important host factors for binding, conferring highly desirable antiviral phenotypes.

[Current status and new challenges of three important imported parasitic diseases].

Following the concerted efforts for nearly 70 years, great achievements have been obtained in parasitic diseases control in China, and some important parasitic diseases have been eliminated or moving towards elimination in the country. With the socioeconomic development, the implementation of the "Road and Belt Initiative" and the increase in the international communication and overseas investment, there is a rise in the number of overseas labors, businessmen, students, travelers, visitors and participants in national and international communication activities, resulting in a gradual increase in the number of cases with parasitic diseases imported from endemic to non-endemic areas of China and from foreign countries to China. The increase in the number of imported cases causes new challenges for the elimination of parasitic diseases in China.

Simple crystallization approach for enhancing function of plant-based madder dye and performance of dyed fabric.

In the present study, the natural madder dye was investigated to the simultaneous extraction and dyeing of cotton (natural fiber) and nylon (synthetic fiber). The optimum dye extraction conditions were found to be 80 °C, 60 min, and 1:6 with ethyl alcohol after madder had been fermenting for 24 hours with water as solvent. Interestingly, crystallization can be done to separate crystal mollugin from dyed solution.

Structural and functional observations of the P151L MID1 mutation reveal alpha4 plays a significant role in X-linked Opitz Syndrome.

Mutations of human MID1 are associated with X-linked Opitz G Syndrome (XLOS), which is characterized by midline birth defects. XLOS-observed mutations within the MID1 B-box1 domain are associated with cleft lip/palate, wide-spaced eyes and hyperspadias. Three of the four XLOS-observed mutations in the B-box1 domain results in unfolding but the structural and functional effects of the P151L mutation is not characterized.

Mini-G proteins: Novel tools for studying GPCRs in their active conformation.

Mini-G proteins are the engineered GTPase domains of Gα subunits. They couple to GPCRs and recapitulate the increase in agonist affinity observed upon coupling of a native heterotrimeric G protein. Given the small size and stability of mini-G proteins, and their ease of expression and purification, they are ideal for biophysical studies of GPCRs in their fully active state.

Structure and dynamics of a constitutively active neurotensin receptor.

Many G protein-coupled receptors show constitutive activity, resulting in the production of a second messenger in the absence of an agonist; and naturally occurring constitutively active mutations in receptors have been implicated in diseases. To gain insight into mechanistic aspects of constitutive activity, we report here the 3.3 Å crystal structure of a constitutively active, agonist-bound neurotensin receptor (NTSR1) and molecular dynamics simulations of agonist-occupied and ligand-free receptor.

[Risk Assessment of Snail Output Via the Mud Balls of Transplanted Seedlings in a Nursery Stock Park in Middle Region of Zhejiang Province].

Objective: To investigate the distribution of snails in a nursery stock park in the middle region of Zhejiang Province and assess the risk of snail output via the mud balls of transplanted seedlings, to provide scientific data for making strategies for snail control.

Methods: We selected three species of seedlings including Osmanthus fragrans (a large tree), Camellia sasanqua (a small tree), and Purpus privet (a type of shrub) in a nursery stock park in a snail-positive middle region of Zhejiang Province during 2014-2016 to calculate the areas of regions with snails and the density of living snails. In 30 trees of each species, the distribution of snails within the seedlings ground diameter (radius of investigation, 100 cm for Osmanthus fragrans; 30 cm for Camellia Sasanqua and Purpus Privet) and in different soil layers (surface and superficial layers, 0-3 cm; deep layer, 3-10 cm) was assessed.

Solution structure of the microtubule-targeting COS domain of MID1.

Unlabelled: The human MID1 protein is required for the proper development during embryogenesis. Mutations of MID1 are associated with X-linked Opitz G syndrome, characterized by midline anomalies. MID1 associates with the microtubules and functions as an ubiquitin E3 ligase, targeting protein phosphatase 2A for ubiquitin-mediated regulation.

Obtaining Soluble Folded Proteins from Inclusion Bodies Using Sarkosyl, Triton X-100, and CHAPS: Application to LB and M9 Minimal Media.

This unit describes a straightforward and efficient method of using sarkosyl to solubilize and recover difficult recombinant proteins, such as GST- and His6 -tagged fusion proteins, that are overexpressed in E. coli. This protocol is especially useful for rescuing recombinant proteins overexpressed in M9 minimal medium.

A new nanocrystalline inorganic-organic hybrid exhibiting semiconducting properties and applications.

A new nanocrystalline inorganic-organic hybrid semiconductor [(BV)2(Ag5Br9)]n (1) with an intriguing windmill-like 1-D [Ag5Br9]n(n-) polymeric chain was assembled. Great efforts were devoted to investigate its semiconducting properties and applications, such as photoluminescence, emission decay lifetime, waste water purification, electrochemistry behavior and dielectric properties.