SNX8 enables lysosome reformation and reverses lysosomal storage disorder.

Lysosomal Storage Disorders (LSDs), which share common phenotypes, including enlarged lysosomes and defective lysosomal storage, are caused by mutations in lysosome-related genes. Although gene therapies and enzyme replacement therapies have been explored, there are currently no effective routine therapies against LSDs. During lysosome reformation, which occurs when the functional lysosome pool is reduced, lysosomal lipids and proteins are recycled to restore lysosome functions. Here we report that the sorting nexin protein SNX8 promotes lysosome tubulation, a process that is required for lysosome reformation, and that loss of SNX8 leads to phenotypes characteristic of LSDs in human cells. SNX8 overexpression rescued features of LSDs in cells, and AAV-based delivery of SNX8 to the brain rescued LSD phenotypes in mice. Importantly, by screening a natural compound library, we identified three small molecules that enhanced SNX8-lysosome binding and reversed LSD phenotypes in human cells and in mice. Altogether, our results provide a potential solution for the treatment of LSDs.

Nature-Inspired Gelatin-Based Adhesive Hydrogel: A Rapid and User-Friendly Solution for Hemostatic Applications.

Conventional hemostatic agents face challenges in achieving rapid hemostasis and effective tissue repair due to limited hemostatic scenarios, suboptimal efficacy, and inadequate adhesion to wet tissues. Drawing inspiration from nature-sourced materials, a gelatin-based adhesive hydrogel (AOT)  is designed, easily prepared and quick to form, driven by Schiff base and multiple hydrogen bonds for applications in arterial and liver bleeding models. AOT exhibits exceptional adhesion to wet tissues (48.67 ± 0.16 kPa) and displays superior hemostatic properties with reduced blood loss and hemostatic time compared to other hydrogels and conventional hemostatic materials. Moreover, AOT exhibits good biocompatibility and biodegradability. In summary, this easily prepared adhesive hydrogel has the potential to supplant traditional hemostatic agents, offering a novel approach to achieve swift sealing of hemostasis and facilitate wound healing and repair in broader application scenarios, owing to its unique advantages.

Polaron induced local spin texture and anomalous Hall effect in the quadrilateral prism-shaped nanotube with Rashba and Dresselhaus spin-orbit coupling.

We theoretically study the spin-texture dynamics and the transverse asymmetric charge deflection induced by the polaron in a quadrilateral prism-shaped nanotube with the Rashba and Dresselhaus spin-orbit coupling (SOC). We reveal the polaron gives rise to the nontrivial local spin textures in the nanotube within the cross section plane. The spins demonstrate oscillations and the oscillating patterns are dependent on the SOC type. For the nanotube containing a segment of the ferromagnetic domain, the sizable asymmetric charge deflections could additionally take place, namely, the anomalous Hall effect. The amount of the deflected charges is determined by the strength and orientations of the ferromagnetic magnetization as well as the SOC type. The work provides a valuable insight of the coherent transport of polaron through a quasi-one-dimensional nanotube with Rashba and Dresselhaus SOC and open avenues for the potential device applications.

Metal-Coordinated Dynamics and Viscoelastic Properties of Double-Network Hydrogels.

Biological soft tissues are intrinsically viscoelastic materials which play a significant role in affecting the activity of cells. As potential artificial alternatives, double-network (DN) gels, however, are pure elastic and mechanically time independent. The viscoelasticization of DN gels is an urgent challenge in enabling DN gels to be used for advanced development of biomaterial applications. Herein, we demonstrate a simple approach to regulate the viscoelasticity of tough double-network (DN) hydrogels by forming sulfonate-metal coordination. Owing to the dynamic nature of the coordination bonds, the resultant hydrogels possess highly viscoelastic, mechanical time-dependent, and self-recovery properties. Rheological measurements are performed to investigate the linear dynamic mechanical behavior at small strains. The tensile tests and cyclic tensile tests are also systematically performed to evaluate the rate-dependent large deformation mechanical behaviors and energy dissipation behaviors of various ion-loaded DN hydrogels. It has been revealed based on the systematic analysis that robust strong sulfonate-Zr4+ coordination interactions not only serve as dynamic crosslinks imparting viscoelastic rate-dependent mechanical performances, but also strongly affect the relative strength of the first PAMPS network, thereby increasing the yielding stress σy and the fracture stress at break σb and reducing the stretch ratio at break λb. It is envisioned that the viscoelasticization of DN gels enables versatile applications in the biomedical and engineering fields.

Enhanced Rupture Force in a Cut-Dispersed Double-Network Hydrogel.

The Kirigami approach is an effective way to realize controllable deformation of intelligent materials via introducing cuts into bulk materials. For materials ranging from ordinary stiff materials such as glass, ceramics, and metals to soft materials, including ordinary hydrogels and elastomers, all of them are all sensitive to the presence of cuts, which usually act as defects to deteriorate mechanical properties. Herein, we study the influence of the cuts on the mechanical properties by introducing "dispersed macro-scale cuts" into a model tough double network (DN) hydrogel (named D-cut gel), which consists of a rigid and brittle first network and a ductile stretchable second network. For comparison, DN gels with "continuous cuts" having the same number of interconnected cuts (named C-cut gel) were chosen. The fracture tests of D-cut gel and C-cut gel with different cut patterns were performed. The fracture observation revealed that crack blunting occurred at each cut tip, and a large wrinkle-like zone was formed where the wrinkles were parallel to the propagation direction of the cut. By utilizing homemade circular polarizing optical systems, we found that introducing dispersed cuts increases the rupture force by homogenizing the stress around the crack tip surrounding every cut, which reduces stress concentration in one certain cut. We believe this work reveals the fracture mechanism of tough soft materials with a kirigami cut structure, which should guide the design of advanced soft and tough materials along this line.

Organic Photodetectors with Extended Spectral Response Range Assisted by Plasmonic Hot-Electron Injection.

Organic photodetectors (OPDs) have aroused intensive attention for signal detection in industrial and scientific applications due to their advantages including low cost, mechanical flexibility, and large-area fabrication. As one of the most common organic light-emitting materials, 8-hydroxyquinolinato aluminum (Alq3) has an absorption wavelength edge of 460 nm. Here, through the introduction of Ag nanoparticles (Ag NPs), the spectral response range of the Alq3-based OPD was successfully extended to the near-infrared range. It was found that introducing Ag NPs can induce rich plasmonic resonances, generating plenty of hot electrons, which could be injected into Alq3 and then be collected. Moreover, as a by-product of introducing Ag NPs, the dark current was suppressed by around two orders of magnitude by forming a Schottky junction on the cathode side. These two effects in combination produced photoelectric signals with significant contrasts at wavelengths beyond the Alq3 absorption band. It was found that the OPD with Ag NPs can stably generate electric signals under illumination by pulsed 850 nm LED, while the output of the reference device included no signal. Our work contributes to the development of low-cost, broadband OPDs for applications in flexible electronics, bio-imaging sensors, etc.

A Novel NDT Scanning System Based on Line Array Fast Neutron Detector and D-T Neutron Source.

A novel non-destructive testing scanning system based on a large-size line array fast neutron detector and compact D-T neutron source has been constructed. The scanning range is up to 1000 mm, and the resolution is better than 1 mm. The fast neutron detection subsystem consists of a polypropylene zinc sulfide scintillator embedded with wavelength-shifting fibers, coupled with a light lens and a scientific CCD camera. With a new rotating tritium target, the lifetime of the compact D-T neutron source could achieve ten hours. The experimental results indicate that the scanning method based on line array fast neutron detector and D-T neutron source is feasible and enables the detection of slits on the order of 0.5 mm in width. Fast neutron tomography has been realized by this detection system too.

Improvement of alfalfa resistance against Cd stress through rhizobia and arbuscular mycorrhiza fungi co-inoculation in Cd-contaminated soil.

Rhizobia and arbuscular mycorrhiza fungi (AMF) are important symbiotic microbes that are advantageous to plants growing in metal-contaminated soil. However, it remains unclear how inoculated microbes affect rhizosphere microbial communities or whether subsequent changes in rhizosphere microbiomes contribute to improving plant resistance under metal stress. This study investigated the effects of rhizobia and AMF inoculation on alfalfa resistance to Cd stress. The response of rhizosphere microbial communities to inoculation and its role in increasing alfalfa' ability to cope with stress were further analyzed using high-throughput sequencing of 16S and ITS rRNA genes. Results showed that single rhizobia or AMF inoculation significantly improved alfalfa resistance to Cd stress, while their co-inoculation resulted in the greatest overall improvement. Improved resistance was reflected by the significant mitigation of Cd-induced lipid peroxidation and reactive oxygen species (ROS) stress caused by increases in antioxidant enzyme activities along with co-inoculation. Furthermore, co-inoculation significantly altered the rhizosphere microbial community structure by decreasing fungal community diversity and increasing bacterial community diversity. Results of partial least squares path modeling (PLS-PM) and variation partitioning analysis (VPA) showed that the rhizosphere bacterial community predominated over the fungal community with respected to improvements in resistance to Cd stress under the co-inoculation treatments. This improvement was specifically seen in the enrichment of certain key bacterial taxa (including Proteobacteria, Actinobacteria, Acidobacteria, and Chloroflexi) induced by the rhizobia and AMF co-inoculation, enhancing alfalfa' ability to uptake rhizosphere nutrients and reduce its release of photosynthetically-derived carbon (C) into soil. Our findings revealed that the co-inoculation of multiple symbiotic microbes can assist plants to effectively cope with Cd stress, providing a greater understanding of rhizosphere bacterial taxa in the microbe-induced phytomanagement.

Micro- and nano-encapsulated metal and alloy-based phase-change materials for thermal energy storage.

An overview of recent literature on the micro- and nano-encapsulation of metallic phase-change materials (PCMs) is presented in this review to facilitate an understanding of the basic knowledge, selection criteria, and classification of commonly used PCMs for thermal energy storage (TES). Metals and alloys with high thermal conductivity can be used as PCMs for rapid heat storage in compact systems owing to their high volumetric TES density. The emerging application of metal PCMs in different fields such as solar thermal energy management, smart wearable devices with thermal comfort control, and cooling of electronic devices call for the need of micro- and nano-TES particles, which can be synthesised in different forms to satisfy specific requirements. As metals are easily oxidised, especially at the micro- and nano-level, encapsulation of metal-based PCM particles is important for sustainable use at high operating temperature in ambient conditions. Recent studies focusing on the encapsulation of metallic PCMs at the micro- and nano-level have been reviewed and classified in terms of the melting point of metal/alloy PCMs used and types of encapsulation materials, such as oxides, polymers, carbon, and metals. The current review is expected to provide an outlook on novel metal and alloy PCMs with function-directed structures and superior TES properties for a broad range of applications.

A moveable neutron imaging facility using D-T neutron source based on a compact accelerator.

A moveable multi-use neutron imaging facility was constructed based on a compact accelerator D-T neutron source, for use in thermal and fast neutron radiography and tomography. Experiments were carried out to investigate the imaging quality for different standard samples. The smallest width of a slit that can be tested by digitized thermal neutron radiography was found to be 0.06 mm, while the smallest diameter of holes tested by digitized fast neutron radiography was 0.5 mm. A gadolinium wire of 0.2 mm in diameter within a multi-material structure was reconstructed clearly with thermal neutron tomography, and holes in a light material were reconstructed with fast neutron tomography.

Synthesis of Au@Cu2O Core-Shell Nanoparticles with Tunable Shell Thickness and Their Degradation Mechanism in Aqueous Solutions.

Metal@semiconductor core-shell nanoparticles (NPs) are widely used in photocatalysts, sensors, and optical applications owing to their unique metal-semiconductor interface and the integration of the properties from both core and shell materials. Although many efforts have been made toward the precise synthesis of Au@Cu2O core-shell structures, the chemical stability of Au@Cu2O aqueous suspensions, which is of great significance in many related applications, is not mentioned in any published research. Herein we report the synthesis of Au@Cu2O core-shell NPs with small shell thickness from 2 to 40 nm through a wet-chemistry method. The UV-vis absorption properties are found to be tunable with Cu2O thickness in the range of 2-40 nm. Furthermore, the chemical stability of Au@Cu2O core-shell nanoparticle suspensions in water/ethanol mixed solvents is investigated. It is found that water/ethanol mixed solvents with a larger amount of water are more likely to deteriorate the stability of Au@Cu2O NPs by oxidizing Cu2O to CuO. The results from this work may provide useful information for the preparation of metal@Cu2O water-based suspensions that are expected to be used for SERS, photocatalyst, or photothermal applications.

Distribution, Origins and Hazardous Effects of Polycyclic Aromatic Hydrocarbons in Topsoil Surrounding Oil Fields: A Case Study on the Loess Plateau, China.

The Loess Plateau has one of the most vulnerable ecological environments in the world, but it also contains abundant oil and gas resources that are regularly exploited, which has resulted in serious environmental problems. Therefore, it is important to analyze the polycyclic aromatic hydrocarbons (PAHs) present in the topsoil of this region. The ∑16PAHs concentrations between 1980-1999 and 2000-2019 ranged from 1134.20-15871.04 and 1010.67-18,068.80 µg kg-1, with average values of 5021.30 and 5662.82 µg kg-1. All samples displayed heavy pollution levels according to European soil quality standards. In addition, among the measured physicochemical properties, the soil organic carbon (SOC) had the greatest influence on PAHs, while soil particle size distribution had the smallest effect. Source apportionment indicated that the two main sources were petroleum source (37.57%) and vehicular traffic source (25.88%). Lastly, an assessment of the carcinogenic risks illustrated that more focus should be placed on the dermal pathway in which the human body is exposed to soil PAHs. Overall, the carcinogenic risks in different populations did not exceed 10-4, but there was still a potential carcinogenic risk in some age groups, especially in adult women.

In situ TEM observation of liquid-state Sn nanoparticles vanishing in a SiO2 structure: a potential synthetic tool for controllable morphology evolution from core-shell to yolk-shell and hollow structures.

Precise design of hollow nanostructures can be realized via various approaches developed in the last two decades, endowing nanomaterials with unique structures and outstanding performances, showing their usefulness in a broad range of fields. Herein, we demonstrate the formation of SnO2@SiO2 hollow nanostructures, for the first time, by interaction between liquid state Sn cores and SiO2 shell structures inside Sn@SiO2 core-shell nanoparticles with real-time observation via in situ transmission electron microscopy (TEM). Based on the in situ results, designed transformation of the nanoparticle structure from core-shell Sn@SiO2 to yolk-shell Sn@SiO2 and hollow SnO2@SiO2 is demonstrated, showing the controllable structure of core-shell Sn@SiO2 nanoparticles via fixing liquid-state Sn inside a SiO2 shell which has a certain Sn containing capacity. The present approach expands the toolbox for the design and preparation of yolk-shell and hollow nanostructures, thus providing us with a new strategy for fabrication of more complicated nanostructures.

Synthesis of Sn/Ag-Sn nanoparticles via room temperature galvanic reaction and diffusion.

Tin (Sn) has a low melting temperature, i.e., 231.9 °C for the bulk, and the capability to form compounds with many metals. The galvanic reaction between Sn nanoparticles (NPs) as the core and silver nitrate at room temperature under argon gas in an organic solvent without any reducing power, was employed for the first time to coat an Ag-Sn intermetallic shell, i.e., Ag3Sn and/or Ag4Sn, on Sn NPs. For spherical Sn NPs, the NPs retained a spherical shape after coating. Uniform and Janus structures consisting of a ß-Sn core with Ag-Sn shell were observed in the resulting NPs and their population related to the input molar ratios of the metal precursors. The observation of the intermetallic shell is general for both spherical and rod-shape Sn NPs. The formation of the intermetallic shell indicated that two reactions occurred sequentially, first reduction of Ag ions to Ag atoms by the Sn core, followed by interdiffusion of Ag and Sn to form the Ag-Sn intermetallic shell.

Designer α1,6-Fucosidase Mutants Enable Direct Core Fucosylation of Intact N-Glycopeptides and N-Glycoproteins.

Core fucosylation of N-glycoproteins plays a crucial role in modulating the biological functions of glycoproteins. Yet, the synthesis of structurally well-defined, core-fucosylated glycoproteins remains a challenging task due to the complexity in multistep chemical synthesis or the inability of the biosynthetic α1,6-fucosyltransferase (FUT8) to directly fucosylate full-size mature N-glycans in a chemoenzymatic approach. We report in this paper the design and generation of potential α1,6-fucosynthase and fucoligase for direct core fucosylation of intact N-glycoproteins. We found that mutation at the nucleophilic residue (D200) did not provide a typical glycosynthase from this bacterial enzyme, but several mutants with mutation at the general acid/base residue E274 of the Lactobacillus casei α1,6-fucosidase, including E274A, E274S, and E274G, acted as efficient glycoligases that could fucosylate a wide variety of complex N-glycopeptides and intact glycoproteins by using α-fucosyl fluoride as a simple donor substrate. Studies on the substrate specificity revealed that the α1,6-fucosidase mutants could introduce an α1,6-fucose moiety specifically at the Asn-linked GlcNAc moiety not only to GlcNAc-peptide but also to high-mannose and complex-type N-glycans in the context of N-glycopeptides, N-glycoproteins, and intact antibodies. This discovery opens a new avenue to a wide variety of homogeneous, core-fucosylated N-glycopeptides and N-glycoproteins that are hitherto difficult to obtain for structural and functional studies.

Glycan Remodeling of Human Erythropoietin (EPO) Through Combined Mammalian Cell Engineering and Chemoenzymatic Transglycosylation.

The tremendous structural heterogeneity of N-glycosylation of glycoproteins poses a great challenge for deciphering the biological functions of specific glycoforms and for developing protein-based therapeutics. We have previously reported a chemoenzymatic glycan remodeling method for producing homogeneous glycoforms of N-glycoproteins including intact antibodies, which consist of endoglycosidase-catalyzed deglycosylation and novel glycosynthase-catalyzed transglycosylation, but its application to complex glycoproteins carrying multiple N-glycans remains to be examined. We report here site-selective chemoenzymatic glycosylation remodeling of recombinant human erythropoietin (EPO) that contains three N-glycans. We found that the generation of a HEK293S GnT I knockout FUT8 overexpressing cell line enabled the production of an unusual Man5GlcNAc2Fuc glycoform, which could be converted to the core-fucosylated GlcNAc-EPO intermediate acceptor for enzymatic transglycosylation. With this acceptor, homogeneous sialylated glycoform or azide-tagged glycoform were produced using the glycosynthase (EndoF3-D165A) catalyzed transglycosylation. Interestingly, a remarkable site-selectivity was observed in the transglycosylation reactions, leading to the introduction of two N-glycans selectively at the Asn-38 and Asn-83 sites, which was confirmed by a detailed MS/MS analysis of the transglycosylation product. Finally, a different N-glycan was attached at the third (Asn-24) site by pushing the enzymatic transglycosylation with a distinct glycan oxazoline, achieving the site-selective glycosylation modification of the protein. This study represents the first example of site-selective chemoenzymatic glycan engineering of complex glycoproteins carrying multiple N-glycans.

A facile synthesis of a complex type N-glycan thiazoline as an effective inhibitor against the antibody-deactivating endo-ß-N-acetylglucosaminidases.

Endo-ß-N-acetylglucosaminidases are a class of endoglycosidases that deglycosylate N-glycans from glycoproteins. We describe here a facile synthesis of a complex type N-glycan thiazoline as a new mechanism-based inhibitor for this class of enzymes. The synthesis started with the readily available sialoglycopeptide (SGP) and its conversion into the glycan thiazoline through several enzymatic and chemical reactions. The synthetic glycan thiazoline showed potent inhibitory activity against several endoglycosidases including the two antibody-deactivating enzymes, Endo-S and Endo-S2, from human pathogen Streptococcus pyogenes, which would be useful as tools for structural and functional studies of these enzymes.

BODIPY-Based Fluorescent Probes for Sensing Protein Surface-Hydrophobicity.

Mapping surface hydrophobic interactions in proteins is key to understanding molecular recognition, biological functions, and is central to many protein misfolding diseases. Herein, we report synthesis and application of new BODIPY-based hydrophobic sensors (HPsensors) that are stable and highly fluorescent for pH values ranging from 7.0 to 9.0. Surface hydrophobic measurements of proteins (BSA, apomyoglobin, and myoglobin) by these HPsensors display much stronger signal compared to 8-anilino-1-naphthalene sulfonic acid (ANS), a commonly used hydrophobic probe; HPsensors show a 10- to 60-fold increase in signal strength for the BSA protein with affinity in the nanomolar range. This suggests that these HPsensors can be used as a sensitive indicator of protein surface hydrophobicity. A first principle approach is used to identify the molecular level mechanism for the substantial increase in the fluorescence signal strength. Our results show that conformational change and increased molecular rigidity of the dye due to its hydrophobic interaction with protein lead to fluorescence enhancement.

Glycosylation of quinone-fused polythiophene for reagentless and label-free detection of E. coli.

In this report, a new polythiophene interface is fabricated containing fused quinone moieties which are then glycosylated to form a carbohydrate platform for bacterial detection. Very importantly, this interface can be used for label-free and reagentless detection, both by electrochemical and Quartz Crystal Microbalance (QCM) transducers and by using the direct pili-mannose binding as well as Concanavalin A (Con A) mediated lipopolysaccharides (LPS)-mannose binding. The conductive polymer's unique collective properties are very sensitive to very minor perturbations, which result in significant changes of electrical conductivity and providing amplified sensitivity and improved limits of detection (i.e., 25 cell/mL for electrochemical sensor and 50 cells/mL for QCM sensor), a widened logarithmic range of detection (i.e., 3-7 for pili-mannose binding and 2-8 for Con A mediated binding), high specificity and selectivity, and an extraordinary reliability by a mechanism of internal validation. With these analytical performances, the described biosensor is envisaged for being capable of differentiating Gram-negative bacterial strain and species, for many important applications.

Highly water-soluble BODIPY-based fluorescent probe for sensitive and selective detection of nitric oxide in living cells.

A highly water-soluble BODIPY dye bearing electron-rich o-diaminophenyl groups at 2,6-positions was prepared as a highly sensitive and selective fluorescent probe for detection of nitric oxide (NO) in living cells. The fluorescent probe displays an extremely weak fluorescence with fluorescence quantum yield of 0.001 in 10 mM phosphate buffer (pH 7.0) in the absence of NO as two electron-rich o-diaminophenyl groups at 2,6-positions significantly quench the fluorescence of the BODIPY dye via photoinduced electron transfer mechanism. The presence of NO in cells enhances the dye fluorescence dramatically. The fluorescent probe demonstrates excellent water solubility, membrane permeability, and compatibility with living cells for sensitive detection of NO.