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The use of water to reduce friction has always played a significant role in a wide range of areas ranging from biology to engineering. Many efforts have been made to extensively investigate the water behavior between two contacted surfaces, but its role in water-based friction remains incompletely understood.Herein, we utilize the sum-frequency generation (SFG) spectroscopy to identify interfacial water structures upon adjusting the wettability of titanium dioxide (TiOIt demonstrates that enhanced wettability induces higher friction on the TiO

To determine the fractional vegetation cover (FVC ) and associated driving factors of modeling in mining areas, six types of data were used as driving factors and three methods—multi-linear regression (MLR ), geographically weighted regression (GWR ), and geographically weighted artificial neural network (GWANN )—were adopted in the modeling. The experiments, conducted in Shengli mining areas located in Xilinhot city, China, show that the MLR model without consideration of spatial heterogeneity and spatial non-stationarity performs the worst and that the GWR model presents obvious location differences, since it predefines a linear relationship which is unable to describe FVC for some locations. The GWANN model, improving on these defects, is the most suitable model for the FVC driving process in mining areas; it outperforms the other two models, with root-mean-square error (RMSE ) and mean absolute percentage error (MAPE ) reaching 0.16 and 0.20. It has improvements of approximately 24% in RMSE and 33% in MAPE compared to the MLR model, and those values grow to 59% and 71% when compared with the GWR model.

One Zn(ii) coordination polymer is used to selectively detect CrO42− and Fe3+ in water via luminescence quenching and enhancement methods.

Land use provides crucial data for earth science research and its accuracy has always been a hot topic. Various auxiliary data are used to improve the classification accuracy of land use. The digital elevation model (DEM) is one of the common auxiliary data since topography directly affects the surface landscape. However, few researches focus on the impact of the DEM on the classification accuracy of images. In this study, the terrain steepness index (TSI) was initially put forward to study the effect of the DEM on the classification accuracy of the land use/cover. Seven areas with different terrain were taken as the studied areas and the classification and regression tree was utilized to derive thematic land use/cover maps. It indicated that the DEM had an impact on classification accuracy in a certain TSI extent. The developed quadratic model accurately described the correlation between the DEM and the TSI. Based on the model, the DEM with 30 m resolution had a positive impact on the classification accuracy, when the TSI varies from 9.106 to 34.014. It was concluded that the TSI index for the DEM could be effectively used in the land use/cover classification.

As a popular traditional fermented beverage, kombucha has been extensively studied for its health benefits. However, the science behind the anti-inflammatory effect of kombucha has not been well studied, and there is an urgent need to uncover the secrets of the anti-inflammatory properties of kombucha. Here, we investigate kombucha's protective effects against lipopolysaccharide (LPS)-induced sepsis and on the intestinal microecology in mice. The contents of reducing sugars, polyphenols, catechins, and organic acids in the kombucha group were identified using various methods. The results showed that the concentrations of acetic acid, gluconic acid, polyphenol, and glucuronic acid in the kombucha group were 55.70 ± 2.57 g L-1, 50.20 ± 1.92 g L-1, 2.36 ± 0.31, and 1.39 ± 0.22 g L-1, respectively. The result also demonstrated that kombucha effectively improves the survival rate from 0% to 40%, and increases the thermoregulation in LPS-treated mice, which showed decreased mobility and had lost their appetite for food. Furthermore, kombucha reduced the levels of tumor necrosis factor-α and interleukins (IL)-1β and IL-6, restored the levels of T cells and macrophages in LPS-challenged mice, alleviated the histopathological damage, and inhibited NF-κB signaling in mice with LPS-induced sepsis. We demonstrated that kombucha effectively prevents cellular immune function disorder in mice at the initial stage of sepsis and exerts an immunomodulatory effect. In addition, the effect of kombucha on the gut microbiota was investigated during sepsis. Kombucha supplementation altered the diversity of the gut microbiota and promoted the growth of butyrate-producing bacteria, which exert anti-inflammatory effects. Our results illustrate the potential of kombucha as a novel anti-inflammatory agent against the development of systemic inflammatory responses associated with sepsis.

Protein coating is a strategy for modifying and improving the surface functional properties of nanomaterials. However, the underlying mechanism behind protein coating formation, which is essential for its practical applications, remains largely unknown. Herein, we investigate the fundamental molecular mechanism of protein coating formation. Polydopamine nanospheres (PDANS) coated with bovine serum albumin (BSA) are examined in this study due to their wide biomedical potential. Our results demonstrate that BSAs can flexibly bind to PDANS and maintain their structural dynamicity. Our findings unveil that regular structure formation arises from BSAs lateral interactions via electrostatic forces. Notably, the protein coating modified PDANS surface enhances cell adhesion and proliferation as well as osteogenic differentiation. Such an enhancement is attributed to complementary surface properties provided by the dynamic PDANS-BSA complex and regular structure caused by BSA-BSA interactions in protein coating formation. This study provides a fundamental understanding of the molecular mechanism of protein coating formation, which facilitates the further development of functional protein-coated nanomaterials and guides the bioengineering decision making for biomedical applications, especially in bone tissue engineering.

Surface soil moisture (SM), as a crucial ecological element, is significant to monitor in semiarid mining areas characterized by aridity and little rainfall. The passive microwave remote sensing, which is not affected by weather, provides more accurate SM information, but the resolution is too coarse for mining areas. The existing downscaling method is usually pointed to natural scenarios like agricultural fields rather than mining areas with high-intensity mining. In this paper, combined with geoinformation related to SM, we designed a convolutional neural network (SM-Residual Dense Net, SM-RDNet) to downscale SMAP/Sentinel-1 Level-2 radiometer/radar soil moisture data (SPL2SMAP_S SM) into 10 m spatial resolution. Based on the in-site measured data, the root mean square error (RMSE) was utilized to verify the downscaling accuracy of SM-RDNet. In addition, we analyzed its performance for different data combinations, vegetation cover types and the advantages compared with random forest (RF). Experimental results show that: (1) The downscaling from the 3 km product with the combination of auxiliary data NDVI + DEM + slope performs best (RMSE 0.0366 m3/m3); (2) Effective data combinations can improve the downscaling accuracy at the range of 0.0477–0.1176 m3/m3 (RMSE); (3) The SM-RDNet shows better spatial completeness, details and accuracy than RF (RMSE improved by 0.0905 m3/m3). The proposed SM-RDNet can effectively obtain the fine-grained SM in semiarid mining areas. Our method bridges the gap between coarse-resolution microwave SM products and ecological applications of small-scale mining areas, and provides data and technical support for future research to explore how the mining effect SM in semiarid mining areas.

Photothermal therapy (PTT) is a promising strategy for cancer treatment, but its clinical application relies heavily on accurate tumor positioning and effective combination. Nanotheranostics has shown superior application in precise tumor positioning and treatment, bringing potential opportunities for developing novel PTT-based therapies. Here, a nanotheranostic agent is proposed to enhance magnetic resonance imaging (MRI)/ near-infrared fluorescence imaging (NIRFI) imaging-guided photo-induced triple-therapy for cancer. Thermosensitive liposomes co-loaded with SPIONs/IR780 and Abemaciclib (SIA-TSLs), peptide ACKFRGD, and click group 2-cyano-6-amino-benzothiazole (CABT) are co-modified on the surface of SIA-TSLs to form SIA-αTSLs. ACKFRGD can be hydrolyzed to expose the 1, 2-thiolamino groups in the presence of cathepsin B in tumors, which click cycloaddition with the cyano group on CABT, resulting in the formation of SIA-αTSLs aggregates. The aggregation of SIA-αTSLs in tumors enhances the MRI/NIRFI imaging capability and enables precise PTT. Photo-induced triple-therapy enhances precision cancer therapy. First, PTT ablates specific tumors and induces ICD via localized photothermal. Second, local tumor heating promotes the rupture of SIA-αTSLs, which release Abemaciclib to block the tumor cell cycle and inhibit Tregs proliferation. Third, injecting GM-CSF into tumor tissue leads to recruitment of dendritic cells and initiation of antitumor immunity. Collectively, these results present a promising nanotheranostic strategy for future cancer therapy.

The suitable thermal environment is a prerequisite for biological survival. In order to evaluate the change of land surface temperature (LST) and its effect on organisms, in this study, the Land sa...

Huperzine A (HupA) is an effective inhibitor of acetylcholinesterase and has attracted great interest as a therapeutic candidate for Alzheimer's disease. However, the use of HupA is limited by resource scarcity as well as by its low yields from Huperzia serrata, its primary plant source. Recent studies have shown that this compound is produced by various endophytic fungi, thereby providing a promising alternative source, as fungi are much more amenable than plants owing to their simpler genetics and the ease of manipulation. In this review, we summarize the progress in research on the methods to increase HupA production, including fermentation conditions, fungal elicitors, gene expression, and the activation of key enzymes. This review provides guidance for further studies on HupA-producing endophytic fungi aimed at efficient HupA synthesis and accumulation, and offers new approaches for studies on the regulation of high-value bioactive secondary metabolites.

Triboluminescence (TL) refers to the luminescence phenomenon at the material surface under the action of pressure or shear. This fascinating phenomenon can directly convert mechanical energy into light emission without the need for other auxiliary components; therefore, it attracts more and more researchers to conduct research in different wavelength ranges, such as X-ray, ultraviolet, visible light, and terahertz. However, there have been few reports on the study of the near-infrared (NIR) range, which is very important in the integrity of the triboluminescence research. In this research, we found that NIR light with a wavelength ranging from 800 to 1000 nm was generated by friction between solid metals and a quartz crystal. Analysis of the cross section of the quartz disk after friction revealed that the TL phenomenon had a strong relationship with the doping of metal grains into the silica. Density functional theory (DFT) and X-ray photoelectron spectroscopy were also conducted to further identify the results. We infer that such light emission arises from the implantation of metal grains into the surface of the quartz, which forms a metal-insulator junction with amorphous silica. Moreover, electron transition between the metal and the insulator, followed by a transition at the center of the defects, causes near-infrared light emission. Our research reveals the infrared luminescence behavior from a different perspective, the transfer of materials, and perhaps deepens the understanding of the near-infrared emission mechanism.

Large pore size of fibrous membrane (FM) deteriorates the cycle lifetime and rate capabilities, and the way of obtaining FM with improved electrolyte wettability and decreased pore size is still challenging. Herein, we report a facile method for the fabrication of the polydopamine modification polyacrylonitrile (PDA@PAN) FM via the combination of the spin coating and electrospinning techniques. The PDA coating increases the fiber diameter and the surface roughness of the PAN fibers, thus decreasing the pore size and mitigating the lithium dendrite formation by uniformly distributing Li-ion flux. Meanwhile, PDA modification not only improves the affinity for electrolyte and enhances the ion conductivity (1.39 mS cm−1), but also doubles the stress strength (13.92 MPa) because of the formation of more adhesion structure. Consequently, both the Li/LiFePO4 and Li/Li4Ti5O12 cells involving PDA@PAN FM demonstrate more stable cycle life and better rate capability compared with those of cells based on PAN FM and Celgard membrane. The work also provides a promising separator fabrication strategy for other energy storage systems.

The adsorption and interaction of sulfanilamide (SA) with a pristine magnesium oxide (MgO) nano-cage was scrutinized through density functional theory (DFT) calculations. All geometries were optimized at M06-2X/6-311G(d,p) level, and the single-point energy calculation was also carried out at the same level of theory. Also, natural bond orbital (NBO) analysis was carried out and the values related to Wiberg bond index (WBI), donor–acceptor interactions, and partial natural charges were inspected. The MgO nano-cage can adsorb SA more strongly with the adsorption energy (Eads) of − 41.74 kcal/mol, corresponding to the stable configurations. In addition, NBO analysis showed that the donor–acceptor interactions with SA and the MgO nano-cage are stronger. Based on our computations, the HOMO–LUMO gap of the MgO nano-cage changed to a great extent following the adsorption of the SA molecule, which corresponds to the most stable configuration that leads to improved electrical conductivity of the MgO nano-cage. The change in the gap determines the sensing mechanism, which is associated with the change in the electrical conductivity. To calculate the recovery time, transition-state theory (TST) was employed. Based on our calculation, Mg12O12–SA complex composites possess a short recovery time for the desorption of SA. The results show that the MgO nano-cage is an ideal candidate to be employed for developing SA sensors with high efficiency.

The abuse application of glyphosate can result in a potential hazard for environment and human, however its ultrasensitive detection remains challenging. Herein, a Cu

Understanding how urban residents process road network information and conduct wayfinding is important for both individual travel and intelligent transportation. However, most existing research is limited to the heterogeneity of individuals’ expression and perception abilities, and the results based on small samples are weakly representative. This paper proposes a quantitative and population-based evaluation method of wayfinding performance on city-scale road networks based on massive trajectory data. It can accurately compute and visualize the magnitude and spatial distribution differences of drivers’ wayfinding performance levels, which is not achieved by conventional methods based on small samples. In addition, a systematic index set of road network features are constructed for correlation analysis. This is an improvement on the current research, which focuses on the influence of single factors. Finally, taking 20,000 taxi drivers in Beijing as a case study, experimental results show the following: (1) Taxi drivers’ wayfinding performances show a spatial pattern of a high level on arterial road networks and a low level on secondary networks, and they are spatially autocorrelated. (2) The correlation factors of taxi drivers’ wayfinding performances mainly include anchor point, road grade, road importance, road complexity, origin-destination length, and complexity, and each factor has a different influence. (3) The path complexity has a higher correlation with the wayfinding performance level than with the path distance. (4) There is a critical point in the taxi drivers’ wayfinding performances in terms of path distance. When the critical value is exceeded, it is difficult for a driver to find a good route based on personal cognition. This research can provide theoretical and technical support for intelligent driving and wayfinding research.

BBO is one of the new metaheuristic optimization algorithms, which is based on the science of biogeography. It can be used to solve optimization problems through the migration and drift of species between habitats. Many improved BBO algorithms have been proposed, but there were still many shortcomings in global optimization, convergence speed, and algorithm complexity. In response to the above problems, this paper proposes an improved BBO algorithm (DCGBBO) by hierarchical tissue-like P system with triggering ablation rules. Membrane computing is a branch of natural computing that aims to abstract computational models (P system) from the structure and function of biological cells and from the collaboration of cell groups such as organs and tissues. In this paper, firstly, a dynamic crossover migration operator is generated to improve the global search ability and also increase the species diversity. Secondly, a dynamic Gaussian mutation operator is introduced to speed up convergence and improve local search capabilities. To guarantee the correctness and feasibility of the mutation, a unified maximum mutation rate is designed. Finally, a hierarchical tissue-like P system with triggering ablation rules is combined with the DCGBBO algorithm, making use of evolution rules and communication rules to achieve migration and mutation of solutions and reduce computational complexity. In the experiments, eight classic benchmark functions and CEC 2017 benchmark functions are applied to demonstrate the effect of our algorithm. We apply the proposed algorithm to segment four colour pictures, and the results proved to be better compared to other algorithms.

Recent years, microfluidic three-dimensional (3D) tumor culture technique has made great progress in tumor microenvironment simulation and drug screening. Meanwhile, as their functionality and complexity increase, it is more difficult for current chip models to selectively collect specific-layer cells from tumoroids for further analysis. Moreover, a simplified and robust method for tumoroid formation with highly consistent size and repeatable 3D morphology is relatively ncessary. Here, we report an ARCHITECT (ARtificial CHIp for Tumor Enables Confocal Topography observation) chip, through a dual-flip strategy to implement straightforward tumoroid establishment. This platform guarantees stable batch-to-batch tumoroids formation and allows high resolution confocal imaging. Moreover, an initial cell density as low as 65 cells per chamber is efficient to deliver a tumoroid. With this ARCHITECT chip, different-layer cells of interest could be collected from tumoroid for label-free quantitative (LFQ) proteomic analysis. For application demonstration, we mainly verified this platform for lung carcinoma (A549) tumoroid construction and proteomic analysis at out layer. Our data indicate that the out-layer cells of A549 tumoroid show extensively distinct proteomic expressions compared to two-dimensional cultured A549 cells. The up-regulated proteins are mainly related to tumorigenicity, proliferation and metastasis. And the differentially expressed proteins are mainly relevant to lipid metabolism pathway which is essential to tumor progression and proliferation. This platform provides a simplified yet robust technique to connect microfluidic tumoroid construction and LFQ proteomic analysis. The simplicity of this technique should open the way to numerous applications such as discovering the innovative targets for cancer treatment, and studying the mophological and proteomic heterogeneity of different-layer cells across the tumoroid.

The natural environment is essential for human survival and development since it provides water resources, land resources, biological resources and climate resources etc. As a developing country, China has witnessed a significant change in the natural environment in recent decades; and therefore, monitoring and mastering the status of the environment is of great significance. Due to the characteristics of large-scale and dynamic observation, remote sensing technology has been an indispensable approach for environmental monitoring. This paper reviews the satellite resources, institutions and policies for environmental monitoring in China, and the advances in research and application of remote sensing from five aspects: ecological index retrieval, environmental monitoring in protected areas, rural areas, urban areas and mining areas. The remote sensing models and methods for various types of environmental monitoring, and the specific applications in China are comprehensively summarized. This paper also points out major challenges existing at the current stage: satellite sensor problems, integrated use challenges of datasets, uncertainty in the retrieval process of ecological variables, scaling effect problems, a low degree of automation, the weak ability of forecasting and comprehensive analysis, and a lack of computational power for massive datasets. Finally, the development trend and future directions are put forward to direct the research and application of environmental monitoring and protection in the new era.

The abuse application of glyphosate can result in a potential hazard for environment and human, however its ultrasensitive detection remains challenging. Herein, a Cu2+ modulated DNA-templated silver nanoclusters (DNA-AgNCs) sensor was constructed to sensitively determine glyphosate based on the turn-on fluorescence strategy. The fluorescence quenching of DNA-AgNCs occurred with the existence of Cu2+. Upon the presence of glyphosate, the functional groups on the surface of glyphosate could chelate with Cu2+, following the fluorescence recovery of DNA-AgNCs. Through the stoichiometric methods, we unveil that Cu2+-trigged fluorescence quenching mode is a combination of static and dynamic quenching with the static mode being predominant. In DNA-AgNCs/Cu2+ system, the carboxylate, amine, and phosphonate groups of glyphosate interact with Cu2+ through chelation, in which the carboxylate oxygen, the phosphonate oxygen atoms, and the monoprotonated secondary amine nitrogen atom and Cu2+ form chelate rings. This fluorescence sensor showed a desired linearity of glyphosate analysis under the optimum conditions, ranging from 15 to 100 μg/L with a low detection down to 5 μg/L. Moreover, the proposed sensor was successfully utilized to measure glyphosate in real samples, indicating a promising application in pesticide residues detection.

This article verified the error between inversed land surface temperature (LST) and measured LST and developed the modified model based on Landsat 8 remote-sensing data. First, a single-channel alg...

Surface water pollution is one of the serious environment pollution problems, posing threat to human and other creatures. Extraction, change detection and environment evaluation of surface water are prerequisite for water resource management. Undoubtedly, remote sensing data play an important role in these researches because of its large geographic coverage and high temporal frequency. In this study, the Tianjin Binhai New Area was chosen as the study area and the surface water extraction method Modified Normalized Difference Water Index (MNDWI) was used by combining with adaptive dynamic threshold to extract surface water and detect its change. Comparing with single-band threshold, model of multi-band spectral relationship, Iterative Self-organizing Data Analysis Technique Algorithm and MNDWI, MNDWI-based adaptive dynamic threshold method performed better, which considered the influence of background. Analysis on dynamic change of water showed the area of lake and river had increased and the area of seawater had decreased. Meanwhile, the correlation analysis between area change of surface water and impact factors indicated both climatic and anthropogenic factors made positive contribution to the present water environment situation. Finally, an improved model of surface water environment evaluation was established to evaluate water quality by combining genetic algorithm (GA) and backpropagation (BP) neural network model. And the test results proved that the optimized GA-BP neural network is better than the single BP neural network. The environment evaluation indicated that water quality of the Haihe River section in the study area was poor. Therefore, water environment protection should be strengthened in this area. Some suggestions on practical management were given accordingly.

Land use directly reflects degree of human development and utilization of land. Intensity analysis of land use is a quantitative method to analyze land use changes. In this paper, land use changes in Tianjin were studied using Thematic Mapper (TM) remote sensing images in 1995, 2000, 2005, 2010 and Operational Land Imager (OLI) remote sensing image in 2015. Land use information was extracted using decision tree classification method based on CART (Classification and Regression Trees) algorithm. This paper introduced land use intensity analysis to analyze its change intensity and stationarity, respectively at interval, category and transition levels. Based on the theory, new models were developed in the transition level to analyze land use change pattern. The analysis quantifies the contribution of a certain land categories to land use change during a specific time interval. The change of land use during 1995–2015 indicated that Tianjin experienced rapid urban development with the area of urban land increased by about 7.5%. This study provided a reference for the sustainable development of land use in Tianjin.

In order to describe and study the communication between the cells or between cells and environment, tissue P system with symport/antiport rules and tissue-like P system with evolutional symport/antiport rules was introduced as a class of distributed parallel computing model, the object can change their location or evolve in the communication process. But the objects and evolutional rules are not specific, so in this paper, a new computing model for P system called tissue-like P system with mutational symport/antiport rules and trigger mechanism (TPMTM) is proposed, where all genetic materials are encoded by binary strings and the evolutional rules are defined by mutational rules. The TPMTM' s computational power is testified. Extraordinary, tissue-like P system with one cell what executing mutational antiport rules of length of mutational position at most 5 or executing mutational symport rules of length of mutational position at most 7 are testified Turing universal. So, this tissue P system with mutational communication rules that we proposed is computable.

Electrical stimulation (ES) is widely applied to promote nerve regeneration. Currently, metal needles are used to exert external ES, which may cause pain and risk of infection. In this work, a multiblock conductive nerve scaffold with self-powered ES by the consumption of glucose and oxygen is prepared. The conductive substrate is prepared by in situ polymerization of polypyrrole (PPy) on the nanofibers of bacterial cellulose (BC). Platinum nanoparticles are electrodeposited on the anode side for glucose oxidation, while nitrogen-doped carbon nanotubes (N-CNTs) are loaded on the cathode side for oxygen reduction. The scaffold shows good mechanical property, flexibility and conductivity. The scaffold can form a potential difference of above 300 mV between the anode and the cathode in PBS with 5 × 10-3 m glucose. Dorsal root ganglions cultured on the Pt-BC/PPy-N-CNTs scaffold are 55% longer in mean neurite length than those cultured on BC/PPy. In addition, in vivo study indicates that the Pt-BC/PPy-N-CNTs scaffold promotes nerve regeneration compared with the BC/PPy group. This paper presents a novel design of a nerve scaffold with self-powered ES. In the future, it can be combined with other features to promote nerve regeneration.

Preparing a separator regulating Li+ flux is considered to be a promising method to solve the Li dendrite problem of lithium metal battery (LMB). Herein, for the first time, the multiscale-structured polyvinylidene fluoride/polyacrylonitrile/vermiculite nanosheets (PVdF/PAN/VNs) fibrous membranes are obtained via a one-step electrospinning method. As-prepared PVdF/PAN/VNs fibrous membrane display the multiscale-structure with VNs embedded into the PVdF/PAN fibers accompanied by high porosity and interpenetrated pore, facilitating in homogenizing Li+ flux distribution at the separator/electrode interface, and thus inhibiting the Li dendrite formation and growth. Meanwhile, because of synergistic effect of PAN and VNs with liquid electrolyte, as-prepared PVdF/PAN/VNs fibrous membrane demonstrates good wettability, high ionic conductivity, strong tensile strength, excellent thermal stability and enhanced electrochemical stability, guaranteeing the improvement of battery performance and safety of LMB. More importantly, compared to the Celgard membrane based cell, as-prepared PVdF/PAN/VNs membrane based Li/Li4Ti5O12 cell shows better rate capability with a discharge capacity of 139.3 mA h g−1 at 10C rate, and the PVdF/PAN/VNs membrane based Li/Li cell displays stable lithium plating/stripping behavior with lower overpotential. This work provides a new strategy of regulating Li+ flux distribution for promoting the practical application of LMBs.

Rich nano channels of zeolites give themselves excellent adsorption capacity, which have been widely used in environmental protection and catalysis. The adsorption process and existential form of the molecules in the nano channels are affected by the spatial confinement and regularity of the nanoporous channels. In this work, the adsorption of glycerol molecules in NaY and USY zeolites nano channels were studied. The results showed that adsorption quantity of glycerol molecules in nano channels and formation of glycerol molecular clusters were significantly affected by the static adsorption time. Due to the spatial confinement of the nanoporous channel, the H⋯O bond length and the HO⋯O angle were reduced. TEM scanning results indicated that the size of glycerol molecular cluster in nano channel was smaller than that of the bulk ones outside nano channel. 1H NMR results suggested that the spin motion of the hydroxyl hydrogen bond was enhanced. Computer simulation results showed that intermolecular hydrogen bonds were formed between the glycerol molecular cluster and oxygen atoms on the channel wall. This work may show new light on the study of molecular immobilization in spatial confinement.

Huntingtin interaction protein 2 (HIP2) is an E2 ubiquitin-conjugating enzyme associated with neurodegenerative diseases, and HIP2 mRNA has been implicated as a potential blood biomarker for Parkinson’s disease (PD). However, it is unclear whether the alteration of HIP2 expression may contribute to the development of PD, and whether the change of HIP2 in blood could reflect its expression in the brain or motor functions in PD patients. In this study, we established a mouse line with HIP2 haploinsufficiency. The reduction of the HIP2 expression led to spontaneous motor function impairment and dopaminergic neuronal loss. Furthermore, HIP2 haploinsufficiency increased the susceptibility of mice to 6-hydroxydopamine (6-OHDA) and caused severe loss of dopaminergic neurons. Interestingly, in a 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) mouse model for PD, we observed concurrent, highly correlated decrease of HIP2 expression in the brain and in the blood. Using blood samples from more than 300 patients, we validated the decreased HIP2 mRNA in PD patients, including de novo patients. Finally, in a 1-year, 20-patient study, we observed reversed blood HIP2 mRNA levels accompanying improved motor and overall daily functions in 75% of the PD patients with instructed Tai Chi training. Therefore, our in vivo studies have indicated HIP2 insufficiency as a contributing factor for PD, and functionally validated blood HIP2 as a useful and reversible biomarker for PD.

OBJECTIVES: This study explored whether TALENs‐mediated non‐homologous end joining (NHEJ) targeting the mutation site can correct the aberrant β‐globin RNA splicing, and ameliorate the β‐thalassaemia phenotype in β(654) mice. MATERIAL AND METHODS: TALENs vectors targeted to the human β‐globin gene (HBB) IVS2‐654C >T mutation in a mouse model were constructed and selected to generate double heterozygous TALENs(+)/β(654) mice. The gene editing and off‐target effects were analysed by sequencing analysis. β‐globin expression was identified by RT‐PCR and Western blot analysis. Various clinical indices including haematologic parameters and tissue pathology were examined to determine the therapeutic effect in these TALENs(+)/β(654) mice. RESULTS: Sequencing analysis revealed that the HBB IVS2‐654C >T point mutation was deleted in over 50% of the TALENs(+)/β(654) mice tested, and off‐target effects were not detected. RT‐PCR and Western blot analysis confirmed the expression of normal β‐globin in TALENs(+)/β(654) mice. The haematologic parameters were significantly improved as compared with their affected littermates. The proportion of nucleated cells in bone marrow was considerably decreased, splenomegaly with extramedullary haematopoiesis was reduced, and significant decreases in iron deposition were seen in spleen and liver of the TALENs(+)/β(654) mice. CONCLUSION: These results suggest effective treatment of the anaemia phenotype in TALENs(+)/β(654) mice following deletion of the mutation site by TALENs, demonstrating a simple and straightforward strategy for gene therapy of β(654)‐thalassaemia in the future.

Mutations in fused in sarcoma (Fus) cause familial amyotrophic lateral sclerosis (ALS) and occasionally frontotemporal dementia. Here we report the establishment and characterization of a novel knockin (KI) rat model expressing a Fus point mutation (R521C) via CRISPR/Cas9. The mutant animals developed adult-onset learning and memory behavioral deficits, with reduced spine density in hippocampal neurons. Remarkably, sleep-wake cycle and circadian abnormalities preceded the onset of cognitive deficit. RNA-seq study further demonstrated altered expression of some key sleep and circadian regulators, such as orexin/hypocretin receptor type 2 and casein kinase 1 epsilon, in the mutant rats. Therefore, we have established a rodent model expressing physiological level of a pathogenic mutant FUS, and we found cognitive impairment as a main behavioral deficit at mid age. Furthermore, we have revealed a new role of FUS in sleep and circadian regulation and demonstrated that functional change in FUS could cause sleep-wake and circadian disturbance as early symptoms.