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NPR1 is a master regulator of the defence transcriptome induced by the plant immune signal salicylic acid1-4. Despite the important role of NPR1 in plant immunity5-7, understanding of its regulatory mechanisms has been hindered by a lack of structural information. Here we report cryo-electron microscopy and crystal structures of Arabidopsis NPR1 and its complex with the transcription factor TGA3. Cryo-electron microscopy analysis reveals that NPR1 is a bird-shaped homodimer comprising a central Broad-complex, Tramtrack and Bric-à-brac (BTB) domain, a BTB and carboxyterminal Kelch helix bundle, four ankyrin repeats and a disordered salicylic-acid-binding domain. Crystal structure analysis reveals a unique zinc-finger motif in BTB for interacting with ankyrin repeats and mediating NPR1 oligomerization. We found that, after stimulation, salicylic-acid-induced folding and docking of the salicylic-acid-binding domain onto ankyrin repeats is required for the transcriptional cofactor activity of NPR1, providing a structural explanation for a direct role of salicylic acid in regulating NPR1-dependent gene expression. Moreover, our structure of the TGA32-NPR12-TGA32 complex, DNA-binding assay and genetic data show that dimeric NPR1 activates transcription by bridging two fatty-acid-bound TGA3 dimers to form an enhanceosome. The stepwise assembly of the NPR1-TGA complex suggests possible hetero-oligomeric complex formation with other transcription factors, revealing how NPR1 reprograms the defence transcriptome.
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Proteínas de Arabidopsis , Arabidopsis , Arabidopsis/metabolismo , Proteínas de Arabidopsis/metabolismo , Fatores de Transcrição de Zíper de Leucina Básica/metabolismo , Microscopia Crioeletrônica , Perfilação da Expressão Gênica , Regulação da Expressão Gênica de Plantas , Imunidade Vegetal , Proteínas de Plantas/metabolismo , Ácido Salicílico/metabolismo , Fatores de Transcrição/metabolismoRESUMO
Ischemic stroke is characterized by the presence of reactive microglia. However, its precise involvement in stroke etiology is still unknown. We used metabolic profiling and showed that chemokine like factor 1 (CKLF1) causes acute microglial inflammation and metabolic reprogramming from oxidative phosphorylation to glycolysis, which was reliant on the AMP-activated protein kinase (AMPK)-mammalian target of rapamycin (mTOR)-hypoxia inducible factor 1α (HIF-1α) signaling pathway. Once activated, microglia enter a chronic tolerant state as a result of widespread energy metabolism abnormalities, which reduces immunological responses, including cytokine release and phagocytosis. Metabolically dysfunctional microglia were also found in mice using genome-wide RNA sequencing after chronic administration of CKLF1, and there was a decrease in the inflammatory response. Finally, we showed that the loss of CKLF1 reversed the defective immune response of microglia, as indicated by the maintenance its phagocytosis to neutrophils, thereby mitigating the long-term outcomes of ischemic stroke. Overall, CKLF1 plays a crucial role in the relationship between microglial metabolic status and immune function in stroke, which prepares a potential therapeutic strategy for ischemic stroke.
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AVC Isquêmico , Acidente Vascular Cerebral , Animais , Camundongos , Citocinas/metabolismo , Tolerância Imunológica , AVC Isquêmico/metabolismo , Mamíferos/metabolismo , Microglia/metabolismo , Acidente Vascular Cerebral/metabolismoRESUMO
Chemokine receptor 5 (CCR5) is one of the main co-receptors of HIV-1, and has been found to be a potential therapeutic target for stroke. Maraviroc is a classic CCR5 antagonist, which is undergoing clinical trials against stroke. As maraviroc shows poor blood-brain barrier (BBB) permeability, it is of interest to find novel CCR5 antagonists suitable for neurological medication. In this study we characterized the therapeutic potential of a novel CCR5 antagonist A14 in treating ischemic stroke mice. A14 was discovered in screening millions compounds in the Chemdiv library based on the molecular docking diagram of CCR5 and maraviroc. We found that A14 dose-dependently inhibited the CCR5 activity with an IC50 value of 4.29 µM. Pharmacodynamic studies showed that A14 treatment exerted protective effects against neuronal ischemic injury both in vitro and vivo. In a SH-SY5Y cell line overexpressing CCR5, A14 (0.1, 1 µM) significantly alleviated OGD/R-induced cell injury. We found that the expression of CCR5 and its ligand CKLF1 was significantly upregulated during both acute and recovery period in focal cortical stroke mice; oral administration of A14 (20 mg·kg-1·d-1, for 1 week) produced sustained protective effect against motor impairment. A14 treatment had earlier onset time, lower onset dosage and much better BBB permeability compared to maraviroc. MRI analysis also showed that A14 treatment significantly reduced the infarction volume after 1 week of treatment. We further revealed that A14 treatment blocked the protein-protein interaction between CCR5 and CKLF1, increasing the activity of CREB signaling pathway in neurons, thereby improving axonal sprouting and synaptic density after stroke. In addition, A14 treatment remarkably inhibited the reactive proliferation of glial cells after stroke and reduced the infiltration of peripheral immune cells. These results demonstrate that A14 is a promising novel CCR5 antagonist for promoting neuronal repair after ischemic stroke. A14 blocked the protein-protein interaction between CKLF1 and CCR5 after stroke by binding with CCR5 stably, improved the infarct area and promoted motor recovery through reversing the CREB/pCREB signaling which was inhibited by activated CCR5 Gαi pathway, and benefited to the dendritic spines and axons sprouting.
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Antagonistas dos Receptores CCR5 , AVC Isquêmico , Neuroblastoma , Acidente Vascular Cerebral , Animais , Humanos , Camundongos , AVC Isquêmico/tratamento farmacológico , Maraviroc/uso terapêutico , Maraviroc/farmacologia , Simulação de Acoplamento Molecular , Receptores CCR5/metabolismo , Acidente Vascular Cerebral/tratamento farmacológico , Antagonistas dos Receptores CCR5/química , Antagonistas dos Receptores CCR5/farmacologiaRESUMO
AMPA receptors are tetrameric ionic glutamate receptors, which mediate 90% fast excitatory synaptic transmission induced by excitatory glutamate in the mammalian central nervous system through the activation or inactivation of ion channels. The alternation of synaptic AMPA receptor number and subtype is thought to be one of the primary mechanisms that involve in synaptic plasticity regulation and affect the functions in learning, memory, and cognition. The increasing of surface AMPARs enhances synaptic strength during long-term potentiation, whereas the decreasing of AMPARs weakens synaptic strength during the long-term depression. It is closely related to the AMPA receptor as well as its subunits assembly, trafficking, and degradation. The dysfunction of any step in these precise regulatory processes is likely to induce the disorder of synaptic transmission and loss of neurons, or even cause neuropsychiatric diseases ultimately. Therefore, it is useful to understand how AMPARs regulate synaptic plasticity and its role in related neuropsychiatric diseases via comprehending architecture and trafficking of the receptors. Here, we reviewed the progress in structure, expression, trafficking, and relationship with synaptic plasticity of AMPA receptor, especially in anxiety, depression, neurodegenerative disorders, and cerebral ischemia.
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Plasticidade Neuronal , Receptores de AMPA , Animais , Ácido Glutâmico/metabolismo , Mamíferos/metabolismo , Plasticidade Neuronal/fisiologia , Transporte Proteico , Receptores de AMPA/metabolismo , Sinapses/metabolismo , Transmissão Sináptica/fisiologiaRESUMO
With the emerging recognition of open scientific hardware, rapid prototyping technology such as three-dimensional (3-D) printing is becoming widely available for fields such as cryobiology, and cryopreservation, where material selection for instruments and hardware has traditionally been problematic due to extreme low temperatures. A better understanding of the mechanical properties of 3-D printing thermoplastics at cryogenic temperatures is essential to material selection, part design, and printing optimization. The goal of the present study was to explore the feasibility of development for a 3-D printed device ('CryoTensileDevice') to hold a test specimen in liquid nitrogen and be mounted in standard mechanical testing systems to evaluate 3-D printing material behaviors at cryogenic temperatures. The CryoTensileDevice was prototyped with flexible filaments with a per-unit material cost of < US$5 and a printing time of < 5 h. The commonly used printing filament polylactic acid (PLA) was selected to evaluate the utility of the CryoTensileDevice. At room temperature, the CryoTensileDevice did not significantly (P > 0.05) affect PLA tensile measurements such as Young's modulus, yield stress, yield strain, stress at break, or strain at break. With the CryoTensileDevice, specimens 3-D printed with PLA at 50%, 75%, and 100% infill rates had comparable tensile properties when tested at room and liquid nitrogen temperatures. The PLA showed superior performance in tensile properties in comparison to acrylonitrile butadiene styrene (ABS). This device can assist characterization of 3-D printing approaches for cryogenic work, and opens a pathway for future innovations to create a variety of 3-D printed devices to study a wide range of material properties for cryogenic applications.
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Hierarchical emulsions are interesting for both scientific researches and practical applications. Hierarchical emulsions prepared by microfluidics require complicated device geometry and delicate control of flow rates. Here, a versatile method is developed to design hierarchical emulsions using microfluidic 3D droplet printing in droplet. The process of droplet printing in droplet mimics the dragonfly laying eggs and has advantages of easy processing and flexible design. To demonstrate the capability of the method, double emulsions and triple emulsions with tunable core number, core size, and core composition are prepared. The hierarchical emulsions are excellent templates for the developments of functional materials. Flattened crescent-moon-shaped particles are then fabricated using double emulsions printed in confined 2D space as templates. The particles are excellent delivery vehicles for 2D interfaces, which can load and transport cargos through a well-defined trajectory under external magnetic steering. Microfluidic 3D droplet printing in droplet provides a powerful platform with improved simplicity and flexibility for the design of hierarchical emulsions and functional materials.
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Microfluídica , Odonatos , Animais , Emulsões , Impressão TridimensionalRESUMO
The weak-value-amplification technique has shown great importance in the measurement of tiny physical effects. Here we introduce a polarization-dependent angular velocity measurement system consisting of two Glan prisms and a true zero-order half-wave plate, where a non-Fourier-limited Gaussian pulse acts as the meter. The angular velocities measurements results agree well with theoretical predictions, and its uncertainties are bounded by the Cramér-Rao bound. We also investigate uncertainties of angular velocities for different numbers of detected photons and the smallest reliable postselection probability, which can reach ${3.42*10^{- 6}}$.
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Staphylococcal protein A (SpA) is an important virulence factor from Staphylococcus aureus responsible for the bacterium's evasion of the host immune system. SpA includes five small three-helix-bundle domains that can each bind with high affinity to many host proteins such as antibodies. The interaction between a SpA domain and the Fc fragment of IgG was partially elucidated previously in the crystal structure 1FC2. Although informative, the previous structure was not properly folded and left many substantial questions unanswered, such as a detailed description of the tertiary structure of SpA domains in complex with Fc and the structural changes that take place upon binding. Here we report the 2.3-Å structure of a fully folded SpA domain in complex with Fc. Our structure indicates that there are extensive structural rearrangements necessary for binding Fc, including a general reduction in SpA conformational heterogeneity, freezing out of polyrotameric interfacial residues, and displacement of a SpA side chain by an Fc side chain in a molecular-recognition pocket. Such a loss of conformational heterogeneity upon formation of the protein-protein interface may occur when SpA binds its multiple binding partners. Suppression of conformational heterogeneity may be an important structural paradigm in functionally plastic proteins.
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Fragmentos Fc das Imunoglobulinas/química , Proteína Estafilocócica A/química , Sequência de Aminoácidos , Sítios de Ligação , Calorimetria , Cristalografia por Raios X , Espectroscopia de Ressonância Magnética , Modelos Moleculares , Dados de Sequência Molecular , Ligação Proteica , Estrutura Secundária de Proteína , Soluções , Staphylococcus aureus/metabolismo , Homologia Estrutural de ProteínaRESUMO
The weak-value-based metrology is very promising and has attracted a lot of attention in recent years because of its remarkable ability in signal amplification. However, it is suggested that the upper limit of the precision of this metrology cannot exceed that of classical metrology because of the low sample size caused by the probe loss during postselection. Nevertheless, a recent proposal shows that this probe loss can be reduced by the power-recycling technique, and thus enhance the precision of weak-value-based metrology. Here we experimentally realize the power-recycled interferometric weak-value-based beam-deflection measurement and obtain the amplitude of the detected signal and white noise by discrete Fourier transform. Our results show that the detected signal can be strengthened by power recycling, and the power-recycled weak-value-based signal-to-noise ratio can surpass the upper limit of the classical scheme, corresponding to the shot-noise limit. This work sheds light on higher precision metrology and explores the real advantage of the weak-value-based metrology over classical metrology.
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FAAP20 is an integral component of the Fanconi anemia core complex that mediates the repair of DNA interstrand crosslinks. The ubiquitin-binding capacity of the FAAP20 UBZ is required for recruitment of the Fanconi anemia complex to interstrand DNA crosslink sites and for interaction with the translesion synthesis machinery. Although the UBZ-ubiquitin interaction is thought to be exclusively encapsulated within the ßßα module of UBZ, we show that the FAAP20-ubiquitin interaction extends beyond such a canonical zinc-finger motif. Instead, ubiquitin binding by FAAP20 is accompanied by transforming a disordered tail C-terminal to the UBZ of FAAP20 into a rigid, extended ß-loop that latches onto the complex interface of the FAAP20 UBZ and ubiquitin, with the invariant C-terminal tryptophan emanating toward I44(Ub) for enhanced binding specificity and affinity. Substitution of the C-terminal tryptophan with alanine in FAAP20 not only abolishes FAAP20-ubiquitin binding in vitro, but also causes profound cellular hypersensitivity to DNA interstrand crosslink lesions in vivo, highlighting the indispensable role of the C-terminal tail of FAAP20, beyond the compact zinc finger module, toward ubiquitin recognition and Fanconi anemia complex-mediated DNA interstrand crosslink repair.
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Proteínas de Grupos de Complementação da Anemia de Fanconi/química , Ubiquitina/química , Reparo do DNA , Proteínas de Grupos de Complementação da Anemia de Fanconi/metabolismo , Modelos Moleculares , Ligação Proteica , Domínios e Motivos de Interação entre Proteínas , Triptofano/química , Ubiquitina/metabolismoRESUMO
We propose a scheme for generation of the stationary continuous-variable entanglement and Einstein-Podolsky-Rosen (EPR) steering between an optical cavity mode and a nanomechanical resonator (NMR) mode. The cavity and the NMR are commonly coupled with two separated quantum dots (QDs), where the two QDs are driven simultaneously by a strong laser field. By adjusting the frequency of the strong laser field, the two QDs are nearly trapped on different dressed states, which is helpful to generate the entanglement between the cavity mode and the NMR mode. Due to the combined resonant interaction of the two QDs with the NMR-cavity subsystem, the photon and the phonon created and (or) annihilated are correlated. In this regime, the optimal entanglement of the two modes is obtained and the purity of the state of the NMR-cavity subsystem is near to 1. Furthermore, the coupling strength between the cavity and two QDs is different from the dot-NMR coupling strength, which leads to the different mean occupation numbers of the cavity and the NMR. In this case, one-way EPR steering is observed. In addition, through analyzing the purity, we find the conditions of the existence for the different types of EPR steering.
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The rapidly approaching smart/wearable energy era necessitates advanced rechargeable power sources with reliable electrochemical properties and versatile form factors. Here, as a unique and promising energy storage system to address this issue, we demonstrate a new class of heterolayered, one-dimensional (1D) nanobuilding block mat (h-nanomat) battery based on unitized separator/electrode assembly (SEA) architecture. The unitized SEAs consist of wood cellulose nanofibril (CNF) separator membranes and metallic current collector-/polymeric binder-free electrodes comprising solely single-walled carbon nanotube (SWNT)-netted electrode active materials (LiFePO4 (cathode) and Li4Ti5O12 (anode) powders are chosen as model systems to explore the proof of concept for h-nanomat batteries). The nanoporous CNF separator plays a critical role in securing the tightly interlocked electrode-separator interface. The SWNTs in the SEAs exhibit multifunctional roles as electron conductive additives, binders, current collectors and also non-Faradaic active materials. This structural/physicochemical uniqueness of the SEAs allows significant improvements in the mass loading of electrode active materials, electron transport pathways, electrolyte accessibility and misalignment-proof of separator/electrode interface. As a result, the h-nanomat batteries, which are easily fabricated by stacking anode SEA and cathode SEA, provide unprecedented advances in the electrochemical performance, shape flexibility and safety tolerance far beyond those achievable with conventional battery technologies. We anticipate that the h-nanomat batteries will open 1D nanobuilding block-driven new architectural design/opportunity for development of next-generation energy storage systems.
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The special "dual" hydrogeological structure in karst areas causes rainfall easily "leaking" into the ground, resulting a unique "karst drought". In these areas, drought and insufficient water resources seriously restrict the sustainable development of agriculture. In order to restore the ecology of karst desertification, develop ecological industries, improve the utilization efficiency of water resources, and advance water-saving agriculture in such areas, literature review method was applied to discuss the suitability of agronomic water-saving measures in karst areas. The results are as follows. (1) Agronomic water-saving measures including tillage, mulching, water-fertilizer coupling, chemical regulation, crop allocation and deficit irrigation can all enhance the crop WUE. For example, deep tillage and deep loosening increased the WUE by 15.1 % and 15.9 % respectively. The WUE of spring wheat under straw mulching increased by 17.17 %-43.01 % compared with that under mulching film. Increased density of intercropping corn and wheat saved 9.85 % of water. (2) The cultural or natural particularity of karst areas limits the application of all agronomic water-saving measures in karst areas, and therefore choices and adjustments are necessary according to local conditions: â No tillage should be adopted because of the high output of labor force; â¡ straw mulching need to be crushed; ⢠the coupling of water and fertilizer reaches better effect when applied to crops several hours before rainfall; ⣠the shallow soil layer and the complexity of preparing water retaining agent make it unsuitable to use water retaining agent; ⤠agroforestry with dwarf and dense planting is more suitable; ⥠crop deficit irrigation can be carried out by using ecological small pools. Based on the above results, proposes are offered in the following. First, it is necessary to construct the optimal model of regional water and fertilizer coupling in karst areas, and apply composite agronomic water-saving measures. Second, it is suggested to establish a model of coordinating forest, grain and grass, and vigorously develop ecologically derivative agroforestry. Third, there is a necessity to strengthen the research and development of technology about soil and water leakage monitoring and resistance, and intensify studies on "five waters" transformation at the basin scale. The research results and implication are an important reference for developing water-saving agriculture, solving the shortage of agricultural water resources, ensuring the sustainability of agriculture and improving farmers' living standards. Rational use of agronomic water-saving measures is of great significance to enhance the utilization efficiency of water resources and boost regional economy in karst desertification areas.
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In karst desertification (KD) regions, surface water (SW) easily enters underground through pore fissures and sinkholes despite the presence of abundant precipitation. Such regions have a typical distribution of "soil above and water below", and, thus, the unique "karst drought" occurs. Hence, an urgent and primary problem in combating KD is to reach highly efficient utilization of water resources in these regions. We selected three karst research areas with different levels of karst desertification and different geomorphic types. By monitoring the storage and transformation of five types of water in the agroforestry system-precipitation, SW, groundwater (GW), soil water (SoW), plant water (PW), the following results were obtained: (1) In KD regions, a positive correlation was found among available precipitation, rainfall, and land evapotranspiration (LE), and LE was approximately equivalent to soil evaporation. (2) To varying degrees, agroforestry brings ecological benefits, including reducing surface runoff, increasing soil infiltration, lowering the transpiration rate, and reducing soil evaporation, thus achieving efficient use of water resources. (3) From 100 % rainfall, the transformation rates of SW, GW, PW, and SoW reached 0.14-12.71 %, 9.43-30.20 %, 9.79-49.97 %, and 40.72-82.58 %, respectively, and SoW showed a larger reserve than the other three types. (4) Drought stress contributes to the improvement of water use efficiency (WUE). Affected by drought stress, WUE was found to be the highest in a medium-intensity karst desertification environment. The transformation mechanisms of the five types of water observed in the agroforestry system provide a reference for efficient utilization of water resources in KD regions as well as theoretical support for addressing karst drought. They are also essential in helping to advance the ecological derivative industry, boosting the economy in karst mountainous areas, and controlling karst desertification.
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This work deals with the fabrication of lignin containing cellulose nanofiber (LCNF)/Ag2Se films for thermoelectric applications. Ag2Se nanoparticles were synthesized within the LCNF network through in situ methods, employing Na2SeO3 and AgNO3 along with microwave energy treatment. LCNF/Ag2Se films fabricated with two LCNF : Ag2Se weight percent ratios (i.e., 50 : 50 and 30 : 70) were used to construct a flexible thermoelectric module. The obtained Ag2Se nanoparticles displayed a uniform size distribution in the LCNF network with smaller dimensions from the microwave energy treated group. The microstructure of LCNF/Ag2Se films was improved by hot-pressing, leading to enhanced film density thermoelectric properties. At a differential temperature of 50 K, films with 50% and 70% of Ag2Se exhibited output voltages of 18 and 21 mV; and Seebeck coefficients of -60 and -70 µV K-1 at 350 K, respectively. When microwave energy was applied, the films at 50% and 70% Ag2Se showed highest output voltages of 19 and 33 mV, respectively, and Seebeck coefficients of -63.3 and -110 µV K-1 at 350 K. The low-cost fabrication process associated with this module opens a pathway for applications such as energy harvesting.
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Polymer waste is currently a big and challenging issue throughout the world. Waste tires represent an important source of polymer waste. Therefore, it is highly desirable to recycle functional fillers from waste tires to develop composite materials for advanced applications. The primary theme of this review involves an overview of developing polystyrene (PS) composites using materials from recycled tires as fillers; waste tire recycling in terms of ground tire rubbers, carbon black, and textile fibers; surface treatments of the fillers to optimize various composite properties; and the mechanical, fire retarding, acoustic, and electromagnetic field (EMI) shielding performances of PS composite materials. The development of composite materials from polystyrene and recycled waste tires provides a novel avenue to achieve reductions in carbon emission goals and closed-loop plastic recycling, which is of significance in the development of circular economics and an environmentally friendly society.
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The medium-intensity karst desertification environment is typically characterized by more rocks and less soil. The abandoned land in the construction areas of the dry-hot river valley hydropower station has more infertile soil, severe land degradation, and very low land productivity. Therefore, it is urgent to improve the soil quality to curb the increasingly degrading land and reuse the construction site. Few studies have focused on the effect of soil restoration and comprehensive evaluation of soil quality with multi-treatment in abandoned land in the dry-hot valley hydropower station construction area. Here, 9 soil restoration measures and 1 control group were installed at the Guangzhao Hydropower Station construction in Guizhou Province, China, for physical and chemical property analysis. In total, 180 physical and 90 chemical soil samples were collected on three occasions in May, August, and December 2022. Soil fertility and quality were evaluated under various measures using membership functions and principal component analysis (PCA). This study showed that almost all measures could enhance soil water storage capacity (The average total soil porosity of 9 soil treatments was 57.56%, while that of the control group was 56.37%). With the increase in soil porosity, soil evaporation became stronger, and soil water content decreased. Nevertheless, no decrease in soil water content was observed in the presence of vegetation cover (soil water content: 16.46% of hairy vetch, 13.99% of clover, 13.77% of the control). They also proved that manure, synthetic fertilizer, and straw could promote total and available nutrients (Soil total nutrient content, or the total content of TNãTPãTK,was presented as: synthetic fertilizer (11.039g kg-2)>fowl manure (10.953g kg-2)>maize straw (10.560g kg-2)>control (9.580g kg-2);Total available nutrient content in soil, or the total content of AN,AP,A,was shown as:fowl manure (1287.670 mg kg-1)>synthetic fertilizer (925.889 mg kg-1)>sheep manure (825.979 mg kg-1)>control (445.486 mg kg-1). They could also promote soil fertility, among which the first two reached the higher comprehensive soil quality. Fertilizer was conducive to improve soil quality and fertility, yet long-term application could cause land degradation like soil non-point source pollution, compaction, and land productivity decline. Ultimately, combining fertilizer with biochar or manure is recommended to improve soil fertility. Biochar and green manure could play an apparent role in soil improvement only when there is abundant soil water. The above views provide theoretical support for curbing soil degradation, improving soil fertility and quality, enhancing land productivity, and promoting the virtuous cycle of the soil ecosystem.
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Conservação dos Recursos Naturais , Solo , Solo/química , China , Conservação dos Recursos Naturais/métodos , Água/análise , Água/química , Fertilizantes/análiseRESUMO
Inspired by creatures, abundant stimulus-responsive hydrogel actuators with diverse functionalities have been manufactured for applications in soft robotics. However, constructing a shape memory and self-sensing bilayer hydrogel actuator with high mechanical strength and strong interfacial bonding still remains a challenge. Herein, a novel bilayer hydrogel with a stimulus-responsive TEMPO-oxidized cellulose nanofibers/poly(N-isopropylacrylamide) (TOCN/PNIPAM) layer and a non-responsive TOCN/polyacrylamide (TOCN/PAM) layer is proposed as a thermosensitive actuator. TOCNs as a nano-reinforced phase provide a high mechanical strength and endow the hydrogel actuator with a strong interfacial bonding. Due to the incorporation of TOCNs, the TOCN/PNIPAM hydrogel exhibits a high compressive strength (~89.2 kPa), elongation at break (~170.7 %) and tensile strength (~24.0 kPa). The prepared PNIPAM/TOCN/PAM hydrogel actuator performs the roles of an encapsulation, jack, temperature-controlled fluid valve and temperature-control manipulator. The incorporation of Fe3+ further endows the bilayer hydrogel actuator with a synergistic performance of shape memory and temperature-driven, which can be used as a temperature-responsive switch to detect ambient temperature. The PNIPAM/TOCN/PAM-Fe3+ conductive hydrogel can be assembled into a flexible sensor and generate sensing signals when driven by temperature changes to achieve real-time feedback. This research may lead to new insights into the design and manufacturing of intelligent flexible soft robots.
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Background: The causal associations between dietary intake and the risk and severity of Inflammatory Arthritis (IA) are currently unknown. Objective: In this study, we aimed to investigate the causal relationship between nine dietary categories (30 types of diet) and IA using Mendelian randomization (MR). Methods: We analyzed data from 30 diets and IA in a genome-wide association study (GWAS). Single nucleotide polymorphisms (SNPs) that could influence the results of MR analyses were screened out through the Mendelian Randomization Pleiotropy RESidual Sum and Outlier (MR-PRESSO) test. SNPs were analyzed through two-sample bidirectional MR using inverse variance weighting, MR-Egger regression, and weighted median method. The multiplicity and heterogeneity of SNPs were assessed using MR-Egger intercept term tests and Cochran's Q tests. FDR correction was used to correct the p-values. Results: IVW results showed that Beef intake [Odds ratio (OR) = 2.862; 95% confidence interval (CI), 1.360-6.021, p = 0.006, p_fdr < 0.05] was positively associated with rheumatoid arthritis(RA); Dried fruit intake (OR = 0.522; 95% CI, 0.349-0.781, p = 0.002, p_fdr < 0.05), and Iron intake (OR = 0.864; 95%CI, 0.777-0.960, p = 0.007, p_fdr < 0.05) were negatively associated with RA, all of which were evidence of significance. Fresh fruit intake (OR = 2.528. 95% CI, 1.063-6.011, p = 0.036, p_fdr > 0.05) was positively associated with psoriatic arthritis (PsA); Cheese intake (OR = 0.579; 95% CI, 0.367-0.914, p = 0.019, p_fdr > 0.05) was negatively associated with PsA; both were suggestive evidence. Processed meat intake (OR = 0.238; 95% CI, 0.100-0.565, p = 0.001, p_fdr < 0.05) was negatively associated with reactive arthritis (ReA), a protective factor, and significant evidence. All exposure data passed the heterogeneity check (Cochrane's Q test p > 0.05) and no directional pleiotropy was detected. Leave-one-out analyses demonstrated the robustness of the causal relationship in the positive results. Conclusion: Our study presents genetic evidence supporting a causal relationship between diet and an increased risk of IA. It also identifies a causal relationship between various dietary modalities and different types of IA. These findings have significant implications for the prevention and management of IA through dietary modifications.
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Material surface micromorphology can modulate cellular behavior and promote osteogenic differentiation through cytoskeletal rearrangement. Bone reconstruction requires precise regulation of gene expression in cells, a process governed by epigenetic mechanisms such as histone modifications, DNA methylation, and chromatin remodeling. We constructed osteon-mimetic concentric microgrooved titanium surfaces with different groove sizes and cultured bone marrow-derived mesenchymal stem cells (BMSCs) on the material surfaces to study how they regulate cell biological behavior and osteogenic differentiation through epigenetics. We found that the cells arranged in concentric circles along the concentric structure in the experimental group, and the concentric microgrooved surface did not inhibit cell proliferation. The results of a series of osteogenic differentiation experiments showed that the concentric microgrooves facilitated calcium deposition and promoted osteogenic differentiation of the BMSCs. Concentric microgrooved titanium surfaces that were 30 µm wide and 10 µm deep promoted osteogenic differentiation of BMSC by increasing WDR5 expression via H3K4 trimethylation upregulation.