[Research progress of silk-based biomaterials for peripheral nerve regeneration].

Objective: To describe the research progress of silk-based biomaterials in peripheral nerve repair and provide useful ideals to accelerate the regeneration of large-size peripheral nerve injury. Methods: The relative documents about silk-based biomaterials used in peripheral nerve regeneration were reviewed and the different strategies that could accelerate peripheral nerve regeneration through building bioactive microenvironment with silk fibroin were discussed. Results: Many silk fibroin tissue engineered nerve conduits have been developed to provide multiple biomimetic microstructures, and different microstructures have different mechanisms of promoting nerve repair. Biomimetic porous structures favor the nutrient exchange at wound sites and inhibit the invasion of scar tissue. The aligned structures can induce the directional growth of nerve tissue, while the multiple channels promote the axon elongation. When the fillers are introduced to the conduits, better growth, migration, and differentiation of nerve cells can be achieved. Besides biomimetic structures, different nerve growth factors and bioactive drugs can be loaded on silk carriers and released slowly at nerve wounds, providing suitable biochemical cues. Both the biomimetic structures and the loaded bioactive ingredients optimize the niches of peripheral nerves, resulting in quicker and better nerve repair. With silk biomaterials as a platform, fusing multiple ways to achieve the multidimensional regulation of nerve microenvironments is becoming a critical strategy in repairing large-size peripheral nerve injury. Conclusion: Silk-based biomaterials are useful platforms to achieve the design of biomimetic hierarchical microstructures and the co-loading of various bioactive ingredients. Silk fibroin nerve conduits provide suitable microenvironment to accelerate functional recovery of peripheral nerves. Different optimizing strategies are available for silk fibroin biomaterials to favor the nerve regeneration, which would satisfy the needs of various nerve tissue repair. Bioactive silk conduits have promising future in large-size peripheral nerve regeneration.

Achieving Tunable Monomeric TADF and Aggregated RTP via Molecular Stacking.

Organic emitters with both thermally activated delayed fluorescence (TADF) and room-temperature phosphorescence (RTP) have attracted widespread interest for their intriguing luminescent properties. Herein, a series of triphenylamine-substituted isoquinoline derivatives possessing monomeric TADF and aggregated RTP properties are reported. As the molecules exhibited various forms of π-π and charge transfer (CT) stacking with different intensities, inter/intramolecular CT can be meticulously modulated to achieve tunable TADF-RTP. Aggregated phosphorescence originates from intermolecular CT initiated by CT dimers, whereas monomeric TADF is facilitated by intramolecular CT enhanced by π-π dimers. Leveraging the properties of these molecules, luminescent materials with tunable TADF-RTP properties in multistates are obtained by molecular substitution position alignment, dealing with different solvents, grinding, adjusting concentration, changing polymer matrix, photoactivation, and heat treatment. This work is critical for a deeper understanding of construction and regulation of the TADF-RTP dual-channel emission, enabling the development of advanced optoelectronic devices with tailored emission properties.

A fructan-type garlic polysaccharide upregulates immune responses in macrophage cells and in immunosuppressive mice.

The anti-inflammatory effects of plant polysaccharides are well known. However, the stimulatory effects of polysaccharides under immunosuppressive conditions and their link with the polysaccharide structure is underexplored. In this work, the immune modulatory effects of a garlic polysaccharide (GP) are investigated via in vitro and vivo methods. It is observed that GP enhance the immune response of macrophages (RAW264.7) as indicated by the elevated levels of nitric oxide, TNF-α and IL-6. The observation that GP are able to stimulate the immune response in vitro was then explored with the use of an immunosuppressed mouse model. Surprisingly, GP exhibited dose-dependent up-regulatory impacts on the cyclophosphamide (CTX) suppressed levels of cytokines such as IFN-γ and IL-6 and immunoglobulins (e.g. IgA and IgG). The GP intervention reversed histopathological damage to the small intestine and spleen and increased fecal short-chain fatty acid levels. Moreover, GP modulates the gut microbiota dysbiosis by increasing the abundance of immunogenic bacteria such as g__norank_f__Erysipelotrichaceae, while inhibiting the over-abundance of g_Bacteroides. Functional predictions indicated that gut biomarkers of GP possessed the functions of glycoside hydrolase family 32 (GH32) and ß-fructofuranosidase. It is concluded that GP is a promising immunostimulant for immune-compromised individuals.

Targeting Fascin1 maintains chondrocytes phenotype and attenuates osteoarthritis development.

Osteoarthritis (OA) is the most common form of arthritic disease, and phenotypic modification of chondrocytes is an important mechanism that contributes to the loss of cartilage homeostasis. This study identified that Fascin actin-bundling protein 1 (FSCN1) plays a pivotal role in regulating chondrocytes phenotype and maintaining cartilage homeostasis. Proteome-wide screening revealed markedly upregulated FSCN1 protein expression in human OA cartilage. FSCN1 accumulation was confirmed in the superficial layer of OA cartilage from humans and mice, primarily in dedifferentiated-like chondrocytes, associated with enhanced actin stress fiber formation and upregulated type I and III collagens. FSCN1-inducible knockout mice exhibited delayed cartilage degeneration following experimental OA surgery. Mechanistically, FSCN1 promoted actin polymerization and disrupted the inhibition of Decorin on TGF-ß1, leading to excessive TGF-ß1 production and ALK1/Smad1/5 signaling activation, thus, accelerated chondrocyte dedifferentiation. Intra-articular injection of FSCN1-overexpressing adeno-associated virus exacerbated OA progression in mice, which was mitigated by an ALK1 inhibitor. Moreover, FSCN1 inhibitor NP-G2-044 effectively reduced extracellular matrix degradation in OA mice, cultured human OA chondrocytes, and cartilage explants by suppressing ALK1/Smad1/5 signaling. These findings suggest that targeting FSCN1 represents a promising therapeutic approach for OA.

A microfluidic paper-based fluorescent sensor integrated with a smartphone platform for rapid on-site detection of omethoate pesticide.

A novel approach combing a fluorescent microfluidic paper strip with a portable smartphone-based sensing platform is developed for rapid and sensitive detection of omethoate pesticide. The detection mechanism of the microfluidic paper strip is based on the fluorescence quenching of graphene oxide (GO) toward the cyanine 3 (Cy3)-labeled aptamer (Cy3-APT). Upon exposure to omethoate, the Cy3-APT detaches from the surface of GO, resulting in considerable fluorescence recovery, which can be visualized through the smartphone-based sensing platform. The images are analyzed through a self-developed app embedded with a pretrained convolutional neural network model, achieving a high regression coefficient of 0.9964 at an omethoate concentration range of 0-750 nM. The smartphone-based platform enables rapid on-site detection of omethoate pesticide in real samples within 10 min, with results comparable to those obtained using standard methods. In short, the proposed microfluidic paper-based fluorescent sensor combined with the smartphone-based sensing platform enhances the detection performance toward organophosphorus pesticides.

Research on the castor oil pressing extraction mechanism based on multi-physics coupling simulation.

Castor oil has been widely used in various fields due to its properties, leading to large attention for its extraction mechanism. To research the castor oil extraction mechanism during pressing, a self-developed uniaxial compression device combined with an in situ observation is established. The effects of pressure, loading speed, and creep time are investigated, and a finite element model coupling with multi-physics is established for castor oil pressing extraction, verified by the seed cake experimental compression strain matching with numerical simulation under the same condition. Simulation results indicated that the pressing oil extraction process can be divided into two stages, Darcy's speed shows the first sharp decreasing stage and the second gradual increasing stage during porosity and pressure interaction. In the first stage, porosity is dominant on Darcy's speed. With porosity decreasing, the pressure effect on Darcy's speed exceeds porosity in the second stage. With seed thickness increasing, Darcy's speed first increases and then decreases. With loading speed increasing, Darcy's speed increases. Darcy's speed decreases constantly with creep time increasing. This study can provide basic theoretical and practical guidance for oil extraction.

Quantifying Plant Signaling Pathways by Integrating Luminescence-Based Biosensors and Mathematical Modeling.

Plants have evolved intricate signaling pathways, which operate as networks governed by feedback to deal with stressors. Nevertheless, the sophisticated molecular mechanisms underlying these routes still need to be comprehended, and experimental validation poses significant challenges and expenses. Consequently, computational hypothesis evaluation gains prominence in understanding plant signaling dynamics. Biosensors are genetically modified to emit light when exposed to a particular hormone, such as abscisic acid (ABA), enabling quantification. We developed computational models to simulate the relationship between ABA concentrations and bioluminescent sensors utilizing the Hill equation and ordinary differential equations (ODEs), aiding better hypothesis development regarding plant signaling. Based on simulation results, the luminescence intensity was recorded for a concentration of 47.646 RLUs for 1.5 µmol, given the specified parameters and model assumptions. This method enhances our understanding of plant signaling pathways at the cellular level, offering significant benefits to the scientific community in a cost-effective manner. The alignment of these computational predictions with experimental results emphasizes the robustness of our approach, providing a cost-effective means to validate mathematical models empirically. The research intended to correlate the bioluminescence of biosensors with plant signaling and its mathematical models for quantified detection of specific plant hormone ABA.

circRUNX2.2, highly expressed in Marek's disease tumor tissues, functions in cis to regulate parental gene RUNX2 expression.

Marek's disease (MD), an immunosuppression disease induced by Marek's disease virus (MDV), is one of the significant diseases affecting the health and productive performance of poultry. The roles of circular RNAs (circRNAs) in MD development were poorly understood. In this study, we found a circRNA derived from exon 6 of RUNX family transcription factor 2 (RUNX2) gene, named circRUNX2.2, was highly expressed in chicken tumorous spleens (TS) induced by MDV. Through fluorescence in situ hybridization and nuclear-cytoplasmic separation assay, we determined circRUNX2.2 was mainly located in the nucleus. Knockout experiments confirmed that the flanking complementary sequences (RCMs) mediated its circularization. Gain of function assay and dual luciferase reporter gene assay revealed that circRUNX2.2 could promote the expression of RUNX2 via binding with its promoter region. RNA antisense purification assay and mass spectrometry assay showed circRUNX2.2 could recruit proteins such as CHD9 protein. Knocking down CHD9 expression decreased the expression of RUNX2 gene, which confirmed the positive regulation that circRUNX2.2 on RUNX2 expression was probably facilitated via recruiting CHD9 protein. Functional experiments showed that circRUNX2.2 promoted the proliferation of the MD lymphoma-derived chicken cell line, MDCC-MSB1, which confirmed the potential oncogenic role of circRNX2.2 in tumor development. In conclusion, we found that the RUNX2-derived circRUNX2.2 can positively regulate the transcription of the parental gene RUNX2 in a cis-acting manner. The high expression of circRUNX2.2 in MD tumor tissues indicated that it might mediate MD lymphoma progression.

Current multi-scale biomaterials for tissue regeneration following spinal cord injury.

Spinal cord injury (SCI) may cause loss of motor and sensory function, autonomic dysfunction, and thus disrupt the quality of life of patients, leading to severe disability and significant psychological, social, and economic burden. At present, existing therapy for SCI have limited ability to promote neural function recovery, and there is an urgent need to develop innovative regenerative approaches to repair SCI. Biomaterials have become a promising strategy to promote the regeneration and repair of damaged nerve tissue after SCI. Biomaterials can provide support for nerve tissue by filling cavities, and improve local inflammatory responses and reshape extracellular matrix structures through unique biochemical properties to create the optimal microenvironment at the SCI site, thereby promoting neurogenesis and reconnecting damaged spinal cord tissue. Considering the importance of biomaterials in repairing SCI, this article reviews the latest progress of multi-scale biomaterials in SCI treatment and tissue regeneration, and evaluates the relevant technologies for manufacturing biomaterials.

Tracing groundwater nitrate sources in an intensive agricultural region integrated of a self-organizing map and end-member mixing model tool.

The traceability of groundwater nitrate pollution is crucial for controlling and managing polluted groundwater. This study integrates hydrochemistry, nitrate isotope (δ15N-NO3- and δ18O-NO3-), and self-organizing map (SOM) and end-member mixing (EMMTE) models to identify the sources and quantify the contributions of nitrate pollution to groundwater in an intensive agricultural region in the Sha River Basin in southwestern Henan Province. The results indicate that the NO3--N concentration in 74% (n = 39) of the groundwater samples exceeded the WHO standard of 10 mg/L. According to the results of EMMTE modeling, soil nitrogen (68.4%) was the main source of nitrate in Cluster-1, followed by manure and sewage (16.5%), chemical fertilizer (11.9%) and atmospheric deposition (3.3%). In Cluster-2, soil nitrogen (60.1%) was the main source of nitrate, with a significant increase in the contribution of manure and sewage (35.5%). The considerable contributions of soil nitrogen may be attributed to the high nitrogen fertilizer usage that accumulated in the soil in this traditional agricultural area. Moreover, it is apparent that most Cluster-2 sampling sites with high contributions of manure and sewage are located around residential land. Therefore, the arbitrary discharge and leaching of domestic sewage may be responsible for these results. Therefore, this study provides useful assistance for the continuous management and pollution control of groundwater in the Sha River Basin.