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In the context of the San Gavain hydroelectric power station diversion tunnel project in Peru, this paper studies the surrounding rock instability mechanism using a combination of numerical simulation methods and model test and presents the enclosing rock instability criterion based on the catastrophe model. The study demonstrates that the distribution of stress and displacement during tunnel excavation is more affected by the presence of laminated joints; the thinner the layer thickness, the more prominent the influence of laminations, and the higher the deformation of the surrounding rock. With the increase in layer thickness, the resultant displacement shows the law of gradual decrease; when the layer thickness is greater than 16 cm, the rate of decrease gradually slows down, and the maximum displacement is 0.201 mm. The failure mode of the layered perimeter rock tunnel with a 45° inclination angle primarily shows up as tensile deformation at the left arch shoulder and shear slip deformation at the right arch foot under the combined action of blasting disturbance load and excavation. Based on the instability analysis of the fold catastrophe model and cups catastrophe model, the influence of bending deformation between layers of surrounding rock is generally greater than shear slip deformation. The instability criterion Δ＜0 exists in all working conditions, bending instability damage may occur in all cases. When the layer thickness is greater than 24 cm, the shear slip instability criterion is greater than zero for 0–2 ms, and the system is always in a stable state, and when the layer thickness is less than 24 cm, the system may be destabilized at 1.5 ms.

Peripheral nerve injury (PNI) seriously affects the health and life of patients, and is an urgent clinical problem that needs to be resolved. Nerve implants prepared from various biomaterials have played a positive role in PNI, but the effect should be further improved and thus new biomaterials is urgently needed. Ovalbumin (OVA) contains a variety of bioactive components, low immunogenicity, tolerance, antimicrobial activity, non-toxicity and biodegradability, and has the ability to promote wound healing, cell growth and antimicrobial properties. However, there are few studies on the application of OVA in neural tissue engineering. In this study, OVA implants with different spatial structures (membrane, fiber, and lyophilized scaffolds) were constructed by casting, electrospinning, and freeze-drying methods, respectively. The results showed that the OVA implants had excellent physicochemical properties and were biocompatible without significant toxicity, and can promote vascularization, show good histocompatibility, without excessive inflammatory response and immunogenicity. The in vitro results showed that OVA implants could promote the proliferation and migration of Schwann cells, while the in vivo results confirmed that OVA implants (the E5/70% and 20 kV 20 μL/min groups) could effectively regulate the growth of blood vessels, reduce the inflammatory response and promote the repair of subcutaneous nerve injury. Further on, the high-throughput sequencing results showed that the OVA implants up-regulated differential expression of genes related to biological processes such as tumor necrosis factor-α (TNF-α), phosphatidylinositide 3-kinases/protein kinase B (PI3K-Akt) signaling pathway, axon guidance, cellular adhesion junctions, and nerve regeneration in Schwann cells. The present study is expected to provide new design concepts and theoretical accumulation for the development of a new generation of nerve regeneration implantable biomaterials.

To understand the seasonal variations in shellfish community structure, the composition and diversity of shellfish in the intertidal zone of the Changshan Archipelago, China, were investigated. We investigated the composition and diversity of shellfish species in the intertidal zone (including NCD1, NCD2, BCD1, BCD2, TJD1, TJD2, DQD1, DQD2, NHD1, and NHD2) of five representative islands and 10 survey stations in the Changshan Archipelago during the low tide period in July and October 2021 and February and May 2022, and the water quality parameters of point water and interstitial water were analyzed. The results showed that the bottom material of the Changshan Archipelago was generally rock or gravel and the salinity fluctuated with the seasons. The salinity was high in summer and fall while low in spring and winter, with an average of 30.92±0.84. Compared with spring, summer, and fall, the temperature changed significantly in winter, with an average of (4.51±0.32) ℃ and the highest temperature being 23.48 ℃ during spring, summer, and fall. In general, the dissolved oxygen in the main islands of Changshan Archipelago (North and South Changshan Islands) was relatively low, with an average of (8.59±0.38) mg/L, while that in Tuoji Island, Daqin Island, and Nanhuangcheng Island was relatively high, with an average of (9.95±0.51) mg/L. A total of 12 species of shellfish were collected in this survey, including Crassostrea sp., Monodonta labio Linnaeus, Littorina brevicula, Mytilus galloprovincialis, Patelloida pygmaea, Chlorostoma rustica, Reishia clavigera, Thais luteostoma, Ocinebrellus inornata, Cellana toreuma, Ruditapes philippinarum, and Rapana venosa. The number of shellfish species in each season was the highest in spring, with an average of eight species, followed by in fall, with an average of six species. Winter had the least number of shellfish species collected, with an average of four species. In addition, the North and South Changshan Islands presented the most shellfish species at eight and nine species, respectively. The number of shellfish collected in DQD was the least (six species). There were differences in shellfish density at different survey sites, among which DQD2 had the highest density, with an average density of 41.26 ind./m2. The lowest density was in NCD2, and the average density was 13.71 ind./m2. In the same season, the shellfish density at different survey sites was different, the proportion of dominant species at different survey sites was also different. In spring, the density of Crassostrea sp., Cellana toreuma, and Chlorostoma rustica was high, while in summer, the density of Crassostrea sp., Mytilus galloprovincialis, Littorina brevicula, and Cellana toreuma was high. In fall, the density of Crassostrea sp., Littorina brevicula, and Mytilus galloprovincialis was the highest, while in winter, the density of Crassostrea sp., Patelloida pygmaea, and Cellana toreuma was the highest. The species diversity (H´) of shellfish in each tidal area of the survey site is shown as middle tidal zone (1.44) > low tidal zone (1.40) > high tidal zone (0.44). Overall, the average shellfish species diversity in the 10 survey sites was spring (1.26) > winter (1.21) > fall (1.11) > summer (0.95). The average evenness index of species (J´) in the 10 survey stations was 0.55, among which the evenness index of DQD2, NCD2, NHD2, and TJD1 shellfish was 0.67, 0.64, 0.64, and 0.55, respectively. The evenness index of shellfish in each tidal area of the survey site was in order of middle tidal zone (0.67) > low tidal zone (0.59) > high tidal zone (0.29). The seasonal change was not obvious. The average shellfish abundance at the survey site was 0.533, including 0.82, 0.68, 0.60, and 0.53 shellfish abundance at NCD2, NHD2, BCD2, and NCD1, respectively. The abundance index of shellfish in each tidal area of the survey site was in order of middle tidal zone (0.56) > low tidal zone (0.52) > high tidal zone (0.17). Overall, the average shellfish abundance in the 10 survey sites was spring (0.681) > fall (0.573) > summer (0.458) > winter (0.418). Seasons (temperatures) have the most obvious impact on the diversity and abundance of intertidal shellfish resources. Anthropogenic activities, such as aquaculture and tourism, also affect the distribution and quantity of shellfish species. The results of this study not only enrich the data of intertidal shellfish resources on islands in China but also provide basic information and reference for biodiversity and environmental protection of intertidal shellfish on the Changshan Islands.

IntroductionGut microbiome plays a crucial role in the health of wild animals. Their structural and functional properties not only reflect the host’s dietary habits and habitat conditions but also provide essential support for ecological adaptation in various environments.MethodsThis study investigated the gut microbiome of Himalayan langurs (Semnopithecus schistaceus) and Xizang macaques (Macaca mulatta vestita) across different geographic regions using 16S rRNA gene and metagenomic sequencing.ResultsResults showed distinct clustering patterns in gut microbiota based on geographic location. Soil had an insignificant impact on host gut microbiome. Himalayan langurs from mid-altitude regions exhibited higher levels of antibiotic resistance genes associated with multidrug resistance, while Xizang macaques from high-altitude regions showed a broader range of resistance genes. Variations in carbohydrate-active enzymes and KEGG pathways indicated unique metabolic adaptations to different environments.DiscussionThese findings provide valuable insights into the health and conservation of these primates and the broader implications of microbial ecology and functional adaptations in extreme conditions.

A central question in neural tissue engineering is how the tissue-engineered nerve (TEN) translates detailed transcriptional signals associated with peripheral nerve regeneration into meaningful biological processes. Here, we report a skin-derived precursor-induced Schwann cell (SKP-SC)-mediated chitosan/silk fibroin-fabricated tissue-engineered nerve graft (SKP–SCs-TEN) that can promote sciatic nerve regeneration and functional restoration nearly to the levels achieved by autologous nerve grafts according to behavioral, histological, and electrophysiological evidence. For achieving better effect of neuroregeneration, this is the first time to jointly apply a dynamic perfusion bioreactor and the ascorbic acid to stimulate the SKP-SCs secretion of extracellular matrix (ECM). To overcome the limitation of traditional tissue-engineered nerve grafts, jointly utilizing SKP-SCs and their ECM components were motivated by the thought of prolongating the effect of support cells and their bioactive cues that promote peripheral nerve regeneration. To further explore the regulatory model of gene expression and the related molecular mechanisms involved in tissue engineering-aided peripheral nerve regeneration, we performed a cDNA microarray analysis of gene expression profiling, a comprehensive bioinformatics analysis and a validation study on the grafted segments and dorsal root ganglia tissues. A wealth of transcriptomic and bioinformatics data has revealed complex molecular networks and orchestrated functional regulation that may be responsible for the effects of SKP-SCs-TEN on promoting peripheral nerve regeneration. Our work provides new insights into transcriptomic features and patterns of molecular regulation in nerve functional recovery aided by SKP-SCs-TEN that sheds light on the broader possibilities for novel repair strategies of peripheral nerve injury.

Tissue regeneration requires exogenous and endogenous signals, and there is increasing evidence that the exogenous microenvironment may play an even more dominant role in the complex process of coordinated multiple cells. The short-distance peripheral nerve showed a spontaneous regenerative phenomenon, which was initiated by the guiding role of macrophages. However, it cannot sufficiently restore long-distance nerve injury by itself. Based on this principle, we firstly constructed a proinflammatory model to prove that abnormal M2 expression reduce the guidance and repair effect of long-distance nerves. Furthermore, a bionic peptide hydrogel scaffold based on self-assembly was developed to envelop M2-derived regenerative cytokines and extracellular vesicles (EVs). The cytokines and EVs were quantified to mimic the guidance and regenerative microenvironment in a direct and mild manner. The bionic scaffold promoted M2 transformation in situ and led to proliferation and migration of Schwann cells, neuron growth and motor function recovery. Meanwhile, the peptide scaffold combined with CX3CL1 recruited more blood-derived M2 macrophages to promote long-distance nerve reconstruction. Overall, we systematically confirmed the important role of M2 in regulating and restoring the injury peripheral nerve. This bionic peptide hydrogel scaffold mimicked and remodeled the local environment for M2 transformation and recruitment, favoring long-distance peripheral nerve regeneration. It can help to explicate regulative effect of M2 may be a cause not just a consequence in nerve repair and tissue integration, which facilitating the development of pro-regenerative biomaterials.

Chitosan and its degradation product, oligosaccharides, have been shown to facilitate peripheral nerve regeneration. However, the underlying mechanisms are not well understood. In this study, we analyzed the protein expression profiles in sciatic nerves after injury using proteomics. A group of proteins related to exosome packaging and transport is up-regulated by chitosan oligosaccharides (COS), implying that exosomes are involved in COS-induced peripheral nerve regeneration. In fact, exosomes derived from fibroblasts (f-EXOs) treated with COS significantly promoted axon extension and regeneration. Exosomal protein identification and functional studies, revealed that TFAP2C is a key factor in neurite outgrowth induced by COS-f-EXOs. Furthermore, we showed that TFAP2C targets the pri-miRNA-132 gene and represses miR-132-5p expression in dorsal root ganglion neurons. Camkk1 is a downstream substrate of miR-132-5p that positively affects axon extension. In rats, miR-132-5p antagomir stimulates CAMKK1 expression and improves axon regeneration and functional recovery in sciatic nerves after injury. Our data reveal the mechanism for COS in axon regeneration, that is COS induce fibroblasts to produce TFAP2C-enriched EXOs, which are then transferred into axons to promote axon regeneration via miR-132-5p/CAMKK1. Moreover, these results show a new facet of fibroblasts in axon regeneration in peripheral nerves.

Peripheral nerve injury (PNI) is a neurological disorder caused by trauma that is frequently induced by accidents, war, and surgical complications, which is of global significance. The severity of the injury determines the potential for lifelong disability in patients. Artificial nerve scaffolds have been investigated as a powerful tool for promoting optimal regeneration of nerve defects. Over the past few decades, bionic scaffolds have been successfully developed to provide guidance and biological cues to facilitate Schwann cell myelination and orientated axonal growth. Numerous assessment techniques have been employed to investigate the therapeutic efficacy of nerve scaffolds in promoting the growth of Schwann cells and axons upon the bioactivities of distinct scaffolds, which have encouraged a greater understanding of the biological mechanisms involved in peripheral nerve development and regeneration. However, it is still difficult to compare the results from different labs due to the diversity of protocols and the availability of innovative technologies when evaluating the effectiveness of novel artificial scaffolds. Meanwhile, due to the complicated process of peripheral nerve regeneration, several evaluation methods are usually combined in studies on peripheral nerve repair. Herein, we have provided an overview of the evaluation methods used to study the outcomes of scaffold-based therapies for PNI in experimental animal models and especially focus on Schwann cell functions and axonal growth within the regenerated nerve.

Abstract The development of self‐healing conductive hydrogels is critical in electroactive nerve tissue engineering. Typical conductive materials such as polypyrrole (PPy) are commonly used to fabricate artificial nerve conduits. Moreover, the field of tissue engineering has advanced toward the use of products such as hyaluronic acid (HA) hydrogels. Although HA‐modified PPy films are prepared for various biological applications, the cell–matrix interaction mechanisms remain poorly understood; furthermore, there are no reports on HA‐modified PPy‐injectable self‐healing hydrogels for peripheral nerve repair. Therefore, in this study, a self‐healing electroconductive hydrogel (HASPy) from HA, cystamine (Cys), and pyrrole‐1‐propionic acid (Py‐COOH), with injectability, biodegradability, biocompatibility, and nerve‐regenerative capacity is constructed. The hydrogel directly targets interleukin 17 receptor A (IL‐17RA) and promotes the expression of genes and proteins relevant to Schwann cell myelination mainly by activating the interleukin 17 (IL‐17) signaling pathway. The hydrogel is injected directly into the rat sciatic nerve‐crush injury sites to investigate its capacity for nerve regeneration in vivo and is found to promote functional recovery and remyelination. This study may help in understanding the mechanism of cell–matrix interactions and provide new insights into the potential use of HASPy hydrogel as an advanced scaffold for neural regeneration.

Abstract Although exosome therapy has been recognized as a promising strategy in the treatment of rheumatoid arthritis (RA), sustained modulation on RA specific pathogenesis and desirable protective effects for attenuating joint destruction still remain challenges. Here, silk fibroin hydrogel encapsulated with olfactory ecto-mesenchymal stem cell-derived exosomes (Exos@SFMA) was photo-crosslinked in situ to yield long-lasting therapeutic effect on modulating the immune microenvironment in RA. This in situ hydrogel system exhibited flexible mechanical properties and excellent biocompatibility for protecting tissue surfaces in joint. Moreover, the promising PD-L1 expression was identified on the exosomes, which potently suppressed Tfh cell polarization via inhibiting the PI3K/AKT pathway. Importantly, Exos@SFMA effectively relieved synovial inflammation and joint destruction by significantly reducing T follicular helper (Tfh) cell response and further suppressing the differentiation of germinal center (GC) B cells into plasma cells. Taken together, this exosome enhanced silk fibroin hydrogel provides an effective strategy for the treatment of RA and other autoimmune diseases.

Numerous studies have conducted in-depth research on the biological and chemical properties of tissue-engineered neural graft (TENG) on peripheral nerve regeneration, while the physical properties of the graft also display a significant impact on the regeneration of the injured nerve. Among them, the elasticity properties of TENG show a significant impact on the adhesion, proliferation, migration and bio-functionality of nerve cells in peripheral nerve regeneration. This review summarizes the latest research progress on elastic biomaterials for peripheral nervous system (PNS), including categories of elastic biomaterials, preparation methods and the effect of elasticity on the growth behavior of nerve cells, etc. In addition, the effect of the elastic substrate on the elasticity of the cell itself is also briefly described. Finally, we analyze and discuss the underlying mechanism by which elastic substrate affects nerve cell behavior.

The molecular network features of spinal cord development that are integral to tissue engineering remain poorly understood in placental mammals, especially in terms of their relationships with vital biological processes such as regeneration. Here, using a large-scale temporal transcriptomic analysis of rat spinal cord from the embryonic stage to adulthood, we show that fluctuating RNA expression levels reflect highly active transcriptional regulation, which may initiate spinal cord patterning. We also demonstrate that microRNAs (miRNAs) and transcriptional factors exhibit a mosaic profile based on their expression patterns, while differential alternative splicing events reveal that alternative splicing may be a driving force for the development of the node of Ranvier. Our study also supports the existence of a negative correlation between innate immunity and intrinsic growth capacity. Epigenetic modifications appear to perform their respective regulatory functions at different stages of development, while guanine nucleotide-binding protein (G protein)-coupled receptors (including olfactory receptors (ORs)) may perform pleiotropic roles in axonal growth. This study provides a valuable resource for investigating spinal cord development and complements the increasing number of single-cell datasets. These findings also provide a genetic basis for the development of novel tissue engineering strategies.

Peripheral nerve injury is a clinically common injury that causes sensory dysfunction and locomotor system degeneration, which seriously affects the quality of the patients’ daily life. Long gapped defects in large nerve are difficult to repair via surgery and limited donor source of autologous nerve greatly challenges the successful nerve repair by transplantation. Significantly, remarkable progress has been made in repairing the peripheral nerve injury using artificial nerve grafts and a variety of products for peripheral nerve repair have emerged been approved globally in recent years. The raw materials of these commercial products includes natural/synthetic polymers, extracellular matrix. Despite a lot of effort, the desirable functional recovery still remains great challenges in long gapped nerve defects. Thus this review discusses the recent development of tissue engineering products for peripheral nerve repair and the design of bionic grafts improving the local microenvironment for accelerating nerve regeneration against locomotor disorder, which may provide potential strategies for the repair of long gaps or thick nerve defects by multifunctional biomaterials.

A novel MgO-C-Al-Si refractory with low carbon content used in bottom-blowing elements was prepared, and its phase composition and microstructural evolution were investigated by XRD, SEM and EDS after being treated at 1200–1600°C in flowing nitrogen. Results show that the samples are composed of MgO, Al4C3, SiC, Al4SiC4, MgAl2O4, Mg3Al2N4 and Al2O3 at 1200–1400°C, while the samples are composed of MgO, Al4C3, SiC, Al4SiC4, Al4Si2C5, MgAl2O4, Mg3Al2N4 and Al2O3 at 1500–1600°C. Al and Si present gradient reactivity at high temperatures and Al has priority over Si to react with MgO, forming MgAl2O4. Based on the microstructure analysis, we find that the higher the temperatures are, the more abundant the products. Al(g), Al2O(g), SiO(g), Mg(g) and CO(g), as the gas–gas reaction substances, react to form many of Al4SiC4 flakes containing Mg, O and N within pores or gaps of the refractory, along with trace amounts of SiC whiskers and MgAl2O4 spinel whiskers. In addition, the surface morphology of the magnesia aggregates is modified by the MgAl2O4 spinels and Al4SiC4 flakes, owing to the synergistic effect of Al and Si. Further, some physical properties are also characterized.

Regeneration of neural tissue is limited following spinal cord injury (SCI). Successful regeneration of injured nerves requires the intrinsic regenerative capability of the neurons and a suitable microenvironment. However, the local microenvironment is damaged, including insufficient intraneural vascularization, prolonged immune responses, overactive immune responses, dysregulated bioenergetic metabolism and terminated bioelectrical conduction. Among them, the immune microenvironment formed by immune cells and cytokines plays a dual role in inflammation and regeneration. Few studies have focused on the role of the immune microenvironment in spinal cord regeneration. Here, we summarize those findings involving various immune cells (neutrophils, monocytes, microglia and T lymphocytes) after SCI. The pathological changes that occur in the local microenvironment and the function of immune cells are described. We also summarize and discuss the current strategies for treating SCI with tissue-engineered biomaterials from the perspective of the immune microenvironment.

The immune system is essential in the process of nerve repair after injury. Successful modulation of the immune response is regarded as an effective approach to improving treatment outcomes. T cells play an important role in the immune response of the nervous system, and their beneficial roles in promoting regeneration have been increasingly recognized. However, the diversity of T-cell subsets also delivers both neuroprotective and neurodegenerative functions. Therefore, this review mainly discusses the beneficial impact of T-cell subsets in the repair of both peripheral nervous system and central nervous system injuries and introduces studies on various therapies based on T-cell regulation. Further discoveries in T-cell mechanisms and multifunctional biomaterials will provide novel strategies for nerve regeneration.

Allohexaploidization and continuous introgression play a key role in the origin and evolution of bread wheat. The genetic bottleneck of bread wheat resulting from limited germplasms involved in the origin and modern breeding may be compensated by gene flow from tetraploid wheat through introgressive hybridization. The inter-ploidy hybridization between hexaploid and tetraploid wheat generates pentaploid hybrids first, which absorbed genetic variations both from hexaploid and tetraploid wheat and have great potential for re-evolution and improvement in bread wheat. Therefore, understanding the effects of the pentaploid hybrid is of apparent significance in our understanding of the historic introgression and in informing breeding. In the current study, two sets of F2 populations of synthetic pentaploid wheat (SPW1 and SPW2) and synthetic hexaploid wheat (SHW1 and SHW2) were created to analyze differences in recombination frequency (RF) of AB genomes and distorted segregation of polymorphic SNP markers through SNP genotyping. Results suggested that (1) the recombination of AB genomes in the SPW populations was about 3- to 4-fold higher than that in the SHW populations, resulting from the significantly (P < 0.01) increased RF between adjacent and linked SNP loci, especially the variations that occurred in a pericentromeric region which would further enrich genetic diversity; (2) the crosses of hexaploid × tetraploid wheat could be an efficient way to produce pentaploid derivatives than the crosses of tetraploid × hexaploid wheat according to the higher germination rate found in the former crosses; (3) the high proportion of distorted segregation loci that skewed in favor of the female parent genotype/allele in the SPW populations might associate with the fitness and survival of the offspring. Based on the presented data, we propose that pentaploid hybrids should increasingly be used in wheat breeding. In addition, the contribution of gene flow from tetraploid wheat to bread wheat mediated by pentaploid introgressive hybridization also was discussed in the re-evolution of bread wheat.

The liver is the most complex vascular anatomy of all human organs, with extremely rich blood flow and fragile texture. Massive liver bleeding usually occurs after traumatic liver injury, causing severe systematic issues. Thus, bleeding control is critical in hindering mortality rates and complications in patients. In this study, non-compression hemostasis materials based on chitosan lactate particles (CLP) were developed for handling liver bleeding after injuries. CLP showed good blood biocompatibility and antibacterial performance against S. aureus. Taking advantage of the vital capacity of CLP to promote red blood cell and platelet adhesion, CLP exhibited in vivo homeostasis properties as non-compression hemostasis materials for traumatic liver injury, both in SD rats, New Zealand rabbits, or in beagles. Whereas CLP has better hemostasis than the commercial hemostatic agent Celox™.

Silk, as a kind of natural fibrin, has been prepared into various biomaterials due to its excellent biocompatibility and mechanicalness. However, there are some controversies on the biocompatibility of silk fibroin (SF), especially when it coexists with sericin. In this study, two kinds of silk from Jiangsu and Zhejiang were degummed with two concentrations of Na2CO3 solution, respectively, to obtain four kinds of silk fibroin. The effects of different degumming treatments on silk fibroin properties were analyzed by means of color reaction, apparent viscosity measurement, and transmission electron microscope and isobaric tags for relative and absolute quantification analyses, and the effects of different silk fibroin membranes on the growth of Schwann cells were evaluated. The results showed that the natural silk from Zhejiang treated with 0.05% Na2CO3 solution had a fuller structure, higher apparent viscosity, and better protein composition. While SF obtained by degumming with 0.5% Na2CO3 solution was more beneficial to cell adhesion and proliferation due to the thorough removal of sericin. This study may provide important theoretical and experimental bases for the selection of biomaterials for fabricating artificial nerve grafts.

Nerve decellularized matrix (NDM) has received much attention due to its natural composition and structural advantages that had proven to be an excellent candidate for peripheral nerve regeneration. However, NDM with simultaneous biocompatibility, promoting nerve regeneration, as well as resistant to infection was rarely reporter. In this study, a porous NDM-CS scaffold with high antimicrobial activity and high biocompatibility was prepared by combining the advantages of both NDM and chitosan (CS) in a one-step method. The NDM-CS scaffold possessed high porosity and hydrophilicity, exhibited excellent biocompatibility which was suitable for cell growth and nutrient exchange. Meanwhile, NDM-CS scaffold had a significant antibacterial effect on both Escherichia coli (E. coli) and Staphylococcus aureus (S. aureus), which could avoid wound infection during the repair process. In addition, the NDM-CS scaffold could support the growth and viability of Schwann cells effectively. Among them, the E2C1 group had the strongest ability to enhance proliferation, polarization and migration of Schwann cells among the three groups. The positive effect on Schwann cells indicated their ability in the process of nerve injury repair. Therefore, this NDM-CS scaffold may have potential prospects for application in neural tissue engineering.

Air-fuel ratio is an important parameter in high-temperature and high-speed heat-airflow test system. If air-fuel ratio of the system is too low, the fuel cannot be fully burned, which will not only reduce the control performance of the gas temperature, but also increase the pollutant emissions of the combustor. In order to solve this problem, it is necessary to identify the air-fuel ratio of the system, get the prediction model of the air-fuel ratio, and adjust the fuel input according to the prediction value of the air-fuel ratio. In order to realize the accurate identification of the air-fuel ratio of the system, this paper briefly analyses the mathematical model of the air-fuel ratio in high-temperature and high-speed heat-airflow test system, and proposes an identification method of the air-fuel ratio based on support vector machine. On the basis of the experimental data, the air-fuel ratio of the system is identified by using different kernels, i.e. firstly, the experimental scheme is designed, and the fuel mass flow rate, air mass flow rate, gas temperature and actual air-fuel ratio of the system are collected under different experimental conditions; then, the collected data are divided into training datasets and test datasets, and the training datasets are trained by support vector machine to obtain identification model of the air-fuel ratio; finally, the identification model is validated with test datasets under different conditions, and the accuracy of the model is obtained. The identification results show that the support vector machine has good identification performance and can accurately approximate the actual dynamic process of the air-fuel ratio. The average absolute error of the identification model is less than 0.05, and the average relative error is less than 0.5% when the test datasets are smaller than the training datasets.

In order to accurately control the gas temperature of a supersonic heat-airflow simulated test system, this paper introduces the working principle of the system, including the fuel supply subsystem and the air supply subsystem, establishes the mathematical model of the system, including the fuel supply subsystem, the air supply subsystem and the gas temperature, and analyses the characteristics of the system. Based on characteristics such as non-linearity, parameter time variations, disturbance and pure time delay exist in the system; a new cascade control scheme that can control both the fuel supply subsystem and the air supply subsystem is proposed to achieve an accurate control of the gas temperature. On this basis, the simulation and experimental studies are carried out by the proposed control algorithm. The results show that the proposed gas temperature cascade control algorithm can achieve a fast, stable and no overshoot control of the gas temperature in a wide operating range, and the control accuracy can reach at ±5°C.

Abstract Background Emerging evidence suggests that neural crest-derived cells (NCCs) present important functions in peripheral nerve regeneration to correct the insufficiency of autogenous Schwann cells. Postmigratory NCCs have been successfully isolated from adult rat bone marrow in our previous work. In this study, we aim to provide neural crest-derived Schwann cell precursors (SCPs) for repair of nerve defects in adult rats, and partially reveal the mechanisms involved in neuroregeneration of cell therapy. Methods A clonal cell line of neural crest precursors of rat bone marrow origin (rBM-NCPs) with SCP identity was expanded in adherent monolayer culture to ensure the stable cell viability of NCPs and potentiate the repair of nerve defects after rBM-NCPs implantation based on tissue engineering nerve grafts (TENG). Here the behavioral, morphological, and electrophysiological detection was performed to evaluate the therapy efficacy. We further investigated the treatment with NCP-conditioned medium (NCP-CM) to sensory neurons after exposure to oxygen-glucose-deprivation (OGD) and partially compared the expression of trophic factor genes in rBM-NCPs with that in mesenchymal stem cells of bone marrow origin (rBM-MSCs). Results It was showed that the constructed TENG with rBM-NCPs loaded into silk fibroin fiber scaffolds/chitosan conduits repaired 10-mm long sciatic nerve defects more efficiently than conduits alone. The axonal regrowth, remyelination promoted the reinnervation of the denervated hind limb muscle and skin and thereby alleviated muscle atrophy and facilitated the rehabilitation of motor and sensory function. Moreover, it was demonstrated that treatment with NCP-CM could restore the cultured primary sensory neurons after OGD through trophic factors including epidermal growth factor (EGF), platelet-derived growth factor alpha (PDGFα), ciliary neurotrophic factor (CNTF), and vascular endothelial growth factor alpha (VEGFα). Conclusions In summary, our findings indicated that monolayer-cultured rBM-NCPs cell-based therapy might effectively repair peripheral nerve defects partially through secreted trophic factors, which represented the secretome of rBM-NCPs differing from that of rBM-MSCs.

Immune cell-derived extracellular vesicles (EVs) have increasingly become the focus of research due to their unique characteristics and bioinspired applications. They are lipid bilayer membrane nanosized vesicles harboring a range of immune cell-derived surface receptors and effector molecules from parental cells. Immune cell-derived EVs are important mediators of intercellular communication that regulate specific mechanisms of adaptive and innate immune responses. However, the mechanisms underlying the antitumor effects of EVs are still being explored. Importantly, immune cell-derived EVs have some unique features, including accessibility, storage, ability to pass through blood-brain and blood-tumor barriers, and loading of various effector molecules. Immune cell-derived EVs have been directly applied or engineered as potent antitumor vaccines or for the diagnosis of clinical diseases. More research applications involving genetic engineering, membrane engineering, and cargo delivery strategies have improved the treatment efficacy of EVs. Immune cell-derived EV-based therapies are expected to become a separate technique or to complement immunotherapy, radiotherapy, chemotherapy and other therapeutic modalities. This review aims to provide a comprehensive overview of the characteristics and functions of immune cell-derived EVs derived from adaptive (CD4+ T, CD8+ T and B cells) and innate immune cells (macrophages, NK cells, DCs, and neutrophils) and discuss emerging therapeutic opportunities and prospects in cancer treatment.

Abstract Background Astrocytes have been shown to produce several pro- and anti-inflammatory cytokines to maintain homeostasis of microenvironment in response to vast array of CNS insults. Some inflammation-related cytokines are responsible for regulating such cell events. Macrophage migration inhibitory factor (MIF) is a proinflammatory cytokine that can be inducibly expressed in the lesioned spinal cord. Unknown is whether MIF can facilitate the production of immunosuppressive factors from astrocytes to tune milieu following spinal cord injury. Methods Following establishment of contusion SCI rat model, correlation of PGE2 synthesis-related protein levels with that of MIF was assayed by Western blot. ELISA assay was used to detect production of PGE2, TNF-α, IL-1β, and IL-6. Immunohistochemistry was performed to observe colocalization of COX2 with GFAP- and S100β-positive astrocytes. The primary astrocytes were treated by various inhibitors to validate relevant signal pathway. Results The protein levels of MIF and COX2, but not of COX1, synchronously increased following spinal cord injury. Treatment of MIF inhibitor 4-IPP to the lesion sites significantly reduced the expression of COX2, mPGES-1, and as a consequence, the production of PGE2. Astrocytes responded robustly to the MIF interference, by which regulated MAPK/COX2/PGE2 signal pathway through coupling with the CD74 membrane receptor. MIF-induced production of PGE2 from astrocytes was able to suppress production of TNF-α, but boosted production of IL-1β and IL-6 in LPS-activated macrophages. Conclusion Collectively, these results reveal a novel function of MIF-mediated astrocytes, which fine-tune inflammatory microenvironment to maintain homeostasis. These suggest an alternative therapeutic strategy for CNS inflammation.

A cascaded deadbeat predictive control strategy with online disturbance compensation is proposed for a three-phase interleaved boost converter in this paper. The topology of the three-phase interleaved converter is symmetric, so the inner loop controller is also designed symmetrically. For the purpose of realizing the error-free tracking of reference value, the deadbeat predictive control method is adopted for inner and outer loops with Luenberger observers, which are designed to estimate and compensate the disturbances of load variation in the power model as well as the unknown resistor of inductance in the current model. To eliminate the influence of a time delay, a two-step predictive control method is adopted in the predictive model. In the aspect of parameter design, the pole placement method is adopted to determine the gain of the observer. A series of simulations and experiments are carried out to test the proposed strategy under steady and dynamic conditions. It is shown that the proposed control strategy has faster dynamic response and stronger robustness against disturbance than the conventional model predictive control.

The surface topographies of artificial implants including surface roughness, surface groove size and orientation, and surface pore size and distribution have a great influence on the adhesion, migration, proliferation, and differentiation of nerve cells in the nerve regeneration process. Optimizing the surface topographies of biomaterials can be a key strategy for achieving excellent cell performance in various applications such as nerve tissue engineering. In this review, we offer a comprehensive summary of the surface topographies of nerve implants and their effects on nerve cell behavior. This review also emphasizes the latest work progress of the layered structure of the natural extracellular matrix that can be imitated by the material surface topology. Finally, the future development of surface topographies on nerve regeneration was prospectively remarked.

Paramyosin is an important myofibrillar protein in molluscan smooth muscle. The full-length cDNA encoding paramyosin has been identified from Yesso scallop Patinopecten yessoensis. The length of paramyosin molecule has been found to be 3715 bp, which contains an open reading frame (ORF) of 2805 bp for 934 amino acid residues. Characterization of P. yessoensis paramyosin reveals the typical structural feature of coiled-coil protein, including six α-helix (α1-α6) and one coil (η) structures. Multiple phosphorylation sites have been predicted at the N-terminus of paramyosin, representing the unique phosphorylation sites in scallops. The highest levels of mRNA and protein expression of paramyosin have been found in foot and the smooth adductor muscle. According to whole-mount in situ hybridization (WISH), strong paramyosin mRNA signals were detected in the symmetric positions of anterior and posterior adductor muscles at late larval stages. These findings support that paramyosin may serve as the most important components for myogenesis and catch regulation in scallops. The present findings will not only help uncover the potential function of myofibrillar proteins in molluscs but also provide molecular evidence to infer evolutionary relationships among invertebrates.

Strong early vigour plays a crucial role in wheat yield improvement by enhancing resource utilization efficiency. Synthetic hexaploid wheat (SHW) combines the elite genes of tetraploid wheat with Aegilops tauschii and has been widely used in wheat genetic improvement for its abundant genetic variation. The two SHWs Syn79 and Syn80 were derived from the crossing of the same tetraploid wheat DOY1 with two different Ae. tauschii accessions, AT333 and AT428, respectively. The Syn80 possessed better early vigour traits than Syn79, theretically caused by their D genome from Ae. tauschii. To dissect their genetic basis in a hexaploid background, 203 recombinant inbred lines (RILs) derived from the cross of Syn79 x Syn80 were developed to detect quantitative trait loci (QTL) for four early biomass related traits: plant height (PH), tiller number (TN), shoot fresh weight (SFW) and shoot dry weight (SDW) per plant, under five different environmental conditions. Determined from the data of SNP markers, two genome regions on 1DS and 7D were stably associated with the four early biomass related traits showing pleiotropic effects. Four stable QTLs QPh.saas-1DS, QTn.saas-1DS, QSfw.saas-1DS and QSdw.saas-1DS explaining 7.92, 15.34, 9.64 and 10.15% of the phenotypic variation, respectively, were clustered in the region of 1DS from AX-94812958 to AX-110910133. Meanwhile, QPh.saas-7D, QTn.saas-7D, QSfw.saas-7D and QSdw.saas-7D were flanked by AX-109917900 and AX-110605376 on 7D, explaining 16.12, 24.35, 15.25 and 13.37% of the phenotypic variation on average, respectively. Moreover, these genomic QTLs on 1DS and 7D enhancing biomass in the parent Syn80 were from Ae. tauschii AT428. These findings suggest that these two QTLs from Ae. tauschii can be expressed stably in a hexaploid background at the jointing stage and be used for wheat improvement.

Lubricant infused surfaces (LISs) are promising platforms to address the icing problems, but their long-term stability remains a significant challenge. In this study, a durable LIS with photothermal response and reversible solid/liquid transformation was fabricated to rapidly thaw frost accumulation and reduce ice accretion. The newly designed LIS was manufactured by infusing low-melting cocoa oil and efficient photothermal Fe3O4 nanoparticles into anodized aluminum oxide substrate. Upon irradiation with infrared light, the Fe3O4 nanoparticles could absorb light energy and melt the solid lubricant into slippery liquid. The dual actions of surface heating and slipperiness of melted lubricant promoted the thawing of frost/ice and de-adhesion of ice block. Additionally, the durability of LIS was strengthened by the combination of the self-healing effect of the melted lubricant, and the robustness of the solid state. The hydrophobic lubricant diminished the lubricant loss during repeating freezing/unfreezing cycles and withstood longtime flowing water impact. The proposed concept of switchable hydrophobic/slippery lubricant will advance the design of durable LISs and provide a promising LIS platform for deicing application. Keywords: Lubricant infused surface, Photothermal, Deicing, Durability

Here, we reported a Han Chinese essential hypertensive pedigree based on clinical hereditary and molecular data. To know the molecular basis on this family, mitochondrial genome of one proband from the family was identified through direct sequencing analysis. The age of onset year and affected degree of patients are different in this family. And matrilineal family members carrying C4375T mutation and belong to Eastern Asian halopgroup C. Phylogenetic analysis shows 4375C is highly conservative in 17 species. It is suggested that these mutations might participate in the development of hypertension in this family. And halopgroup C might play a modifying role on the phenotype in this Chinese hypertensive family.

O-GlcNAcylation is a nutrient-driven post-translational modification known as a metabolic sensor that links metabolism to cellular function. Recent evidences indicate that the activation of O-GlcNAc pathway is a potential pro-survival pathway and that acute enhancement of this response is conducive to the survival of cells and tissues. 2-(4-Methoxyphenyl)ethyl-2-acetamido-2-deoxy-β-d-pyranoside (SalA-4g), is a salidroside analogue synthesized in our laboratory by chemical structure-modification, with a phenyl ring containing a para-methoxy group and a sugar ring consisting of N-acetylglucosamine. We have previously shown that SalA-4g elevates levels of protein O-GlcNAc and improves neuronal tolerance to ischemia. However, the specific target of SalA-4g regulating O-GlcNAcylation remains unknown. To address these questions, in this study, we have focused on mitochondrial network homeostasis mediated by O-GlcNAcylation in SalA-4g’s neuroprotection in primary cortical neurons under ischemic-like conditions. O-GlcNAc-modified mitochondria induced by SalA-4g demonstrated stronger neuroprotection under oxygen glucose deprivation and reoxygenation stress, including the improvement of mitochondrial homeostasis and bioenergy, and inhibition of mitochondrial apoptosis pathway. Blocking mitochondrial protein O-GlcNAcylation with OSMI-1 disrupted mitochondrial network homeostasis and antagonized the protective effects of SalA-4g. Collectively, these data demonstrate that mitochondrial homeostasis mediated by mitochondrial protein O-GlcNAcylation is critically involved in SalA-4g neuroprotection.

Despite the existence of many attempts at nerve tissue engineering, there is no ideal strategy to date for effectively treating defective peripheral nerve tissue. In the present study, well-aligned poly (L-lactic acid) (PLLA) nanofibers with varied nano-porous surface structures were designed within different ambient humidity levels using the stable jet electrospinning (SJES) technique. Nanofibers have the capacity to inhibit bacterial adhesion, especially with respect to Staphylococcus aureus (S. aureus). It was noteworthy to find that the large nano-porous fibers were less detrimentally affected by S. aureus than smaller fibers. Large nano-pores furthermore proved more conducive to the proliferation and differentiation of neural stem cells (NSCs), while small nano-pores were more beneficial to NSC migration. Thus, this study concluded that well-aligned fibers with varied nano-porous surface structures could reduce bacterial colonization and enhance cellular responses, which could be used as promising material in tissue engineering, especially for neuro-regeneration.

Biofilms formed on skin wound lead to inflammation and a delay of healing. In the present work, a novel textile pile debridement material was prepared and treated by plasma. Samples before and after plasma treatment were characterized by a series of methods, including scanning electron microscopy (SEM), atomic force microscopy (AFM), X-ray photoelectron spectroscopy (XPS), and water uptake capacity. Besides, mechanical, coagulation, and in vitro biofilm removal performances of the textile pile debridement material were evaluated, with a medical gauze as a control. The results demonstrate that the plasma treatment produced corrosions and oxygen-containing polar groups on the fiber surface, offering an enhanced water uptake capacity of the textile pile debridement material. In addition, compressive tests certify the mechanical performances of the textile pile debridement material in both dry and wet conditions. The results from a kinetic clotting time test suggest a favorable ability to promote blood coagulation. Furthermore, the results of an MTT cell viability assay, SEM, and confocal laser scanning microscopy (CLSM) illustrate that the textile pile debridement material demonstrates a more superior in vitro biofilm removal performance than medical gauze. All of these characterizations suggest that the textile pile debridement material can offer a feasible application for clinical wound debridement.

PGC-1α plays a central role in hepatic gluconeogenesis and has been implicated in the onset of type 2 diabetes. Acetylation is an important posttranslational modification for regulating the transcriptional activity of PGC-1α. Here, we show that PCAF is a pivotal acetyltransferase for acetylating PGC-1α in both fasted and diabetic states. PCAF acetylates two lysine residues K328 and K450 in PGC-1α, which subsequently triggers its proteasomal degradation and suppresses its transcriptional activity. Adenoviral-mediated expression of PCAF in the obese mouse liver greatly represses gluconeogenic enzyme activation and glucose production and improves glucose homeostasis and insulin sensitivity. Moreover, liver-specific knockdown of PCAF stimulates PGC-1α activity, resulting in an increase in blood glucose and hepatic glucose output. Our results suggest that PCAF might be a potential pharmacological target for developing agents against metabolic disorders associated with hyperglycemia, such as obesity and diabetes.

According to the problem that the mathematical model of the fuel supply system of the high-temperature high-speed wind tunnel is hard to be established, this article uses the method which combines the mechanism modeling method and system identification to establish the equivalence mathematical model of the fuel supply system. First, according to the working principle of the system, the original mathematical model of the fuel supply system is established using mechanism modeling method; the characteristics of the system are analyzed, and the unknown parameters and time-varying parameters are ascertained, that is to say, the prior knowledge of the system is obtained. Then, unknown uncertain parameters of the system are estimated using least square method, so the equivalence mathematical model of the fuel supply system can be obtained. The simulation and experimental results show that the mathematical model of the fuel supply system established in this article has high precision and can be used as an actual model in the control of the fuel flow rate.

Peripheral nerve injury represents a critical clinical challenge. Employing tissue engineering, biomimetic scaffolds mimicking the biophysical and biochemical cues of the native extracellular matrix have shown promise. Specifically, conductive matrices, mirroring neural tissue's electrical properties, hold potential for neural tissue repair. However, the synergistic impact of conductivity and biomolecules on injured peripheral nerves remains unexplored. In this study, conductive hydrogels via a three-step click chemical reaction method, incorporating silk fibroin, graphene oxide, and Polyethylene Glycol Diacrylate is crafted. The inclusion of fibroblast exosomes yielded a synergistic effect, enhancing recovery from peripheral nerve injuries. Graphene oxide heightened the electron transmission capacity of the hydrogels, while fibroblast exosomes endowed them with the ability to modulate cellular behaviors. This resulted in enhanced axon and myelin regeneration. Furthermore, the hydrogel facilitated vascular regeneration during peripheral nerve recovery through the VEGF/NOTCH signaling pathway. Transplanting conductive hydrogel conduits laden with fibroblast exosomes led to substantial functional recovery in a rat sciatic nerve transection model. Consequently, a novel strategy to expedite the intricate repair of peripheral nerve injuries is proposed. [ABSTRACT FROM AUTHOR]