Abstract Introducing concentration gradients of nerve growth factor (NGF) into conduits for repairing of peripheral nerve injury is crucial for nerve regeneration and guidance. Herein, combining ...differential adsorption of NGF/silk fibroin (SF) coating, the gradient of NGF-immobilized membranes (G-Ms) and nanofibrous nerve conduits (G-nNCs) were successfully fabricated. The efficacy of NGF gradients was confirmed by a quantitative comparison of dorsal root ganglia (DRG) neurite outgrowth on the G-Ms or uniform NGF-immobilized membranes (U-Ms). Significantly, the neurite turning ratio was 0.48 ± 0.11 for G-M group, but it was close to zero for U-M group. The neurite length of DRGs in the middle of the G-Ms was significantly longer than that of U-M group, even though the average NGF concentration was approximated. Furthermore, 12 weeks after implantation in rats with a 14 mm gap of sciatic nerve injury, G-nNCs achieved satisfying outcomes of nerve regeneration associated with morphological and functional improvements, which was superior to that of the uniform NGF-immobilized nNCs (U-nNCs). Sciatic function index (SFI), compound muscle action potentials (CMAPs), total number of myelinated nerve fibers, thickness of myelin sheath were similar for the G-nNCs and autografts, with the G-nNCs having a higher density of axons than the autografts. Our results demonstrated the significant role of introducing NGF gradients into scaffolds in promoting nerve regeneration.
Growth factors (GFs) play a crucial role in directing stem cell behavior and transmitting information between different cell populations for tissue regeneration. However, their utility as ...therapeutics is limited by their short half‐life within the physiological microenvironment and significant side effects caused by off‐target effects or improper dosage. “Smart” materials that can not only sustain therapeutic delivery over a treatment period but also facilitate on‐demand release upon activation are attracting significant interest in the field of GF delivery for tissue engineering. Three properties are essential in engineering these “smart” materials: 1) the cargo vehicle protects the encapsulated therapeutic; 2) release is targeted to the site of injury; 3) cargo release can be modulated by disease‐specific stimuli. The aim of this review is to summarize the current research on stimuli‐responsive materials as intelligent vehicles for controlled GF delivery; Five main subfields of tissue engineering are discussed: skin, bone and cartilage, muscle, blood vessel, and nerve. Challenges in achieving such “smart” materials and perspectives on future applications of stimuli‐responsive GF delivery for tissue regeneration are also discussed.
“Smart” materials that can achieve on demand release of therapeutics in response to biological stimuli on the disease sites attract growing interest in the field of tissue engineering. This review focuses on summarizing recent advances in stimuli‐responsive growth factor release strategies for tissue regeneration with improved efficacy and mitigated side effect.
Automatically building three-dimensional (3D) engineering geological models of sedimentary layer is still challenging. In particular, there is a lack of practical and scientific methods for ...constructing models of strata containing stratum lenses and pinch-out. This study develops an engineering geological structure modeling method, called the multi-scale drill control method, for strata containing stratum lenses and stratum pinch-out using drill data. Based on the stratigraphic code classification strategy, this approach first determines n levels of stratigraphic columns in the study area and the spatial distribution and occupation relationships of each stratum inside. Thereafter, geological surfaces are interpolated, intersected, corrected, and built by following the order of the stratigraphic column from top to bottom and from coarsest to finest level. Subsequently, surfaces with 0 thickness between the top and bottom surfaces are removed, and the vertical side surfaces are constructed. Finally, geo-bodies are built on seamless surfaces to conduct model creation. As required by modelers, models of different scales are applied, or multi-scaled models are mixed for use, thus providing support for later geological analysis. The case study with complicated geological conditions indicates that the method can accurately reproduce the geo-bodies' geometry and distribution, significantly enhancing geological model building efficiency.
•An automatic 3D modeling method of sedimentary engineering layers was proposed.•The method can build multi-scale models of sedimentary engineering layers automatically.•The method can construct models containing strata lenses and strata pinch-out.•The case study indicts the validity, feasibility, and efficiency of the proposed method.
Post-traumatic stress disorder (PTSD)-associated cognitive dysfunction significantly disturbs patients’ quality of life and will to live. However, its underlying mechanism is as yet unknown. Recent ...researches indicate that blood–brain barrier (BBB) breakdown is responsible for early cognitive dysfunction. Microglia might participate in remodeling of BBB-associated tight junction and regulating BBB integrity. Nevertheless, it is unclear whether microglia activation and BBB injury involve in PTSD-associated cognitive dysfunction. Hence, we established an animal model of PTSD, single prolonged stress (SPS), and investigated permeability changes in the hippocampus and further explored the effects of microglia on BBB remodeling. The Y maze was used to assess the changes of cognitive function. The sodium fluorescein (NaFlu) assay and western blotting analysis were employed to detect BBB integrity changes. Minocycline was administered to inhibit microglial activation. Immunofluorescence stains were used to assess the activation states in microglia. The results showed that SPS-exposed rats exhibited poorer cognitive performance, higher passage of NaFlu, and lower expression of tight junction proteins (occludin and claudin 5) in the hippocampus on the day after SPS, but no difference on the 7th day. Inhibition of microglial activation by minocycline attenuated poor cognitive performance and BBB impairment including the extravasation of NaFlu and protein levels of the tight junction. Taken together, the present study indicates that BBB impairment may underlie the shared pathological basis of PTSD and cognitive dysfunction. Microglial activation may involve in BBB remodeling at the early stage of SPS.
With the rapid development of cities in northwest China, there has been an increasing focus on groundwater pollution in plateau cities, specifically the common occurrence of nitrate pollution. The ...special climatic, geological, and geomorphological characteristics of plateau and river valley cities contribute to distinct groundwater chemical characteristics. Therefore, the formation and evolution process of groundwater nitrate contamination differs from that of plain cities. To explore these issues, we conducted an analysis of eight major ions in various groups of water samples obtained from rivers, springs, and groundwater in Haidong. By utilizing factor analysis and correlation analysis, we were able to identify the characteristics and formation of groundwater chemistry and nitrate pollution in Haidong. Our findings reveal that the chemical characteristics of groundwater in Haidong are primarily controlled by rock weathering, mineral dissolution, and evaporation, leading to the formation of highly mineralized groundwater. Additionally, the excessive nitrate content in certain areas is a result of domestic sewage discharge and agricultural fertilizer use, exceeding Chinese drinking water health standards. Furthermore, for cities located in valleys, the geological structure significantly impacts the nitrate content of groundwater in different regions. Areas with obstructed groundwater flow tend to have higher nitrate levels, whereas regions with unobstructed groundwater experience lower nitrate concentrations. Notably, shallow groundwater is more vulnerable to nitrate pollution compared to deep groundwater. This study holds great significance in understanding the chemical characteristics of groundwater and the formation and evolution of nitrate pollution in highland river valley cities.
In order to detect multi-ship encounter situations and improve the safety of navigation, this paper proposed a model which was able to mine multi-ship encounter situations from Automatic ...identification system (AIS) data and analyze the encounter spatial-temporal process and make collision avoidance decisions. Pairwise encounters identification results and ship motion index were combined into a ship encounter graph network which can use the complex network theory to describe the encounter spatial-temporal process. Network average degree, network average distance and network average clustering coefficient were selected. Based on the recognition results of pairwise encounter identification results, a discrete multi-ship encounter network is constructed. The process of multi-ship encounters from simple to complex to simple is mined based on the process of average network degree from 0 to 0 to obtain a continuous spatial-temporal process. The results can be used for multi-ship encounter situation awareness, multi-ship collision avoidance decision-making and channel navigation evaluation, and also provide data for machine learning. Quaternary dynamic ship domain, fuzzy logic and the weighted PageRank algorithm were used to rank the whole network risk, which is critical to “key ship collision avoidance.” This method overcame the problem that the traditional collision risk evaluation method is only applicable to the difference between two ships and ship perception. The risk rank combined with the artificial potential field method was used. Compared with the traditional artificial potential field method, this method has fewer turns and a smoother trajectory.
Accurately depicting the spatial structure characteristics of Quaternary loose sedimentary strata is not only of great significance for the research of Quaternary geological evolution, but also for ...the analysis of spatial variation characteristics of the inner hydrogeological and engineering geological attributes of the strata. In this study, an approach for constructing a 3D geological model of Quaternary loose sedimentary strata is proposed based on global stratigraphical discrete points. The approach obtains the discrete control point set of each stratum by using limited borehole data for interpolation and encryption, and the contact relationships and intersection modes of adjacent strata can be determined via the analysis of stratigraphic sequence; finally, taking these as the professional basis, the construction of the 3D geological model of Quaternary loose sedimentary strata can be carried out. This application can not only accurately describe the three-dimensional spatial distribution characteristics of the Quaternary loose sedimentary strata, it can also be used to perform a layered simulation of the spatial variation characteristics of the inner geological properties of the Quaternary loose sedimentary strata, such as lithology, porosity, and water content, by taking the three-dimensional spatial framework of each stratum as the simulation boundary. Finally, this study takes the citizen center of Xiong’an new area as an example in order to verify the reliability and advancement of the 3D geological modeling scheme.
Immunotherapy is a class of promising anticancer treatments that has recently gained attention due to surging numbers of FDA approvals and extensive preclinical studies demonstrating efficacy. ...Nevertheless, further clinical implementation has been limited by high variability in patient response to different immunotherapeutic agents. These treatments currently do not have reliable predictors of efficacy and may lead to side effects. The future development of additional immunotherapy options and the prediction of patient‐specific response to treatment require advanced screening platforms associated with accurate and rapid data interpretation. Advanced engineering approaches ranging from sequencing and gene editing, to tumor organoids engineering, bioprinted tissues, and organs‐on‐a‐chip systems facilitate the screening of cancer immunotherapies by recreating the intrinsic and extrinsic features of a tumor and its microenvironment. High‐throughput platform development and progress in artificial intelligence can also improve the efficiency and accuracy of screening methods. Here, these engineering approaches in screening cancer immunotherapies are highlighted, and a discussion of the future perspectives and challenges associated with these emerging fields to further advance the clinical use of state‐of‐the‐art cancer immunotherapies are provided.
Advanced engineering approaches and progress in artificial intelligence can contribute to the development of cancer immunotherapy by uncovering alternative treatment targets and identifying hallmarks of treatment response, efficacy, and side effects. Screening approaches, including sequencing, gene editing, tumor organoids engineering, bioprinting, and organs‐on‐a‐chip, combined with high‐throughput screening and artificial intelligence are promising in accelerating broader application of cancer immunotherapy for a larger population.
This study aims to explore the regulatory effect of S-ketamine on the mechanical allodynia, anxiety-like behaviors and microglia activation in adult male rats exposed to an animal model of ...post-traumatic stress disorder (PTSD). The rat PTSD model was established by the exposure to single-prolonged stress (SPS), and 1 day later, rats were intraperitoneally injected with 5 mg/kg S-ketamine or normal saline, respectively. Paw withdrawal mechanical threshold was measured 2 days before, and 1, 3, 5, 7, 10, 14, 21 and 28 days after injection to assess mechanical allodynia in the SPS-exposed rats. For anxiety-like behaviors, the open field test and elevated plus maze test were performed at 7 and 14 days after S-ketamine treatment in the SPS-exposed rats, respectively. SPS-induced rats presented pronounced mechanical allodynia and anxiety-like behaviors, which were alleviated by S-ketamine treatment. After behavioral tests, rats were sacrificed for collecting the anterior cingulate cortex (ACC), prefrontal cortex (PFC), dorsal striatum, and periaqueductal gray (PAG). Protein levels of TNF-α, IL-1β, p-NF-κB, and NF-κB in brain regions were examined by Western blot. In addition, microglia activation in each brain region was determined by immunofluorescence staining of the microglia-specific biomarker Iba-1. Interestingly, pro-inflammatory cytokines were significantly upregulated in the dorsal striatum and PAG, rather than ACC and PFC. Activated microglia was observed in the dorsal striatum and PAG as well, and upregulated p-NF-κB was detected in the dorsal striatum. Inflammatory response, phosphorylation of NF-κB and microglia activation in certain brain regions were significantly alleviated by S-ketamine treatment. Collectively, S-ketamine is a promising drug in alleviating mechanical allodynia, anxiety-like behaviors, and pro-inflammatory responses in discrete brain regions in a model of PTSD.
As a minimally invasive drug delivery platform, microneedles (MNs) overcome many drawbacks of the conventional transdermal drug delivery systems, therefore are favorable in biomedical applications. ...Microneedles with a combined burst and sustained release profile and maintained therapeutic molecular bioactivity could further broaden its applications as therapeutics. Here, we developed a double-network microneedles (DN MNs) based on gelatin methacrylate and acellular neural matrix (GelMA-ACNM). ACNM could function as an early drug release matrix, whereas the addition of GelMA facilitates sustained drug release. In particular, the double-network microneedles comprising GelMA-ACNM hydrogel has distinctive biological features in maintaining drug activity to meet the needs of application in treating different diseases. In this study, we prepared the double-network microneedles and evaluated its morphology, mechanical properties, drug release properties and biocompatibility, which shows great potential for delivery of therapeutic molecules that needs different release profiles in transdermal treatment.
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