Inspirational Story of Agriculture at Living with The Land Attraction at EPCOT.

Since its debut in 1982, The Land has embodied Walt Disney's vision, capturing the attention of millions of EPCOT guests with venues focusing on agriculture and environmental stewardship and sustainability. The Land pavilion spans over eight acres in the World Nature section of EPCOT at the Walt Disney World Resort in Lake Buena Vista, Florida. The pavilion houses three attractions, namely Soarin' Around the World, Awesome Planet, and the Living with The Land boat ride, complemented by a greenhouse walking tour entitled Behind the Seeds and two restaurants. Each attraction derives inspiration from nature and challenges mankind to be responsible stewards of planet earth. This feature article focuses on the Living with The Land boat ride attraction, which traverses greenhouses showcasing agricultural technologies and crops from around the world. The sections below describe both how various show elements are designed to engage guests and how the show is made possible by applying relevant science and technology.

Searching for the optimal precondition procedure for mesenchymal stem/stromal cell treatment: Facts and perspectives.

Mesenchymal stem/stromal cells are potential optimal cell sources for stem cell therapies, and pretreatment has proven to enhance cell vitality and function. In a recent publication, Li et al explored a new combination of pretreatment conditions. Here, we present an editorial to comment on their work and provide our view on mesenchymal stem/stromal cell precondition.

The role of lncRNA NEAT1 in human cancer chemoresistance.

Chemotherapy is currently one of the most effective methods in clinical cancer treatment. However, chemotherapy resistance is an important reason for poor chemotherapy efficacy and prognosis, which has become an urgent problem to be solved in the field of cancer chemotherapy. Therefore, it is very important to deeply study and analyze the mechanism of cancer chemotherapy resistance and its regulatory factors. Long non-coding RNA nuclear paraspeckle assembly transcript 1 (LncRNA NEAT1) has been shown to be closely associated with chemotherapy resistance in cancer. NEAT1 induces cancer cell resistance to chemotherapeutic drugs by regulating cell apoptosis, cell cycle, drug transport and metabolism, DNA damage repair, EMT, autophagy, cancer stem cell characteristics, and metabolic reprogramming. This indicates that NEAT1 may be an important target to overcome chemotherapy resistance and is expected to be a potential biomarker to predict the effect of chemotherapy. This article summarizes the expression characteristics and clinical characteristics of NEAT1 in different cancers, and deeply discusses the regulatory role of NEAT1 in cancer chemotherapy resistance and related molecular mechanisms, aiming to clarify NEAT1 as a new target to overcome cancer chemotherapy resistance and the feasibility of chemotherapy sensitizers, with a view to providing a potential therapeutic direction for overcoming the dilemma of cancer resistance in the future.

Threshold effects between caffeine intake and urine flow rate: a population-based cross-sectional study.

PURPOSE: The potential benefits of caffeine intake are currently receiving much attention and exploration. Urine flow rate (UFR) is an objective index to comprehensively reflect bladder function. The aim of this study was to investigate the association between caffeine intake and UFR using the National Health and Nutrition Examination Survey (NHANES) database. METHODS: 14,142 participants were enrolled in this study. Weighted multivariate adjusted regression models were used to explore the relationship between caffeine intake and UFR. The dose-response relationships were explored using a restricted cubic spline (RCS) and a threshold effect analysis was conducted based on the inflection points identified by the two-segment linear regression model. In addition, subgroup analysis and sensitivity analysis were applied. RESULTS: The findings suggested that the intake of caffeine was correlated with improved UFR [Model 3: 0.091 (0.057, 0.126), P value < 0.001]. In addition, the RCS supported a nonlinear relationship between them. The analysis of threshold effect further revealed a specific level of caffeine intake (34.51 mg/day) that exhibited a significant enhancement in UFR. Finally, through re-analyzing the data set obtained after multiple imputation (MI), we obtained similar results. CONCLUSION: This study found a nonlinear beneficial relationship between caffeine intake and UFR, and revealed the recommended intake of caffeine. The values varied by gender, race, education, and smoking status.

The N545S and K717N substitution at the N-glycosylation sites of the S2 subunit of avian infectious bronchitis virus can significantly enhance viral pathogenicity.

The S2 subunit of infectious bronchitis virus (IBV) is a heavily glycosylated protein that can impact various characteristics of the virus. It is currently known that N-glycosylation modifications are predominantly located on the S2 subunit. However, the exact role of their N-glycosylation modification remains undisclosed. To elucidate the function of these N-glycosylation sites, we identified 14 common sites distributed on the S2 subunit of the 5 genotypes of IBV in present study. Subsequently, we selected 7 sites to generate mutants and assessed their impact on viral virulence, replication ability, and antigenicity. Our finding revealed that only 2 substitutions, N545S and K717N, increased the viral replication titer and antigenicity, and ultimately the pathogenicity in chicks. To delve into the mechanisms underlying this increased pathogenicity, we discovered that K717N can change the structure of antigenic epitopes. The N545S substitution not only influenced antigenic epitope structure, but also enhanced the ability of the virus to enter CEKs during the early stages of viral replication. These results suggest that the enhanced viral pathogenicity associated with N545S and K717N substitutions is multifaceted, with acceleration of the viral membrane fusion process and alterations in epitope structure representing crucial factors in the capability of N-glycosylation modifications to boost viral virulence. These insights provide valuable guidance for the efficient development of live attenuated vaccines.

Prospects, advances and biological applications of MOF-based platform for the treatment of lung cancer.

Nowadays in our society, lung cancer is exhibiting a high mortality rate and threat to human health. Conventional diagnostic techniques used in the field of lung cancer often necessitate the use of extensive instrumentation, exhibit a tendency for false positives, and are not suitable for widespread early screening purposes. Conventional approaches to treat lung cancer primarily involve surgery, chemotherapy, and radiotherapy. However, these broad-spectrum treatments suffer from drawbacks such as imprecise targeting and significant side effects, which restrict their widespread use. Metal-organic frameworks (MOFs) have attracted significant attention in the diagnosis and treatment of lung cancer owing to their tunable electronic properties and structures and potential applications. These porous nanomaterials are formed through the intricate assembly of metal centers and organic ligands, resulting in highly versatile frameworks. Compared to traditional diagnostic and therapeutic modalities, MOFs can improve the sensitivity of lung cancer biomarker detection in the diagnosis of lung cancer. In terms of treatment, they can significantly reduce side effects and improve therapeutic efficacy. Hence, this perspective provides an overview concerning the advancements made in the field of MOFs as potent biosensors for lung cancer biomarkers. It also delves into the latest research dealing with the use of MOFs as carriers for drug delivery. Additionally, it explores the applications of MOFs in various therapeutic approaches, including chemodynamic therapy, photodynamic therapy, photothermal therapy, and immunotherapy. Furthermore, this review comprehensively analyses potential applications of MOFs as biosensors in the field of lung cancer diagnosis and combines different therapeutic approaches aiming for enhanced therapeutic efficacy. It also presents a concise overview of the existing obstacles, aiming to pave the way for future advancements in lung cancer diagnosis and treatment.

1,25-Dihydroxyvitamin D3 reduces early mortality post severe burn injury via alleviating endotoxemia, oxidative stress and inflammation.

Severe burn patients frequently suffer from 1,25-Dihydroxyvitamin D3 (1,25-[OH]2-D3) deficiency. In this study, we investigated the effect of 1,25-[OH]2-D3 on early mortality post severe burn and potential underlying mechanisms. Our results indicate that 1,25-[OH]2-D3 significantly reduced early mortality in mice post severe burn injury. A decrease in serum lipopolysaccharide levels and an increase in serum superoxide dismutase activity were found after administration of 1,25-[OH]2-D3. Furthermore, 1,25-[OH]2-D3 demonstrated protective effects on both intestinal and lung histology and ameliorated lung inflammation. Its anti-inflammatory effect was further confirmed in airway epithelial cells. In conclusion, our study provides evidence that 1,25-[OH]2-D3 has a significant impact on the reduction of early mortality post severe burn injury, possibly through its ability to alleviate endotoxemia, oxidative stress, and inflammation. Our findings highlight the potential of 1,25-[OH]2-D3 to protect the intestinal mucosal barrier in the early stage following major burn injury and opens up new avenues for clinical application of 1,25-[OH]2-D3 in burn patients.

Fe3O4 Nanoparticles Embedded into Pyridinic-N-Rich Carbon Nanohoneycomb with Strong dx2-Pz Orbital Hybridization for High-Performance Electromagnetic Wave Absorption.

Carbon-based magnetic nanocomposites as promising lightweight electromagnetic wave (EMW) absorbents are expected to address critical issues caused by electromagnetic pollution. Herein, Fe3O4 nanoparticles embedded into a 3D N-rich porous carbon nanohoneycomb (Fe3O4@NC) were developed via the pyrolysis of an in-situ-polymerized compound of m-phenylenediamine initiated by FeCl2 in the presence of NaCl crystals as templates. Results demonstrate that Fe3O4@NC features highly dispersed Fe3O4 nanoparticles into an ultrahigh specific pyridinic-N doping carbon matrix, resulting in excellent impedance matching characteristics and electromagnetic wave absorbing capability with the biggest effective absorption bandwidth (EAB) of up to 7.1 GHz and the minimum reflective loss (RLmin) of up to -65.5 dB in the thin thickness of 2.5 and 2.3 mm, respectively, which also outperforms the majority of carbon-based absorbers reported. Meanwhile, its high absorption performance is further demonstrated by an ethylene propylene diene monomer wave absorbing patch filled with 8.0 wt % Fe3O4@NC, which can completely shield a 5G signal in a mobile phone. In addition, theory calculation reveals that there is a strongest dx2-Pz orbital hybridization interaction between Fe3O4 clusters and pyridinic-N dopants in the carbon network, compared with other kinds of N dopants, which can not only generate more dipoles of carbon networks but also increase net magnetic moments of Fe3O4, thereby leading to a coupling effect of efficient dielectric and magnetic losses. This work provides new insights into the precise design and synthesis of carbon-based magnetic composites with specific interface interactions and morphological effects for high-efficiency EMW absorption materials.

Experimental study on migration characteristics of LNAPL in the aquitard under pumping conditions.

Research on the migration behaviors of contaminants in the aquitard has been deficient for an extended period. Clay is commonly employed as an impermeable layer or barrier to stop the migration of contaminants. However, under certain conditions, the clay layer may exhibit permeability to water, thereby allowing contaminants to infiltrate and potentially contaminate adjacent aquifers. Consequently, it holds immense importance to scrutinize and investigate the migration characteristics of light non-aqueous phase liquid (LNAPL) within the aquitard for the purposes of groundwater pollution control and remediation. To evaluate the environmental risk posed by organic contaminants in the aquitard, an experimental model was formulated and devised to monitor the LNAPL concentration in the aquitard under pumping conditions. The correlation between pumping rate and LNAPL concentration was investigated. A self-developed plexiglass sandbox model was used to simulate the migration characteristics of LNAPL in the aquitard under pumping conditions. Four experimental scenarios were designed, varying pumping rates, aquitard thicknesses, and groundwater level changes. The LNAPL concentration curve was derived by systematically tracking and analyzing LNAPL levels at various locations within the aquitard. The results indicated that higher pumping rates corresponded to increased migration of LNAPL, resulting in greater LNAPL ingress into the pumping well during extraction. A thicker aquitard demonstrated a more pronounced inhibitory effect on LNAPL, leading to an extended penetration time of LNAPL within the aquitard. The drawdown within the aquitard exerted a discernible influence on LNAPL migration, with the LNAPL concentration continuing to decrease in tandem with declining water levels during pumping. These research findings can establish a scientific foundation for the control and remediation of contaminants within aquitards.

Exploring optimal incubation conditions and characteristics of methane oxidizing organisms in deep-sea environments.

Anaerobic methanotrophic archaea (ANME) play key roles in buffering the methane budget in the deep-sea environment. This study aimed to explore the optimal environmental conditions for ANME enrichment. The result showed that the sample at 10.5 MPa contained the largest copy numbers of methyl-coenzyme M reductase alpha subunit (mcrA) gene (1.1 × 106 copies/g) compared to any other pressures and the sample at 4 °C contained higher mcrA gene (1.6 × 106 copies/g) than other temperatures. The optimal enrichment pressure for ANME-2c is 10.5 MPa at 4 °C, with an optimal subsequent incubation for ANME-2c less than 211th days. Moreover, the beta nearest taxon index was significantly correlated with the incubation time (P<0.05). Total inorganic carbon and sulfate ion were key environmental factors driving community construction. This study offers insights into how ANME-2c was enriched and how species coexist in shared habitats during enrichment.

Uptake of zinc from the soil to the wheat grain: Nonlinear process prediction based on artificial neural network and geochemical data.

Trace elements in plants primarily derive from soils, subsequently influencing human health through the food chain. Therefore, it is essential to understand the relationship of trace elements between plants and soils. Since trace elements from soils absorbed by plants is a nonlinear process, traditional multiple linear regression (MLR) models failed to provide accurate predictions. Zinc (Zn) was chosen as the objective element in this case. Using soil geochemical data, artificial neural networks (ANN) were utilized to develop predictive models that accurately estimated Zn content within wheat grains. A total of 4036 topsoil samples and 73 paired rhizosphere soil-wheat samples were collected for the simulation study. Through Pearson correlation analysis, the total content of elements (TCEs) of Fe, Mn, Zn, and P, as well as the available content of elements (ACEs) of B, Mo, N, and Fe, were significantly correlated with the Zn bioaccumulation factor (BAF). Upon comparison, ANN models outperformed MLR models in terms of prediction accuracy. Notably, the predictive performance using ACEs as input factors was better than that using TCEs. To improve the accuracy, a two-step model was established through multiple testing. Firstly, ACEs in the soil were predicted using TCEs and properties of the rhizosphere soil as input factors. Secondly, the Zn BAF in grains was predicted using ACE as input factors. Consequently, the content of Zn in wheat grains corresponding to 4036 topsoil samples was predicted. Results showed that 85.69 % of the land was suitable for cultivating Zn-rich wheat. This finding offers a more accurate method to predict the uptake of trace elements from soils to grains, which helps to warn about abnormal levels in grains and prevent potential health risks.

New Monoterpenoid Glycosides from the Fruits of Hypericum patulum Thunb.

The whole Hypericum patulum Thunb. plant is utilized in traditional medicine for its properties of clearing heat, detoxifying, soothing meridians, relaxing the liver, and stopping bleeding. In folk medicine, it is frequently used to treat hepatitis, colds, tonsillitis, and bruises. Phytochemical investigation of a 30% ethanol extract of the fresh ripe fruits of H. patulum has resulted in the isolation of two new pinane-type monoterpenoid glycosides 1-2, named patulumside E-F, and three new chain-shaped monoterpenoid glycosides 3-5, named patulumside G-H, J. Their structures were determined using extensive spectroscopic techniques, such as HR-ESI-MS, 1D and 2D NMR spectroscopy, and electronic circular dichroism (ECD) calculation. The anti-inflammatory activities of these compounds were evaluated in the LPS-induced RAW264.7 cells. This research represents the inaugural comprehensive phytochemical study of H. patulum, paving the way for further exploration of monoterpenoid glycosides.

Multiomic meta-analysis suggests a correlation between steroid hormone-related genes and litter size in goats.

Litter size is a key indicator of production performance in livestock. However, its genetic basis in goats remains poorly understood. In this work, a genome-wide selection sweep analysis (GWSA) on 100 published goat genomes with different litter rates was performed for the first time to identify candidate genes related to kidding rate. This analysis was combined with the public RNA-sequencing data of ovary tissues (follicular phase) from high- and low-yielding goats. A total of 2278 genes were identified by GWSA. Most of these genes were enriched in signaling pathways related to ovarian follicle development and hormone secretion. Moreover, 208 differentially expressed genes between groups were obtained from the ovaries of goats with different litter sizes. These genes were substantially enriched in the cholesterol and steroid synthesis signaling pathways. Meanwhile, the weighted gene co-expression network was used to perform modular analysis of differentially expressed genes. The results showed that seven modules were reconstructed, of which one module showed a very strong correlation with litter size (r = -0.51 and p-value <0.001). There were 51 genes in this module, and 39 hub genes were screened by Pearson's correlation coefficient between core genes > 0.4, correlation coefficient between module members > 0.80 and intra-module connectivity ≥5. Finally, based on the results of GWSA and hub gene Venn analysis, seven key genes (ACSS2, HECW2, KDR, LHCGR, NAMPT, PTGFR and TFPI) were found to be associated with steroid synthesis and follicle growth development. This work contributes to understanding of the genetic basis of goat litter size and provides theoretical support for goat molecular breeding.

PoRVA G9P[23] and G5P[7] infections differentially promote PEDV replication by reprogramming glutamine metabolism.

PoRVA and PEDV coinfections are extremely common in clinical practice. Although coinfections of PoRVA and PEDV are known to result in increased mortality, the underlying mechanism remains unknown. Here, we found that PoRVA infection promoted PEDV infection in vivo and in vitro and that PoRVA G9P[23] (RVA-HNNY strain) enhanced PEDV replication more significantly than did PoRVA G5P[7] (RVA-SXXA strain). Metabolomic analysis revealed that RVA-HNNY more efficiently induced an increase in the intracellular glutamine content in porcine small intestinal epithelial cells than did RVA-SXXA, which more markedly promoted ATP production to facilitate PEDV replication, whereas glutamine deprivation abrogated the effect of PoRVA infection on promoting PEDV replication. Further studies showed that PoRVA infection promoted glutamine uptake by upregulating the expression of the glutamine transporter protein SLC1A5. In SLC1A5 knockout cells, PoRVA infection neither elevated intracellular glutamine nor promoted PEDV replication. During PoRVA infection, the activity and protein expression levels of glutamine catabolism-related enzymes (GLS1 and GLUD1) were also significantly increased promoting ATP production through glutamine anaplerosis into the TCA cycle. Consistent with that, siRNAs or inhibitors of GLS1 and GLUD1 significantly inhibited the promotion of PEDV replication by PoRVA. Notably, RVA-HNNY infection more markedly promoted SLC1A5, GLS1 and GLUD1 expression to more significantly increase the uptake and catabolism of glutamine than RVA-SXXA infection. Collectively, our findings illuminate a novel mechanism by which PoRVA infection promotes PEDV infection and reveal that the modulation of glutamine uptake is key for the different efficiencies of PoRVA G9P[23] and PoRVA G5P[7] in promoting PEDV replication.

The Convergence of Sonodynamic Therapy and Cuproptosis in the Dual-Responsive Biomimetic CytoNano for Precision Mitochondrial Intervention in Cancer Treatment.

The integration of sonodynamic therapy (SDT) with cuproptosis for targeted cancer treatment epitomizes a significant advancement in oncology. Herein, we present a dual-responsive therapeutic system, "CytoNano", which combines a cationic liposome infused with copper-nitride nanoparticles and oxygen-rich perfluorocarbon (Lip@Cu3N/PFC-O2), all enveloped in a biomimetic coating of neutrophil membrane and acid-responsive carboxymethylcellulose. CytoNano leverages the cellular mimicry of neutrophils and acid-responsive materials, enabling precise targeting of tumors and their acidic microenvironment. This strategic design facilitates the targeted release of Lip@Cu3N/PFC-O2 within the tumor, enhancing cancer cell uptake and mitochondrial localization. Consequently, it amplifies the therapeutic efficacy of both Cu3N-driven SDT and cuproptosis while preserving healthy tissues. Additionally, CytoNano's ultrasound responsiveness enhances intratumoral oxygenation, overcoming physiological barriers and initiating a combined sonodynamic-cuproptotic effect that induces multiple cell death pathways. Thus, we pioneer a biomimetic approach in precise sonodynamic cuproptosis, revolutionizing cancer therapy.

CRISPR/Cas12a-mediated DNA-AgNC label-free logical gate for multiple microRNAs' assay.

CRISPR/Cas system has been widely applied in the assay of disease-related nucleic acids. However, it is still challenging to use CRISPR/Cas system to detect multiple nucleic acids at the same time. Herein, we combined the preponderance of DNA logic circuit, label-free, and CRISPR/Cas technology to construct a label-free "AND" logical gate for multiple microRNAs detection with high specificity and sensitivity. With the simultaneous input of miRNA-155 and miRNA-141, the logic gate starts, and the activation chain of Cas12a is destroyed; thus, the activity is inhibited and the fluorescence of the signal probe ssDNA-AgNCs is turned on. The detection limit of this method for simultaneous quantitative detection of double target is 84 fmol/L (S/N = 3). In this "AND" logic gate, it is only necessary for the design of a simple DNA hairpin probe, which is inexpensive and easy, and since this method involves only one signal output, the data processing is very simple. What is more important, in this strategy two types of microRNAs can be monitored simultaneously by only using CRISPR/Cas12a and a type of crRNA, which offers a new design concept for the exploitation of single CRISPR/Cas system for multiple nucleic acid assays.

Trends and age-period-cohort effect on incidence of hepatitis B from 2008 to 2022 in Guangzhou, China.

Hepatitis B virus (HBV) infection is highly prevalent in Guangzhou, China. This study aimed to examine the long-term trend of HB incidence from 2008 to 2022 and the independent impacts of age, period, and cohort on the trends. HBV data were collected from the China Information System for Disease Control and Prevention. Joinpoint regression was utilized to examine temporal trends, and an age-period-cohort model was employed to estimate the effects of age, period, and cohort. A total of 327,585 HBV cases were included in this study. The incidence of chronic and acute HB showed a decreasing trend in Guangzhou over the past 15 years, with an average annual percent change of - 4.31% and - 16.87%, respectively. Age, period, and cohort all exerted significant effects. The incidence of HB was higher in males than in females and non-central areas compared to central areas. Age groups of 0-4 years and 15-24 years were identified as high-risk groups. The period relative risks for chronic HB incidence decreased initially and then stabilized. Cohorts born later had lower risks. Chronic HB incidences remain high in Guangzhou, especially among males, younger individuals, and residents of non-central areas. More efforts are still needed to achieve hepatitis elimination targets.

A homologous membrane-camouflaged self-assembled nanodrug for synergistic antitumor therapy.

Limited success has been achieved in ferroptosis-induced cancer treatment due to the challenges related to low production of toxic reactive oxygen species (ROS) and inherent ROS resistance in cancer cells. To address this issue, a self-assembled nanodrug have been investigated that enhances ferroptosis therapy by increasing ROS production and reducing ROS inhibition. The nanodrug is constructed by allowing doxorubicin (DOX) to interact with Fe2+ through coordination interactions, forming a stable DOX-Fe2+ chelate, and this chelate further interacts with sorafenib (SRF), resulting in a stable and uniform nanoparticle. In tumor cells, overexpressed glutathione (GSH) triggers the disassembly of nanodrug, thereby activating the drug release. Interestingly, the released DOX not only activates nicotinamide adenine dinucleotide phosphate oxidase 4 (NOX4) to produce abundant H2O2 production for enhanced ROS production, but also acts as a chemotherapeutics agent, synergizing with ferroptosis. To enhance tumor selectivity and improve the blood clearance, the nanodrug is coated with a related cancer cell membrane, which enhances the selective inhibition of tumor growth and metastasis in a B16F10 mice model. Our findings provide valuable insights into the rational design of self-assembled nanodrug for enhanced ferroptosis therapy in cancer treatment. STATEMENT OF SIGNIFICANCE: Ferroptosis is a non-apoptotic form of cell death induced by the iron-regulated lipid peroxides (LPOs), offering a promising potential for effective and safe anti-cancer treatment. However, two significant challenges hinder its clinical application: 1) The easily oxidized nature of Fe2+ and the low concentration of H2O2 leads to a low efficiency of intracellular Fenton reaction, resulting in poor therapeutic efficacy; 2) The instinctive ROS resistance of cancer cells induce drug resistance. Therefore, we developed a simple and high-efficiency nanodrug composed of self-assembling by Fe2+ sources, H2O2 inducer and ROS resistance inhibitors. This nanodrug can effectively deliver the Fe2+ sources into tumor tissue, enhance intracellular concentration of H2O2, and reduce ROS resistance, achieving a high-efficiency, precise and safe ferroptosis therapy.

Sensory ASIC3 channel exacerbates psoriatic inflammation via a neurogenic pathway in female mice.

Psoriasis is an immune-mediated skin disease associated with neurogenic inflammation, but the underlying molecular mechanism remains unclear. We demonstrate here that acid-sensing ion channel 3 (ASIC3) exacerbates psoriatic inflammation through a sensory neurogenic pathway. Global or nociceptor-specific Asic3 knockout (KO) in female mice alleviates imiquimod-induced psoriatic acanthosis and type 17 inflammation to the same extent as nociceptor ablation. However, ASIC3 is dispensable for IL-23-induced psoriatic inflammation that bypasses the need for nociceptors. Mechanistically, ASIC3 activation induces the activity-dependent release of calcitonin gene-related peptide (CGRP) from sensory neurons to promote neurogenic inflammation. Botulinum neurotoxin A and CGRP antagonists prevent sensory neuron-mediated exacerbation of psoriatic inflammation to similar extents as Asic3 KO. In contrast, replenishing CGRP in the skin of Asic3 KO mice restores the inflammatory response. These findings establish sensory ASIC3 as a critical constituent in psoriatic inflammation, and a promising target for neurogenic inflammation management.

The Masquelet induced membrane technique with PRP-FG-nHA/PA66 scaffold can heal a rat large femoral bone defect.

BACKGROUND: Masquelet membrane induction technology is one of the treatment strategies for large bone defect (LBD). However, the angiogenesis ability of induced membrane decreases with time and autologous bone grafting is associated with donor site morbidity. This study investigates if the PRP-FG-nHA/PA66 scaffold can be used as a spacer instead of PMMA to improve the angiogenesis ability of induced membrane and reduce the amount of autologous bone graft. METHODS: Platelet rich plasma (PRP) was prepared and PRP-FG-nHA/PA66 scaffold was synthesized and observed. The sustained release of VEGFA and porosity of the scaffold were analyzed. We established a femur LBD model in male SD rats. 55 rats were randomly divided into four groups depending on the spacer filled in the defect area. "Defect only" group (n = 10), "PMMA" group (n = 15), "PRP-nHA/PA66" group (n = 15) and "PRP-FG-nHA/PA66" group (n = 15 ). At 6 weeks, the spacers were removed and the defects were grafted. The induced membrane and bone were collected and stained. The bone formation was detected by micro-CT and the callus union was scored on a three point system. RESULTS: The PRP-FG-nHA/PA66 scaffold was porosity and could maintain a high concentration of VEGFA after 30 days of preparation. The induced membrane in PRP-FG-nHA/PA66 group was thinner than PMMA, but the vessel density was higher.The weight of autogenous bone grafted in PRP-FG-nHA/PA66 group was significantly smaller than that of PMMA group. In PRP-FG-nHA/PA66 group, the bone defect was morphologically repaired. CONCLUSION: The study showed that PRP-FG-nHA/PA66 scaffold can significantly reduce the amount of autologous bone graft, and can achieve similar bone defect repair effect as PMMA. Our findings provide some reference and theoretical support for the treatment of large segmental bone defects in humans.