Study on the Length of Smoke Backlayering of Double-Source Fire in Tunnels.

In order to predict the smoke backlayering length of double-source fire in tunnels, this paper deduced the dimensional expressions for smoke backlayering length by theoretical analysis and proposed a prediction formula for smoke backlayering length in single-source fire on the basis of the Fire Dynamics Simulator. Based on the results, the paper proposed a method for studying the smoke backlayering length of double-source fire in the tunnel. By introducing the fire power influence coefficient α and the distance influence coefficient ß, the formula for predicting smoke backlayering length in single-source fire was revised to obtain a new formula for predicting the smoke backlayering length of double-source fire. By comparing the formula prediction value with the simulation value, it is found that the prediction formula is almost accurate. This study will be helpful for understanding the multisource tunnel fire and predicting the smoke backlayering length of double-source fire in tunnels, which can provide guidance for tunnel fire rescue.

Application prospects of the 2BS cell-adapted China fixed rabies virus vaccine strain 2aG4-B40.

BACKGROUND: Rabies is a fatal zoonotic disease whose pathogenesis has not been fully elucidated, and vaccination is the only effective method for protecting against rabies virus infection. Most inactivated vaccines are produced using Vero cells, which are African green monkey kidney cells, to achieve large-scale production. However, there is a potential carcinogenic risk due to nonhuman DNA contamination. Thus, replacing Vero cells with human diploid cells may be a safer strategy. In this study, we developed a novel 2BS cell-adapted rabies virus strain and analysed its sequence, virulence and immunogenicity to determine its application potential as a human diploid cell inactivated vaccine. METHODS AND RESULTS: The 2BS cell-adapted rabies virus strain 2aG4-B40 was established by passage for 40 generations and selection of plaques in 2BS cells. RNA sequence analysis revealed that mutations in 2BS cell-adapted strains were not located at key sites that regulate the production of neutralizing antibodies or virulence in the aG strain (GQ412744.1). The gradual increase in virulence (remaining above 7.0 logLD50/ml from the 40th to 55th generation) and antigen further indicated that these mutations may increase the affinity of the adapted strains for human diploid cells. Identification tests revealed that the 2BS cell-adapted virus strain was neutralized by anti-rabies serum, with a neutralization index of 19,952. PrEP and PEP vaccination and the NIH test further indicated that the vaccine prepared with the 2aG4-B40 strain had high neutralizing antibody levels (2.24 to 46.67 IU/ml), immunogenicity (protection index 270) and potency (average 11.6 IU/ml). CONCLUSIONS: In this study, a 2BS cell-adapted strain of the 2aG4 rabies virus was obtained by passage for 40 generations. The results of sequencing analysis and titre determination of the adapted strain showed that the mutations in the adaptive process are not located at key sequence regions of the virus, and these mutations may enhance the affinity of the adapted strain for human diploid cells. Moreover, vaccines made from the adapted strain 2aG4-B40 had high potency and immunogenicity and could be an ideal candidate rabies virus strain for inactivated vaccine preparation.

Multimaterial Printing of Serpentine Microarchitectures with Synergistic Mechanical/Piezoelectric Stimulation for Enhanced Cardiac-Specific Functional Regeneration.

Recreating the natural heart's mechanical and electrical environment is crucial for engineering functional cardiac tissue and repairing infarcted myocardium in vivo. In this study, multimaterial-printed serpentine microarchitectures are presented with synergistic mechanical/piezoelectric stimulation, incorporating polycaprolactone (PCL) microfibers for mechanical support, polyvinylidene fluoride (PVDF) microfibers for piezoelectric stimulation, and magnetic PCL/Fe3O4 for controlled deformation via an external magnet. Rat cardiomyocytes in piezoelectric constructs, subjected to dynamic mechanical stimulation, exhibit advanced maturation, featuring superior sarcomeric structures, improved calcium transients, and upregulated maturation genes compared to non-piezoelectric constructs. Furthermore, these engineered piezoelectric cardiac constructs demonstrate significant structural and functional repair of infarcted myocardium, as evidenced by enhanced ejection and shortening fraction, reduced fibrosis and inflammation, and increased angiogenesis. The findings underscore the therapeutic potential of piezoelectric cardiac constructs for myocardial infarction therapy.

K2CO3-Catalyzed (3 + 2) Cycloaddition Reaction of N-2,2,2-Trifluoroethylisatin Ketimines with Azodicarboxylates: Access to Spirooxindoles Containing Trifluoromethyl-1,2,4-triazolines.

Potassium carbonate-catalyzed (3 + 2) cycloaddition reaction between N-2,2,2-trifluoroethylisatin ketimines and azodicarboxylates has been developed, constructing a series of novel N-heterocycle infused spirooxindoles in good to excellent yields (up to 98%) under milder conditions. The presence of both biologically active oxindole and trifluoromethyl-1,2,4-triazoline moieties in these novel spirocyclic compounds would provide new lead structures in the discovery of heterocyclic compounds with potential pharmaceutical activities.

Re-exploration of tetrahydro-ß-carboline scaffold: Discovery of selective histone deacetylase 6 inhibitors with neurite outgrowth-promoting and neuroprotective activities.

Histone deacetylase 6 (HDAC6) has drawn more and more attention for its potential application in Alzheimer's disease (AD) therapy. A series of tetrahydro-ß-carboline (THßC) hydroxamic acids with aryl linker were synthesized. In enzymatic assay, all compounds exhibited nanomolar IC50 values. The most promising compound 11d preferentially inhibited HDAC6 (IC50, 8.64 nM) with approximately 149-fold selectivity over HDAC1. Molecular simulation revealed that the hydroxamic acid of 11d could bind to the zinc ion by a bidentate chelating manner. In vitro, 11d induced neurite outgrowth of PC12 cells without producing toxic effects and showed obvious neuroprotective activity in a model of H2O2-induced oxidative stress.

Leaf-venation-directed cellular alignment for macroscale cardiac constructs with tissue-like functionalities.

Recapitulating the complex structural, mechanical, and electrophysiological properties of native myocardium is crucial to engineering functional cardiac tissues. Here, we report a leaf-venation-directed strategy that enables the compaction and remodeling of cell-hydrogel hybrids into highly aligned and densely packed organizations in predetermined patterns. This strategy contributes to interconnected tubular structures with cell alignment along the hierarchical channels. Compared to randomly-distributed cells, the engineered leaf-venation-directed-cardiac tissues from neonatal rat cardiomyocytes manifest advanced maturation and functionality as evidenced by detectable electrophysiological activity, macroscopically synchronous contractions, and upregulated maturation genes. As a demonstration, human induced pluripotent stem cell-derived leaf-venation-directed-cardiac tissues are engineered with evident structural and functional improvement over time. With the elastic scaffolds, leaf-venation-directed tissues are assembled into 3D centimeter-scale cardiac constructs with programmed mechanical properties, which can be delivered through tubing without affecting cell viability. The present strategy may generate cardiac constructs with multifaceted functionalities to meet clinical demands.

Spatial interpolation of regional PM2.5 concentrations in China during COVID-19 incorporating multivariate data.

During specific periods when the PM2.5 variation pattern is unusual, such as during the coronavirus disease 2019 (COVID-19) outbreak, epidemic PM2.5 regional interpolation models have been relatively little investigated, and little consideration has been given to the residuals of optimized models and changes in model interpolation accuracy for the PM2.5 concentration under the influence of epidemic phenomena. Therefore, this paper mainly introduces four interpolation methods (kriging, empirical Bayesian kriging, tensor spline function and complete regular spline function), constructs geographically weighted regression (GWR) models of the PM2.5 concentration in Chinese regions for the periods from January-June 2019 and January-June 2020 by considering multiple factors, and optimizes the GWR regression residuals using these four interpolation methods, thus achieving the purpose of enhancing the model accuracy. The PM2.5 concentrations in many regions of China showed a downward trend during the same period before and after the COVID-19 outbreak. Atmospheric pollutants, meteorological factors, elevation, zenith wet delay (ZWD), normalized difference vegetation index (NDVI) and population maintained a certain relationship with the PM2.5 concentration in terms of linear spatial relationships, which could explain why the PM2.5 concentration changed to a certain extent. By evaluating the model accuracy from two perspectives, i.e., the overall interpolation effect and the validation set interpolation effect, the results showed that all four interpolation methods could improve the numerical accuracy of GWR to different degrees, among which the tensor spline function and the fully regular spline function achieved the most stable effect on the correction of GWR residuals, followed by kriging and empirical Bayesian kriging.

Identification and characterization of Colletotrichum fioriniae and C. fructicola that cause anthracnose in pecan.

Pecan (Carya illinoinensis Wang. K. Koch) is a deciduous tree of the Juglandaceae family with important economic value worldwide. Anthracnose of the pecan leaves and shuck is a devastating disease faced by pecan-growing areas in China. However, the causal species occurring on pecan remain largely unidentified. we collected samples of diseased pecan from the provinces of China, Leaves and fruits affected by anthracnose were sampled and subjected to fungus isolation, The morphological characters of all strains were observed and compared; Multi-locus phylogenetic analyses [Internally transcribed spacer (ITS), Actin (ACT), Calmodulin (CAL), Chitin synthase (CHS1), Glyceraldehyde 3-phosphate dehydrogenase (GAPDH), and b-tubulin (TUB2)] were performed on selected representative strains; examine their pathogenicity on leaves of pecan.The results showed that: (1) resulting in a total of 11 Colletotrichum isolates, Two Colletotrichum species were identifified to be C. fioriniae and C. fructicola; (2) Pathogenicity tests revealed that both species caused black spots on pecan leaves and fruit, The virulence of the different isolates varied substantially, with C. fioriniae PCJD179 being the most virulent; (3) The susceptibility levels of pecan tree varieties, 'Mahan' and 'Kanza', were determined, No significant differences were observed in the lesion sizes produced by the various isolates in 'Kanza', while there were signifificant differences in 'Mahan'. This study is thefifirst to determine that C. fructicola and C. fioriniaecan cause anthracnose in pecan in China. It improves the understanding of the species that cause anthracnose in pecan and provides useful information for the effective control of this disease in China.

Cloning and Functional Characterization of a Novel ß-GRP Gene From Melanotus cribricollis.

In this study, a novel ß-1,3-glucan recognition protein gene (ß-GRP) was identified from Melanotus cribricollis, and its potential role in the immune response was investigated. The full length of ß-GRP cDNA (Accession Number: MT941530) was 1644 bp, encoding a protein composed of 428 amino acids. The theoretical molecular weight and the isoelectric point were 51.53 kDa and 6.17, respectively. The amino acid sequence of ß-GRP from M. cribricollis was closely related to that of. ß-GRP-like from Photinus pyralis, and was predicted to contain conserved GH16 domain without glucanase active site. The results of real-time quantitative PCR showed that fungal infection of Metarhizium pingshaense may significantly upregulated the expression level of ß-GRP gene. The RNAi suppression of ß-GRP gene expression significantly increased the corrected cumulative mortality. Meanwhile, antimicrobial peptide genes defensin and lysozyme were significantly downregulated after interference of ß-GRP. Taken together, these results suggest that ß-GRP of M. cribricollis probably participates in the host immune system by mediating the expression of antimicrobial peptides. This study provides comprehensive insights into the innate immune system of insect larvae.

IL-1ß-Triggered Long Non-coding RNA CHRF Induces Non-Small Cell Lung Cancer by Modulating the microRNA-489/Myd88 Axis.

Background: Long noncoding RNAs (LncRNAs) possess crucial roles in carcinogenesis. The current study aims to evaluate the effects of interleukin-1ß (IL-1ß)-mediated lncRNA cardiac hypertrophy-related factor (CHRF)/microRNA-489 (miR-489)/myeloid differentiation factor 88 (Myd88) on non-small-cell lung cancer (NSCLC). Methods: Initially, the expression of IL-1ß and lncRNA CHRF in NSCLC cells and tissues was determined, respectively. H460 cell line with highest lncRNA CHRF expression was selected for in vitro experimentations. Afterward, the interaction among lncRNA CHRF, miR-489, and Myd88 was verified with their significance in cell functions and tumorigenicity and lung metastasis analyzed following. Results: IL-1ß and lncRNA CHRF was remarkably upregulated in NSCLC. IL-1ß was able to elevate lncRNA CHRF expression. Additionally, lncRNA CHRF targeted miR-489 and miR-489 targeted Myd88. Moreover, functional assay results suggested that under IL-1ß treatment, lncRNA CHRF induced NSCLC cell malignant properties and tumorigenicity and lung metastasis through modulation of miR-489/Myd88 axis. Conclusion: Taken together, our findings revealed that IL-1ß-induced elevation of lncRNA CHRF aggravated NSCLC through modulation of miR-489/Myd88 axis, which provides a novel direction for NSCLC therapy development.

Archaea is more important than bacteria in driving soil stoichiometry in phosphorus deficient habitats.

Phosphorus deficiency is a critical limit on the cycling of carbon (C), nitrogen (N) and phosphorus (P) in forest ecosystems. Despite the pivotal roles of microbes in driving the biogeochemical cycling of C/N/P, our knowledge on the relationships of soil bacteria and archaea to P deficiency in forest ecosystems remains scarce. Here, we studied 110 acidic soils (average pH 4.5) collected across 700-km subtropical forests with a gradient of available phosphorus (AP) ranging from 0.21 to 17.6 mg/kg. We analyzed the soil C/N/P stoichiometry and studied soil bacterial and archaeal diversity/abundance via high throughput sequencing and qPCR approaches. Our results show that soil P decoupled with N or C when below 3 mg/kg but coupled with C and N when above 3 mg/kg. Archaeal diversity and abundance were significantly higher in low AP (< 3 mg/kg) soils than in high AP (>3 mg/kg) soils, while bacterial were less changed. Compared with bacteria, archaea are more strongly related with soil stoichiometry (C:N, C:P, N:P), especially when AP was less than 3 mg/kg. Taxonomic and functional composition analysis further confirmed that archaeal rather than bacterial taxonomic composition was significantly related with functional composition of microbial communities. Taken together, our results show that archaea are more important than bacteria in driving soil stoichiometry in phosphorus deficient habitats and suggest a niche differentiation of soil bacteria and archaea in regulating the soil C/N/P cycling in subtropical forests.

Immune response and potential therapeutic strategies for the SARS-CoV-2 associated with the COVID-19 pandemic.

Following onset of the first recorded case of Coronavirus disease 2019 (COVID-19) in December 2019, more than 269 million cases and over 5.3 million deaths have been confirmed worldwide. COVID-19 is a highly infectious pneumonia, caused by a novel virus called severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Currently, it poses a severe threat to human health across the globe, a trend that is likely to persist in the foreseeable future. This paper reviews SARS-CoV-2 immunity, the latest development of anti-SARS-CoV-2 drugs as well as exploring in detail, immune escape induced by SARS-CoV-2. We expect that the findings will provide a basis for COVID-19 prevention and treatment.

Three epitope-distinct human antibodies from RenMab mice neutralize SARS-CoV-2 and cooperatively minimize the escape of mutants.

Coronavirus disease 2019 (COVID-19), a pandemic disease caused by the newly emerging severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has caused more than 3.8 million deaths to date. Neutralizing antibodies are effective therapeutic measures. However, many naturally occurring mutations at the receptor-binding domain (RBD) have emerged, and some of them can evade existing neutralizing antibodies. Here, we utilized RenMab, a novel mouse carrying the entire human antibody variable region, for neutralizing antibody discovery. We obtained several potent RBD-blocking antibodies and categorized them into four distinct groups by epitope mapping. We determined the involved residues of the epitope of three representative antibodies by cryo-electron microscopy (Cryo-EM) studies. Moreover, we performed neutralizing experiments with 50 variant strains with single or combined mutations and found that the mixing of three epitope-distinct antibodies almost eliminated the mutant escape. Our study provides a sound basis for the rational design of fully human antibody cocktails against SARS-CoV-2 and pre-emergent coronaviral threats.

Organic carbon dot coating for superhydrophobic aluminum alloy surfaces.

A novel fluorine-free and silicon-free superhydrophobic aluminum alloy (treated-Al) is fabricated by chemical etching using hydrochloric acid and hydrogen peroxide and modified with an organic carbon dot (OCD) coating. The water contact angle (CA) of the treated-Al surface increases with the OCD concentration. When etched aluminum (etched-Al) is modified with 0.5 mg/ml OCDs, a CA of 161.4° is achieved, which indicates good nonwettability. SEM results verify that porous microstructures with cavities are uniformly distributed on the surface of etched-Al, in contrast to the bare aluminum alloy, which forms a primary rough structure. After treatment with 0.5 mg/ml OCDs, a nanoparticle coating is dispersed on the rough structures of treated-Al-0.5, which can trap air and make a water droplet essentially rest on a layer of air. The treated-Al-0.5 material has good self-cleaning properties and can sweep away contaminants at both 20 and 0°C. The Ecorr and Icorr of treated-Al-0.5 are - 0.56 V and 2.82 × 10-6 A/cm2, respectively, which shows good anticorrosion performance.

[A calcium-sensing receptor polymorphism at E942K promotes the proliferation of gastric cancer cells via Ca2+ and ERK1/2 pathways].

The study was designed to investigate the effects and mechanism of a calcium-sensing receptor (CaSR) polymorphism at E942K on the proliferation of gastric cancer cells. Single nucleotide polymorphisms (SNPs) were detected between gastric cancers group and normal controls group by DNA sequence analysis. The cell model was constructed by transfection of E942K mutant plasmid and wild-type (WT) plasmid into SGC-7901 and HEK-293 cells. The effect of E942K mutation on cell proliferation ability was detected by CCK8 and cell clone formation experiments. The effect of E942K mutation on calcium signaling was detected by calcium imaging. Western blot experiments were used to detect changes in phosphorylation levels of key proteins ERK1/2 and ß-catenin in downstream signaling pathways after E942K mutation. The results showed that the mutation rate of E942K in gastric cancer group was significantly higher than that in normal control group (P < 0.05). CCK8 and cell clone formation experiments showed that E942K mutation significantly improved the proliferation ability of SGC-7901 gastric cancer cells and HEK-293 cells. E942K mutation enhanced calcium signaling in SGC-7901 and HEK-293 cells. E942K mutation enhanced ERK1/2 phosphorylation without affecting ß-catenin phosphorylation. The results suggest that E942K mutation in CaSR may ultimately promote the proliferation of gastric cancer cells by enhancing intracellular calcium signaling and ERK1/2 phosphorylation. These results have potential clinical implications for the diagnosis and targeted therapy of gastric cancer.

Exosomes-carried microRNA-26b-5p regulates microglia M1 polarization after cerebral ischemia/reperfusion.

Exosome and microRNAs (miRs) are implicated in ischemia/reperfusion (I/R) process. In this study, I/R mouse model was established, and exosomes derived from human umbilical cord mesenchymal stem cells (hUCMSCs) were isolated, identified, and injected to I/R mice to observe nerve injury and microglia M1 polarization. The differentially expressed genes in I/R microglia from databases were analyzed, and miRs differentially expressed in exosomes-treated microglia were analyzed by microarray. miR-26b-5p expression in hUCMSCs was intervened. Besides, microglia was extracted and co-cultured with SH-SY5Y or PC12 cells in oxygen-glucose deprivation/reperfusion (OGD/R) models to simulate I/R in vivo. Additionally, Toll-like receptor (TLR) activator GS-9620 was added to microglia. Exosomes alleviated nerve injury and inhibited M1 polarization in microglia. After I/R modeling, CH25H expression in microglia was upregulated but decreased after exosome treatment. miR-26b-5p was upregulated in microglia after exosome treatment and could target CH25H. Reduction in exosomal miR-26b-5p reversed the effects of hUCMSCs-exos on microglia. TLR pathway was activated in microglia after I/R but exosomes prevented its activation. Exosomal miR-26b-5p could repress M1 polarization of microglia by targeting CH25H to inactivate the TLR pathway, so as to relieve nerve injury after cerebral I/R. This investigation may offer new approaches for I/R treatment.

The Gut Microbiota in Camellia Weevils Are Influenced by Plant Secondary Metabolites and Contribute to Saponin Degradation.

The camellia weevil (CW [Curculio chinensis]) is a notorious host-specific predator of the seeds of Camellia species in China, causing seed losses of up to 60%. The weevil is capable of overcoming host tree chemical defenses, while the mechanisms of how these beetles contend with the toxic compounds are still unknown. Here, we examined the interaction between the gut microbes of CW and camellia seed chemistry and found that beetle-associated bacterial symbionts mediate tea saponin degradation. We demonstrate that the gut microbial community profile of CW was significantly plant associated, and the gut bacterial community associated with CW feeding on Camellia oleifera seeds is enriched with genes involved in tea saponin degradation compared with those feeding on Camellia sinensis and Camellia reticulata seeds. Twenty-seven bacteria from the genera Enterobacter, Serratia, Acinetobacter, and Micrococcus subsisted on tea saponin as a sole source of carbon and nitrogen, and Acinetobacter species are identified as being involved in the degradation of tea saponin. Our results provide the first metagenome of gut bacterial communities associated with a specialist insect pest of Camellia trees, and the results are consistent with a potential microbial contribution to the detoxification of tree-defensive chemicals.IMPORTANCE The gut microbiome may play an important role in insect-plant interactions mediated by plant secondary metabolites, but the microbial communities and functions of toxic plant feeders are still poorly characterized. In the present study, we provide the first metagenome of gut bacterial communities associated with a specialist weevil feeding on saponin-rich and saponin-low camellia seeds, and the results reveal the correlation between bacterial diversity and plant allelochemicals. We also used cultured microbes to establish their saponin-degradative capacity outside the insect. Our results provide new experimental context to better understand how gut microbial communities are influenced by plant secondary metabolites and how the resistance mechanisms involving microbes have evolved to deal with the chemical defenses of plants.

Ti3C2Tx MXene Interface Layer Driving Ultra-Stable Lithium-Iodine Batteries with Both High Iodine Content and Mass Loading.

Lithium-iodine (Li-I2) batteries are promising candidates for next-generation electrochemical energy storage systems due to their high energy density and the excellent kinetic rates of I2 cathodes. However, dissolution of iodine and iodide has hindered their widespread adoption for practical applications. Herein, a Ti3C2Tx MXene foam with a three-dimensional hierarchical porous architecture is proposed as a cathode-electrolyte interface layer in Li-I2 batteries, enabling high-rate and ultrastable cycling performance at a high iodine content and loading mass. Theoretical calculations and empirical characterizations indicate that Ti3C2Tx MXene sheets with high metallic conductivity not only provide strong chemical binding with iodine species to suppress the shuttle effect but also facilitate fast redox reactions during cell cycling. As a result, the Li-I2 battery using a cathode with 70 wt % I2 cycled stably for over 1000 cycles at a rate of 2 C, even at an ultrahigh loading mass of 5.2 mg cm-2. To the best of the authors' knowledge, this is the highest reported loading at such a high iodine content. This work suggests that using a Ti3C2Tx MXene interface layer can enable the design and application of high-energy Li-I2 batteries.

RNA-sequencing analysis of fungi-induced transcripts from the bamboo wireworm Melanotus cribricollis (Coleoptera: Elateridae) larvae.

Larvae of Melanotus cribricollis, feed on bamboo shoots and roots, causing serious damage to bamboo in Southern China. However, there is currently no effective control measure to limit the population of this underground pest. Previously, a new entomopathogenic fungal strain isolated from M. cribricollis larvae cadavers named Metarhizium pingshaense WP08 showed high pathogenic efficacy indoors, indicated that the fungus could be used as a bio-control measure. So far, the genetic backgrounds of both M. cribricollis and M. pingshaense WP08 were blank. Here, we analyzed the whole transcriptome of M. cribricollis larvae, infected with M. pingshaense WP08 or not, using high-throughput next generation sequencing technology. In addition, the transcriptome sequencing of M. pingshaense WP08 was also performed for data separation of those two non-model species. The reliability of the RNA-Seq data was also validated through qRT-PCR experiment. The de novo assembly, functional annotation, sequence comparison of four insect species, and analysis of DEGs, enriched pathways, GO terms and immune related candidate genes were operated. The results indicated that, multiple defense mechanisms of M. cribricollis larvae are initiated to protect against the more serious negative effects caused by fungal infection. To our knowledge, this was the first report of transcriptome analysis of Melanotus spp. infected with a fungus, and it could provide insights to further explore insect-fungi interaction mechanisms.

Sympathetic denervation-induced MSC mobilization in distraction osteogenesis associates with inhibition of MSC migration and osteogenesis by norepinephrine/adrb3.

The sympathetic nervous system regulates bone formation and resorption under physiological conditions. However, it is still unclear how the sympathetic nerves affect stem cell migration and differentiation in bone regeneration. Distraction osteogenesis is an ideal model of bone regeneration due to its special nature as a self-engineering tissue. In this study, a rat model of mandibular distraction osteogenesis with transection of cervical sympathetic trunk was used to demonstrate that sympathetic denervation can deplete norepinephrine (NE) in distraction-induced bone callus, down-regulate ß3-adrenergic receptor (adrb3) in bone marrow mesenchymal stem cells (MSCs), and promote MSC migration from perivascular regions to bone-forming units. An in vitro Transwell assay was here used to demonstrate that NE can inhibit stroma-derived factor-1 (SDF-1)-induced MSC migration and expression of the migration-related gene matrix metalloproteinase-2 (MMP-2) and downregulate that of the anti-migration gene tissue inhibitor of metalloproteinase-3 (TIMP-3). Knockdown of adrb3 using siRNA abolishes inhibition of MSC migration. An in vitro osteogenic assay was used to show that NE can inhibit the formation of MSC bone nodules and expression of the osteogenic marker genes alkaline phosphatase (ALP), osteocalcin (OCN), and runt-related transcription factor-2 (RUNX2), but knockdown of adrb3 by siRNA can abolish such inhibition of the osteogenic differentiation of MSCs. It is here concluded that sympathetic denervation-induced MSC mobilization in rat mandibular distraction osteogenesis is associated with inhibition of MSC migration and osteogenic differentiation by NE/adrb3 in vitro. These findings may facilitate understanding of the relationship of MSC mobilization and sympathetic nervous system across a wide spectrum of tissue regeneration processes.