ABSTRACT
Sneezing and coughing are primary symptoms of many respiratory viral infections and allergies. It is generally assumed that sneezing and coughing involve common sensory receptors and molecular neurotransmission mechanisms. Here, we show that the nasal mucosa is innervated by several discrete populations of sensory neurons, but only one population (MrgprC11+MrgprA3-) mediates sneezing responses to a multitude of nasal irritants, allergens, and viruses. Although this population also innervates the trachea, it does not mediate coughing, as revealed by our newly established cough model. Instead, a distinct sensory population (somatostatin [SST+]) mediates coughing but not sneezing, unraveling an unforeseen sensory difference between sneezing and coughing. At the circuit level, sneeze and cough signals are transmitted and modulated by divergent neuropathways. Together, our study reveals the difference in sensory receptors and neurotransmission/modulation mechanisms between sneezing and coughing, offering neuronal drug targets for symptom management in respiratory viral infections and allergies.
ABSTRACT
With a growing global concern over food safety and animal welfare issues, the livestock and veterinary industries are undergoing unprecedented changes. These changes have not only brought challenges within each industry, but also brought unprecedented opportunities for development. In this context, the search for natural and safe products that can effectively replace traditional veterinary drugs has become an important research direction in the fields of animal husbandry and veterinary medicine. Oregano essential oil (OEO), as a natural extract, is gradually emerging in the fields of animal husbandry and veterinary medicine with its unique antibacterial, antioxidant, and multiple other biological activities. OEO not only has a wide antibacterial spectrum, effectively fighting against a variety of pathogenic microorganisms, but also, because of its natural properties, helps us to avoid traditional veterinary drugs that may bring drug residues or cause drug resistance problems. This indicates OEO has great application potential in animal disease treatment, animal growth promotion, and animal welfare improvement. At present, the application of OEO in the fields of animal husbandry and veterinary medicine has achieved preliminary results. Studies have shown that adding OEO to animal feed can significantly improve the growth performance and health status of animals and reduce the occurrence of disease. At the same time, pharmacokinetic studies in animals show that the absorption, distribution, metabolism, and excretion processes of OEO in animals shows good bioavailability. In summary, oregano essential oil (OEO), as a substitute for natural veterinary drugs with broad application prospects, is gradually becoming a research hotspot in the field of animal husbandry and veterinary medicine. In the future, we look forward to further tapping the potential of OEO through more research and practice and making greater contributions to the sustainable development of the livestock and veterinary industries.
ABSTRACT
The goose astrovirus (GAstV), a key pathogen causing visceral gout and high mortality in geese, has spread widely in China, with frequent outbreaks in recent years. Outbreaks and transmissions of this virus have been reported across China, causing considerable economic losses to the goose industry worldwide, with losses exceeding tens of billions in China alone. However, there is still no effective prevention strategy against this virus. Therefore, continuous monitoring of the genetic diversity of dominant GAstV strains is crucial for developing targeted vaccines and appropriate therapeutics. As a crucial region for goose breeding in China, Hebei Province has previously lacked reports on the epidemiology of GAstV. Hence, investigating the epidemiology of GAstV in Hebei Province is highly important. From January 2019 to December 2021, 474 samples suspected of having a GAstV infection were collected in Hebei Province in this study. Through detailed histological observations, pathological examinations, virus isolation and identification, and genetic diversity analysis, we found that GAstV-2 has become the predominant circulating genotype. However, the presence of GAstV-1 and mixed infections cannot be ignored and should receive increased attention. The findings of this study not only deepened our understanding of GAstV in waterfowl in China but also provided scientific evidence for developing effective prevention and control measures, thereby promoting the healthy development of the goose industry in China.
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This study selected five typical types of chemical industry volatile organic compounds (VOCs) emission characteristics in China for analysis. The results from 70 source samples showed that alkanes were the dominant VOCs category from synthetic material industry sources, petrochemical industry sources, and coating industry sources (accounting for 43%, 63%, and 68%, respectively); olefins were the main VOCs category from the daily supplies chemical industry (46%); and halogenated hydrocarbons were the dominate VOCs category from specialty chemicals industry account source emissions (43%). Additionally, the machine learning method was applied in this study to analyze the marker components of the above industries. The results showed that decane and tetrahydrofuran were the source markers of the synthetic material industry; n-butanol and toluene were the markers of the daily supplies industry source; 1,2,3-trimethylbenzene and 1,3,5-trimethylbenzene were the markers of the petrochemical industry source; propylene and 3-methyl pentane were the source markers of the coating industry; and P-Xylene and cumene were the markers of the specialty chemicals industry source. The maximum incremental reactivity method (MIR) was used to estimate the ozone formation potential (OFP) of different VOCs-sources. The calculation results showed that when considering per unit TVOCs concentration emissions, the contribution to the ozone generation potential was in the order of the daily supplies chemical industry, specialty chemical industry, petrochemical industry, synthetic material industry, and coating industry. Therefore, we suggest that more attention should be paid to the key active species emitted by various industry sources rather than only the total amount of VOCs emissions in future ozone prevention and control efforts.
ABSTRACT
BACKGROUND: Jianpi Gushen Huayu Decoction (JPGS) has been used to clinically treat diabetic nephropathy (DN) for many years. However, the protective mechanism of JPGS in treating DN remains unclear. AIM: To evaluate the therapeutic effects and the possible mechanism of JPGS on DN. METHODS: We first evaluated the therapeutic potential of JPGS on a DN mouse model. We then investigated the effect of JPGS on the renal metabolite levels of DN mice using non-targeted metabolomics. Furthermore, we examined the effects of JPGS on c-Jun N-terminal kinase (JNK)/P38-mediated apoptosis and the inflammatory responses mediated by toll-like receptor 4 (TLR4)/nuclear factor-kappa B (NF-κB)/NOD-like receptor family pyrin domain containing 3 (NLRP3). RESULTS: The ameliorative effects of JPGS on DN mice included the alleviation of renal injury and the control of inflammation and oxidative stress. Untargeted metabolomic analysis revealed that JPGS altered the metabolites of the kidneys in DN mice. A total of 51 differential metabolites were screened. Pathway analysis results indicated that nine pathways significantly changed between the control and model groups, while six pathways significantly altered between the model and JPGS groups. Pathways related to cysteine and methionine metabolism; alanine, tryptophan metabolism; aspartate and glutamate metabolism; and riboflavin metabolism were identified as the key pathways through which JPGS affects DN. Further experimental validation showed that JPGS treatment reduced the expression of TLR4/NF-κB/NLRP3 pathways and JNK/P38 pathway-mediated apoptosis related factors. CONCLUSION: JPGS could markedly treat mice with streptozotocin (STZ)-induced DN, which is possibly related to the regulation of several metabolic pathways found in kidneys. Furthermore, JPGS could improve kidney inflammatory responses and ameliorate kidney injuries in DN mice via the TLR4/NF-κB/NLRP3 pathway and inhibit JNK/P38 pathway-mediated apoptosis in DN mice.
ABSTRACT
Ghost imaging (GI) has been widely used in the applications including spectral imaging, 3D imaging, and other fields due to its advantages of broad spectrum and anti-interference. Nevertheless, the restricted sampling efficiency of ghost imaging has impeded its extensive application. In this work, we propose a novel foveated pattern affine transformer method based on deep learning for efficient GI. This method enables adaptive selection of the region of interest (ROI) by combining the proposed retina affine transformer (RAT) network with minimal computational and parametric quantities with the foveated speckle pattern. For single-target and multi-target scenarios, we propose RAT and RNN-RAT (recurrent neural network), respectively. The RAT network enables an adaptive alteration of the fovea of the variable foveated patterns spot to different sizes and positions of the target by predicting the affine matrix with a minor number of parameters for efficient GI. In addition, we integrate a recurrent neural network into the proposed RAT to form an RNN-RAT model, which is capable of performing multi-target ROI detection. Simulations and experimental results show that the method can achieve ROI localization and pattern generation in 0.358â ms, which is a 1 × 105 efficiency improvement compared with the previous methods and improving the image quality of ROI by more than 4â dB. This approach not only improves its overall applicability but also enhances the reconstruction quality of ROI. This creates additional opportunities for real-time GI.
ABSTRACT
The coronavirus disease 2019 (COVID-19) pandemic caused by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) and its variants has resulted in global economic losses and posed a threat to human health. The pandemic highlights the urgent need for an efficient, easily producible, and broad-spectrum vaccine. Here, we present a potentially universal strategy for the rapid and general design of vaccines, focusing on the design and testing of omicron BA.5 RBD-conjugated self-assembling ferritin nanoparticles (NPs). The covalent bonding of RBD-Fc to protein A-ferritin was easily accomplished through incubation, resulting in fully multivalent RBD-conjugated NPs that exhibited high structural uniformity, stability, and efficient assembly. The ferritin nanoparticle vaccine synergistically stimulated the innate immune response, Tfh-GCB-plasma cell-mediated activation of humoral immunity and IFN-γ-driven cellular immunity. This nanoparticle vaccine induced a high level of cross-neutralizing responses and protected golden hamsters challenged with multiple mutant strains from infection-induced clinical disease, providing a promising strategy for broad-spectrum vaccine development for SARS-CoV-2 prophylaxis. In conclusion, the nanoparticle conjugation platform holds promise for its potential universality and competitive immunization efficacy and is expected to facilitate the rapid manufacturing and broad application of next-generation vaccines.
Subject(s)
COVID-19 , Nanoparticles , Animals , Cricetinae , Humans , SARS-CoV-2 , COVID-19/prevention & control , COVID-19 Vaccines , Immunity, Innate , Ferritins/genetics , Nanovaccines , Antibodies, Neutralizing , Antibodies, ViralABSTRACT
Soil N mineralization is a key process of nutrient cycling in ecosystems. The mechanism of the seasonal distribution of precipitation on soil N mineralization remains unclear. We conducted a precipitation manipulation experiment in a subtropical forest in the middle and lower reaches of the Yangtze River in China from 2020 to 2022, with three treatments, including control (CK), decreased precipitation in the dry season with extremely increased precipitation in the wet season (T1), and decreased precipitation in the dry season with proportionally increased precipitation in the wet season (T2). With in situ resin core method, we explored the effect of seasonal distribution of precipitation on soil N mineralization. The results showed that T1 and T2 significantly decreased dry season net nitrification rate by 57.9% and 72.5% and the net N mineralization rate by 82.5% and 89.6%, respectively, and significantly increased wet season net nitrification rate by 64.3% and 79.5% and net N mineralization rate by 64.2% and 81.1%, respectively. Proportionally increased precipitation in the wet season was more conducive to soil N mine-ralization process than extremely increased precipitation in the wet season. Results of the structural equation model showed that change in seasonal distribution of precipitation could significantly affect soil N mineralization processes in the subtropical forest by changing soil water content, ammonium nitrogen, microbial biomass nitrogen, and soil C:N. Our results had important reference for understanding soil nitrogen cycling and other ecological processes, and were conducive to more accurate assessment on the impacts of future changes in seasonal precipitation pattern on subtropical forest ecosystems.
Subject(s)
Ecosystem , Nitrogen , Nitrogen/analysis , Seasons , Soil/chemistry , Soil Microbiology , Forests , ChinaABSTRACT
BACKGROUND: The spinal inflammatory signal often spreads to distant segments, accompanied by widespread pain symptom under neuropathological conditions. Multiple cytokines are released into the cerebrospinal fluid (CSF), potentially inducing the activation of an inflammatory cascade at remote segments through CSF flow. However, the detailed alteration of CSF in neuropathic pain and its specific role in widespread pain remain obscure. METHODS: A chronic constriction injury of the infraorbital nerve (CCI-ION) model was constructed, and pain-related behavior was observed on the 7th, 14th, 21st, and 28th days post surgery, in both vibrissa pads and hind paws. CSF from CCI-ION rats was transplanted to naïve rats through intracisternal injection, and thermal and mechanical allodynia were measured in hind paws. The alteration of inflammatory cytokines in CCI-ION's CSF was detected using an antibody array and bioinformatic analysis. Pharmacological intervention targeting the changed cytokine in the CSF and downstream signaling was performed to evaluate its role in widespread pain. RESULTS: CCI-ION induced local pain in vibrissa pads together with widespread pain in hind paws. CCI-ION's CSF transplantation, compared with sham CSF, contributed to vibrissa pad pain and hind paw pain in recipient rats. Among the measured cytokines, interleukin-6 (IL-6) and leptin were increased in CCI-ION's CSF, while interleukin-13 (IL-13) was significantly reduced. Furthermore, the concentration of CSF IL-6 was correlated with nerve injury extent, which gated the occurrence of widespread pain. Both astrocytes and microglia were increased in remote segments of the CCI-ION model, while the inhibition of astrocytes in remote segments, but not microglia, significantly alleviated widespread pain. Mechanically, astroglial signal transducer and activator of transcription 3 (STAT3) in remote segments were activated by CSF IL-6, the inhibition of which significantly mitigated widespread pain in CCI-ION. CONCLUSION: IL-6 was induced in the CSF of the CCI-ION model, triggering widespread pain via activating astrocyte STAT3 signal in remote segments. Therapies targeting IL-6/STAT3 signaling might serve as a promising strategy for the widespread pain symptom under neuropathological conditions.
Subject(s)
Interleukin-6 , Neuralgia , Rats , Animals , Interleukin-6/metabolism , Rats, Sprague-Dawley , STAT3 Transcription Factor/metabolism , Gliosis/complications , Constriction , Hyperalgesia/etiology , Hyperalgesia/drug therapy , Neuralgia/drug therapy , CytokinesABSTRACT
Alisol B 23-acetate (AB23A) has been demonstrated to have beneficial effects on nonalcoholic steatohepatitis (NASH). However, the mechanisms of AB23A on NASH remain unclear. This study aimed to investigate the mechanisms underlying the metabolic regulatory effects of AB23A on NASH. We used AB23A to treat mice with NASH, which was induced by a methionine and choline deficient (MCD) diet. We initially investigated therapeutic effect and resistance to oxidation and inflammation of AB23A on NASH. Subsequently, we performed untargeted metabolomic analyses and relative validation assessments to evaluate the metabolic regulatory effects of AB23A. AB23A reduced lipid accumulation, ameliorated oxidative stress and decreased pro-inflammatory cytokines in the liver. Untargeted metabolomic analysis found that AB23A altered the metabolites of liver. A total of 55 differential metabolites and three common changed pathways were screened among the control, model and AB23A treatment groups. Further tests validated the effects of AB23A on modulating common changed pathway-involved factors. AB23A treatment can ameliorate NASH by inhibiting oxidative stress and inflammation. The mechanism of AB23A on NASH may be related to the regulation of alanine, aspartate and glutamate metabolism, d-glutamine and d-glutamate metabolism, and arginine biosynthesis pathways.
Subject(s)
Non-alcoholic Fatty Liver Disease , Mice , Animals , Non-alcoholic Fatty Liver Disease/metabolism , Methionine/metabolism , Methionine/pharmacology , Choline , Liver/metabolism , Racemethionine/metabolism , Racemethionine/pharmacology , Diet , Inflammation/metabolism , Mice, Inbred C57BL , Disease Models, AnimalABSTRACT
Adult hippocampal neurogenesis (AHN), essential for the plasticity of hippocampal structure and function, may be disrupted in Alzheimer's disease (AD). However, the relationship between the changes in AHN and AD-related pathology in humans remains uncertain. By utilizing advanced immunostaining techniques, we could identify multiple biomarkers representing different stages of AHN in postmortem human hippocampal tissue that exhibited various AD-related neuropathological changes. In this study, we observed a significant presence of neurogenic cells in the hippocampus's dentate gyrus (DG) region in 30 individuals, including 14 individuals diagnosed with AD-related neuropathological changes and the remaining 16 individuals without any neurological diseases. Further investigation revealed that patients with AD exhibited pronounced astrogliosis and reduced neurogenesis. Specifically, the number of neuroblasts, immature and early mature granule cells decreased significantly as AD advanced. Although the number of neural stem cells (NSCs) remained unchanged in AD patients compared with mentally healthy individuals, they tended to be more quiescent state regulated by Notch and bone morphogenetic protein (BMP) signaling pathways. These abnormalities were strongly associated with the neuropathological alterations in AD patients. These research findings provide potential insights into the underlying mechanisms that underpin the pathogenesis of AD.
Subject(s)
Alzheimer Disease , Neural Stem Cells , Adult , Humans , Alzheimer Disease/pathology , Neurogenesis , Hippocampus/pathology , Neurons/pathology , Neural Stem Cells/metabolismABSTRACT
The crucial reservoir of antibiotic resistance genes (ARGs) within the chicken intestinal microbiome poses a serious threat to both animal and human health. In China, the overuse of antibiotics has significantly contributed to the proliferation of ARGs in the chicken intestinal microbiome, which is a serious concern. However, there has been relatively little research on the diversity of resistance genes in the chicken intestinal microbiome since the implementation of the National Pilot Work Program for Action to Reduce the Use of Veterinary Antimicrobial Drugs in China. The objective of this study was to analyze the diversity of antibiotic resistance genes carried by the chicken intestinal microbiome in both standard farms (SFs), which implement antibiotic reduction and passed national acceptance, and nonstandard farms (NSFs), which do not implement antibiotic reductions, in Hebei Province. Fresh fecal samples of broiler chickens were collected from SFs (n = 4) and NSF (n = 1) and analyzed using high-throughput qPCR technology. Our findings revealed that all five farms exhibited a wide range of highly abundant ARGs, with a total of 201 ARGs and 7 MGEs detected in all fecal samples. The dominant ARGs identified conferred resistance to aminoglycosides, macrolide-lincosamide-streptomycin B (MLSB), and tetracycline antibiotics. Cellular protection mechanisms were found to be the primary resistance mechanism for these ARGs. The analysis of the co-occurrence network demonstrated a significant positive correlation between the abundance of MGEs and ARGs. The SF samples showed a significantly lower relative abundance of certain ARGs than the NSF samples (p < 0.05). The results of this study show that the abundance of ARGs demonstrated a downward trend after the implementation of the National Pilot Work Program for Action to Reduce the Usage of Veterinary Antimicrobial Drugs in Hebei Province, China.
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Coronavirus disease 2019 (COVID-19) seriously threatens public health safety and the global economy, which warrant effective prophylactic and therapeutic approaches. Currently, vaccination and establishment of immunity have significantly reduced the severity and mortality of COVID-19. However, in regard to COVID-19 vaccines, the broad-spectrum protective efficacy against SARS-CoV-2 variants and the blocking of virus transmission need to be further improved. In this study, an optimum oral COVID-19 vaccine candidate, rVSVΔG-Sdelta, was selected from a panel of vesicular stomatitis virus (VSV)-based constructs bearing spike proteins from different SARS-CoV-2 strains. After chitosan modification, rVSVΔG-Sdelta induced both local and peripheral antibody response, particularly, broad-spectrum and long-lasting neutralizing antibodies against SARS-CoV-2 persisted for 1 year. Cross-protection against SARS-CoV-2 WT, Beta, Delta, BA.1, and BA.2 strains was achieved in golden hamsters, which presented as significantly reduced viral replication in the respiratory tract and alleviated pulmonary pathology post SARS-CoV-2 challenge. Overall, this study provides a convenient, oral-delivered, and effective oral mucosal vaccine against COVID-19, which would supplement pools and facilitate the distribution of COVID-19 vaccines.
Subject(s)
COVID-19 , Chitosan , Animals , Cricetinae , Humans , SARS-CoV-2 , COVID-19 Vaccines , Mesocricetus , COVID-19/prevention & control , Adjuvants, Immunologic , Antibodies, Neutralizing , Antibodies, Viral , Spike Glycoprotein, Coronavirus/geneticsABSTRACT
Hebei Province is an important area for breeding broiler chickens in China, but the antimicrobial resistance and prevalence of Escherichia coli (E. coli) are still unclear. A total of 180 cloacal samples from broiler farms in Hebei Province were collected and used for the isolation and identification of E. coli. The isolates were subjected to resistance phenotyping, resistance profiling, and genotyping, and some multiresistant strains were subjected to multilocus sequence typing (MLST). The results showed that 175 strains were isolated. Among both types of broiler farms, the ampicillin resistance rate was the highest, and the meropenem resistance rate was the lowest. Serious multiresistance was present in both types of broiler farms. Thirty strains of multidrug-resistant E. coli were typed by MLST to obtain a total of 18 ST types, with ST10 being the most prevalent. This study was to simply analyze the antimicrobial resistance and prevalence of E. coli in broiler chickens in Hebei Province after the implementation of the pilot work program of action to reduce the use of veterinary antimicrobials in standard farms (SFs) and nonstandard farms (NSFs). This study will provide a research basis and data support for the prevention and control of E. coli in Hebei.
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Ghost imaging is a novel imaging technique that utilizes the intensity correlation property of an optical field to retrieve information of the scene being measured. Due to the advantages of simple structure, high detection efficiency, etc., ghost imaging exhibits broad application prospects in the fields of space remote sensing, optical encryption transmission, medical imaging, and so on. At present, ghost imaging is gradually developing toward practicality, in which ghost imaging of moving targets is becoming a much-needed breakthrough link. At this stage, we can improve the imaging speed and improve the imaging quality to seek a more optimized ghost imaging scheme for moving targets. Based on the principle of moving target ghost imaging, this review summarizes and compares the existing methods for ghost imaging of moving targets. It also discusses the research direction and the technical challenges at the current stage to provide references for further promotion of the instantiation of ghost imaging applications.
ABSTRACT
Panoramic ghost imaging (PGI) is a novel method by only using a curved mirror to enlarge the field of view (FOV) of ghost imaging (GI) to 360°, making GI a breakthrough in the applications with a wide FOV. However, high-resolution PGI with high efficiency is a serious challenge because of the large amount of data. Therefore, inspired by the variant-resolution retina structure of human eye, a foveated panoramic ghost imaging (FPGI) is proposed to achieve the coexistence of a wide FOV, high resolution and high efficiency on GI by reducing the resolution redundancy, and further to promote the practical applications of GI with a wide FOV. In FPGI system, a flexible variant-resolution annular pattern structure via log-rectilinear transformation and log-polar mapping is proposed to be used for projection, which can allocate the resolution of the region of interest (ROI) and the other region of non-interest (NROI) by setting related parameters in the radial and poloidal directions independently to meet different imaging requirements. In addition, in order to reasonably reduce the resolution redundancy and avoid the loss of the necessary resolution on NROI, the variant-resolution annular pattern structure with a real fovea is further optimized to keep the ROI at any position in the center of 360° FOV by flexibly changing the initial position of the start-stop boundary on the annular pattern structure. The experimental results of the FPGI with one fovea and multiple foveae demonstrate that, compared to the traditional PGI, the proposed FPGI not only can improve the imaging quality on the ROIs with a high resolution and flexibly remain a lower-resolution imaging on the NROI with different required resolution reduction; but also reduce the reconstruction time to improve the imaging efficiency due to the reduction of the resolution redundancy.
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Poultry farms are a complex environment for close contact between humans and animals. Accumulating evidence has indicated that pathogens and drug resistance genes in chicken houses may pose a serious threat to public health and economic concerns. However, insufficient knowledge of the indoor aerosol microbiome and resistome profiles of layer hen houses hampers the understanding of their health effects. Environmental surveillance of antibiotic resistance may contribute to a better understanding and management of the human exposure risk of bioaerosols under the environmental conditions of chicken houses. In addition, the chicken house has a long operation cycle, and the bacterial diversity and antibiotic resistance genes of aerosols in different periods may be different. In this study, air samples were collected from 18 chicken houses on three farms, including the early laying period (EL), peak laying period (PL), and late laying period (LL). 16S rRNA gene sequencing and metagenomics were used to study the composition of the bacteria and resistome in aerosols of layer hen houses and the results showed that they varied with laying period. The highest alpha diversity of bacteria was observed in PL bioaerosols. The dominant bacterial phyla included Firmicutes, Bacteroidetes and Proteobacteria. Three potential pathogenic bacterial genera (Bacteroides, Corynebacterium and Fusobacterium) were found. The most abundant ARG type was aminoglycosides in all laying periods. In total, 22 possible ARG host genera were detected. ARG subtypes and abundance were both higher in LL. Network analysis also showed higher co-occurrence patterns between the bacteria and resistome in bioaerosols. The laying period plays an important role in the bacterial community and resistome in layer house aerosols.
Subject(s)
Anti-Bacterial Agents , Bacteria , Animals , Humans , Anti-Bacterial Agents/pharmacology , RNA, Ribosomal, 16S/genetics , Drug Resistance, Microbial , Chickens , Aerosols , Genes, Bacterial/geneticsABSTRACT
BACKGROUND: Astrocyte activation, which is polarized into classical neurotoxic A1, neuroprotective A2, A-pan, etc., is thought to be involved in the transition from acute to chronic post-thoracotomy pain. The C3aR receptor associated with astrocyte-neuron and -microglia interactions is necessary for A1 astrocytes polarization. This study aimed to determine whether C3aR in astrocytes mediates post-thoracotomy pain by inducing A1 expression in a rat thoracotomy pain model. METHODS: A rat thoracotomy pain model was employed. The mechanical withdraw threshold was measured to evaluate pain behavior. Lipopolysaccharide (LPS) was injected intraperitoneally to induce A1. Intrathecal injection of AAV2/9-rC3ar1 shRNA-GFAP was used to knock down in vivo C3aR expression in astrocytes. The expression of associated phenotypic markers before and after intervention was assessed by RT-PCR, western blot, co-immunofluorescence, and single-cell RNA sequencing. RESULTS: C3aR downregulation was found to inhibit LPS-induced A1 astrocytes activation, decrease the expression of C3aR, C3, and GFAP, which were activated from acute to chronic pain, and alleviate the mechanical withdrawal threshold and chronic pain incidence. In addition, more A2 astrocytes were activated in the model group that did not develop chronic pain. C3aR downregulation increased the number of A2 astrocytes upon LPS exposure. Knockdown of C3aR also decreased the activation of M1 microglia induced by LPS or thoracotomy. CONCLUSIONS: Our study confirmed that C3aR-induced A1 polarization contributes to chronic post-thoracotomy pain. Inhibition of A1 activation via C3aR downregulation increases anti-inflammatory A2 and decreases pro-inflammatory M1 activation, which may also be involved in the mechanism of chronic post-thoracotomy pain.
Subject(s)
Astrocytes , Chronic Pain , Animals , Male , Rats , Astrocytes/metabolism , Chronic Pain/metabolism , Lipopolysaccharides/pharmacology , Microglia/metabolism , Thoracotomy/adverse effectsABSTRACT
Neuropathic pain is difficult to treat in clinical practice, and the underlying mechanisms are insufficiently elucidated. Previous studies have demonstrated that the neuronal Fc-gamma-receptor type I (FcγRI) of the dorsal root ganglion (DRG) mediates antigen-specific pain. However, the mechanisms of neuronal FcγRI in neuropathic pain remain to be explored. Here, it is found that the activation of FcγRI-related signals in primary neurons induces neuropathic pain in a rat model. This work first reveals that sciatic nerve injury persistently activates neuronal FcγRI-related signaling in the DRG, and conditional knockout (CKO) of the FcγRI-encoding gene Fcgr1 in rat DRG neurons significantly alleviates neuropathic pain after nerve injury. C-reactive protein (CRP) is increased in the DRG after nerve injury, and CRP protein of the DRG evokes pain by activating neuronal FcγRI-related signals. Furthermore, microinjection of naive IgG into the DRG alleviates neuropathic pain by suppressing the activation of neuronal FcγRI. These results indicate that the activation of neuronal CRP/FcγRI-related signaling plays an important role in the development of neuropathic pain in chronic constriction injury (CCI) rats. The findings may provide novel insights into the neuroimmune responses after peripheral nerve injury and suggest potential therapeutic targets for neuropathic pain.
Subject(s)
Neuralgia , Peripheral Nerve Injuries , Rats , Animals , C-Reactive Protein , Rats, Sprague-Dawley , Receptors, IgG/metabolism , Feedback , Neuralgia/etiology , Neuralgia/metabolism , Peripheral Nerve Injuries/complicationsABSTRACT
Orf is an important zoonotic disease caused by the Orf virus (ORFV) which can cause contagious pustular dermatitis in goats and sheep. Orf is widespread in most sheep-raising countries in the world, causing huge economic losses. Although diagnostic methods for ORFV infection already exist, it is still necessary to develop a time-saving, labor-saving, specific, low-cost and visual diagnostic method for rapid detection of ORFV in the field and application in grassroots laboratories. This study establishes a DNA extraction-free, real-time, visual recombinase-aided amplification (RAA) method for the rapid detection of ORFV. This method is specific to ORFV and does not cross-react with other common DNA viruses. The detection limits of the real-time RAA and visual judgment of the RAA assay at 95% probability were 13 and 21 copies per reaction for ORFV, respectively. Compared with qPCR, the sensitivity and specificity of the real-time RAA assay were 100%, and those of the visual RAA assay were 92.31% and 100.0%, respectively. The DNA extraction-free visual detection method of RAA established in this study can meet the needs of rapid onsite detection and grassroots laboratories and has important reference value and significance for the early diagnosis of diseased animals.