Chronic Heat Stress Induces Oxidative Stress and Induces Inflammatory Injury in Broiler Spleen via TLRs/MyD88/NF-κB Signaling Pathway in Broilers.

The spleen is the largest peripheral immune organ of the organism, accounting for 25% of the total lymphoid tissue of the body. During HS, the spleen is damaged due to the elevated environment, which seriously affects life performance and broilers' health. This study aimed to investigate the mechanism of chronic HS damage to broiler spleen tissues. The broilers were typically raised until they reached 21 days of age, after which they were arbitrarily allocated into two groups: an HS group and a cntrol group. The HS group was subjected to a temperature of 35 °C for 10 h each day, starting at 21 days of age. At 35 and 42 days of age, spleen and serum samples were obtained from the broilers. The results showed that after HS, a significant decrease in productive performance was observed at 42 days of age (p < 0.01), and the spleen index, and bursa index were significantly decreased (p < 0.01). T-AOC of the organism was significantly decreased (p < 0.05), GSH-PX, SOD, and CAT antioxidant factors were significantly decreased (p < 0.01), and MDA was significantly elevated (p < 0.01). HS also led to a significant increase in cytokines IL-6, TNF-α, and INF-γ and a significant decrease in IL-4 in the spleen. The histopathologic results showed that the spleen's red-white medulla was poorly demarcated. The cells were sparsely arranged after HS. After HS, the expression of TLRs, MYD88, and NF-κB genes increased significantly. The expression of HSP70 increased significantly, suggesting that HS may induces an inflammatory response in broiler spleens through this signaling pathway, which may cause pathological damage to broiler spleens, leading to a decrease in immune function and progressively aggravating HS-induced damage with the prolongation of HS.

SLS4D: Sparse Latent Space for 4D Novel View Synthesis.

Neural radiance fields (NeRF) have achieved great success in novel view synthesis and 3D representation for static scenarios. Existing dynamic NeRFs usually exploit a locally dense grid to fit the deformation fields; however, they fail to capture the global dynamics and concomitantly yield models of heavy parameters. We observe that the 4D space is inherently sparse. Firstly, the deformation fields are sparse in spatial but dense in temporal due to the continuity of motion. Secondly, the radiance fields are only valid on the surface of the underlying scene, usually occupying a small fraction of the whole space. We thus represent the 4D scene using a learnable sparse latent space, a.k.a. SLS4D. Specifically, SLS4D first uses dense learnable time slot features to depict the temporal space, from which the deformation fields are fitted with linear multi-layer perceptions (MLP) to predict the displacement of a 3D position at any time. It then learns the spatial features of a 3D position using another sparse latent space. This is achieved by learning the adaptive weights of each latent feature with the attention mechanism. Extensive experiments demonstrate the effectiveness of our SLS4D: It achieves the best 4D novel view synthesis using only about 6% parameters of the most recent work.

Preparation of novel gallic acid-based dummy-template molecularly imprinted polymer adsorbents for rapid adsorption of dibutyl phthalate from water.

Phthalate esters (PAEs) are plasticizers widely used in the industry and easily released into the environment, posing a serious threat to human health. Molecularly imprinted polymers (MIPs) are important as selective adsorbents for the removal of PAEs. In this study, three kinds of mussel-inspired MIPs for the removal of PAEs were first prepared with gallic acid (GA), hexanediamine (HD), tannic acid (TA), and dopamine (DA) under mild conditions. The adsorption results showed that the MIP with low cost derived from GA and HD (GAHD-MIP) obtained the highest adsorption capacity among these materials. Furthermore, 97.43% of equilibrium capacity could be reached within the first 5 min of adsorption. Especially, the dummy template of diallyl phthalate (DAP) with low toxicity was observed to be more suitable to prepare MIPs than dibutyl phthalate (DBP), although DBP was the target of adsorption. The adsorption process was in accordance with the pseudo-second-order kinetics model. In the isotherm analysis, the adsorption behavior agreed with the Freundlich model. Additionally, the material maintained high adsorption performance after 7 cycles of regeneration tests. The GAHD-MIP adsorbents in this study, with low cost, rapid adsorption equilibrium, green raw materials, and low toxicity dummy template, provide a valuable reference for the design and development of new MIPs.

SPS: Accurate and Real-Time Semantic Positioning System Based on Low-Cost DEM Maps.

This paper presents a Semantic Positioning System (SPS) to enhance the accuracy of mobile device geo-localization in outdoor urban environments. Although the traditional Global Positioning System (GPS) can offer a rough localization, it lacks the necessary accuracy for applications such as Augmented Reality (AR). Our SPS integrates Geographic Information System (GIS) data, GPS signals, and visual image information to estimate the 6 Degree-of-Freedom (DoF) pose through cross-view semantic matching. This approach has excellent scalability to support GIS context with Levels of Detail (LOD). The map data representation is Digital Elevation Model (DEM), a cost-effective aerial map that allows for fast deployment for large-scale areas. However, the DEM lacks geometric and texture details, making it challenging for traditional visual feature extraction to establish pixel/voxel level cross-view correspondences. To address this, we sample observation pixels from the query ground-view image using predicted semantic labels. We then propose an iterative homography estimation method with semantic correspondences. To improve the efficiency of the overall system, we further employ a heuristic search to speedup the matching process. The proposed method is robust, real-time, and automatic. Quantitative experiments on the challenging Bund dataset show that we achieve a positioning accuracy of 73.24%, surpassing the baseline skyline-based method by 20%. Compared with the state-of-the-art semantic-based approach on the Kitti dataset, we improve the positioning accuracy by an average of 5%.

Spin singlet pairing of bismuth in titania.

The formation of electron and hole traps in semiconductors via atomistic defects is the fundamental microscopic mechanism for tuning the electronic and photonic properties of these materials. Here we find in experiments that bismuth atoms doped into anatase TiO2 as substituents can appear as paired diatomic defects. Through first-principles density functional theory calculations, we reveal that the observed bismuth pair is separated by a medium distance of 6.37 Å through a delicate balance of Pauli repulsion and effective attractive interaction. We further clarify that the effective attractive interaction is related to the exchange coupling between the two bismuth defect states, which also leads to the formation of a spin singlet electronic state of the two unpaired electrons. Our study brings up a new type of defect state in TiO2, and motivates further experimental and theoretical studies of multi-electronic states in materials.

LptM promotes oxidative maturation of the lipopolysaccharide translocon by substrate binding mimicry.

Insertion of lipopolysaccharide (LPS) into the bacterial outer membrane (OM) is mediated by a druggable OM translocon consisting of a ß-barrel membrane protein, LptD, and a lipoprotein, LptE. The ß-barrel assembly machinery (BAM) assembles LptD together with LptE at the OM. In the enterobacterium Escherichia coli, formation of two native disulfide bonds in LptD controls translocon activation. Here we report the discovery of LptM (formerly YifL), a lipoprotein conserved in Enterobacteriaceae, that assembles together with LptD and LptE at the BAM complex. LptM stabilizes a conformation of LptD that can efficiently acquire native disulfide bonds, whereas its inactivation makes disulfide bond isomerization by DsbC become essential for viability. Our structural prediction and biochemical analyses indicate that LptM binds to sites in both LptD and LptE that are proposed to coordinate LPS insertion into the OM. These results suggest that, by mimicking LPS binding, LptM facilitates oxidative maturation of LptD, thereby activating the LPS translocon.

Living Magnetotactic Microrobots Based on Bacteria with a Surface-Displayed CRISPR/Cas12a System for Penaeus Viruses Detection.

Bacterial microrobots are an emerging living material in the field of diagnostics. However, it is an important challenge to make bacterial microrobots with both controlled motility and specific functions. Herein, magnetically driven diagnostic bacterial microrobots are prepared by standardized and modular synthetic biology methods. To ensure mobility, the Mms6 protein is displayed on the surface of bacteria and is exploited for magnetic biomineralization. This gives the bacterial microrobot the ability to cruise flexibly and rapidly with a magnetization intensity up to about 18.65 emu g-1. To achieve the diagnostic function, the Cas12a protein is displayed on the bacterial surface and is used for aquatic pathogen nucleic acid detection. This allows the bacterial microrobot to achieve sensitive, rapid, and accurate on-site nucleic acid detection, with detection limits of 8 copies µL-1 for decapod iridescent virus 1 (DIV1) and 7 copies µL-1 for white spot syndrome virus (WSSV). In particular, the diagnostic results based on the bacterial microrobots remained consistent with the gold standard test results when tested on shrimp tissue. This approach is a flexible and customizable strategy for building bacterial microrobots, providing a reliable and versatile solution for the design of bacterial microrobots.

Chronic heat stress induces lung injury in broiler chickens by disrupting the pulmonary blood-air barrier and activating TLRs/NF-κB signaling pathway.

As an important respiratory organ, the lung is susceptible to damage during heat stress due to the accelerated breathing frequency caused by an increase in environmental temperature. This can affect the growth performance of animals and endanger their health. This study aimed to explore the mechanism of lung tissue damage caused by heat stress. Broilers were randomly divided into a control group (Control) and a heat stress group (HS). The HS group was exposed to 35°C heat stress for 12 h per d from 21-days old, and samples were taken from selected broilers at 28, 35, and 42-days old. The results showed a significant increase in lactate dehydrogenase (LDH) activity in the serum and myeloperoxidase (MPO) activity in the lungs of broiler chickens across all 3 age groups after heat stress (P < 0.01), while the total antioxidant capacity (T-AOC) was significantly enhanced at 35-days old (P < 0.01). Heat stress also led to significant increases in various proinflammatory factors in serum and expression levels of HSP60 and HSP70 in lung tissue. Histopathological results showed congestion and bleeding in lung blood vessels, shedding of pulmonary epithelial cells, and a large amount of inflammatory infiltration in the lungs after heat stress. The mRNA expression of TLRs/NF-κB-related genes showed an upward trend (P < 0.05) after heat stress, while the mRNA expression of MLCK, a gene related to pulmonary blood-air barrier, significantly increased after heat stress, and the expression levels of MLC, ZO-1, and occludin decreased in contrast. This change was also confirmed by Western blotting, indicating that the pulmonary blood-air barrier is damaged after heat stress. Heat stress can cause damage to the lung tissue of broiler chickens by disrupting the integrity of the blood-air barrier and increasing permeability. This effect is further augmented by the activation of TLRs/NF-κB signaling pathways leading to an intensified inflammatory response. As heat stress duration progresses, broiler chickens develop thermotolerance, which gradually mitigates the damaging effects induced by heat stress.

Au-Fe3O4 nanozyme coupled with CRISPR-Cas12a for sensitive and visual antibiotic resistance diagnosing.

The accumulation and spread of antibiotic resistance bacteria (ARB) in the environment may accelerate the formation of superbugs and seriously threaten the health of all living beings. The timeliness and accurate diagnosing of antibiotic resistance is essential to controlling the propagation of superbugs in the environment and formulating effective public health management programs. Herein, we developed a speedy, sensitive, accurate, and user-friendly colorimetric assay for antibiotic resistance, via a synergistic combination of the peroxidase-like property of the Au-Fe3O4 nanozyme and the specific gene identification capability of the CRISPR-Cas12a. Once the CRISPR-Cas12a system recognizes a target resistance gene, it activates its trans-cleavage activity and subsequently releases the Au-Fe3O4 nanozymes, which oxidizes the 3,3,5,5-tetramethylbenzidine (TMB) with color change from transparent to blue. The diagnosing signals could be captured and analyzed by a smartphone. This method detected kanamycin-resistance genes, ampicillin-resistance genes, and chloramphenicol-resistance genes by simple operation steps with high sensitivity (<0.1 CFU µL-1) and speediness (<1 h). This approach may prove easy for the accurate and sensitive diagnosis of the ARGs or ARB in the field, thus surveilling and controlling the microbial water quality flexibly and efficiently.

Towards Point of Care CRISPR-Based Diagnostics: From Method to Device.

Rapid, accurate, and portable on-site detection is critical in the face of public health emergencies. Infectious disease control and public health emergency policymaking can both be aided by effective and trustworthy point of care tests (POCT). A very promising POCT method appears to be the clustered regularly interspaced short palindromic repeats and associated protein (CRISPR/Cas)-based molecular diagnosis. For on-site detection, CRISPR/Cas-based detection can be combined with multiple signal sensing methods and integrated into smart devices. In this review, sensing methods for CRISPR/Cas-based diagnostics are introduced and the advanced strategies and recent advances in CRISPR/Cas-based POCT are reviewed. Finally, the future perspectives of CRISPR and POCT are summarized and prospected.

Reconstruction of Gap-Free Land Surface Temperature at a 100 m Spatial Resolution from Multidimensional Data: A Case in Wuhan, China.

Land surface temperatures (LST) are vital parameters in land surface-atmosphere interactions. Constrained by technology and atmospheric interferences, LST retrievals from various satellite sensors usually return missing data, thus negatively impacting analyses. Reconstructing missing data is important for acquiring gap-free datasets. However, the current reconstruction methods are limited for maintaining spatial details and high accuracies. We developed a new gap-free algorithm termed the spatial feature-considered random forest regression (SFRFR) model; it builds stable nonlinear relationships to connect the LST with related parameters, including terrain elements, land coverage types, spectral indexes, surface reflectance data, and the spatial feature of the LST, to reconstruct the missing LST data. The SFRFR model reconstructed gap-free LST data retrieved from the Landsat 8 satellite on 27 July 2017 in Wuhan. The results show that the SFRFR model exhibits the best performance according to the various evaluation metrics among the SFRFR, random forest regression and spline interpolation, with a coefficient of determination (R2) reaching 0.96, root-mean-square error (RMSE) of 0.55, and mean absolute error (MAE) of 0.55. Then, we reconstructed gap-free LST data gathered in Wuhan from 2016 to 2021 to analyze urban thermal environment changes and found that 2020 presented the coolest temperatures. The SFRFR model still displayed satisfactory results, with an average R2 of 0.91 and an MAE of 0.63. We further discuss and discover the factors affecting the visual performance of SFRFR and identify the research priority to circumvent these disadvantages. Overall, this study provides a simple, practical method for acquiring gap-free LST data to help us better understand the spatiotemporal LST variation process.

Real-Time Globally Consistent 3D Reconstruction With Semantic Priors.

Maintaining global consistency continues to be critical for online 3D indoor scene reconstruction. However, it is still challenging to generate satisfactory 3D reconstruction in terms of global consistency for previous approaches using purely geometric analysis, even with bundle adjustment or loop closure techniques. In this article, we propose a novel real-time 3D reconstruction approach which effectively integrates both semantic and geometric cues. The key challenge is how to map this indicative information, i.e., semantic priors, into a metric space as measurable information, thus enabling more accurate semantic fusion leveraging both the geometric and semantic cues. To this end, we introduce a semantic space with a continuous metric function measuring the distance between discrete semantic observations. Within the semantic space, we present an accurate frame-to-model semantic tracker for camera pose estimation, and semantic pose graph equipped with semantic links between submaps for globally consistent 3D scene reconstruction. With extensive evaluation on public synthetic and real-world 3D indoor scene RGB-D datasets, we show that our approach outperforms the previous approaches for 3D scene reconstruction both quantitatively and qualitatively, especially in terms of global consistency.

Premelting layer during ice growth: role of clusters.

The premelting layer plays an important role in ice growth, but there is a significant gap in our knowledge between the atomistic premelting surface structure and the macroscopic growth mechanism. In this work, using large-scale molecular dynamics simulation, we reveal the existence of clusters on the premelting surface, as an intermediate feature bridging the gap. We show the spontaneous formation and evolution of clusters, and they form a stable distribution determined by the growth rate. We demonstrate how this stable distribution is related to the growth mode of ice, connected by the growth of clusters. We come to a bilayer-by-bilayer growth mode at simulation-reachable high growth rates, but another mechanism, namely "cluster stacking", is speculated to exist at lower growth rates. This work builds a connection between the microscopic structure of the premelting layer and the macroscopic growth of ice, making a step forward toward the full understanding of premelting and ice growth.

LuxS modulates motility and secretion of extracellular protease in fish pathogen Vibrio harveyi.

Vibrio harveyi can cause infections and diseases in a variety of marine vertebrates and invertebrates, which are harmful to the aquaculture industry. The LuxS quorum-sensing system regulates the expression of virulence factors in a wide variety of pathogenic bacteria. In this study, an in-frame deletion of the luxS gene was constructed to reveal the role of LuxS in the physiology and virulence of V. harveyi. Statistical analysis showed no significant differences in the growth ability, biofilm formation, antibiotic susceptibility, virulence by intraperitoneal injection, and ability of V. harveyi to colonize the spleen and liver of the pearl gentian grouper between the wild-type (WT) and luxS mutant. However, deletion of luxS decreased the secretion of extracellular protease, while increasing swimming and swarming abilities. Simultaneously, a luxS-deleted mutant showed overproduction of lateral flagella, and an intact luxS complemented this defect. Since motility is flagella dependent, 16 V. harveyi flagella biogenesis related genes were selected for further analysis. Based on quantitative real-time reverse transcription-PCR (qRT-PCR), the expression levels of these genes, including the polar flagella genes flaB, flhA, flhF, flhB, flhF, fliS, and flrA and the lateral flagella genes flgA, flgB, fliE, fliF, lafA, lafK, and motY, were significantly upregulated in the ΔluxS: pMMB207 (ΔluxS+) strain as compared with the V. harveyi 345: pMMB207 (WT+) and C-ΔluxS strains during the early, mid-exponential, and stationary growth phases. Our results indicate that LuxS plays an important role in controlling motility, flagella biogenesis, and extracellular protease secretion in V. harveyi.

Research progress on the biological modifications of implant materials in 3D printed intervertebral fusion cages.

Anterior spine decompression and reconstruction with bone grafts and fusion is a routine spinal surgery. The intervertebral fusion cage can maintain intervertebral height and provide a bone graft window. Titanium fusion cages are the most widely used metal material in spinal clinical applications. However, there is a certain incidence of complications in clinical follow-ups, such as pseudoarticulation formation and implant displacement due to nonfusion of bone grafts in the cage. With the deepening research on metal materials, the properties of these materials have been developed from being biologically inert to having biological activity and biological functionalization, promoting adhesion, cell differentiation, and bone fusion. In addition, 3D printing, thin-film, active biological material, and 4D bioprinting technology are also being used in the biofunctionalization and intelligent advanced manufacturing processes of implant devices in the spine. This review focuses on the biofunctionalization of implant materials in 3D printed intervertebral fusion cages. The surface modifications of implant materials in metal endoscopy, material biocompatibility, and bioactive functionalizationare summarized. Furthermore, the prospects and challenges of the biofunctionalization of implant materials in spinal surgery are discussed. Fig.a.b.c.d.e.f.g As a pre-selected image for the cover, I really look forward to being selected. Special thanks to you for your comments.

In vitroadipogenesis and long-term adipocyte culture in adipose tissue-derived cell banks.

There is a critical need to developin vitroculture systems appropriate for the expansion of adipose tissue, in order to gain new insights into metabolic diseases and to assist in the restoration of tissue defects. Conventional two- or three-dimensional (2D or 3D)in vitromodels of adipocytes require a combination of supplements to induce adipocyte maturation that greatly increases the cost of large-scale industrial production. In the present study, a microporous, perforated bacterial cellulose (BC)-assisted culture system was developed that promoted the adhesion, proliferation, and adipogenic differentiation of preadipocytes. Additionally, the system maintained the cells as mature unilocular adipocytesex vivoin normal cell culture medium in long-term culture. All cells were derived from isolated adipose tissue without the use of expensive enzymes for tissue digestion. In contrast to culture in hard tissue culture plates, preadipocytes in the soft 3D environments formed multidimensional interlaced cell contacts, undergoing significant spontaneous lipid accumulation and could be cultured for up to threemonths in maintenance medium. More importantly, the cultured adipose tissue-derived cell bank created here was able to produce injury repair activators that promoted the proliferation of fibroblasts with little fibrosis and the functional differentiation of myoblasts, displaying the potential for use in adipose reconstruction. Thus, the present study demonstrates the potential of a mechanically flexible BC scaffold to generate volume tunable adipose constructs and provides a low-cost and user-friendly strategy for large-scale industrial production of adipose tissue.

Functional characterization of VscCD, an important component of the type â ¢ secretion system of Vibrio harveyi.

Vibrio harveyi is a Gram-negative bacterium that occurs widely in the ocean and a kind of pathogenic bacteria associated with vibriosis in grouper. We investigated whether the VscCD protein of the type Ⅲ secretion system (T3SS) was important for pathogenicity of V. harveyi. Mutations to the vscC and vscD genes (ΔvscCD) and complementation of the ΔvscCD mutant (C-ΔvscCD) were created. Moreover, the biological characteristics of the wild-type (WT) and mutant strains of V. harveyi 345 were compared. The results showed that deletion of the vscCD genes had no effect on bacterial growth, swimming/swarming ability, secretion of extracellular protease, or biofilm formation. However, as compared with the V. harveyi 345: pMMB207 (WT+) and complementary (C-ΔvscCD) strains, the ΔvscCD: pMMB207 (ΔvscCD+) mutant displayed decreased resistance to acid stress, H2O2, and antibiotics. In addition, infection of the pearl gentian grouper (♀Epinephelus fuscoguttatus × â™‚Epinephelus lanceolatu) showed that as compared with the WT+ and C-ΔvscCD strains, the ΔvscCD+ strain significantly reduced cumulative mortality of the host. The colonization ability of the ΔvscCD+ mutant in the spleen and liver tissues of the pearl gentian grouper was significantly lower than that of the WT+ and C-ΔvscCD strains. In the early stage of infection with the ΔvscCD+ strain, the expression levels of IL-1ß, IL-16, TLR3, TNF-α, MHC-Iα, and CD8α were up-regulated to varying degrees. As compared with the WT+ and C-ΔvscCD strains, luxR expression was significantly up-regulated in the ΔvscCD+ strain, while the expression of vcrH and vp1668 was significantly down-regulated. As an important component of the T3SS, VscCD seemed to play a significant role in the pathogenesis of V. harveyi.

Percutaneous spinal endoscopy with unilateral interlaminar approach to perform bilateral decompression for central lumbar spinal stenosis: radiographic and clinical assessment.

BACKGROUND: Recently, a percutaneous spinal endoscopy unilateral posterior interlaminar approach to perform bilateral decompression has been proposed for use in treatment of lumbar spinal stenosis, As a development and supplement to traditional surgery, its advantages regarding therapeutic effects and prognosis, such as minor soft tissue damage, little intraoperative blood loss, and a quick return to daily life. However, there are few analyses of this surgery with a follow-up of more than 1 year,we conducted this study in order to quantitatively investigate radiographic and clinical efficacies of this surgery for central lumbar spinal stenosis. MATERIALS AND METHODS: Forty-six patients with central lumbar spinal stenosis were enrolled from January 2017 to July 2018. The visual analog scale (VAS) for back pain and leg pain, Oswestry disability index (ODI), modified MacNab criteria were used to evaluate clinical efficiency at preoperative and postoperative time points. The intervertebral height index (IHI), cross-sectional area of the spinal canal (CSAC), calibrated disc signal (CDS) and spinal stability were examined to assess radiographic decompression efficiency via magnetic resonance imaging and X-ray at preoperative and postoperative time points. RESULTS: The VAS score for lower back pain and leg pain improved from 7.50 ± 0.78 to 1.70 ± 0.66 and from 7.30 ± 0.79 to 1.74 ± 0.68, respectively, and the ODI improved from 72.35 ± 8.15 to 16.15 ± 4.51. In terms of modified MacNab criteria, 91.3% of the patients achieved good or excellent outcomes. Furthermore, significant changes after surgery were observed for the percentage of CSAC, increasing from 125.3 ± 53.9 to 201.4 ± 78 mm2; however, no significant differences were observed for the remaining measurement indicators. CONCLUSIONS: The clinical and radiographic efficacies of this surgery for central lumbar spinal stenosis were good in short-term follow-up, and this surgery did not cause meaningful changes in IHI, CDS, and spine stability in short-term follow-up. The effect of long-term follow-up needs further investigation.

Comprehensive analysis of N6-methyladenosine (m6A) modification during the degeneration of lumbar intervertebral disc in mice.

OBJECTIVE: To study the N6-methyladenosine (m6A) modification pattern of nucleus pulposus (NP) tissue during intervertebral disc degeneration (IDD). METHODS: A standing mouse model was generated, and staining and imaging methods were used to evaluate the IDD model. Methylated RNA immunoprecipitation with next-generation sequencing (MeRIP-seq) was used to analyze m6A methylation-associated transcripts in the NP, and real-time quantitative polymerase chain reaction (qRT-PCR) was used to detect the expression of methylation-related enzymes and conduct bio-informatics analysis. RESULTS: The standing mouse model caused IDD. Continuous axial pressure changed the expression of related methylases in degenerated NP tissue. Relative to the control group, the expression levels of KIAA1429, METTL14, METTL3, METTL4, WTAP, DGCR8, EIF3A and YTHDC1 in the experimental group were higher, while those of FTO, ELAVL1, HNRNPC1 and SRSF2 were lower. We identified 985 differentially expressed genes through MeRIP-Seq, among which 363 genes were significantly up-regulated, and 622 genes were significantly down-regulated. In addition, among the 9648 genes counted, 1319 m6A peaks with significant differences in methylation were identified, among which 933 were significantly up-regulated, and 386 were significantly down-regulated. Genes and pathways that were enriched in IDD have been identified. CONCLUSION: The results of this study elucidated the m6A methylation pattern of NP tissue in degenerated lumbar intervertebral disc of mice and provided new perspectives and clues for research on and the treatment of lumbar disc degeneration. THE TRANSLATIONAL POTENTIAL OF THIS ARTICLE: As one of the important causes of low back and leg pain, intervertebral disc degeneration brings a huge economic burden to the society, family and medical system. Therefore, understanding the molecular and cellular mechanisms of intervertebral disc degeneration is of great significance for guiding clinical treatment. In this study, methylated RNA immunoprecipitation with next-generation sequencing on mice lumbar nucleus pulposus tissues found that differentially expressed genes and changes in the expression of related methylases, confirming that RNA methylation is involved in intervertebral disc degeneration. The process provides new vision and clues for future research on intervertebral disc degeneration.

Gut-Liver Immune Response and Gut Microbiota Profiling Reveal the Pathogenic Mechanisms of Vibrio harveyi in Pearl Gentian Grouper (Epinephelus lanceolatus♂ × E. fuscoguttatus♀).

Vibrio harveyi causes vibriosis in nearly 70% of grouper (Epinephelus sp.), seriously limiting grouper culture. As well as directly inhibiting pathogens, the gut microbiota plays critical roles in immune homeostasis and provides essential health benefits to its host. However, there is still little information about the variations in the immune response to V. harveyi infection and the gut microbiota of grouper. To understand the virulence mechanism of V. harveyi in the pearl gentian grouper, we investigated the variations in the pathological changes, immune responses, and gut bacterial communities of pearl gentian grouper after exposure to differently virulent V. harveyi strains. Obvious histopathological changes were detected in heart, kidney, and liver. In particular, nodules appeared and huge numbers of V. harveyi cells colonized the liver at 12 h postinfection (hpi) with highly virulent V. harveyi. Although no V. harveyi was detected in the gut, the infection simultaneously induced a gut-liver immune response. In particular, the expression of 8 genes associated with cellular immune processes, including genes encoding inflammatory cytokines and receptors, and pattern recognition proteins, was markedly induced by V. harveyi infection, especially with the highly virulent V. harveyi strain. V. harveyi infection also induced significant changes in gut bacterial community, in which Vibrio and Photobacterium increased but Bradyrhizobium, Lactobacillus, Blautia, and Faecalibaculum decreased in the group infected with the highly virulent strain, with accounting for 82.01% dissimilarity. Correspondingly, four bacterial functions related to bacterial pathogenesis were increased by infection with highly virulent V. harveyi, whereas functions involving metabolism and genetic information processing were reduced. These findings indicate that V. harveyi colonizes the liver and induces a gut-liver immune response that substantially disrupts the composition of and interspecies interactions in the bacterial community in fish gut, thereby altering the gut-microbiota-mediated functions and inducing fish death.