Phlorizin Limits Bovine Viral Diarrhea Virus Infection in Mice via Regulating Gut Microbiota Composition.

Phlorizin (PHZ) is one of the main pharmacologically active ingredients in Lithocarpus polystachyus. We have previously shown that PHZ inhibits the replication of bovine viral diarrhea virus (BVDV), but the exact antiviral mechanism, especially in vivo, is still unknown. Here, we further confirm that PHZ has good protective effects in BVDV-infected mice. We analyzed BVDV-induced CD3+, CD4+, and CD8+ T cells among peripheral blood lymphocytes and found that PHZ significantly restored their percentage. Metagenomic analyses revealed that PHZ markedly improved the richness and diversity of intestinal microbiota and increased the abundance of potentially health-related microbes (families Lachnosipiraceae, Ruminococcaceae, and Oscillospiraceae). Specifically, the relative abundance of short chain fatty acid (SCFA)-producing bacteria, including Lachnospiraceae_UCG-006, unclassified_f_Ruminococcaceae, Oscillibacter, Intestinimonas, Blautia, and Lachnoclostridium increased significantly after PHZ treatment. Interestingly, BVDV-infected mice that received fecal microbiota from PHZ-treated mice (PHZ-FMT) had a significantly lower viral load in the duodenum and jejunum than untreated mice. Pathological lesions of duodenum and jejunum were also greatly reduced in the PHZ-FMT group, confirming a significant antiviral effect. These findings show that gut microbiota play an important role in PHZ's antiviral activity and suggest that their targeted intervention might be a promising endogenous strategy to prevent and control BVDV.

PI3K/AKT mediated De novo fatty acid synthesis regulates RIG-1/MDA-5-dependent type I IFN responses in BVDV-infected CD8+T cells.

Bovine viral diarrhea virus (BVDV) has caused massive economic losses in the cattle business worldwide. Fatty acid synthase (FASN), a key enzyme of the fatty acid synthesis (FAS) pathway, has been shown to support virus replication. To investigate the role of fatty acids (FAs) in BVDV infection, we infected CD8+T lymphocytes obtained from healthy cattle with BVDV in vitro. During early cytopathic (CP) and noncytopathic (NCP) BVDV infection in CD8+ T cells, there is an increase in de novo lipid biosynthesis, resulting in elevated levels of free fatty acids (FFAs) and triglycerides (TG). BVDV infection promotes de novo lipid biosynthesis in a dose-dependent manner. Treatment with the FASN inhibitor C75 significantly reduces the phosphorylation of PI3K and AKT in BVDV-infected CD8+ T cells, while inhibition of PI3K with LY294002 decreases FASN expression. Both CP and NCP BVDV strains promote de novo fatty acid synthesis by activating the PI3K/AKT pathway. Further investigation shows that pharmacological inhibitors targeting FASN and PI3K concurrently reduce FFAs, TG levels, and ATP production, effectively inhibiting BVDV replication. Conversely, the in vitro supplementation of oleic acid (OA) to replace fatty acids successfully restored BVDV replication, underscoring the impact of abnormal de novo fatty acid metabolism on BVDV replication. Intriguingly, during BVDV infection of CD8+T cells, the use of FASN inhibitors prompted the production of IFN-α and IFN-ß, as well as the expression of interferon-stimulated genes (ISGs). Moreover, FASN inhibitors induce TBK-1 phosphorylation through the activation of RIG-1 and MDA-5, subsequently activating IRF-3 and ultimately enhancing the IFN-1 response. In conclusion, our study demonstrates that BVDV infection activates the PI3K/AKT pathway to boost de novo fatty acid synthesis, and inhibition of FASN suppresses BVDV replication by activating the RIG-1/MDA-5-dependent IFN response.

The gut microbiota contributes to the infection of bovine viral diarrhea virus in mice.

Bovine viral diarrhea virus (BVDV) is prevalent worldwide and causes significant economic losses. Gut microbiota is a large microbial community and has a variety of biological functions. However, whether there is a correlation between gut microbiota and BVDV infection and what kind of relation between them have not been reported. Here, we found that gut microbiota composition changed in normal mice after infecting with BVDV, but mainly the low abundance microbe was affected. Interestingly, BVDV infection significantly reduced the diversity of gut microbiota and changed its composition in gut microbiota-dysbiosis mice. Furthermore, compared with normal mice of BVDV infection, there were more viral loads in the duodenum, jejunum, spleen, and liver of the gut microbiota-dysbiosis mice. However, feces microbiota transplantation (FMT) reversed these effects. The data above indicated that the dysbiosis of gut microbiota was a key factor in the high infection rate of BVDV. It is found that the IFN-I signal was involved by investigating the underlying mechanisms. The inhibition of the proliferation and increase in the apoptosis of peripheral blood lymphocytes (PBL) were also observed. However, FMT treatment reversed these changes by regulating PI3K/Akt, ERK, and Caspase-9/Caspase-3 pathways. Furthermore, the involvement of butyrate in the pathogenesis of BVDV was also further confirmed. Our results showed for the first time that gut microbiota acts as a key endogenous defense mechanism against BVDV infection; moreover, targeting regulation of gut microbiota structure and abundance may serve as a new strategy to prevent and control the disease.IMPORTANCEWhether the high infection rate of BVDV is related to gut microbiota has not been reported. In addition, most studies on BVDV focus on in vitro experiments, which limits the study of its prevention and control strategy and its pathogenic mechanism. In this study, we successfully confirmed the causal relationship between gut microbiota and BVDV infection as well as the potential molecular mechanism based on a mouse model of BVDV infection and a mouse model of gut microbiota dysbiosis. Meanwhile, a mouse model which is more susceptible to BVDV provided in this study lays an important foundation for further research on prevention and control strategy of BVDV and its pathogenesis. In addition, the antiviral effect of butyrate, the metabolites of butyrate-producing bacteria, has been further revealed. Overall, our findings provide a promising prevention and control strategy to treat this infectious disease which is distributed worldwide.

Human MARCH1, 2, and 8 block Ebola virus envelope glycoprotein cleavage via targeting furin P domain.

Membrane-associated RING-CH (MARCH) family proteins were recently reported to inhibit viral replication through multiple modes. Previous work showed that human MARCH8 blocked Ebola virus (EBOV) glycoprotein (GP) maturation. Our study here demonstrates that human MARCH1 and MARCH2 share a similar pattern to MARCH8 in restricting EBOV GP-pseudotyped viral infection. Human MARCH1 and MARCH2 retain EBOV GP at the trans-Golgi network, reduce its cell surface display, and impair EBOV GP-pseudotyped virions infectivity. Furthermore, we uncover that the host proprotein convertase furin could interact with human MARCH1/2 and EBOV GP intracellularly. Importantly, the furin P domain is verified to be recognized by MARCH1/2/8, which is critical for their blocking activities. Besides, bovine MARCH2 and murine MARCH1 also impair EBOV GP proteolytic processing. Altogether, our findings confirm that MARCH1/2 proteins of different mammalian origins showed a relatively conserved feature in blocking EBOV GP cleavage, which could provide clues for subsequent MARCHs antiviral studies and may facilitate the development of novel strategies to antagonize enveloped virus infection.

Blockade of BTLA alone or in combination with PD-1 restores the activation and proliferation of CD8+ T cells during in vitro infection with NCP BVDV.

Bovine viral diarrhea virus (BVDV) infection can result in typical peripheral blood lymphopenia and immune dysfunction. However, the molecular mechanism underlying the onset of lymphopenia remains unclear. B and T lymphocyte attenuator (BTLA) is a novel immune checkpoint molecule that primarily inhibits activation and proliferation of T cells. Blockade of BTLA with antibodies can boost the proliferation and anti-viral immune functions of T cells. Nonetheless, the immunomodulatory effects of BTLA in CD8+ T cells during BVDV infection remain unknown. Therefore, BTLA expression was measured in bovine peripheral blood CD8+ T cells infected with BVDV in vitro. Furthermore, the effects of BTLA or PD-1 blockade on CD8+ T cell activation, proliferation, and anti-viral immunological activities were investigated, as well as expression of signaling molecules downstream of BTLA, both alone and in combination. The results demonstrated that BTLA and PD-1 mRNA and protein levels were considerably increased in CD8+ T cells infected with cytopathic and non-cytopathic (NCP) BVDV. Surprisingly, as compared to blockade of either BTLA or PD-1, blockade of both dramatically increased proliferation and expression of CD25 and p-EKR of CD8+ T cells infected with NCP BVDV. Furthermore, blockade of BTLA, but not PD-1, had no effect on BVDV replication or IFN-γ expression. These findings confirmed the immunomodulatory roles of BTLA during BVDV infection, as well as the synergistic role of BTLA and PD-1 in NCP BVDV infection, thereby providing new insights to promote activation and the anti-viral immunological activities of CD8+ T cells.

The activation of liver X receptors in Madin-Darby bovine kidney cells and mice restricts infection by bovine viral diarrhea virus.

Bovine viral diarrhea virus (BVDV) is prevalent worldwide and is an important pathogen that represents a serious threat to the development of the cattle industry by causing significant economic losses. Liver X receptors (LXRs) are members of the nuclear receptor superfamily and have become attractive therapeutic targets for cardiovascular disease. In the present study, we found that LXRs in both Madin-Darby bovine kidney (MDBK) cells and mice were associated with BVDV infection. GW3965, an agonist for LXRs, significantly inhibited BVDV RNA and protein levels in MDBK cells. In vivo studies in a mouse model also confirmed the inhibitory role of GW3965 in BVDV replication and the ameliorating effect of GW3965 on pathological injury to the duodenum. In vitro investigations of the potential mechanisms involved showed that GW3965 significantly inhibited BVDV-induced increases in cholesterol levels and viral internalization. Furthermore, the antiviral activity of GW3965 was significantly reduced following cholesterol replenishment, thus demonstrating that cholesterol was involved in the resistance of GW3965 to BVDV replication. Further studies indicated the role of ATP-binding cassette transporter A1 (ABCA1) and cholesterol-25-hydroxylase (CH25H) in the antiviral activity of GW3965. We also demonstrated the significant antiviral effect of 25hydroxycholesterol (25HC), a product of the catalysis of cholesterol by CH25H. In addition, the anti-BVDV effects of demethoxycurcumin (DMC), cyanidin-3-O-glucoside (C3G), and saikosaponin-A (SSA), three natural agonizts of LXRs, were also confirmed in both MDBK cells and mice. However, the antiviral activities of these agents were weakened by SR9243, a synthetic inhibitor of LXRs. For the first time, our research demonstrated that the activation of LXRs can exert significant anti-BVDV effects in MDBK cells and mice.

Tungsten Nitride/Tungsten Oxide Nanosheets for Enhanced Oxynitride Intermediate Adsorption and Hydrogenation in Nitrate Electroreduction to Ammonia.

Electrochemical NO3- reduction reaction (NO3RR) is a promising technique for green NH3 synthesis. Tungsten oxide (WO3) has been regarded as an effective electrocatalyst for electrochemical NH3 synthesis. However, the weak adsorption and the sluggish hydrogenation of oxynitride intermediates (NOx, e.g., *NO3 and *NO2) over WO3 materials hinder the efficiency of converting NO3- to NH3. Herein, we design a heterostructure of tungsten nitride (WN) and WO3 (WN/WO3) nanosheets to optimize *NO3 and *NO2 adsorptions and facilitate *NO2 hydrogenations to achieve a highly efficient electrochemical NO3RR to produce NH3. Theoretical calculations predict that locally introducing WN into WO3 will shorten the distance between adjacent W atoms, resulting in *NO3 and *NO2 being strongly adsorbed on W active sites in the form of bidentate ligands instead of the relatively weak monodentate ligands. Furthermore, WN facilitates H2O dissociation to supply the requisite protons, which is beneficial for *NO2 hydrogenations. Inspired by theoretical prediction, WN/WO3 nanosheets are successfully fabricated through a high-temperature nitridation process. The transmission electron microscopy, X-ray photoelectron spectroscopy, and X-ray absorption near-edge spectroscopy investigations confirm that the amorphous WN has been locally introduced in situ into WO3 nanosheets to form a composite heterostructure. The as-prepared WN/WO3 nanosheets exhibit a high Faraday efficiency of 88.9 ± 7.2% and an appreciable yield rate of 8.4 mg h-1 cm-2 toward NH3 production, which is much higher than that of individual WO3 and WN. The enhanced adsorption and hydrogenation behaviors of *NOx over WN/WO3 are characterized by in situ Fourier-transform infrared spectroscopy, consistent with the theoretical predictions. This work develops facile and effective heterostructure nanomaterials to tune the adsorption and hydrogenation of NOx for boosting the efficiency from NO3- to NH3.

Total flavones from Sonchus arvensis L. ameliorate colitis by adjusting the gut microbiota.

OBJECTIVE: Sonchus arvensis L. is traditional Chinese food and medicine. We investigated protective effects of flavones from Sonchus arvensis L. (SAF) on colitis induced by dextran sulfate sodium (DSS) in mice by regulating gut microbiota (GM). METHOD: C57BL/6 mice were divided randomly: control group (CL); DSS group (ML); positive control + DSS group (AN); SAF + DSS (FE) group. The protective effects of SAF on ulcerative colitis (UC) were estimated by food intake, water intake, bodyweight loss, diarrhea, blood in stools, colon length, histology, disease activity index (DAI) score, and blood parameters. The sequencing of 16S rRNA gene was detected to investigate effect of SAF on GM. RESULTS: SAF attenuate bodyweight loss significantly. The DAI score was lower in FE group than that in ML group. Colon length was improved significantly in ML group. Pathologic changes could be ameliorated after SAF was administered to UC mice. SAF improved blood parameters of model mice. 16S rRNA sequencing revealed that it was very important to ameliorate colitis with bacteria of the phylum Verrucomicrobiota, class Verrucomicrobiae, order Verrucomicrobiales, family Akkermansiaceae, and genus Akkermansia. CONCLUSION: The SAF protective effect against colitis induced by DSS in mice may have a connection with GM diversity.

Research on multi-target data association of the infrared fish-eye warning system.

The multi-target data association method is studied in order to realize multi-target tracking in infrared fish-eye warning system. The Neural Joint Probabilistic Data Association (NJPDA) algorithm is analyzed. It is found that the NJPDA algorithm only considers the distance information between the measurement and the target in the data association process, and its tracking accuracy needs to be further improved. Therefore, a new method fused with direction information is proposed based on the NJPDA algorithm. The proposed algorithm defines the concept of direction difference, introduces the direction information of target motion, and modifies the likelihood function by Gaussian weighting method, so as to fuse the direction information of target motion into the calculation of data interconnection probability. Experimental results demonstrate that the tracking success rate of the proposed algorithm is nearly 10 % higher than that of JPDA and NJPDA algorithms and its consuming time meets the real-time requirement of the infrared fish-eye warning system.

Bridge Model Updating Based on Wavelet Neural Network and Wind-Driven Optimization.

Aging, corrosive environments, and inadequate maintenance may result in performance deterioration of civil infrastructures, and finite element model updating is a commonly employed structural health monitoring procedure in civil engineering to reflect the current situation and to ensure the safety and serviceability of structures. Using the finite element model updating process to obtain the relationship between the structural responses and updating parameters, this paper proposes a method of using the wavelet neural network (WNN) as the surrogate model combined with the wind-driven optimization (WDO) algorithm to update the structural finite element model. The method was applied to finite element model updating of a continuous beam structure of three equal spans to verify its feasibility, the results show that the WNN can reflect the nonlinear relationship between structural responses and the parameters and has an outstanding simulation performance; the WDO has an excellent ability for optimization and can effectively improve the efficiency of model updating. Finally, the method was applied to update a real bridge model, and the results show that the finite element model update based on WDO and WNN is applicable to the updating of a multi-parameter bridge model, which has practical significance in engineering and high efficiency in finite element model updating. The differences between the updated values and measured values are all within the range of 5%, while the maximum difference was reduced from -10.9% to -3.6%. The proposed finite element model updating method is applicable and practical for multi-parameter bridge model updating and has the advantages of high updating efficiency, reliability, and practical significance.

Programmable multifunctional metasurface for polarization, phase, and amplitude manipulation.

Metasurfaces have shown extraordinary capability in individually manipulating various electromagnetic (EM) properties, including polarization, phase, and amplitude. However, it is still a challenge to manipulate these EM properties in one metasurface simultaneously. In this paper, a programmable multifunctional metasurface (PMFMS) is demonstrated with polarization, phase, and amplitude manipulation abilities. By controlling tunable coding states and changing the direction of incident waves, the PMFMS can operate as a transmission cross-polarization converter, spatial wave manipulator, and low-RCS radome. Besides, the PMFMS possesses an ultra-wideband property, which can operate from 6.5 to 10.2 GHz with 44.3% relative bandwidth. More importantly, multiple functionalities can also be achieved in reflection operating mode by reassembling the PMFMS. As a proof of concept, the PMFMS is fabricated and experimentally verified. Measured results are in good agreement with simulated results. Benefiting from multifunctional EM manipulations in an ultra-wideband, such a design can be applied in wireless communication systems, radar detection, and EM stealth platform.

Preparation of Escherichia coli ghost of anchoring bovine Pasteurella multocida OmpH and its immunoprotective effect.

Pasteurella multocida is a pathogen that can infect humans and animals. A ghost is an empty bacterial body devoid of cytoplasm and nucleic acids that can be efficiently presented by antigen-presenting cells. To study a novel ghost vector vaccine with cross-immune protection, we used bacteriophage PhiX174 RF1 and Pasteurella multocida standard strain CVCC393 as templates to amplify the split genes E and OmpH to construct a bidirectional expression vector E'-OmpH-pET28a-ci857-E. This is proposed to prepare a ghost Escherichia coli (engineered bacteria) capable of attaching and producing Pasteurella multocida OmpH on the inner membrane of Escherichia coli (BL21). The aim is to assess the antibody levels and the effectiveness of immune protection by conducting a mouse immunoprotective test. The bidirectional expression vector E'-OmpH-pET28a-ci857-E was successfully constructed. After induction by IPTG, identification by SDS-PAGE, western blot, ghost culture and transmission electron microscope detection, it was proven that the Escherichia coli ghost anchored to Pasteurella multocida OmpH was successfully prepared. The immunoprotective test in mice showed that the antibody levels of Pasteurella multocida inactivated vaccine, OmpH, ghost (aluminum glue adjuvant) and ghost (Freund's adjuvant) on day 9 after immunization were significantly different from those of the PBS control group (P < 0.01). The immune protection rates were 100%, 80%, 75%, and 65%, respectively, and the PBS negative control was 0%, which proved that they all had specific immune protection effects. Therefore, this study lays the foundation for the further study of ghosts as carriers of novel vaccine-presenting proteins.

Lumped Plasticity Model and Hysteretic Performance of Ultra-High-Performance Concrete Rocking Pier.

Rocking piers using ultra-high-performance concrete (UHPC) have high damage-control capacity and self-centering characteristics that can limit the post-earthquake recovery time of bridges. To study the hysteretic behavior of UHPC rocking piers, a lumped plasticity model is proposed that comprises two parallel rotational springs and which can accurately calculate their force-displacement hysteretic behavior. Three states of the rocking piers, decompression, yield, and large deformation, are considered in this study. The model is verified based on existing experimental results, and the hysteretic characteristics of the UHPC rocking piers, such as strength, stiffness, and energy dissipation, are further analyzed. The research results show that the lumped plasticity analysis model proposed in this study can predict the force-displacement hysteretic behavior of the rocking piers accurately. Moreover, the hysteretic performance of the UHPC rocking piers is better than that of rocking piers using normal-strength concrete. An increase in the energy dissipation reinforcement ratio, pre-stressed tendon ratio, and initial pre-stress improves the lateral stiffness and strength of the UHPC rocking piers. However, the increase in the pre-stressed tendon ratio and initial pre-stress reduces their energy-dissipation capacity.

Characterization and heterologous expression of plasmalogen synthase MeHAD from Megasphaera elsdenii.

Plasmalogens (Pls) are vinyl-ether bond-containing glycerophospholipids or glycosyl diradyl glycerols, and are of great importance in the physiological functions and stability of cell membrane. Here, we identified and characterized that the plasmalogen synthase MeHAD from anaerobic Megasphaera elsdenii was responsible for vinyl-ether bond formation. Different from the 2-hydroxyacyl-CoA dehydratase (HAD) family plasmalogen synthase PlsA-PlsR which are encoded by two genes in Clostridium perfringens, the HAD homolog (MeHAD) encoded by a single gene MELS_0169 was found in M. elsdenii. By heterologous expression of the MeHAD gene into a nonplasmalogen-producing Escherichia coli strain, the expressed MeHAD was found to be located in the cell membrane region. Plasmalogens were detected in the recombinant strain using GC-MS and LC-MS, demonstrating that MeHAD was the key enzyme for plasmalogen synthesis. Moreover, the synthesized plasmalogens could enhance the oxidative stress-resistance and osmotic pressure-resistance of the recombinant strain, probably due to the ROS scavenging and decreased membrane permeability by the plasmalogens, respectively. The four-cysteine (Cys125, Cys164, Cys445 and Cys484) site-mutant of MeHAD, which were predicted binding to the [4Fe-4S] cluster, was unable to synthesize plasmalogens, indicating that the cysteines are important for the catalytic activity of MeHAD. Our results revealed the single gene encoded plasmalogen synthase in M. elsdenii and established a recombinant E. coli strain with plasmalogen production potential.

Electronically reconfigurable transmitarray for fully independent beam manipulation in two divided frequency bands.

Electronically reconfigurable transmitarray (ERTA) combines the advantages of optic theory and coding metasurface mechanism with the characteristic of low-loss spatial feed and real-time beam manipulation. Designing a dual-band ERTA is challenging due to multiple factors, including large mutual coupling generated by dual-band operation and separate phase control in each band. In this paper, a dual-band ERTA is demonstrated with the capability of fully independent beam manipulation in two divided bands. This dual-band ERTA is constructed by two kinds of orthogonally polarized reconfigurable elements which share the aperture in an interleaved way. The low coupling is achieved by utilizing polarization isolation and a backed cavity connected to the ground. To separately control the 1-bit phase in each band, a hierarchical bias method is elaborately presented. As proof of concept, a dual-band ERTA prototype composed of 15 × 15 upper-band elements and 16 × 16 lower-band elements is designed, fabricated, and measured. Experimental results verify that fully independent beam manipulation with orthogonal polarization is implemented in 8.2-8.8 GHz and 11.1-11.4 GHz. The proposed dual-band ERTA may be a suitable candidate for space-based synthetic aperture radar imaging.

Banxia Xiexin decoction alleviates AS co-depression disease by regulating the gut microbiome-lipid metabolic axis.

ETHNOPHARMACOLOGICAL RELEVANCE: Banxia Xiexin decoction (BXD) is a classic Chinese herbal formulation consisting of 7 herbs including Pinelliae Rhizoma, Scutellariae Radix, Zingiberis Rhizoma, Ginseng Radix, Glycyrrhizae Radix, Coptidis Rhizoma, and Jujubae Fructus, which can exert effects on lowering lipids and alleviating depressive mood disorders via affecting gastrointestinal tract. AIM OF THE STUDY: The pathogenesis of atherosclerosis (AS) co-depression disease has not been well studied, and the current clinical treatment strategies are not satisfactory. As a result, it is critical to find novel methods of treatment. Based on the hypothesis that the gut microbiome may promote the development of AS co-depression disease by regulating host lipid metabolism, this study sought to evaluate the effectiveness and action mechanism of BXD in regulation of the gut microbiome via an intervention in AS co-depression mice. MATERIALS AND METHODS: To determine the primary constituents of BXD, UPLC-Q/TOF-MS analysis was carried out. Sixteen C56BL/6 mice were fed normal chow as a control group; 64 ApoE-/- mice were randomized into four groups (model group and three treatment groups) and fed high-fat chow combined with daily bind stimulation for sixteen weeks to develop the AS co-depression mouse model and were administered saline or low, medium or high concentrations of BXD during the experimental modeling period. The antidepressant efficacy of BXD was examined by weighing, a sucrose preference test, an open field test, and a tail suspension experiment. The effectiveness of BXD as an anti-AS treatment was evaluated by means of biochemical indices, the HE staining method, and the Oil red O staining method. The impacts of BXD on the gut microbiome structure and brain (hippocampus and prefrontal cortex tissue) lipids in mice with the AS co-depression model were examined by 16S rDNA sequencing combined with lipidomics analysis. RESULTS: The main components of BXD include baicalin, berberine, ginsenoside Rb1, and 18 other substances. BXD could improve depression-like behavioral characteristics and AS-related indices in AS co-depression mice; BXD could regulate the abundance of some flora (phylum level: reduced abundance of Proteobacteria and Deferribacteres; genus level: reduced abundance of Clostridium_IV, Helicobacter, and Pseudoflavonifractor, Acetatifactor, Oscillibacter, which were significantly different). The lipidomics analysis showed that the differential lipids between the model and gavaged high-dose BXD (BXH) groups were enriched in glycerophospholipid metabolism, and lysophosphatidylcholine (LPC(20:3)(rep)(rep)) in the hippocampus and LPC(20:4)(rep) in the prefrontal cortex both showed downregulation in BXH. The correlation analysis illustrated that the screened differential lipids were mainly linked to Deferribacteres and Actinobacteria. CONCLUSION: BXD may exert an anti-AS co-depression therapeutic effect by modulating the abundance of some flora and thus intervening in peripheral lipid and brain lipid metabolism (via downregulation of LPC levels).

Anti-BVDV Activity of Traditional Chinese Medicine Monomers Targeting NS5B (RNA-Dependent RNA Polymerase) In Vitro and In Vivo.

Natural products have emerged as "rising stars" for treating viral diseases and useful chemical scaffolds for developing effective therapeutic agents. The nonstructural protein NS5B (RNA-dependent RNA polymerase) of NADL strain BVDV was used as the action target based on a molecular docking technique to screen herbal monomers for anti-BVDV viral activity. The in vivo and in vitro anti-BVDV virus activity studies screened the Chinese herbal monomers with significant anti-BVDV virus effects, and their antiviral mechanisms were initially explored. The molecular docking screening showed that daidzein, curcumin, artemisinine, and apigenin could interact with BVDV-NADL-NS5B with the best binding energy fraction. In vitro and in vivo tests demonstrated that none of the four herbal monomers significantly affected MDBK cell activity. Daidzein and apigenin affected BVDV virus replication mainly in the attachment and internalization phases, artemisinine mainly in the replication phase, and curcumin was active in the attachment, internalization, replication, and release phases. In vivo tests demonstrated that daidzein was the most effective in preventing and protecting BALB/C mice from BVDV infection, and artemisinine was the most effective in treating BVDV infection. This study lays the foundation for developing targeted Chinese pharmaceutical formulations against the BVDV virus.

Virus-like particle-based nanocarriers as an emerging platform for drug delivery.

New nanocarrier technologies are emerging, and they have great potential for improving drug delivery, targeting efficiency and bioavailability. Virus-like particles (VLPs) are natural nanoparticles from animal and plant viruses and bacteriophages. Hence, VLPs present several great advantages, such as morphological uniformity, biocompatibility, reduced toxicity and easy functionalisation. VLPs can deliver many active ingredients to the target tissue and have great potential as a nanocarrier to overcome the limitations associated with other nanoparticles. This review will focus primarily on the construction and applications of VLPs, particularly as a novel nanocarrier to deliver active ingredients. Herein, the main methods for the construction, purification and characterisation of VLPs, as well as various VLP-based materials used in delivery systems are summarised. The biological distribution of VLPs in drug delivery, phagocyte-mediated clearance and toxicity are also discussed.

Sonchus arvensis L. water extract attenuates dextran sulfate sodium-induced colitis by adjusting gut microbiota.

Sonchus arvensisL. (SA) is a traditional Chinese food and medicine termed "Ju Mai Cai". The aim of this study was to investigate the protective effects of an aqueous extract of SA on dextran sulfate sodium (DSS) - induced colitis in mice by adjusting the diversity of gut microbiota. Male C57BL/6 mice were randomly divided into four groups: CL (control group); ML group (DSS only); SA group (SA extract); and MS group (SA extract + DSS). The protective effect of SA on ulcerative disease was estimated by several analyses (i.e., body weight loss, diarrhea, bloody stools, disease activity index scores, and hematoxylin and eosin staining). The effect of SA on gut microbiota was determined by analysis of the 16S ribosomal RNA gene sequences. The results indicated that MS significantly attenuated the body weight loss. The disease activity index scores were markedly lower in the MS group versus in the ML group. Moreover, the length of the colon was significantly improved in the MS groups versus in the ML group. Pathological changes were markedly improved following the administration of SA to mice with DSS-induced ulcerative disease. The results of Beta diversity analysis revealed that the composition of gut microbiota was significantly different between groups. Taken together, the results indicated that SA extract may prevent ulcerative colitis.

Spatial- and Temporal-Trajectory Analysis of the Crested Ibis (Nipponia nippon) by Fusing Multiple Sources of Data.

The Crested Ibis (Nipponia nippon) is an endangered animal with an extremely high ecological, humanistic, and scientific value. However, this species still faces survival challenges, due to rapidly shrinking foraging grounds, the serious interference of human behavior, and increased habitat requirements. Geographical environment is a significant factor affecting Crested Ibis behavior-pattern analysis and habitat protection. The spatial and temporal trajectory contains habitat location and period information, a vital record of the Crested Ibis' habits, and the basis of all research. Nevertheless, there are only a handful of studies on the missing trajectory data and fusing multiple sources of environmental data-research methods. We studied the spatial and temporal habitat use of the tracked Crested lbis by fusing multiple data-sources in China. This paper adopts the LSTM (long short-term memory) model to supplement the missing trajectory data and perform cluster mining; and a random forest model is used to predict the habitat of the Crested Ibis with high fitting accuracy (R2 = 84.9%). The results show that the Crested Ibis distribution-pattern is characterized by high altitude and proximity to woodland and rivers. Additionally, the habitat dependence on the village implicates human agricultural activities in positively impacting its reproduction. This paper provides a complete method for analyzing Crested Ibis' spatial and temporal trajectory by fusing multi-source data, which is crucial for protecting the survival and reproduction of the Crested Ibis.