DEAD-box RNA helicase RH20 positively regulates RNAi-based antiviral immunity in plants by associating with SGS3/RDR6 bodies.

RNA silencing plays a crucial role in defending against viral infections in diverse eukaryotic hosts. Despite extensive studies on core components of the antiviral RNAi pathway such as DCLs, AGOs and RDRs proteins, host factors involved in antiviral RNAi remain incompletely understood. In this study, we employed the proximity labelling approach to identify the host factors required for antiviral RNAi in Nicotiana benthamiana. Using the barley stripe mosaic virus (BSMV)-encoded γb, a viral suppressor of RNA silencing (VSR), as the bait protein, we identified the DEAD-box RNA helicase RH20, a broadly conserved protein in plants and animals with a homologous human protein known as DDX5. We demonstrated the interaction between RH20 and BSMV γb. Knockdown or knockout of RH20 attenuates the accumulation of viral small interfering RNAs, leading to increased susceptibility to BSMV, while overexpression of RH20 enhances resistance to BSMV, a process requiring the cytoplasmic localization and RNA-binding activity of RH20. In addition to BSMV, RH20 also negatively regulates the infection of several other positive-sense RNA viruses, suggesting the broad-spectrum antiviral activity of RH20. Mechanistic analysis revealed the colocalization and interaction of RH20 with SGS3/RDR6, and disruption of either SGS3 or RDR6 undermines the antiviral function of RH20, suggesting RH20 as a new component of the SGS3/RDR6 bodies. As a counter-defence, BSMV γb VSR subverts the RH20-mediated antiviral defence by interfering with the RH20-SGS3 interaction. Our results uncover RH20 as a new positive regulator of antiviral RNAi and provide new potential targets for controlling plant viral diseases.

Crop antiviral defense: Past and future perspective.

Viral pathogens not only threaten the health and life of humans and animals but also cause enormous crop yield losses and contribute to global food insecurity. To defend against viral pathogens, plants have evolved an intricate immune system to perceive and cope with such attacks. Although most of the fundamental studies were carried out in model plants, more recent research in crops has provided new insights into the antiviral strategies employed by crop plants. We summarize recent advances in understanding the biological roles of cellular receptors, RNA silencing, RNA decay, hormone signaling, autophagy, and ubiquitination in manipulating crop host-mediated antiviral responses. The potential functions of circular RNAs, the rhizosphere microbiome, and the foliar microbiome of crops in plant-virus interactions will be fascinating research directions in the future. These findings will be beneficial for the development of modern crop improvement strategies.

Expanded PAH analysis of household air pollution in a rural region of China with high lung cancer incidence.

The domestic combustion of locally sourced smoky (bituminous) coal in Xuanwei and Fuyuan counties, China, is responsible for some of the highest lung cancer rates in the world. Recent research has pointed to methylated PAHs (mPAHs), particularly 5-methylchrysene (5MC), within coal combustion products as a driving factor. Here we describe measurements of mPAHs in Xuanwei and Fuyuan derived from controlled burnings (i.e., water boiling tests, WBT, n = 27) representing exposures during stove use, and an exposure assessment (EA) study (n = 116) representing 24 h weighted exposures. Using smoky coal has led to significantly higher concentrations of known and likely human carcinogens than using smokeless coal, including 5MC (3.7 ng/m3 vs. 1.0 ng/m3 for EA samples and 100.8 ng/m3 vs. 2.2 ng/m3 for WBT samples), benzo[a]pyrene (38.0 ng/m3 vs. 7.9 ng/m3 for EA samples and 455.3 ng/m3 vs. 12.0 ng/m3 for WBT samples) and 7,12-dimethylbenz[a]anthracene (1.9 ng/m3 vs. 0.2 ng/m3 for EA samples and 47.7 ng/m3 vs. 0.6 ng/m3 for WBT samples). Mixed effect models for both EA samples and WBT samples revealed clear variation in mPAHs concentrations depending on smoky coal source while stove ventilation was consistently found to reduce measured concentrations (by up to nine fold and 65 fold for EA and WBT samples respectively when using smoky coal). Fuel type had a larger influence on mPAHs concentrations than stove type. These findings indicate that users of smoky coal experience exposure to many PAHs, including known and suspected human carcinogens (especially during cooking activities), many of which are not routinely tested for. Collectively, this provides insights into the potential etiologies of lung cancer in the region and further highlights the importance of targeting clean fuel transitions and stove refinements as the final goal for reducing household air pollution and its associated health risks.

Pituitary-derived small extracellular vesicles promote liver repair by its cargo miR-143-3p.

The small Extracellular vesicles (sEV) has been recognized to be significant for intercellular communication due to their ability to transfer important cellular cargoes like miRNAs through circulation. The pituitary gland has not been clearly known about the role of its secreted sEV under normal physiological conditions. And Liver disease is a global public health burden. The present study is the first to investigate the effect of pituitary sEV on the liver. Sequencing and qRT-PCR revealed miR-143-3p is one of the richest in the pituitary sEV. MiR-143 Knockout (KO) mice resulted in a remarkable decrease in insulin-like growth factor 1 (IGF-1) levels and a significant increase in insulin-like growth factor binding protein 5 (IGFBP5) levels along with a reduction in liver primary cell growth. More importantly, compared with miR-143-KO-sEV, WT-sEV possesses a more robust capacity to improve miR-143 KO mice liver repair through the Wnt/ß-catenin pathway after an acute injury caused by carbon tetrachloride (CCl4). Our results indicate that pituitary-derived sEV promotes hepatocyte proliferation and liver repair by its cargo miR-143-3p and provides new insight into the regulation mechanism of the pituitary-liver axis, and open a new window for endocrine regulation by using sEV.

Assessment of isolation strategies to remove caseins for high-quality milk-derived extracellular vesicles.

Increasing studies have highlighted the significance of milk-derived extracellular vesicles (MEVs) in mother-newborn integration, as well as their application as novel drug delivery systems and diagnostic biomarkers. However, conventional ultracentrifugation (UC) often results in the co-precipitation of casein micelles in MEV pellets. In this study, we compared methods with different principles to screen the optimal pretreatment in caseins removal, and found that isoelectric precipitation by hydrochloric acid (HA) could most effectively remove caseins in porcine milk. We further characterized MEV populations isolated by UC and HA/UC from diverse aspects, including particle methodology via nanoparticle tracking analysis (NTA) and transmission electron microscopy (TEM), RNA and protein contents, and purity analysis. Importantly, the proliferative and anti-inflammatory effects of MEVs were evaluated in vitro, showing the superiority of MEVs via HA/UC in functionality compared with UC. Our results suggest that HA pretreatment before ultracentrifugation could effectively remove caseins and other protein complexes, leading to MEVs via HA/UC with higher purity and more significant effects in vitro. This study provides valuable insights for the advancement of MEVs isolation techniques across different species and accurate function analysis of MEVs.

[Corrigendum] Succinate promotes skeletal muscle protein synthesis via Erk1/2 signaling pathway.

Following the publication of the above article, the authors realized that, in Fig. 1D on p. 7363, the data panel selected for the '0.5 mM Succinate' group was duplicated in Fig. 1B (Control) in another article of theirs published in FASEB J ("α­Ketoglutarate prevents skeletal muscle protein degradation and muscle atrophy through PHD3/ADRB2 pathway": doi: 10.1096/fj.201700670R) due to the fact that they had inadvertently confused the layout of the two figures. The authors apologize for this error. Secondly, in terms of the quantification of the blots shown in Fig. 2A, ß­actin was not in fact used as a loading control; the phosphoproteins were normalized against the levels of the relative total protein, and the layout of Fig. 2A has been revised to reflect this (note that the the figure legend for Fig. 2 has also been revised: The last sentence no longer reads, "ß­actin was used as a loading control."). The revised versions of Figs. 1 and 2 are shown on the next page. Note that these errors did not affect the results or the main conclusions reported in the study, and no corrections were required either to the descriptions in the text or to the histograms shown in these figures. All the authors approve of the publication of this corrigendum, and the authors are grateful to the Editor of Molecular Medicine Reports for allowing them the opportunity to publish this. The authors regret their oversight in allowing these errors to be included in the paper, and apologize to the readership for any inconvenience caused. [Molecular Medicine Reports 16: 7361­7366, 2017; DOI: 10.3892/mmr.2017.7554].

Proxitome profiling reveals a conserved SGT1-NSL1 signaling module that activates NLR-mediated immunity.

Suppressor of G2 allele of skp1 (SGT1) is a highly conserved eukaryotic protein that plays a vital role in growth, development, and immunity in both animals and plants. Although some SGT1 interactors have been identified, the molecular regulatory network of SGT1 remains unclear. SGT1 serves as a co-chaperone to stabilize protein complexes such as the nucleotide-binding leucine-rich repeat (NLR) class of immune receptors, thereby positively regulating plant immunity. SGT1 has also been found to be associated with the SKP1-Cullin-F-box (SCF) E3 ubiquitin ligase complex. However, whether SGT1 targets immune repressors to coordinate plant immune activation remains elusive. In this study, we constructed a toolbox for TurboID- and split-TurboID-based proximity labeling (PL) assays in Nicotiana benthamiana and used the PL toolbox to explore the SGT1 interactome during pre- and post-immune activation. The comprehensive SGT1 interactome network we identified highlights a dynamic shift from proteins associated with plant development to those linked with plant immune responses. We found that SGT1 interacts with Necrotic Spotted Lesion 1 (NSL1), which negatively regulates salicylic acid-mediated defense by interfering with the nucleocytoplasmic trafficking of non-expressor of pathogenesis-related genes 1 (NPR1) during N NLR-mediated response to tobacco mosaic virus. SGT1 promotes the SCF-dependent degradation of NSL1 to facilitate immune activation, while salicylate-induced protein kinase-mediated phosphorylation of SGT1 further potentiates this process. Besides N NLR, NSL1 also functions in several other NLR-mediated immunity. Collectively, our study unveils the regulatory landscape of SGT1 and reveals a novel SGT1-NSL1 signaling module that orchestrates plant innate immunity.

Dynamic Mechanical Properties and Modified Material Constitutive Model for Hot Forged Ti2AlNb over Wide Ranges of Temperature and Strain Rate.

In this paper, the stress-strain curves of Ti2AlNb are established based on uniaxial impact tests over wide ranges of temperature and strain rate. The Ti2AlNb exhibited the work hardening effect but did not show an obvious yield stage during a quasi-static compression test. In the SHPB test, an obvious temperature softening effect was found, the strain rate strengthening effect was detected when the strain rate was 4000-8000 s-1, and the strain rate softening effect was detected in the range of 8000-12,000 s-1. A function describing the effect of strain rate on the strain rate strengthening parameters under various temperatures was proposed to modify the basic J-C constitutive model. The relative errors between the experimental measured value and predicted values in various experimental conditions with a modified J-C model were less than 5.0%. The results verified that the modified J-C model could accurately describe the dynamic mechanical properties of Ti2AlNb at high temperatures and strain rates. The research could help to illustrate the cutting mechanism and finite element simulation of Ti2AlNb alloy.

Organic Trace Elements Improve the Eggshell Quality via Eggshell Formation Regulation during the Late Phase of the Laying Cycle.

The quality of eggshells is critical to the egg production industry. The addition of trace elements has been shown to be involved in eggshell formation. Organic trace elements have been found to have higher biological availability than inorganic trace elements. However, the effects of organic trace elements additive doses on eggshell quality during the laying period of commercial laying hens required further investigation. This experiment aims to explore the potential mechanisms of different doses of organic trace elements replacing inorganic elements to remodel the eggshell quality of egg-laying hens during the laying period. A total of 360 healthy hens (Lohmann Pink, 45-week-old) were randomly divided into four treatments, with six replications per treatment and 15 birds per replication. The dietary treatments included a basal diet supplemented with inorganic iron, copper, zinc and manganese at commercial levels (CON), a basal diet supplemented with organic iron, copper, zinc and manganese at 20% commercial levels (LOT), a basal diet supplemented with organic iron, copper, zinc and manganese at 30% commercial levels (MOT), and a basal diet supplemented with organic iron, copper, zinc and manganese at 40% commercial levels (HOT). The trial lasted for 8 weeks. The results of the experiment showed that the replacement of organic trace elements did not significantly affect the production performance of laying hens (p > 0.05). Compared with inorganic trace elements, the MOT and HOT groups improved the structure of the eggshells, enhanced the hardness and thickness of the eggshells, increased the Haugh unit of the eggs, reduced the proportion of the mammillary layer in the eggshell, and increased the proportion of the palisade layer (p < 0.05). In addition, the MOT and HOT groups also increased the enzyme activity related to carbonate transport in the blood, the expression of uterine shell gland-related genes (CA2, OC116, and OCX32), and the calcium and phosphorus content in the eggshells (p < 0.05). We also found that the MOT group effectively reduced element discharge in the feces and enhanced the transportation of iron (p < 0.05). In conclusion, dietary supplementation with 30-40% organic micronutrients were able to improve eggshell quality in aged laying hens by modulating the activity of serum carbonate transport-related enzymes and the expression of eggshell deposition-related genes.

Exceptionally gigantic aurora in the polar cap on a day when the solar wind almost disappeared.

Revealing the origins of aurorae in Earth's polar cap has long been a challenge since direct precipitation of energetic electrons from the magnetosphere is not always expected in this region of open magnetic field lines. Here, we introduce an exceptionally gigantic aurora filling the entire polar cap region on a day when the solar wind had almost disappeared. By combining ground-based and satellite observations, we proved that this unique aurora was produced by suprathermal electrons streaming directly from the Sun, which is known as "polar rain." High-sensitivity imaging from the ground has visualized complex spatial structures of the polar rain aurora possibly manifesting the internal pattern of the solar wind or even the organizations in the chromosphere of the Sun.

Zn2+-dependent association of cysteine-rich protein with virion orchestrates morphogenesis of rod-shaped viruses.

The majority of rod-shaped and some filamentous plant viruses encode a cysteine-rich protein (CRP) that functions in viral virulence; however, the roles of these CRPs in viral infection remain largely unknown. Here, we used barley stripe mosaic virus (BSMV) as a model to investigate the essential role of its CRP in virus morphogenesis. The CRP protein γb directly interacts with BSMV coat protein (CP), the mutations either on the His-85 site in γb predicted to generate a potential CCCH motif or on the His-13 site in CP exposed to the surface of the virions abolish the zinc-binding activity and their interaction. Immunogold-labeling assays show that γb binds to the surface of rod-shaped BSMV virions in a Zn2+-dependent manner, which enhances the RNA binding activity of CP and facilitates virion assembly and stability, suggesting that the Zn2+-dependent physical association of γb with the virion is crucial for BSMV morphogenesis. Intriguingly, the tightly binding of diverse CRPs to their rod-shaped virions is a general feature employed by the members in the families Virgaviridae (excluding the genus Tobamovirus) and Benyviridae. Together, these results reveal a hitherto unknown role of CRPs in the assembly and stability of virus particles, and expand our understanding of the molecular mechanism underlying virus morphogenesis.

Implementation and Evaluation of Discharge Planning for Patients Undergoing Umbilical Cord Blood Transplantation.

BACKGROUND Umbilical cord blood transplantation (UCBT) patients have high rates of unplanned readmissions and poor quality of life (QoL). The aim of this study was to evaluate the effects of discharge planning on unplanned readmissions, self-efficacy, QoL, and clinical outcomes. MATERIAL AND METHODS Patients who received their first UCBT from April 2022 to March 2023 were included. Participants (n=72) were assigned to a control group (CG: received usual care) or an intervention group (IG: received discharge planning from admission to 100 days after UCBT). The cumulative readmission rates 30 days after discharge and 100 days after UCBT were analyzed using the log-rank test. Self-efficacy and QoL were assessed at admission and 100 days after UCBT using the General Self-Efficacy Scale and FACT-BMT version 4, clinical outcomes derived from medical records. RESULTS Sixty-six patients completed the study. Discharge planning did not reduce readmission rates 30 days after discharge (20.59% vs 31.25%, P=0.376) or 100 days after UCBT (29.41% vs 34.38%, P=0.629). However, the IG showed significantly better self-efficacy (P<0.001), and except for social and emotional well-being, all the other dimensions and 3 total scores of FACT-BMT in the IG were higher than for the controls at 100 days after UCBT (P<0.05). CONCLUSIONS The discharge planning program can improve self-efficacy and QoL of UCBT recipients. The implementation of discharge planning for patients undergoing UCBT was necessary for successful hospital-to-home transitions.

Quasi-bound states in the continuum for electromagnetic induced transparency and strong excitonic coupling.

Advancing on previous reports, we utilize quasi-bound states in the continuum (q-BICs) supported by a metasurface of TiO2 meta-atoms with broken inversion symmetry on an SiO2 substrate, for two possible applications. Firstly, we demonstrate that by tuning the metasurface's asymmetric parameter, a spectral overlap between a broad q-BIC and a narrow magnetic dipole resonance is achieved, yielding an electromagnetic induced transparency analogue with a 50 µs group delay. Secondly, we have found that, due to the strong coupling between the q-BIC and WS2 exciton at room temperature and normal incidence, by integrating a single layer of WS2 to the metasurface, a 37.9 meV Rabi splitting in the absorptance spectrum with 50% absorption efficiency is obtained. These findings promise feasible two-port devices for visible range slow-light characteristics or nanoscale excitonic coupling.

Effects of emulsifiers on lipid metabolism and performance of yellow-feathered broilers.

BACKGROUND: Reducing production costs while producing high-quality livestock and poultry products is an ongoing concern in the livestock industry. The addition of oil to livestock and poultry diets can enhance feed palatability and improve growth performance. Emulsifiers can be used as potential feed supplements to improve dietary energy utilization and maintain the efficient productivity of broilers. Therefore, further investigation is warranted to evaluate whether dietary emulsifier supplementation can improve the efficiency of fat utilization in the diet of yellow-feathered broilers. In the present study, the effects of adding emulsifier to the diet on lipid metabolism and the performance of yellow-feathered broilers were tested. A total of 240 yellow-feasted broilers (21-day-old) were randomly divided into 4 groups (6 replicates per group, 10 broilers per replicate, half male and half female within each replicate). The groups were as follows: the control group (fed with basal diet), the group fed with basal diet supplemented with 500 mg/kg emulsifier, the group fed with a reduced oil diet (reduced by 1%) supplemented with 500 mg/kg emulsifier, and the group fed with a reduced oil diet supplemented with 500 mg/kg emulsifier. The trial lasted for 42 days, during which the average daily feed intake, average daily gain, and feed-to-gain ratio were measured. Additionally, the expression levels of lipid metabolism-related genes in the liver, abdominal fat and each intestinal segment were assessed. RESULTS: The results showed that compared with the basal diet group, (1) The average daily gain of the basal diet + 500 mg/kg emulsifier group significantly increased (P < 0.05), and the half-even-chamber rate was significantly increased (P < 0.05); (2) The mRNA expression levels of Cd36, Dgat2, Apob, Fatp4, Fabp2, and Mttp in the small intestine were significantly increased (P < 0.05). (3) Furthermore, liver TG content significantly decreased (P < 0.05), and the mRNA expression level of Fasn in liver was significantly decreased (P < 0.05), while the expression of Apob, Lpl, Cpt-1, and Pparα significantly increased (P < 0.05). (4) The mRNA expression levels of Lpl and Fatp4 in adipose tissue were significantly increased (P < 0.05), while the expression of Atgl was significantly decreased (P < 0.05). (5) Compared with the reduced oil diet group, the half-evading rate and abdominal fat rate of broilers in the reduced oil diet + 500 mg/kg emulsifier group were significantly increased (P < 0.05), and the serum level of LDL-C increased significantly (P < 0.05)0.6) The mRNA expression levels of Cd36, Fatp4, Dgat2, Apob, and Mttp in the small intestine were significantly increased (P < 0.05). 7) The mRNA expression levels of Fasn and Acc were significantly decreased in the liver (P < 0.05), while the mRNA expression levels of Lpin1, Dgat2, Apob, Lpl, Cpt-1, and Pparα were significantly increased (P < 0.05). CONCLUSIONS: These results suggest that dietary emulsifier can enhance the fat utilization efficiency of broilers by increasing the small intestinal fatty acid uptake capacity, inhibiting hepatic fatty acid synthesis and promoting hepatic TG synthesis and transport capacity. This study provides valuable insights for the potential use of emulsifier supplementation to improve the performance of broiler chickens.

High temperature and humidity in the environment disrupt bile acid metabolism, the gut microbiome, and GLP-1 secretion in mice.

High temperature and humidity in the environment are known to be associated with discomfort and disease, yet the underlying mechanisms remain unclear. We observed a decrease in plasma glucagon-like peptide-1 levels in response to high-temperature and humidity conditions. Through 16S rRNA gene sequencing, alterations in the gut microbiota composition were identified following exposure to high temperature and humidity conditions. Notably, changes in the gut microbiota have been implicated in bile acid synthesis. Further analysis revealed a decrease in lithocholic acid levels in high-temperature and humidity conditions. Subsequent in vitro experiments demonstrated that lithocholic acid increases glucagon-like peptide-1 secretion in NCI-H716 cells. Proteomic analysis indicated upregulation of farnesoid X receptor expression in the ileum. In vitro experiments revealed that the combination of lithocholic acid with farnesoid X receptor inhibitors resulted in a significant increase in GLP-1 levels compared to lithocholic acid alone. In this study, we elucidate the mechanism by which reduced lithocholic acid suppresses glucagon-like peptide 1 via farnesoid X receptor activation under high-temperature and humidity condition.

Oral administration of PEDV-dissolved Alg-CS gel induces high and sustained mucosal immunity in mice.

Porcine epidemic diarrhea (PED) is a serious disease in piglets that leads to high mortality. An effective measure that provides higher IgA levels in the intestine and milk is required to decrease losses. Porcine epidemic diarrhea virus (PEDV) was dissolved in calcium alginate (Alg) and combined with chitosan (CS) via electrostatic interactions between cationic chitosan and anionic alginate to create a porous gel (Alg-CS+PEDV). The gel was used to immunize mice orally or in combination with subcutaneous injections of inactivated PEDV vaccine. At 12 and 24 days after immunization, levels of IgA and IgG in Alg-CS+PEDV were higher than with normal PEDV oral administration. At 24 days after immunization, the concentration of IFN-γ in Alg-CS+PEDV was higher than with normal PEDV oral administration. Furthermore, oral administration combining subcutaneous immunization induced higher levels of IgG and IgA than oral administration alone. Our study provides a new method for the preparation and administration of oral vaccines to achieve enhanced mucosal immunity against PEDV.

The Effects of Optimal Dietary Vitamin D3 on Growth and Carcass Performance, Tibia Traits, Meat Quality, and Intestinal Morphology of Chinese Yellow-Feathered Broiler Chickens.

This study aimed to assess the effects of different dietary vitamin D3 (VD3) levels on growth and carcass performance, tibia traits, meat quality, and intestinal morphology of yellow-feathered broilers. One-day-old broilers (n = 1440) were assigned into four treatment groups with six replicates per group, and each replicate contained 60 chicks. Dietary VD3 significantly improved the growth performance and carcass traits of broilers, and only low-dose VD3 supplementation decreased the abdominal fat percentage. High-dose VD3 supplementation improved intestinal morphology in the finisher stage, while the b* value of breast muscle meat color decreased markedly under VD3 supplementation (p < 0.05). Serum Ca and P levels and the tibia composition correlated positively with dietary VD3 supplementation at the early growth stage. The weight, length, and ash contents of the tibia increased linearly with increasing dietary VD3, with maximum values achieved in the high-dose group at all three stages. Intestinal 16S rRNA sequencing and liver transcriptome analysis showed that dietary VD3 might represent an effective treatment in poultry production by regulating lipid and immune-related metabolism in the gut-liver axis, which promotes the metabolism through the absorption of calcium and phosphorus in the intestine and improves their protective humoral immunity and reduces infection mortality. Dietary VD3 positively affected the growth-immunity and bone development of broilers during the early stage, suggesting strategies to optimize poultry feeding.

Extracellular Vesicles: A Crucial Player in the Intestinal Microenvironment and Beyond.

The intestinal ecological environment plays a crucial role in nutrient absorption and overall well-being. In recent years, research has focused on the effects of extracellular vesicles (EVs) in both physiological and pathological conditions of the intestine. The intestine does not only consume EVs from exogenous foods, but also those from other endogenous tissues and cells, and even from the gut microbiota. The alteration of conditions in the intestine and the intestinal microbiota subsequently gives rise to changes in other organs and systems, including the central nervous system (CNS), namely the microbiome-gut-brain axis, which also exhibits a significant involvement of EVs. This review first gives an overview of the generation and isolation techniques of EVs, and then mainly focuses on elucidating the functions of EVs derived from various origins on the intestine and the intestinal microenvironment, as well as the impacts of an altered intestinal microenvironment on other physiological systems. Lastly, we discuss the role of microbial and cellular EVs in the microbiome-gut-brain axis. This review enhances the understanding of the specific roles of EVs in the gut microenvironment and the central nervous system, thereby promoting more effective treatment strategies for certain associated diseases.

Protective effect of Enterococcus faecium against ethanol-induced gastric injury via extracellular vesicles.

Recently, Enterococcus has been shown to have gastric protective functions, and the mechanisms by which Enterococcus modulates gastric function are still being investigated. Herein, we investigated how Enterococcus faecium (Efm) and E. faecium-derived extracellular vesicles (EVs) (EfmEVs) exert protective effect against ethanol-induced gastric injury by investigating the effect of EfmEVs on gastric mucosal ulcer scoring, histological lesion, mucosal glycoprotein production, acidity, anti-oxidative function, and inflammatory responses in rat. Pretreatment with Efm showed significant reduction of ethanol-induced gastric injury, as evidenced by the lowering of ulcer index, histological lesion, gastric pH, and inflammatory responses and the enhancement of mucosal glycoprotein production and anti-oxidative function. Further functional studies on three bioactive components [inactivated Efm, EfmEVs (EVs), and EV-free supernatants] of the bacterial culture showed that EVs are mostly responsible for the gastroprotective effect. Moreover, EV secretion is beneficial for the gastroprotective effect of Efm. Hence, EVs mediated the protective effect of Efm against ethanol-induced gastric injury by lowering inflammatory responses and enhancing anti-oxidative function and may be a potent anti-inflammatory and anti-oxidative strategy to alleviate hyperinflammatory gastrointestinal tract conditions.IMPORTANCEThis study indicated that Enterococcus faecium provided a protective effect against rat gastric injury, which involved improvement of the mucosal glycoprotein production, anti-oxidative function, and inflammatory responses. Furthermore, we confirmed that three bioactive components (inactivated Efm, extracellular vesicles, and EV-free supernatants) of E. faecium culture also contributed to the gastroprotective effect. Importantly, E. faecium-derived EVs showed an effective impact for the gastroprotective effect.

Oral delivery of miR-146a-5p overexpression plasmid-loaded Pickering double emulsion modulates intestinal inflammation and the gut microbe.

The function of miRNAs in intestinal inflammatory injury regulation has been studied extensively. However, the targeted delivery of these functional nucleic acid molecules to specific organs through encapsulation carriers and exerting their functional effects remain critical challenges for further research. Here, we constructed miR-146a-5p overexpression plasmid and validated the anti-inflammatory properties in the cell model. Then, the plasmid was encapsulated by the Pickering double emulsion system to investigate the role of Pickering double emulsion system in LPS-induced acute intestinal inflammatory injury. The results showed that the Pickering double emulsion system could effectively protect the integrity of plasmids in the intestinal tract, alleviate intestinal inflammatory injury, and upregulate the relative abundance of Lactobacillus reuteri. Mechanically, in vivo and in vitro experiments have shown that miR-146a-5p inhibits TLR4/NF-κB pathway to alleviate intestinal inflammation. In addition, miR-146a-5p can also regulate intestinal homeostasis by targeting the RNA polymerase sigma factor RpoD and α-galactosidase A, thereby affecting the growth of Lactobacillus reuteri. Above all, this study reveals a potential mechanism for miR-146a-5p to treat intestinal inflammation and provides a new delivery strategy for miRNAs to regulate intestinal homeostasis.