Development of a "Rigid-Flexible" Structure at the Interface Through Aramid Nanofibers@MXene to Enhance Mechanical Properties of Carbon Fiber/Polyamide Composites.

With the increasing development of nanomaterials, the construction of multiscale nanostructured interphase has emerged as a viable technique to reinforce carbon fiber-reinforced polymer composites. Here, "flexible" aramid nanofibers (ANFs) were first introduced on the surface of carbon fibers (CF) by electrophoretic deposition (EPD), and then "rigid" MXene sheets were grafted by ultrasonic impregnation. This feasible two-step treatment introduces a hierarchical "rigid-flexible" structure at the CF/polyamide (PA) interface. Results showed that this "rigid-flexible" multilayer structure improved the roughness, chemical bonding, mechanical interlocking, and wettability of CF/PA composites. At the same time, the modulus variation between the fiber and the matrix is significantly smoothed due to the increased thickness of the interfacial layer, increasing the payload transfer from the PA matrix to the fiber and decreasing the stress concentration. Compared to the desized CF, the interlaminar shear strength (ILSS) and tensile strength of the modified CF-ANF@MX0.2/PA composite increased by 50.02 and 36.11%, respectively. This innovative interfacial design and feasible treatment method facilitate the construction of firmly interacting interfacial layers in CF/PA composites, offering broad prospects for the production of high-performance CF/PA composites.

Molecular engineering of a new method for effective removal of cadmium from water.

Cadmium (Cd) is a widespread and highly toxic environmental pollutant, seriously threatening animal and plant growth. Therefore, monitoring and employing robust tools to enrich and remove Cd from the environment is a major challenge. In this work, by conjugating a fluorescent indicator (CCP) with a functionalized glass slide, a special composite material (CCPB) was constructed to enrich, remove, and monitor Cd2+ in water rapidly. Then Cd2+ could be effectively eluted by immersing the Cd-enriched CCPB in an ethylenediaminetetraacetic acid (EDTA) solution. With this, the CCPB was continuously reused. Its recovery of Cd2+was above and below 100 % after multiple uses by flame atomic absorption spectrometry (FAAS), which was excellent for practical use in enriching and removing Cd2+ in real aqueous samples. Therefore, CCPB is an ideal material for monitoring, enriching, and removing Cd2+ in wastewater, providing a robust tool for future practical applications of Cd enrichment and removal in the environment.

Neo-construction of a SO2-tunable near-infrared ratiometric fluorescent probe for high-fidelity diagnosis and evaluation hazards of Cd2+-induced liver injury.

Cadmium-contaminated water and food are seriously hazardous to the human health, especially liver injury. To understand the entanglement relationship between cadmium ion (Cd2+)-induced liver injury and the biomarker sulfur dioxide (SO2), a reliable bioanalytical tool is urgently needed, detecting SO2 to diagnose and evaluate the extent of liver injury in vivo. Herein, based on the Förster resonance energy transfer (FRET) mechanism, a novel SO2-tunable NIR ratiometric fluorescent probe (SMP) was developed, it was used to diagnose and treat liver injury induced by Cd2+ in biosystems. Specifically, it was constructed by conjugating a NIR dicyanoisophorone with a NIR benzopyranate as the donor and acceptor, respectively, and the ratiometric response of SO2- regulated by the Michael addition reaction. In addition, SMP exhibits rapid reaction time (<15 s), two well-resolved emission peaks (68 nm) with less cross-talk between channels for high imaging resolution, superior selectivity, and low limit of detection (LOD=80.3 nM) for SO2 detection. Impressively, SMP has been successfully used for intracellular ratiometric imaging of Cd2+-induced SO2 and diagnostic and therapeutic evaluation in liver injury mice models with satisfactory results. Therefore, SMP may provide a powerful molecular tool for revealing the occurrence and development relationship between SO2 and Cd2+-induced liver injury. ENVIRONMENTAL IMPLICATION: Cadmium ions are one of the well-known toxic environmental pollutants, which are enriched in the human body through inhalation of cadmium-contaminated air or from the food chain, leading to damage in various organs, especially liver injury. Therefore, we developed a novel fluorescent probe that can specifically detect SO2 in Cd2+-induced liver injury, which is critically important for the diagnosis and evaluation of Cd2+-induced liver injury diseases. The specific detection of SO2 of this probe has been successfully demonstrated in live HepG2 cells and Cd2+-induced liver injury mice.

Activatable fluorescent probes for early diagnosis and evaluation of liver injury.

With the increase in people's living standards, the number of patients suffering from liver injury keeps on increasing. Traditional diagnostic methods can no longer meet the needs of early and accurate diagnosis due to their limitations in application. However, fluorescent probes based on different fluorophores and nanomaterials have been gradually lighting up medical research due to their unique properties, such as high specificity and non-invasiveness. In addition, accurate identification of the different types of liver injury biomarkers can significantly improve the level of early diagnosis. Therefore, this review reviews the fluorescent probes used in the detection of biomarkers of liver injury over recent years and briefly summarizes the corresponding biomarkers of different types of liver injury. Impressively, this review also lists the structures and the response mechanisms of the different probes, and concludes with an outlook, suggesting directions in which improvements can be made. Finally, we hope that this review will contribute to the further development of fluorescent probes for the early diagnosis and assessment of liver injury.

Advances in the study of antisense long­stranded non­coding RNAs in tumors (Review).

Long­stranded non­coding RNAs (lncRNAs) are RNAs that consist of >200 nucleotides. The majority of lncRNAs do not encode proteins but have been revealed to mediate a variety of important physiological functions. Antisense­lncRNAs (AS­lncRNAs) are transcribed from the opposite strand of a protein or non­protein coding gene as part of the antisense strand of the coding gene. AS­lncRNAs can serve an important role in the tumorigenesis, prognosis, metastasis and drug resistance of a number of malignancies. This has been reported to be exerted through various mechanisms, such as endogenous competition, promoter interactions, direct interactions with mRNAs, acting as 'scaffolds' to regulate mRNA half­life, interactions with 5­untranslated regions and regulation of sense mRNAs. AS­lncRNAs have been found to either inhibit or promote tumor aggressiveness by regulating cell proliferation, energy metabolism, inflammation, inflammatory­carcinoma transformation, invasion, migration and angiogenesis. In addition, accumulating evidence has documented that AS­lncRNAs can regulate tumor therapy resistance. Therefore, targeting aberrantly expressed AS­lncRNAs for cancer treatment may prove to be a promising approach to reverse therapy resistance. In the present review, research advances on the role of AS­lncRNAs in tumor occurrence and development were summarized, with the aim of providing novel ideas for further research in this field.

Fluorescence probes evaluated the hydrogen peroxide level in rice roots under cadmium ion stress.

Abiotic stress and oxidative stress are closely related to the health status of plants. Plants will produce oxidative stress under abiotic stress, induce mitochondrial dysfunction, cause programmed cell death, and decrease plant survival rate. It is well known that rice is an essential crop for humans, but its cadmium tolerance is poor. Therefore, it is crucial to determine whether cadmium stress causes oxidative stress in rice in order to guide rice cultivation. Hydrogen peroxide (H2O2), a highly reactive oxygen species (ROS), is one of the most critical signals in corps under oxidative stress. In this work, we adopted a near-infrared (NIR) H2O2 fluorescent probe YFE-1 and a cadmium ion (Cd2+) fluorescent probe SCP to observe the fluctuation of H2O2 in rice roots under Cd2+ co-incubation conditions. Due to the advantages of fast response (within 2 min), a large Stokes shift (181 nm), good selectivity, and a low detection limit (LOD:26.4 nM), YFE-1 achieved the visualization of H2O2 produced by Cd2+ stress in rice roots. This study provides a new idea for assessing the risk of oxidative stress of Cd2+ in rice roots. It is expected to guide the control of Cd2+ in the rice planting industry to improve rice yield.

Design of a versatile and selective electrochemical sensor based on dummy molecularly imprinted PEDOT/laser-induced graphene for nitroaromatic explosives detection.

Considering the formidable explosive power and human carcinogenicity of nitroaromatic explosives, the implementation of an accurate and sensitive detection technology is imperative for ensuring public safety and monitoring post-blast environmental contamination. In the present work, a versatile and selective electrochemical sensor based on dummy molecularly imprinted poly (3,4-ethylenedioxythiophene)/laser-induced graphene (MIPEDOT/LIG) was successfully developed and the specific detection of multiple nitroaromatic explosives was realized in the single sensor. The accessible and nontoxic trimesic acid (TMA) and superior 3, 4-ethylenedioxythiophene (EDOT) were selected as the dummy-template and the functional monomer, respectively. The interaction between the functional monomer and the template, and the morphology, electrochemical properties and detection performance of the sensor were comprehensively investigated by ultraviolet-visible spectroscopy, Fourier-transform infrared spectroscopy, scanning electron microscopy, cyclic voltammetry, and differential pulse voltammetry. Benefiting from the alliance of TMA and EDOT, the MIPEDOT/LIG sensor manifested outstanding selectivity and sensitivity for 2,4,6-trinitrotolueen (TNT), 2,4,6-trinitrophenol (TNP), 2,4-dinitrotoluene (DNT), 1,3,5-trinitrobenzene (TNB), 2,4-dinitrophenol (DNP), and 1,3-dinitrobenzene (DNB) (representative nitroaromatic explosives) with limits of determination of 1.95 ppb, 3.06 ppb, 2.49 ppb, 1.67 ppb, 1.94 ppb, and 4.56 ppb, respectively. The sensor also exhibited extraordinary reliability and convenience for environmental sample detection. Therefore, a perfect combination of versatility and selectivity in the MIPEDOT/LIG sensor was achieved. The findings of this work provide a new direction for the development of multi-target electrochemical sensors using a versatile dummy template for explosives detection.

A solvent-responsive terbium-organic framework for photocatalytic CO2 reduction.

A Tb-MOF with a 5,5,6-c 3-nodal net, {[Tb(DTDA)1.5·2H2O]·DMF·8H2O}n (AQNU-4), has been synthesized (DTDA = 2',5'-diethoxy-[1,1':4',1''-terphenyl]-4,4''-dicarboxylic acid). AQNU-4 contains a 1-periodic secondary building unit (rod SBU) and has an unusual topological type with the point symbol {32·44·62·7·8}{32·46·5·6}{32·46·52·65}. Efficient light harvesting and electron-hole separation make AQNU-4 an effective photocatalyst for use in the CO2 reduction reaction (CO2RR). Interestingly, as a photocatalyst, AQNU-4 shows an obvious solvent dependence during the catalytic process. In cyclohexanone in particular, it shows the highest CO2 to CO conversion, reaching 138.65 µmol g-1 h-1, making AQNU-4 a good solvent-responsive MOF material.

Spatial-temporal evolution of production-living-ecological space and layout optimization strategy in eco-sensitive areas: a case study of typical area on the Qinghai-Tibetan Plateau, China.

To achieve sustainable development goals and to solve environmental problems, land resources in eco-sensitive areas should be used and optimized. Qinghai, which is an important eco-sensitive area in China, represents a typical ecological vulnerable region on the Qinghai-Tibetan Plateau. Using land use/cover data for 2000, 2010 and 2020, this study applied a series of quantitative methods to analyze the spatial pattern and structure of the production-living-ecological space (PLES) in Qinghai. The results indicated that the spatial pattern of the PLES in Qinghai was stable over time, but the spatial distribution was very different. The structure of the PLES in Qinghai was stable, and the proportion of each space from high to low was ecological (81.01%), production (18.13%) and living (0.86%). We found that the proportion of ecological space in both the Qilian Mountains and the Three River Headwaters Region was lower than the rest of the study area, except for the Yellow River-Huangshui River Valley. Our study objectively and credibly presented the characteristics of the PLES in an important eco-sensitive area in China. This study further formulated targeted policy suggestions to provide a basis for regional sustainable development, ecological environment protection, and land and space optimization in Qinghai.

Hijacking of Host Plasminogen by Mesomycoplasma (Mycoplasma) hyopneumoniae via GAPDH: an Important Virulence Mechanism To Promote Adhesion and Extracellular Matrix Degradation.

Mesomycoplasma hyopneumoniae is the etiological agent of mycoplasmal pneumonia of swine (MPS), which causes substantial economic losses to the world's swine industry. Moonlighting proteins are increasingly being shown to play a role in the pathogenic process of M. hyopneumoniae. Glyceraldehyde-3-phosphate dehydrogenase (GAPDH), a key enzyme in glycolysis, displayed a higher abundance in a highly virulent strain of M. hyopneumoniae than in an attenuated strain, suggesting that it may have a role in virulence. The mechanism by which GAPDH exerts its function was explored. Flow cytometry and colony blot analysis showed that GAPDH was partly displayed on the surface of M. hyopneumoniae. Recombinant GAPDH (rGAPDH) was able to bind PK15 cells, while the adherence of a mycoplasma strain to PK15 was significantly blocked by anti-rGAPDH antibody pretreatment. In addition, rGAPDH could interact with plasminogen. The rGAPDH-bound plasminogen was demonstrated to be activated to plasmin, as proven by using a chromogenic substrate, and to further degrade the extracellular matrix (ECM). The critical site for GAPDH binding to plasminogen was K336, as demonstrated by amino acid mutation. The affinity of plasminogen for the rGAPDH C-terminal mutant (K336A) was significantly decreased according to surface plasmon resonance analysis. Collectively, our data suggested that GAPDH might be an important virulence factor that facilitates the dissemination of M. hyopneumoniae by hijacking host plasminogen to degrade the tissue ECM barrier. IMPORTANCE Mesomycoplasma hyopneumoniae is a specific pathogen of pigs that is the etiological agent of mycoplasmal pneumonia of swine (MPS), which is responsible for substantial economic losses to the swine industry worldwide. The pathogenicity mechanism and possible particular virulence determinants of M. hyopneumoniae are not yet completely elucidated. Our data suggest that GAPDH might be an important virulence factor in M. hyopneumoniae that facilitates the dissemination of M. hyopneumoniae by hijacking host plasminogen to degrade the extracellular matrix (ECM) barrier. These findings will provide theoretical support and new ideas for the research and development of live-attenuated or subunit vaccines against M. hyopneumoniae.

Warming influences CO2 emissions from China's coastal saltmarsh wetlands more than changes in precipitation.

Coastal wetlands are an important carbon sink but are sensitive to climate changes. The response of CO2 emissions to these changes differs under different hydroclimatic conditions. Here, this article used meta-analysis to synthesize data from Chinese coastal salt marshes, to analyze sensitivities for CO2 emissions, and then to assess the relative contributions of air temperature (Ta) and precipitation (Pre). This article used the ratio between potential evaporation (Ep) and Pre to divide Chinese coastal saltmarshes into water- (Ep/Pre > 1) and energy-limited regions (Ep/Pre ≤ 1). Results show that emissions are more sensitive to both Pre and Ta in water-limited regions (E¯ = 0.60 eV, slope = 0.37) than in energy-limited regions (E¯ = 0.23 eV, slope = 0.04). Comparing the relative effects of changes in Ta (△CO2 = 21.86 mg m-2 h-1) and Pre (△CO2 = 7.19 mg m-2 h-1) on CO2 emissions shows that warming contributes more to changes in CO2 emissions. The response of emissions to changes in Pre is asymmetric and shows that warmer and drier may have antagonistic effects, while warmer and wetter may have synergistic effects. There was a 2.15 mg m-2 h-1 change in emissions in energy-limited regions when Pre increased by 139.69 mm, and a decrease of -0.15 mg m-2 h-1 in emissions when Pre decreased by 1.28 mm in water-limited regions. Climate change has the greatest impact on Phragmites australis in CO2 emissions, especially under warmer and wetter conditions in energy-limited regions. This indicates that warming drives CO2 emissions, while changes in Pre (resulting in wetter or dryer conditions) can mitigate or strengthen CO2 emissions from coastal wetlands in China. This article offers a new perspective and suggests that differences in hydroclimatic conditions should be considered when discussing carbon emissions from coastal wetlands.

A metabolic intervention strategy to break evolutionary adaptability of tumor for reinforced immunotherapy.

The typical hallmark of tumor evolution is metabolic dysregulation. In addition to secreting immunoregulatory metabolites, tumor cells and various immune cells display different metabolic pathways and plasticity. Harnessing the metabolic differences to reduce the tumor and immunosuppressive cells while enhancing the activity of positive immunoregulatory cells is a promising strategy. We develop a nanoplatform (CLCeMOF) based on cerium metal-organic framework (CeMOF) by lactate oxidase (LOX) modification and glutaminase inhibitor (CB839) loading. The cascade catalytic reactions induced by CLCeMOF generate reactive oxygen species "storm" to elicit immune responses. Meanwhile, LOX-mediated metabolite lactate exhaustion relieves the immunosuppressive tumor microenvironment, preparing the ground for intracellular regulation. Most noticeably, the immunometabolic checkpoint blockade therapy, as a result of glutamine antagonism, is exploited for overall cell mobilization. It is found that CLCeMOF inhibited glutamine metabolism-dependent cells (tumor cells, immunosuppressive cells, etc.), increased infiltration of dendritic cells, and especially reprogrammed CD8+ T lymphocytes with considerable metabolic flexibility toward a highly activated, long-lived, and memory-like phenotype. Such an idea intervenes both metabolite (lactate) and cellular metabolic pathway, which essentially alters overall cell fates toward the desired situation. Collectively, the metabolic intervention strategy is bound to break the evolutionary adaptability of tumors for reinforced immunotherapy.

IFITM3 is a host restriction factor that inhibits porcine transmissible gastroenteritis virus infection.

Interferon-induced transmembrane proteins (IFITMs) play an important role in the innate immune response triggered by viral infection. Transmissible gastroenteritis virus (TGEV) causes severe diarrhea, vomiting and dehydration in piglets, resulting in huge economic losses to the swine industry. In this study, we showed that IFITM3 inhibits the replication of TGEV and interferes with the binding of TGEV to PK15 cells. Moreover, the inhibitory effect of IFITM3 on TGEV circumvents the upregulation of inflammatory cytokines. Subsequently, we found that the M22A mutant loses part of the antiviral effect of IFITM3 on TGEV; in contrast, the K24A mutant enhances the antiviral effect of IFITM3. Notably, our data shows a synergistic effect between IFITM3 and CQ, which further amplifies the antiviral effect against TGEV.

Ultra-broadband perfect absorber using triple-layer nanofilm in a long-wave near-infrared regime.

Plasmonic absorbers have received considerable attention because of their promising applications in solar cells, controllable thermal emission, and infrared detection. Most proposed plasmonic absorbers are fabricated with a precisely designed surface-pattern, which require complex manufacturing process and are costly. Herein, we propose a simple plasmonic absorber composed of a triple-layer Ti/SiO2/TiN nanosystem. The maximal absorption reaches 99.8% from 1554 nm to 1565 nm, and an average absorption of 95.3% is achieved in the long-wave near-infrared range (from 1100 nm to 2500 nm). The synergistic effect of the upper surface plasmon resonance and the Fabry-Perot resonance in the Ti/SiO2/TiN cause the high absorption. Additionally, the effects of the incident angle, polarization state, structural materials, and geometric parameters on the absorption performance are investigated in detail. The proposed near-infrared absorber has potential application prospects in solar collectors, thermal emitters, and solar cells, owing to its high absorption, ultra-broadband bandwidth, insensitivity to incident angle and polarization state, low cost, and simple preparation process.

Selection of internal reference gene for normalization of reverse transcription-quantitative polymerase chain reaction analysis in Mycoplasma hyopneumoniae.

Mycoplasma hyopneumoniae is the etiological agent of swine enzootic pneumonia (EP), which resulting in considerable economic losses in pig farming globally. Reverse transcription-quantitative polymerase chain reaction (RT-qPCR) is a major tool for gene expression studies. However, no internal reference genes for normalization of RT-qPCR data of M. hyopneumoniae have been reported. The aim of this study was to screen the most stable genes for RT-qPCR analysis in M. hyopneumoniae under different conditions. Therefore, a total of 13 candidate internal reference genes (rpoC, Lipo, sgaB, oppB, hypo621, oppF, gyrB, uvrA, P146, prfA, proS, gatB, and hypo499) of M. hyopneumoniae filtered according to the reported quantitative proteomic analysis and the 16S rRNA internal reference gene frequently used in other bacteria were selected for RT-qPCR analysis. The mRNAs from different virulence strains (168, 168 L, J, NJ, and LH) at five different growth phases were extracted. The corresponding cycle threshold (Ct) values of the 25 reverse transcribed cDNAs using the 14 candidate genes were determined. Different internal reference genes or combinations were then screened for expression stability analysis using various statistical tools and algorithms, including geNorm, BestKeeper, and NormFinder software, to ensure the reliability of the analysis. Through further comprehensive evaluation of the RefFinder software, it is concluded that the gatB gene was the most suitable internal reference gene for samples of the different virulence strains in different growth phases for M. hyopneumoniae, followed by prfA, hypo499, and gyrB.

Pathogenic or Therapeutic: The Mediating Role of Gut Microbiota in Non-Communicable Diseases.

Noncommunicable diseases (NCDs) lead to 41 million deaths every year and account for 71% of all deaths worldwide. Increasing evidence indicates that gut microbiota disorders are closely linked to the occurrence and development of diseases. The gut microbiota, as a potential transmission medium, could play a key role in the transmission and treatment of diseases. The gut microbiota makes noncommunicable diseases communicable. New methods of the prevention and treatment of these diseases could be further explored through the gut microbiota.

Understanding the key functions of Myosins in viral infection.

Myosins, a class of actin-based motor proteins existing in almost any organism, are originally considered only involved in driving muscle contraction, reshaping actin cytoskeleton, and anchoring or transporting cargoes, including protein complexes, organelles, vesicles. However, accumulating evidence reveals that myosins also play vital roles in viral infection, depending on viral species and infection stages. This review systemically summarizes the described various myosins, the performed functions, and the involved mechanisms or molecular pathways during viral infection. Meanwhile, the existing issues are also discussed. Additionally, the important technologies or agents, including siRNA, gene editing, and myosin inhibitors, would facilitate dissecting the actions and mechanisms for described and undescribed myosins, which could be adopted to prevent or control viral infection are also characterized.

Akkermansia muciniphila Protects Against Psychological Disorder-Induced Gut Microbiota-Mediated Colonic Mucosal Barrier Damage and Aggravation of Colitis.

Psychological disorders are associated with increased risk of severe inflammatory bowel disease (IBD) by causing gut microbiota dysbiosis and colonic mucosal barrier damage. However, the interaction between chronic restraint stress (CRS), gut microbiota composition, and colonic mucus remains unclear. We demonstrated that mice under CRS conditions exhibited alterations in microbiota composition, disruption of colonic mucus, and aggravation of colitis. In addition, the abundance of Akkermansia muciniphila was significantly decreased in mice under CRS and UC patients with depression, and positively associated with the expression of MUC2. After antibiotic treatment, the recipient mice colonized with CRS microbiota showed barrier defects and severe colitis. Administration of Akkermansia muciniphila was found to restore colonic mucus and modify the gut microbiota. We confirm that CRS-mediated gut microbiota dysbiosis results in colonic mucosal barrier damage and aggravation of colitis. Our results suggest that A. muciniphila is expected to be a potential probiotic to protect and treat colonic mucus that is involved in IBD with psychological disorders.

Depression and anxiety in patients with active ulcerative colitis: crosstalk of gut microbiota, metabolomics and proteomics.

Patients with ulcerative colitis (UC) have a high prevalence of mental disorders, such as depression and anxiety. Gut microbiota imbalance and disturbed metabolism have been suggested to play an important role in either UC or mental disorders. However, little is known about their detailed multi-omics characteristics in patients with UC and depression/anxiety. In this prospective observational study, 240 Chinese patients were enrolled, including 129 patients with active UC (69 in Phase 1 and 60 in Phase 2; divided into depression/non-depression or anxiety/non-anxiety groups), 49 patients with depression and anxiety (non-UC), and 62 healthy people. The gut microbiota of all subjects was analyzed using 16S rRNA sequencing. The serum metabolome and proteome of patients with UC in Phase 2 were analyzed using liquid chromatography/mass spectrometry. Associations between multi-omics were evaluated by correlation analysis. The prophylactic effect of candidate metabolites on the depressive-like behavior of mice with colitis was investigated. In total, 58% of patients with active UC had depression, while 50% had anxiety. Compared to patients with UC without depression/anxiety, patients with UC and depression/anxiety had lower fecal microbial community richness and diversity, with more Lactobacillales, Sellimonas, Streptococcus, and Enterococcus but less Prevotella_9 and Lachnospira. Most metabolites (e.g., glycochenodeoxycholate) were increased in the serum, while few metabolites, including 2'-deoxy-D-ribose and L-pipecolic acid, were decreased, accompanied by a general reduction in immunoglobulin proteins. These related bacteria, metabolites, and proteins were highly connected. A prophylactic administration of 2'-deoxy-D-ribose and L-pipecolic acid significantly reduced the depressive-like behaviors in mice with colitis and alleviated the inflammatory cytokine levels in their colon, blood and brain. This study has identified a comprehensive multi-omics network related to depression and anxiety in active UC. It is composed of a certain set of gut microbiota, metabolites, and proteins, which are potential targets for clinical intervention for patients with UC and depression/anxiety.

A next-generation probiotic: Akkermansia muciniphila ameliorates chronic stress-induced depressive-like behavior in mice by regulating gut microbiota and metabolites.

Major depressive disorder (MDD) is a neurasthenic disease, which is the second-largest burden of disease globally. Increasing studies have revealed that depression is associated with abnormalities in gut microbiota and metabolites. Several species of bacteria have been classified as psychobiotics, which confer mental health benefits through interactions with commensal gut microbiota. Therefore, it is essential to identify new psychobiotics and elucidate their mechanisms in the treatment of depression. This study aims to evaluate the antidepressant effect of Akkermansia muciniphila (AKK) in a mouse model of depression induced by chronic restraint stress (CRS). C57BL/6 male mice were divided into three groups: mice subjected to CRS, mice not subjected to CRS, and mice treated with AKK for 3 weeks. Behavioral tests were performed, and hormone, neurotransmitter, and brain-derived neurotrophic factor (BDNF) levels were measured. Cecal microbiota was analyzed using 16S rRNA gene sequencing, and serum metabolites were detected using untargeted metabolomics. In addition, correlations between altered gut microbiota and metabolites with significant variations in serum associated with AKK ameliorating depression were analyzed using Pearson's correlation coefficient. The results revealed that AKK significantly ameliorated depressive-like behavior and restored abnormal variations in depression-related molecular (corticosterone, dopamine, and BDNF). Moreover, AKK altered chronic stress-induced gut microbial abnormalities. Untargeted metabolomics analysis revealed 23 potential biomarkers in serum that could be associated with the mechanisms underlying CRS-induced depression and the therapeutic effects of AKK. Pearson's correlation coefficient analysis revealed that AKK predominantly upregulated ß-alanyl-3-methyl-L-histidine and edaravone to relieve depression. Furthermore, ß-alanyl-3-methyl-L-histidine and edaravone exhibited the antidepressant phenotype in mice subjected to CRS. In conclusion, the study demonstrated that AKK ameliorates chronic stress-induced depressive symptoms in mice by regulating gut microbiota and metabolites. KEY POINTS: • AKK reduces depressive-like behaviors induced by chronic stress. • AKK regulates the gut microbial structure and metabolomics of serum under the chronic stress. • Antidepressant effect of AKK correlates with the increase of ß-alanyl-3-methyl-l-histidine and edaravone.