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The heart is an autoimmune-prone organ. It is crucial for the heart to keep injury-induced autoimmunity in check to avoid autoimmune-mediated inflammatory disease. However, little is known about how injury-induced autoimmunity is constrained in hearts. Here, we reveal an unknown intramyocardial immunosuppressive program driven by Tbx1, a DiGeorge syndrome disease gene that encodes a T-box transcription factor (TF). We found induced profound lymphangiogenic and immunomodulatory gene expression changes in lymphatic endothelial cells (LECs) after myocardial infarction (MI). The activated LECs penetrated the infarcted area and functioned as intramyocardial immune hubs to increase the numbers of tolerogenic dendritic cells (tDCs) and regulatory T (Treg) cells through the chemokine Ccl21 and integrin Icam1, thereby inhibiting the expansion of autoreactive CD8+ T cells and promoting reparative macrophage expansion to facilitate post-MI repair. Mimicking its timing and implementation may be an additional approach to treating autoimmunity-mediated cardiac diseases.
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The development of next-generation electronics requires scaling of channel material thickness down to the two-dimensional limit while maintaining ultralow contact resistance1,2. Transition-metal dichalcogenides can sustain transistor scaling to the end of roadmap, but despite a myriad of efforts, the device performance remains contact-limited3-12. In particular, the contact resistance has not surpassed that of covalently bonded metal-semiconductor junctions owing to the intrinsic van der Waals gap, and the best contact technologies are facing stability issues3,7. Here we push the electrical contact of monolayer molybdenum disulfide close to the quantum limit by hybridization of energy bands with semi-metallic antimony ([Formula: see text]) through strong van der Waals interactions. The contacts exhibit a low contact resistance of 42 ohm micrometres and excellent stability at 125 degrees Celsius. Owing to improved contacts, short-channel molybdenum disulfide transistors show current saturation under one-volt drain bias with an on-state current of 1.23 milliamperes per micrometre, an on/off ratio over 108 and an intrinsic delay of 74 femtoseconds. These performances outperformed equivalent silicon complementary metal-oxide-semiconductor technologies and satisfied the 2028 roadmap target. We further fabricate large-area device arrays and demonstrate low variability in contact resistance, threshold voltage, subthreshold swing, on/off ratio, on-state current and transconductance13. The excellent electrical performance, stability and variability make antimony ([Formula: see text]) a promising contact technology for transition-metal-dichalcogenide-based electronics beyond silicon.
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Akkermansia muciniphila is a mucin-degrading probiotic that colonizes the gastrointestinal tract. Genomic analysis identified a set of genes involved in the biosynthesis of corrin ring, including the cobalt factor II methyltransferase CbiL, in some phylogroups of A. muciniphila, implying a potential capacity for de novo synthesis of cobalamin. In this work, we determined the crystal structure of CbiL from A. muciniphila at 2.3 Å resolution. AmCbiL exists as a dimer both in solution and in crystal, and each protomer consists of two α/ß domains, the N-terminal domain and the C-terminal domain, consistent with the folding of typical class III MTases. The two domains create an open trough, potentially available to bind the substrates SAM and cobalt factor II. Sequence and structural comparisons with other CbiLs, assisted by computer modeling, suggest that AmCbiL should have cobalt factor II C-20 methyltransferase activity. Our results support that certain strains of A. muciniphila may be capable of synthesizing cobalamin de novo.
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Akkermansia , Metiltransferasas , Modelos Moleculares , Metiltransferasas/química , Metiltransferasas/metabolismo , Metiltransferasas/genética , Akkermansia/enzimología , Cristalografía por Rayos X , Secuencia de Aminoácidos , Proteínas Bacterianas/química , Proteínas Bacterianas/metabolismo , Proteínas Bacterianas/genética , Vitamina B 12/metabolismo , Vitamina B 12/química , Conformación ProteicaRESUMEN
Macrophages are innate immunity cells which play pivotal roles in infectious immunity. Aeromonas veronii is a zoonotic agent capable of causing sepsis and poses a serious threat to public health. However, few studies have focused on miRNA-mRNA integration analysis to address the immune mechanisms of macrophage response to A. veronii infection. Herein, we characterized the immunophysiological, biochemical, and transcriptome changes of macrophage under A. veronii infection. We found that macrophages infected with A. veronii released large amounts of cytokines and triggered NLRP3-dependent pyroptosis. Subsequently, 603 differentially expressed miRNAs (DEMIs) and 3693 differentially expressed mRNAs (DEMs) were identified by RNA-seq analysis under A. veronii infection. Moreover, integrated analysis of miRNA-mRNA yielded 66 miRNA-target gene pairs composed of 41 DEMIs and 27 DEMs. We next identified the Toll-like receptor, NOD-like receptor, TNF and NF-κB pathways as necessary for macrophage to respond to A. veronii infection. miR-847 and miR-627 were involved in macrophage response to A. veronii infection by negatively regulating Pannexin-1 and thioredoxin interacting protein (TXNIP). Our findings elucidate the molecular mechanism of macrophage response to A. veronii infection at the miRNA level, providing many candidate miRNAs and mRNAs therapeutic targets for the prevention and treatment of A. veornii infectious diseases.
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The H9N2 avian influenza virus (AIV) is spreading worldwide. Presence of H9N2 virus tends to increase the chances of infection with other pathogens which can lead to more serious economic losses. In a previous study, a regulated delayed lysis Salmonella vector was used to deliver a DNA vaccine named pYL233 encoding M1 protein, mosaic HA protein and chicken GM-CSF adjuvant. To further increase its efficiency, chitosan as a natural adjuvant was applied in this study. The purified plasmid pYL233 was coated with chitosan to form a DNA containing nanoparticles (named CS233) by ionic gel method and immunized by intranasal boost immunization in birds primed by oral administration with Salmonella strain. The CS233 DNA nanoparticle has a particle size of about 150 nm, with an encapsulation efficiency of 93.2 ± 0.12 % which protected the DNA plasmid from DNase I digestion and could be stable for a period of time at 37°. After intranasal boost immunization, the CS233 immunized chickens elicited higher antibody response, elevated CD4+ T cells and CD8+ T cells activation and increased T-lymphocyte proliferation, as well as increased productions of IL-4 and IFN-γ. After challenge, chickens immunized with CS233 resulted in the lowest levels of pulmonary virus titer and viral shedding as compared to the other challenge groups. The results showed that the combination of intranasal immunization with chitosan-coated DNA vaccine and oral immunization with regulatory delayed lytic Salmonella strain could enhance the immune response and able to provide protection against H9N2 challenge.
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AIMS: To detect the expression of autophagy components, p38 MAPK (p38) and phosphorylated forkhead box transcription factor O-1 (pFoxO1) in pulmonary vascular endothelial cells of chronic thromboembolic pulmonary hypertension (CTEPH) rats and to investigate the possible mechanism through which tissue factor (TF) regulates autophagy. METHODS: Pulmonary artery endothelial cells (PAECs) were isolated from CTEPH (CTEPH group) and healthy rats (control group (ctrl group)) which were cocultured with TF at different time points including 12 h, 24 h, 48 h and doses including 0 nM,10 nM, 100 nM, 1µM, 10µM, 100µM and cocultured with TFPI at 48 h including 0 nM, 2.5 nM, 5 nM. The expression of forkhead box transcription factor O-1 (FoxO1), pFoxO1, p38, Beclin-1 and LC3B in PAECs was measured. Coimmunoprecipitation (co-IP) assays were used to detect the interaction between FoxO1 and LC3. RESULTS: The protein expression of p-FoxO1/FoxO1 was significantly lower in the CTEPH groups (cocultured with TF from 0 nM to 100 µM) than in the ctrl group at 12 h, 24 h, and 48 h (P < 0.05) and was significantly lower in the CTEPH groups (cocultured with TFPI from 0 nM to 5 nM) than in the ctrl group at 48 h (P < 0.05). The protein expression of p38 in the CTEPH groups treated with 0 nM, 10 nM, 100 nM or 1 µM TF for 48 h significantly increased than ctrl groups (P < 0.05) and was significantly increased in the CTEPH groups (cocultured with TFPI concentration from 0 nM to 5 nM) than in the ctrl group at 48 h (P < 0.05). The protein expression of Beclin1 at the same concentration (cocultured with TF from 0 nM to 100 µM) was significantly lower in the CTEPH groups than ctrl groups after 24 h and 48 h (P < 0.05) and was significantly decreased in the CTEPH groups (cocultured with TFPI concentration from 2.5 nM to 5 nM) than in the ctrl group at 48 h (P < 0.05). The protein expression of LC3-II/LC3-I at the same concentration (cocultured with TF 0 nM, 1 µM, 10 µM, and 100 µM) was significantly lower in the CTEPH than in the ctrl groups after 12 h (P < 0.05) and was significantly lower in the CTEPH groups (cocultured with TFPI concentration from 0 nM to 5 nM) than in the ctrl group at 48 h (P < 0.05). There were close interactions between FoxO1 and LC3 in the control and CTEPH groups at different doses and time points. CONCLUSION: The autophagic activity of PAECs from CTEPH rats was disrupted. TF, FoxO1 and p38 MAPK play key roles in the autophagic activity of PAECs. TF may regulate autophagic activity through the p38 MAPK-FoxO1 pathway.
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Autofagia , Células Endoteliales , Hipertensión Pulmonar , Arteria Pulmonar , Ratas Sprague-Dawley , Tromboplastina , Proteínas Quinasas p38 Activadas por Mitógenos , Animales , Autofagia/fisiología , Proteínas Quinasas p38 Activadas por Mitógenos/metabolismo , Arteria Pulmonar/metabolismo , Arteria Pulmonar/patología , Ratas , Masculino , Células Endoteliales/metabolismo , Células Cultivadas , Tromboplastina/metabolismo , Tromboplastina/biosíntesis , Hipertensión Pulmonar/metabolismo , Embolia Pulmonar/metabolismo , Embolia Pulmonar/patología , Enfermedad Crónica , Transducción de Señal/fisiología , Proteína Forkhead Box O1RESUMEN
C-type lectins (CTLs) execute critical functions in multiple immune responses of crustaceans as a member of pattern recognition receptors (PRRs) family. In this study, a novel CTL was identified from the exoskeleton of the oriental river prawn Macrobrachium nipponense (MnLec3). The full-length cDNA of MnLec3 was 1150 bp with an open reading frame of 723 bp, encoding 240 amino acids. MnLec3 protein contained a signal peptide and one single carbohydrate-recognition domain (CRD). MnLec3 transcripts were widely distributed at the exoskeleton all over the body. Significant up-regulation of MnLec3 in exoskeleton after Aeromonas hydrophila challenged suggested the involvement of MnLec3 as well as the possible function of the exoskeleton in immune response. In vitro tests with recombinant MnLec3 protein (rMnLec3) manifested that it had polysaccharide binding activity, a wide spectrum of bacterial binding activity and agglutination activity only for tested Gram-negative bacteria (Escherichia coli, Vibrio anguillarum and A. hydrophila). Moreover, rMnLec3 significantly promoted phagocytic ability of hemocytes against A. hydrophila in vivo. What's more, MnLec3 interference remarkably impaired the survivability of the prawns when infected with A. hydrophila. Collectively, these results ascertained that MnLec3 derived from exoskeleton took an essential part in immune defense of the prawns against invading bacteria as a PRR.
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Aeromonas hydrophila , Secuencia de Aminoácidos , Proteínas de Artrópodos , Regulación de la Expresión Génica , Hemocitos , Inmunidad Innata , Lectinas Tipo C , Palaemonidae , Fagocitosis , Filogenia , Alineación de Secuencia , Animales , Palaemonidae/inmunología , Palaemonidae/genética , Lectinas Tipo C/genética , Lectinas Tipo C/inmunología , Lectinas Tipo C/química , Proteínas de Artrópodos/genética , Proteínas de Artrópodos/inmunología , Proteínas de Artrópodos/química , Hemocitos/inmunología , Inmunidad Innata/genética , Aeromonas hydrophila/fisiología , Alineación de Secuencia/veterinaria , Regulación de la Expresión Génica/inmunología , Perfilación de la Expresión Génica/veterinaria , Secuencia de Bases , Exoesqueleto/inmunología , Exoesqueleto/químicaRESUMEN
Acute myeloid leukemia (AML) is an aggressive hematopoietic malignancy with poor prognosis and high recurrence rate. The discovery of more effective therapeutic strategies for AML plays a crucial role. The present work showed that E35, a novel derivative of emodin, significantly inhibited cell proliferation and induced autophagy and apoptosis in AML cells. Treatment with E35 markedly induced Beclin-1, LC3-II, cleaved Caspase-9 and PARP, and suppressed mitogen-activated protein kinase (MAPK) pathway. E35 exposure evoked autophagic activity prior to apoptosis induction, and autophagy inhibition by 3-methyladenine (3-MA) dramatically increased E35-induced apoptosis in both AML cell lines and patient-derived AML cells. Nevertheless, study on AML xenograft model showed that the combination E35 with 3-MA exhibited much more inhibitory effects on leukemia cell growth in vivo. No obvious adverse reactions occurred in the xenograft animals administered E35 alone or its cotreatment with 3-MA. These findings suggest that E35 could exert anti-leukemia effects, and that the combination of E35 and autophagy inhibitor might prove a more highly efficient strategy for AML treatment.
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In clear cell renal cell carcinoma (ccRCC), glycolysis is enhanced mainly because of the increased expression of key enzymes in glycolysis. Hence, the discovery of new molecular biomarkers for glycolysis may help guide and establish a precise system of diagnosis and treatment for ccRCC. Expression profiles of 1079 tumor samples of ccRCC patients (including 311 patients treated with everolimus or nivolumab) were downloaded from public databases. Proteomic profiles of 232 ccRCC samples were obtained from Fudan University Shanghai Cancer Center (FUSCC). Biological changes, tumor microenvironment and prognostic differences were explored between samples with various glycolysis characteristics. There were significant differences in CD8+ effector T cells, epithelial-to-mesenchymal transition and pan-fibroblast TGFb between the Low and High glyScore groups. The tumor mutation burden of the Low glyScore group was lower than that of the High glyScore group. And higher glyScore was significantly associated with worse overall survival (OS) in 768 ccRCC patients (P < .0001). External validation in FUSCC cohort also indicated that glyScore was of strong ability for predicting OS (P < .05). GlyScore may serve as a biomarker for predicting everolimus response in ccRCC patients due to its significant associations with progression-free survival (PFS). And glyScore may also predict overall survival in patients treated with nivolumab. We calculated the glyScore in ccRCC and the defined glyScore was of strong ability for predicting OS. In addition, glyScore may also serve as a biomarker for predicting PFS in patients treated with everolimus and could predict OS in patients treated with nivolumab.
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Carcinoma de Células Renales , Neoplasias Renales , Humanos , Carcinoma de Células Renales/tratamiento farmacológico , Carcinoma de Células Renales/genética , Carcinoma de Células Renales/metabolismo , Neoplasias Renales/tratamiento farmacológico , Neoplasias Renales/genética , Neoplasias Renales/diagnóstico , Nivolumab , Everolimus/uso terapéutico , Proteómica , China , Pronóstico , Biomarcadores de Tumor/genética , Biomarcadores de Tumor/metabolismo , Glucólisis , Microambiente TumoralRESUMEN
BACKGROUND: The heterogeneity limits the effective application of immune checkpoint inhibitors for patients with stomach adenocarcinoma (STAD). Precise immunotyping can help select people who may benefit from immunotherapy and guide postoperative management by describing the characteristics of tumor microenvironment. METHODS: Gene expression profiles and clinical information of patients were collected from ACRG and TCGA-STAD datasets. The immune subtypes (ISs) were identified by consensus clustering analysis. The tumor immune microenvironments (TIME) of each IS were characterized using a series of immunogenomics methods and further confirmed by multiplex immunohistochemistry (mIHC) staining in clinical samples. Two online datasets and one in-house dataset were utilized to construct and validate a prognostic immune-related gene (IRG) signature. RESULTS: STAD patients were stratified into five reproducible ISs. IS1 (immune deserve subtype) had low immune infiltration and the highest degree of HER2 gene mutation. With abundant CD8+ T cells infiltration and activated cytotoxicity reaction, patients in the IS2 (immune-activated subtype) had the best overall survival (OS). IS3 and IS4 subtypes were both in the reactive stroma state and indicated the worst prognosis. However, IS3 (immune-inhibited subtype) was characterized by enrichment of FAP+ fibroblasts and upregulated TGF-ß signaling pathway, while IS4 (activated stroma subtype) was characterized by enrichment of ACTA2+ fibroblasts. In addition, mIHC staining confirmed that TGF-ß upregulated FAP+ fibroblasts were independent risk factor of OS. IS5 (chronic inflammation subtype) displayed moderate immune cells infiltration and had a relatively good survival. Lastly, we developed a nine-IRG signature model with a robust performance on overall survival prognostication. CONCLUSIONS: The immunotyping is indicative for characterize the TIME heterogeneity and the prediction of tumor prognosis for STADs, which may provide valuable stratification for the design of future immunotherapy.
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Adenocarcinoma , Neoplasias Gástricas , Humanos , Linfocitos T CD8-positivos , Fibroblastos , Pronóstico , Microambiente TumoralRESUMEN
Vaccination is still the most promising strategy for combating influenza virus pandemics. However, the highly variable characteristics of influenza virus make it difficult to develop antibody-based universal vaccines, until now. Lung tissue-resident memory T cells (TRM), which actively survey tissues for signs of infection and react rapidly to eliminate infected cells without the need for a systemic immune reaction, have recently drawn increasing attention towards the development of a universal influenza vaccine. We previously designed a sequential immunization strategy based on orally administered Salmonella vectored vaccine candidates. To further improve our vaccine design, in this study, we used two different dendritic cell (DC)-targeting strategies, including a single chain variable fragment (scFv) targeting the surface marker DC-CD11c and DC targeting peptide 3 (DCpep3). Oral immunization with Salmonella harboring plasmid pYL230 (S230), which displayed scFv-CD11c on the bacterial surface, induced dramatic production of spleen effector memory T cells (TEM). On the other hand, intranasal boost immunization using purified DCpep3-decorated 3M2e-ferritin nanoparticles in mice orally immunized twice with S230 (S230inDC) significantly stimulated the differentiation of lung CD11b+ DCs, increased intracellular IL-17 production in lung CD4+ T cells and elevated chemokine production in lung sections, such as CXCL13 and CXCL15, as determined by RNAseq and qRTâPCR assays, resulting in significantly increased percentages of lung TRMs, which could provide efficient protection against influenza virus challenge. The dual DC targeting strategy, together with the sequential immunization approach described in this study, provides us with a novel "prime and pull" strategy for addressing the production of protective TRM cells in vaccine design.
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Subtipo H1N1 del Virus de la Influenza A , Virus de la Influenza A , Vacunas contra la Influenza , Infecciones por Orthomyxoviridae , Ratones , Animales , Células T de Memoria , Pulmón , Células Dendríticas , Infecciones por Orthomyxoviridae/prevención & controlRESUMEN
PROBLEM: Artificial intelligence has been widely investigated for diagnosis and treatment strategy design, with some models proposed for detecting oral pharyngeal, nasopharyngeal, or laryngeal carcinoma. However, no comprehensive model has been established for these regions. AIM: Our hypothesis was that a common pattern in the cancerous appearance of these regions could be recognized and integrated into a single model, thus improving the efficacy of deep learning models. METHODS: We utilized a point-wise spatial attention network model to perform semantic segmentation in these regions. RESULTS: Our study demonstrated an excellent outcome, with an average mIoU of 86.3%, and an average pixel accuracy of 96.3%. CONCLUSION: The research confirmed that the mucosa of oral pharyngeal, nasopharyngeal, and laryngeal regions may share a common appearance, including the appearance of tumors, which can be recognized by a single artificial intelligence model. Therefore, a deep learning model could be constructed to effectively recognize these tumors.
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Inteligencia Artificial , Carcinoma , Humanos , Sistema Respiratorio , SemánticaRESUMEN
RBM45 is an RNA-binding protein involved in neural development, whose aggregation is associated with neurodegenerative diseases, such as amyotrophic lateral sclerosis (ALS) and frontotemporal lobar dementia (FTLD). However, the mechanisms of RNA-binding and aggregation of RBM45 remain unelucidated. Here, we report the crystal structure of the N-terminal tandem RRM domains of human RBM45 in complex with single-stranded DNA (ssDNA). Our structural and biochemical results revealed that both the RRM1 and RRM2 of RBM45 recognized the GAC sequence of RNA/ssDNA. Two aromatic residues and an arginine residue in each RRM were critical for RNA-binding, and the interdomain linker was also involved in RNA-binding. Two RRMs formed a pair of antiparallel RNA-binding sites, indicating that the N-terminal tandem RRM domains of RBM45 bound separate GAC motifs in one RNA strand or GAC motifs in different RNA strands. Our findings will be helpful in the identification of physiologic targets of RBM45 and provide evidence for understanding the physiologic and pathologic functions of RBM45.
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Proteínas del Tejido Nervioso/química , Proteínas de Unión al ARN/química , ARN/química , Cristalografía por Rayos X , ADN de Cadena Simple/química , Humanos , Modelos Moleculares , Proteínas del Tejido Nervioso/metabolismo , Motivos de Nucleótidos , Unión Proteica , ARN/metabolismo , Motivo de Reconocimiento de ARN , Proteínas de Unión al ARN/metabolismoRESUMEN
Silicosis is a diffuse fibrotic lung disease in which excessive inflammatory responses are triggered by silica exposure. Pyroptosis, a pro-inflammatory mode of programmed cell death, is mediated by gasdermin and may play a pivotal role in the development of silicosis. The caspase-1 inhibitor, VX-765, was used in vivo and in vitro to investigate the effects of silica-induced early inflammatory injury and later lung fibrosis. Our findings show that VX-765 reduces inflammatory lung injury by inhibiting silica-induced pyroptosis of alveolar macrophages in a silicosis mouse model. VX-765 limits the infiltration of inflammatory M1 alveolar macrophages, decreasing expression of inflammatory cytokines, including IL-1ß, TNF-α, IL-6, CCL2, and CCL3, and down-regulating endogenous DAMPs and inflammatory immune-related cell pattern recognition receptors TLR4 and NLRP3. Furthermore, VX-765 alleviates fibrosis by down-regulating α-smooth muscle actin (α-SMA), collagen, and fibronectin. In this study, we illustrate that Alveolar macrophages pyroptosis occur in the early stages of silicosis, and VX-765 can alleviate the development of silicosis by inhibiting the pyroptosis signaling pathway. These results may provide new insight into the prevention and treatment of early-stage silicosis.
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Inhibidores de Caspasas , Lesión Pulmonar , Fibrosis Pulmonar , Piroptosis , Silicosis , Animales , Ratones , Lesión Pulmonar/inducido químicamente , Lesión Pulmonar/tratamiento farmacológico , Lesión Pulmonar/patología , Macrófagos Alveolares/efectos de los fármacos , Piroptosis/efectos de los fármacos , Dióxido de Silicio/toxicidad , Silicosis/tratamiento farmacológico , Inhibidores de Caspasas/farmacología , Inhibidores de Caspasas/uso terapéutico , Fibrosis Pulmonar/inducido químicamente , Fibrosis Pulmonar/tratamiento farmacológicoRESUMEN
Intelligent transportation systems (ITS) urgently need to realize vehicle identification, dynamic monitoring, and traffic flow monitoring under high-speed motion conditions. Vehicle tracking based on radio frequency identification (RFID) and electronic vehicle identification (EVI) can obtain continuous observation data for a long period of time, and the acquisition accuracy is relatively high, which is conducive to the discovery of rules. The data can provide key information for urban traffic decision-making research. In this paper, an RFID tag motion trajectory tracking method based on RF multiple features for ITS is proposed to analyze the movement trajectory of vehicles at important checkpoints. The method analyzes the accurate relationship between the RSSI, phase differences, and driving distances of the tag. It utilizes the information weight method to obtain the weights of multiple RF characteristics at different distances. Then, it calculates the center point of the common area where the vehicle may move under multi-antenna conditions, confirming the actual position of the vehicle. The experimental results show that the average positioning error of moving RFID tags based on dual-frequency signal phase differences and RSSI is less than 17 cm. This method can provide real-time, high-precision vehicle positioning and trajectory tracking solutions for ITS application scenarios such as parking guidance, unmanned vehicle route monitoring, and vehicle lane change detection.
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Wetlands in the Yarlung Tsangpo River Basin (YTR) on the Qinghai-Tibet Plateau provide immense soil organic carbon (SOC) storage, which is highly susceptible to climate warming and requires urgent deciphering SOC stabilization mechanisms of long-term protection of SOC against decomposition. Conflicting views exist regarding whether persistent SOC is controlled by molecular features or by mineral protection. As such, this study quantified SOC stability using two thermal indices (TG-T50, and DSC), described molecular features of SOC using pyrolysis-gas chromatography-mass spectrometry, and measured SOC protection by minerals using a chemical extraction method. Results indicated SOC of topsoils had higher thermal stability, with TG-T50 and DSC-T50 of 337.61 °C and 384.58 °C, than that of subsoils with TG-T50 and DSC-T50 of 337.32 and 382.67 °C, respectively. We found subsoils had significantly higher proportions of aliphatic and aromatic compounds, while existed higher SOC associated with minerals. It seemed SOC stabilization differed with soil depths, in which mineral protection dictated SOC thermal stability in topsoils while molecular features posed a more important constraint on SOC stabilization in subsoils. Overall, our findings support the hypothesis of physical and chemical protection but emphasized that SOC thermal stability largely depended on to extent of the combination between molecular features and mineral protection, which explained 55% in topsoils and 73% in subsoils, respectively.
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Carbono , Suelo , Suelo/química , Carbono/análisis , Tibet , Humedales , Minerales/análisisRESUMEN
Social recommender systems are expected to improve recommendation quality by incorporating social information when there is little user-item interaction data. Therefore, how to effectively fuse interaction information and social information becomes a hot research topic in social recommendation, and how to mine and exploit the heterogeneous information in the interaction and social space becomes the key to improving recommendation performance. In this paper, we propose a social recommendation model based on basic spatial mapping and bilateral generative adversarial networks (MBSGAN). First, we propose to map the base space to the interaction and social space, respectively, in order to overcome the issue of heterogeneous information fusion in two spaces. Then, we construct bilateral generative adversarial networks in both interaction space and social space. Specifically, two generators are used to select candidate samples that are most similar to user feature vectors, and two discriminators are adopted to distinguish candidate samples from high-quality positive and negative examples obtained from popularity sampling, so as to learn complex information in the two spaces. Finally, the effectiveness of the proposed MBSGAN model is verified by comparing it with both eight social recommendation models and six models based on generative adversarial networks on four public datasets, Douban, FilmTrust, Ciao, and Epinions.
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The study investigated the effect of Buyang Huanwu Decoction(BYHWD) on endogenous biomarkers in the urine of rats with chronic inflammation induced by lipopolysaccharide(LPS) using ultra-high performance liquid chromatography-quadrupole-time-of-flight-mass spectrometry(UPLC-Q-TOF-MS), aiming to elucidate the molecular mechanism underlying the therapeutic effect of BYHWD on chronic inflammation from a metabolomics perspective. Male SD rats were randomly divided into a normal group, a model group, and low-, medium-, and high-dose BYHWD groups(7.5, 15, and 30 g·kg~(-1)). The model group and BYHWD groups received tail intravenous injection of LPS(200 µg·kg~(-1)) on the first day of each week, followed by oral administration of BYHWD once a day for four consecutive weeks. Urine samples were collected at the end of the administration period, and UPLC-Q-TOF-MS was used to analyze the metabolic profiles of the rat urine in each group. Multivariate statistical analysis methods such as principal component analysis(PCA), partial least squares-discriminant analysis(PLS-DA), and orthogonal partial least squares-discriminant analysis(OPLS-DA) were used to analyze the effect of BYHWD on endogenous metabolites. One-way ANOVA and variable importance for the projection(VIP) were used to screen for potential biomarkers related to chronic inflammation. The identified biomarkers were subjected to pathway and enrichment analysis using MetaboAnalyst 5.0. A total of 25 potential biomarkers were screened and identified in the rat urine in this experiment. Compared with the normal group, the model group showed significant increases in the levels of 14 substances(P<0.05) and significant decreases in the levels of 11 substances(P<0.05). BYHWD was able to effectively reverse the trend of most endogenous biomarkers. Compared with the model group, BYHWD significantly down-regulated 13 biomarkers(P<0.05) and up-regulated 10 biomarkers(P<0.05). The metabolic products were mainly related to the biosynthesis of pantothenic acid and coenzyme A, tryptophan metabolism, retinol metabolism, and propionate metabolism. BYHWD has therapeutic effect on chronic inflammation induced by LPS, which may be related to its ability to improve the levels of endogenous metabolites, enhance the body's anti-inflammatory and antioxidant capabilities, and restore normal metabolic activity.
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Lipopolisacáridos , Metabolómica , Ratas , Masculino , Animales , Cromatografía Líquida de Alta Presión/métodos , Ratas Sprague-Dawley , Metabolómica/métodos , Inflamación/tratamiento farmacológico , Biomarcadores/orinaRESUMEN
Micro(nano)plastics are emerging environmental contaminants of concern. The prevalence of micro(nano)plastics in soils has aroused increasing interest regarding their potential effects on soil biota including terrestrial plants. With the rapid increase in published studies on plant uptake and impacts of micro(nano)plastics, a review summarizing the current research progress and highlighting future needs is warranted. A growing body of evidence indicates that many terrestrial plants can potentially take up micro(nano)plastics via roots and translocate them to aboveground portions via the vascular system, primarily driven by the transpiration stream. Exposure to micro(nano)plastics can cause a variety of effects on the biometrical, biochemical, and physiological parameters of terrestrial plants, but the specific effects vary considerably as a function of plastic properties, plant species, and experimental conditions. The presence of micro(nano)plastics can also affect the bioavailability of other associated toxicants to terrestrial plants. Based on analysis of the available literature, this review identifies current knowledge gaps and suggests prospective lines for further research.
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Plantas , Plásticos , Estudios Prospectivos , SueloRESUMEN
Vps75 is a histone chaperone that interacts with the fungal-specific histone acetyltransferase Rtt109 and stimulates its acetylation activity on histone H3. Here we report the crystal structure of Vps75 of Candida albicans, one of the most common fungal pathogens. CaVps75 exists as a headphone-like dimer that forms a large negatively charged region on its concave side, showing the potential to bind positively charged regions of histones. The distal ends of the concave side of the CaVps75 dimer are positively charged and each has one more α helix than yeast Vps75. CaVps75 exhibits ionic strength- and concentration-dependent higher oligomerization in solution. In the crystal, two dimers are bound through electrostatic interactions between charged regions on the concave side of their earmuff domains, and this inter-dimer interaction differs from the currently known inter-dimer interactions of Vps75s. Our results will help to understand the role of Vps75 in C. albicans.