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Macrophage polarization is vital to mounting a host defense or repairing tissue in various liver diseases. Excessive activation of the NLR family pyrin domain containing 3 (NLRP3) inflammasome is related to the orchestration of inflammation and alcohol-associated liver disease (ALD) pathology. Rab GTPases play critical roles in regulating vesicular transport. In this study we investigated the role of Rab11b in ALD, aiming to identify effective therapeutic targets. Here, we first demonstrated a decreased expression of Rab11b in macrophages from ALD mice. Knockdown of Rab11b by macrophage-specific adeno-associated virus can alleviate alcohol induced liver inflammation, injury and steatosis. We found that LPS and alcohol stimulation promoted Rab11b transferring from the nucleus to the cytoplasm in bone marrow-derived macrophages (BMDM) cells. Rab11b specifically activated the NLRP3 inflammasome in BMDMs and RAW264.7 cells to induce M1 macrophage polarization. Rab11b overexpression in BMDMs inhibited autophagic flux, leading to the suppression of LC3B-mediated NLRP3 degradation. We conclude that impaired Rab11b could alleviate alcohol-induced liver injury via autophagy-mediated NLRP3 degradation.
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OBJECTIVES: To observe the effect of moxibustion at "Xinshu" (BL15) and "Feishu" (BL13) on transient receptor potential vanilloid type 1(TRPV1), calcitonin gene-related peptide (CGRP), and serum interleukin-10 (IL-10) in the myocardial tissue of rats with chronic heart failure (CHF), so as to explore its underlying mechanisms in improvement of CHF. METHODS: Male SD rats were randomly divided into the normal, model, moxibustion, capsaicin, moxibustion + capsaicin, and moxibustion + solvent groups, with 10 rats in each group. The CHF model was established by permanent ligation of the anterior descending branch of the left coronary artery. Mild moxibustion was applied to bilateral BL13 and BL15 for 30 min once daily for 4 weeks. Rats in the capsaicin group were smeared with capsaicin in the acupoint area once a day for 4 weeks. For rats of the moxibustion + capsaicin and moxibustion + solvent groups, capsaicin and solvent were applied to the acupoint area before moxibustion for 4 weeks, respectively. The ejection fraction (EF) and left ventricular fractional shortening rate (FS) were examined by echocardiography. HE staining was used to observe the myecardial morphological structure. The mRNA and protein expression levels of TRPV1, CGRP and galectin-3 (Gal-3) in myocardial tissue were detected by real-time quantitative PCR and Western blot, respectively. The content of IL-10 in serum was detected by ELISA. RESULTS: After modeling, the pathological changes of myocardium (as cardiac muscle fiber disorder, inflammatory cell infiltration, etc.) were obvious, and the EF, FS, serum IL-10, protein and mRNA exspression of TRPV1 and CGRP were significantly decreased (P<0.01) in the model group compared with the normal group, while the protein and mRNA exspression of Gal-3 were significantly up-regulated (P<0.01). Following the interventions, the above-mentioned indexes were all reversed in moxibustion, capsaicin, and moxibustion + capsaicin groups (P<0.01), and the effect of moxibustion + capsaicin was the best (P<0.05, P<0.01). CONCLUSIONS: Moxibustion can reduce myocardial injury and improve cardiac function in CHF rats, which may be related to its effects in up-regulating the expression of TRPV1 and CGRP, and down-regulating the expression of Gal-3 to alleviate myocardial fibrosis.
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Pontos de Acupuntura , Peptídeo Relacionado com Gene de Calcitonina , Insuficiência Cardíaca , Interleucina-10 , Moxibustão , Miocárdio , Ratos Sprague-Dawley , Canais de Cátion TRPV , Animais , Canais de Cátion TRPV/genética , Canais de Cátion TRPV/metabolismo , Insuficiência Cardíaca/terapia , Insuficiência Cardíaca/metabolismo , Insuficiência Cardíaca/genética , Masculino , Ratos , Peptídeo Relacionado com Gene de Calcitonina/genética , Peptídeo Relacionado com Gene de Calcitonina/metabolismo , Humanos , Miocárdio/metabolismo , Interleucina-10/genética , Interleucina-10/metabolismoRESUMO
OBJECTIVES: To observe the effect of moxibustion at "Xinshu"(BL15) and "Feishu"(BL13) combined with intraperitoneal injection of benazepril on cardiac function and phosphorylation of protein kinase R-like endoplasmic reticulum kinase (PERK) and eukaryotic initiation factor 2α (elF2α) proteins in myocardium of rats with chronic heart failure (CHF), so as to explore its potential mechanism underlying improvement of CHF. METHODS: A total of 42 male SD rats were randomly assigned to blank control (n=10), CHF model (n=7), medication (benazepril, n=8), moxibustion (n=8) and moxibustion+benazepril (n=9) groups, after cardiac ultrasound model identification and elimination of the dead. The CHF model was established by intraperitoneal injection of doxorubicin hydrochloride (DOX), once every week for 6 weeks. Mild moxibustion was applied to bilateral BL15 and BL13 regions for 20 min, once daily for 3 weeks. The rats of the medication group and moxibustion+benazepril group (benazepril was given first, followed by moxibustion) received intraperitoneal injection of benazepril (0.86 mg/kg) solution once daily for 3 weeks . The cardiac ejection fraction (EF) and left ventricular fractional shortening (FS) were measured using echocardiography. Histopathological changes of the cardiac muscle tissue were observed under light microscope after hematoxylin-eosin (H.E.) staining. Serum contents of B-type brain natriuretic peptide (BNP) and angiotensin â ¡ (Angâ ¡) were measured by enzyme-linked immunosorbent assay (ELISA). The expressions of phospho-PERK (p-PERK) and phospho-elF2α (p-elF2α) in the myocardium were detected by Western blot. RESULTS: Compared with the blank control group, the EF and FS of the left cardiac ventricle were significantly decreased (P<0.01), while the contents of serum BNP and Angâ ¡, and expression levels of p-PERK and p-eIF2α significantly increased in the model group (P<0.01). In comparison with the model group, both the decreased EF and FS and the increased BNP and Angâ ¡ contents as well as p-PERK and p-elF2α expression levels were reversed by moxibustion, medication and moxibustion+benazepril (P<0.01). The effects of moxibustion+benazepril were markedly superior to those of simple moxibustion and simple medication in raising the levels of EF and FS rate and in down-regulating the contents of BNP, Ang â ¡, levels of p-PERK and p-elF2α (P<0.01, P<0.05). Outcomes of H.E. staining showed irregular arrangement of cardiomyocytes, cell swelling, vacuole and inflammatory infiltration in the model group, which was relatively milder in the 3 treatment groups. The effects of moxibustion+benazepril were superior to those of moxibustion or benazepril. CONCLUSIONS: Moxibustion combined with Benazepril can improve the cardiac function in CHF rats, which may be related to its functions in down-regulating the expression levels of myocardial p-PERK and p-elF2α to inhibit endoplasmic reticulum stress response.
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Benzazepinas , Insuficiência Cardíaca , Moxibustão , Ratos , Masculino , Animais , Ratos Sprague-Dawley , Injeções Intraperitoneais , Fosforilação , Insuficiência Cardíaca/tratamento farmacológico , Doença Crônica , Estresse do Retículo EndoplasmáticoRESUMO
Colorectal cancer (CRC) has emerged as the third most prevalent and second deadliest cancer worldwide. Metabolic reprogramming is a key hallmark of cancer cells. Phosphoglycerate dehydrogenase (PHGDH) is over-expressed in multiple cancers, including CRC. Although the role of PHGDH in metabolism has been extensively investigated, its effects on CRC development remains to be elucidated. In the present study, it was demonstrated that PHGDH expression was significantly up-regulated in colorectal cancer. PHGDH expression was positively correlated with that of the aryl hydrocarbon receptor (AhR) and its target genes, CYP1A1 and CYP1B1, in CRC cells. Knockdown of PHGDH reduced AhR levels and activity, as well as the ratio of reduced to oxidized glutathione. The selective AhR antagonist stemregenin 1 induced cell death through reactive oxygen species-dependent autophagy in CRC cells. PHGDH knockdown induced CRC cell sensitivity to stemregenin 1 via the autophagy pathway. Our findings suggest that PHGDH modulates AhR signaling and the redox-dependent autophagy pathway in CRC, and that the combination of inhibition of both PHGDH and AhR may be a novel therapeutic strategy for CRC.
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Neoplasias Colorretais , Receptores de Hidrocarboneto Arílico , Humanos , Autofagia/genética , Linhagem Celular Tumoral , Neoplasias Colorretais/metabolismo , Fosfoglicerato Desidrogenase/deficiência , Fosfoglicerato Desidrogenase/genética , Receptores de Hidrocarboneto Arílico/antagonistas & inibidores , Receptores de Hidrocarboneto Arílico/genética , Receptores de Hidrocarboneto Arílico/metabolismoRESUMO
The solute carrier (SLC) family, with more than 400 membrane-bound proteins, facilitates the transport of a wide array of substrates such as nutrients, ions, metabolites, and drugs across biological membranes. Amino acid transporters (AATs) are membrane transport proteins that mediate transfer of amino acids into and out of cells or cellular organelles. AATs participate in many important physiological functions including nutrient supply, metabolic transformation, energy homeostasis, redox regulation, and neurological regulation. Several AATs have been found to significantly impact the progression of human malignancies, and dysregulation of AATs results in metabolic reprogramming affecting tumor growth and progression. However, current clinical therapies that directly target AATs have not been developed. The purpose of this review is to highlight the structural and functional diversity of AATs, the molecular mechanisms in human diseases such as tumors, kidney diseases, and emerging therapeutic strategies for targeting AATs.
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Sistemas de Transporte de Aminoácidos , Neoplasias , Humanos , Sistemas de Transporte de Aminoácidos/genética , Aminoácidos/metabolismo , Neoplasias/tratamento farmacológico , Neoplasias/metabolismo , Membrana Celular/metabolismoRESUMO
BACKGROUND: Coronary microvascular dysfunction (CMD) is an important feature of obstructive hypertrophic cardiomyopathy (oHCM). Angiographic microvascular resistance (AMR) offers a potent means for assessing CMD. This study sought to evaluate the prognostic value of CMD burden calculated by AMR among oHCM patients. METHODS: We retrospectively screened all patients diagnosed with oHCM from Fuwai Hospital between January 2017 and November 2021. Off-line AMR assessments were performed for all 3 major coronary vessels by the independent imaging core laboratory. Patients were followed every 6 months post discharge via office visit or telephone contacts. The primary outcome was major adverse cardiovascular events (MACE), including all-cause death, and unplanned rehospitalization for heart failure. RESULTS: A total of 342 patients presented with oHCM diseases enrolled in the present analyses. Mean age was 49.7, 57.6 % were men, mean 3-vessel AMR was 6.9. At a median follow-up of 18 months, high capability of 3-vessel AMR in predicting MACE was identified (AUC: 0.70) with the best cut-off value of 7.04. The primary endpoint of MACE was significantly higher in high microvascular resistance group (3-vessel AMR ≥ 7.04) as compared with low microvascular resistance group (56.5 % vs. 16.5 %; HR: 5.13; 95 % CI: 2.46-10.7; p < 0.001), which was mainly driven by the significantly higher risk of heart failure events in high microvascular resistance group. Additionally, 3-vessel AMR (HR: 4.37; 95 % CI: 1.99-9.58; p < 0.001), and age (per 1 year increase, HR: 1.03; 95 % CI: 1.01-1.06; p = 0.02) were independently associated with MACE. CONCLUSION: The present retrospective study demonstrated that the novel angiography-based AMR was a useful tool for CMD evaluation among patients with oHCM. High microvascular resistance as identified by 3-vessel AMR (≥7.04) was associated with worse prognosis.
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Cardiomiopatia Hipertrófica , Insuficiência Cardíaca , Isquemia Miocárdica , Masculino , Humanos , Feminino , Estudos Retrospectivos , Angiografia Coronária/métodos , Assistência ao Convalescente , Alta do Paciente , Prognóstico , Cardiomiopatia Hipertrófica/diagnóstico por imagem , Insuficiência Cardíaca/diagnóstico por imagemRESUMO
Ferroptosis is an iron-dependent, non-apoptotic form of regulated cell death and has been implicated in the occurrence and development of various diseases, including heart disease, nervous system diseases and cancer. Ferroptosis induction recently emerged as an attractive strategy for cancer therapy. Ferroptosis has become a potential target for intervention in these diseases or injuries in relevant preclinical models. This review summarizes recent progress on the mechanisms of ferroptosis resistance in cancer, highlights redox status and metabolism's role in it. Combination therapy for ferroptosis has great potential in cancer treatment, especially malignant tumors that are resistant to conventional therapies. This review will lead us to have a comprehensive understanding of the future exploration of ferroptosis and cancer therapy. A deeper understanding of the relationship between ferroptosis resistance and metabolism reprogramming may provide new strategies for tumor treatment and drug development based on ferroptosis.
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Ferroptose , Cardiopatias , Neoplasias , Humanos , Terapia Combinada , Desenvolvimento de Medicamentos , Neoplasias/tratamento farmacológicoRESUMO
Despite recent advances have been made in clinical treatments of breast cancer, the general prognosis of patients remains poor. Therefore, it is imperative to develop a more effective therapeutic strategy. Lysine demethylase 4B (KDM4B) has been reported to participate in breast cancer development recently, but its exact biological role in breast cancer remains unclear. Here, we observed that KDM4B was down-regulated in human primary BRCA tissues and the low levels of KDM4B expression were correlated with poor survival. Gain- and loss-of-function experiments showed that KDM4B inhibited the proliferation and metastasis of breast cancer cells. Besides, knockdown of KDM4B promoted the epithelial-mesenchymal transition (EMT) and cell stemness in breast cancer cells. Mechanistically, KDM4B down-regulates PHGDH by decreasing the enrichment of H3K36me3 on the promoter region of PHGDH. Knockdown of PHGDH could significantly reversed proliferation, migration, EMT, and cell stemness induced by KDM4B silencing in breast cancer cells. Collectively, we propose a model for a KDM4B/PHGDH axis that provides novel insight into breast cancer development, which may serve as a potential factor for predicting prognosis and a therapeutic target for breast cancer.
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Neoplasias da Mama , Humanos , Feminino , Regulação para Cima , Regulação para Baixo , Neoplasias da Mama/patologia , Linhagem Celular Tumoral , Transição Epitelial-Mesenquimal , Histona Desmetilases com o Domínio Jumonji/genética , Histona Desmetilases com o Domínio Jumonji/metabolismoRESUMO
The developments in polarized light have spawned a multitude of novel applications in optical fiber systems, but the design and fabrication of practical fiber wave plates with high degree of integration still remain a challenging issue. To address this problem, an all-fiber spun wave plate (SWP) for arbitrary state of polarization (SOP) conversion is proposed in this work, and its principle is analyzed with Mueller matrix. Simulations are conducted to exhibit the arbitrary SOP conversion capability of the proposed SWP, and two key parameters, including the maximum spinning rate (ξmax) and linear birefringence (δ), are investigated for efficient conversion of desired SOP. Different functions to increase the spinning rate ξ from 0 to ξmax, computational efficiency and accuracy related to N are discussed in detail. Furthermore, the depolarization effect caused by retardation of SWP is also considered. The results of this research suggest that the proposed SWP exhibits promising performance in arbitrary SOP conversion, and the meticulous analysis of the numerical computation, design, and implementation of SWP presented in this work can provide novel insights for devloping fiber wave plates.
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Using blue laser diodes (LDs) to pump Pr:YLF crystals can directly realize visible-band laser output. Compared with the traditional frequency doubling and LD direct output method, it has the advantages of simple design, compact structure, and high beam quality. For solid-state lasers, pump-induced thermal effects of gain media are the principal limiting factors for the desired high-power output. In this paper, internal temperature space model distribution of a rectangular cross-section Pr:YLF crystal is established. On this basis, the temperature distribution, thermal stress distribution, and thermal focal length variation of single-end pumped and double-end pumped laser crystals are analyzed. The results are verified by COMSOL simulations and experimental measurements. To our knowledge, this analysis is the first to examine the thermal effect of a rectangular cross-section Pr:YLF crystal, analyzing the limit power that the crystal can withstand, which paves the way for better performances of visible lasers with stable and high-power output.
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Optical soliton molecules exhibiting behaviors analogous to matter molecules have been the hotspot in the dissipative system for decades. Based on the dispersion Fourier transformation technique, the real-time spectral interferometry has become the popular method to reveal the internal dynamics of soliton molecules. The rising degrees of freedom in pace with the increased constitutes of soliton molecules yield more intriguing sights into the internal motions. Yet the soliton molecules with three or more pulses are rarely investigated owing to the exponentially growing complexity. Here, we present both experimental and theoretical studies on the soliton molecules containing three solitons. Different assemblies of the constitutes are categorized as different types of soliton triplet akin to the geometric isomer, including equally-spaced triplet and unequally-spaced triplet. Typical soliton triplets with different dynamics including regular internal motions, hybrid phase dynamics and complex dynamics involving separation evolution are experimentally analyzed and theoretically simulated. Specifically, the energy difference which remains elusive in experiments are uncovered through the simulation of diverse triplets with plentiful dynamics. Moreover, the multi-dimensional interaction space is proposed to visualize the internal motions in connection with the energy exchange, which play significant roles in the interplays among the solitons. Both the experimental and numerical simulations on the isomeric soliton triplets would release a larger number of degrees of freedom and motivate the potentially artificial configuration of soliton molecules for various ultrafast applications, such as all-optical buffering and multiple encoding for telecommunications.
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Esophageal cancer (ESCA) is the seventh most frequent and deadly neoplasm. Due to the lack of early diagnosis and high invasion/metastasis, the prognosis of ESCA remains very poor. Herein, we identify skin-related signatures as the most deficient signatures in invasive ESCA, which are regulated by the transcription factor ZNF750. Of note, we find that TRIM29 level strongly correlated with the expression of many genes in the skin-related signatures, including ZNF750. TRIM29 is significantly down-regulated due to hypermethylation of its promoter in both ESCA and precancerous lesions compared to normal tissues. Low TRIM29 expression and high methylation levels of its promoter are associated with malignant progression and poor clinical outcomes in ESCA patients. Functionally, TRIM29 overexpression markedly hinders proliferation, migration, invasion, and epithelial-mesenchymal transition of esophageal cancer cells, whereas opposing results are observed when TRIM29 is silenced in vitro. In addition, TRIM29 inhibits metastasis in vivo. Mechanistically, TRIM29 downregulation suppresses the expression of the tumor suppressor ZNF750 by activating the STAT3 signaling pathway. Overall, our study demonstrates that TRIM29 expression and its promoter methylation status could be potential early diagnostic and prognostic markers. It highlights the role of the TRIM29-ZNF750 signaling axis in modulating tumorigenesis and metastasis of esophageal cancer.
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Self-assembly of particle-like dissipative solitons, in the presence of mutual interactions, emphasizes the vibrant concept of soliton molecules in varieties of laser resonators. Controllable manipulation of the molecular patterns, held by the degrees of freedom of internal motions, still remains challenging to explore more efficient and subtle tailoring approaches for the increasing demands. Here, we report a new phase-tailored quaternary encoding format based on the controllable internal assembly of dissipative soliton molecules. Artificial manipulation of the energy exchange of soliton-molecular elements stimulates the deterministic harnessing of the assemblies of internal dynamics. Self-assembled soliton molecules are tailored into four phase-defined regimes, thus constituting the phase-tailored quaternary encoding format. Such phase-tailored streams are endowed with great robustness and are resistant to significant timing jitter. All these results experimentally demonstrate the programmable phase tailoring and exemplify the application of the phase-tailored quaternary encoding, prospectively promoting high-capacity all-optical storage.
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Orthodenticle homeobox (OTX1) is reported to be involved in numerous cancers, but the expression level and molecular function of OTX1 in gallbladder cancer (GBC) remain unknown. Here, we found the elevated level of OTX1 associated with poor prognosis in human gallbladder cancer. In vitro and in vivo studies of human gallbladder cancer cell lines demonstrated that overexpression of OTX1 promoted cell proliferation, whereas the downregulation inhibited it. Additionally, we found a tight correlation between the serum level of taurodeoxycholic acid (TDCA) and OTX1 expression. TDCA-induced activation of YAP1 by phosphorylation inhibition contributed to the transcriptional activation of OTX1. Mechanistically, we identified that OTX1 activated AKT signaling pathway by transactivating the expression of IFITM3 and thus promoted the proliferation of GBC cells. Taken together, our results showed that TDCA-YAP1-dependent expression of OTX1 regulated IFITM3 and affected GBC proliferation via the AKT signaling pathway. Our experiments also suggested that OTX1 is a novel therapeutic target for GBC.
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Neoplasias da Vesícula Biliar , Humanos , Linhagem Celular Tumoral , Proliferação de Células/fisiologia , Neoplasias da Vesícula Biliar/metabolismo , Proteínas de Membrana/metabolismo , Fatores de Transcrição Otx/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo , Proteínas de Ligação a RNA/metabolismo , Transdução de Sinais , Ácido Taurodesoxicólico/farmacologiaRESUMO
The use of alkaline salt lands for crop production is hindered by a scarcity of knowledge and breeding efforts for plant alkaline tolerance. Through genome association analysis of sorghum, a naturally high-alkaline-tolerant crop, we detected a major locus, Alkaline Tolerance 1 (AT1), specifically related to alkaline-salinity sensitivity. An at1 allele with a carboxyl-terminal truncation increased sensitivity, whereas knockout of AT1 increased tolerance to alkalinity in sorghum, millet, rice, and maize. AT1 encodes an atypical G protein γ subunit that affects the phosphorylation of aquaporins to modulate the distribution of hydrogen peroxide (H2O2). These processes appear to protect plants against oxidative stress by alkali. Designing knockouts of AT1 homologs or selecting its natural nonfunctional alleles could improve crop productivity in sodic lands.
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Álcalis , Produtos Agrícolas , Subunidades gama da Proteína de Ligação ao GTP , Proteínas de Plantas , Tolerância ao Sal , Sorghum , Produtos Agrícolas/genética , Produtos Agrícolas/fisiologia , Peróxido de Hidrogênio/metabolismo , Oryza/genética , Oryza/fisiologia , Estresse Oxidativo/genética , Melhoramento Vegetal , Salinidade , Álcalis/análise , Álcalis/toxicidade , Bicarbonato de Sódio/análise , Bicarbonato de Sódio/toxicidade , Carbonatos/análise , Carbonatos/toxicidade , Tolerância ao Sal/genética , Sorghum/genética , Sorghum/fisiologia , Subunidades gama da Proteína de Ligação ao GTP/genética , Subunidades gama da Proteína de Ligação ao GTP/fisiologia , Proteínas de Plantas/genética , Proteínas de Plantas/fisiologia , Aquaporinas/metabolismo , Produção Agrícola , Loci Gênicos , Solo/químicaRESUMO
This study explored the effects of Lactiplantibacillus plantarum (previously Lactobacillus plantarum) BW2013 on mucosal integrity and gut microbiota of mice with dextran sulfate sodium (DSS)-induced colitis. The results show that the clinical symptoms in DSS-modelled ulcerative colitis (UC) were improved by L. plantarum BW2013 via decreasing disease activity index scores and suppressing inflammatory cell infiltration. Furthermore, L. plantarum BW2013 decreased the levels of diamine oxidase activity, myeloperoxidase, and D-lactic acid. The mRNA expression of ZO-1, occludin, and claudin-1 was upregulated by L. plantarum BW2013, which also increased IL-10 and reduced TNF-α, IL-1ß, and IL-6 in the colon. 16S rDNA sequencing showed that L. plantarum BW2013 enhanced α-diversity. L. plantarum BW2013 upregulated significantly the abundance of unidentfied Lachnospiraceae, Lactococcus, Rikenella, Lactobacillus, and Odoribacter, which had an inhibitory effect on inflammation and a protective effect on the integrity of the mucosa. These results demonstrate that L. plantarum BW2013 alleviates DSS-modelled UC by protecting mucosal integrity and ameliorating the composition of gut microbiota.
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Colite Ulcerativa , Colite , Microbioma Gastrointestinal , Animais , Camundongos , Colite/induzido quimicamente , Colite Ulcerativa/induzido quimicamente , Colite Ulcerativa/metabolismo , Mucosa Intestinal/metabolismo , Modelos Animais de Doenças , Camundongos Endogâmicos C57BLRESUMO
Objective:To explore application of mixed teaching platform in the clinical practice teaching of the laboratory medicine in Children's hospitals.Methods:We constructed a mixed online and offline teaching platform based on the Laboratory Quality Management System (LQMS) in the Children's Hospital of Chongqing Medical University. The undergraduates from Batch 2016 ( n=15) and Batch 2018 ( n=12) of College of Laboratory Medicine of Chongqing Medical University were taken as control group and experimental group respectively. Traditional teaching method was adopted by the control group, and the mixed teaching method was adopted by the experimental group. The results of two groups' clinical practice assessment, rate of outstanding students (total score ≥ 90) and rate of satisfaction (score ≥ 90) were compared to evaluate the teaching effect. SPSS 17.0 was used to conduct t-test and Chi-square test. Results:The database of teaching platform includes 68 teaching cases, 198 pieces of courseware, 305 clinical cases and 3 036 atlases. The test bank has accumulated 4 657 tests, covering clinical laboratory, immunology, biochemistry, microbiology and blood transfusion. The results of students in experimental group were significantly better than those of the control group [the score of clinical practice assessment: (85.90±5.04) vs. (78.90±6.75)( P<0.05); rate of outstanding students: 33.3% (4/12) vs. 6.7% (1/15), P>0.05; rate of satisfaction: 86.7% (13/15) vs. 100.0% (12/12) ( P>0.05). Conclusion:The mixed online and offline teaching platform based on the LQMS is highly recognized by students and can significantly improve the effect of clinical practice teaching, which can provide typical medical case teaching at any time and make up for limited case type in children's hospital.
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Innate immunity is critical for the early detection and elimination of viral invasion. Extracellular signals are crucial for host resistance; however, how extracellular factors prepare the innate immunity for rapid antiviral response remains elusive. Here, we find that serum deprivation largely restricts the innate antiviral responses to RNA and DNA viruses. When serum is supplied, serine/threonine-protein kinase 38-like (STK38L), induced by serum response factor (SRF), phosphorylates IRF3 at Ser303, which prevents IRF3 from proteasome-mediated degradation in the rest state (non-infected), and ensures that enough IRF3 is called in the primed state (infected). STK38L-deficient mice exhibit compromised innate antiviral responses and elevated viral proliferation and mortality. Moreover, lysophosphatidic acid (LPA) or sphingosine 1-phosphate (S1P), the crucial activators of SRF, rescue immunosuppression caused by serum deprivation. These findings identify the SRF-STK38L-IRF3 axis as a novel mechanism that maintains the host in a pro-active state when not infected, which ensures the rapid immune response against virus.
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Antivirais , Vírus , Animais , Camundongos , Antivirais/farmacologia , Imunidade Inata , Fator Regulador 3 de Interferon/metabolismo , Fosforilação , Vírus/metabolismo , Proteínas Serina-Treonina Quinases/metabolismoRESUMO
Mild, convenient, and effective TBAI-catalyzed S-H and N-H insertion reactions of α-diazoesters with thiophenols and aromatic amines under metal-free conditions have been described, furnishing a straightforward and general platform for the synthesis of various thioethers and 2-amino-2-oxoacetates in moderate to excellent yields. Moreover, this strategy features simple operation, mild conditions, broad substrate scope, and easy scale-up.