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The link between type I IFN and adaptive immunity, especially T-cell immunity, in JDM still remained largely unclear. This study aimed to understand the effect of elevated type I IFN signaling on CD8+ T cell-associated muscle damage in juvenile dermatomyositis (JDM). This study used flow cytometry (FC) and RTâPCR were used to examine the circulating cell ratio and type I IFN response. And scRNA-seq was used to examine peripheral immunity in 6 active JDM patients, 3 stable JDM patients, 3 juvenile IMNM patients and 3 age-matched healthy children. In vivo validation experiments were conducted using a mouse model induced by STING agonists and an experimental autoimmune myositis model (EAM). In vitro experiments were conducted using isolated CD8+ T-cells from JDM patients and mice. We found that active JDM patients showed an extensive type I IFN response and a decreased CD8+ T-cell ratio in the periphery (P < 0.05), which was correlated with muscle involvement (P < 0.05). Both new active JDM patients and all active JDM patients showed decreased CD8+ TCM cell ratios compared with age and gender matched stable JDM patients (P < 0.05). Compared with new pediatirc systemic lupus erythematosus (SLE) patients, new active JDM patients displayed decreased CD8+ T-cell and CD8+ TCM cell ratios (P < 0.05). Active JDM patient skeletal muscle biopsies displayed an elevated type I IFN response, upregulated MHC-I expression and CD8+ T-cell infiltration, which was validated in EAM mice. sc-RNAseq demonstrated that type I IFN signalling is the kinetic factor of abnormal differentiation and enhances the cytotoxicity of peripheral CD8+ T cells in active JDM patients, which was confirmed by in vivo and in vitro validation experiments. In summary, the elevated type I IFN signalling affected the differentiation and function of CD8+ T cells in active JDM patients. Skeletal muscle-infiltrating CD8+ T cells might migrate from the periphery under the drive of type I IFN and increased MHC I signals. Therapies targeting autoantigen-specific CD8+ T cells may represent a potential new treatment direction.
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Autoantígenos , Linfócitos T CD8-Positivos , Dermatomiosite , Interferon Tipo I , Músculo Esquelético , Transdução de Sinais , Humanos , Linfócitos T CD8-Positivos/imunologia , Linfócitos T CD8-Positivos/metabolismo , Interferon Tipo I/metabolismo , Animais , Músculo Esquelético/imunologia , Músculo Esquelético/metabolismo , Músculo Esquelético/patologia , Camundongos , Transdução de Sinais/imunologia , Autoantígenos/imunologia , Feminino , Dermatomiosite/imunologia , Dermatomiosite/patologia , Dermatomiosite/metabolismo , Masculino , Criança , Modelos Animais de Doenças , Adolescente , Pré-EscolarRESUMO
BACKGROUND: Rice ratooning has traditionally been an important component of the rice cropping system in China. However, compared with the rice of the first harvest, few studies on factors effecting ratoon rice yield have been conducted. Because ratoon rice is a one-season rice cultivated using axillary buds that germinate on rice stakes and generate panicles after the first crop's harvest, its production is mainly affected by the growth of axillary buds. The objectives of this study were to evaluate the sprouting mechanism of axillary buds to improve the ratoon rice yield. RESULTS: First, we observed the differentiation and growth dynamics of axillary buds at different nodes of Shanyou 63, and found that they differentiated from bottom to top before the heading of the mother stem, and that they developed very slowly. After heading they differentiated from top to bottom, and the ones on the top, especially the top 2nd node, developed much faster than those at the other nodes. The average length and dry weight of the axillary buds were significantly greater than those at other nodes by the yellow ripe stage, and they differentiated into pistils and stamens by 6 d after the yellow ripe stage. The morphology of vegetative organs from regenerated tillers of Shanyou 63 also suggested the superior growth of the upper buds, which was regulated by hormones, in ratoon rice. Furthermore, a comprehensive proteome map of the rice axillary buds at the top 2nd node before and after the yellow ripe stage was established, and some proteins involved in steroid biosynthesis were significantly increased. Of these, four took part in brassinosteroid (BR) biosynthesis. Thus, BR signaling may play a role in the germination of axillary buds of ratoon rice. CONCLUSIONS: The data provide insights into the molecular mechanisms underlying BR signaling, and may allow researchers to explore further the biological functions of endogenous BRs in the germination of axillary buds of ratoon rice.
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Brassinosteroides/metabolismo , Flores/fisiologia , Germinação , Oryza/fisiologia , Transdução de SinaisRESUMO
OBJECTIVES: To compare the effectiveness of remineralizing agents in the prevention and reversal of white spot lesions (WSLs), which occur during fixed orthodontic treatment, through a systematic review and network meta-analysis. MATERIALS AND METHODS: We reviewed controlled randomized clinical trial (RCT) data querying nine databases combined with a manual search (last search date: March 10, 2020). Of 2273 identified studies, 36 RCTs were finally included. After study selection and data extraction, pair-wise and network meta-analyses were performed to analyze the effectiveness of remineralizing agents in the prevention and reversal of WSLs in the short term (≤ 3 months) and long term (> 3 months). The risk of bias was assessed based on the Cochrane guidelines. Statistical heterogeneity, inconsistencies, and cumulative ranking were also evaluated. RESULTS: In terms of WSL prevention, sodium fluoride (NaF) varnish had the highest cumulative ranking for the short-term decalcification index (99.3%); acidulated phosphate fluoride (APF) foam ranked first for long-term incidence (96.9%), followed by difluorosilane (Dfs) varnish and high-concentration fluoride toothpaste (HFT) (79.4% and 77.4%, respectively). In the reversal of WSLs, no significant difference was found among different agents or their combinations for the two available outcomes (short-term integrated fluorescence loss and short-term percentage of fluorescence loss). CONCLUSIONS: In the prevention of WSLs, APF foam showed the best remineralizing effectiveness in the long term (after debonding), followed by Dfs varnish and HFT. It is unclear whether remineralizing agents can effectively reverse WSLs based on the existing evidence. CLINICAL RELEVANCE: APF foam may be recommended as a remineralizing agent for preventing orthodontically induced WSLs. PROSPERO REGISTRATION NUMBER: CRD42019116852.
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Cárie Dentária , Remineralização Dentária , Cariostáticos/uso terapêutico , Cárie Dentária/prevenção & controle , Humanos , Metanálise em Rede , Cremes DentaisRESUMO
Bacteria form complex multicellular structures on solid surfaces known as biofilms, which allow them to survive in harsh environments. A hallmark characteristic of mature biofilms is the high-level antibiotic tolerance (up to 1,000 times) compared with that of planktonic cells. Here, we report our new findings that biofilm cells are not always more tolerant to antibiotics than planktonic cells in the same culture. Specifically, Escherichia coli RP437 exhibited a dynamic change in antibiotic susceptibility during its early-stage biofilm formation. This phenomenon was not strain specific. Upon initial attachment, surface-associated cells became more sensitive to antibiotics than planktonic cells. By controlling the cell adhesion and cluster size using patterned E. coli biofilms, cells involved in the interaction between cell clusters during microcolony formation were found to be more susceptible to ampicillin than cells within clusters, suggesting a role of cell-cell interactions in biofilm-associated antibiotic tolerance. After this stage, biofilm cells became less susceptible to ampicillin and ofloxacin than planktonic cells. However, when the cells were detached by sonication, both antibiotics were more effective in killing the detached biofilm cells than the planktonic cells. Collectively, these results indicate that biofilm formation involves active cellular activities in adaption to the attached life form and interactions between cell clusters to build the complex structure of a biofilm, which can render these cells more susceptible to antibiotics. These findings shed new light on bacterial antibiotic susceptibility during biofilm formation and can guide the design of better antifouling surfaces, e.g., those with micron-scale topographic structures to interrupt cell-cell interactions.IMPORTANCE Mature biofilms are known for their high-level tolerance to antibiotics; however, antibiotic susceptibility of sessile cells during early-stage biofilm formation is not well understood. In this study, we aim to fill this knowledge gap by following bacterial antibiotic susceptibility during early-stage biofilm formation. We found that the attached cells have a dynamic change in antibiotic susceptibility, and during certain phases, they can be more sensitive to antibiotics than planktonic counterparts in the same culture. Using surface chemistry-controlled patterned biofilm formation, cell-surface and cell-cell interactions were found to affect the antibiotic susceptibility of attached cells. Collectively, these findings provide new insights into biofilm physiology and reveal how adaptation to the attached life form may influence antibiotic susceptibility of bacterial cells.
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Antibacterianos/farmacologia , Biofilmes/efeitos dos fármacos , Escherichia coli/efeitos dos fármacos , Escherichia coli/fisiologia , Aderência Bacteriana/efeitos dos fármacos , Farmacorresistência Bacteriana , Testes de Sensibilidade MicrobianaRESUMO
Avulsion fracture of the ischial tuberosity (AFIT) is a rare adolescent sports injury. At present, there is no consensus on its therapeutic paradigm, but conservative treatment appears to be the predominate choice. Furthermore, the degree of fracture displacement (DFD) remains as an important factor in determining whether AFIT needs internal fixation. The aim of the present study was to review and update the injury mechanism, clinical manifestations, imaging examination, diagnosis and differential diagnosis, and treatment of AFIT. A literature search was performed on a variety of databases using text words, and the results were limited to the English language. This review provides an important reference for the diagnosis and treatment of AFIT. AFIT can be easily misdiagnosed. Therefore, a detailed medical history and imaging examination are crucial for a correct diagnosis and differential diagnosis. For the choice of treatment of AFIT, it is necessary to consider not only the size of the fracture and DFD, but also the long-term functional needs of the patient.
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Fixação Interna de Fraturas/métodos , Ísquio/lesões , Ísquio/cirurgia , Adolescente , Traumatismos em Atletas/diagnóstico , Diagnóstico Diferencial , Feminino , Fraturas Ósseas/cirurgia , Humanos , MasculinoRESUMO
Background: Evidence has suggested that microRNAs (miRNAs) may play an important role in the pathogenesis of psychiatric disorders (PDs), but the results remain inconclusive. We aimed to identify specific differentially expressed miRNAs and their overlapping miRNA expression profiles in schizophrenia (SZ), major depression disorder (MDD), and bipolar disorder (BD), the three major PDs. Methods: The literatures up to September 30, 2023 related to peripheral blood miRNAs and PDs were searched and screened from multiple databases. The differences in miRNA levels between groups were illustrated by the standardized mean difference (SMD) and 95% confidence interval (95% CI). Results: In total, 30 peripheral blood miRNAs were included in the meta-analysis, including 16 for SZ, 12 for MDD, and 2 for BD, each was reported in more than 3 independent studies. Compared with the control group, miR-181b-5p, miR-34a-5p, miR-195-5p, miR-30e-5p, miR-7-5p, miR-132-3p, miR-212-3p, miR-206, miR-92a-3p and miR-137-3p were upregulated in SZ, while miR-134-5p, miR-107 and miR-99b-5p were downregulated. In MDD, miR-124-3p, miR-132-3p, miR-139-5p, miR-182-5p, miR-221-3p, miR-34a-5p and miR-93-5p were upregulated, while miR-144-5p and miR-135a-5p were downregulated. However, we failed to identify statistically differentially expressed miRNAs in BD. Interestingly, miR-132-3p and miR-34a-5p were upregulated in both SZ and MDD. Conclusions: Our study identified 13 differentially expressed miRNAs in SZ and 9 in MDD, among which miR-132-3p and miR-34a-5p were upregulated in both SZ and MDD by systematically analyzing qualified studies. These miRNAs may be used as potential biomarkers for the diagnosis of SZ and MDD in the future. Systematic Review Registration: http://www.crd.york.ac.uk/PROSPERO, identifier CRD42023486982.
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Ulcerative colitis (UC) is a common chronic inflammatory disease that causes serious harm to human health. Probiotics have the effect of improving UC. This study evaluated the preventative potential of water-in-oil-in-water (W1/O/W2) emulsions containing both probiotics and fish oil on UC and associated anxiety-like behavior using a mice model. UC model was established in mice by administering dextran sulfate sodium salt (DSS). Free probiotics, probiotic-loaded emulsions, or fish oil and probiotic co-loaded emulsions were then orally administered to the mice. Various bioassays, histological studies, 16s rDNA gene sequencing, and behavioral experiments were conducted to assess changes in the intestinal environment, microbiota, and anxiety-like behavior of the mice. The fish oil and probiotic co-loaded emulsions significantly reduced the inflammatory response by enhancing tight junction protein secretion (ZO-1, Occludin, and Claudin-1), inhibiting pro-inflammatory factors (TNF-α, and IL-1ß), and promoting short-chain fatty acids (SCFAs) production. These emulsions also modified the gut microbiota by promoting beneficial bacteria and suppressing pathogenic bacteria, thereby restoring a balanced gut microbiota. Notably, the emulsions containing both probiotics and fish oil also ameliorated anxiety-like behavior in the mice. The co-delivery of probiotics and fish oil using W1/O/W2 emulsions has shown significant promise in relieving UC and its associated anxiety-like behavior. These findings provide novel insights into the development of advanced therapeutic strategies for treating UC.
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Colite Ulcerativa , Emulsões , Óleos de Peixe , Microbioma Gastrointestinal , Probióticos , Animais , Colite Ulcerativa/tratamento farmacológico , Colite Ulcerativa/induzido quimicamente , Emulsões/química , Probióticos/farmacologia , Óleos de Peixe/farmacologia , Camundongos , Microbioma Gastrointestinal/efeitos dos fármacos , Masculino , Modelos Animais de Doenças , Camundongos Endogâmicos C57BL , Água , Sulfato de Dextrana/efeitos adversos , HumanosRESUMO
BACKGROUND: Hexokinase I (HK1) is highly expressed in a variety of malignancies, regulates glycolytic pathway in cancer cells, and thus considered to be one of the promising molecular targets for cancer therapy. Nonetheless, the development of a specific inhibitor against HK1 remains elusive. PURPOSE: This study aims to elucidate the mechanism by which oridonin inhibits the proliferation and immune evasion of bladder cancer cells, specifically through the suppression of HK1. METHODS: To examine the mechanisms by which oridonin directly binds to cysteines of HK1 and inhibits bladder cancer growth, this study utilized a variety of methods. These included the Human Proteome Microarray, Streptavidin-agarose affinity assay, Biolayer Interferometry (BLI) ainding analysis, Mass Spectrometry, Cellular Thermal Shift Assay, Extracellular Acidification Rate measurement, and Xenotransplant mouse models. RESULTS: As indicated by our current findings, oridonin forms a covalent bond with Cys-813, located adjacently to glucose-binding domain of HK1. This suppresses the enzymatic activity of HK1, leading to an effective reduction of glycolysis, which triggers cell death via apoptosis in cells derived from human bladder cancer. Significantly, oridonin also inhibits lactate-induced PD-L1 expression in bladder cancer. Furthermore, pairing oridonin with a PD-L1 inhibitor amplifies the cytotoxicity of CD8+ T cells against bladder cancer. CONCLUSION: This research strongly suggests that oridonin serves as a covalent inhibitor of HK1. Moreover, it indicates that functional cysteine residue of HK1 could operate as viable targets for selective inhibition. Consequently, oridonin exhibits substantial potential for the evolution of anti-cancer agents targeting the potential therapeutic target HK1 via metabolism immunomodulation.
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Antineoplásicos , Diterpenos do Tipo Caurano , Neoplasias da Bexiga Urinária , Animais , Camundongos , Humanos , Linhagem Celular Tumoral , Neoplasias da Bexiga Urinária/tratamento farmacológico , Diterpenos do Tipo Caurano/farmacologia , Diterpenos do Tipo Caurano/química , Antineoplásicos/farmacologia , Proliferação de Células , ApoptoseRESUMO
BACKGROUND: Genomic variants outside of the canonical splicing site (±2) may generate abnormal mRNA splicing, which are defined as non-canonical splicing variants (NCSVs). However, the clinical interpretation of NCSVs in neurodevelopmental disorders (NDDs) is largely unknown. METHODS: We investigated the contribution of NCSVs to NDDs from 345,787 de novo variants (DNVs) in 47,574 patients with NDDs. We performed functional enrichment and protein-protein interaction analysis to assess the association between genes carrying prioritised NCSVs and NDDs. Minigene was used to validate the impact of NCSVs on mRNA splicing. FINDINGS: We observed significantly more NCSVs (p = 0.02, odds ratio [OR] = 2.05) among patients with NDD than in controls. Both canonical splicing variants (CSVs) and NCSVs contributed to an equal proportion of patients with NDD (0.76% vs. 0.82%). The candidate genes carrying NCSVs were associated with glutamatergic synapse and chromatin remodelling. Minigene successfully validated 59 of 79 (74.68%) NCSVs that led to abnormal splicing in 40 candidate genes, and 9 of the genes (ARID1B, KAT6B, TCF4, SMARCA2, SHANK3, PDHA1, WDR45, SCN2A, SYNGAP1) harboured recurrent NCSVs with the same variant present in more than two unrelated patients with NDD. Moreover, 36 of 59 (61.02%) NCSVs are novel clinically relevant variants, including 34 unreported and 2 clinically conflicting interpretations or of uncertain significance NCSVs in the ClinVar database. INTERPRETATION: This study highlights the common pathology and clinical importance of NCSVs in unsolved patients with NDD. FUNDING: The present study was funded by grants from the National Natural Science Foundation of China, China Postdoctoral Science Foundation, the Hunan Youth Science and Technology Innovation Talent Project, the Provincial Natural Science Foundation of Hunan, The Scientific Research Program of FuRong laboratory, and the Natural Science Project of the University of Anhui Province.
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Transtornos do Neurodesenvolvimento , Adolescente , Humanos , Mutação , Transtornos do Neurodesenvolvimento/genética , Splicing de RNA/genética , Éxons , RNA Mensageiro , Histona Acetiltransferases/genética , Proteínas de Transporte/genéticaRESUMO
BACKGROUND: Osteonecrosis of the humeral head is an uncommon subchondral bone disease with many etiologies, and there is currently no definite evidence to support an optimal surgical treatment plan. We report a case of surgical treatment of left humeral head necrosis. To the best of our knowledge, this is the youngest patient with non-drug-induced humeral head necrosis and the largest collapsed area. CASE PRESENTATION: The case involved a 16-year-old male who injured his left shoulder 1 year ago. The patient was admitted to the hospital because of shoulder pain after activity in the year following the injury. During the physical examination, the left glenohumeral joint space was tender, the pain was obvious when the shoulder joint was rotated and squeezed, and the active and passive range of motion was normal. X-ray, magnetic resonance imaging, and computed tomography + 3D computed tomography scans all showed subchondral osteonecrosis of the left humeral head. Left humeral head lesion removal and autologous osteochondral transplantation were performed, and the patient was followed up. CONCLUSION: Non-drug-induced humeral head necrosis is rare. Autologous osteochondral transplantation is currently one of the most mature and effective treatment methods. The short-term curative effect in this patient is satisfactory, but the patient is young and has a large collapsed area, so long-term follow-up is worthwhile.
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Osteonecrose , Articulação do Ombro , Masculino , Humanos , Adolescente , Cabeça do Úmero/diagnóstico por imagem , Cabeça do Úmero/cirurgia , Cabeça do Úmero/patologia , Articulação do Ombro/diagnóstico por imagem , Articulação do Ombro/cirurgia , Articulação do Ombro/patologia , Ombro/cirurgia , Osteonecrose/diagnóstico por imagem , Osteonecrose/etiologia , Osteonecrose/cirurgia , Resultado do Tratamento , Necrose/patologia , Amplitude de Movimento ArticularRESUMO
BACKGROUND: Light stimulation at a specific wavelength triggers various responses in insects and can be used for pest control. To develop efficient and ecofriendly photophysical pest control methods, the effects of green light on locomotion, growth (molting and eclosion) and reproduction in Nilaparvata lugens (Stål) (BPH), a major rice pest, were studied. Transcriptomics and transmission electron microscopy (TEM) were used to investigate the mechanisms involved. RESULTS: BPH adults showed disrupted daily locomotion patterns following green light treatment at night and exhibited abnormal locomotion peaks. Total 6-day locomotion of brachypterous adults was significantly greater than in the control group. The durations of growth stages 1-4 were all shorter under green light treatment than in the control, whereas the time from fourth molting to eclosion (stage 5) was significantly longer. When BPH adults under green light treatment began laying eggs, the egg hatching ratio (36.69%) was significantly lower than in the control (47.49%). Moreover, in contrast to the control, BPH molting and eclosion events tended to happen more at night. Transcriptome analysis proved that green light significantly affected the expression of genes involved in cuticular proteins, chitin deacetylase and chitinase, which are related to cuticular development. TEM observations confirmed abnormal cuticular development in nymph and adult BPHs (endocuticle, exocuticle and pore canals) under green light treatment. CONCLUSION: Green light treatment at night notably affected locomotion, growth and reproduction in BPH, thus providing a novel idea for controlling this pest. © 2023 Society of Chemical Industry.
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Hemípteros , Oryza , Animais , Hemípteros/fisiologia , Ninfa , ReproduçãoRESUMO
Aqueous probiotic suspensions were dispersed in an oil phase consisting of fish oil and medium chain triglycerides to form W1/O emulsions. These emulsions were then homogenized with an aqueous solution containing soybean protein isolate and sodium alginate to form W1/O/W2 emulsions. Fish oil was used to promote the growth of the probiotics and increase their ability to adhere to the intestinal mucosa. Sodium alginate increased the viscosity, stability, and probiotic encapsulation efficiency of the double emulsions, which was mainly attributed to its interactions with adsorbed soy proteins. The encapsulation efficiency of the probiotics in the double emulsions was relatively high (>96%). In vitro simulated digestion experiments showed that the double emulsions significantly increased the number of viable probiotics remaining after passing through the entire gastrointestinal tract. This study suggests that encapsulation of probiotics in double emulsions may increase their viability under gastrointestinal conditions, thereby enhancing their efficacy in functional foods.
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Óleos de Peixe , Probióticos , Emulsões , Água , Alginatos , Proteínas de SojaRESUMO
The diversity of root endophytic microorganisms, which is closely related to plant life activities, is known to vary with the plant growth stage. This study on the ratooning rice Jiafuzhan explored the diversity of the root endophytic bacteria and fungi and their dynamics during the plant life cycle. By sequencing the 16S ribosomal ribonucleic acid (16S rRNA) and internal transcribed spacer (ITS) genes, 12,154 operational taxonomic units (OTUs) and 497 amplicon sequence variants (ASVs) were obtained, respectively. The root endophytic microorganisms of rice in the seedling, tillering, jointing, heading, and mature stages of the first crop and at 13, 25, and 60 days after regeneration (at the heading, full heading, and mature stages of the second crop, respectively) were analyzed using diversity and correlation analyses. There were significant differences in the α-diversity and ß-diversity of root endophytic bacteria and fungi in the growth stage. Additionally, linear discriminant analysis (LDA) effect size (LEfSe) analysis revealed biomarker bacteria for each growth stage, but biomarker fungi did not exist in every stage. Moreover, the correlation analysis showed that the bacterial and fungal biomarkers interacted with each other. Furthermore, the nitrogen-fixing genus Bradyrhizobium existed in all growth stages. These findings indicate the pattern of root endophytic microorganisms of ratooning rice at different growth stages, and they provide new insights into the high yield of the second crop of ratooning rice (in light of the abundance of various bacteria and fungi).
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BACKGROUND: Although the aberrant activation of NOTCH1 pathway causes a malignant progression of renal cell carcinoma (RCC), the precise molecular mechanisms behind the potential action of pro-oncogenic NOTCH1/HES1 axis remain elusive. Here, we examined the role of tumor suppressive miR-138-2 in the regulation of NOTCH1-HES1-mediated promotion of RCC. METHODS: This study employed bioinformatics, xenotransplant mouse models, ChIP assay, luciferase reporter assay, functional experiments, real-time PCR and Western blot analysis to explore the mechanisms of miR-138-2 in the regulation of NOTCH1-HES1-mediated promotion of RCC, and further explored miR-138-2-containing combination treatment strategies. RESULTS: There existed a positive correlation between down-regulation of miR-138 and the aberrant augmentation of NOTCH1/HES1 regulatory axis. Mechanistically, HES1 directly bound to miR-138-2 promoter region and thereby attenuated the transcription of miR-138-5p as well as miR-138-2-3p. Further analysis revealed that miR-138-5p as well as miR-138-2-3p synergistically impairs pro-oncogenic NOTCH1 pathway through the direct targeting of APH1A, MAML1 and NOTCH1. CONCLUSIONS: Collectively, our current study strongly suggests that miR-138-2 acts as a novel epigenetic regulator of pro-oncogenic NOTCH1 pathway, and that the potential feedback regulatory loop composed of HES1, miR-138-2 and NOTCH1 contributes to the malignant development of RCC. From the clinical point of view, this feedback regulatory loop might be a promising therapeutic target to treat the patients with RCC.
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Carcinoma de Células Renais , Neoplasias Renais , MicroRNAs , Animais , Humanos , Camundongos , Carcinoma de Células Renais/genética , Carcinoma de Células Renais/metabolismo , Linhagem Celular Tumoral , Proliferação de Células , Regulação para Baixo , Regulação Neoplásica da Expressão Gênica , Neoplasias Renais/genética , Neoplasias Renais/metabolismo , MicroRNAs/genética , MicroRNAs/metabolismo , Receptor Notch1/genética , Receptor Notch1/metabolismo , Fatores de Transcrição HES-1/genética , Fatores de Transcrição HES-1/metabolismoRESUMO
Bacterial biofilms are formed on environmental surfaces and host tissues, and facilitate host colonization and antibiotic resistance by human pathogens. Bacteria often express multiple adhesive proteins (adhesins), but it is often unclear whether adhesins have specialized or redundant roles. Here, we show how the model biofilm-forming organism Vibrio cholerae uses two adhesins with overlapping but distinct functions to achieve robust adhesion to diverse surfaces. Both biofilm-specific adhesins Bap1 and RbmC function as a "double-sided tape": they share a ß-propeller domain that binds to the biofilm matrix exopolysaccharide, but have distinct environment-facing domains. Bap1 adheres to lipids and abiotic surfaces, while RbmC mainly mediates binding to host surfaces. Furthermore, both adhesins contribute to adhesion in an enteroid monolayer colonization model. We expect that similar modular domains may be utilized by other pathogens, and this line of research can potentially lead to new biofilm-removal strategies and biofilm-inspired adhesives.
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Vibrio cholerae , Humanos , Vibrio cholerae/metabolismo , Proteínas de Bactérias/metabolismo , Biofilmes , Adesinas Bacterianas , Polissacarídeos/químicaRESUMO
Studies in recent years have highlighted an elaborate crosstalk between T cells and bone cells, suggesting that T cells may be alternative therapeutic targets for the maintenance of bone homeostasis. Here, it is reported that systemic administration of low-dose staphylococcal enterotoxin C2 (SEC2) 2M-118, a form of mutant superantigen, dramatically alleviates ovariectomy (OVX)-induced bone loss via modulating T cells. Specially, SEC2 2M-118 treatment increases trabecular bone mass significantly via promoting bone formation in OVX mice. These beneficial effects are largely diminished in T-cell-deficient nude mice and can be rescued by T-cell reconstruction. Neutralizing assays determine interferon gamma (IFN-γ) as the key factor that mediates the beneficial effects of SEC2 2M-118 on bone. Mechanistic studies demonstrate that IFN-γ stimulates Janus kinase/signal transducer and activator of transcription (JAK-STAT) signaling, leading to enhanced production of nitric oxide, which further activates p38 mitogen-activated protein kinase (MAPK) and Runt-related transcription factor 2 (Runx2) signaling and promotes osteogenic differentiation. IFN-γ also directly inhibits osteoclast differentiation, but this effect is counteracted by proabsorptive factors tumor necrosis factor alpha (TNF-α) and interleukin 1 beta (IL-1ß) secreted from IFN-γ-stimulated macrophages. Taken together, this work provides clues for developing innovative approaches which target T cells for the prevention and treatment of osteoporosis.
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Pseudoligosita yasumatsui and Anagrus nilaparvatae are both egg parasitoids of the brown planthopper, Nilaparvata lugens (Stål) (BPH). In this study, we obtained a stable strain of P. yasumatsui reproduced via thelytoky through indoor rearing and screening. We assessed the parasitism capacity of this strain on eggs of N. lugens by comparing the parasitism preference and circadian rhythm of this strain to that of A. nilaparvatae, which is proved as the dominant egg parasitoid species of BPH in rice fields. The findings indicated that both egg parasitoids could parasitize fertilized and unfertilized BPH eggs, however, with a significant preference for fertilized eggs. The daily parasitization volume of P. yasumatsui was slightly higher than that of A. nilaparvatae. Both egg parasitoids preferred parasitizing 1-3-day-old BPH eggs, but the parasitism amount of 5-6-day-old BPH eggs by P. yasumatsui is higher than that by A. nilaparvatae. The parasitism events of both species of egg parasitoid wasps occurred primarily from 7:00-15:00 and the parasitism amount at night accounted for less than 15% of the total amount. The results indicate that this strain of P. yasumatsui reproduced via thelytoky could be valuable for rice planthopper control.
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Bacterial biofilms are communities of cells enclosed in an extracellular polymeric matrix in which cells adhere to each other and to foreign surfaces. The development of a biofilm is a dynamic process that involves multiple steps, including cell-surface attachment, matrix production, and population expansion. Increasing evidence indicates that biofilm adhesion is one of the main factors contributing to biofilm-associated infections in clinics and biofouling in industrial settings. This review focuses on describing biofilm adhesion strategies among different bacteria, including Vibrio cholerae, Pseudomonas aeruginosa, and Staphylococcus aureus. Techniques used to characterize biofilm adhesion are also reviewed. An understanding of biofilm adhesion strategies can guide the development of novel approaches to inhibit or manipulate biofilm adhesion and growth.
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The brown planthopper (BPH) is one of the main pests endangering rice yields. The development of rice varieties harboring resistance genes is the most economical and effective method of managing BPH. To identify new BPH resistance-related genes, a total of 123 rice varieties were assessed for resistance and durable resistance. Three varieties were immune, and nine were highly resistant to BPH. After whole-genome resequencing of all 123 varieties, 1,897,845 single nucleotide polymorphisms (SNPs) were identified. Linkage disequilibrium (LD) decay analysis showed that the average LD of the SNPs at 20 kb was 0.30 (r2) and attenuated to half value (~0.30) at a distance of about 233 kb. A genome-wide association study (GWAS) of durable resistance to BPH was conducted using the Fast-MLM model. One quantitative trait locus, identified on chromosome 2, included 13 candidate genes. Two candidate genes contained a leucine-rich repeat and CC-NBS-LRR or NB-ARC domains, which might confer resistance to pests or diseases. Interestingly, LOC_Os02g27540 was highly expressed and was induced by BPH; GWAS identified potential rice genes coding for durable resistance to BPH. This study helps to elucidate the mechanism of durable resistance to BPH in rice and provides essential genetic information for breeding and functional verification of resistant varieties.
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BACKGROUND: Nonconcentric reduction of hip posterior dislocation caused by the acetabular labrum rim fracture is rare. There has been very little study on the feasibility of arthroscopically treatment and medium and mid-term evaluation to this pathology. The objectives of the current study were: (1) Is the arthroscopically assisted technique feasible to this manage this injury? (2) What is the effectiveness of arthroscopic treatment for nonconcentric reduction of hip posterior dislocation caused by acetabular labrum rim fracture. HYPOTHESIS: Arthroscopically assisted procedure is an alternative treatment modality for nonconcentric reduction of hip posterior dislocation caused by acetabular labrum rim fracture. PATIENTS AND METHODS: Thirteen of 257 posterior hip dislocations who were admitted to our hospital from February 2008 to March 2017 were included: 9 males and 4 females, with an average age of 23.7 (15-36) years. All of them underwent hip posterior dislocation and nonconcentric reduction related to acetabular labrum rim fracture. All of them had arthroscopic reduction and fixation of the rim fracture. Visual Analogic Score (VAS) score, modified Harris score, Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) score and the last follow-up radiographs were analyzed respectively. Postoperative complication and the need for secondary operation were recorded during the process. RESULTS: The incidence rate of this pathology was nearly 5%. Twelve out of 13 patients were followed up for an average of 42 (range, 26-68) months. At the final follow-up, VAS score was decreased from 5.2±0.9 (range, 4.0-6.1) preoperatively to 0.5±0.5 (range, 0.0-1.0) (p<0.0001), modified Harris score and WOMAC score were increased statistically significant from 32±8 (range, 28-40) and 30±5 (range, 25-35) to 94±5 (range, 89-99) and 95±4 (range, 91-99) respectively (p<0.0001). All patients have had completely concentric reduction and returned to activities of daily life. There was not any hip arthroscopic complication such as sciatic nerve injury and intra-abdominal fluid extravasation. Besides, there were no aseptic necrosis and revision case. CONCLUSION: Arthroscopically assisted procedure is an alternative treatment modality for nonconcentric reduction of hip posterior dislocation caused by the acetabular labrum rim fracture without surgical dislocation procedure. Good clinical results can be achieved without any complications related to the surgical procedure. LEVEL OF EVIDENCE: Level IV, therapeutic case series.