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Messenger ribonucleic acid (mRNA) was discovered in 1961 as an intermediary for transferring genetic information from DNA to ribosomes for protein synthesis. The COVID-19 pandemic brought worldwide attention to mRNA vaccines. The emergency use authorization of two COVID-19 mRNA vaccines, BNT162b2 and mRNA-1273, were major achievements in the history of vaccine development. Lipid nanoparticles (LNPs), one of the most superior non-viral delivery vectors available, have made many exciting advances in clinical translation as part of the COVID-19 vaccine and therefore has the potential to accelerate the clinical translation of many gene drugs. In addition, due to these small size, biocompatibility and excellent biodegradability, LNPs can efficiently deliver nucleic acids into cells, which is particularly important for current mRNA therapeutic regimens. LNPs are composed cationic or pH-dependent ionizable lipid bilayer, polyethylene glycol (PEG), phospholipids, and cholesterol, represents an advanced system for the delivery of mRNA vaccines. Furthermore, optimization of these four components constituting the LNPs have demonstrated enhanced vaccine efficacy and diminished adverse effects. The incorporation of biodegradable lipids enhance the biocompatibility of LNPs, thereby improving its potential as an efficacious therapeutic approach for a wide range of challenging and intricate diseases, encompassing infectious diseases, liver disorders, cancer, cardiovascular diseases, cerebrovascular conditions, among others. Consequently, this review aims to furnish the scientific community with the most up-to-date information regarding mRNA vaccines and LNP delivery systems.
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Inherited non-hemolytic anemia is a group of rare bone marrow disorders characterized by erythroid defects. Although concerted efforts have been made to explore the underlying pathogenetic mechanisms of these diseases, the understanding of the causative mutations are still incomplete. Here we identify in a diseased pedigree that a gain-of-function mutation in toll-like receptor 8 (TLR8) is implicated in inherited non-hemolytic anemia. TLR8 is expressed in erythroid lineage and erythropoiesis is impaired by TLR8 activation whereas enhanced by TLR8 inhibition from erythroid progenitor stage. Mechanistically, TLR8 activation blocks annexin A2 (ANXA2)-mediated plasma membrane localization of STAT5 and disrupts EPO signaling in HuDEP2 cells. TLR8 inhibition improves erythropoiesis in RPS19+/- HuDEP2 cells and CD34+ cells from healthy donors and inherited non-hemolytic anemic patients. Collectively, we identify a gene implicated in inherited anemia and a previously undescribed role for TLR8 in erythropoiesis, which could potentially be explored for therapeutic benefit in inherited anemia.
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Anemia , Eritropoese , Receptor 8 Toll-Like , Humanos , Eritropoese/genética , Receptor 8 Toll-Like/metabolismo , Receptor 8 Toll-Like/genética , Feminino , Anemia/genética , Masculino , Linhagem , Eritropoetina/metabolismo , Eritropoetina/genética , Adulto , Transdução de Sinais , Mutação , Células Eritroides/metabolismo , Animais , Células Precursoras Eritroides/metabolismoRESUMO
Four vanillic acid-degrading bacterial strains, named LR5S13T, LR5S20, and M4R5S39T and LN1S58, were isolated from Kalidium cuspidatum rhizosphere and bulk soils, respectively. Phylogenetic analysis based on 16S rRNA gene as well as core genome revealed that LR5S13T and LR5S20 clustered closely with each other and with Halomonas ventosae Al12T, and that the two strains shared the highest similarities (both 99.3 %) with H. ventosae Al12T, in contrast, M4R5S39T and LN1S58 clustered together and with Halomonas heilongjiangensis 9-2T, and the two strains shared the highest similarities (99.4 and 99.2 %, respectively) with H. heilongjiangensis 9-2T. The average nucleotides identities based on BLAST (ANIb) and digital DNA-DNA hybridization (dDDH) values of strains LR5S13T to LR5S20, and M4R5S39T to LN1S58, were both higher than the threshold values for delineation of a species. The ANIb and dDDH values of the four strains to their closely relatives were lower than the threshold values. All four strains take phosphatidylethanolamine, phosphatidylglycerol, and diphosphatidylglycerol as the major polar lipids, Summed Feature 8, Summed Feature 3, and C16:0 as the major fatty acids. Based on the phylogenetic and phenotypic results, the four strains should be classified as two novel Halomonas species. Therefore, Halomonas rhizosphaerae sp. nov. (type strain LR5S13T = KCTC 8016T = CGMCC 1.62049T) and Halomonas kalidii (type strain M4R5S39T = KCTC 8015T = CGMCC 1.62047T) are proposed. The geographical distribution analysis based on 16S rRNA gene revealed that the two novel species are widely distributed across the globe, specifically in highly saline habits, especially in Central and Eastern Asia.
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Halomonas , Hidroxibenzoatos , Halomonas/genética , Fosfolipídeos , Análise de Sequência de DNA , Filogenia , RNA Ribossômico 16S/genética , Ácidos Graxos/análise , DNA , DNA Bacteriano/genética , Técnicas de Tipagem Bacteriana , Hibridização de Ácido NucleicoRESUMO
This prospective clinical investigation focused on the addition of venetoclax and decitabine to myeloablative conditioning regimens, targeting high-risk and elderly individuals undergoing allogeneic hematopoietic stem cell transplantation. In total, 19 patients were enrolled in the trial between December 2021 and February 2023, and their progress was monitored for a median follow-up period of 258 days, ranging from 35 to 544 days. In the initial regimen (n=11), venetoclax was administered at a dosage of 400 mg per day from day -14 to day -1, while in the modified regimen (n=8), it was administered from day -14 to day -5. Decitabine was orally administered at a dosage of 20mg/m2/day from day -7 to day -3. Grade 3/4 adverse events observed included hematological events, hypertension, infections, allergy, and increased amylase. In the entire cohort, the overall survival (OS) and relapse-free survival (RFS) rates at 6 months were 63% (95% CI, 45-89) and 63% (95% CI, 45-89), respectively. The non-relapse mortality (NRM) rate at 6 months was 37% (95% CI, 16-58), while the cumulative incidence of relapse (CIR) was 0. However, the incidence of grade II-IV acute graft-versus-host disease (aGVHD) and grade III-IV aGVHD within 100 days was found to be 31% (95% CI, 12-53) and 26% (95% CI, 9-47), respectively. These rates indicate a relatively high occurrence, making it less suitable to administer the regimen to elderly patients. Therefore, further high-quality studies are required to enhance the conditioning regimen specifically for high-risk and elderly patients diagnosed with myeloid neoplasms. Clinical trial registration: ChiCTR2100050272.
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Doença Enxerto-Hospedeiro , Transplante de Células-Tronco Hematopoéticas , Leucemia Mieloide Aguda , Transtornos Mieloproliferativos , Neoplasias , Humanos , Idoso , Decitabina , Estudos Prospectivos , Neoplasias/complicações , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Doença Enxerto-Hospedeiro/epidemiologia , Doença Enxerto-Hospedeiro/etiologia , Doença Enxerto-Hospedeiro/prevenção & controle , Transtornos Mieloproliferativos/complicações , Recidiva , Condicionamento Pré-Transplante/efeitos adversos , Leucemia Mieloide Aguda/complicações , BussulfanoRESUMO
Due to the unique and excellent biological, physical, and chemical properties of peptide hydrogels, their application in the biomedical field is extremely wide. The applications of peptide hydrogels are closely related to their unique responsiveness and excellent properties. However, its defects in mechanical properties, stability, and toxicity limit its application in the food field. In this review, we focus on the fabrication methods of peptide hydrogels through the physical, chemical, and biological stimulations. In addition, the functional design of peptide hydrogels by the incorporation with materials is discussed. Meanwhile, the excellent properties of peptide hydrogels such as the stimulus responsiveness, biocompatibility, antimicrobial properties, rheology, and stability are reviewed. Finally, the application of peptide hydrogel in the food field is summarized and prospected.
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Hidrogéis , Peptídeos , Hidrogéis/química , Peptídeos/química , Reologia , Tecnologia de AlimentosRESUMO
Purpose: Patients with hematological diseases are at high risk of carbapenem-resistant Enterobacteriaceae (CRE) infection, and CRE-related bloodstream infection (BSI) is associated with high mortality risk. Therefore, developing a predictive risk model for subsequent BSI in hematological patients with CRE isolated from perianal swabs could be used to guide preventive strategies. Methods: This was a single-center retrospective cohort study at a tertiary blood diseases hospital, including all hematological patients hospitalized from 10 October 2017 to 31 July 2021. We developed a predictive model using multivariable logistic regression and internally validated it using enhanced bootstrap resampling. Results: Of 421 included patients with CRE isolated from perianal swabs, BSI due to CRE occurred in 59. According to the multivariate logistic analysis, age (OR[odds ratio]=1.04, 95% CI[confidence interval]: 1.01-1.06, P=0.004), both meropenem and imipenem minimal inhibitory concentration (MIC) of the isolate from perianal swabs>8ug/mL (OR=5.34, 95% CI: 2.63-11.5, P<0.001), gastrointestinal symptoms (OR=3.67, 95% CI: 1.82-7.58, P<0.001), valley absolute neutrophil count (109/L)>0.025 (OR=0.07, 95% CI: (0.02-0.19, P<0.001) and shaking chills at peak temperature (OR=6.94, 95% CI: (2.60-19.2, P<0.001) were independently associated with CRE BSI within 30 days and included in the prediction model. At a cut-off of prediction probability ≥ 21.5% the model exhibited a sensitivity, specificity, positive predictive value and negative predictive value of 79.7%, 85.6%, 96.27% and 47.47%. The discrimination and calibration of the prediction model were good on the derivation data (C-statistics=0.8898; Brier score=0.079) and enhanced bootstrapped validation dataset (adjusted C-statistics=0.881; adjusted Brier score=0.083). The risk prediction model is freely available as a mobile application at https://liujia1992.shinyapps.io/dynnomapp/. Conclusion: A prediction model based on age, meropenem and imipenem MIC of isolate, gastrointestinal symptoms, valley absolute neutrophil count and shaking chills may be used to better inform interventions in hematological patients with CRE isolated from perianal swabs.
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BACKGROUND: Bacillus velezensis SW5, with good enzyme production ability, was isolated and identified in our laboratory from fermented fish sauce. Its galactosidase has been expressed in Escherichia coli, which could hydrolyze lactose in milk. The present study aims to express a novel serine protease gene (SPr-SW5) of this strain by Bacillus subtilis WB800N, and applies the expressed enzyme in hydrolysis of anchovy to prepare antioxidant substances, aiming to alleviate the waste of low-value fish resources. RESULTS: SPr-SW5 with the open reading frame of 1353 bp encodes a serine protease (SPr-SW5) with 450 amino acids. The theoretical molecular weight and isoelectric point are 47.2 kDa and 5.22, respectively. The successful expression of SPr-SW5 in B. subtilis WB800N was confirmed by a skim milk plate test. Its optimal temperature and pH were 50 °C and 8.0, respectively. SPr-SW5 activity was increased by Ca2+ and Zn2+ , but inhibited by Fe3+ . Furthermore, SPr-SW5 was tolerant to 1% Tween-40 and Tween-80; however, its activity was strongly inhibited by 10 mm phenylmethylsulfonyl fluoride. Additionally, SPr-SW5 could be capable of hydrolyzing anchovy, the hydrolysate (AHP) at 10 g L-1 , with 2,2-diphenyl-1-picrylhydrazyl and hydroxyl (·OH) scavenging rates of 73.21% and 79.71%, displaying good antioxidant activity. CONCLUSION: The novel SPr-SW5 was successfully expressed in B. subtilis WB800N. It exhibited excellent temperature stability and good tolerance to several metal ions. In addition, the anchovy hydrolyzed by expressed SPr-SW5 has good antioxidant ability. Overall, this research lays a good foundation for SPr-SW5 with respect to exploration and application in the food industry as enzyme preparation. © 2023 Society of Chemical Industry.
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Polissorbatos , Serina Proteases , Animais , Serina Proteases/química , Serina Proteases/metabolismo , Hidrólise , Antioxidantes , Serina Endopeptidases , Temperatura , Concentração de Íons de HidrogênioRESUMO
The treatment and surfactant recovery of soil washing/flushing effluent containing high levels of surfactants and organic pollutants are critical for the surfactant-assisted remediation of soils and waste management due to their complexity and high-potential risks. Combination of waste activated sludge material (WASM) and a kinetic-based two-stage system design was introduced in this study as a novel strategy for the separation of phenanthrene and pyrene from Tween 80 solutions. The results showed that WASM can effectively sorb phenanthrene and pyrene with high affinities (Kd) of 2325.5 L·kg-1 and 9911.2 L·kg-1, respectively. This allowed a high-level recovery of Tween 80 of 90.47 ± 1.86%, with selectivity of up to 69.7. In addition, a two-stage design was constructed, and the results showed an improved reaction time (approximately 5% of equilibrium time in conventional single-stage process) and increased the separation levels of phenanthrene or pyrene from Tween 80 solutions. For instance, the minimal total operating time for the sorption of 99% pyrene from 1.0 g·L-1 Tween 80 was only 23.0 min in the two-stage process compared to that of 480 min with a 71.9% removal level in the single-stage system. Results indicated that the combination of low-cost waste WASH and two-stage design was a high-efficiency and time-saving way to recover surfactants from soil washing effluents.
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Fenantrenos , Hidrocarbonetos Policíclicos Aromáticos , Poluentes do Solo , Tensoativos , Polissorbatos , Esgotos , Hidrocarbonetos Policíclicos Aromáticos/análise , Pirenos , Lipoproteínas , Solo , Poluentes do Solo/análiseRESUMO
Mastering nuclear fusion, which is an abundant, safe, and environmentally competitive energy, is a great challenge for humanity. Tokamak represents one of the most promising paths toward controlled fusion. Obtaining a high-performance, steady-state, and long-pulse plasma regime remains a critical issue. Recently, a big breakthrough in steady-state operation was made on the Experimental Advanced Superconducting Tokamak (EAST). A steady-state plasma with a world-record pulse length of 1056 s was obtained, where the density and the divertor peak heat flux were well controlled, with no core impurity accumulation, and a new high-confinement and self-organizing regime (Super I-mode = I-mode + e-ITB) was discovered and demonstrated. These achievements contribute to the integration of fusion plasma technology and physics, which is essential to operate next-step devices.
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Resveratrol has several functions, including protection of the heart and nervous system and exerts antidiabetic, anti-inflammatory, anti-aging, and antitumor effects. It is reported to impede the occurrence and development of tumors in cancer cell lines, animal models, and clinical studies. In vitro and in vivo experiments show that it exerts preventive or adjuvant therapeutic effects in pancreatic, colorectal, prostate, liver, and lung cancers. Mechanistic research reports show that resveratrol can induce tumor cell apoptosis and autophagy, inhibit cell cycle and angiogenesis, regulate nuclear factors and cyclooxygenase signal transduction pathways, and inhibit carcinogens' metabolic activation and alter tumor-related expression patterns; anti-oxidation affects tumor cell proliferation, metastasis, and apoptosis. However, the exact mechanism underlying its action remains unclear. This review highlights multiple aspects of the biological impacts and mechanisms underlying resveratrol action on the occurrence and development of lung cancer.
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Neoplasias Pulmonares , Estilbenos , Masculino , Animais , Resveratrol/farmacologia , Resveratrol/uso terapêutico , Transdução de Sinais , Anti-Inflamatórios/farmacologia , Proliferação de Células , Apoptose , Neoplasias Pulmonares/tratamento farmacológico , Linhagem Celular Tumoral , Estilbenos/farmacologia , Estilbenos/uso terapêuticoRESUMO
Lung adenocarcinoma (LUAD) is a malignant tumor that occurs in the lungs. Numerous reports have substantiated the participation of long non-coding RNAs (lncRNAs) in the tumorigenesis of LUAD. Previously, lncRNA alpha-2-macroglobulin antisense RNA 1 (A2M-AS1) was confirmed to be an important regulator in the biological processes of LUAD and dysregulation of A2M-AS1 was associated with non-small cell lung cancer (NSCLC) progression. However, the precise mechanism of A2M-AS1 in LUAD has not been elucidated. Therefore, our study was designed to investigate the detailed molecular mechanism of A2M-AS1 in LUAD. Herein, the expression of lncRNA A2M-AS1, microRNA (miRNA) miR-587, and bone morphogenetic protein 3 (BMP3) in LUAD cell lines and tissues were detected by real-time quantitative polymerase chain reaction (RT-qPCR) and western blotting. The viability, proliferation, migration and invasion of LUAD cells were tested by cell counting kit-8 (CCK-8), colony formation and Transwell assays. In vivo tumor growth was investigated by xenograft animal experiment. Interactions among A2M-AS1, miR-587 and BMP3 were measured by RNA pulldown and luciferase reporter assays. In this study, A2M-AS1 was downregulated in LUAD tissues and cells and related to poor prognosis in LUAD patients. A2M-AS1 overexpression suppressed LUAD cell proliferation, migration and invasion in vitro and inhibited tumor growth in vivo. Mechanistically, A2M-AS1 directly bound with miR-587 to promote BMP3 expression in LUAD cells. Low expression of BMP3 was found in LUAD tissues and cells and was closely correlated with poor prognosis in LUAD patients. BMP3 deficiency reserved the inhibitory influence of A2M-AS1 overexpression on LUAD cell behaviors. Overall, A2M-AS1 inhibits cell growth and aggressiveness via regulating the miR-587/BMP3 axis in LUAD.
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Adenocarcinoma de Pulmão , Proteína Morfogenética Óssea 3 , Neoplasias Pulmonares , MicroRNAs , RNA Longo não Codificante , alfa-Macroglobulinas , Animais , Humanos , Adenocarcinoma/genética , Adenocarcinoma/metabolismo , Adenocarcinoma/patologia , alfa-Macroglobulinas/genética , alfa-Macroglobulinas/metabolismo , Proteína Morfogenética Óssea 3/genética , Proteína Morfogenética Óssea 3/metabolismo , Carcinoma Pulmonar de Células não Pequenas/genética , Carcinoma Pulmonar de Células não Pequenas/metabolismo , Carcinoma Pulmonar de Células não Pequenas/patologia , Proliferação de Células/genética , Proliferação de Células/fisiologia , Pulmão/metabolismo , Pulmão/patologia , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/metabolismo , Neoplasias Pulmonares/patologia , MicroRNAs/genética , MicroRNAs/metabolismo , RNA Longo não Codificante/genética , RNA Longo não Codificante/metabolismo , Adenocarcinoma de Pulmão/genética , Adenocarcinoma de Pulmão/metabolismo , Adenocarcinoma de Pulmão/patologia , Invasividade Neoplásica/genética , Invasividade Neoplásica/fisiopatologia , Metástase Neoplásica/genética , Metástase Neoplásica/patologia , Metástase Neoplásica/fisiopatologia , Sobrevivência Celular/genética , Sobrevivência Celular/fisiologia , Progressão da DoençaRESUMO
Background: Esophageal cancer is the most prevalent digestive system tumor. Due to a lack of characteristic symptoms and early diagnosis, a confirmed esophageal cancer is typically detected at a progressively harmful stage. Therefore, it is critical to investigate the molecular mechanisms governing the formation and progression of esophageal cancer in order to identify new treatment targets for esophageal cancer early detection. Methods: We first screened the differentially expressed gene LINC00240 in the TCGA database. Multivariate analysis and Cox regression were performed, and a nomogram was constructed for internal validation. The correlation between LINC00240 and immune cells was analyzed using the TIMER database. The possible mechanism of action was explored through GSEA enrichment analysis. Then, in 43 esophageal cancer tissues, paracancour tissues, and cell lines, the LINC00240 expression was found. Transwell assays, CCK-8, and clone formation assays were utilized to assess the impact of LINC00240 on the metastasis of esophageal cancer cells. The binding activity of LINC00240 to downstream miRNAs was assessed using the luciferase reporter gene. Results: TCGA database showed that LINC00240 expression was increased in cancer tissues compared to adjacent tissues. The C-index of the nomogram is 0.712 (0.666-0.758), and the prediction model has good accuracy. According to the TIMER database, the LINC00240 expression is linked to immune infiltration and may be crucial in encouraging the immune escape of tumor cells. Gene enrichment analysis depicts that LINC00240 could influence the biological events of esophageal cancer by taking part in pathways such as affecting the cell cycle. LINC00240 expression was substantially greater in the plasma of esophageal cancer patients (3.94 ± 1.55) than in the normal control group (2.13 ± 0.89). Plasma expression of LINC00240 was linked to the degree of differentiation (P=0.0345) and TNM stage (P=0.0409). Knocked down LINC00240 inhibited esophageal cancer cells proliferation, lone formation, and invasion. LINC00240 might bind itself to miR-26a-5p and influence its expression. MiR-26a-5p inhibitor can dramatically limit the ability of LINC00240 knockdown on plate colony formation and relocation of esophageal cancerous cells was demonstrated in colony formation and migration experiments. Conclusion: LINC00240 expression is elevated in esophageal cancerous tissues, and knocking down LINC00240 decreases esophageal cancer cell proliferation, clone formation, invasion, and migration via miR-26a-5p. As a result, LINC00240 could be a novel target for esophageal cancer patients' early diagnosis and treatment.
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Neoplasias Esofágicas , MicroRNAs , RNA Longo não Codificante , Humanos , RNA Longo não Codificante/genética , RNA Longo não Codificante/metabolismo , Sincalida/genética , Sincalida/metabolismo , Linhagem Celular Tumoral , Neoplasias Esofágicas/genética , Neoplasias Esofágicas/patologia , MicroRNAs/genética , MicroRNAs/metabolismo , Proliferação de Células/genética , Movimento Celular/genética , Regulação Neoplásica da Expressão GênicaRESUMO
Lung adenocarcinoma (LUAD) is one of the most prevalent forms of lung cancer. Competitive endogenous RNA (ceRNA) plays an important role in the pathogenesis of lung cancer. Phosphatase and tensin homolog (PTEN) is one of the most frequently deleted tumour suppressor genes in LUAD. The present study aimed to identify a novel PTEN-associated-ceRNA regulatory network and identify potential prognostic markers associated with LUAD. Transcriptome sequencing profiles of 533 patients with LUAD were obtained from TCGA database, and differentially expressed genes (DEGs) were screened in LUAD samples with PTEN high- (PTENhigh) and low- (PTENlow) expression. Eventually, an important PTEN-related marker was identified, namely, the LINC00460/miR-150-3p axis. Furthermore, the predicted target genes (EME1/HNRNPAB/PLAUR/SEMA3A) were closely related to overall survival and prognosis. The LINC00460/miR-150-3p axis was identified as a clinical prognostic factor through Cox regression analysis. Methylation analyses suggested that abnormal regulation of the predicted target genes might be caused by hypomethylation. Furthermore, immune infiltration analysis showed that the LINC00460/miR-150-3p axis could alter the levels of immune infiltration in the tumour immune microenvironment, and promote the clinical progression of LUAD. To specifically induce PTEN deletion in the lungs, we constructed an STP mouse model (SFTPC-rtTA/tetO-cre/Ptenflox/+). Quantitative PCR (qPCR) and immunohistochemical (IHC) analysis were used to detect predicted target genes. Therefore, we revealed that the PTEN-related LINC00460/miR-150-3p axis based on ceRNA mechanism plays an important role in the development of LUAD and provides a new direction and theoretical basis for its targeted therapy.
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Hemorrhagic cystitis (HC) is a common complication of allogeneic hematopoietic stem cell transplantation (HSCT). The incidence is about 7% to 68%, and some patients have to suffer a long period of frequent, urgent, and painful urination, which brings great pain. This study aimed to analyze risk factors of HC and its effect on patient survival. We collected the medical records of 859 patients who underwent HSCT at our hospital between August 2016 and August 2020. Patients with and without HC were matched using propensity score matching at a 1:1 ratio based on sex, age, and diagnosis, and logistic regression analyses were used to identify factors associated with HC. We used Kaplan-Meier curves to analyze the survival rates of patients in the HC and non-HC groups. We also analyzed the relationship between BK viral load and the occurrence of HC using receiver operating characteristic curve (ROC) analysis. After propensity score matching, there were 131 patients each in the HC and non-HC groups. In the HC group, 89 patients (67.9%) had mild HC (stage II°) and 43 (32.1%) had severe HC (stage III-IV). The median interval between stem cell transplantation and HC development was 31 (3-244) days. Univariate analysis indicated that donor age, hematopoietic stem cell source, HLA, acute graft-versus-host disease, busulfan, anti-thymocyte globulin (ATG), total body irradiation, cytomegalovirus (CMV) (urine), and BK polyomavirus (BKV) (urine) were significantly associated with HC. ATG, CMV (urine), and BKV (urine) were independent risk factors for HC based on the multivariate analysis. The Kaplan-Meier survival analysis showed no significant difference between the HC and non-HC groups (Pâ=â.14). The 1- and 2-year survival rates in the HC group were 78.4% and 69.6%, respectively, and the corresponding rates in the non-HC group were 84.4% and 80.7%, respectively. ROC analysis indicated that a urine BKV load of 1â×â107âcopies/mL was able to stratify the risk of HC. In conclusion, when the BKV load is >1â×â107, we need to be aware of the potential for the development of HC.
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Nonimmune cells can have immunomodulatory roles that contribute to healthy development. However, the molecular and cellular mechanisms underlying the immunomodulatory functions of erythroid cells during human ontogenesis remain elusive. Here, integrated, single-cell transcriptomic studies of erythroid cells from the human yolk sac, fetal liver, preterm umbilical cord blood (UCB), term UCB and adult bone marrow (BM) identified classical and immune subsets of erythroid precursors with divergent differentiation trajectories. Immune-erythroid cells were present from the yolk sac to the adult BM throughout human ontogenesis but failed to be generated in vitro from human embryonic stem cells. Compared with classical-erythroid precursors, these immune-erythroid cells possessed dual erythroid and immune regulatory networks, showed immunomodulatory functions and interacted more frequently with various innate and adaptive immune cells. Our findings provide important insights into the nature of immune-erythroid cells and their roles during development and diseases.
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Células Precursoras Eritroides , Transcriptoma , Adulto , Diferenciação Celular/genética , Células Eritroides , Sangue Fetal , Humanos , Recém-Nascido , Saco VitelinoRESUMO
Two Gram-stain-positive, non-motile, strictly aerobic, yellow-coloured, rod-shaped bacterial strains, designated LR1S40T and M4N3S171T, were isolated from rhizosphere and bulk saline soil of Suaeda salsa collected in Inner Mongolia, China. Phylogenetic trees based on 16S rRNA gene and whole genome sequences showed that the two strains clustered tightly with strains of the genus Ruania. Strains LR1S40T and M4N3S171T had 95.5% 16S rRNA gene similarity to each other, and strain LR1S40T had 98.8, 98.7, 97.4 and <97.0% similarity to Ruania alkalisoli RN3S43T, Ruania rhizosphaerae LNNU 22110T, Ruania alba YIM 93306T and all other current type strains, while strain M4N3S171T had 98.6 and <97.0% similarity to R. alba YIM 93306T, and all other current type strains, respectively. The average nucleotide identity based on blast (ANIb) and digital DNA-DNA hybridization (dDDH) values of LR1S40T and M4N3S171T with each other and to the other type strains of Ruania were well below the threshold values (95% for ANIb, 70% for dDDH) for differentiating a species. Diphosphatidylglycerol and phosphatidylglycerol were the major polar lipids in both strains. The predominant menaquinone in both strains was both MK-8. The genome of strain LR1S40T consisted of a 3557440 bp circular chromosome, with a G+C content of 71.1 mol%, while the genome of strain M4N3S171T consisted of 4270413 bp, with a G+C content of 67.6 mol%. The phylogenetic, physiological and phenotypic characteristics allowed discrimination of the two strains from their relatives. The names Ruania suaedae sp. nov. [type strain LR1S40T (=CGMCC 1.19028T=KCTC 49726T)] and Ruania halotolerans sp. nov. [type strain M4N3S171T (=CGMCC 1. 19142T=KCTC 49727T)] are therefore proposed. During the publication of Haloactinobacterium kanbiaonis, Haloactinobacterium glacieicola (type strain T3246-1T), which was selected as the reference strain for the identification of H. kanbiaonis, was reclassified as Occultella glacieicola. The two phylogenetic trees showed that H. kanbiaonis HY164T tightly clustered with Occultella aeris F300T, and had the highest 16S rRNA gene similarity (99.8%) to O. aeris F300T. Based on the phylogenetic analysis and the publication record, Haloactinobacterium kanbiaonis should be reclassified as Occultella kanbiaonis comb. nov.
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Actinobacteria , Técnicas de Tipagem Bacteriana , Composição de Bases , DNA Bacteriano/genética , Ácidos Graxos/química , Fosfolipídeos , Filogenia , RNA Ribossômico 16S/genética , Análise de Sequência de DNA , SoloRESUMO
Three strains of members of the family Bacillaceae, which can inhibit the growth of some Gram-stain-positive strains, designated M4U3P1T, HD4P25T and RD4P76T, were isolated from Suaeda salsa halophytes in Baotou, Inner Mongolia, PR China. A phylogenetic analysis based on the 16S rRNA gene and the whole genome sequences revealed that HD4P25T clustered with Cytobacillus luteolus YIM 93174T with a similarity of 98.4â%, and RD4P76T shared the highest similarity of 16S rRNA gene with Bacillus mesophilus SA4T (97.5â%). M4U3P1T clustered with strains of genera Salipaludibacillus and Alkalicoccus based on whole-genome sequence analyses, but its 16S rRNA gene had the highest similarity to 'Evansella tamaricis' EGI 80668 (96.1â%). The average nucleotide's identity by blast (ANIb) and digital DNA-DNA hybridization (dDDH) values of the three isolated strains to their close relatives were well below the threshold value for identifying a novel species.On the basis of the phylogenetic, physiological and phenotypic results, Paenalkalicoccus suaedae gen. nov., sp. nov. [type strain M4U3P1T (=CGMCC 1.17076T=JCM 33851T)], Cytobacillus suaedae sp. nov. [type strain HD4P25T (=CGMCC 1.18651T =JCM 34524T)], and Bacillus suaedae sp. nov. [type strain RD4P76T (=CGMCC 1.18659T=JCM 34525T)] were proposed, respectively. All three species are ubiquitous in the bulk saline-alkaline soils, but only the species represented by strain RD4P76T was widely distributed in the rhizosphere soil, the above-ground part and the roots of S. salsa. The species represented by M4U3P1T can be detected in the roots of S. salsa, and rarely detected in the above-ground parts of S. salsa. The species represented by HD4P25T was rarely detected in the interior of S. salsa. The three strains could inhibit some of the Gram-stain-positive bacteria (i.e. members of the genera Planococcus, Zhihengliuella and Sanguibacter) in the saline-alkali soil. A genomic analysis of these three strains revealed that they can synthesize different antagonistic compounds, such as aminobenzoate and bacitracin or subtilisin.
Assuntos
Bacillaceae , Bacillus , Chenopodiaceae , Bacillaceae/genética , Bacillus/genética , Técnicas de Tipagem Bacteriana , Composição de Bases , Chenopodiaceae/microbiologia , DNA Bacteriano/genética , Ácidos Graxos/química , Fosfolipídeos , Filogenia , RNA Ribossômico 16S/genética , Plantas Tolerantes a Sal , Análise de Sequência de DNA , SoloRESUMO
Ribosomal protein dysfunction causes diverse human diseases, including Diamond-Blackfan anemia (DBA). Despite the universal need for ribosomes in all cell types, the mechanisms underlying ribosomopathies, which are characterized by tissue-specific defects, are still poorly understood. In the present study, we analyzed the transcriptomes of single purified erythroid progenitors isolated from the bone marrow of DBA patients. These patients were categorized into untreated, glucocorticoid (GC)-responsive and GC-non-responsive groups. We found that erythroid progenitors from untreated DBA patients entered S-phase of the cell cycle under considerable duress, resulting in replication stress and the activation of P53 signaling. In contrast, cell cycle progression was inhibited through induction of the type 1 interferon pathway in treated, GC-responsive patients, but not in GC-non-responsive patients. Notably, a low dose of interferon alpha treatment stimulated the production of erythrocytes derived from DBA patients. By linking the innately shorter cell cycle of erythroid progenitors to DBA pathogenesis, we demonstrated that interferon-mediated cell cycle control underlies the clinical efficacy of glucocorticoids. Our study suggests that interferon administration may constitute a new alternative therapeutic strategy for the treatment of DBA. The trial was registered at www.chictr.org.cn as ChiCTR2000038510.