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1.
PLoS One ; 15(3): e0230736, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32214380

RESUMO

Recent advances in single-molecule fluorescent imaging have enabled quantitative measurements of transcription at a single gene copy, yet an accurate understanding of transcriptional kinetics is still lacking due to the difficulty of solving detailed biophysical models. Here we introduce a stochastic simulation and statistical inference platform for modeling detailed transcriptional kinetics in prokaryotic systems, which has not been solved analytically. The model includes stochastic two-state gene activation, mRNA synthesis initiation and stepwise elongation, release to the cytoplasm, and stepwise co-transcriptional degradation. Using the Gillespie algorithm, the platform simulates nascent and mature mRNA kinetics of a single gene copy and predicts fluorescent signals measurable by time-lapse single-cell mRNA imaging, for different experimental conditions. To approach the inverse problem of estimating the kinetic parameters of the model from experimental data, we develop a heuristic optimization method based on the genetic algorithm and the empirical distribution of mRNA generated by simulation. As a demonstration, we show that the optimization algorithm can successfully recover the transcriptional kinetics of simulated and experimental gene expression data. The platform is available as a MATLAB software package at https://data.caltech.edu/records/1287.

2.
J Hazard Mater ; 392: 122478, 2020 Mar 05.
Artigo em Inglês | MEDLINE | ID: mdl-32193118

RESUMO

Microorganisms play a vital role in soil biochemical process in contaminated managed ecosystems. In the present study, a field investigation was conducted in farmland around an industrial intensive region contaminated with cadmium, and the changes of microbial assemblages in contaminated soils were assessed by 16S rRNA sequencing and the further statistical analysis. The results revealed obvious variations in microbial richness between referenced and contaminated soils, with Proteobacteri, Chloroflexi, Actinobacteria, Acidobacteria and Nitrospirae dominating the studied communities around the industrial intensive region. Redundancy analysis and Spearman correlation heatmap revealed that about 68.95 % of overall variation in microbial community composition was explained by soil physiochemical properties and Cd existence, among which pH, soil total phosphorus, total nitrogen, organic carbon (OC) and available Cd were identified as dominant factors. No significant difference was found in the similarities and Beta-diversity analysis among different groups. In conclusion, this study revealed the ecological effects of physiochemical parameters and Cd stress on the diversity and abundance of microbial communities, and these findings provided the detailed and integrated correlation between the main factors and microbial indexes in Cd contaminated farmland around the industrial intensive region.

3.
Adv Exp Med Biol ; 1248: 143-166, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32185710

RESUMO

Immunotherapy with checkpoint inhibitor has been successfully applied in treatment for multiple cancer types, especially for patients at advanced stage. However, response rate of this promising therapy is low, thus requiring biomarkers for precise medication to reduce the ineffective treatment. With multiple retrospective clinical studies, more and more candidate prognostic factors have been identified with possible mechanic explanation, including the basic clinical characteristics (e.g., age and gender), molecular features (e.g., PD-L1 expression and tumor mutation burden). After validation in independent patient cohorts with large sample size, several markers have been approved as companion biomarkers. However, validation and combinations of all the possible candidate biomarkers are still challenging to predict the treatment outcomes. In this chapter, we will summarize and introduce the prognostic factors and biomarkers for checkpoint inhibitor-based immunotherapy.

4.
Gen Physiol Biophys ; 39(1): 79-87, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-32039827

RESUMO

Glucose triggers glucagon-like peptide (GLP)-1 secretion from L cells involving several glucose sensors including sodium-glucose transporter (SGLT)1, glucose transporter (GLUT)2, and sweet taste receptors (STRs). This study investigated the effects of different glucose concentrations on GLP-1 secretion, intracellular concentrations of Ca2+ and cAMP, glucose uptake, and protein levels of SGLT1, GLUT2, and STRs in STC-1 cells. Low glucose (5.6 mM) increased GLP-1 secretion, intracellular Ca2+ concentration, and SGLT1 protein level compared with glucose-free group. GLP-1 secretion and intracellular Ca2+ concentration triggered by low glucose were inhibited by the SGLT1 inhibitor. GLP-1 secretion or intracellular Ca2+ concentration in high-glucose (25, 100, 200 mM) groups was significantly higher than that of low-glucose group. Elevation of cAMP level was observed in concentration-dependent manner, and decreased glucose uptake was observed in 100 or 200 mM glucose group. High glucose increased protein levels of STRs and GLUT2 in comparison to low-glucose group. GLP-1 secretion and intracellular levels of Ca2+ and cAMP triggered by high glucose were inhibited in the presence of the GLUT2 or STR inhibitor. These results suggest that SGLT1 is dominantly responsible for GLP-1 secretion triggered by low glucose, and that STRs and GLUT2 are involved in GLP-1 secretion induced by high glucose.


Assuntos
Células Enteroendócrinas , Linhagem Celular , Peptídeo 1 Semelhante ao Glucagon , Glucose
5.
J Reconstr Microsurg ; 2020 Feb 10.
Artigo em Inglês | MEDLINE | ID: mdl-32040964

RESUMO

BACKGROUND: Immunosuppression risks are a major concern with vascularized composite allotransplantation (VCA). As an emerging strategy, the antirejection role played by mesenchymal stem cells (MSCs) is receiving attention. However, the current literature reports are inconclusive regarding the robustness of the MSC monotherapy. Using a rat forelimb VCA model, this study tested the robustness of the immunomodulation efficacy of gingival-derived MSCs (GMSCs) and bone marrow-derived MSCs (BMMSCs). METHODS: Forelimbs were transplanted on pairs of major histocompatibility complex-incompatible rats (Wistar-Kyoto donor, Lewis [LEW] recipient). Twenty-four LEW rats were randomly divided into four groups, including control (no treatment) and three treatment groups: rapamycin (2 mg/kg/day for 28 days, postoperatively), BMMSC and GMSC, both of which received donor-derived stem cells administered intravenously on postoperative days (PODs) 0, 3, 7, and 14. Rejection was considered as 80% skin necrosis of the allograft. Microcomputed tomography (µCT) was performed to evaluate healing at osteosynthesis site. On POD 14, limbs from each group underwent histological analysis and rejection grading using the Banff system. RESULTS: Both BMMSC (15.0 days) and GMSC (14.7 days) treatment failed to prolong VCA survival in comparison with the control group (13.8 days; p > 0.050), while the rapamycin significantly delayed acute VCA rejection (24.5 days; p = 0.003). Micro-CT imaging revealed no gross visual difference across all groups. Histology revealed that the control group was most severely affected (grades III and IV) followed by MSC (grade II) and rapamycin (grade I). CONCLUSION: MSC monotherapy, both BMMSC and GMSC, did not inhibit rejection in our VCA model. Skin immunogenicity is an important issue in promoting rejection, and a concomitant immunosuppression regimen should be considered to prolong allograft survival.

6.
Ecotoxicol Environ Saf ; 192: 110294, 2020 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-32044601

RESUMO

Cadmium (Cd) and nickel (Ni) in soil have caused serious environmental problems and increased healthy risks to humans and biota, it is vital important and necessary to develop effective methods to resolve the combined contaminated problems. In this study, strains L5 and L6 with good heavy metal resistant and immobilizing capacities were isolated from Cd and Ni contaminated soil. Bacterial characteristic experiment illustrated that many functional groups (-OH, -NH2 and -COO et al.) were distributed on the surface of L5 and L6. Under the stress of heavy metals, bacterial appearances were distorted. The pot experiment indicated that the concentrations of HOAc-extractable Cd and Ni in soil reduced 6.26-15.33% and 13.31-19.53% with the inoculation of L5 and L6. In addition, the immobilization rates on Cd and Ni improved 61.27-128.50% and 23.69-39.66% with re-inoculation of strains L5 and L6 at 30 days, respectively. After inoculation of strains L5 and L6 for 60 days, the activities of FDA hydrolysis, acid phosphatase, urease, invertase and dehydrogenase in soil increased obviously. Furthermore, bacterial diversity indexes and community structure of soil were also improved. Thus, given the beneficial remediation effects of the isolated strains, L5 and L6 have great potentials for heavy metals contaminated soil remediation.

7.
J Hazard Mater ; 388: 122065, 2020 04 15.
Artigo em Inglês | MEDLINE | ID: mdl-31954306

RESUMO

Bioremediation of cadmium polluted soil using biochar (BC) and plant growth promotion bacteria (PGPB) have been widely concerned. In our study, a novel Cd immobilizing PGPB strain TZ5 was isolated based on the Cd immobilizing potential and plant growth promotion (PGP) traits. Further, changes of surface morphology and functional groups of TZ5 cells were observed after exposed to Cd2+ by SEM-EDS and FTIR analyses. Then, the strain TZ5 was successfully loaded on BC as biochemical composites material (BCM). Pot experiment indicated that the percentage of acetic acid-extractable Cd in BCM treatments significantly decreased by 11.34 % than control. Meanwhile, BCM significantly increased the dry weight of ryegrass by 77.78 %, and decreased the Cd concentration of ryegrass by 48.49 %, compared to control. Microbial counts and soil enzyme activities in rhizosphere were both significantly improved by BCM. Furthermore, the proportion of relative abundance of Bacillus genus was enhanced after treated by BCM, which indicated that the strain TZ5 was successfully colonized in the rhizosphere. This study provided a practical strategy for bioremediation of Cd contaminated soil.

8.
Int Immunopharmacol ; 80: 106152, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-31926447

RESUMO

Acute lung injury (ALI) is a devastating clinical disorder with a high mortality rate and for which there is no effective treatment. The main characteristic of ALI is uncontrolled inflammation, and macrophages play a critical role in the development of this disorder. Trametinib, an inhibitor of MAPK/ERK kinase (MEK) activity that possesses anti-inflammatory properties, has been approved for clinical use. Herein, the influence of trametinib and its underlying mechanism were investigated using a lipopolysaccharide (LPS)-induced murine ALI model. We found that trametinib treatment prevented the LPS-facilitated expression of proinflammatory mediators in macrophages, and this anti-inflammatory action was closely correlated with suppression of the MEK-ERK-early growth response (Egr)-1 pathway. Furthermore, trametinib treatment alleviated LPS-induced ALI in mice, and attenuated edema, proinflammatory mediator production, and neutrophil infiltration. Trametinib pretreatment also attenuated the MEK-ERK-Egr-1 pathway in lung tissues. In conclusion, these data demonstrate that trametinib pretreatment suppresses inflammation in LPS-activated macrophages in vitro and protects against murine ALI established by LPS administration in vivo through inhibition of the MEK-ERK-Egr-1 pathway. Therefore, trametinib might have therapeutic potential for ALI.

9.
J Cell Biochem ; 2020 Jan 06.
Artigo em Inglês | MEDLINE | ID: mdl-31904144

RESUMO

DNA damage checkpoints act as a supervisor by preventing the course of cell cycle upon DNA damage and keeping the steadiness of genome. Checkpoint kinase 1 (CHK1) cannot be ignore in the etiology of numerous human cancers including nasopharyngeal cancer (NPC). To discuss genetic polymorphisms of CHK1 rs492510 in the occurrence of NPC was our objective. Rs492510 polymorphism of CHK1 was genotyped in 684 patients with NPC and 823 cancer-free controls. We utilize logistic regression models to appraise the correlation of rs492510 and susceptibility of NPC. Comparative expression level about CHK1 in nasopharyngeal carcinoma tissues were determined by real-time polymerase chain reaction. And we made use of Dual-Luciferase Reporter Assay to assess the transcriptional ability of CHK1 with different rs492510 allele. Adjusting multivariate logistic regression based on age, sex, body mass index, smoking, and drinking status showed that CHK1 rs492510 GA + GG genotype carriers presented prominent higher risk in NPC (odds ratio = 1.376, 95% confidence interval: 1.087-1.742; P = .008). As a consequence, we revealed that CHK1 relative expression levels in NPC tissues was higher than rhinitis tissues. Besides, the expressions of CHK1 in rs492510 GA genotype carriers were higher compared with people in AA genotype. The G allele of rs492510 generated remarkable higher transcription activity of CHK1 vs A allele by luciferase reporter assay. Our study considered that single nucleotide polymorphism rs492510 could increase transcription activity of CHK1 with the functionality, contributing to the susceptibility of NPC.

10.
Chemosphere ; 242: 125251, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-31896185

RESUMO

A novel nano-composite material (CMC-FeS@HA) combining the advantages of humic acid (HA) and FeS was synthesized to remediate hexavalent chromium (Cr(VI)) contaminated soil along with chromium (Cr) resistant microflora. The characteristic analysis confirmed the successful synthesis of the nano-composite, which provided further mechanism evidence of its detoxification effect on polluted soil. Energy Dispersive System analysis proved the adsorption of the microbe consortium (MC) for Cr. After remediation, Cr(VI) in all treatments was dramatically reduced and the leachable Cr in soil treated by CMC-FeS@HA and MC decreased 89.14% compared with control. The result of BCR sequential extraction showed that Cr was stabilized, whose form changed to oxidizable and residual from HOAC-extractable. Besides, CMC-FeS@HA, as a sustained-release acid with high biocompatibility, could continuously decrease the pH of strongly alkaline soil and created a suitable micro-ecological environment for soil microorganisms. Moreover, CMC-FeS@HA dramatically improved soil physicochemical property, soil microbial activity (dehydrogenase, hydrolase, urease, and invertase activities), and soil microecological diversity. In total, this study provided a useful technology for soil remediation, which innovatively combined chemical remediation and microbial-remediation with a positive effect on soil quality, providing a good approach for the multiple technology combination in the environmental cause.


Assuntos
Cromo/análise , Recuperação e Remediação Ambiental/métodos , Poluentes do Solo/análise , Adsorção , Poluição Ambiental/análise , Substâncias Húmicas/análise , Oxirredução , Solo/química
11.
Environ Pollut ; 257: 113558, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31708284

RESUMO

A soil heavy metal decontamination system was developed based on the immobilization of bioavailable metal fraction by iron-biochar nano-complex (BC@Fe3O4) and the uptake by Chromium (Cr) hyperaccumulator Leersia hexandra (L. hexandra) under the assistance of metal resistant microbe consortium (MC). In this system, L. hexandra was able to accumulate 485.1-785.0 mg kg-1 in root and 147.5-297.2 mg kg-1 of Cr in its aerial part. With MC assistance, more Cr could be translocated to the aerial part of L. hexandra, which dramatically improved its remediation potential. Meanwhile, BC@Fe3O4 application decreased bioavailable Cr in soil and reduced soil toxicity, which contributed to soil microbial community adaption and L. hexandra performance under high level of Cr concentration (elevated microbial activity, decreased plant stress response, enhanced L. hexandra growth and accumulation) without negative influence on accumulation efficiency. Moreover, details of the possible mechanistic insight into metal removal were discussed, which indicated a negative correlation of the extractable Cr with soil microecology and hyperaccumulator performance. Furthermore, the resistant bacteria successfully altered soil microbial community, enhanced its diversity, which was in favor of the soil quality improvement.

12.
Chemosphere ; 242: 125164, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-31669989

RESUMO

Phytoremediation is an economical strategy to harvest cadmium (Cd) from contaminated soil, but the efficiency of phytoremediation was affected by many factors. This study investigated the potential of Serratia sp. K3 (K3) assisted with straw biogas residue (SBR) or leavening fertilizer (LF) on improving the Cd migration efficiency and micro-environment in soil-vetiveria zizanioides L. system. The results showed that the acid soluble Cd in soil was increased by 2.83-29.79% in treatments compared with control (CK). In addition, Cd accumulation in the roots and shoots of vetiveria zizanioides were significantly enhanced by the combination of K3 and SBR/LF. Especially, the translocation factor of Cd increased by 21.53-62.37% in groups with K3 compared with the groups without K3, correspondingly. Furthermore, SBR/LF effectively changed bacterial community structure, and improved bacterial abundance. Relative abundance of functional genes related with carbohydrate/energy/amino acid metabolism were increased in groups of SBRB/LFB rhizosphere compared with CK. These results provide insight into the change of phytoremediation efficiency and soil bacterial communities in the vetiveria zizanioides rhizosphere after inoculation. This study may provide a promising method for improving phytoremediation in Cd contaminated soil.


Assuntos
Cádmio/análise , Vetiveria/crescimento & desenvolvimento , Fertilizantes/análise , Serratia/crescimento & desenvolvimento , Microbiologia do Solo , Poluentes do Solo/análise , Bioacumulação , Biodegradação Ambiental , Cádmio/metabolismo , Vetiveria/metabolismo , Esterco/análise , Microbiota , Rizosfera , Serratia/metabolismo , Cogumelos Shiitake/química , Solo/química , Poluentes do Solo/metabolismo , Resíduos Sólidos/análise
13.
Neurobiol Dis ; 134: 104630, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31678404

RESUMO

Multiple sclerosis (MS) is a chronic autoimmune demyelinating disease characterized by the autoimmune attack of oligodendrocytes, leading to demyelination and progressive functional deficits. CXC chemokine receptor 2 (CXCR2) is recently reported to orchestrate the migration, proliferation and differentiation of oligodendrocyte precursor cells (OPCs), which implies its possible involvement in the demyelinating process. Here, we used a CXCR2 antagonist, compound 2, as a tool to investigate the role of CXCR2 in demyelination and the underlying mechanism. The primary cultured oligodendrocytes and cuprizone (CPZ)-intoxicated mice were applied in the present study. The results showed that compound 2 significantly promoted OPC proliferation and differentiation. In the demyelinated lesions of CPZ-intoxicated mice, vigorous OPC proliferation and myelin repair was observed after compound 2 treatment. Subsequent investigation of the underlying mechanisms identified that upon inhibition of CXCR2, compound 2 treatment upregulated Ki67, transcription factor 2 (Olig2) and Caspr expression, activated PI3K/AKT/mTOR signaling, ultimately promoted OPCs differentiation and enhanced remyelination. In conclusion, our results demonstrated that CXCR2 antagonism efficiently promoted OPC differentiation and enhanced remyelination in CPZ-intoxicated mice, supporting CXCR2 as a promising therapeutic target for the treatment of chronic demyelinating diseases such as MS.

14.
Cancer Immunol Immunother ; 69(1): 135-145, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31807878

RESUMO

Development of personalized cancer vaccines based on neoantigens has become a new direction in cancer immunotherapy. Two forms of cancer vaccines have been widely studied: tumor-associated antigen (including proteins, peptides, or tumor lysates)-pulsed dendritic cell (DC) vaccines and protein- or peptide-adjuvant vaccines. However, different immune modalities may produce different therapeutic effects and immune responses when the same antigen is used. Therefore, it is necessary to choose a more effective neoantigen vaccination method. In this study, we compared the differences in immune and anti-tumor effects between neoantigen-pulsed DC vaccines and neoantigen-adjuvant vaccines using murine lung carcinoma (LL2) candidate neoantigens. The enzyme-linked immunospot (ELISPOT) assay showed that 4/6 of the neoantigen-adjuvant vaccines and 6/6 of the neoantigen-pulsed DC vaccines induced strong T-cell immune responses. Also, 2/6 of the neoantigen-adjuvant vaccines and 5/6 of the neoantigen-pulsed DC vaccines exhibited potent anti-tumor effects. The results indicated that the neoantigen-pulsed DC vaccines were superior to the neoantigen-adjuvant vaccines in both activating immune responses and inhibiting tumor growth. Our fundings provide an experimental basis for the selection of immune modalities for the use of neoantigens in individualized tumor immunotherapies.


Assuntos
Antígenos de Neoplasias/imunologia , Vacinas Anticâncer/imunologia , Células Dendríticas/imunologia , Imunoterapia/métodos , Neoplasias/terapia , Adjuvantes Imunológicos/administração & dosagem , Animais , Antígenos de Neoplasias/metabolismo , Vacinas Anticâncer/administração & dosagem , Linhagem Celular Tumoral/transplante , Células Dendríticas/metabolismo , Células Dendríticas/transplante , Modelos Animais de Doenças , Feminino , Humanos , Imunogenicidade da Vacina , Camundongos , Neoplasias/imunologia , Linfócitos T/imunologia
15.
Clin Cancer Res ; 26(1): 256-264, 2020 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-31573954

RESUMO

PURPOSE: Treatment outcomes for childhood acute lymphoblastic leukemia (ALL) have improved steadily, but a significant proportion of patients still experience relapse due to drug resistance, which is partly explained by inherited and/or somatic genetic alternations. Recently, we and others have identified genetic variants in the ARID5B gene associated with susceptibility to ALL and also with relapse. In this study, we sought to characterize the molecular pathway by which ARID5B affects antileukemic drug response in patients with ALL. EXPERIMENTAL DESIGN: We analyzed association of ARID5B expression in primary human ALL blasts with molecular subtypes and treatment outcome. Subsequent mechanistic studies were performed in ALL cell lines by manipulating ARID5B expression isogenically, in which we evaluated drug sensitivity, metabolism, and molecular signaling events. RESULTS: ARID5B expression varied substantially by ALL subtype, with the highest level being observed in hyperdiploid ALL. Lower ARID5B expression at diagnosis was associated with the risk of ALL relapse, and further reduction was noted at ALL relapse. In isogenic ALL cell models in vitro, ARID5B knockdown led to resistance specific to antimetabolite drugs (i.e., 6-mercaptopurine and methotrexate), without significantly affecting sensitivity to other antileukemic agents. ARID5B downregulation significantly inhibited ALL cell proliferation and caused partial cell-cycle arrest. At the molecular level, the cell-cycle checkpoint regulator p21 (encoded by CDKN1A) was most consistently modulated by ARID5B, plausibly as its direct transcription regulation target. CONCLUSIONS: Our data indicate that ARID5B is an important molecular determinant of antimetabolite drug sensitivity in ALL, in part, through p21-mediated effects on cell-cycle progression.

16.
Clin Genet ; 97(1): 25-38, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31432497

RESUMO

DNA mismatch repair (MMR) status was considered to be a potential prognostic factor for colorectal cancer (CRC) but with conflicting reports, and varied in terms of TNM stages. Its relationship with prognosis in stage II-III CRC had not yet been systematically established. Therefore, we retrieved eligible studies published through May 2019, and screened out 51 studies that reported survival data (overall survival [OS] and/or disease-free survival [DFS]) in 28 331 CRC patients at stage II-III, totally 16.4% of whom were characterized as deficient MMR (dMMR). Significant associations of dMMR status were observed with longer OS (Hazard Ratio [HR] = 0.74, 95% CI: 0.68-0.82; P < .001), as well as DFS (HR = 0.67, 95% CI: 0.59-0.75, P < .001). However, dMMR patients received no statistically significant benefit from fluoropyrimidine-based treatment for either OS (HR = 0.84, 95%CI: 0.60-1.17; P = .31) or DFS (HR = 0.83, 95%CI: 0.60-1.15; P = .27), compared with that in proficient MMR (pMMR) patients for both OS (HR = 0.55, 95% CI: 0.43-0.71; P < .001) and DFS (HR = 0.60, 95% CI: 0.50-0.73; P < .001). Our analysis indicate that dMMR CRC patients at stage II-III had higher OS and DFS than pMMR ones, and fluoropyrimidine-based chemotherapy could improve survival in pMMR patients rather than dMMR ones.

17.
Appl Biochem Biotechnol ; 190(2): 660-673, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31422559

RESUMO

The loss of allograft from chronic damage is still the major risk that renal transplant recipients face today. Biomarkers for early detection of chronic damage are needed to improve the long-term graft survival. This study aimed to identify long non-coding RNA (lncRNA) biomarkers associated with chronic damage and graft loss after renal transplantation. Gene Expression Omnibus (GEO) datasets including GSE57387 (n = 101), GSE21374 (n = 282), and GSE25902 (n = 24) from three high-quality studies were analyzed. By repurposing the publicly available array-based data coupled with Affymetrix Human Exon 1.0 ST and Human U133 Plus 2.0 arrays, we obtained expression profiles of 11323 and 3383 lncRNAs in biopsies after renal transplantation, respectively. The logistic regression model and Cox regression model were applied to identify lncRNAs associated with chronic damage and graft survival. High AC093673.5 expression was identified as significantly associated with the three endpoints including chronic damage, progressive chronic histological damage, and graft failure across these three datasets. A six-lncRNA signature was created to predict renal allograft at risk of chronic damage with a high predictive ability (AUC = 0.94). Gene set enrichment analysis (GSEA) indicated that our lncRNA signature was related with allograft rejection and immunity. Our study highlights the importance of lncRNAs in chronic graft damage and allograft loss, supporting their potential role as prognosis biomarkers.

18.
Ann Surg Oncol ; 27(3): 703-715, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-31646453

RESUMO

BACKGROUND: The optimal surgical method for cT1N0 lung adenocarcinoma remains controversial. OBJECTIVE: The aim of this study was to evaluate the differences in clinical outcomes of sublobar resection and lobectomy for cT1N0 lung adenocarcinoma patients. METHODS: We included 1035 consecutive patients with cT1N0 lung adenocarcinoma who underwent surgery at our institute from January 2011 to December 2016. The surgical approach, either sublobar resection or lobectomy, was determined at the discretion of each surgeon. A propensity-matched analysis incorporating total tumor diameter, solid component diameter, consolidation-to-tumor (C/T) ratio, and performance status was used to compare the clinical outcomes of the sublobar resection and lobectomy groups. RESULTS: Sublobar resection and lobectomy were performed for 604 (58.4%; wedge resection/segmentectomy: 470/134) and 431 (41.6%) patients, respectively. Patients in the sublobar resection group had smaller total tumor diameters, smaller solid component diameters, lower C/T ratios, and better performance status. More lymph nodes were dissected in the lobectomy group. Patients in the sublobar resection group had better perioperative outcomes. A multivariable analysis revealed that the solid component diameter and serum carcinoembryonic antigen level are independent risk factors for tumor recurrence. After propensity matching, 284 paired patients in each group were included. No differences in overall survival (OS; p = 0.424) or disease-free survival (DFS; p = 0.296) were noted between the two matched groups. CONCLUSIONS: Sublobar resection is not inferior to lobectomy regarding both DFS and OS for cT1N0 lung adenocarcinoma patients. Sublobar resection may be a feasible surgical method for cT1N0 lung adenocarcinoma.

19.
J Hazard Mater ; 385: 121587, 2020 Mar 05.
Artigo em Inglês | MEDLINE | ID: mdl-31744727

RESUMO

Plant growth-promoting rhizobacteria (PGPR) assisted accumulator has been proposed as a phytoextraction method to clean cadmium (Cd) in contaminated soil, while the mechanisms were few studied regrading PGPR-soil-accumulator as an assemble. In this study, we revealed the possible mechanisms of the plant growth-promotion strain SNB6 on enhancing the Cd phytoextration of vetiver grass by the analysis of the whole genome of SNB6, soil biochemical properties and plant growth response. Results showed that SNB6 encoded numerous genes needed for Cd tolerance, Cd mobilization and plant growth promotion. SNB6 increased HOAc-extractable Cd that showed a positive correlation with Cd uptake in accumulator. In addition, SNB6 improved the biochemical activities (bioavailability of nutritional substances, bacterial count, soil respiration and enzyme activity) in rhizosphere soil. Moreover, the antioxidative enzymes activities of accumulator were significantly enhanced by SNB6. Consequently, SNB6 promoted Cd uptake and biomass of accumulator, thus enhancing the Cd phytoextraction. The maximum Cd extractions in root, stem and leaf reached to 289.47 mg/kg, 88.33 mg/kg and 59.38 mg/kg, respectively. Meanwhile, the total biomass of accumulator was increased by 9.68-45.99% in SNB6 treatment. These findings could be conducive to the understanding the mechanisms of PGPR on enhancing the Cd phytoextraction of accumulator.

20.
J Hazard Mater ; 386: 121628, 2020 Mar 15.
Artigo em Inglês | MEDLINE | ID: mdl-31744729

RESUMO

This study reported an efficient novel chromium reducing bacteria (Bacillus sp. CRB-B1) and investigated its removal mechanism. Bacillus sp. CRB-B1 could effectively reduce high level Cr(VI), under a wide range of shaking velocity (125-200 rpm), temperature (33-41 °C), pH (6-9). The co-existing ions Cd2+ and NO3- inhibited its Cr(VI) reduction capacity, while Cu2+ enhanced the reduction efficiency. In addition, Bacillus sp. CRB-B1 could reduce Cr(VI) using glucose and fructose as an electron donor. Micro-characterization analysis confirmed the Cr(VI) reduction and adsorption ability of Bacillus sp. CRB-B1. Cells degeneration result indicated that Cr(VI) removal was mainly bioreduction rather than biosorption. The cell-free suspension had a Cr(VI) removal rate of 68.5.%, which was significantly higher than that of cell-free extracts and cell debris, indicating Cr(VI) reduction mainly occurs extracellularly, and possibly mediated by extracellular reductase. The reduced Cr was mainly distributed in the extracellular suspension, and a small amount was accumulated in the cells. In conclusion, Bacillus sp. CRB-B1 was a highly efficient Cr(VI) reducing bacteria, which has potential in the remediation of Cr(VI)-containing water and soil.

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