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1.
J Hazard Mater ; 421: 126707, 2022 01 05.
Artigo em Inglês | MEDLINE | ID: mdl-34315018

RESUMO

Triclosan (TCS) is an antimicrobial ingredient that has been widely incorporated in consumer products. TCS can cause hepatic damage by disturbing lipid metabolism, which is often accompanied with gut microbiota dysbiosis. However, the effects of gut microbiota on the TCS-induced liver injury are still unknown. Therefore, we constructed a mouse model based on five-week-old male C57BL/6 mice to investigate the effects of dietary TCS exposure (40 ppm) on liver injury. We found that TCS treatment for 4 weeks dramatically disturbed gut microbiota homeostasis, resulting in overproduction of lipopolysaccharides (LPS) and deficiency of secondary bile acids such as deoxycholic acid (DCA) and lithocholic acid (LCA). In addition, TCS considerably increased intestinal permeability by reducing mucus excretion and expression of tight junction proteins (ZO-1, occludin and claudin 4), which facilitated translocation of LPS. The LPS accumulation in blood contributed to liver injury by triggering the inflammatory response via TLR4 pathway. In summary, this study provides novel insights into the underlying mechanisms of TCS-associated liver injury induced by gut microbiota via the gut-liver axis, and contributes to better interpretation of the health impact of the environmentally emerging contaminant TCS.


Assuntos
Doença Hepática Crônica Induzida por Substâncias e Drogas , Microbioma Gastrointestinal , Triclosan , Animais , Fígado , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Triclosan/toxicidade
2.
Bioact Mater ; 8: 478-493, 2022 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-34541414

RESUMO

Vascular calcification (VC) is a common characteristic of aging, diabetes, chronic renal failure, and atherosclerosis. The basic component of VC is hydroxyapatite (HAp). Nano-sized HAp (nHAp) has been identified to play an essential role in the development of pathological calcification of vasculature. However, whether nHAp can induce calcification in vivo and the mechanism of nHAp in the progression of VC remains unclear. We discovered that nHAp existed both in vascular smooth muscle cells (VSMCs) and their extracellular matrix (ECM) in the calcified arteries from patients. Synthetic nHAp had similar morphological and chemical properties as natural nHAp recovered from calcified artery. nHAp stimulated osteogenic differentiation and accelerated mineralization of VSMCs in vitro. Synthetic nHAp could also directly induce VC in vivo. Mechanistically, nHAp was internalized into lysosome, which impaired lysosome vacuolar H+-ATPase for its acidification, therefore blocked autophagic flux in VSMCs. Lysosomal re-acidification by cyclic-3',5'-adenosine monophosphate (cAMP) significantly enhanced autophagic degradation and attenuated nHAp-induced calcification. The accumulated autophagosomes and autolysosomes were converted into calcium-containing exosomes which were secreted into ECM and accelerated vascular calcium deposit. Inhibition of exosome release in VSMCs decreased calcium deposition. Altogether, our results demonstrated a repressive effect of nHAp on lysosomal acidification, which inhibited autophagic degradation and promoted a conversion of the accumulated autophagic vacuoles into exosomes that were loaded with undissolved nHAp, Ca2+, Pi and ALP. These exosomes bud off the plasma membrane, deposit within ECM, and form calcium nodules. Vascular calcification was thus accelerated by nHAP through blockage of autophagic flux in VSMCs.

3.
J Hazard Mater ; 422: 126844, 2022 01 15.
Artigo em Inglês | MEDLINE | ID: mdl-34399210

RESUMO

The transmission of airborne antibiotic resistance genes (ARGs) loaded on particle is a significant global public health concern. Up to date, the dispersal pattern of airborne ARGs remains unclear despite their critical role in multiregional transmission. In this study, airborne ARGs loaded on fine particulate matter (PM2.5) and source tracking based on the airflow trajectories were performed by the potential source contribution function (PSCF) and concentration weighted trajectory (CWT) model. The results show that the absolute abundance of ARG subtypes were generally twice times higher in the winter season than that in the summer season, which could be attributable to winter haze events with high particulate matter concentrations in Handan. Exogenous input from serious haze events and local release of ARGs loaded on PM2.5 of air masses may cause higher levels of ARGs in the winter. Moreover, based on the positive correlation between the abundance of ARGs and PM2.5 concentration, a source tracing model of airborne ARGs was proposed to the estimate of ARGs release and dissemination. This study highlights airborne ARGs transmission loaded on PM2.5 of air masses, which facilitating the global spread of antibiotic resistance.

4.
J Hazard Mater ; 423(Pt A): 127055, 2022 Feb 05.
Artigo em Inglês | MEDLINE | ID: mdl-34523494

RESUMO

Nitrated energetics are widespread contaminants due to their improper disposal from ammunition facilities. Different classes of nitrated energetics commonly co-exist in ammunition wastewater, but co-removal of the classes has hardly been documented. In this study, we evaluated the catalytic destruction of three types of energetics using palladium (Pd0) nano-catalysts deposited on H2-transfer membranes in membrane catalyst-film reactors (MCfRs). This work documented nitro-reduction of 2,4,6-trinitrotoluene (TNT), as well as, for the first time, denitration of hexahydro-1,3,5-trinitro-1,3,5-triazine (RDX) and pentaerythritol tetranitrate (PETN) over Pd0 at ambient temperature. The catalyst-specific activity was 20- to 90-fold higher than reported for other catalyst systems. Nitrite (NO2-) released from RDX and PETN also was catalytically reduced to dinitrogen gas (N2). Continuous treatment of a synthetic wastewater containing TNT, RDX, and PETN (5 mg/L each) for more than 20 hydraulic retention times yielded removals higher than 96% for all three energetics. Furthermore, the concentrations of NO2- and NH4+ were below the detection limit due to subsequent NO2- reduction with > 99% selectivity to N2. Thus, the MCfR provides a promising strategy for sustainable catalytic removal of co-existing energetics in ammunition wastewater.

5.
J Hazard Mater ; 423(Pt B): 127220, 2022 Feb 05.
Artigo em Inglês | MEDLINE | ID: mdl-34844350

RESUMO

The development of antimicrobial resistance (AMR) is accelerated by the selective pressure exerted by the widespread use of antimicrobial drugs, posing an increasing danger to public health. However, long-term spatiotemporal variation in AMR genes in microorganisms, particularly in bacterial pathogens in response to antibiotic consumption, is not fully understood. Here, we used the NCBI RefSeq database to collect 478 whole-genome sequences for Serratia marcescens ranging from 1961 up to 2019, to document global long-term AMR trends in S. marcescens populations. In total, 100 AMR gene subtypes (16 AMR gene types) were detected in the genomes of S. marcescens populations. We identified 3 core resistance genes in S. marcescens genomes, and a high diversity of AMR genes was observed in S. marcescens genomes after corresponding antibiotics were discovered and introduced into clinical practice, suggesting the adaptation of S. marcescens populations to challenges with therapeutic antibiotics. Our findings indicate spatiotemporal variation of AMR genes in S. marcescens populations in relation to antibiotic consumption and suggest the potential transmission of S. marcescens isolates harboring AMR genes among countries and between the environment and the clinic, representing a public health threat that necessitates international solidarity to overcome.

6.
Talanta ; 238(Pt 1): 122992, 2022 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-34857325

RESUMO

High specific selectivity is the continuous goal of exploit glycoprotein-imprinted materials. Boronate-affinity-oriented surface imprinting can limit the heterogeneity of imprinted cavities, and PEGylation can reduce the nonspecific adsorption of imprinted materials towards non-target molecules. However, there are no reports on the integration of the above two advantages. Herein, we first integrated the boronate-affinity-oriented surface imprinting and PEGylation, and fabricated PEGylated boronate-affinity-oriented surface imprinting magnetic nanoparticles (PBSIMN) with horseradish peroxidase (HRP) as a model glycoprotein template. The successful synthesis of PBSIMN was demonstrated in detail by various characterization. Compared with non-PEGylated control, the PBSIMN showed greater adsorption capacity for HRP, and faster adsorption rate. To evaluate the improved performance, the PBSIMN was linked with hydrophilic boronic acid-modified/fluorescein isothiocyanate-loaded graphene oxide (BFGO), and used for the detection of HRP in real samples. Because PEGylation led to decrease of non-specific binding on PBSIMN, the proposed strategy provided ultrahigh sensitivity with limit of detection of 6.0 fg mL-1 for HRP, which were an order of magnitude lower than the non-PEGylated counterparts. When spiked with 0.05, 0.5 and 5.0 mg mL-1, recoveries of HRP were in the range of 97.4%-101.8% with relative standard deviation (RSD) no more than 5.4% for mouse serum, and between 98.2% and 103.2% with RSD no more than 5.0% human serum. This work indicates that the boronate-affinity-oriented surface imprinting and PEGylation can improve the performance of imprinted materials.

7.
Artigo em Inglês | MEDLINE | ID: mdl-34850344

RESUMO

Effluent from wastewater treatment plants (WWTP) is an important source of organophosphate esters (OPEs) in the receiving rivers. In this paper, the concentration and distribution of seven OPEs in the water samples were determined, and the discharge was estimated. The results showed that the total removal rate of Σ7OPEs in water phase in WWTP was 57.2%. The average concentrations of Σ7OPEs in influent and effluent of the WWTP during rainy period were 3956.1 ± 1897.3 ng/L and 1461.9 ± 846.3 ng/L, respectively, which were about 4 times larger than those in influent water (978.2 ± 166.5 ng/L) and effluent (418.3 ± 12.0 ng/L) during non-rainy period, indicating that rainfall has a marked impact on the load of OPEs in WWTP and the receiving water. It was estimated that the average daily discharge of Σ7OPEs in the effluent of WWTP was 157.9 g, and the daily per capita contribution of the population in the area to the OPEs in the influent was 0.414 mg. During the shift of labour-intensive manufacturing from the coastal developed areas to inland regions, OPEs were widely used and produced in Southwest China. The total amount of OPEs emissions and its control should be taken into consideration.

8.
Brief Bioinform ; 2021 Nov 30.
Artigo em Inglês | MEDLINE | ID: mdl-34850817

RESUMO

Vaccines have made gratifying progress in preventing the 2019 coronavirus disease (COVID-19) pandemic. However, the emergence of variants, especially the latest delta variant, has brought considerable challenges to human health. Hence, the development of robust therapeutic approaches, such as anti-COVID-19 drug design, could aid in managing the pandemic more efficiently. Some drug design strategies have been successfully applied during the COVID-19 pandemic to create and validate related lead drugs. The computational drug design methods used for COVID-19 can be roughly divided into (i) structure-based approaches and (ii) artificial intelligence (AI)-based approaches. Structure-based approaches investigate different molecular fragments and functional groups through lead drugs and apply relevant tools to produce antiviral drugs. AI-based approaches usually use end-to-end learning to explore a larger biochemical space to design antiviral drugs. This review provides an overview of the two design strategies of anti-COVID-19 drugs, the advantages and disadvantages of these strategies and discussions of future developments.

9.
Lancet Reg Health Am ; : 100134, 2021 Nov 25.
Artigo em Inglês | MEDLINE | ID: mdl-34849505

RESUMO

Background: Phase 3 trials found mRNA-1273 was highly effective in preventing COVID-19. We conducted a prospective cohort study at Kaiser Permanente Southern California (KPSC) to determine the real-world vaccine effectiveness (VE) of mRNA-1273 in preventing COVID-19 infection and severe disease. Methods: For this planned interim analysis, individuals aged ≥18 years receiving 2 doses of mRNA-1273 ≥24 days apart (18/12/2020-31/03/2021) were 1:1 matched to randomly selected unvaccinated individuals by age, sex, and race/ethnicity, with follow-up through 30/06/2021. Outcomes were COVID-19 infection (SARS-CoV-2 positive molecular test or COVID-19 diagnosis code) or severe disease (COVID-19 hospitalization and COVID-19 hospital death). Adjusted hazard ratios (aHR) and confidence intervals (CI) for COVID-19 outcomes comparing vaccinated and unvaccinated individuals were estimated by Cox proportional hazards models accounting for multiple comparisons. Adjusted VE was calculated as (1-aHR)x100. Whole genome sequencing was performed on SARS-CoV-2 positive specimens from the KPSC population. Findings: This analysis included 352,878 recipients of 2 doses of mRNA-1273 matched to 352,878 unvaccinated individuals. VE (99·3% CI) against COVID-19 infection was 87·4% (84·8-89·6%). VE against COVID-19 hospitalization and hospital death was 95·8% (90·7-98·1%) and 97·9% (66·9-99·9%), respectively. VE was higher against symptomatic (88·3% [98·3% CI: 86·1-90·2%]) than asymptomatic COVID-19 (72·7% [53·4-84·0%]), but was generally similar across age, sex, and racial/ethnic subgroups. VE among individuals with history of COVID-19 ranged from 8·2-33·6%. The most prevalent variants were Alpha (41·6%), Epsilon (17·5%), Delta (11·5%), and Gamma (9·1%), with Delta increasing to 54·0% of variants by June 2021. Interpretation: These interim results provide reassuring evidence of the VE of 2 doses of mRNA-1273 across age, sex, and racial/ethnic subgroups, and against asymptomatic and symptomatic COVID-19, and severe COVID-19 outcomes. Among individuals with history of COVID-19, mRNA-1273 vaccination may offer added protection beyond immunity acquired from prior infection. Longer follow-up is needed to fully evaluate VE of mRNA-1273 against emerging SARS-CoV-2 variants. Funding: Moderna Inc.

10.
Br J Haematol ; 2021 Dec 03.
Artigo em Inglês | MEDLINE | ID: mdl-34859418

RESUMO

One of the most complex issues with haploidentical stem cell transplantation (haplo-SCT) is donor selection, given that multiple haploidentical donors are often available for a given recipient. To develop evidence-based guidance for donor selection in the setting of anti-thymocyte globulin-based haplo-SCT, we performed a prospective cohort study of 512 patients with haematological malignancies who had haplo-SCT to determine which donor variables were most important in favouring transplant outcomes. Increasing donor age was associated with poorer overall survival (OS) [hazard ratio (HR) 1·08, P = 0·044]. Female donors to male recipients was significantly associated with higher non-relapse mortality (NRM; HR 2·05, P = 0·006). Furthermore, increasing donor age had a higher risk of Grades 3-4 acute graft-versus-host disease (aGVHD; HR 1·17, P = 0·005), female donors to male recipients was associated with a higher risk of Grades 2-4 aGVHD (HR 1·50, P = 0·022). Sibling donors had superior OS, disease-free survival, and NRM than parental donors in patients aged <35 years. However, sibling donors had higher NRM than offspring donors in patients aged ≥35 years. A younger donor, usually a young sibling in younger recipients (aged <35 years) or a young offspring in older patients (aged ≥35 years) and avoiding female donors to male recipients should be preferred when multiple haploidentical donors are available.

11.
Nat Commun ; 12(1): 6283, 2021 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-34725330

RESUMO

Ethylene/polar monomer coordination copolymerization offers an attractive way of making functionalized polyolefins. However, ethylene copolymerization with industrially relevant short chain length alkenoic acid remain a big challenge. Here we report the efficient direct copolymerization of ethylene with vinyl acetic acid by tetranuclear nickel complexes. The protic monomer can be extended to acrylic acid, allylacetic acid, ω-alkenoic acid, allyl alcohol, and homoallyl alcohol. Based on X-ray analysis of precatalysts, control experiments, solvent-assisted electrospray ionization-mass spectrometry detection of key catalytic intermediates, and density functional theory studies, we propose a possible mechanistic scenario that involves a distinctive vinyl acetic acid enchainment enabled by Ni···Ni synergistic effects. Inspired by the mechanistic insights, binuclear nickel catalysts are designed and proved much more efficient for the copolymerization of ethylene with vinyl acetic acid or acrylic acid, achieving the highest turnover frequencies so far for both ethylene and polar monomers simultaneously.

12.
Molecules ; 26(21)2021 Oct 27.
Artigo em Inglês | MEDLINE | ID: mdl-34770884

RESUMO

Semiconducting metal oxides can detect low concentrations of NO2 and other toxic gases, which have been widely investigated in the field of gas sensors. However, most studies on the gas sensing properties of these materials are carried out at high temperatures. In this work, Hollow SnO2 nanofibers were successfully synthesized by electrospinning and calcination, followed by surface modification using ZnO to improve the sensitivity of the SnO2 nanofibers sensor to NO2 gas. The gas sensing behavior of SnO2/ZnO sensors was then investigated at room temperature (~20 °C). The results showed that SnO2/ZnO nanocomposites exhibited high sensitivity and selectivity to 0.5 ppm of NO2 gas with a response value of 336%, which was much higher than that of pure SnO2 (13%). In addition to the increase in the specific surface area of SnO2/ZnO-3 compared with pure SnO2, it also had a positive impact on the detection sensitivity. This increase was attributed to the heterojunction effect and the selective NO2 physisorption sensing mechanism of SnO2/ZnO nanocomposites. In addition, patterned electrodes of silver paste were printed on different flexible substrates, such as paper, polyethylene terephthalate and polydimethylsiloxane using a facile screen-printing process. Silver electrodes were integrated with SnO2/ZnO into a flexible wearable sensor array, which could detect 0.1 ppm NO2 gas after 10,000 bending cycles. The findings of this study therefore open a general approach for the fabrication of flexible devices for gas detection applications.

13.
Artigo em Inglês | MEDLINE | ID: mdl-34769764

RESUMO

Internet media may exacerbate public confusion and anxiety about COVID-19. New media health literacy (NMHL) is considered to play a protective role against health-related misinformation from the media for individuals to maintain their health. The current study aims to examine the relationship among Taiwanese adults' NMHL, health status, anxiety, and prevention behaviors during the COVID-19 pandemic. This cross-sectional study was conducted through an online survey, and 342 responses were included in the analysis. The survey tools include Health Status, COVID-19-Related New Media Health Literacy, COVID-19 Anxiety, and COVID-19 Preventive Behaviors. The research showed that both functional and critical prosuming literacy had positive relationships with health status. Functional consumption literacy had a weak negative correlation with COVID-19 anxiety. Furthermore, critical consumption literacy had a positive relationship with COVID-19 preventive behaviors. Therefore, individuals' health, anxiety, and prevention behaviors are affected by different aspects of COVID-19-related new media health literacy. Compared to their consuming media literacy, Taiwanese adults have insufficient prosuming media literacy in regard to COVID-19 health issues.


Assuntos
COVID-19 , Letramento em Saúde , Adulto , Ansiedade/epidemiologia , Ansiedade/prevenção & controle , Estudos Transversais , Nível de Saúde , Humanos , Pandemias , SARS-CoV-2 , Inquéritos e Questionários , Taiwan/epidemiologia
14.
Front Oncol ; 11: 750218, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34790576

RESUMO

Twenty patients with relapsed B-ALL after HSCT were treated with CAR T cell therapy and were evaluated for efficacy and safety. Twelve patients previously received haploidentical transplantation, while 8 patients received HLA-matched transplantation. The median relapse time was 12 months (range, 4 to 72). Thirteen patients received autologous CAR T cells, and 7 patients received allogeneic CAR T cells, which were derived from transplant donors. The median infusion dose was 2.9×106/kg (range, 0.33 to 12×106/kg). Nineteen patients were evaluated for efficacy, among which 17 patients (89.5%) achieved MRD negative. The CR rates in the HLA-matched transplantation group and haploidentical transplantation group were 100% (7/7) and 83.3% (10/12), respectively. The median follow-up time was 9.80 months (range, 2.40 to 64.97). Ten patients (50%) died of relapse, 3 patients (15%) died of infection, and 1 patient (5%) died of aGVHD. Fifteen patients (75%) developed CRS, including 3 (20%) grade 1 CRS, 6 (40%) grade 2 CRS, and 6 (40%) grade 3 CRS. Ten patients (50%) developed aGVHD, including 1 (10%) grade I aGVHD, 6 (60%) grade II aGVHD, and 3 (30%) grade III aGVHD. The log rank test showed that CAR T cell origin was correlated with aGVHD occurrence in the haploidentical transplantation group (P = 0.005). The authors' study indicated that the initial efficacy and safety of CAR T cell therapy for patients with post-transplant relapse were satisfactory. However, aGVHD was a concern in patients with a history of haploidentical transplantation occupied with allogeneic CAR T cells, which warrants clinical attention.

15.
Neuroimage ; : 118730, 2021 Nov 14.
Artigo em Inglês | MEDLINE | ID: mdl-34788663

RESUMO

Gratitude shapes individuals' behaviours and impacts the harmony of society. Many previous studies focused on its association with prosocial behaviours. A possibility that gratitude can lead to moral violation has been overlooked until recently. Nevertheless, the neurocognitive mechanisms of gratitude-induced moral violation are still unclear. On the other hand, though neural correlates of the gratitude's formation have been examined, the neural underpinnings of gratitude-induced behaviour remain unknown. For addressing these two overlapped research gaps, we developed novel tasks to investigate how participants who had received voluntary (Gratitude group) or involuntary help (Control group) punished their benefactors' unfairness with functional magnetic resonance imaging (fMRI). The Gratitude group punished their benefactors less than the Control group. The self-report and computational modelling results demonstrated a crucial role of the boosted protection tendency on behalf of benefactors in the gratitude-induced injustice. The fMRI results showed that activities in the regions associated with mentalizing (temporoparietal junction) and reward processing (ventral medial prefrontal cortex) differed between the groups and were related to the gratitude-induced injustice. They suggest that grateful individuals concern for benefactors' benefits, value chances to interact with benefactors, and refrain from action that perturbs relationship-building (i.e., exert less punishment on benefactors' unfairness), which reveal a dark side of gratitude and enrich the gratitude theory (i.e., the find-bind-remind theory). Our findings provide psychological, computational, and neural accounts of the gratitude-induced behaviour and further the understanding of the nature of gratitude.

16.
Cancer Cell Int ; 21(1): 597, 2021 Nov 07.
Artigo em Inglês | MEDLINE | ID: mdl-34743698

RESUMO

BACKGROUND: Aberrant autophagy and preternatural elevated glycolysis are prevalent in bladder cancer (BLCA) and are both related to malignant progression. However, the regulatory relationship between autophagy and glycolytic metabolism remains largely unknown. We imitated starvation conditions in the tumour microenvironment and found significantly increased levels of autophagy and aerobic glycolysis, which both regulated the progression of BLCA cells. We further explored the regulatory relationships and mechanisms between them. METHODS: We used immunoblotting, immunofluorescence and transmission electron microscopy to detect autophagy levels in BLCA cells under different treatments. Lactate and glucose concentration detection demonstrated changes in glycolysis. The expression of lactate dehydrogenase A (LDHA) was detected at the transcriptional and translational levels and was also silenced by small interfering RNA, and the effects on malignant progression were further tested. The underlying mechanisms of signalling pathways were evaluated by western blot, immunofluorescence and immunoprecipitation assays. RESULTS: Starvation induced autophagy, regulated glycolysis by upregulating the expression of LDHA and caused progressive changes in BLCA cells. Mechanistically, after starvation, the ubiquitination modification of Axin1 increased, and Axin1 combined with P62 was further degraded by the autophagy-lysosome pathway. Liberated ß-catenin nuclear translocation increased, binding with LEF1/TCF4 and promoting LDHA transcriptional expression. Additionally, high expression of LDHA was observed in cancer tissues and was positively related to progression. CONCLUSION: Our study demonstrated that starvation-induced autophagy modulates glucose metabolic reprogramming by enhancing Axin1 degradation and ß-catenin nuclear translocation in BLCA, which promotes the transcriptional expression of LDHA and further malignant progression.

17.
Chin Med J (Engl) ; 134(21): 2535-2543, 2021 Oct 14.
Artigo em Inglês | MEDLINE | ID: mdl-34748524

RESUMO

BACKGROUND: It is crucial to differentiate accurately glioma recurrence and pseudoprogression which have entirely different prognosis and require different treatment strategies. This study aimed to assess the diagnostic accuracy of dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) as a tool for distinguishing glioma recurrence and pseudoprogression. METHODS: According to particular criteria of inclusion and exclusion, related studies up to May 1, 2019, were thoroughly searched from several databases including PubMed, Embase, Cochrane Library, and Chinese biomedical databases. The quality assessment of diagnostic accuracy studies was applied to evaluate the quality of the included studies. By using the "mada" package in R, the heterogeneity, overall sensitivity, specificity, and diagnostic odds ratio were calculated. Moreover, funnel plots were used to visualize and estimate the publication bias in this study. The area under the summary receiver operating characteristic (SROC) curve was computed to display the diagnostic efficiency of DCE-MRI. RESULTS: In the present meta-analysis, a total of 11 studies covering 616 patients were included. The results showed that the pooled sensitivity, specificity, and diagnostic odds ratio were 0.792 (95% confidence interval [CI] 0.707-0.857), 0.779 (95% CI 0.715-0.832), and 16.219 (97.5% CI 9.123-28.833), respectively. The value of the area under the SROC curve was 0.846. In addition, the SROC curve showed high sensitivities (>0.6) and low false positive rates (<0.5) from most of the included studies, which suggest that the results of our study were reliable. Furthermore, the funnel plot suggested the existence of publication bias. CONCLUSIONS: While the DCE-MRI is not the perfect diagnostic tool for distinguishing glioma recurrence and pseudoprogression, it was capable of improving diagnostic accuracy. Hence, further investigations combining DCE-MRI with other imaging modalities are required to establish an efficient diagnostic method for glioma patients.


Assuntos
Glioma , Recidiva Local de Neoplasia , Glioma/diagnóstico por imagem , Humanos , Imageamento por Ressonância Magnética , Recidiva Local de Neoplasia/diagnóstico por imagem , Curva ROC , Sensibilidade e Especificidade
18.
Artigo em Inglês | MEDLINE | ID: mdl-34747464

RESUMO

OBJECTIVES: The msr(E)-mph(E) operon exists widely in diverse species of bacteria and msr(E) and mph(E) genes confer high resistance to macrolides. We aimed to explore whether macrolides regulate the transcription of the operon. METHODS: Antibiotic resistance genes in clinical isolates of Klebsiella pneumoniae were analysed by WGS. The transcription of the msr(E)-mph(E) operon was investigated by quantitative PCR. Construction of enhanced green fluorescent protein (eGFP) reporter plasmids, gene knockout and complementation experiments were used to further explore the induction mechanism of macrolides for the operon. Sequence analysis was finally used to investigate whether the operon exists widely in diverse species of bacteria. RESULTS: We originally found that the treatment of a pandrug-resistant isolate of K. pneumoniae (KP1517) with macrolides obviously up-regulated the msr(E)-mph(E) operon, which was further confirmed in another nine clinical isolates of K. pneumoniae. The induction mechanism of macrolides for the operon was partly elucidated. Macrolides could activate the operon promoter, and the J10/J35 regions (J10: 5'-AGTTATCAT-3'; J35: 5'-TTGTCT-3') of the promoter were determined. Histone-like nucleoid-structuring protein (HNS) and cAMP receptor protein (CRP) were involved in the erythromycin-mediated activation of the operon promoter. The 476 strains of bacteria carrying the msr(E)-mph(E) operon currently in the NCBI database are mainly Acinetobacter baumannii (158; 33%), K. pneumoniae (95; 20%), Escherichia coli (26; 5%) and Proteus mirabilis (25; 5%). They were mainly isolated from human clinical samples (287; 60%) and had a wide geographical distribution. CONCLUSIONS: Macrolides could activate transcription of the msr(E)-mph(E) operon through HNS and CRP in K. pneumoniae and E. coli, and this might occur in diverse species of bacteria.

19.
Oncol Lett ; 22(6): 847, 2021 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-34733365

RESUMO

Non-small cell lung cancer (NSCLC) is one of the most malignant cancer types. N6-methyladenosine (m6A), an abundant eukaryotic mRNA modification, has been observed in multiple diseases, particularly cancer. Methyltransferase-like 14 (METTL14) is a central component of the m6A methyltransferase complex and has been reported to promote tumor development in several cancer types. The present study aimed to investigate the role of METTL14 in NSCLC. Relevant clinical and mRNA sequencing data for m6A-related genes were downloaded from The Cancer Genome Atlas database. R software was used to evaluate the expression of m6A regulators in NSCLC. The biological functions of METTL14 were evaluated using Cell Counting Kit-8, colony formation, Transwell migration and western blot analyses. The results demonstrated that METTL14 expression was upregulated in NSCLC tissues and cell lines, and its expression was high in cancer tissues from patients with NSCLC with all four stages (I, II, III and IV) of disease. METTL14 downregulation inhibited cell proliferation and migration in A549 and SK-MES-1 lung cancer cell lines. Knockdown of METTL14 in lung cancer cell lines increased E-cadherin expression and suppressed N-cadherin expression. Furthermore, METTL14 downregulation reduced the expression levels of the transcription factor Twist and the p-AKT/AKT ratio. In conclusion, the present findings revealed that silencing of METTL14 suppressed NSCLC malignancy by inhibiting Twist-mediated activation of AKT signaling. These data suggest that METTL14 may be a potential therapeutic target for NSCLC.

20.
Front Immunol ; 12: 692079, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34737735

RESUMO

Long non-coding RNAs (lncRNAs) in immune cells play critical roles in tumor cell-immune cell interactions. This study aimed to characterize the landscape of tumor-infiltrating immune-related lncRNAs (Ti-lncRNAs) and reveal their correlations with prognoses and immunotherapy response in head and neck squamous cell carcinoma (HNSCC). We developed a computational model to identify Ti-lncRNAs in HNSCC and analyzed their associations with clinicopathological features, molecular alterations, and immunotherapy response. A signature of nine Ti-lncRNAs demonstrated an independent prognostic factor for both overall survival and disease-free survival among the cohorts from Fudan University Shanghai Cancer Center, The Cancer Genome Atlas, GSE41613, and GSE42743. The Ti-lncRNA signature scores in immune cells showed significant associations with TP53 mutation, CDKN2A mutation, and hypoxia. Inferior signature scores were enriched in patients with high levels of PDCD1 and CTLA4 and high expanded immune gene signature (IGS) scores, who displayed good response to PD-1 blockade in HNSCC. Consistently, superior clinical response emerged in melanoma patients with low signature scores undergoing anti-PD-1 therapy. Moreover, the Ti-lncRNA signature was a prognostic factor independent of PDCD1, CTLA4, and the expanded IGS score. In conclusion, tumor-infiltrating immune profiling identified a prognostic Ti-lncRNA signature indicative of clinical response to PD-1 blockade in HNSCC.

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