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1.
ACS EST Air ; 1(9): 1164-1176, 2024 Sep 13.
Artigo em Inglês | MEDLINE | ID: mdl-39295742

RESUMO

Wildfire is one of the main sources of PM2.5 (particulate matter with aerodynamic diameter < 2.5 µm) in the Alaskan summer. The complexity in wildfire smokes, as well as limited coverage of ground measurements, poses a big challenge to estimate surface PM2.5 during wildfire season in Alaska. Here we aim at proposing a quick and direct method to estimate surface PM2.5 over Alaska, especially in places exposed to strong wildfire events with limited measurements. We compare the AOD-surface PM2.5 conversion factor (η = PM2.5/AOD; AOD, aerosol optical depth) from the chemical transport model GEOS-Chem (ηGC) and from observations (ηobs). We show that ηGC is biased high compared to ηobs under smoky conditions, largely because GEOS-Chem assigns the majority of AOD (67%) within the planetary boundary layer (PBL) when AOD > 1, inconsistent with satellite retrievals from CALIOP. The overestimation in ηGC can be to some extent improved by increasing the injection height of wildfire emissions. We constructed a piecewise function for ηobs across different AOD ranges based on VIIRS-SNPP AOD and PurpleAir surface PM2.5 measurements over Alaska in the 2019 summer and then applied it on VIIRS AOD to derive daily surface PM2.5 over continental Alaska in the 2021 and 2022 summers. The derived satellite PM2.5 shows a good agreement with corrected PurpleAir PM2.5 in Alaska during the 2021 and 2022 summers, suggesting that aerosol vertical distribution likely represents the largest uncertainty in converting AOD to surface PM2.5 concentrations. This piecewise function, η'obs, shows the capability of providing an observation-based, quick and direct estimation of daily surface PM2.5 over the whole of Alaska during wildfires, without running a 3-D model in real time.

2.
Lancet Haematol ; 11(10): e751-e760, 2024 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-39059405

RESUMO

BACKGROUND: Some challenges still exist with single-target B-cell maturation antigen (BCMA) chimeric antigen receptor (CAR) T-cell therapies due to variable or negative BCMA expression, although they have yielded remarkable efficacy in relapsed or refractory multiple myeloma. We developed anti-BCMA/GPRC5D bispecific CARs to mitigate the limitations and potentiate the functions of CAR T cells. METHODS: This single-arm, phase 1 trial was conducted at the Affiliated Hospital of Xuzhou Medical University (Xuzhou, China). The trial enrolled patients aged 18-75 years with relapsed or refractory multiple myeloma and an Eastern Cooperative Oncology Group performance status of 0-3. Anti-BCMA/GPRC5D bispecific CAR T cells were administered at 0·5 × 106, 1·0 × 106, 2·0 × 106, and 4·0 × 106 CAR T cells per kg in the dose-escalation phase, with additional patients included at the dose selected for the dose-expansion phase. The primary endpoint was safety, which included dose-limiting toxicity and maximum tolerated dose. Activity was also evaluated as a secondary endpoint. The maximum tolerated dose was chosen for the dose-expansion phase. Safety and activity analyses were done in all patients who received anti-BCMA/GPRC5D bispecific CAR T cells as defined in the protocol. This trial is registered with ClinicalTrials.gov (NCT05509530) and is complete. FINDINGS: Between Sept 1, 2022, and Nov 3, 2023, 24 patients were enrolled and underwent apheresis. Three patients were excluded after apheresis (two patients discontinued due to rapid disease progression and one patient was withdrawn because of failed manufacture of CAR T cells), so 21 patients were infused with anti-BCMA/GPRC5D bispecific CAR T cells. Median follow-up was 5·8 months (IQR 5·2-6·7). Median age was 62 years (IQR 56-67). Eight (38%) patients were male, and 13 (62%) female. All patients were Chinese. At the 4·0 × 106 CAR T cells per kg dose, two patients had dose-limiting toxicities, of whom one died of subarachnoid haemorrhage (which was not considered to be related to the study treatment). The maximum tolerated dose was identified as 2·0 × 106 CAR T cells per kg. The most common grade 3 or worse adverse events were haematological toxicities in 19 (90%) patients (except lymphopenia). 15 (71%) patients had cytokine release syndrome, of which all cases were grade 1 or 2. One case of grade 1 immune effector cell-associated neurotoxicity syndrome (ICANS) was observed in a patient who received 4·0 × 106 CAR T cells per kg. No ICANS or grade 3 or worse organ toxicities were observed in patients who received 0·5-2·0 × 106 CAR T cells per kg. The overall response rate was 86% (18 of 21 patients), with 13 (62%) patients having a complete response or better, and 17 (81%) patients having measurable residual disease negativity. Of the 12 patients who received 2·0 × 106 CAR T cells per kg (three in the dose-escalation phase and an addition nine in the dose-expansion phase), the overall response rate was 92% (11 of 12 patients) with nine (75%) patients having a complete response or better. INTERPRETATION: Anti-BCMA/GPRC5D bispecific CAR T cells show a good safety profile and encouraging activity in patients with relapsed or refractory multiple myeloma. FUNDING: National Natural Science Foundation of China. TRANSLATION: For the Chinese translation of the abstract see Supplementary Materials section.


Assuntos
Antígeno de Maturação de Linfócitos B , Imunoterapia Adotiva , Mieloma Múltiplo , Receptores de Antígenos Quiméricos , Humanos , Mieloma Múltiplo/terapia , Mieloma Múltiplo/imunologia , Pessoa de Meia-Idade , Antígeno de Maturação de Linfócitos B/imunologia , Masculino , Feminino , Idoso , Imunoterapia Adotiva/métodos , Imunoterapia Adotiva/efeitos adversos , Adulto , Receptores de Antígenos Quiméricos/imunologia , Adulto Jovem , Linfócitos T/imunologia , Linfócitos T/transplante
3.
J Hazard Mater ; 476: 135060, 2024 Sep 05.
Artigo em Inglês | MEDLINE | ID: mdl-38943887

RESUMO

Offshore waters have a high incidence of oil pollution, which poses an elevated risk of ecological damage. The microbial community composition and metabolic mechanisms influenced by petroleum hydrocarbons vary across different marine regions. However, research on metabolic strategies for in-situ petroleum degradation and pollution adaptation remains in its nascent stages. This study combines metagenomic techniques with gas chromatography-mass spectrometry (GC-MS) analysis. The data show that the genera Pseudoalteromonas, Hellea, Lentisphaera, and Polaribacter exhibit significant oil-degradation capacity, and that the exertion of their degradation capacity is correlated with nutrient and oil pollution stimuli. Furthermore, tmoA, badA, phdF, nahAc, and fadA were found to be the key genes involved in the degradation of benzene, polycyclic aromatic hydrocarbons, and their intermediates. Key genes (INSR, SLC2A1, and ORC1) regulate microbial adaptation to oil-contaminated seawater, activating oil degradation processes. This process enhances the biological activity of microbial communities and accounts for the geographical variation in their compositional structure. Our results enrich the gene pool for oil pollution adaptation and degradation and provide an application basis for optimizing bioremediation intervention strategies.


Assuntos
Biodegradação Ambiental , Hidrocarbonetos , Microbiota , Poluição por Petróleo , Petróleo , Água do Mar , Poluentes Químicos da Água , Petróleo/metabolismo , Água do Mar/microbiologia , Poluentes Químicos da Água/metabolismo , Hidrocarbonetos/metabolismo , Bactérias/metabolismo , Bactérias/genética , Bactérias/classificação , Oceanos e Mares , Adaptação Fisiológica , Cromatografia Gasosa-Espectrometria de Massas
4.
Aquat Toxicol ; 273: 106996, 2024 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-38852546

RESUMO

Naphthenic acids (NAs) are important pollutants in marine crude oils and have obvious toxic effects on marine organisms. However, the effects of NAs on the intestine are largely unknown. Thus, we evaluated the effects of NAs exposure in the intestines of marine medaka. Fish were experimentally exposed to NAs (0.5 mg/L, 5 mg/L, and 10 mg/L) for 96 h and monitored for changes in intestinal histology, markers of oxidative stress, and intestinal microbiome responses. Significant mucosal damage, inflammation, and oxidative stress were observed in the intestines of marine medaka after exposure to NAs. In addition, significant changes in the gut microbiota were observed. Specifically, the relative abundance of Proteobacteria decreased, while that of Verrucomicrobiota increased in the high-concentration exposure group. In addition, nutrient synthesis and metabolism in the gut were affected. The results of this study contribute to a better understanding of the ecological risk of different concentrations of NAs to marine organisms. CAPSULE ABSTRACT: Changes in the gut microbial community of marine medaka (Oryzias melastigma) caused by naphthenic acids in the marine environment were investigated through the assessment of gut inflammatory factors and comprehensive analysis using 16S rDNA high-throughput sequencing. The results indicated the induction of intestinal inflammation and changes in the structural composition of the intestinal flora.


Assuntos
Ácidos Carboxílicos , Disbiose , Microbioma Gastrointestinal , Intestinos , Oryzias , Poluentes Químicos da Água , Animais , Microbioma Gastrointestinal/efeitos dos fármacos , Poluentes Químicos da Água/toxicidade , Ácidos Carboxílicos/toxicidade , Disbiose/veterinária , Disbiose/induzido quimicamente , Intestinos/efeitos dos fármacos , Intestinos/patologia , Estresse Oxidativo/efeitos dos fármacos
5.
ACS EST Air ; 1(4): 223-233, 2024 Apr 12.
Artigo em Inglês | MEDLINE | ID: mdl-38633207

RESUMO

The Multi-Angle Imager for Aerosols (MAIA), supported by NASA and the Italian Space Agency, is planned for launch into space in 2025. As part of its mission goal, outputs from a chemical transport model, the Unified Inputs for Weather Research and Forecasting Model coupled with Chemistry (UI-WRF-Chem), will be used together with satellite data and surface observations for estimating surface PM2.5. Here, we develop a method to improve UI-WRF-Chem with surface observations at the U.S. embassy in Ethiopia, one of MAIA's primary target areas in east Africa. The method inversely models the diurnal profile and amount of anthropogenic aerosol and trace gas emissions. Low-cost PurpleAir sensor data are used for validation after applying calibration functions obtained from the collocated data at the embassy. With the emission updates in UI-WRF-Chem, independent validation for February 2022 at several different PurpleAir sites shows an increase in the linear correlation coefficients from 0.1-0.7 to 0.6-0.9 between observations and simulations of the diurnal variation of surface PM2.5. Furthermore, even by using the emissions optimized for February 2021, the UI-WRF-Chem forecast for March 2022 is also improved. Annual update of monthly emissions via inverse modeling has the potential and is needed to improve MAIA's estimate of surface PM2.5.

6.
BMC Plant Biol ; 24(1): 143, 2024 Feb 28.
Artigo em Inglês | MEDLINE | ID: mdl-38413873

RESUMO

BACKGROUND: Solar radiation is primarily composed of ultraviolet radiation (UVR, 200 - 400 nm) and photosynthetically active radiation (PAR, 400 - 700 nm). Ultraviolet-B (UVB) radiation accounts for only a small proportion of sunlight, and it is the primary cause of plant photodamage. The use of chlorofluorocarbons (CFCs) as refrigerants caused serious ozone depletion in the 1980s, and this had led to an increase in UVB. Although CFC emissions have significantly decreased in recent years, UVB radiation still remains at a high intensity. UVB radiation increase is an important factor that influences plant physiological processes. Ulva prolifera, a type of macroalga found in the intertidal zone, is intermittently exposed to UVB. Alternative oxidase (AOX) plays an important role in plants under stresses. This research examines the changes in AOX activity and the relationships among AOX, photosynthesis, and reactive oxygen species (ROS) homeostasis in U. prolifera under changes in UVB and photosynthetically active radiation (PAR). RESULTS: UVB was the main component of solar radiation impacting the typical intertidal green macroalgae U. prolifera. AOX was found to be important during the process of photosynthesis optimization of U. prolifera due to a synergistic effect with non-photochemical quenching (NPQ) under UVB radiation. AOX and glycolate oxidase (GO) worked together to achieve NADPH homeostasis to achieve photosynthesis optimization under changes in PAR + UVB. The synergism of AOX with superoxide dismutase (SOD) and catalase (CAT) was important during the process of ROS homeostasis under PAR + UVB. CONCLUSIONS: AOX plays an important role in the process of photosynthesis optimization and ROS homeostasis in U. prolifera under UVB radiation. This study provides further insights into the response of intertidal macroalgae to solar light changes.


Assuntos
Algas Comestíveis , Proteínas Mitocondriais , Oxirredutases , Proteínas de Plantas , Alga Marinha , Raios Ultravioleta , Ulva , Espécies Reativas de Oxigênio , Fotossíntese/fisiologia , Aclimatação
7.
Folia Microbiol (Praha) ; 69(2): 373-382, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-37490214

RESUMO

CRISPR/Cas technology is a powerful tool for genome engineering in Aspergillus oryzae as an industrially important filamentous fungus. Previous study has reported the application of the CRISPR/Cpf1 system based on the Cpf1 (LbCpf1) from Lachnospiraceae bacterium in A. oryzae. However, multiplex gene editing have not been investigated using this system. Here, we presented a new CRISPR/Cpf1 multiplex gene editing system in A. oryzae, which contains the Cpf1 nuclease (FnCpf1) from Francisella tularensis subsp. novicida U112 and CRISPR-RNA expression cassette. The crRNA cassette consisted of direct repeats and guide sequences driven by the A. oryzae U6 promoter and U6 terminator. Using the constructed FnCpf1 gene editing system, the wA and pyrG genes were mutated successfully. Furthermore, simultaneous editing of wA and pyrG genes in A. oryzae was performed using two guide sequences targeting these gene loci in a single crRNA array. This promising CRISPR/Cpf1 genome-editing system provides a powerful tool for genetically engineering A. oryzae.


Assuntos
Aspergillus oryzae , Francisella , Edição de Genes , Aspergillus oryzae/genética , RNA Guia de Sistemas CRISPR-Cas
8.
Lancet Planet Health ; 7(12): e963-e975, 2023 12.
Artigo em Inglês | MEDLINE | ID: mdl-38056967

RESUMO

BACKGROUND: Long-term improvements in air quality and public health in the continental USA were disrupted over the past decade by increased fire emissions that potentially offset the decrease in anthropogenic emissions. This study aims to estimate trends in black carbon and PM2·5 concentrations and their attributable mortality burden across the USA. METHODS: In this study, we derived daily concentrations of PM2·5 and its highly toxic black carbon component at a 1-km resolution in the USA from 2000 to 2020 via deep learning that integrated big data from satellites, models, and surface observations. We estimated the annual PM2·5-attributable and black carbon-attributable mortality burden at each 1-km2 grid using concentration-response functions collected from a national cohort study and a meta-analysis study, respectively. We investigated the spatiotemporal linear-regressed trends in PM2·5 and black carbon pollution and their associated premature deaths from 2000 to 2020, and the impact of wildfires on air quality and public health. FINDINGS: Our results showed that PM2·5 and black carbon estimates are reliable, with sample-based cross-validated coefficients of determination of 0·82 and 0·80, respectively, for daily estimates (0·97 and 0·95 for monthly estimates). Both PM2·5 and black carbon in the USA showed significantly decreasing trends overall during 2000 to 2020 (22% decrease for PM2·5 and 11% decrease for black carbon), leading to a reduction of around 4200 premature deaths per year (95% CI 2960-5050). However, since 2010, the decreasing trends of fine particles and premature deaths have reversed to increase in the western USA (55% increase in PM2·5, 86% increase in black carbon, and increase of 670 premature deaths [460-810]), while remaining mostly unchanged in the eastern USA. The western USA showed large interannual fluctuations that were attributable to the increasing incidence of wildfires. Furthermore, the black carbon-to-PM2·5 mass ratio increased annually by 2·4% across the USA, mainly due to increasing wildfire emissions in the western USA and more rapid reductions of other components in the eastern USA, suggesting a potential increase in the relative toxicity of PM2·5. 100% of populated areas in the USA have experienced at least one day of PM2·5 pollution exceeding the daily air quality guideline level of 15 µg/m3 during 2000-2020, with 99% experiencing at least 7 days and 85% experiencing at least 30 days. The recent widespread wildfires have greatly increased the daily exposure risks in the western USA, and have also impacted the midwestern USA due to the long-range transport of smoke. INTERPRETATION: Wildfires have become increasingly intensive and frequent in the western USA, resulting in a significant increase in smoke-related emissions in populated areas. This increase is likely to have contributed to a decline in air quality and an increase in attributable mortality. Reducing fire risk via effective policies besides mitigation of climate warming, such as wildfire prevention and management, forest restoration, and new revenue generation, could substantially improve air quality and public health in the coming decades. FUNDING: National Aeronautics and Space Administration (NASA) Applied Science programme, NASA MODIS maintenance programme, NASA MAIA satellite mission programme, NASA GMAO core fund, National Oceanic and Atmospheric Administration (NOAA) GEO-XO project, NOAA Atmospheric Chemistry, Carbon Cycle, and Climate (AC4) programme, and NOAA Educational Partnership Program with Minority Serving Institutions.


Assuntos
Poluentes Atmosféricos , Aprendizado Profundo , Material Particulado , Fuligem , Incêndios Florestais , Humanos , Poluentes Atmosféricos/efeitos adversos , Poluentes Atmosféricos/análise , Carbono/efeitos adversos , Carbono/análise , Estudos de Coortes , Material Particulado/efeitos adversos , Material Particulado/análise , Fuligem/efeitos adversos , Fuligem/análise , Incêndios Florestais/mortalidade , Estados Unidos/epidemiologia , Mortalidade/tendências
9.
Appl Environ Microbiol ; 89(10): e0090923, 2023 10 31.
Artigo em Inglês | MEDLINE | ID: mdl-37702504

RESUMO

Kojic acid (KA) is a valuable secondary metabolite that is regulated by zinc finger proteins in Aspergillus oryzae. However, only two such proteins have been characterized to function in kojic acid production of A. oryzae to date. In this study, we identified a novel zinc finger protein, AoZFA, required for kojic acid biosynthesis in A. oryzae. Our results showed that disruption of AozfA led to increased expression of kojA and kojR involved in kojic acid synthesis, resulting in enhanced kojic acid production, while overexpression of AozfA had the opposite effect. Furthermore, deletion of kojR in the AozfA disruption strain abolished kojic acid production, whereas overexpression of kojR enhanced it, indicating that AoZFA regulates kojic acid production by affecting kojR. Transcriptional activation assay revealed that AoZFA is a transcriptional activator. Interestingly, when kojR was overexpressed in the AozfA overexpression strain, the production of kojic acid failed to be rescued, suggesting that AozfA plays a distinct role from kojR in kojic acid biosynthesis. Moreover, we found that AozfA was highly induced by zinc during early growth stages, and its overexpression inhibited the growth promoted by zinc, whereas its deletion had no effect, suggesting that AoZFA is non-essential but has a role in the response of A. oryzae to zinc. Overall, these findings provide new insights into the roles of zinc finger proteins in the growth and kojic acid production of A. oryzae.IMPORTANCEKojic acid (KA) is an economically valuable secondary metabolite produced by Aspergillus oryzae due to its vast biological activities. Genetic modification of A. oryzae has emerged as an efficient strategy for enhancing kojic acid production, which is dependent on the mining of genes involved in kojic acid synthesis. In this study, we have characterized a novel zinc-finger protein, AoZFA, as a negative regulator of kojic acid production by affecting kojR. AozfA is an excellent target for improving kojic acid production without any effects on the growth of A. oryzae. Furthermore, the simultaneous modification of AozfA and kojR exerts a more significant promotional effect on kojic acid production than the modification of single genes. This study provides new insights for the regulatory mechanism of zinc finger proteins in the growth and kojic acid production of A. oryzae.


Assuntos
Aspergillus oryzae , Aspergillus oryzae/genética , Aspergillus oryzae/metabolismo , Proteínas Fúngicas/metabolismo , Pironas/metabolismo , Zinco/metabolismo , Dedos de Zinco
10.
Environ Res ; 237(Pt 1): 116918, 2023 Nov 15.
Artigo em Inglês | MEDLINE | ID: mdl-37611786

RESUMO

Hexavalent chromium is a toxic metal that can induce severe chromium contamination of soil, posing a potential risk to human health and ecosystems. In recent years, the immobilization of Cr(VI) using remediation materials including inorganic materials, organic materials, microbial agents, and composites has exhibited great potential in remediating Cr(VI)-contaminated soil owing to the environmental-friendliness, short period, simple operation, low cost, applicability on an industrial scale, and high efficiency of these materials. Therefore, a systematical summary of the current progress on various remediation materials is essential. This work introduces the production (sources) of remediation materials and examines their characteristics in detail. Additionally, a critical summary of recent research on the utilization of remediation materials for the stabilization of Cr(VI) in the soil is provided, together with an evaluation of their remediation efficiencies toward Cr(VI). The influences of remediation material applications on soil physicochemical properties, microbial community structure, and plant growth are summarized. The immobilization mechanisms of remediation materials toward Cr(VI) in the soil are illuminated. Importantly, this study evaluates the feasibility of each remediation material application for Cr(VI) remediation. The latest knowledge on the development of remediation materials for the immobilization of Cr(VI) in the soil is also presented. Overall, this review will provide a reference for the development of remediation materials and their application in remediating Cr(VI)-contaminated soil.

11.
Environ Res ; 237(Pt 1): 116913, 2023 Nov 15.
Artigo em Inglês | MEDLINE | ID: mdl-37597830

RESUMO

Dissolved organic matter (DOM) derived from wetland plants played a critical role in CWs pollutant migration. This study investigated the character and release pattern of DOM derived from two wetland plants, Phragmites australis and Cladophora sp., and the interaction between DOM with phenanthrene (PHE), benzo(a)pyrene (Bap), and benzo [k]fluoranthene (BkF) under different physical conditions were also studied using spectroscopic techniques. DOM release was related to plant species and withering stage. Humic acid (HA)-like fractions (C3 and C5) were dominated in P. australis (52%) and completely withered Cladophora sp. groups (55%), while protein-like fractions (C1 and C2) dominated in early withered Cladophora sp. groups (52%). Due to the cell and tissue structure difference among plants and their withering stage, DOM derived from early withered P. australis revealed a two-stage slow-fast phase, while other groups were linearly released (R2 0.87207-0.97091). A strong correlation existed between HA-like fractions and water quality index, reflecting the critical influence of plant decay in CWs operation performance. The analysis with Stern-Volmer equation indicated that plant-based DOM interacted with PAHs to form ground state complexes with possible involvement of π-π interaction, hydrogen bonding and cation bridging effect. Aromatic, molecular weight, and hydrophilicity of both DOM and PAHs affected their binding with the interaction capability in the order of BKF > Bap > PHE and C3 > C5 > C2 > C1 > C4. Besides, alkaline environment and high DO condition was highly unsuitable for the combination. Scientific management and appropriate operating condition were important in optimizing operation performance and controlling pollutant migration in CWs.

12.
J Transl Med ; 21(1): 533, 2023 08 08.
Artigo em Inglês | MEDLINE | ID: mdl-37553713

RESUMO

BACKGROUND: Accurately predicting the outcome of isocitrate dehydrogenase (IDH) wild-type glioblastoma (GBM) remains hitherto challenging. This study aims to Construct and Validate a Robust Prognostic Model for IDH wild-type GBM (COVPRIG) for the prediction of overall survival using a novel metric, gene-gene (G × G) interaction, and explore molecular and cellular underpinnings. METHODS: Univariate and multivariate Cox regression of four independent trans-ethnic cohorts containing a total of 800 samples. Prediction efficacy was comprehensively evaluated and compared with previous models by a systematic literature review. The molecular underpinnings of COVPRIG were elucidated by integrated analysis of bulk-tumor and single-cell based datasets. RESULTS: Using a Cox-ph model-based method, six of the 93,961 G × G interactions were screened to form an optimal combination which, together with age, comprised the COVPRIG model. COVPRIG was designed for RNA-seq and microarray, respectively, and effectively identified patients at high risk of mortality. The predictive performance of COVPRIG was satisfactory, with area under the curve (AUC) ranging from 0.56 (CGGA693, RNA-seq, 6-month survival) to 0.79 (TCGA RNAseq, 18-month survival), which can be further validated by decision curves. Nomograms were constructed for individual risk prediction for RNA-seq and microarray-based cohorts, respectively. Besides, the prognostic significance of COVPRIG was also validated in GBM including the IDH mutant samples. Notably, COVPRIG was comprehensively evaluated and externally validated, and a systemic review disclosed that COVPRIG outperformed current validated models with an integrated discrimination improvement (IDI) of 6-16%. Moreover, integrative bioinformatics analysis predicted an essential role of METTL1+ neural-progenitor-like (NPC-like) malignant cell in driving unfavorable outcome. CONCLUSION: This study provided a powerful tool for the outcome prediction for IDH wild-type GBM, and preliminary molecular underpinnings for future research.


Assuntos
Neoplasias Encefálicas , Glioblastoma , Humanos , Glioblastoma/genética , Glioblastoma/patologia , Isocitrato Desidrogenase/genética , Neoplasias Encefálicas/genética , Neoplasias Encefálicas/patologia , Prognóstico , Nomogramas , Metiltransferases
13.
Chemosphere ; 337: 139207, 2023 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-37364639

RESUMO

Atrazine is a toxic endocrine disruptor. Biological treatment methods are considered to be effective. In the present study, a modified version of the algae-bacteria consortia (ABC) was established and a control was simultaneously set up to investigate the synergistic relationship between bacteria and algae and the mechanism by which atrazine is metabolized by those microorganisms. The total nitrogen (TN) removal efficiency of the ABC reached 89.24% and the atrazine concentration was reduced to below the level recommended by the Environment Protection Agency (EPA) regulatory standards within 25 days. The protein signal released from the extracellular polymeric substances (EPS) secreted by the microorganisms triggered the resistance mechanism of the algae, and the conversion of humic acid to fulvic acid and electron transfer constituted the synergistic mechanism between the bacteria and algae. The mechanism by which atrazine is metabolized by the ABC mainly consists of hydrogen bonding, H-pi interactions, and cation exchange with atzA for hydrolysis, followed by a reaction with atzC for decomposition to non-toxic cyanuric acid. Proteobacteria was the dominant phylum for bacterial community evolution under atrazine stress, and the analysis revealed that the removal of atrazine within the ABC was mainly dependent on the proportion of Proteobacteria and the expression of degradation genes (p < 0.01). EPS played a major role in the removal of atrazine within the single bacteria group (p < 0.01).


Assuntos
Atrazina , Atrazina/análise , Águas Residuárias , Bactérias/genética , Bactérias/metabolismo , Biodegradação Ambiental
14.
Zhongguo Shi Yan Xue Ye Xue Za Zhi ; 31(3): 783-787, 2023 Jun.
Artigo em Chinês | MEDLINE | ID: mdl-37356940

RESUMO

OBJECTIVE: To investigate the effect of hemoglobin (Hb) on the efficacy of chimeric antigen receptor T cell therapy (CAR-T) in patients with multiple myeloma (MM). METHODS: From June 2017 to December 2020, 76 MM patients who received CAR-T therapy in the Department of Hematology, The Affiliated Hospital of Xuzhou Medical University, with complete clinical data and evaluable efficacy, were selected as the research objects. According to the receiver operating characteristic (ROC) curve, the best cut-off value was obtained. The patients were divided into groups on the basis of Hb 105.5 g/L as the cut-off value. The age, sex, serum calcium, ß2-microglobulin, serum creatinine, lactate dehydrogenase (LDH), and the influencing factors of CAR-T treatment efficacy in MM patients were analyzed. RESULTS: Hb was an influencing factor of efficacy. Univariate analysis showed that Hb, LDH, and albumin affected the efficacy of CAR-T therapy. Multivariate analysis showed that Hb ( OR=1.039, 95% CI: 1.002-1.078) and LDH ( OR=1.014, 95% CI: 1.000-1.027) were the influencing factors for the efficacy of CAR-T therapy. CONCLUSION: The efficacy of CAR-T therapy in MM patients with low Hb is poor, and Hb is a factor affecting the efficacy of CAR-T therapy.


Assuntos
Doenças Hematológicas , Mieloma Múltiplo , Receptores de Antígenos Quiméricos , Humanos , Mieloma Múltiplo/tratamento farmacológico , Imunoterapia Adotiva , Resultado do Tratamento
15.
Ecotoxicol Environ Saf ; 253: 114700, 2023 Mar 15.
Artigo em Inglês | MEDLINE | ID: mdl-36863161

RESUMO

Naphthenic acids (NAs) are typical contaminants in heavily crude oil. Benzo[a]pyrene (B[a]P) is also a component of crude oil, but their combined effects have not been systematically explored. In this study, zebrafish (Danio rerio) were used as the test organisms, and behavioral indicators and enzyme activities were used as toxicity indicators. Combined with the effects of environmental concentrations, the toxic effects of low concentrations of commercially available NAs (0.5 mg/LNA) and benzo[a]pyrene (0.8 µg/LBaP) at single and compound exposures (0.5 mg/LNA and 0.8 µg/LBaP) were assayed in zebrafish, and transcriptome sequencing technology was used to explore the molecular mechanism of the two compounds affecting zebrafish from the molecular biology level. Sensitive molecular markers that could indicate the presence of contaminants were screened. The results showed that (1) zebrafish in the NA and BaP exposure groups exhibited increased locomotor behavior, and the mixed exposure group exhibited inhibition of locomotor behavior. Oxidative stress biomarkers showed increased activity under single exposure and decreased activity under the mixed exposure. (2) NA stress led to changes in the activity of transporters and the intensity of energy metabolism; BaP directly stimulates the pathway of actin production. When the two compounds are combined, the excitability of neurons in the central nervous system is decreased, and the actin-related genes are down-regulated. (3) After BaP and Mix treatments, genes were enriched in the cytokine-receptor interaction and actin signal pathway, while NA increased the toxic effect on the mixed treatment group. In general, the interaction between NA and BaP has a synergistic effect on the transcription of zebrafish nerve and motor behavior-related genes, resulting in increased toxicity under combined exposure. The changes in expression of various zebrafish genes are manifested in the changes in the normal movement behavior of zebrafish and the intensification of oxidative stress in the apparent behavior and physiological indicators. CAPSULE ABSTRACT: We investigated the toxicity and genetic alterations caused by NA, B[a]P, and their mixtures in zebrafish in an aquatic environment using transcriptome sequencing technology and comprehensive behavioral analysis. These changes involved energy metabolism, the generation of muscle cells, and the nervous system.


Assuntos
Petróleo , Poluentes Químicos da Água , Animais , Transcriptoma , Peixe-Zebra/genética , Benzo(a)pireno/toxicidade , Actinas , Petróleo/toxicidade , Poluentes Químicos da Água/toxicidade
16.
Environ Pollut ; 324: 121420, 2023 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-36906058

RESUMO

Petroleum hydrocarbons are significant new persistent organic pollutants for marine oil spill risk areas. Oil trading ports, in turn, have become major bearers of the risk of offshore oil pollution. However, studies on the molecular mechanisms of microbial degradation of petroleum pollutants by natural seawater are limited. Here, an in situ microcosm study was conducted. Combined with metagenomics, differences in metabolic pathways and in the gene abundances of total petroleum hydrocarbons (TPH) are revealed under different conditions. About 88% degradation of TPH was shown after 3 weeks of treatment. The positive responders to TPH were concentrated in the genera Cycloclasticus, Marivita and Sulfitobacter of the orders Rhodobacterales and Thiotrichales. The genera Marivita, Roseobacter, Lentibacter and Glaciecola were key degradation species when mixing dispersants with oil, and all of the above are from the Proteobacteria phylum. The analysis showed that the biodegradability of aromatic compounds, polycyclic aromatic hydrocarbon and dioxin were enhanced after the oil spill, and genes with higher abundances of bphAa, bsdC, nahB, doxE and mhpD were found, but the photosynthesis-related mechanism was inhibited. The dispersant treatment effectively stimulated the microbial degradation of TPH and then accelerated the succession of microbial communities. Meanwhile, functions such as bacterial chemotaxis and carbon metabolism (cheA, fadeJ and fadE) were better developed, but the degradation of persistent organic pollutants such as polycyclic aromatic hydrocarbons was weakened. Our study provides insights into the metabolic pathways and specific functional genes for oil degradation by marine microorganisms and will help improve the application and practice of bioremediation.


Assuntos
Poluição por Petróleo , Petróleo , Petróleo/metabolismo , Poluentes Orgânicos Persistentes , Hidrocarbonetos/metabolismo , Água do Mar/química , Biodegradação Ambiental
17.
Chemosphere ; 311(Pt 1): 136968, 2023 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-36283429

RESUMO

The plastic concentration in terrestrial systems is orders of magnitude higher than that found in marine ecosystems, which has raised global concerns about their potential risk to agricultural sustainability. Previous research on the transport of nanoplastics in soil relied heavily on the qualitative prediction of the mean-field extended Derjaguin-Landau-Verwey-Overbeek theory (XDLVO), but direct and quantitative measurements of the interfacial forces between single nanoplastics and porous media are lacking. In this study, we conducted multiscale investigations ranging from column transport experiments to single particle measurements. The maximum effluent concentration (C/C0) of amino-modified nanoplastics (PS-NH2) was 0.94, whereas that of the carboxyl-modified nanoplastics (PS-COOH) was only 0.33, indicating PS-NH2 were more mobile than PS-COOH at different ionic strengths (1-50 mM) and pH values (5-9). This phenomenon was mainly attributed to the homogeneous aggregation of PS-COOH. In addition, the transport of PS-NH2 in the quartz sand column was inhibited with the increase of ionic strength and pH, and pH was the major factor governing their mobility. The transport of PS-COOH was inhibited with increasing ionic strength and decreasing pH. Hydrophilicity/hydrophobicity-mediated interactions and particle heterogeneity strongly interfered with interfacial forces, leading to the qualitative prediction of XDLVO, contrary to experimental observations. Through the combination of XDLVO and colloidal atomic force microscopy, accurate and quantitative interfacial forces can provide compelling insight into the fate of nanoparticles in the soil environment.


Assuntos
Ecossistema , Microplásticos , Porosidade , Quartzo , Areia
18.
Environ Microbiol ; 24(12): 6267-6278, 2022 12.
Artigo em Inglês | MEDLINE | ID: mdl-36250814

RESUMO

Ferroptosis is a newly discovered form of cell death accompanied by iron accumulation and lipid peroxidation. Both biotic and abiotic stresses can induce ferroptosis in plant cells. In the case of plant interactions with pathogenic Phytophthora oomycetes, the roles of ferroptosis are still largely unknown. Here, we performed transcriptome analysis on soybean plants treated with the biocontrol agent Pythium oligandrum, a soilborne and non-pathogenic oomycete capable of inducing plant resistance against Phytophthora sojae infection. Expression of homologous soybean genes involved in ferroptosis and resistance was reprogrammed upon P. oligandrum treatment. Typical hallmarks for characterizing ferroptosis were detected in soybean hypocotyl cells, including decreased glutathione (GSH) level, accumulation of ferric ions, and lipid peroxidation by reactive oxygen species (ROS). Meanwhile, ferroptosis-like cell death was triggered by P. oligandrum to suppress P. sojae infection in soybean. Protection provided by P. oligandrum could be attenuated by the ferroptosis inhibitor ferrostatin-1 (Fer-1), suggesting the critical role of ferroptosis in soybean resistance against P. sojae. Taken together, these results demonstrate that ferroptosis is a P. oligandrum-inducible defence mechanism against oomycete infection in soybean.


Assuntos
Ferroptose , Phytophthora , Pythium , Glycine max/genética , Doenças das Plantas/prevenção & controle , Doenças das Plantas/genética , Resistência à Doença/genética
19.
Front Pharmacol ; 13: 965661, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36204225

RESUMO

Dexmedetomidine (DEX) is a highly selective α2 receptor agonist that is routinely used in the clinic for sedation and anesthesia. Recently, an increasing number of studies have shown that DEX has a protective effect against brain injury caused by traumatic brain injury (TBI), subarachnoid hemorrhage (SAH), cerebral ischemia and ischemia-reperfusion (I/R), suggesting its potential as a neuroprotective agent. Here, we summarized the neuroprotective effects of DEX in several models of neurological damage and examined its mechanism based on the current literature. Ultimately, we found that the neuroprotective effect of DEX mainly involved inhibition of inflammatory reactions, reduction of apoptosis and autophagy, and protection of the blood-brain barrier and enhancement of stable cell structures in five way. Therefore, DEX can provide a crucial advantage in neurological recovery for patients with brain injury. The purpose of this study was to further clarify the neuroprotective mechanisms of DEX therefore suggesting its potential in the clinical management of the neurological injuries.

20.
ACS Omega ; 7(39): 34801-34809, 2022 Oct 04.
Artigo em Inglês | MEDLINE | ID: mdl-36211058

RESUMO

The herbaceous peony (Paeonia lactiflora Pall.) is a traditional rare flower in China, and production of its cut flowers has developed gradually in many places of the world. However, the inflorescence stems of some P. lactiflora cultivars have such low mechanical strength that the cut flower production was severely restricted. To better understand the causes of this problem from a protein expression level, two P. lactiflora cultivars with different inflorescence stem mechanical strengths were analyzed by two-dimensional electrophoresis and MALDI-TOF/MS. More than 1700 clear protein spots were detected, 53 of which varied significantly. Moreover, 23 of the differentially expressed proteins were identified and confirmed and are involved in various biological processes such as metabolism, protein biosynthesis and transport, signal transduction, and defensive response. Especially, cinnamyl alcohol dehydrogenase (CAD) and xyloglucan endotransglucosylase/hydrolase (XTH) were strongly connected to the inflorescence stem mechanical strength in P. lactiflora.

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