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1.
Environ Sci Technol ; 58(18): 7758-7769, 2024 May 07.
Artigo em Inglês | MEDLINE | ID: mdl-38669205

RESUMO

Polycyclic aromatic hydrocarbon (PAH) exposure is suspected to be linked to oxidative damage. Herein, ten PAH human exposure biomarkers [hydroxylated PAH metabolites (OH-PAHs)] and five oxidative stress biomarkers (OSBs) were detected in urine samples collected from participants living in a rural area (n = 181) in Northwestern China. The median molar concentration of ΣOH-PAHs in urine was 47.0 pmol mL-1. The 2-hydroxynaphthalene (2-OHNap; median: 2.21 ng mL-1) was the dominant OH-PAH. The risk assessment of PAH exposure found that hazard index (HI) values were <1, indicating that the PAH exposure of rural people in Jingyuan would not generate significant cumulative risks. Smokers (median: 0.033) obtained higher HI values than nonsmokers (median: 0.015, p < 0.01), suggesting that smokers face a higher health risk from PAH exposure than nonsmokers. Pearson correlation and multivariate linear regression analysis revealed that ΣOH-PAH concentrations were significant factors in increasing the oxidative damage to deoxyribonucleic acid (DNA) (8-hydroxy-2'-deoxyguanosine, 8-OHdG), ribonucleic acid (RNA) (8-oxo-7,8-dihydroguanine, 8-oxoGua), and protein (o, o'-dityrosine, diY) (p < 0.05). Among all PAH metabolites, only 1-hydroxypyrene (1-OHPyr) could positively affect the expression of all five OSBs (p < 0.05), suggesting that urinary 1-OHPyr might be a reliable biomarker for PAH exposure and a useful indicator for assessing the impacts of PAH exposure on oxidative stress. This study is focused on the relation between PAH exposure and oxidative damage and lays a foundation for the study of the health effect mechanism of PAHs.


Assuntos
Biomarcadores , Estresse Oxidativo , Hidrocarbonetos Policíclicos Aromáticos , População Rural , Hidrocarbonetos Policíclicos Aromáticos/urina , Humanos , China , Medição de Risco , Biomarcadores/urina , Masculino , Feminino , Exposição Ambiental , Pessoa de Meia-Idade , Adulto
2.
J Phys Chem A ; 128(9): 1611-1619, 2024 Mar 07.
Artigo em Inglês | MEDLINE | ID: mdl-38382059

RESUMO

Thermally activated delayed fluorescence (TADF) emitters based on the triptycene skeleton demonstrate exceptional performance, superior stability, and low efficiency roll-off. Understanding the interplay between the luminescent properties of triptycene-TADF molecules and their assembly environments, along with their excited-state characteristics, necessitates a comprehensive theoretical exploration. Herein, we predict the photophysical properties of triptycene-TADF molecules in a thin film environment using the quantum mechanics/molecular mechanics method and quantify their substantial dependency on the heavy atom effects and reorganization energies using the Marcus-Levich theory. Our calculated photophysical properties for two recently reported molecules closely align with experimental values. We design three novel triptycene-TADF molecules by incorporating chalcogen elements (O, S, and Se) to modify the acceptor units. These newly designed molecules exhibit reduced reorganization energies and enhanced reverse intersystem crossing (RISC) rates. The heavy atom effect amplifies spin-orbit coupling, thereby facilitating the RISC process, particularly at a remarkably high rate of ∼109 s-1.

3.
Bioinformatics ; 38(7): 1895-1903, 2022 03 28.
Artigo em Inglês | MEDLINE | ID: mdl-35134108

RESUMO

MOTIVATION: Protein model quality assessment is a key component of protein structure prediction. In recent research, the voxelization feature was used to characterize the local structural information of residues, but it may be insufficient for describing residue-level topological information. Design features that can further reflect residue-level topology when combined with deep learning methods are therefore crucial to improve the performance of model quality assessment. RESULTS: We developed a deep-learning method, DeepUMQA, based on Ultrafast Shape Recognition (USR) for the residue-level single-model quality assessment. In the framework of the deep residual neural network, the residue-level USR feature was introduced to describe the topological relationship between the residue and overall structure by calculating the first moment of a set of residue distance sets and then combined with 1D, 2D and voxelization features to assess the quality of the model. Experimental results on the CASP13, CASP14 test datasets and CAMEO blind test show that USR could supplement the voxelization features to comprehensively characterize residue structure information and significantly improve model assessment accuracy. The performance of DeepUMQA ranks among the top during the state-of-the-art single-model quality assessment methods, including ProQ2, ProQ3, ProQ3D, Ornate, VoroMQA, ProteinGCN, ResNetQA, QDeep, GraphQA, ModFOLD6, ModFOLD7, ModFOLD8, QMEAN3, QMEANDisCo3 and DeepAccNet. AVAILABILITY AND IMPLEMENTATION: The DeepUMQA server is freely available at http://zhanglab-bioinf.com/DeepUMQA/. SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.


Assuntos
Aprendizado Profundo , Proteínas/química , Redes Neurais de Computação , Biologia Computacional/métodos
4.
Environ Sci Technol ; 56(15): 10699-10709, 2022 08 02.
Artigo em Inglês | MEDLINE | ID: mdl-35849551

RESUMO

The absorption, translocation, and biotransformation behaviors of organophosphate esters (OPEs) and diesters (OPdEs) in a hydroponic system were investigated. The lateral root was found as the main accumulation and biotransformation place of OPEs and OPdEs in lettuce. The nontarget analysis using high-resolution mass spectrometry revealed five hydroxylated metabolites and five conjugating metabolites in the OPE exposure group, among which methylation, acetylation, and palmitoyl conjugating OPEs were reported as metabolites for the first time. Particularly, methylation on phosphate can be a significant process for plant metabolism, and methyl diphenyl phosphate (MDPP) accounted for the majority of metabolites. The translocation factor values of most identified OPE metabolites are negatively associated with their predicted logarithmic octanol-water partitioning coefficient (log Kow) values (0.75-2.45), indicating that hydrophilicity is a dominant factor in the translocation of OPE metabolites in lettuce. In contrast, palmitoyl conjugation may lead to an enhanced acropetal translocation and those with log Kow values < 0 may have limited translocation potential. Additionally, OPE diesters produced from the biotransformation of OPEs in lettuce showed a higher acropetal translocation potential than those exposed directly. These results further emphasize the necessity to consider biotransformation as an utmost important factor in the accumulation and acropetal translocation potential of OPEs in plants.


Assuntos
Retardadores de Chama , Lactuca , Biotransformação , China , Monitoramento Ambiental/métodos , Ésteres , Retardadores de Chama/análise , Hidroponia , Lactuca/metabolismo , Organofosfatos/análise , Fosfatos/análise
5.
Opt Express ; 29(15): 24151-24160, 2021 Jul 19.
Artigo em Inglês | MEDLINE | ID: mdl-34614665

RESUMO

Smart structures with tunable electromagnetic characteristics are required for camouflaging high-value targets, such as land warfare moving equipment, in continuously changing complex electromagnetic environments. The targets must control their radar cross section (RCS) to avoid detection and tracking. Frequency selective surfaces (FSSs) are the next-generation smart structures in which active RCS control is realized via impedance loading. In this paper, a multistate transformable FSS absorber/reflector that operates in the 3.9-11.0 GHz band is introduced and analyzed. The reflectivity amplitude of this absorber/reflector could be smoothly changed from 0 to -10 dB in 6.0-8.0 GHz. Each unit cell of the FSS structure consisted of four symmetrical diamond-shaped patterns, and the adjacent units were connected by PIN diodes. The absorption intensity of the FSS could be changed from 0 to -10 dB by adjusting the PIN bias voltage, which was applied via a simple bias network. The multistate switching characteristic of the FSS was verified by simulations and measurements. The results showed that adjustable absorbing intensity and switchable working states are the desirable characteristics that allow high-value targets to adapt to changing electromagnetic environments. Our work will bridge the gap between the available stealth strategies and practical applications, such as moving stealth vehicles.

6.
Langmuir ; 37(39): 11520-11525, 2021 Oct 05.
Artigo em Inglês | MEDLINE | ID: mdl-34555896

RESUMO

Lead halide perovskite quantum dots (QDs) are known as prospective optoelectronic device materials because of their excellent luminescence, extraordinary photoelectric performance, and specific octahedron framework. Herein, we report a cost-effective approach for synthesizing highly stable CH3NH3PbBr3 QDs in low-polarity binary solvents without nitrogen protection. The CH3NH3PbBr3 QDs are tunable from 1.2 to 4.2 nm by adjusting the proportion of oleic acid and oleylamine as capping ligands. The photoluminescence quantum yield of CH3NH3PbBr3 QDs can reach 87.4%. The fluorescence can maintain over 80% of its earliest emission intensity under the atmosphere after 5 days, which is much better than that (∼10%) of QDs with ligand-assisted reprecipitation. The possible reaction mechanism of preparing CH3NH3PbBr3 QDs was also addressed. Notably, such a strategy can be applied extensively in the preparation of other lead halide perovskite QDs. Furthermore, the as-prepared thick PMMA-coated CH3NH3PbBr3 QDs were further conjoined with a red luminescence powder on a blue InGaN chip to obtain a powerful efficiency (45.4 lm W-1) warm white light-emitting diode.

7.
Int J Mol Sci ; 22(11)2021 Jun 02.
Artigo em Inglês | MEDLINE | ID: mdl-34199611

RESUMO

Temperature influences the physiological processes and ecology of both hosts and endophytes; however, it remains unclear how long noncoding RNAs (lncRNAs) modulate the consequences of temperature-dependent changes in host-pathogen interactions. To explore the role of lncRNAs in culm gall formation induced by the smut fungus Ustilago esculenta in Zizania latifolia, we employed RNA sequencing to identify lncRNAs and their potential cis-targets in Z. latifolia and U. esculenta under different temperatures. In Z. latifolia and U. esculenta, we identified 3194 and 173 lncRNAs as well as 126 and four potential target genes for differentially expressed lncRNAs, respectively. Further function and expression analysis revealed that lncRNA ZlMSTRG.11348 regulates amino acid metabolism in Z. latifolia and lncRNA UeMSTRG.02678 regulates amino acid transport in U. esculenta. The plant defence response was also found to be regulated by lncRNAs and suppressed in Z. latifolia infected with U. esculenta grown at 25 °C, which may result from the expression of effector genes in U. esculenta. Moreover, in Z. latifolia infected with U. esculenta, the expression of genes related to phytohormones was altered under different temperatures. Our results demonstrate that lncRNAs are important components of the regulatory networks in plant-microbe-environment interactions, and may play a part in regulating culm swelling in Z. latifolia plants.


Assuntos
Doenças das Plantas/genética , Poaceae/genética , RNA Longo não Codificante/genética , Transcriptoma/genética , Endófitos/genética , Endófitos/patogenicidade , Interações Hospedeiro-Patógeno/genética , Doenças das Plantas/parasitologia , Poaceae/crescimento & desenvolvimento , Análise de Sequência de RNA , Temperatura , Ustilago/genética , Ustilago/patogenicidade
8.
Microb Pathog ; 143: 104107, 2020 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-32120003

RESUMO

Ustilago esculenta, a smut fungus, can induce the formation of culm galls in Zizania latifolia, a vegetable consumed in many Asian countries. Specifically, the mycelia-teliospore (M-T) strain of U. esculenta induces the Jiaobai (JB) type of gall, while the teliospore (T) strain induces the Huijiao (HJ) type. The underlying molecular mechanism responsible for the formation of the two distinct types of gall remains unclear. Our results showed that most differentially expressed genes relevant to effector proteins were up-regulated in the T strain compared to those in the M-T strain during gall formation, and the expression of teliospore formation-related genes was higher in the T strain than the M-T strain. Melanin biosynthesis was also clearly induced in the T strain. The T strain exhibited stronger pathogenicity and greater teliospore production than the M-T strain. We evaluated the implications of the gene regulatory networks in the development of these two type of culm gall in Z. latifolia infected with U. esculenta and suggested potential targets for genetic manipulation to modify the gall type for this crop.


Assuntos
Basidiomycota/metabolismo , Expressão Gênica , Tumores de Planta/microbiologia , Poaceae/microbiologia , Basidiomycota/genética , Basidiomycota/patogenicidade , Expressão Gênica/fisiologia , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Transcriptoma
9.
BMC Cancer ; 18(1): 259, 2018 03 06.
Artigo em Inglês | MEDLINE | ID: mdl-29510676

RESUMO

BACKGROUND: Non-small-cell lung cancer (NSCLC) is characterized by abnormalities of numerous signaling proteins that play pivotal roles in cancer development and progression. Many of these proteins have been reported to be correlated with clinical outcomes of NSCLC. However, none of them could provide adequate accuracy of prognosis prediction in clinical application. METHODS: A total of 384 resected NSCLC specimens from two hospitals in Beijing (BJ) and Chongqing (CQ) were collected. Using immunohistochemistry (IHC) staining on stored formalin-fixed paraffin-embedded (FFPE) surgical samples, we examined the expression levels of 75 critical proteins on BJ samples. Random forest algorithm (RFA) and support vector machines (SVM) computation were applied to identify protein signatures on 2/3 randomly assigned BJ samples. The identified signatures were tested on the remaining BJ samples, and were further validated with CQ independent cohort. RESULTS: A 6-protein signature for adenocarcinoma (ADC) and a 5-protein signature for squamous cell carcinoma (SCC) were identified from training sets and tested in testing sets. In independent validation with CQ cohort, patients can also be divided into high- and low-risk groups with significantly different median overall survivals by Kaplan-Meier analysis, both in ADC (31 months vs. 87 months, HR 2.81; P <  0.001) and SCC patients (27 months vs. not reached, HR 9.97; P <  0.001). Cox regression analysis showed that both signatures are independent prognostic indicators and outperformed TNM staging (ADC: adjusted HR 3.07 vs. 2.43, SCC: adjusted HR 7.84 vs. 2.24). Particularly, we found that only the ADC patients in high-risk group significantly benefited from adjuvant chemotherapy (P = 0.018). CONCLUSIONS: Both ADC and SCC protein signatures could effectively stratify the prognosis of NSCLC patients, and may support patient selection for adjuvant chemotherapy.


Assuntos
Adenocarcinoma/patologia , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Biomarcadores Tumorais/metabolismo , Carcinoma Pulmonar de Células não Pequenas/patologia , Carcinoma de Células Escamosas/patologia , Neoplasias Pulmonares/patologia , Adenocarcinoma/tratamento farmacológico , Adenocarcinoma/metabolismo , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Carcinoma Pulmonar de Células não Pequenas/metabolismo , Carcinoma de Células Escamosas/tratamento farmacológico , Carcinoma de Células Escamosas/metabolismo , Feminino , Seguimentos , Perfilação da Expressão Gênica , Regulação Neoplásica da Expressão Gênica , Humanos , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/metabolismo , Masculino , Pessoa de Meia-Idade , Prognóstico , Estudos Prospectivos , Transdução de Sinais , Taxa de Sobrevida , Análise Serial de Tecidos
10.
Fish Shellfish Immunol ; 72: 1-8, 2018 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-29074130

RESUMO

Zebrafish were exposed to 0, 2.5 and 5 µg/L cadmium (Cd) for 10 weeks, and then each group was exposed to 26 °C(control) and 32 °C (high temperature) for 7 days. 22 indicators were compared between 26 °C and 32 °C in the spleen, including body weight, LPO and NO levels, activity levels of Cu/Zn-SOD, CAT and iNOS, MTs protein levels, and mRNA levels of Nrf2, Cu/Zn-SOD, CAT, HSF1, HSF2, HSP70, MTF-1, MTs, IL-6, IL-10, IL-1ß, TNF-α, iNOS and NF-κB. Most indicators were not significantly affected by heat in fish from no Cd pollution. However, almost all of indicators were responsive to heat in fish pre-exposed to Cd. Several indicators were sensitive to heat in fish pre-exposed to 2.5 µg/L Cd such as iNOS activities, and mRNA levels of iNOS and IL-10. Most other indicators were sensitive to heat in fish pre-exposed to 5 µg/L. The mRNA levels of HSP70 and MTF-1 were up-regulated by heat in fish pre-exposed to 0, 2.5 and 5 µg/L Cd. However, the magnitude of increase was the greatest in fish pre-exposed to 5 µg/L Cd. These differences between control and high temperature would serve as biomarkers to distinguish healthy from Cd-polluted group. The findings imply that metal pollution history should be carefully considered when screening heat biomarkers in fish.


Assuntos
Cádmio/metabolismo , Temperatura Alta/efeitos adversos , Imunidade Inata , Estresse Oxidativo , Poluentes Químicos da Água/metabolismo , Peixe-Zebra/metabolismo , Animais , Biomarcadores/metabolismo , Relação Dose-Resposta a Droga , Feminino , Masculino
11.
J Mater Sci Mater Med ; 29(4): 37, 2018 Mar 19.
Artigo em Inglês | MEDLINE | ID: mdl-29556818

RESUMO

Microstructure, tribological property and corrosion resistance of orthopedic implant materials CoCrW-3 wt.% Cu fabricated by selective laser melting (SLM) process were systematically investigated with CoCrW as control. Equaxied γ-phase together with the inside {111} < 112 > type twin and platelet ε-phase was found in both the Cu-bearing and Cu-free alloys. Compared to the Cu-free alloy, the introduction of 3 wt.% Cu significantly increased the volume fraction of the ε-phase. In both alloys, the hardness of ε-phase zone was rather higher (~4 times) than that of γ-phase zone. The wear factor of 3 wt.% Cu-bearing alloy possessed smaller wear factor, although it had higher friction coefficient compared with Cu-free alloys. The ε-phase in the CoCr alloy would account for reducing both abrasive and fatigue wear. Moreover, the Cu-bearing alloy presented relatively higher corrosion potential Ecorr and lower corrosion current density Icorr compared to the Cu-free alloy. Accordingly, 3 wt.% Cu addition plays a key role in enhancing the wear resistance and corrosion resistance of CoCrW alloys, which indicates that the SLM CoCrW-3Cu alloy is a promising personalized alternative for traditional biomedical implant materials.


Assuntos
Ligas de Cromo , Cobalto , Cobre , Lasers , Tungstênio , Materiais Biocompatíveis , Corrosão , Materiais Dentários , Teste de Materiais
12.
J Biol Chem ; 290(16): 10395-405, 2015 Apr 17.
Artigo em Inglês | MEDLINE | ID: mdl-25681446

RESUMO

Excessive nuclear factor κB (NF-κB) activation should be precisely controlled as it contributes to multiple immune and inflammatory diseases. However, the negative regulatory mechanisms of NF-κB activation still need to be elucidated. Various types of polyubiquitin chains have proved to be involved in the process of NF-κB activation. Many negative regulators linked to ubiquitination, such as A20 and CYLD, inhibit IκB kinase activation in the NF-κB signaling pathway. To find new NF-κB signaling regulators linked to ubiquitination, we used a small scale siRNA library against 51 ubiquitin-associated domain-containing proteins and screened out UBXN1, which contained both ubiquitin-associated and ubiquitin regulatory X (UBX) domains as a negative regulator of TNFα-triggered NF-κB activation. Overexpression of UBXN1 inhibited TNFα-triggered NF-κB activation, although knockdown of UBXN1 had the opposite effect. UBX domain-containing proteins usually act as valosin-containing protein (VCP)/p97 cofactors. However, knockdown of VCP/p97 barely affected UBXN1-mediated NF-κB inhibition. At the same time, we found that UBXN1 interacted with cellular inhibitors of apoptosis proteins (cIAPs), E3 ubiquitin ligases of RIP1 in the TNFα receptor complex. UBXN1 competitively bound to cIAP1, blocked cIAP1 recruitment to TNFR1, and sequentially inhibited RIP1 polyubiquitination in response to TNFα. Therefore, our findings demonstrate that UBXN1 is an important negative regulator of the TNFα-triggered NF-κB signaling pathway by mediating cIAP recruitment independent of VCP/p97.


Assuntos
Proteínas Adaptadoras de Transdução de Sinal/genética , Regulação da Expressão Gênica , NF-kappa B/genética , Proteínas Adaptadoras de Transdução de Sinal/antagonistas & inibidores , Proteínas Adaptadoras de Transdução de Sinal/metabolismo , Adenosina Trifosfatases/antagonistas & inibidores , Adenosina Trifosfatases/genética , Adenosina Trifosfatases/metabolismo , Proteínas de Ciclo Celular/antagonistas & inibidores , Proteínas de Ciclo Celular/genética , Proteínas de Ciclo Celular/metabolismo , Linhagem Celular Tumoral , Genes Reporter , Células HEK293 , Células HeLa , Humanos , Proteínas Inibidoras de Apoptose/genética , Proteínas Inibidoras de Apoptose/metabolismo , Luciferases/genética , Luciferases/metabolismo , NF-kappa B/antagonistas & inibidores , NF-kappa B/metabolismo , Complexo de Proteínas Formadoras de Poros Nucleares/genética , Complexo de Proteínas Formadoras de Poros Nucleares/metabolismo , Ligação Proteica , Estrutura Terciária de Proteína , Proteólise/efeitos dos fármacos , RNA Interferente Pequeno/genética , RNA Interferente Pequeno/metabolismo , Proteínas de Ligação a RNA/genética , Proteínas de Ligação a RNA/metabolismo , Receptores Tipo I de Fatores de Necrose Tumoral/genética , Receptores Tipo I de Fatores de Necrose Tumoral/metabolismo , Transdução de Sinais , Bibliotecas de Moléculas Pequenas , Fator de Necrose Tumoral alfa/farmacologia , Proteína com Valosina
13.
Small Methods ; : e2301508, 2024 Feb 20.
Artigo em Inglês | MEDLINE | ID: mdl-38375977

RESUMO

Perovskite nanocrystals are embedded into metal-organic frameworks (MOFs) to create composites with high light absorption coefficients, tunable electronic properties, high specific surface area, and metal atom tunability for enhanced photocatalytic carban dioxide (CO2 ) reduction. However, existing perovskite-MOF structures with a large particle size are achieved based on Pb source adsorption into the pores of MOFs, which can significantly break down the porous structure, thereby resulting in a decreased specific surface area and impacting CO2 adsorption. Herein, a novel perovskite-MOF structure based on the synthesis of bimetallic Pb-containing MOFs and post-processing to convert Pb to CsPbBr3 nanocrystals (NCs) is proposed. It is discovered that the additional Pb is not introduced by adsorption, but instead engages in coordination and generates Pb-N. The produced ZIF-8@CsPbBr3 NCs are ≈40 nm and have an ultra-high specific surface area of 1325.08 m2 g-1 , and excellent photovoltaic characteristics, which are beneficial for photocatalytic CO2 reduction. The electronic conversion rate of composites is 450 mol g-1 h-1 , which is more than three times that of pure perovskites. Additionally, the superior reduction capacity is sustained after undergoing four cycles. Density Functional Thoery (DFT) simulations are used to explore the 3D charge density at the ZIF-8@CsPbBr3 NCs interface to better understand the electrical structure.

14.
Adv Sci (Weinh) ; 11(1): e2305653, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-37985644

RESUMO

Tumors usually display fetal-like characteristics, and many oncofetal proteins have been identified. However, fetal-like reprogramming of RNA splicing in hepatocellular carcinoma (HCC) is poorly understood. Here, it is demonstrated that the expression of epithelial splicing regulatory protein 2 (ESRP2), an RNA splicing factor, is suppressed in fetal hepatocytes and HCC, in parallel with tumor progression. By combining RNA-Seq with splicing analysis, it is identified that ESRP2 controls the fetal-to-adult switch of multiple splice isoforms in HCC. Functionally, ESRP2 suppressed cell proliferation and migration by specifically switching the alternative splicing (AS) of the TAK1 gene and restraining the expression of the fetal and oncogenic isoform, TAK1_ΔE12. Notably, aberrant TAK1 splicing led to the activation of p38MAPK signaling and predicted poor prognosis in HCC patients. Further investigation revealed that TAK1_ΔE12 protein interacted closely with TAB3 and formed liquid condensation in HCC cells, resulting in p38MAPK activation, enhanced cell migration, and accelerated tumorigenesis. Loss of ESRP2 sensitized HCC cells to TAK1 kinase inhibitor (TAK1i), promoting pyroptotic cell death and CD8+ T cell infiltration. Combining TAK1i with immune checkpoint therapy achieved potent tumor regression in mice. Overall, the findings reveal a previously unexplored onco-fetal reprogramming of RNA splicing and provide novel therapeutic avenues for HCC.


Assuntos
Carcinoma Hepatocelular , Neoplasias Hepáticas , Humanos , Camundongos , Animais , Carcinoma Hepatocelular/genética , Carcinoma Hepatocelular/metabolismo , Neoplasias Hepáticas/genética , Neoplasias Hepáticas/metabolismo , Hepatócitos/metabolismo , Processamento Alternativo/genética , Isoformas de Proteínas/genética , RNA/metabolismo , Proteínas de Ligação a RNA/metabolismo
15.
Nat Commun ; 15(1): 829, 2024 Jan 27.
Artigo em Inglês | MEDLINE | ID: mdl-38280866

RESUMO

Soil organisms are affected by the presence of predatory protists. However, it remains poorly understood how predatory protists can affect plant disease incidence and how fertilization regimes can affect these interactions. Here, we characterise the rhizosphere bacteria, fungi and protists over eleven growing seasons of tomato planting under three fertilization regimes, i.e conventional, organic and bioorganic, and with different bacterial wilt disease incidence levels. We find that predatory protists are negatively associated with disease incidence, especially two ciliophoran Colpoda OTUs, and that bioorganic fertilization enhances the abundance of predatory protists. In glasshouse experiments we find that the predatory protist Colpoda influences disease incidence by directly consuming pathogens and indirectly increasing the presence of pathogen-suppressive microorganisms in the soil. Together, we demonstrate that predatory protists reduce bacterial wilt disease incidence in tomato plants via direct and indirect reductions of pathogens. Our study provides insights on the role that predatory protists play in plant disease, which could be used to design more sustainable agricultural practices.


Assuntos
Solanum lycopersicum , Incidência , Microbiologia do Solo , Eucariotos , Bactérias , Solo
16.
Neurospine ; 21(1): 303-313, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38317550

RESUMO

OBJECTIVE: To compare the long-term clinical and radiographic outcomes of transforaminal endoscopic lumbar discectomy (TELD) versus microdiscectomy (MD). METHODS: The data of 154 patients with lumbar disc herniation (LDH) who underwent TELD (n = 89) or MD (n = 65) were retrospectively analyzed. The patients' clinical outcomes were evaluated using visual analogue scales for leg and low back pain, the Japanese Orthopaedic Association (JOA) score, and the Oswestry Disability Index (ODI). The evolution of radiographic manifestations was observed during follow-up. Potential risk factors for a poor clinical outcome were investigated. RESULTS: During a mean follow-up of 5.5 years (range, 5-7 years), the recurrence rate was 4.49% in the TELD group and 1.54% in the MD group. All scores significantly improved from preoperatively to postoperatively in both groups (p < 0.01). The improvement in the ODI and JOA scores was significantly greater in the TELD than MD group (p < 0.05). Forty-seven patients (52.8%) in the TELD group and 32 (49.2%) in the MD group had Modic changes before surgery, most of which showed no changes at the last follow-up. The degeneration grades of 292 discs (71.0%) were unchanged at the last follow-up, while 86 (20.9%) showed improvement, mostly at the upper adjacent segment. No significant difference was observed in the intervertebral height index or paraspinal muscle-disc ratio. CONCLUSION: Both TELD and MD provide generally satisfactory long-term clinical outcomes for patients with LDH. TELD can be used as a reliable alternative to MD with less surgical trauma. Modic type II changes, decreased preoperative intervertebral height, and a high body mass index are predictors of a poor prognosis.

17.
Toxics ; 11(6)2023 May 27.
Artigo em Inglês | MEDLINE | ID: mdl-37368588

RESUMO

Metal pollution may lead to a variety of diseases; for this reason, it has become a matter of public concern worldwide. However, it is necessary to use biomonitoring approaches to assess the risks posed to human health by metals. In this study, the concentrations of 14 metal elements in 181 urine samples obtained from the general population of Gansu Province, China, were analyzed using inductively coupled plasma mass spectrometry. Eleven out of fourteen target elements had detection frequencies above 85%, namely, Cr, Ni, As, Se, Cd, Al, Fe, Cu and Rb. The concentrations of most metal elements in the urine of our subjects corresponded to the medium levels of subjects in other regional studies. Gender exerted a significant influence (p < 0.05) on the concentrations of Tl, Rb and Zn. The concentrations of Ni, As, Pb, Sr, Tl, Zn, Cu and Se showed significant differences among different age groups and the age-related concentration trends varied among these elements. There were significant differences in the urine concentrations of Zn and Sr between those subjects in the group who were frequently exposed to soil (exposed soil > 20 min/day) and those in the group who were not, indicating that people in regular contact with soil may be more exposed to metals. This study provides useful information for evaluating the levels of metal exposure among general populations.

18.
Chemosphere ; 326: 138494, 2023 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-36966925

RESUMO

The prevalence of metabolic syndrome (MetS) is increasing at an alarming rate worldwide, particularly among elderly individuals. Exposure to various metals has been linked to the development of MetS. However, limited studies have focused attention on the elderly population living in active mining districts. Participants with MetS (N = 292) were matched for age (±2 years old) and sex with a healthy subject (N = 292). We measured the serum levels of 14 metals in older people aged 65-85 years. Conditional logistic regression, restricted cubic spline model, multiple linear regression, and Bayesian Kernel Machine Regression (BKMR) were applied to estimate potential associations between multiple metals and the risk of MetS. Serum levels of Sb and Fe were significantly higher than the controls (0.58 µg/L vs 0.46 µg/L, 2167 µg/L vs 2042 µg/L, p < 0.05), while Mg was significantly lower (20035 µg/L vs 20,394 µg/L, p < 0.05). An increased risk of MetS was associated with higher serum Sb levels (adjusted odds ratio (OR) = 1.61 for the highest tertile vs. the lowest tertile, 95% CI = 1.08-2.40, p-trend = 0.018) and serum Fe levels (adjusted OR = 1.55 for the highest tertile, 95% CI = 1.04-2.33, p-trend = 0.032). Higher Mg levels in serum may have potential protective effects on the development of MetS (adjusted OR = 0.61 for the highest tertile, 95% CI = 0.41-0.91, p-trend = 0.013). A joint exposure analysis by the BKMR model revealed that the mixture of 12 metals (except Tl and Cd) was associated with increased risk of MetS. Our results indicated that exposure to Sb and Fe might increase the risk of MetS in an elderly population living in mining-intensive areas. Further work is needed to confirm the protective effect of Mg on MetS.


Assuntos
Síndrome Metabólica , Humanos , Idoso , Síndrome Metabólica/epidemiologia , Estudos de Casos e Controles , Teorema de Bayes , Análise Multivariada , China/epidemiologia
19.
Sci Total Environ ; 845: 157251, 2022 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-35817099

RESUMO

Phthalate diesters (PAEs) are prevalent and potentially toxic to human health. The university dormitory represents a typical and relatively uniform indoor environment. This study evaluated the concentrations of phthalate monoesters (mPAEs) in urine samples from 101 residents of university status, and the concentrations of PAEs in dust collected from 36 corresponding dormitories. Di-(2-ethylhexyl) phthalate (DEHP, median: 68.0 µg/g) was the major PAE in dust, and mono-ethyl phthalate (47.9 %) was the most abundant mPAE in urine. The levels of both PAEs in dormitory dust and mPAEs in urine were higher in females than in males, indicating higher PAE exposure in females. Differences in lifestyles (dormitory time and plastic product use frequency) may also affect human exposure to PAEs. Moreover, there were significant positive correlations between the estimated daily intakes of PAEs calculated by using concentrations of PAEs in dust (EDID) and mPAEs in urine (EDIU), suggesting that PAEs in dust could be a significant source of human exposure to PAEs. The value of EDID/EDIU for low molecular weight PAEs (3-6 carbon atoms in their backbone) was lower than that of high molecular weight PAEs. The contribution rate of various pathways to PAE exposure illustrated that non-dietary ingestion (87.8 %) was the major pathway of human exposure to PAEs in dust. Approximately 4.95 % of university students' hazard quotients of DEHP were >1, indicating that there may be some health risks associated with DEHP exposure among PAEs. Furthermore, it is recommended that some measures be taken to reduce the production and application of DEHP.


Assuntos
Dietilexilftalato , Ácidos Ftálicos , China , Poeira/análise , Ésteres/análise , Feminino , Humanos , Masculino , Sobrepeso , Ácidos Ftálicos/análise , Medição de Risco , Estudantes , Universidades
20.
ISME J ; 16(8): 1932-1943, 2022 08.
Artigo em Inglês | MEDLINE | ID: mdl-35461357

RESUMO

Plant health is strongly impacted by beneficial and pathogenic plant microbes, which are themselves structured by resource inputs. Organic fertilizer inputs may thus offer a means of steering soil-borne microbes, thereby affecting plant health. Concurrently, soil microbes are subject to top-down control by predators, particularly protists. However, little is known regarding the impact of microbiome predators on plant health-influencing microbes and the interactive links to plant health. Here, we aimed to decipher the importance of predator-prey interactions in influencing plant health. To achieve this goal, we investigated soil and root-associated microbiomes (bacteria, fungi and protists) over nine years of banana planting under conventional and organic fertilization regimes differing in Fusarium wilt disease incidence. We found that the reduced disease incidence and improved yield associated with organic fertilization could be best explained by higher abundances of protists and pathogen-suppressive bacteria (e.g. Bacillus spp.). The pathogen-suppressive actions of predatory protists and Bacillus spp. were mainly determined by their interactions that increased the relative abundance of secondary metabolite Q genes (e.g. nonribosomal peptide synthetase gene) within the microbiome. In a subsequent microcosm assay, we tested the interactions between predatory protists and pathogen-suppressive Bacillus spp. that showed strong improvements in plant defense. Our study shows how protistan predators stimulate disease-suppressive bacteria in the plant microbiome, ultimately enhancing plant health and yield. Thus, we suggest a new biological model useful for improving sustainable agricultural practices that is based on complex interactions between different domains of life.


Assuntos
Eucariotos , Microbiologia do Solo , Bactérias/genética , Eucariotos/genética , Fungos/genética , Doenças das Plantas/microbiologia , Solo/química
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