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1.
Mol Cell ; 81(16): 3262-3274.e3, 2021 08 19.
Artigo em Inglês | MEDLINE | ID: mdl-34214466

RESUMO

N-degron pathways are a set of proteolytic systems that target the N-terminal destabilizing residues of substrates for proteasomal degradation. Recently, the Gly/N-degron pathway has been identified as a new branch of the N-degron pathway. The N-terminal glycine degron (Gly/N-degron) is recognized by ZYG11B and ZER1, the substrate receptors of the Cullin 2-RING E3 ubiquitin ligase (CRL2). Here we present the crystal structures of ZYG11B and ZER1 bound to various Gly/N-degrons. The structures reveal that ZYG11B and ZER1 utilize their armadillo (ARM) repeats forming a deep and narrow cavity to engage mainly the first four residues of Gly/N-degrons. The α-amino group of the Gly/N-degron is accommodated in an acidic pocket by five conserved hydrogen bonds. These structures, together with biochemical studies, decipher the molecular basis for the specific recognition of the Gly/N-degron by ZYG11B and ZER1, providing key information for future structure-based chemical probe design.


Assuntos
Proteínas de Ciclo Celular/ultraestrutura , Glicina/química , Conformação Proteica , Receptores de Citocinas/ultraestrutura , Sequência de Aminoácidos/genética , Proteínas de Ciclo Celular/química , Proteínas de Ciclo Celular/genética , Cristalografia por Raios X , Glicina/genética , Células HEK293 , Humanos , Complexo de Endopeptidases do Proteassoma/genética , Complexo de Endopeptidases do Proteassoma/ultraestrutura , Ligação Proteica/genética , Domínios Proteicos/genética , Proteólise , Receptores de Citocinas/química , Receptores de Citocinas/genética , Especificidade por Substrato , Ubiquitina/genética
2.
Nat Chem Biol ; 20(9): 1164-1175, 2024 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-38773330

RESUMO

The C-terminal to LisH (CTLH) complex is a ubiquitin ligase complex that recognizes substrates with Pro/N-degrons via its substrate receptor Glucose-Induced Degradation 4 (GID4), but its function and substrates in humans remain unclear. Here, we report PFI-7, a potent, selective and cell-active chemical probe that antagonizes Pro/N-degron binding to human GID4. Use of PFI-7 in proximity-dependent biotinylation and quantitative proteomics enabled the identification of GID4 interactors and GID4-regulated proteins. GID4 interactors are enriched for nucleolar proteins, including the Pro/N-degron-containing RNA helicases DDX21 and DDX50. We also identified a distinct subset of proteins whose cellular levels are regulated by GID4 including HMGCS1, a Pro/N-degron-containing metabolic enzyme. These data reveal human GID4 Pro/N-degron targets regulated through a combination of degradative and nondegradative functions. Going forward, PFI-7 will be a valuable research tool for investigating CTLH complex biology and facilitating development of targeted protein degradation strategies that highjack CTLH E3 ligase activity.


Assuntos
Ligação Proteica , Humanos , Proteólise , Células HEK293 , Sondas Moleculares/química , Sondas Moleculares/metabolismo , RNA Helicases DEAD-box/metabolismo , Ubiquitina-Proteína Ligases/metabolismo , Degrons , Receptores de Interleucina-17
3.
Proc Natl Acad Sci U S A ; 119(30): e2203218119, 2022 07 26.
Artigo em Inglês | MEDLINE | ID: mdl-35867826

RESUMO

The exposed N-terminal or C-terminal residues of proteins can act, in cognate sequence contexts, as degradation signals (degrons) that are targeted by specific E3 ubiquitin ligases for proteasome-dependent degradation by N-degron or C-degron pathways. Here, we discovered a distinct C-degron pathway, termed the Gln/C-degron pathway, in which the B30.2 domain of E3 ubiquitin ligase TRIM7 (TRIM7B30.2) mediates the recognition of proteins bearing a C-terminal glutamine. By determining crystal structures of TRIM7B30.2 in complexes with various peptides, we show that TRIM7B30.2 forms a positively charged binding pocket to engage the "U"-shaped Gln/C-degron. The four C-terminal residues of a substrate play an important role in C-degron recognition, with C-terminal glutamine as the principal determinant. In vitro biochemical and cellular experiments were used to further analyze the substrate specificity and selective degradation of the Gln/C-degron by TRIM7.


Assuntos
Glutamina , Proteólise , Proteínas com Motivo Tripartido , Ubiquitina-Proteína Ligases , Glutamina/metabolismo , Humanos , Domínios Proteicos , Especificidade por Substrato , Proteínas com Motivo Tripartido/química , Proteínas com Motivo Tripartido/metabolismo , Ubiquitina-Proteína Ligases/química , Ubiquitina-Proteína Ligases/metabolismo
4.
J Am Chem Soc ; 146(12): 8098-8109, 2024 Mar 27.
Artigo em Inglês | MEDLINE | ID: mdl-38477574

RESUMO

Determining the structures of previously unseen compounds from experimental characterizations is a crucial part of materials science. It requires a step of searching for the structure type that conforms to the lattice of the unknown compound, which enables the pattern matching process for characterization data, such as X-ray diffraction (XRD) patterns. However, this procedure typically places a high demand on domain expertise, thus creating an obstacle for computer-driven automation. Here, we address this challenge by leveraging a deep-learning model composed of a union of convolutional residual neural networks. The accuracy of the model is demonstrated on a dataset of over 60,000 different compounds for 100 structure types, and additional categories can be integrated without the need to retrain the existing networks. We also unravel the operation of the deep-learning black box and highlight the way in which the resemblance between the unknown compound and a structure type is quantified based on both local and global characteristics in XRD patterns. This computational tool opens new avenues for automating structure analysis on materials unearthed in high-throughput experimentation.

5.
Br J Cancer ; 130(4): 597-612, 2024 03.
Artigo em Inglês | MEDLINE | ID: mdl-38184692

RESUMO

BACKGROUND: The expression of Egl-9 family hypoxia-inducible factor 3 (EGLN3) is notably decreased in various malignancies, including gastric cancer (GC). While the predominant focus has been on the hydroxylase activity of EGLN3 for its antitumour effects, recent findings have suggested nonenzymatic roles for EGLN3. METHODS: This study assessed the clinical significance of EGLN3 expression in GC and explored the connection between EGLN3 DNA promoter methylation and transcriptional silencing. To investigate the effect of EGLN3 on GC cells, a gain-of-function strategy was adopted. RNA sequencing was conducted to identify the key effector molecules and signalling pathways associated with EGLN3. RESULTS: EGLN3 expression was significantly reduced in GC tissues, correlating with poorer patient prognosis. EGLN3 hypermethylation disrupts transcriptional equilibrium, contributing to deeper tumour invasion and lymph node metastasis, thus exacerbating GC progression. Conversely, restoration of EGLN3 expression in GC cells substantially inhibited cell proliferation and metastasis. EGLN3 was also found to impede the malignant progression of GC cells by downregulating Jumonji C domain-containing protein 8-mediated activation of the NF-κB pathway, independent of its hydroxylase activity. CONCLUSIONS: EGLN3 has the potential to hinder the spread of GC cells through a nonenzymatic mechanism, thereby shedding light on the complex nature of GC progression.


Assuntos
NF-kappa B , Neoplasias Gástricas , Humanos , NF-kappa B/genética , NF-kappa B/metabolismo , Neoplasias Gástricas/patologia , Transdução de Sinais/genética , Metilação de DNA , Regulação Neoplásica da Expressão Gênica , Oxigenases de Função Mista/genética , Linhagem Celular Tumoral , Proliferação de Células/genética , Prolina Dioxigenases do Fator Induzível por Hipóxia/genética , Prolina Dioxigenases do Fator Induzível por Hipóxia/metabolismo
6.
Hum Genet ; 143(3): 331-342, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38478153

RESUMO

Accurate discrimination of pathogenic and nonpathogenic variation remains an enormous challenge in clinical genetic testing of inherited retinal diseases (IRDs) patients. Computational methods for predicting variant pathogenicity are the main solutions for this dilemma. The majority of the state-of-the-art variant pathogenicity prediction tools disregard the differences in characteristics among different genes and treat all types of mutations equally. Since missense variants are the most common type of variation in the coding region of the human genome, we developed a novel missense mutation pathogenicity prediction tool, named Prediction of Deleterious Missense Mutation for IRDs (PdmIRD) in this study. PdmIRD was tailored for IRDs-related genes and constructed with the conditional random forest model. Population frequencies and a newly available prediction tool were incorporated into PdmIRD to improve the performance of the model. The evaluation of PdmIRD demonstrated its superior performance over nonspecific tools (areas under the curves, 0.984 and 0.910) and an existing eye abnormalities-specific tool (areas under the curves, 0.975 and 0.891). We also demonstrated the submodel that used a smaller gene panel further slightly improved performance. Our study provides evidence that a disease-specific model can enhance the prediction of missense mutation pathogenicity, especially when new and important features are considered. Additionally, this study provides guidance for exploring the characteristics and functions of the mutated proteins in a greater number of Mendelian disorders.


Assuntos
Mutação de Sentido Incorreto , Doenças Retinianas , Humanos , Biologia Computacional/métodos , Predisposição Genética para Doença , Testes Genéticos/métodos , Doenças Retinianas/diagnóstico , Doenças Retinianas/genética
7.
Small ; : e2403267, 2024 Jul 10.
Artigo em Inglês | MEDLINE | ID: mdl-38982953

RESUMO

Carbon-based perovskite solar cells (PSCs) coupled with solution-processed hole transport layers (HTLs) have shown potential owing to their combination of low cost and high performance. However, the commonly used poly(3-hexylthiophene) (P3HT) semicrystalline-polymer HTL dominantly shows edge-on molecular orientation, in which the alkyl side chains directly contact the perovskite layer, resulting in an electronically poor contact at the perovskite/P3HT interface. The study adopts a synergetic strategy comprising of additive and solvent engineering to transfer the edge-on molecular orientation of P3HT HTL into 3D molecular orientation. The target P3HT HTL possesses improved charge transport as well as enhanced moisture-repelling capability. Moreover, energy level alignment between target P3HT HTL and perovskite layer is realized. As a result, the champion devices with small (0.04 cm2) and larger areas (1 cm2) deliver notable efficiencies of 20.55% and 18.32%, respectively, which are among the highest efficiency of carbon-electrode PSCs.

8.
Small ; 20(2): e2305219, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-37658514

RESUMO

Materials with negative thermal expansion (NTE) attract significant research attention owing to their unique physical properties and promising applications. Although ferroelectric phase transitions leading to NTE are widely investigated, information on antiferroelectricity-induced NTE remains limited. In this study, single-crystal and polycrystalline Pb2 CoMoO6 samples are prepared at high pressure and temperature conditions. The compound crystallizes into an antiferroelectric Pnma orthorhombic double perovskite structure at room temperature owing to the opposite displacements dominated by Pb2+ ions. With increasing temperature to 400 K, a structural phase transition to cubic Fm-3m paraelectric phase occurs, accompanied by a sharp volume contraction of 0.41%. This is the first report of an antiferroelectric-to-paraelectric transition-induced NTE in Pb2 CoMoO6 . Moreover, the compound also exhibits remarkable NTE with an average volumetric coefficient of thermal expansion αV = -1.33 × 10-5 K-1 in a wide temperature range of 30-420 K. The as-prepared Pb2 CoMoO6 thus serves as a prototype material system for studying antiferroelectricity-induced NTE.

9.
Drug Metab Dispos ; 52(3): 180-187, 2024 Feb 14.
Artigo em Inglês | MEDLINE | ID: mdl-38123352

RESUMO

Two open-label, phase 1 studies (NCT05064449, NCT05098041) investigated the effects of cytochrome P450 (CYP) 3A inhibition (via itraconazole), UDP glucuronosyltransferase (UGT) 1A9 inhibition (via mefenamic acid), and CYP3A induction (via rifampin) on the pharmacokinetics of soticlestat and its metabolites M-I and M3. In period 1 of both studies, participants received a single dose of soticlestat 300 mg. In period 2, participants received itraconazole on days 1-11 and soticlestat 300 mg on day 5 (itraconazole/mefenamic acid study; part 1); mefenamic acid on days 1-7 and soticlestat 300 mg on day 2 (itraconazole/mefenamic acid study; part 2); or rifampin on days 1-13 and soticlestat 300 mg on day 11 (rifampin study). Twenty-eight healthy adults participated in the itraconazole/mefenamic acid study (14 per part) and 15 participated in the rifampin study (mean age, 38.1-40.7 years; male, 79-93%). For maximum observed concentration, the geometric mean ratios (GMRs) of soticlestat + itraconazole, mefenamic acid, or rifampin to soticlestat alone were 116.6%, 107.3%, and 13.2%, respectively, for soticlestat; 10.7%, 118.0%, and 266.1%, respectively, for M-I, and 104.6%, 88.2%, and 66.6%, respectively, for M3. For area under the curve from time 0 to infinity, the corresponding GMRs were 124.0%, 100.6%, and 16.4% for soticlestat; 13.3%, 117.0%, and 180.8% for M-I; and 120.3%, 92.6%, and 58.4% for M3. Soticlestat can be administered with strong CYP3A and UGT1A9 inhibitors, but not strong CYP3A inducers (except for antiseizure medications, which will be further evaluated in ongoing phase 3 studies). In both studies, all treatment-emergent adverse events were mild or moderate. SIGNIFICANCE STATEMENT: These drug-drug interaction studies improve our understanding of the potential changes that may arise in soticlestat exposure in patients being treated with CYP3A inhibitors, UGT1A9 inhibitors, or CYP3A inducers. The results build on findings from previously published soticlestat studies and provide important information to help guide clinical practice. Soticlestat has shown positive phase 2 results and is currently in phase 3 development for the treatment of seizures in patients with Dravet syndrome and Lennox-Gastaut syndrome.


Assuntos
Citocromo P-450 CYP3A , Piperidinas , Piridinas , Rifampina , Adulto , Humanos , Masculino , Citocromo P-450 CYP3A/metabolismo , Rifampina/efeitos adversos , Indutores do Citocromo P-450 CYP3A/efeitos adversos , Indutores do Citocromo P-450 CYP3A/farmacocinética , Itraconazol/efeitos adversos , UDP-Glucuronosiltransferase 1A , Voluntários Saudáveis , Ácido Mefenâmico , Interações Medicamentosas , Inibidores do Citocromo P-450 CYP3A/efeitos adversos , Área Sob a Curva
10.
Crit Rev Biotechnol ; 44(2): 255-274, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-36658718

RESUMO

As the demand for tea (Camellia sinensis) has grown across the world, the amount of biomass waste that has been produced during the harvesting process has also increased. Tea consumption was estimated at about 6.3 million tonnes in 2020 and is anticipated to reach 7.4 million tonnes by 2025. The generation of tea waste (TW) after use has also increased concurrently with rising tea consumption. TW includes clipped stems, wasted tea leaves, and buds. Many TW-derived products have proven benefits in various applications, including energy generation, energy storage, wastewater treatment, and pharmaceuticals. TW is widely used in environmental and energy-related applications. Energy recovery from low- and medium-calorific value fuels may be accomplished in a highly efficient manner using pyrolysis, anaerobic digestion, and gasification. TW-made biochar and activated carbon are also promising adsorbents for use in environmental applications. Another area where TW shows promise is in the synthesis of phytochemicals. This review offers an overview of the conversion procedures for TW into value-added products. Further, the improvements in their applications for energy generation, energy storage, removal of different contaminants, and extraction of phytochemicals have been reviewed. A comprehensive assessment of the sustainable use of TWs as environmentally acceptable renewable resources is compiled in this review.


Assuntos
Chá , Resíduos
11.
Inorg Chem ; 63(42): 19964-19971, 2024 Oct 21.
Artigo em Inglês | MEDLINE | ID: mdl-39385599

RESUMO

A B-site ordered double perovskite oxide Cd2CrSbO6 was synthesized under high-pressure and high-temperature conditions. The compound crystallizes to a monoclinic structure with a space group of P21/n. The charge configuration is confirmed to be that of Cd2+/Cr3+/Sb5+. The magnetic Cr3+ ions form a tetrahedral structural frustrated lattice, while a long-range ferromagnetic phase transition is found to occur at TC = 16.5 K arising from the superexchange interaction via the Cr-O-Cd-O-Cr pathway. Electrical transport measurements indicate that Cd2CrSbO6 is an insulator that can be described by the Mott 3D variable range hopping mechanism. First-principles calculations reproduce well the ferromagnetic and insulating ground state of Cd2CrSbO6 with an energy band gap of 1.55 eV. The intrinsic ferromagnetic insulating nature qualifies Cd2CrSbO6 as a promising candidate for possible spintronics applications.

12.
Environ Sci Technol ; 58(15): 6804-6813, 2024 Apr 16.
Artigo em Inglês | MEDLINE | ID: mdl-38512799

RESUMO

The pervasive contamination of novel brominated flame retardants (NBFRs) in remote polar ecosystems has attracted great attention in recent research. However, understanding regarding the trophic transfer behavior of NBFRs in the Arctic and Antarctic marine food webs is limited. In this study, we examined the occurrence and trophodynamics of NBFRs in polar benthic marine sediment and food webs collected from areas around the Chinese Arctic Yellow River Station (n = 57) and Antarctic Great Wall Station (n = 94). ∑7NBFR concentrations were in the range of 1.27-7.47 ng/g lipid weight (lw) and 0.09-1.56 ng/g lw in the Arctic and Antarctic marine biota, respectively, among which decabromodiphenyl ethane (DBDPE) was the predominant compound in all sample types. The biota-sediment bioaccumulation factors (g total organic carbon/g lipid) of NBFRs in the Arctic (0.85-3.40) were 4-fold higher than those in the Antarctica (0.13-0.61). Trophic magnification factors (TMFs) and their 95% confidence interval (95% CI) of individual NBFRs ranged from 0.43 (95% CI: 0.32, 0.60) to 1.32 (0.92, 1.89) and from 0.34 (0.24, 0.49) to 0.92 (0.56, 1.51) in the Arctic and Antarctic marine food webs, respectively. The TMFs of most congeners were significantly lower than 1, indicating a trophic dilution potential. This is one of the very few investigations on the trophic transfer of NBFRs in remote Arctic and Antarctic marine ecosystems, which provides a basis for exploring the ecological risks of NBFRs in polar regions.


Assuntos
Retardadores de Chama , Regiões Antárticas , Retardadores de Chama/análise , Cadeia Alimentar , Ecossistema , Bioacumulação , Regiões Árticas , Monitoramento Ambiental , Lipídeos , Éteres Difenil Halogenados/análise
13.
Environ Res ; 247: 118227, 2024 Apr 15.
Artigo em Inglês | MEDLINE | ID: mdl-38253192

RESUMO

The current study aimed to assess the effectiveness of biochar formed from algae in the removal of Cr(VI) through the process of impregnating brown algae Sargassum hemiphyllum with KHCO3. The synthesis of KHCO3-activated biochar (KBAB-3), demonstrating remarkable adsorption capabilities for Cr(VI), was accomplished utilizing a mixture of brown algae and KHCO3 in a mass ratio of 1:3, followed by calcination at a temperature of 700 °C. Based on the empirical evidence, it can be observed that KBAB-3 shown a significant ability to adsorb Cr(VI) within a range of 60-160 mg g-1 across different environmental conditions. In addition, the KBAB-3 material demonstrated the advantageous characteristic of easy separation, allowing for the continued maintenance of a high efficiency in removing Cr(VI) even after undergoing numerous cycles of reuse. In conclusion, the application of KBAB-3, a novel adsorbent, exhibits considerable prospects for effective removal of Cr(VI) from diverse water sources in the near future.


Assuntos
Carvão Vegetal , Phaeophyceae , Poluentes Químicos da Água , Adsorção , Poluentes Químicos da Água/análise , Cromo/análise , Água , Cinética
14.
Environ Res ; 263(Pt 1): 120011, 2024 Sep 14.
Artigo em Inglês | MEDLINE | ID: mdl-39284486

RESUMO

Microalgae-assisted bioremediation, enriched by nanomaterial integration, offers a sustainable approach to environmental pollution mitigation while harnessing microalgae's potential as a biocatalyst and biorefinery resource. This strategy explores the interaction between microalgae, nanomaterials, and bioremediation, advancing sustainability objectives. The potent combination of microalgae and nanomaterials highlights the biorefinery's promise in effective pollutant removal and valuable algal byproduct production. Various nanomaterials, including metallic nanoparticles and semiconductor quantum dots, are reviewed for their roles in inorganic and organic pollutant removal and enhancement of microalgae growth. Limited studies have been conducted to establish nanomaterial's (CeO2, ZnO, Fe3O4, Al2O3, etc.) role on microalgae in pollution remediation; most studies cover inorganic pollutants (heavy metals and nutrients) remediation, exhibited 50-300% bioremediation efficiency improvement; however, some studies cover antibiotics and toxic dyes removal efficiency with 19-95% improvement. These aspects unveil the complex mechanisms underlying nanomaterial-pollutant-microalgae interactions, focusing on adsorption, photocatalysis, and quantum dot properties. Strategies to enhance bioremediation efficiency are discussed, including pollutant uptake improvement, real-time control, tailored nanomaterial design, and nutrient recovery. The review assesses recent advancements, navigates challenges, and envisions a sustainable future for bioremediation, underlining the transformative capacity of nanomaterial-driven microalgae-assisted bioremediation. This work aligns with Sustainable Development Goals 6 (Clean Water and Sanitation) and 12 (Responsible Consumption and Production) by exploring nanomaterial-enhanced microalgae bioremediation for sustainable pollution management and resource utilization.

15.
Environ Res ; 252(Pt 4): 119143, 2024 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-38751000

RESUMO

In this study, biochar derived from chestnut shells was synthesized through pyrolysis at varying temperatures from 300 °C to 900 °C. The study unveiled that the pyrolysis temperature is pivotal in defining the physical and chemical attributes of biochar, notably its adsorption capabilities and its role in activating peracetic acid (PAA) for the efficient removal of acetaminophen (APAP) from aquatic environments. Notably, the biochar processed at 900 °C, referred to as CN900, demonstrated an exceptional adsorption efficiency of 55.8 mg g-1, significantly outperforming its counterparts produced at lower temperatures (CN300, CN500, and CN700). This enhanced performance of CN900 is attributed to its increased surface area, improved micro-porosity, and a greater abundance of oxygen-containing functional groups, which are a consequence of the elevated pyrolysis temperature. These oxygen-rich functional groups, such as carbonyls, play a crucial role in facilitating the decomposition of the O-O bond in PAA, leading to the generation of reactive oxygen species (ROS) through electron transfer mechanisms. This investigation contributes to the development of sustainable and cost-effective materials for water purification, underscoring the potential of chestnut shell-derived biochar as an efficient adsorbent and catalyst for PAA activation, thereby offering a viable solution for environmental cleanup efforts.


Assuntos
Acetaminofen , Carvão Vegetal , Ácido Peracético , Pirólise , Poluentes Químicos da Água , Carvão Vegetal/química , Acetaminofen/química , Poluentes Químicos da Água/química , Ácido Peracético/química , Adsorção , Purificação da Água/métodos
16.
Environ Toxicol ; 39(2): 723-735, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-37676967

RESUMO

BACKGROUND: Lung adenocarcinoma (LUAD) is the prevalent malignancy worldwide. The aim is to explore differentially expressed genes (DEGs) associated with immune infiltration and survival time of LUAD patients, and predict transcriptional factors for shedding new light on molecular mechanisms and individual therapy of LUAD. METHOD: ScRNA-seq data of LUAD patients was downloaded from GSE148071 and analyzed by R packages. The clustering and protein-protein interaction network were constructed for screening DEGs. Gene Set Enrichment Analysis (GSEA) and GO enrichment analysis were performed in epithelial cell subgroups with high differentiation potential. Potential regulatory transcription factors were predicted. RESULTS: Sixteen epithelial cell types were required and top 20 genes were identified on cell subgroup Epi4 with the highest differentiation potential associated with poor prognosis of LUAD in PPI network. GSEA and GO annotation results showed that cell subgroup Epi4 was enriched in the biological processes of cell proliferation and energy metabolism, and positively regulated the function of cell proliferation. TPI1 was significantly highly expressed in LUAD samples (p < .0001). TPI1 demonstrated a negative correlation with the infiltration levels of CD8+ T cells, CD4+ T cells, B cells, and activated mast cells, whilst manifesting a positive correlation with the infiltration levels of resident mast cells, Th2 cells, and MDSC. Epi4 was regulated by transcription factors MXD3 and GATA4. CONCLUSION: Overexpression of TPI1 was identified as a novel biomarker for LUAD, and potential regulatory transcription factors MXD3 and GATA4 regulated the proliferation of LUAD with the poor prognosis, which may serve as potential targets to suppress the proliferation of LUAD.


Assuntos
Adenocarcinoma de Pulmão , Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , Humanos , Carcinoma Pulmonar de Células não Pequenas/genética , Transcriptoma , Neoplasias Pulmonares/genética , Células Epiteliais , Fatores de Transcrição , Análise de Sequência de RNA
17.
J Environ Manage ; 370: 122942, 2024 Oct 19.
Artigo em Inglês | MEDLINE | ID: mdl-39427621

RESUMO

The pervasive issue of microplastics in aquatic environments presents a formidable challenge to traditional water treatment methodologies, including those utilizing KMnO4. This study pioneers advanced oxidation processes (AOPs) method aimed at improving the degradation of PE microplastics by employing a dual treatment strategy that combines KMnO4 oxidation with UV irradiation. Detailed analysis of the surface modifications and chemical functional groups of the treated PE microplastics revealed the establishment of Mn-O-Mn linkages on their surfaces. Weight reductions of 3.9%, 4.9%, and 7.5% were observed for the KMnO4/UVA, KMnO4/UVB, and KMnO4/UVC treatments over seven days, respectively. The emergence of carboxyl and hydroxyl groups played a crucial role in accelerating the degradation process. Notably, the combined application of UVC rays and KMnO4 resulted in the most effective degradation of PE microplastics observed in our study. The process significantly enhanced the formation of MnO2 particles from KMnO4 oxidation, with concentrations ranging from 0.036 to 0.070 mM for KMnO4/UVA, 0.066-0.097 mM for KMnO4/UVB, and 0.086-0.180 mM for KMnO4/UVC. Furthermore, the influence of varying pH levels, KMnO4 concentrations, and different water sources on the degradation efficacy was investigated. The pivotal role of free radicals and reactive manganese species in promoting the degradation of PE microplastics was identified. A comparative evaluation with treatments solely utilizing KMnO4 or UV light highlighted the enhanced effectiveness of the combined approach, demonstrating its potential as an efficient solution for reducing microplastic contamination in aquatic systems.

18.
Environ Geochem Health ; 46(11): 424, 2024 Sep 24.
Artigo em Inglês | MEDLINE | ID: mdl-39316302

RESUMO

Per- and poly-fluoroalkyl substances (PFAS) are persistent organic pollutants that severely threaten the environment and human health due to their distinct chemical composition, extensive production, widespread distribution, bioaccumulation in nature, and long-term persistence. This review focuses on the occurrence and sources of PFAS in seafood, with a particular emphasis on advanced detection methods viz. nanoparticle-based, biosensor-based, and metal-organic frameworks-based, and mass spectrometric techniques. The challenges associated with these advanced detection technologies are also discussed. Recent research and regulatory updates about PFAS, including hazardous and potential health effects, epidemiological studies, and various risk assessment models, have been reviewed. In addition, the need for global monitoring programs and regulations on PFAS are critically reviewed by underscoring their crucial role in protecting human health and the environment. Further, approaches for reducing PFAS in seafood are highlighted with future innovative remediation directions. Although advanced PFAS analytical methods are available, selectivity, sample preparation, and sensitivity are still significant challenges associated with detection of PFAS in seafood matrices.  Moreover, crucial research gaps and solutions to essential concerns are critically explored in this review.


Assuntos
Monitoramento Ambiental , Fluorocarbonos , Alimentos Marinhos , Poluentes Químicos da Água , Alimentos Marinhos/análise , Fluorocarbonos/análise , Poluentes Químicos da Água/análise , Humanos , Monitoramento Ambiental/métodos , Contaminação de Alimentos/análise , Animais , Medição de Risco , Espectrometria de Massas/métodos
19.
Physiol Mol Biol Plants ; 30(7): 1071-1084, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-39100882

RESUMO

Lonicera japonica Flos is a valuable herb in the Lonicerae family. While transcriptomic studies on L. japonica have focused on different tissues (stems, leaves, flowers) or flowering stages, few have investigated the molecular mechanisms underlying chemical composition synthesis influenced by exogenous factors, such as foliar fertilization. Moreover, most transcriptomic studies on L. Japonica have been conducted on chlorogenic acid and luteoloside, and the molecular synthesis mechanism of the overall chemical composition has not been analyzed. Methods: We conducted a single-factor, four-level foliar fertilization experiment using yeast polysaccharides. Different yeast polysaccharides concentrations were sprayed on L. japonica for six consecutive days with dynamic sampling. High-performance liquid chromatography determined the active ingredients in each group. The two groups exhibiting the most significant differences were selected for transcriptomic analysis to identify key synthetic genes responsible for L. japonica's active ingredients. Key results: Principal component analysis conducted on samples collected on September 8 revealed significant differences in the active ingredient amounts between the 0.1 g/L yeast polysaccharides treatment group and the control group. Transcriptome sequencing analysis identified 218 significantly differentially expressed genes, including 60 upregulated and 158 downregulated genes. Twelve differential genes involved in the chemical components synthesis pathway of L. japonica under yeast polysaccharides treatment were identified: PAL1, PAL2, PAL3, 4CL1, 4CL, CHS1, CHS2, CHS, CHI1, CHI2, F3H, and SOH. Conclusions: This study contributes to the theoretical understanding of essential synthetic genes associated with L. japonica's active ingredients. It offers data support for further gene exploration and sheds light on the molecular mechanisms underlying L. japonica quality formation. These findings hold significant implications for enhancing the content of secondary metabolites of L. japonica. Supplementary Information: The online version contains supplementary material available at 10.1007/s12298-024-01482-1.

20.
J Food Sci Technol ; 61(5): 847-860, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38487279

RESUMO

Polyunsaturated fatty acids (PUFAs) found in microalgae, primarily omega-3 (ω-3) and omega-6 (ω-6) are essential nutrients with positive effects on diseases such as hyperlipidemia, atherosclerosis, and coronary risk. Researchers still seek improvement in PUFA yield at a large scale for better commercial prospects. This review summarizes advancements in microalgae PUFA research for their cost-effective production and potential applications. Moreover, it discusses the most promising cultivation modes using organic and inorganic sources. It also discusses biomass hydrolysates to increase PUFA production as an alternative and sustainable organic source. For cost-effective PUFA production, heterotrophic, mixotrophic, and photoheterotrophic cultivation modes are assessed with traditional photoautotrophic production modes. Also, mixotrophic cultivation has fascinating sustainable attributes over other trophic modes. Furthermore, it provides insight into growth phase (stage I) improvement strategies to accumulate biomass and the complementing effects of other stress-inducing strategies during the production phase (stage II) on PUFA enhancement under these cultivation modes. The role of an excessive or limiting range of salinity, nutrients, carbon source, and light intensity were the most effective parameter in stage II for accumulating higher PUFAs such as ω-3 and ω-6. This article outlines the commercial potential of microalgae for omega PUFA production. They reduce the risk of diabetes, cardiovascular diseases (CVDs), cancer, and hypertension and play an important role in their emerging role in healthy lifestyle management.

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