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1.
Sci Total Environ ; 954: 176537, 2024 Sep 26.
Artigo em Inglês | MEDLINE | ID: mdl-39332731

RESUMO

The widespread mining and application of rare earth elements (REEs) have led to their continuous accumulation in the environment, with increasing concentrations in soil. The interaction between the most abundant REEs, cerium (Ce), and the prevalent hexagonal birnessite (HB) in the environment is worth attention. HB is one of the most effective metal oxides for the oxidation of arsenite [As(III)] and subsequent adsorption, and thus for arsenic (As) immobilization. Therefore, in this study, we investigated the effect of the presence of Ce(III) ion on the HB formation process and the influence of generating minerals on the oxidation and removal of As(III). Research has found that the interfacial reactions of REEs in manganese (Mn) minerals not only affect their cycling but also alter the properties of the Mn minerals, thereby affecting the environmental fate of As. The results indicated that the presence of Ce ions affected the structure of HB during mineral synthesis and reduced the crystallinity of the conversion products. Their substitution for Mn(IV) in the lattice increased the specific surface area of minerals, reduced particle size, and produced more hydroxyl groups that were conducive to the immobilization of As(III). Meanwhile, Ce(III) was oxidized to Ce(IV) during the formation of Ce-bearing hexagonal birnessite (Ce-HB), and CeO2 nanoparticles were formed on the mineral surface and the removal rate of As(III) by Ce-HB was greatly improved. When the As concentration was lower than 6 mg·L-1, the removal effect of Ce-HB could reach the drinking water standard. However, the oxidation rate decreased due to the decrease in the proportion of Mn(IV). This study fundamentally reveals the behavior of HB coexisting with Ce in the migration and transformation of As(III) in the environment.

2.
Int Immunopharmacol ; 141: 113026, 2024 Nov 15.
Artigo em Inglês | MEDLINE | ID: mdl-39216234

RESUMO

Senescence represents a major risk factor promoting liver fibrosis progression. Sirtuin 1 (SIRT1), an essential regulator of cellular senescence, may be involved in developing liver fibrosis. However, the role and mechanism of SIRT1 in liver fibrosis development were largely unknown. We constructed the liver fibrosis in aged rats induced by carbon tetrachloride (CCl4) and then transfected with GFP-SIRT1 adenoviral vectors. After that, we performed acetylomic analysis of liver tissue in aged rats to identify potential substrates of SIRT1. Furthermore, replicative senescent rat hepatocytes were pretreated with siRNA HnRNP U, SIRT1 adenoviral vectors, resveratrol, and siRNA SIRT1, following stimulation with H2O2. We found that the protein levels of SIRT1 and HnRNP U were down-regulation in aged rat liver fibrotic tissues, with an accumulation of NLRP3 inflammasome and activation of the p53/p21 pathway in liver tissue, as well as an increased level of plasma IL-1ß secretion. In comparison, these effects were reversed by overexpressing SIRT1 with adenoviral vectors. Acetylation of HnRNP U and its sites at K28 and K787 might be potential targets for SIRT1-mediated liver fibrosis in aged rats. Silencing HnRNP U reduced H2O2-induced up-regulation expression of p53, p21, and NLRP3 inflammasome at protein levels. Additionally, H2O2 induced high acetylation of HnRNP U in senescent hepatocytes, whereas overexpressing SIRT1 with adenoviral vectors and resveratrol deacetylate HnRNP U to inhibit NLRP3 inflammasome and the p53/p21 pathway. Besides, the silence of SIRT1 aggravated H2O2-induced p53-related senescence and NLRP3-related inflammation in senescent hepatocytes. Our findings suggested that deacetylation of HnRNPU mediated by SIRT1 attenuated liver fibrosis in the elderly by inhibiting p53/p21 pathway and NLRP3-related inflammation.


Assuntos
Senescência Celular , Cirrose Hepática , Proteína 3 que Contém Domínio de Pirina da Família NLR , Sirtuína 1 , Proteína Supressora de Tumor p53 , Animais , Sirtuína 1/metabolismo , Sirtuína 1/genética , Proteína 3 que Contém Domínio de Pirina da Família NLR/metabolismo , Proteína 3 que Contém Domínio de Pirina da Família NLR/genética , Proteína Supressora de Tumor p53/metabolismo , Proteína Supressora de Tumor p53/genética , Cirrose Hepática/metabolismo , Cirrose Hepática/patologia , Masculino , Ratos , Acetilação , Ratos Sprague-Dawley , Hepatócitos/metabolismo , Envelhecimento/metabolismo , Fígado/patologia , Fígado/metabolismo , Inflamassomos/metabolismo , Tetracloreto de Carbono , Peróxido de Hidrogênio/metabolismo , Inflamação/metabolismo , Interleucina-1beta/metabolismo , Resveratrol/farmacologia , Resveratrol/uso terapêutico , Inibidor de Quinase Dependente de Ciclina p21/metabolismo , Inibidor de Quinase Dependente de Ciclina p21/genética
3.
J Pathol ; 264(1): 42-54, 2024 09.
Artigo em Inglês | MEDLINE | ID: mdl-38956451

RESUMO

Ovarian high-grade serous carcinoma (HGSC) originates in the fallopian tube, with secretory cells carrying a TP53 mutation, known as p53 signatures, identified as potential precursors. p53 signatures evolve into serous tubal intraepithelial carcinoma (STIC) lesions, which in turn progress into invasive HGSC, which readily spreads to the ovary and disseminates around the peritoneal cavity. We recently investigated the genomic landscape of early- and late-stage HGSC and found higher ploidy in late-stage (median 3.1) than early-stage (median 2.0) samples. Here, to explore whether the high ploidy and possible whole-genome duplication (WGD) observed in late-stage disease were determined early in the evolution of HGSC, we analysed archival formalin-fixed paraffin-embedded (FFPE) samples from five HGSC patients. p53 signatures and STIC lesions were laser-capture microdissected and sequenced using shallow whole-genome sequencing (sWGS), while invasive ovarian/fallopian tube and metastatic carcinoma samples underwent macrodissection and were profiled using both sWGS and targeted next-generation sequencing. Results showed highly similar patterns of global copy number change between STIC lesions and invasive carcinoma samples within each patient. Ploidy changes were evident in STIC lesions, but not p53 signatures, and there was a strong correlation between ploidy in STIC lesions and invasive ovarian/fallopian tube and metastatic samples in each patient. The reconstruction of sample phylogeny for each patient from relative copy number indicated that high ploidy, when present, occurred early in the evolution of HGSC, which was further validated by copy number signatures in ovarian and metastatic tumours. These findings suggest that aberrant ploidy, suggestive of WGD, arises early in HGSC and is detected in STIC lesions, implying that the trajectory of HGSC may be determined at the earliest stages of tumour development. © 2024 The Author(s). The Journal of Pathology published by John Wiley & Sons Ltd on behalf of The Pathological Society of Great Britain and Ireland.


Assuntos
Cistadenocarcinoma Seroso , Neoplasias das Tubas Uterinas , Neoplasias Ovarianas , Proteína Supressora de Tumor p53 , Humanos , Feminino , Neoplasias Ovarianas/genética , Neoplasias Ovarianas/patologia , Cistadenocarcinoma Seroso/genética , Cistadenocarcinoma Seroso/patologia , Neoplasias das Tubas Uterinas/genética , Neoplasias das Tubas Uterinas/patologia , Proteína Supressora de Tumor p53/genética , Carcinoma in Situ/genética , Carcinoma in Situ/patologia , Gradação de Tumores , Variações do Número de Cópias de DNA , Mutação , Genômica/métodos , Sequenciamento Completo do Genoma , Ploidias , Pessoa de Meia-Idade , Biomarcadores Tumorais/genética , Progressão da Doença
4.
J Colloid Interface Sci ; 673: 365-372, 2024 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-38878371

RESUMO

As promising prospects for renewable power harvesting, two-dimensional (2D) nanochannels for osmotic energy capture in a reverse electrodialysis arrangement have garnered significant attention. However, existing 2D nanochannel membranes have shown limited power generation capabilities due to challenges in balancing ion flux and selectivity. Here, we construct montmorillonite (MMT)/TEMPO-mediated oxidation cellulose nanofibers (TOCNFs) nanocomposite membranes for enhanced ion transmembrane transport. The intercalation of TOCNFs not only enlarges the interlayer distance, but also provides abundant space charge inside the nanochannels. Benefiting from the strong ion selectivity and high ion flux, the composite membrane achieves a remarkable power output of ∼16.57 W/m2 in the gradient of artificial seawater and river water, exceeding that of the state-of-the-art heterogeneous membrane-based osmotic energy conversion systems. Both experimental and theoretical findings confirm that the synergism of space and surface charge plays a crucial role in promoting osmotic energy conversion. This research contributes valuable insights into the optimization of 2D membranes for efficient clean energy harvesting purposes.

5.
J Hepatol ; 81(4): 667-678, 2024 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-38782118

RESUMO

BACKGROUND & AIMS: Hepatocellular carcinoma (HCC) is a highly fatal cancer characterized by high intra-tumor heterogeneity (ITH). A panoramic understanding of its tumor evolution, in relation to its clinical trajectory, may provide novel prognostic and treatment strategies. METHODS: Through the Asia-Pacific Hepatocellular Carcinoma trials group (NCT03267641), we recruited one of the largest prospective cohorts of patients with HCC, with over 600 whole genome and transcriptome samples from 123 treatment-naïve patients. RESULTS: Using a multi-region sampling approach, we revealed seven convergent genetic evolutionary paths governed by the early driver mutations, late copy number variations and viral integrations, which stratify patient clinical trajectories after surgical resection. Furthermore, such evolutionary paths shaped the molecular profiles, leading to distinct transcriptomic subtypes. Most significantly, although we found the coexistence of multiple transcriptomic subtypes within certain tumors, patient prognosis was best predicted by the most aggressive cell fraction of the tumor, rather than by overall degree of transcriptomic ITH level - a phenomenon we termed the 'bad apple' effect. Finally, we found that characteristics throughout early and late tumor evolution provide significant and complementary prognostic power in predicting patient survival. CONCLUSIONS: Taken together, our study generated a comprehensive landscape of evolutionary history for HCC and provides a rich multi-omics resource for understanding tumor heterogeneity and clinical trajectories. IMPACT AND IMPLICATIONS: This prospective study, utilizing comprehensive multi-sector, multi-omics sequencing and clinical data from surgically resected hepatocellular carcinoma (HCC), reveals critical insights into the role of tumor evolution and intra-tumor heterogeneity (ITH) in determining the prognosis of HCC. These findings are invaluable for oncology researchers and clinicians, as they underscore the influence of distinct evolutionary paths and the 'bad apple' effect, where the most aggressive tumor fraction dictates disease progression. These insights not only enhance prognostic accuracy post-surgical resection but also pave the way for personalized treatment strategies tailored to specific tumor evolutionary and transcriptomic profiles. The coexistence of multiple subtypes within the same tumor prompts a re-appraisal of the utilities of depending on single samples to represent the entire tumor and suggests the need for clinical molecular imaging. This research thus marks a significant step forward in the clinical understanding and management of HCC, underscoring the importance of integrating tumor evolutionary dynamics and multi-omics biomarkers into therapeutic decision-making. CLINICAL TRIAL NUMBER: NCT03267641 (Observational cohort).


Assuntos
Carcinoma Hepatocelular , Neoplasias Hepáticas , Transcriptoma , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Carcinoma Hepatocelular/genética , Carcinoma Hepatocelular/patologia , Carcinoma Hepatocelular/mortalidade , Variações do Número de Cópias de DNA , Evolução Molecular , Neoplasias Hepáticas/genética , Neoplasias Hepáticas/patologia , Neoplasias Hepáticas/mortalidade , Mutação , Prognóstico , Estudos Prospectivos
6.
Sci Total Environ ; 929: 172638, 2024 Jun 15.
Artigo em Inglês | MEDLINE | ID: mdl-38643869

RESUMO

BACKGROUND: Although both air pollution and aging are related to the development of liver cirrhosis, the role of biological aging in association of the mixture of fine particulate matter (PM2.5) and its constituents with liver cirrhosis was unknown. METHODS: This case-control retrospective study included 100 liver cirrhosis patients and 100 control subjects matched by age and sex. The concentrations of PM2.5 and its constituents were estimated for patients using machine-learning methods. The clinical biomarkers were used to calculate biological age using the Klemera-Doubalmethod (KDM) algorithms. Individual associations of PM2.5 and its constituents or biological age with liver cirrhosis were analyzed by generalized linear models. WQS and BKMR were applied to analyze association of mixture of PM2.5 and its constituents with liver cirrhosis. The mediation effect of biological age on associations of PM2.5 and its constituents with liver cirrhosis was further explored. RESULTS: we found that each 1-unit increment in NH4+, NO3-, SO42- and biological age were related to 3.618-fold (95%CI: 1.896, 6.904), 1.880-fold (95%CI: 1.319, 2.680), 2.955-fold (95%CI: 1.656, 5.272) and 1.244-fold (95%CI: 1.093, 1.414) increased liver cirrhosis. Both WQS and BKMR models showed that the mixture of PM2.5 and its constituents was related to increased liver cirrhosis. Furthermore, the mediated proportion of biological age on associations of NH4+ and SO42- with liver cirrhosis were 14.7 % and 14.6 %, respectively. CONCLUSIONS: Biological aging may partly explain the exposure to PM2.5 and its constituents in association with increased risk for liver cirrhosis, implying that delaying the aging process may be a key step for preventing PM2.5-related liver cirrhosis risk.


Assuntos
Poluentes Atmosféricos , Cirrose Hepática , Material Particulado , Sulfatos , Humanos , Material Particulado/análise , Poluentes Atmosféricos/análise , Feminino , Masculino , Estudos de Casos e Controles , Pessoa de Meia-Idade , Sulfatos/análise , Compostos de Amônio , Estudos Retrospectivos , Poluição do Ar/estatística & dados numéricos , Exposição Ambiental/estatística & dados numéricos , Idoso , Envelhecimento
7.
Small ; 20(28): e2309128, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38308414

RESUMO

The osmotic energy conversion properties of biomimetic light-stimulated nanochannels have aroused great interest. However, the power output performance is limited by the low light-induced current and energy conversion efficiency. Here, nanochannel arrays with simultaneous modification of ZnO and di-tetrabutylammonium cis-bis(isothiocyanato)bis(2,20-bipyridyl-4,40-dicarboxylato) ruthenium (II) (N719) onto anodic aluminum oxide (AAO) to combine the nano-confined effect and heterojunction is designed, which demonstrate rectified ion transport behavior due to the asymmetric composition, structure and charge. High cation selectivity and ion flux contribute to the high power density of ≈7.33 W m-2 by mixing artificial seawater and river water. Under light irradiation, heterojunction promoted the production and separation of exciton, enhanced cation selectivity, and improved the utilization efficiency of osmotic energy, providing a remarkable power density of ≈18.49 W m-2 with an increase of 252% and total energy conversion efficiency of 30.43%. The work opens new insights into the biomimetic nanochannels for high-performance energy conversion.

8.
Genome Biol ; 24(1): 144, 2023 06 20.
Artigo em Inglês | MEDLINE | ID: mdl-37340508

RESUMO

Phylogenetic trees based on copy number profiles from multiple samples of a patient are helpful to understand cancer evolution. Here, we develop a new maximum likelihood method, CNETML, to infer phylogenies from such data. CNETML is the first program to jointly infer the tree topology, node ages, and mutation rates from total copy numbers of longitudinal samples. Our extensive simulations suggest CNETML performs well on copy numbers relative to ploidy and under slight violation of model assumptions. The application of CNETML to real data generates results consistent with previous discoveries and provides novel early copy number events for further investigation.


Assuntos
Variações do Número de Cópias de DNA , Neoplasias , Humanos , Filogenia , Taxa de Mutação
9.
Small ; 19(37): e2301512, 2023 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-37154221

RESUMO

The covalent organic frameworks (COFs) membrane with ordered and confined one-dimensional channel has been considered as a promising material to harvest the salinity gradient energy from the seawater and river water. However, the application of the COFs in the field of energy conversion still faces the challenges in membrane preparation. Herein, energy harvesting is achieved by taking advantage of a COFs membrane where TpDB-HPAN is synthesized via layer-by-layer self-assembly strategy at room temperature. The carboxy-rich TpDB COFs can be expediently assembled onto the substrate with an environmental-friendly method. The increased open-circuit voltage (Voc ) endows TpDB-HPAN membrane with a remarkable energy harvesting performance. More importantly, the application perspective is also illuminated by the cascade system. With the advantages of green synthesis, the TpDB-HPAN membrane can be considered as a low-cost and promising candidate for energy conversion.

10.
Nature ; 618(7964): 383-393, 2023 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-37258665

RESUMO

The earliest events during human tumour initiation, although poorly characterized, may hold clues to malignancy detection and prevention1. Here we model occult preneoplasia by biallelic inactivation of TP53, a common early event in gastric cancer, in human gastric organoids. Causal relationships between this initiating genetic lesion and resulting phenotypes were established using experimental evolution in multiple clonally derived cultures over 2 years. TP53 loss elicited progressive aneuploidy, including copy number alterations and structural variants prevalent in gastric cancers, with evident preferred orders. Longitudinal single-cell sequencing of TP53-deficient gastric organoids similarly indicates progression towards malignant transcriptional programmes. Moreover, high-throughput lineage tracing with expressed cellular barcodes demonstrates reproducible dynamics whereby initially rare subclones with shared transcriptional programmes repeatedly attain clonal dominance. This powerful platform for experimental evolution exposes stringent selection, clonal interference and a marked degree of phenotypic convergence in premalignant epithelial organoids. These data imply predictability in the earliest stages of tumorigenesis and show evolutionary constraints and barriers to malignant transformation, with implications for earlier detection and interception of aggressive, genome-instable tumours.


Assuntos
Transformação Celular Neoplásica , Evolução Clonal , Lesões Pré-Cancerosas , Seleção Genética , Neoplasias Gástricas , Humanos , Transformação Celular Neoplásica/genética , Transformação Celular Neoplásica/patologia , Evolução Clonal/genética , Instabilidade Genômica , Mutação , Neoplasias Gástricas/genética , Neoplasias Gástricas/patologia , Lesões Pré-Cancerosas/genética , Lesões Pré-Cancerosas/patologia , Organoides/metabolismo , Organoides/patologia , Aneuploidia , Variações do Número de Cópias de DNA , Análise de Célula Única , Proteína Supressora de Tumor p53/deficiência , Proteína Supressora de Tumor p53/genética , Progressão da Doença , Linhagem da Célula
11.
Environ Technol ; 44(19): 2924-2945, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-35225746

RESUMO

Lead and cadmium are toxic to human, animal, and plant health; they enhance oxidative stress indirectly while simultaneously acting through other toxicodynamic mechanisms. In this study, pristine vermiculite (VER) was functionalized with butylamine (BUT) and a novel organoclay (BUT-VER) adsorbent material was produced for simultaneous removal of Pb(II) and Cd(II) in aquatic medium. The adsorbents were characterized by spectroscopic, microscopic, spectrometric, and potentiometric techniques. The adsorption affecting parameters, including pH, time, initial concentration, temperature, and co-existing cations were investigated and optimized. The kinetic data results were in better agreement with pseudo-second-order (PSO) model (R2 > 0.992). Multiple isotherm models were used to study the adsorption system and results showed that adsorption was monolayer. The BUT-VER showed an improvement in adsorption capacity in a single system (Pb(II): from 134.2 to 160.6 mg g-1) and (Cd(II): from 51.1 to 58.9 mg g-1) while in binary system (Pb(II): from 107.3 to 114.5 mg g-1) and (Cd(II): from 33.7 to 39.7 mg g-1), respectively. Furthermore, BUT-VER was tested in real river water and removed efficiency of >99% was achieved in just 1 h. The dominant mechanisms were electrostatic attraction and complexation. BUT-VER was regenerated for five consecutive cycles and showed >90% removal efficiency. These findings suggest that the proposed inexpensive adsorbent has the potential for practical applications of toxic metals removal from water.


Assuntos
Cádmio , Poluentes Químicos da Água , Humanos , Cádmio/química , Butilaminas , Chumbo/análise , Adsorção , Rios , Água/química , Íons/química , Poluentes Químicos da Água/química , Cinética , Concentração de Íons de Hidrogênio
12.
Small ; 18(35): e2203104, 2022 09.
Artigo em Inglês | MEDLINE | ID: mdl-35931455

RESUMO

Smart modulation of bioelectric signals is of great significance for the development of brain-computer interfaces, bio-computers, and other technologies. The regulation and transmission of bioelectrical signals are realized through the synergistic action of various ion channels in organisms. The bionic nanochannels, which have similar physiological working environment and ion rectification as their biological counterparts, can be used to construct ion rectifier bridges to modulate the bioelectric signals. Here, the artificial smart ionic rectifier bridge with light response is constructed by anodic aluminum oxide (AAO)/poly (spiropyran acrylate) (PSP) nanochannels. The output ion current of the rectifier bridge can be switched between "ON" and "OFF" states by irradiation with UV and visible (Vis) light, and the conversion efficiency (η) of the system in "ON" state is ≈70.5%. The controllable modulation of brain wave-like signal can be realized by ionic rectifier bridge. The ion transport properties and processes of ion rectifier bridges are explained using theoretical calculations based on Poisson-Nernst-Planck (PNP) equations. These findings have significant implications for the understanding of the intelligent ionic circuit and combination of artificial smart ionic channels to organisms, which provide new avenues for development of intelligent ion devices.


Assuntos
Ondas Encefálicas , Canais Iônicos , Transporte de Íons , Íons , Luz
13.
Natl Sci Rev ; 9(3): nwab192, 2022 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-35382356

RESUMO

Intra-tumor heterogeneity (ITH) is a key challenge in cancer treatment, but previous studies have focused mainly on the genomic alterations without exploring phenotypic (transcriptomic and immune) heterogeneity. Using one of the largest prospective surgical cohorts for hepatocellular carcinoma (HCC) with multi-region sampling, we sequenced whole genomes and paired transcriptomes from 67 HCC patients (331 samples). We found that while genomic ITH was rather constant across stages, phenotypic ITH had a very different trajectory and quickly diversified in stage II patients. Most strikingly, 30% of patients were found to contain more than one transcriptomic subtype within a single tumor. Such phenotypic ITH was found to be much more informative in predicting patient survival than genomic ITH and explains the poor efficacy of single-target systemic therapies in HCC. Taken together, we not only revealed an unprecedentedly dynamic landscape of phenotypic heterogeneity in HCC, but also highlighted the importance of studying phenotypic evolution across cancer types.

14.
Small ; 18(20): e2107600, 2022 05.
Artigo em Inglês | MEDLINE | ID: mdl-35324064

RESUMO

Many materials with nanofluidic channels are exploited to achieve salinity gradient energy conversion. However, most materials are fragile, difficult to process, or only prepared into a limited size, which greatly restricts their practical application in the future. Herein, a covalent organic polymers membrane with high mechanical property and stability is fabricated, which can keep integrity in harsh conditions for up to 1 month. In addition, by using the sol-gel approach, a large-area membrane with an area of 26 × 26 cm is expediently fabricated in lab conditions. When the membrane is applied to salinity gradient energy conversion, the maximum output power density is up to 6.21 W m-2 . This work provides a simple method for the fabrication of large-area membrane for salinity gradient energy conversion in future real-world applications.


Assuntos
Polímeros , Salinidade , Eletricidade , Fenômenos Físicos
15.
Mol Plant Pathol ; 23(5): 707-719, 2022 05.
Artigo em Inglês | MEDLINE | ID: mdl-35184365

RESUMO

Viral suppressors of RNA silencing (VSRs) are encoded by diverse viruses to counteract the RNA silencing-mediated defence mounted by the virus-infected host cells. In this study, we identified the NSs protein encoded by tomato zonate spot virus (TZSV) as a potent VSR, and used a potato virus X (PVX)-based heterologous expression system to demonstrate TZSV NSs as a viral pathogenicity factor that intensified PVX symptoms in Nicotiana benthamiana. We then used a yeast two-hybrid screen to identify the suppressor of gene silencing 3 protein of N. benthamiana (NbSGS3), a known component of the plant RNA silencing pathway, as an interaction partner of TZSV NSs. We verified this interaction in plant cells with bimolecular fluorescence complementation, subcellular colocalization, and co-immunoprecipitation. We further revealed that the NSs-NbSGS3 interaction correlated with the VSR activity of TZSV NSs. TZSV NSs reduced the concentration of NbSGS3 protein in plant cells, probably through the ubiquitination and autophagy pathways. Interestingly, TZSV infection, but not NSs overexpression, significantly up-regulated the NbSGS3 transcript levels. Our data indicate that TZSV NSs suppresses RNA silencing of the host plant and enhances TZSV pathogenicity through its interaction with NbSGS3. This study reveals a novel molecular mechanism of NSs-mediated suppression of plant host antiviral defence.


Assuntos
Potexvirus , Solanum lycopersicum , Doenças das Plantas/genética , Plantas , Interferência de RNA , Nicotiana
16.
Nat Genet ; 53(8): 1187-1195, 2021 08.
Artigo em Inglês | MEDLINE | ID: mdl-34211178

RESUMO

Central to tumor evolution is the generation of genetic diversity. However, the extent and patterns by which de novo karyotype alterations emerge and propagate within human tumors are not well understood, especially at single-cell resolution. Here, we present 3D Live-Seq-a protocol that integrates live-cell imaging of tumor organoid outgrowth and whole-genome sequencing of each imaged cell to reconstruct evolving tumor cell karyotypes across consecutive cell generations. Using patient-derived colorectal cancer organoids and fresh tumor biopsies, we demonstrate that karyotype alterations of varying complexity are prevalent and can arise within a few cell generations. Sub-chromosomal acentric fragments were prone to replication and collective missegregation across consecutive cell divisions. In contrast, gross genome-wide karyotype alterations were generated in a single erroneous cell division, providing support that aneuploid tumor genomes can evolve via punctuated evolution. Mapping the temporal dynamics and patterns of karyotype diversification in cancer enables reconstructions of evolutionary paths to malignant fitness.


Assuntos
Neoplasias Colorretais/genética , Neoplasias Colorretais/patologia , Análise de Célula Única/métodos , Proliferação de Células/genética , Cromatina/genética , Cromossomos Humanos , Dosagem de Genes , Humanos , Cariótipo , Cariotipagem , Microscopia Confocal , Mitose , Organoides/crescimento & desenvolvimento , Organoides/patologia , Fuso Acromático/genética
17.
PeerJ ; 9: e11810, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34316414

RESUMO

Aquaporins (AQPs) are a class of highly conserved integral membrane proteins that facilitate the uptake and transport of water and other small molecules across cell membranes. However, little is known about AQP genes in pomegranate (Punica granatum L.) and their potential role in water accumulation of the outer seed coat. We identified 38 PgrAQP genes in the pomegranate genome and divided them into five subfamilies based on a comparative analysis. Purifying selection played a role in the evolution of PgrAQP genes and a whole-genome duplication event in Myrtales may have contributed to the expansion of PgrTIP, PgrSIP, and PgrXIP genes. Transcriptome data analysis revealed that the PgrAQP genes exhibited different tissue-specific expression patterns. Among them, the transcript abundance of PgrPIPs were significantly higher than that of other subfamilies. The mRNA transcription levels of PgrPIP1.3, PgrPIP2.8, and PgrSIP1.2 showed a significant linear relationship with water accumulation in seed coats, indicating that PgrPIP1.3/PgrPIP2.8 located in the plasma membrane and PgrSIP1.2 proteins located on the tonoplast may be involved in water accumulation and contribute to the cell expansion of the outer seed coat, which then develops into juicy edible flesh. Overall, our results provided not only information on the characteristics and evolution of PgrAQPs, but also insights on the genetic improvement of outer seed coats.

18.
ACS Appl Mater Interfaces ; 13(29): 35197-35206, 2021 Jul 28.
Artigo em Inglês | MEDLINE | ID: mdl-34266231

RESUMO

Nanoconfinement ion transport, similar to that of biological ion channels, has attracted widespread research interest and offers prospects for broad applications in energy conversion and nanofluidic diodes. At present, various methods were adopted to improve the rectification performance of nanofluidic diodes including geometrical, chemical, and electrostatic asymmetries. However, contributions of the confinement effects within the channels were neglected, which can be a crucial factor for ion rectification behavior. In this research, we report an "ion pool"-structured nanofluidic diode to improve the confinement effect of the system, which was constructed based on an anodic aluminum oxide (AAO) nanoporous membrane sandwiched between zeolitic imidazolate framework 8 (ZIF-8) and tungsten oxide (WO3) thin membranes. A high rectification ratio of 192 is obtained through this nanofluidic system due to ions could be enriched or depleted sufficiently within the ion pool. Furthermore, this high-rectification-ratio ion pool-structured nanofluidic diode possessed pH-responsive and excellent ion selectivity. We developed it as a pH-responsive power gating for a salinity gradient harvesting device by controlling the surface charge density of the ion pool nanochannel narrow ends with different pH values, and hence, the ionic gate is switched between On and Off states, with a gating ratio of up to 27, which exhibited 8 times increase than ZIF-8-AAO and AAO-WO3 composite membranes. Significantly, the peculiar ion pool structure can generate high rectification ratios due to the confinement effect, which then achieves high gating ratios. Such ion pool-structured nanochannels created new avenues to design and optimize nanofluidic diodes and boosted their applications in energy conversion areas.

19.
J Phys Chem Lett ; 12(23): 5587-5592, 2021 Jun 17.
Artigo em Inglês | MEDLINE | ID: mdl-34109791

RESUMO

The confinement effect of biological ion channels regulates the transport of molecules and ions due to angstrom-sized pores. The structure of the potassium channel has a selection region (3-4 Å), a cavity (10 Å), and a gated region, while ZIF-8 has intrinsic pores with a 3.4 Å aperture and an 11.6 Å cavity similar to those of the potassium channel. Inspired by this, we constructed the glass/ZIF-8 hybrid membrane through an electrochemical growth process to explore the kinetics of the ion transmembrane by I-V curves and electrochemical impedance spectroscopy. These complementary approaches yield highly correlated results that show that ion transportation of the ZIF-8 membrane follows Arrhenius behavior. The rates of ions are controlled by the transmembrane activation energy, in which the ionic charge and radius play an important role.


Assuntos
Imidazóis/farmacocinética , Estruturas Metalorgânicas/farmacocinética , Metais Alcalinoterrosos/farmacocinética , Nanotecnologia/métodos , Canais de Potássio/farmacocinética , Imidazóis/química , Canais Iônicos/química , Canais Iônicos/farmacocinética , Transporte de Íons/fisiologia , Cinética , Estruturas Metalorgânicas/química , Metais Alcalinoterrosos/química , Canais de Potássio/química
20.
Sci Total Environ ; 725: 138358, 2020 Jul 10.
Artigo em Inglês | MEDLINE | ID: mdl-32464746

RESUMO

Minimization of cadmium (Cd) accumulation in wheat is an effective method to prevent Cd-related health risks to humans. To understand the underlying mechanisms of restricting Cd transport, the role of nodes in Cd restriction was studied in eight Chinese wheat cultivars. The Cd accumulation differed significantly among the cultivars. The grain Cd concentrations were mainly dependent on the Cd concentrations in the roots and shoots. The Cd transport in the shoots controlled the wheat grain Cd accumulations. Nodes in the wheat stem have distinct functions in the transfer, distribution, and restriction of Cd. The node connected to the panicle showed the lowest translocation factors. The area of the vascular bundles, especially the diffuse vascular bundles, in the junctional node with the flag leaf was the key factor in restricting Cd transfer to the wheat grain. There was a significant relation between these areas and the grain Cd concentrations. The conclusion of this study is that screening or breeding cultivars with low Cd concentrations in the roots or with smaller areas of diffuse vascular bundles in the junctional nodes with the flag leaf is an effective strategy to decrease Cd concentration in wheat grains.


Assuntos
Cádmio/análise , Poluentes do Solo/análise , Grão Comestível/química , Humanos , Folhas de Planta/química , Raízes de Plantas/química , Triticum
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