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1.
Nano Lett ; 24(25): 7645-7653, 2024 Jun 26.
Artigo em Inglês | MEDLINE | ID: mdl-38875704

RESUMO

Understanding the nucleation and growth mechanism of 3d transition bimetallic nanocrystals (NCs) is crucial to developing NCs with tailored nanostructures and properties. However, it remains a significant challenge due to the complexity of 3d bimetallic NCs formation and their sensitivity to oxygen. Here, by combining in situ electron microscopy and synchrotron X-ray techniques, we elucidate the nucleation and growth pathways of Fe-Ni NCs. Interestingly, the formation of Fe-Ni NCs emerges from the assimilation of Fe into Ni clusters together with the reduction of Fe-Ni oxides. Subsequently, these NCs undergo solid-state phase transitions, resulting in two distinct solid solutions, ultimately dominated by γ-Fe3Ni2. Furthermore, we deconvolve the interplays between local coordination and electronic state concerning the growth temperature. We directly visualize the oxidation-state distributions of Fe and Ni at the nanoscale and investigate their changes. This work may reshape and enhance the understanding of nucleation and growth in atomic crystallization.

2.
Zhongguo Shi Yan Xue Ye Xue Za Zhi ; 32(3): 685-692, 2024 Jun.
Artigo em Chinês | MEDLINE | ID: mdl-38926954

RESUMO

OBJECTIVE: To analyze the characteristics and prognosis of patients with mucormycosis after chemotherapy for acute leukemia, and to strengthen understanding of the disease. METHODS: 7 cases of acute leukemia (AL) patients diagnosed with mucormycosis by metagenomic next generation sequencing (mNGS) after chemotherapy at the First Affiliated Hospital of Bengbu Medical College from October 2021 to June 2022 were collected, and their clinical data, including clinical characteristics, diagnosis, treatment, and prognosis, were retrospectively analyzed. RESULTS: Among the 7 patients with AL complicated with mucormycosis, there were 3 males and 4 females, with a median age of 52(20-59) years. There were 6 cases of acute myeloid leukemia (AML) and 1 case of acute lymphocytic leukemia (ALL). Extrapulmonary involvement in 4 cases, including 1 case suspected of central nervous system involvement. The median time for the occurrence of mucor infection was 16(6-69) days after chemotherapy and 19(14-154) days after agranulocytosis. The main clinical manifestations of mucormycosis were fever (7/7), cough (3/7), chest pain (3/7) and dyspnea (1/7). The most common chest CT imaging findings were nodules, patchy or mass consolidation (6/7). All patients were treated with posaconazole or voriconazole prophylaxis during neutropenia phase. 5 patients died within 8 months, and the median time from diagnosis to death was 1 month. CONCLUSION: Although prophylactic antifungal therapy is adopted, patients with acute leukemia still have a risk of mucor infection during the neutropenia phase. Fever is the main manifestation in the early stage of mucor infection. The use of intravenous antifungal drugs alone is ineffective and there is a high mortality rate in acute leukemia patients with mucormycosis.


Assuntos
Leucemia Mieloide Aguda , Mucormicose , Leucemia-Linfoma Linfoblástico de Células Precursoras , Humanos , Mucormicose/diagnóstico , Masculino , Feminino , Adulto , Pessoa de Meia-Idade , Prognóstico , Estudos Retrospectivos , Leucemia Mieloide Aguda/complicações , Leucemia Mieloide Aguda/tratamento farmacológico , Leucemia-Linfoma Linfoblástico de Células Precursoras/complicações , Leucemia-Linfoma Linfoblástico de Células Precursoras/tratamento farmacológico , Antifúngicos/uso terapêutico , Adulto Jovem , Leucemia/complicações , Leucemia/tratamento farmacológico
3.
Cancer Lett ; 597: 217074, 2024 Jun 18.
Artigo em Inglês | MEDLINE | ID: mdl-38901667

RESUMO

Oncogene activation through DNA amplification or overexpression is a crucial driver of cancer initiation and progression. The FOXK2 gene, located on chromosome 17q25, encodes a transcription factor with a forkhead DNA-binding domain. Analysis of genomic datasets reveals that FOXK2 is frequently amplified and overexpressed in breast cancer, correlating with poor patient survival. Knockdown of FOXK2 significantly inhibited breast cancer cell proliferation, migration, anchorage-independent growth, and delayed tumor growth in a xenograft mouse model. Additionally, inhibiting FOXK2 sensitized breast cancer cells to chemotherapy. Co-overexpression of FOXK2 and mutant PI3KCA transformed non-tumorigenic MCF-10A cells, suggesting a role for FOXK2 in PI3KCA-driven tumorigenesis. CCNE2, PDK1, and ESR1 were identified as transcriptional targets of FOXK2 in MCF-7 cells. Small-molecule inhibitors of CCNE2/CDK2 (dinaciclib) and PDK1 (dichloroacetate) exhibited synergistic anti-tumor effects with PI3KCA inhibitor (alpelisib) in vitro. Inhibition of FOXK2 by dinaciclib synergistically enhanced the anti-tumor effects of alpelisib in a xenograft mouse model. Collectively, these findings highlight the oncogenic function of FOXK2 and suggest that FOXK2 and its downstream genes represent potential therapeutic targets in breast cancer.

5.
mSystems ; 9(4): e0105523, 2024 Apr 16.
Artigo em Inglês | MEDLINE | ID: mdl-38501864

RESUMO

Plant-associated diazotrophs strongly relate to plant nitrogen (N) supply and growth. However, our knowledge of diazotrophic community assembly and microbial N metabolism in plant microbiomes is largely limited. Here we examined the assembly and temporal dynamics of diazotrophic communities across multiple compartments (soils, epiphytic and endophytic niches of root and leaf, and grain) of three cereal crops (maize, wheat, and barley) and identified the potential N-cycling pathways in phylloplane microbiomes. Our results demonstrated that the microbial species pool, influenced by site-specific environmental factors (e.g., edaphic factors), had a stronger effect than host selection (i.e., plant species and developmental stage) in shaping diazotrophic communities across the soil-plant continuum. Crop diazotrophic communities were dominated by a few taxa (~0.7% of diazotrophic phylotypes) which were mainly affiliated with Methylobacterium, Azospirillum, Bradyrhizobium, and Rhizobium. Furthermore, eight dominant taxa belonging to Azospirillum and Methylobacterium were identified as keystone diazotrophic taxa for three crops and were potentially associated with microbial network stability and crop yields. Metagenomic binning recovered 58 metagenome-assembled genomes (MAGs) from the phylloplane, and the majority of them were identified as novel species (37 MAGs) and harbored genes potentially related to multiple N metabolism processes (e.g., nitrate reduction). Notably, for the first time, a high-quality MAG harboring genes involved in the complete denitrification process was recovered in the phylloplane and showed high identity to Pseudomonas mendocina. Overall, these findings significantly expand our understanding of ecological drivers of crop diazotrophs and provide new insights into the potential microbial N metabolism in the phyllosphere.IMPORTANCEPlants harbor diverse nitrogen-fixing microorganisms (i.e., diazotrophic communities) in both belowground and aboveground tissues, which play a vital role in plant nitrogen supply and growth promotion. Understanding the assembly and temporal dynamics of crop diazotrophic communities is a prerequisite for harnessing them to promote plant growth. In this study, we show that the site-specific microbial species pool largely shapes the structure of diazotrophic communities in the leaves and roots of three cereal crops. We further identify keystone diazotrophic taxa in crop microbiomes and characterize potential microbial N metabolism pathways in the phyllosphere, which provides essential information for developing microbiome-based tools in future sustainable agricultural production.


Assuntos
Microbiota , Microbiota/genética , Agricultura , Solo/química , Nitrogênio/análise , Produtos Agrícolas/metabolismo , Desenvolvimento Vegetal
6.
Cell Death Dis ; 15(3): 221, 2024 Mar 16.
Artigo em Inglês | MEDLINE | ID: mdl-38493218

RESUMO

Angiogenesis plays an essential role in the microenvironment of hepatocellular carcinoma (HCC). HOXD3 is involved in the metastasis and invasion of HCC cells; Whereas the underlying molecular mechanisms in the microenvironment of HCC remain unknown. Wound healing, transwell invasion, tube formation and spheroid sprouting assays were carried out to identify the effects of HCC-HOXD3-exosomes and genes on the migration of HCC cells. ChIP-PCR was applied to test the binding region of HOXD3 on CCR6, Med15, and CREBBP promoter. Exosome isolation and mRNA-seq were applied to examine the morphological characteristics of exosomes and the contained mRNA in exosomes. Co-IP and Immunofluorescence assays were used to demonstrate the role of CREBBP in the chromatin conformation of CCL20. The nude mice were used to identify the function of genes in regulating migration of HCC in vivo. In this study, integrated cellular and bioinformatic analyses revealed that HOXD3 targeted the promoter region of CCR6 and induced its transcription. CCR6 was delivered by exosomes to endothelial cells and promoted tumour migration. Overexpression of CCR6 promoted metastasis, invasion in HCCs and angiogenesis in endothelial cells (ECs), whereas its downregulation suppressed these functions. The role of HOXD3 in the metastasis and invasion of HCC cells was reversed after the suppression of CCR6. Furthermore, CCL20 was demonstrated as the ligand of CCR6, and its high expression was found in HCC tissues and cells, which was clinically associated with the poor prognosis of HCC. Mechanistically, HOXD3 targets the promoter regions of CREBBP and Med15, which affect CCL20 chromatin conformation by regulating histone acetylation and expression of Pol II to enhance the migration of HCCs. This study demonstrated the function of the HOXD3-CREBBP/Med15-CCL20-CCR6 axis in regulating invasion and migration in HCC, thus providing new therapeutic targets for HCC.


Assuntos
Carcinoma Hepatocelular , Exossomos , Neoplasias Hepáticas , Animais , Camundongos , Carcinoma Hepatocelular/patologia , Neoplasias Hepáticas/patologia , Cromatina , Células Endoteliais/metabolismo , Exossomos/metabolismo , Angiogênese , Camundongos Nus , Linhagem Celular Tumoral , RNA Mensageiro , Movimento Celular/genética , Proliferação de Células , Microambiente Tumoral/genética , Receptores CCR6/genética , Receptores CCR6/metabolismo
7.
J Environ Manage ; 355: 120504, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38447513

RESUMO

Ammonia-oxidation process directly contribute to soil nitrous oxide (N2O) emissions in agricultural soils. However, taxonomy of the key nitrifiers (within ammonia oxidising bacteria (AOB), archaea (AOA) and complete ammonia oxidisers (comammox Nitrospira)) responsible for substantial N2O emissions in agricultural soils is unknown, as is their regulation by soil biotic and abiotic factors. In this study, cumulative N2O emissions, nitrification rates, abundance and community structure of nitrifiers were investigated in 16 agricultural soils from major crop production regions of China using microcosm experiments with amended nitrogen (N) supplemented or not with a nitrification inhibitor (nitrapyrin). Key nitrifier groups involved in N2O emissions were identified by comparative analyses of the different treatments, combining sequencing and random forest analyses. Soil cumulative N2O emissions significantly increased with soil pH in all agricultural soils. However, they decreased with soil organic carbon (SOC) in alkaline soils. Nitrapyrin significantly inhibited soil cumulative N2O emissions and AOB growth, with a significant inhibition of the AOB Nitrosospira cluster 3a.2 (D11) abundance. One Nitrosospira multiformis-like OTU phylotype (OTU34), which was classified within the AOB Nitrosospira cluster 3a.2 (D11), had the greatest importance on cumulative N2O emissions and its growth significantly depended on soil pH and SOC contents, with higher growth at high pH and low SOC conditions. Collectively, our results demonstrate that alkaline soils with low SOC contents have high N2O emissions, which were mainly driven by AOB Nitrosospira cluster 3a.2 (D11). Nitrapyrin can efficiently reduce nitrification-related N2O emissions by inhibiting the activity of AOB Nitrosospira cluster 3a.2 (D11). This study advances our understanding of key nitrifiers responsible for high N2O emissions in agricultural soils and their controlling factors, and provides vital knowledge for N2O emission mitigation in agricultural ecosystems.


Assuntos
Ecossistema , Solo , Solo/química , Amônia/química , Carbono , Oxirredução , Archaea , Nitrificação , Microbiologia do Solo
8.
Cancer Biol Ther ; 25(1): 2322207, 2024 12 31.
Artigo em Inglês | MEDLINE | ID: mdl-38465665

RESUMO

BACKGROUND: CASC21 was reported to be a hotspot gene in cervical cancer. The relationship between CASC21 genetic polymorphisms and cervical cancer has not been reported. Genetic factors influence the occurrence of cervical cancer. Thus, we explored the correlation between CASC21 polymorphisms and cervical cancer. METHODS: A total of 973 participants within 494 cervical cancer cases and 479 healthy controls were recruited. Five single nucleotide polymorphisms (SNPs) in the CASC21 gene were genotyped using the Agena MassARRAY platform. Chi-squared test, logistic regression analysis, odds ratio (OR), multifactor dimensionality reduction (MDR), and 95% confidence interval (95%CI) were used for data analysis. RESULTS: In the overall analysis, rs16902094 (p = .014, OR = 1.86, 95% CI = 1.12-3.08) and rs16902104 (p = .014, OR = 1.86, 95% CI = 1.12-3.09) had the risk-increasing correlation with the occurrence of cervical cancer. Stratification analysis showed that rs16902094 and rs16902104 were still associated with cervical cancer risk in the subgroups with age > 51, BMI < 24 kg/m2, smokers, and patients with cervical squamous cell carcinoma. MDR analysis displayed that rs16902094 (.49%) and rs16902104 (.52%) were the main influential attribution factor for cervical cancer risk. CONCLUSION: Our finding firstly determined that two CASC21 SNPs (rs16902094, rs16902104) were associated with an increased risk of cervical cancer, which adds to our knowledge regarding the effect of CASC21 on cervical carcinogenesis.


Assuntos
Carcinoma de Células Escamosas , Neoplasias do Colo do Útero , Feminino , Humanos , Neoplasias do Colo do Útero/genética , Neoplasias do Colo do Útero/patologia , Predisposição Genética para Doença , Carcinoma de Células Escamosas/genética , Genótipo , Polimorfismo de Nucleotídeo Único , Estudos de Casos e Controles , China/epidemiologia
9.
Microb Biotechnol ; 17(3): e14435, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38465781

RESUMO

The use of microbial inoculant is a promising strategy to improve plant health, but their efficiency often faces challenges due to difficulties in successful microbial colonization in soil environments. To this end, the application of biostimulation products derived from microbes is expected to resolve these barriers via direct interactions with plants or soil pathogens. However, their effectiveness and mechanisms for promoting plant growth and disease resistance remain elusive. In this study, we showed that root irrigation with the extracts of Streptomyces ahygroscopicus strain 769 (S769) solid fermentation products significantly reduced watermelon Fusarium wilt disease incidence by 30% and increased the plant biomass by 150% at a fruiting stage in a continuous cropping field. S769 treatment led to substantial changes in both bacterial and fungal community compositions, and induced a highly interconnected microbial association network in the rhizosphere. The root transcriptome analysis further suggested that S769 treatment significantly improved the expression of the MAPK signalling pathway, plant hormone signal transduction and plant-pathogen interactions, particular those genes related to PR-1 and ethylene, as well as genes associated with auxin production and reception. Together, our study provides mechanistic and empirical evidences for the biostimulation products benefiting plant health through coordinating plant and rhizosphere microbiome interaction.


Assuntos
Citrullus , Fusarium , Microbiota , Citrullus/genética , Citrullus/microbiologia , Rizosfera , Transcriptoma , Doenças das Plantas/prevenção & controle , Doenças das Plantas/microbiologia , Microbiologia do Solo , Solo , Raízes de Plantas/microbiologia
10.
Dalton Trans ; 53(10): 4823-4832, 2024 Mar 05.
Artigo em Inglês | MEDLINE | ID: mdl-38372568

RESUMO

Hydrogen peroxide (H2O2) electrosynthesis via the two-electron oxygen reduction reaction (2e- ORR) represents a green alternative to the energy-intensive anthraquinone process. However, the practical application of this method is limited by the lack of cost-effective and high-performance electrocatalysts. Reported here is a hybrid catalyst composed of nickel (Ni) clusters immobilized onto the surface of two-dimensional siloxene nanosheets (Ni/siloxene), which exhibits excellent efficiency and selectivity in electrocatalytic oxygen reduction to H2O2 in an alkaline medium, demonstrating a standard 2e- pathway with >95% H2O2 selectivity across a wide potential range. Experimental results disclose that the high performance of Ni/siloxene can be traced to a synergy of the Ni clusters and the oxygen-rich surface of siloxene. Density functional theory (DFT) calculations further reveal a weakened interaction between Ni/siloxene and *OOH and the consequently reduced energy barrier for the *OOH protonation toward H2O2 desorption, thus leading to a high 2e- ORR reactivity and selectivity. This work provides a valuable and practical guidance for designing high-performance 2e- ORR electrocatalysts based on the rational engineering of the metal-support interaction.

11.
ACS Appl Mater Interfaces ; 16(10): 12486-12499, 2024 Mar 13.
Artigo em Inglês | MEDLINE | ID: mdl-38417104

RESUMO

Due to the limitation of the high-value-added products obtained from electrocatalytic CO2 reduction within an acid environment, introducing additional elements can expand the diversity of the products obtained during the CO2 reduction reaction (CO2RR) and nitrogen reduction reaction (NRR). Thus, coelectroreduction of CO2 and N2 is a new strategy for producing acetamide (CH3CONH2) via both C-C and C-N bond coupling using Cu-based nitrogen-carbon nanosheets. CO2 can reduce to CO, and a key ketene (*C═C═O) can be generated from *CO*CO dimerization; this ketene is postulated as an intermediate in the formation of acetamide. However, most studies focus on promoting the C-C bond formation. Here, we propose that C-N bond coupling can form acetamide through the interaction of *C═C═O with NH3. The acetamide is formed via a nucleophilic attack between *NH3 and the *C═C═O intermediate. The C-N coupling mechanism was successfully applied to expand the variety of nitrogen-containing products obtained from CO2 and N2 coreduction. Thus, we successfully screened Cu2-based graphite and Cu-based C3N4 as catalysts that can produce C2+ compounds by integrating CO dimerization with acetamide synthesis. In addition, we observed that Cu2-based C2N and Cu-based C3N4 catalysts are suitable for the NRR. Cu-based C3N4 showed high CO2RR and NRR activities with small negative limiting potential (UL) values of -0.83 and -0.58 V compared to those of other candidates, respectively. The formation of *COHCOH from *COHCO was considered the rate-determining step (RDS) during acetamide electrosynthesis. The limiting potential value of Cu2-based C2N was only -0.46 V for NH3 synthesis, and the formation of *NNH was via the RDS via an alternating path. The adsorption energy difference analysis both CO2 and N2 compare with the hydrogen evolution reaction (HER), suggesting that Cu2-based C2N exhibited the highest CO2RR and NRR selectivity among the 13 analyzed catalysts. The results of this study provide innovative insights into the design principle of Cu-based nitrogen-carbon electrocatalysts for generating highly efficient C-N coupling products.

12.
Nat Commun ; 15(1): 634, 2024 Jan 20.
Artigo em Inglês | MEDLINE | ID: mdl-38245504

RESUMO

Hydrogen-Bonded organic frameworks (HOFs) are a type of emerging porous materials. At present, little research has been conducted on their solution state. This work demonstrates that HOFs fragment into small particles while maintaining their original assemblies upon dispersing in solvents, as confirmed by Cryo-electron microscopy coupled with 3D electron diffraction technology. 1D and 2D-Nuclear Magnetic Resonance (NMR) and zeta potential analyses indicate the HOF-based colloid solution and the isolated molecular solution have significant differences in intermolecular interactions and aggregation behavior. Such unique solution processibility allows for fabricating diverse continuous HOF membranes with high crystallinity and porosity through solution-casting approach on various substrates. Among them, HOF-BTB@AAO membranes show high C3H6 permeance (1.979 × 10-7 mol·s-1·m-2·Pa-1) and excellent separation performance toward C3H6 and C3H8 (SF = 14). This continuous membrane presents a green, low-cost, and efficient separation technology with potential applications in petroleum cracking and purification.

13.
Technol Cancer Res Treat ; 23: 15330338231225861, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38225189

RESUMO

The development of 1,8-naphthalimide derivatives as cell probes, DNA targeting agents, and anti-tumor drugs is one of the research hotspots in the field of medicine. Naphthalimide compounds are a kind of DNA embedder, which can change the topological structure of DNA by embedding in the middle of DNA base pairs, and then affect the recognition and action of topoisomerase on DNA. Aminofide and mitonafide are the first 2 drugs to undergo clinical trials. They have good DNA insertion ability, can embed DNA double-stranded structure, and induce topoisomerase II to cut part of pBR322DNA, but not yet entered the market due to their toxicity. In this paper, the design and structure-activity relationship of mononaphthalimide and bisaphthalimide compounds were studied, and the relationship between the structure of naphthalimide and anti-tumor activity was analyzed and discussed. It was found that a variety of structural modifications were significant in improving anti-tumor activity and reducing toxicity.


Assuntos
Antineoplásicos , Neoplasias , Humanos , Naftalimidas/farmacologia , Naftalimidas/química , Naftalimidas/uso terapêutico , Relação Estrutura-Atividade , Neoplasias/tratamento farmacológico , Neoplasias/genética , DNA/genética , DNA/química , DNA/uso terapêutico , Antineoplásicos/uso terapêutico , Linhagem Celular Tumoral
14.
Water Res ; 249: 120913, 2024 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-38039818

RESUMO

Estuary acts as a hotspot of greenhouse gases (GHGs, including CO2, CH4 and N2O) to the atmosphere. However, the GHGs budgets, including input/output fluxes through interfaces and biogeochemical source/sink processes in water columns, of the estuarine systems are still not well constrained due to the lacking of comprehensive observational data. Here, we presented the spatial distributions of GHGs of surface/bottom water and sediment porewater along the Pearl River Estuary (PRE) and adjacent region during summertime. The incorporation of the monitoring for the sediment-water interface (SWI) with these of the water-air interface (WAI) allows us to close the budget revealing additional information of internal consumption/production processes of the three GHGs. The oversaturated CO2 (481-7573 µatm), CH4 (289-16,990 %) and N2O (108-649 %) in surface water suggested PRE is a significant GHGs source to the atmosphere, in which CO2 is the major contributor accounting for 90 % of total global warming potential (GWP), leaving 2.8 % from CH4, and 7.2 % from N2O. Addition to the river input, the SWI releases GHGs to the overlying water with fluxes of 3.5 × 107, 10.8 × 104 and 0.7 × 104 mol d-1 for CO2, CH4 and N2O, respectively. Although all three GHGs exhibited emission to the atmosphere, our mass balance calculation showed that 16.9× 107 mol d-1 of CO2 and 1.0 × 104 mol d-1 of N2O were consumed, respectively, inside the estuary water body, while extra-production (13.8 × 104 mol d-1) of CH4 was demanded in the water body to support its output flux. This is the first experiment quantitatively assessing the importance of internal carbon and nitrogen biogeochemical processes in the PRE. Our finding is of guiding significance to constrain the GHGs budget and draw up realistic pathways for modeling works of GHGs prediction.


Assuntos
Gases de Efeito Estufa , Gases de Efeito Estufa/análise , Dióxido de Carbono , Rios , Estuários , Monitoramento Ambiental , Metano/análise , Óxido Nitroso/análise , Água , China
15.
Small ; 20(21): e2307758, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38100187

RESUMO

Metal halide nanocrystals (MHNCs) embedded in a polymer matrix as flexible X-ray detector screens is an effective strategy with the advantages of low cost, facile preparation, and large area flexibility. However, MHNCs easily aggregate during preparation, recombination, under mechanical force, storage, or high operating temperature. Meanwhile, it shows an unmatched refractive index with polymer, resulting in low light yield. The related stability and properties of the device remain a huge unrevealed challenge. Herein, a composite screen (CZBM@AG-PS) by integrating MHNCs (Cs2ZnBr4: Mn2+ as an example) into silica aerogel (AG) and embedded in polystyrene (PS) is successfully developed. Further characterization points to the high porosity AG template that can effectively improve the dispersion of MHNCs in polymer detector screens, essentially decreasing nonradiative transition, Rayleigh scattering, and performance aging induced by aggregation in harsh environments. Furthermore, the higher light output and lower optical crosstalk are also achieved by a novel light propagation path based on the MHNCs/AG and AG/PS interfaces. Finally, the optimized CZBM@AG-PS screen shows much enhanced light yield, spatial resolution, and temperature stability. Significantly, the strategy is proven universal by the performance tests of other MHNCs embedded composite films for ultra-stable and efficient X-ray imaging.

16.
Plant J ; 118(1): 90-105, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38113332

RESUMO

Necrotrophic fungal plant pathogens employ cell death-inducing proteins (CDIPs) to facilitate infection. However, the specific CDIPs and their mechanisms in pathogenic processes of Sclerotinia sclerotiorum, a necrotrophic pathogen that causes disease in many economically important crop species, have not yet been clearly defined. This study found that S. sclerotiorum secretes SsXyl2, a glycosyl hydrolase family 11 xylanase, at the late stage of hyphal infection. SsXyl2 targets the apoplast of host plants to induce cell death independent of xylanase activity. Targeted disruption of SsXyl2 leads to serious impairment of virulence, which can be recovered by a catalytically impaired SsXyl2 variant, thus supporting the critical role of cell death-inducing activity of SsXyl2 in establishing successful colonization of S. sclerotiorum. Remarkably, infection by S. sclerotiorum induces the accumulation of Nicotiana benthamiana hypersensitive-induced reaction protein 2 (NbHIR2). NbHIR2 interacts with SsXyl2 at the plasma membrane and promotes its localization to the cell membrane and cell death-inducing activity. Furthermore, gene-edited mutants of NbHIR2 displayed increased resistance to the wild-type strain of S. sclerotiorum, but not to the SsXyl2-deletion strain. Hence, SsXyl2 acts as a CDIP that manipulates host cell physiology by interacting with hypersensitive induced reaction protein to facilitate colonization by S. sclerotiorum. These findings provide valuable insights into the pathogenic mechanisms of CDIPs in necrotrophic pathogens and lead to a more promising approach for breeding resistant crops against S. sclerotiorum.


Assuntos
Ascomicetos , Melhoramento Vegetal , Plantas , Virulência , Nicotiana , Morte Celular , Doenças das Plantas/microbiologia
17.
Nat Genet ; 55(12): 2175-2188, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-37985817

RESUMO

Cervical squamous cell carcinoma (CSCC) exhibits a limited response to immune-checkpoint blockade. Here we conducted a multiomic analysis encompassing single-cell RNA sequencing, spatial transcriptomics and spatial proteomics, combined with genetic and pharmacological perturbations to systematically develop a high-resolution and spatially resolved map of intratumoral expression heterogeneity in CSCC. Three tumor states (epithelial-cytokeratin, epithelial-immune (Epi-Imm) and epithelial senescence), recapitulating different stages of squamous differentiation, showed distinct tumor immune microenvironments. Bidirectional interactions between epithelial-cytokeratin malignant cells and immunosuppressive cancer-associated fibroblasts form an immune exclusionary microenvironment through transforming growth factor ß pathway signaling mediated by FABP5. In Epi-Imm tumors, malignant cells interact with natural killer and T cells through interferon signaling. Preliminary analysis of samples from a cervical cancer clinical trial ( NCT04516616 ) demonstrated neoadjuvant chemotherapy induces a state transition to Epi-Imm, which correlates with pathological complete remission following treatment with immune-checkpoint blockade. These findings deepen the understanding of cellular state diversity in CSCC.


Assuntos
Carcinoma de Células Escamosas , Neoplasias do Colo do Útero , Feminino , Humanos , Carcinoma de Células Escamosas/tratamento farmacológico , Carcinoma de Células Escamosas/genética , Neoplasias do Colo do Útero/genética , Inibidores de Checkpoint Imunológico , Relevância Clínica , Ecossistema , Multiômica , Queratinas/metabolismo , Queratinas/uso terapêutico , Microambiente Tumoral/genética , Proteínas de Ligação a Ácido Graxo/uso terapêutico
18.
Math Biosci Eng ; 20(9): 16114-16130, 2023 08 08.
Artigo em Inglês | MEDLINE | ID: mdl-37920005

RESUMO

Under the background that asymptomatic virus carriers have infectivity for an infectious disease, we establish a difference equations model with vaccination and virus testing in this paper. Assuming that the vaccine is 100% effective for susceptible people but cannot stop the infectivity of asymptomatic virus carriers, we study how to combine vaccination and virus testing at the beginning of an epidemic to effectively block the spread of infectious disease in different population sizes. By considering the daily processing capacity of the vaccine and daily proportion of testing, the corresponding numerical simulation results are obtained. It is shown that when vaccine availability and virus testing capacity are insufficient, a reasonable combination of the above two measures can slow down or even block the spread of infectious disease. Single virus testing or vaccination can also block the spread of infectious disease, but this requires a lot of manpower, material and financial resources. When the daily proportion of virus testing is fixed, the ratio of the minimum daily processing capacity of vaccines used to block the spread of infectious disease to the corresponding population size is rather stable. It demonstrates that effective protective measures of the same infectious disease in countries and regions with different population sizes can be used as a reference. These results also provide a certain reference for decision makers on how to coordinate vaccines and virus testing resources to curb the spread of such an infectious disease in a certain population size.


Assuntos
Doenças Transmissíveis , Epidemias , Vacinas , Humanos , Doenças Transmissíveis/epidemiologia , Vacinação/métodos , Epidemias/prevenção & controle , Simulação por Computador
19.
Nat Commun ; 14(1): 6993, 2023 11 01.
Artigo em Inglês | MEDLINE | ID: mdl-37914731

RESUMO

Adult skeletal muscle regeneration is mainly driven by muscle stem cells (MuSCs), which are highly heterogeneous. Although recent studies have started to characterize the heterogeneity of MuSCs, whether a subset of cells with distinct exists within MuSCs remains unanswered. Here, we find that a population of MuSCs, marked by Gli1 expression, is required for muscle regeneration. The Gli1+ MuSC population displays advantages in proliferation and differentiation both in vitro and in vivo. Depletion of this population leads to delayed muscle regeneration, while transplanted Gli1+ MuSCs support muscle regeneration more effectively than Gli1- MuSCs. Further analysis reveals that even in the uninjured muscle, Gli1+ MuSCs have elevated mTOR signaling activity, increased cell size and mitochondrial numbers compared to Gli1- MuSCs, indicating Gli1+ MuSCs are displaying the features of primed MuSCs. Moreover, Gli1+ MuSCs greatly contribute to the formation of GAlert cells after muscle injury. Collectively, our findings demonstrate that Gli1+ MuSCs represents a distinct MuSC population which is more active in the homeostatic muscle and enters the cell cycle shortly after injury. This population functions as the tissue-resident sentinel that rapidly responds to injury and initiates muscle regeneration.


Assuntos
Doenças Musculares , Células Satélites de Músculo Esquelético , Humanos , Músculo Esquelético/metabolismo , Proteína GLI1 em Dedos de Zinco/genética , Proteína GLI1 em Dedos de Zinco/metabolismo , Células Satélites de Músculo Esquelético/metabolismo , Doenças Musculares/metabolismo , Diferenciação Celular
20.
Nanomicro Lett ; 15(1): 228, 2023 Oct 13.
Artigo em Inglês | MEDLINE | ID: mdl-37831204

RESUMO

Single-atom catalysts (SACs) have garnered increasingly growing attention in renewable energy scenarios, especially in electrocatalysis due to their unique high efficiency of atom utilization and flexible electronic structure adjustability. The intensive efforts towards the rational design and synthesis of SACs with versatile local configurations have significantly accelerated the development of efficient and sustainable electrocatalysts for a wide range of electrochemical applications. As an emergent coordination avenue, intentionally breaking the planar symmetry of SACs by adding ligands in the axial direction of metal single atoms offers a novel approach for the tuning of both geometric and electronic structures, thereby enhancing electrocatalytic performance at active sites. In this review, we briefly outline the burgeoning research topic of axially coordinated SACs and provide a comprehensive summary of the recent advances in their synthetic strategies and electrocatalytic applications. Besides, the challenges and outlooks in this research field have also been emphasized. The present review provides an in-depth and comprehensive understanding of the axial coordination design of SACs, which could bring new perspectives and solutions for fine regulation of the electronic structures of SACs catering to high-performing energy electrocatalysis.

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