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1.
Mol Cell ; 83(2): 298-313.e8, 2023 Jan 19.
Artigo em Inglês | MEDLINE | ID: mdl-36603579

RESUMO

Post-translational modifications (PTMs) of proteins are crucial to guarantee the proper biological functions in immune responses. Although protein phosphorylation has been extensively studied, our current knowledge of protein pyrophosphorylation, which occurs based on phosphorylation, is very limited. Protein pyrophosphorylation is originally considered to be a non-enzymatic process, and its function in immune signaling is unknown. Here, we identify a metabolic enzyme, UDP-N-acetylglucosamine pyrophosphorylase 1 (UAP1), as a pyrophosphorylase for protein serine pyrophosphorylation, by catalyzing the pyrophosphorylation of interferon regulatory factor 3 (IRF3) at serine (Ser) 386 to promote robust type I interferon (IFN) responses. Uap1 deficiency significantly impairs the activation of both DNA- and RNA-viruse-induced type I IFN pathways, and the Uap1-deficient mice are highly susceptible to lethal viral infection. Our findings demonstrate the function of protein pyrophosphorylation in the regulation of antiviral responses and provide insights into the crosstalk between metabolism and innate immunity.


Assuntos
Fator Regulador 3 de Interferon , Interferon Tipo I , Animais , Camundongos , Imunidade Inata , Fator Regulador 3 de Interferon/genética , Fator Regulador 3 de Interferon/metabolismo , Interferon Tipo I/genética , Interferon Tipo I/metabolismo , Fosforilação , Transdução de Sinais , Galactosiltransferases/metabolismo
2.
Mol Cell ; 83(2): 281-297.e10, 2023 Jan 19.
Artigo em Inglês | MEDLINE | ID: mdl-36586411

RESUMO

As a key component of the inflammasome, NLRP3 is a critical intracellular danger sensor emerging as an important clinical target in inflammatory diseases. However, little is known about the mechanisms that determine the kinetics of NLRP3 inflammasome stability and activity to ensure effective and controllable inflammatory responses. Here, we show that S-palmitoylation acts as a brake to turn NLRP3 inflammasome off. zDHHC12 is identified as the S-acyltransferase for NLRP3 palmitoylation, which promotes its degradation through the chaperone-mediated autophagy pathway. Zdhhc12 deficiency in mice enhances inflammatory symptoms and lethality following alum-induced peritonitis and LPS-induced endotoxic shock. Notably, several disease-associated mutations in NLRP3 are associated with defective palmitoylation, resulting in overt NLRP3 inflammasome activation. Thus, our findings identify zDHHC12 as a repressor of NLRP3 inflammasome activation and uncover a previously unknown regulatory mechanism by which the inflammasome pathway is tightly controlled by the dynamic palmitoylation of NLRP3.


Assuntos
Autofagia Mediada por Chaperonas , Inflamassomos , Animais , Camundongos , Aciltransferases , Autofagia , Inflamassomos/metabolismo , Inflamação/induzido quimicamente , Inflamação/genética , Lipoilação , Camundongos Endogâmicos C57BL , Proteína 3 que Contém Domínio de Pirina da Família NLR/genética , Proteína 3 que Contém Domínio de Pirina da Família NLR/metabolismo
3.
Nature ; 627(8004): 586-593, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38355797

RESUMO

Over half of hepatocellular carcinoma (HCC) cases diagnosed worldwide are in China1-3. However, whole-genome analysis of hepatitis B virus (HBV)-associated HCC in Chinese individuals is limited4-8, with current analyses of HCC mainly from non-HBV-enriched populations9,10. Here we initiated the Chinese Liver Cancer Atlas (CLCA) project and performed deep whole-genome sequencing (average depth, 120×) of 494 HCC tumours. We identified 6 coding and 28 non-coding previously undescribed driver candidates. Five previously undescribed mutational signatures were found, including aristolochic-acid-associated indel and doublet base signatures, and a single-base-substitution signature that we termed SBS_H8. Pentanucleotide context analysis and experimental validation confirmed that SBS_H8 was distinct to the aristolochic-acid-associated SBS22. Notably, HBV integrations could take the form of extrachromosomal circular DNA, resulting in elevated copy numbers and gene expression. Our high-depth data also enabled us to characterize subclonal clustered alterations, including chromothripsis, chromoplexy and kataegis, suggesting that these catastrophic events could also occur in late stages of hepatocarcinogenesis. Pathway analysis of all classes of alterations further linked non-coding mutations to dysregulation of liver metabolism. Finally, we performed in vitro and in vivo assays to show that fibrinogen alpha chain (FGA), determined as both a candidate coding and non-coding driver, regulates HCC progression and metastasis. Our CLCA study depicts a detailed genomic landscape and evolutionary history of HCC in Chinese individuals, providing important clinical implications.


Assuntos
Carcinoma Hepatocelular , Genoma Humano , Sequenciamento de Nucleotídeos em Larga Escala , Neoplasias Hepáticas , Mutação , Sequenciamento Completo do Genoma , Humanos , Ácidos Aristolóquicos/metabolismo , Carcinogênese , Carcinoma Hepatocelular/genética , Carcinoma Hepatocelular/virologia , China , Cromotripsia , Progressão da Doença , DNA Circular/genética , População do Leste Asiático/genética , Evolução Molecular , Genoma Humano/genética , Vírus da Hepatite B/genética , Mutação INDEL/genética , Fígado/metabolismo , Neoplasias Hepáticas/genética , Neoplasias Hepáticas/virologia , Mutação/genética , Metástase Neoplásica/genética , Fases de Leitura Aberta/genética , Reprodutibilidade dos Testes
4.
Proc Natl Acad Sci U S A ; 121(13): e2315407121, 2024 Mar 26.
Artigo em Inglês | MEDLINE | ID: mdl-38502699

RESUMO

Organic electrodes mainly consisting of C, O, H, and N are promising candidates for advanced batteries. However, the sluggish ionic and electronic conductivity limit the full play of their high theoretical capacities. Here, we integrate the idea of metal-support interaction in single-atom catalysts with π-d hybridization into the design of organic electrode materials for the applications of lithium (LIBs) and potassium-ion batteries (PIBs). Several types of transition metal single atoms (e.g., Co, Ni, Fe) with π-d hybridization are incorporated into the semiconducting covalent organic framework (COF) composite. Single atoms favorably modify the energy band structure and improve the electronic conductivity of COF. More importantly, the electronic interaction between single atoms and COF adjusts the binding affinity and modifies ion traffic between Li/K ions and the active organic units of COFs as evidenced by extensive in situ and ex situ characterizations and theoretical calculations. The corresponding LIB achieves a high reversible capacity of 1,023.0 mA h g-1 after 100 cycles at 100 mA g-1 and 501.1 mA h g-1 after 500 cycles at 1,000 mA g-1. The corresponding PIB delivers a high reversible capacity of 449.0 mA h g-1 at 100 mA g-1 after 150 cycles and stably cycled over 500 cycles at 1,000 mA g-1. This work provides a promising route to engineering organic electrodes.

5.
Proc Natl Acad Sci U S A ; 121(27): e2406884121, 2024 Jul 02.
Artigo em Inglês | MEDLINE | ID: mdl-38935562

RESUMO

Degeneracy and symmetry have a profound relation in quantum systems. Here, we report gate-tunable subband degeneracy in PbTe nanowires with a nearly symmetric cross-sectional shape. The degeneracy is revealed in electron transport by the absence of a quantized plateau. Utilizing a dual gate design, we can apply an electric field to lift the degeneracy, reflected as emergence of the plateau. This degeneracy and its tunable lifting were challenging to observe in previous nanowire experiments, possibly due to disorder. Numerical simulations can qualitatively capture our observation, shedding light on device parameters for future applications.

6.
Hum Mol Genet ; 32(1): 79-92, 2023 01 01.
Artigo em Inglês | MEDLINE | ID: mdl-35921230

RESUMO

Non-small cell lung cancer (NSCLC) is one of the most malignant epithelial tumors. Studies have suggested that DNA hypermethylation of promoters and abnormal histone modifications could induce tumor suppressor genes (TSGs) downregulation in NSCLC. However, the exact mechanism of TSGs downregulation remains unclear. In this study, we found that there is no difference in the regions of most TSGs promoters in NSCLC. Moreover, we found that there is no DNA methylation difference in the region of VILL promoter in NSCLC compared with adjacent tissue samples by pyrosequencing. We further demonstrated that VILL was markedly reactivated in A549 and H1703 cells infected with miR-26A1 lentivirus while this activation was inhibited by JQ1, an enhancer inhibitor. In addition, we identified that miR-26A1 could function as a tumor suppressor to inhibit proliferation and metastasis of NSCLC cells. Chromatin immunoprecipitation assays revealed that overexpression of miR-26A1 could significantly induce the enrichment of H3K27ac at the enhancer regions in A549 cells. To sum up, our findings revealed that enhancer-mediated TSGs regulation occured in NSCLC, suggesting that miR-26A1 could serve as a key regulator and may be a potential therapeutic target for NSCLC.


Assuntos
Carcinoma Pulmonar de Células não Pequenas , Genes Supressores de Tumor , Neoplasias Pulmonares , MicroRNAs , Humanos , Células A549 , Carcinoma Pulmonar de Células não Pequenas/genética , Linhagem Celular Tumoral , Movimento Celular , Proliferação de Células/genética , Regulação Neoplásica da Expressão Gênica/genética , Neoplasias Pulmonares/genética , MicroRNAs/genética
7.
Proc Natl Acad Sci U S A ; 119(42): e2202133119, 2022 10 18.
Artigo em Inglês | MEDLINE | ID: mdl-36215479

RESUMO

Unfolded protein response (UPR) is the mechanism by which cells control endoplasmic reticulum (ER) protein homeostasis. ER proteostasis is essential to adapt to cell proliferation and regeneration in development and tumorigenesis, but mechanisms linking UPR, growth control, and cancer progression remain unclear. Here, we report that the Ire1/Xbp1s pathway has surprisingly oncogenic and tumor-suppressive roles in a context-dependent manner. Activation of Ire1/Xbp1s up-regulates their downstream target Bip, which sequesters Yorkie (Yki), a Hippo pathway transducer, in the cytoplasm to restrict Yki transcriptional output. This regulation provides an endogenous defensive mechanism in organ size control, intestinal homeostasis, and regeneration. Unexpectedly, Xbp1 ablation promotes tumor overgrowth but suppresses invasiveness in a Drosophila cancer model. Mechanistically, hyperactivated Ire1/Xbp1s signaling in turn induces JNK-dependent developmental and oncogenic cell migration and epithelial-mesenchymal transition (EMT) via repression of Yki. In humans, a negative correlation between XBP1 and YAP (Yki ortholog) target gene expression specifically exists in triple-negative breast cancers (TNBCs), and those with high XBP1 or HSPA5 (Bip ortholog) expression have better clinical outcomes. In human TNBC cell lines and xenograft models, ectopic XBP1s or HSPA5 expression alleviates tumor growth but aggravates cell migration and invasion. These findings uncover a conserved crosstalk between the Ire1/Xbp1s and Hippo signaling pathways under physiological settings, as well as a crucial role of Bip-Yki interaction in tumorigenesis that is shared from Drosophila to humans.


Assuntos
Proteínas de Drosophila , Proteínas Serina-Treonina Quinases , Animais , Carcinogênese/metabolismo , Proteínas de Ligação a DNA/genética , Proteínas de Ligação a DNA/metabolismo , Drosophila/metabolismo , Proteínas de Drosophila/genética , Proteínas de Drosophila/metabolismo , Retículo Endoplasmático/metabolismo , Endorribonucleases , Via de Sinalização Hippo , Humanos , Proteínas Serina-Treonina Quinases/genética , Resposta a Proteínas não Dobradas , Proteína 1 de Ligação a X-Box/genética , Proteína 1 de Ligação a X-Box/metabolismo
8.
Nano Lett ; 24(15): 4658-4664, 2024 Apr 17.
Artigo em Inglês | MEDLINE | ID: mdl-38563608

RESUMO

Planar Josephson junctions are predicted to host Majorana zero modes. The material platforms in previous studies are two-dimensional electron gases (InAs, InSb, InAsSb, and HgTe) coupled to a superconductor such as Al or Nb. Here, we introduce a new material platform for planar JJs, the PbTe-Pb hybrid. The semiconductor, PbTe, was grown as a thin film via selective area epitaxy. The Josephson junction was defined by a shadow wall during the deposition of superconductor Pb. Scanning transmission electron microscopy reveals a sharp semiconductor-superconductor interface. Gate-tunable supercurrents and multiple Andreev reflections are observed. A perpendicular magnetic field causes interference patterns of the switching current, exhibiting Fraunhofer-like and SQUID-like behaviors. We further demonstrate a prototype device for Majorana detection wherein phase bias and tunneling spectroscopy are applicable.

9.
BMC Genomics ; 25(1): 530, 2024 May 30.
Artigo em Inglês | MEDLINE | ID: mdl-38816813

RESUMO

BACKGROUND: Skeletal muscle development and fat deposition have important effects on meat quality. The study of regulating skeletal muscle development and fat deposition is of great significance in improving the quality of carcass and meat. In the present study, whole transcriptome sequencing (including RNA-Seq and miRNA-Seq) was performed on the longissimus dorsi muscle (LDM) of Jinfen White pigs at 1, 90, and 180 days of age. RESULTS: The results showed that a total of 245 differentially expressed miRNAs were screened in any two comparisons, which may be involved in the regulation of myogenesis. Among them, compared with 1-day-old group, miR-22-5p was significantly up-regulated in 90-day-old group and 180-day-old group. Functional studies demonstrated that miR-22-5p inhibited the proliferation and differentiation of porcine skeletal muscle satellite cells (PSCs). Pearson correlation coefficient analysis showed that long non-coding RNA (lncRNA) LOC106505926 and CXXC5 gene had strong negative correlations with miR-22-5p. The LOC106505926 and CXXC5 were proven to promote the proliferation and differentiation of PSCs, as opposed to miR-22-5p. In terms of mechanism, LOC106505926 functions as a molecular sponge of miR-22-5p to modulate the expression of CXXC5, thereby inhibits the differentiation of PSCs. In addition, LOC106505926 regulates the differentiation of porcine preadipocytes through direct binding with FASN. CONCLUSIONS: Collectively, our results highlight the multifaceted regulatory role of LOC106505926 in controlling skeletal muscle and adipose tissue development in pigs and provide new targets for improving the quality of livestock products by regulating skeletal muscle development and fat deposition.


Assuntos
Diferenciação Celular , Lipogênese , MicroRNAs , Desenvolvimento Muscular , RNA Longo não Codificante , Animais , RNA Longo não Codificante/genética , Desenvolvimento Muscular/genética , Suínos , MicroRNAs/genética , MicroRNAs/metabolismo , Lipogênese/genética , Diferenciação Celular/genética , Proliferação de Células , Células Satélites de Músculo Esquelético/metabolismo , Células Satélites de Músculo Esquelético/citologia , Músculo Esquelético/metabolismo , Músculo Esquelético/crescimento & desenvolvimento , Células Cultivadas
10.
Mol Cancer ; 23(1): 131, 2024 Jun 26.
Artigo em Inglês | MEDLINE | ID: mdl-38918817

RESUMO

Tumor immune microenvironment (TIME) consists of intra-tumor immunological components and plays a significant role in tumor initiation, progression, metastasis, and response to therapy. Chimeric antigen receptor (CAR)-T cell immunotherapy has revolutionized the cancer treatment paradigm. Although CAR-T cell immunotherapy has emerged as a successful treatment for hematologic malignancies, it remains a conundrum for solid tumors. The heterogeneity of TIME is responsible for poor outcomes in CAR-T cell immunotherapy against solid tumors. The advancement of highly sophisticated technology enhances our exploration in TIME from a multi-omics perspective. In the era of machine learning, multi-omics studies could reveal the characteristics of TIME and its immune resistance mechanism. Therefore, the clinical efficacy of CAR-T cell immunotherapy in solid tumors could be further improved with strategies that target unfavorable conditions in TIME. Herein, this review seeks to investigate the factors influencing TIME formation and propose strategies for improving the effectiveness of CAR-T cell immunotherapy through a multi-omics perspective, with the ultimate goal of developing personalized therapeutic approaches.


Assuntos
Imunoterapia Adotiva , Neoplasias , Receptores de Antígenos Quiméricos , Microambiente Tumoral , Humanos , Microambiente Tumoral/imunologia , Neoplasias/terapia , Neoplasias/imunologia , Imunoterapia Adotiva/métodos , Receptores de Antígenos Quiméricos/imunologia , Receptores de Antígenos Quiméricos/metabolismo , Receptores de Antígenos Quiméricos/genética , Animais , Genômica/métodos , Linfócitos T/imunologia , Linfócitos T/metabolismo
11.
Gastroenterology ; 164(3): 407-423.e17, 2023 03.
Artigo em Inglês | MEDLINE | ID: mdl-36574521

RESUMO

BACKGROUND & AIMS: Lack of thorough knowledge about the complicated immune microenvironment (IM) within a variety of liver metastases (LMs) leads to inappropriate treatment and unsatisfactory prognosis. We aimed to characterize IM subtypes and investigate potential mechanisms in LMs. METHODS: Mass cytometry was applied to characterize immune landscape of a primary liver cancers and liver metastases cohort. Transcriptomic and whole-exome sequencing were used to explore potential mechanisms across distinct IM subtypes. Single-cell transcriptomic sequencing, multiplex fluorescent immunohistochemistry, cell culture, mouse model, Western blot, quantitative polymerase chain reaction, and immunohistochemistry were used for validation. RESULTS: Five IM subtypes were revealed in 100 LMs and 50 primary liver cancers. Patients featured terminally exhausted (IM1) or rare T-cell-inflamed (IM2 and IM3) immune characteristics showed worse outcome. Increased intratumor heterogeneity, enriched somatic TP53, KRAS, APC, and PIK3CA mutations and hyperactivated hypoxia signaling accounted for the formation of vicious subtypes. SLC2A1 promoted immune suppression and desert via increasing proportion of Spp1+ macrophages and their inhibitory interactions with T cells in liver metastatic lesions. Furthermore, SLC2A1 promoted immune escape and LM through inducing regulatory T cells, including regulatory T cells and LAG3+CD4+ T cells in primary colorectal cancer. CONCLUSIONS: The study provided integrated multi-omics landscape of LM, uncovering potential mechanisms for vicious IM subtypes and confirming the roles of SLC2A1 in regulating tumor microenvironment remodeling in both primary tumor and LM lesions.


Assuntos
Neoplasias Hepáticas , Multiômica , Animais , Camundongos , Mutação , Neoplasias Hepáticas/patologia , Sequenciamento do Exoma , Microambiente Tumoral
12.
Small ; 20(14): e2306295, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-37992255

RESUMO

Dual-atom catalysts exhibit higher reactivity and selectivity than the single-atom catalysts. The pyrolysis of bimetal salt precursors is the most typical method for synthesizing dual-atomic catalysts; however, the finiteness of bimetal salts limits the variety of dual-atomic catalysts. In this study, a confined synthesis strategy for synthesizing dual-atomic catalysts is developed. Owing to the in situ synthesis of zeolitic imidazolate frameworks in the pores of covalent organic frameworks (COFs), the migration and aggregation of metal atoms are suppressed adequately during the pyrolysis process. The resultant catalyst contains abundant Zn─Co dual atomic sites with 2.8 wt.% Zn and 0.5 wt.% Co. The catalyst exhibits high reactivity toward oxygen reduction reaction with a half-wave potential of 0.86 V, which is superior to that of the commercial Pt/C catalyst. Theoretical calculations reveal that the Zn atoms in the Zn─Co dual atomic sites promote the formation of intermediate OOH*, and thus contribute to high catalytic performance. This study provides new insights into the design of dual-atom catalysts using COFs.

13.
Small ; 20(28): e2308801, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38295007

RESUMO

The N-doped carbon materials are supposed to be the efficient oxygen reduction reaction (ORR) catalysts with the undefined N-doped carbon ring groups. It is essential to well define the role of the nitrogen atoms of these carbon structures in active behavior. Even though, the covalent organic frameworks (COFs) with precise structures are well developed, but unable to exclude the polar linkages influence. This study presents a series of pyridine-containing COFs linked via nonpolar carbon-carbon double bonds (C = C). Their catalytic activity and selectivity for 2e- ORR are successfully modulated by locating the embedded pyridine nitrogen in the backbones through the linking modes of pyridine moieties within the frameworks. Such phenomena can be attributed to their different binding abilities toward O2, leading to the different binding strength of the intermediate OH* to the catalytic sites, also verified by the theoretical calculation. This work provides us a new insight to design high-efficiency ORR catalysts through the exact location of pyridine nitrogen.

14.
Small ; : e2403655, 2024 Jun 16.
Artigo em Inglês | MEDLINE | ID: mdl-38881262

RESUMO

Developing advanced functional carbon materials is essential for electrocatalysis, caused by their vast merits for boosting many key energy conversion reactions. Herein, the covalent organic frameworks (COFs) is utilized on metal-organic frameworks (MOFs) as the template, under the controllable metal atoms thermal migration process successfully in situ constructs Pd-Co alloy nanoparticles on hollow cubic graphene. The electrocatalytic oxygen reduction reaction (ORR) evaluation showed excellent performances with a half-wave potential of 0.866 V, and a limited current density of 4.975 mA cm-2, that superior to the commercial Pt/C and Co nanoparticles. The contrast experiments and X-ray absorption spectrum demonstrated the aggregated electrons at highly dispersed Pd atoms on Co nanoparticle that promoted the main activities. This work not only enlightens the novel carbon materials designing strategies but also suggests heterogeneous electrocatalysis.

15.
Small ; : e2310847, 2024 Feb 22.
Artigo em Inglês | MEDLINE | ID: mdl-38385814

RESUMO

Sensing pressure and temperature are two important functions of human skin that integrate different types of tactile receptors. In this paper, a deformable artificial flexible multi-stimulus-responsive sensor is demonstrated that can distinguish mechanical pressure from temperature by measuring the impedance and the electrical phase at the same frequency without signal interference. The electrical phase, which is used for measuring the temperature, is totally independent of the pressure by controlling the surface micro-shapes and the ion content of the ionic film. By doping the counter-ion exchange reagent into the ionic liquid before pouring, the upper temperature measuring limit increases from 35 to 50 °C, which is higher than the human body temperature and the ambient temperature on Earth. The sensor shows high sensitivity to pressure (up to 0.495 kPa-1 ) and a wide temperature sensing range (-10 to 50 °C). A multimodal ion-electronic skin (IEM -skin) with an 8 × 8 multi-stimulus-responsive sensor array is fabricated and can successfully sense the distribution of temperature and pressure at the same time. Finally, the sensors are used for monitoring the touching motions of a robot-arm finger controlled by a remote interactive glove and successfully detect the touching states and the temperature changes of different objects.

16.
Opt Lett ; 49(7): 1816-1819, 2024 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-38560872

RESUMO

Flexible optoelectronic platforms, which integrate optoelectronic devices on a flexible substrate, are promising in more complex working environments benefiting from the mechanical flexibility. Herein, for the first time to the best of our knowledge, a flexible GaN-based vertical cavity surface-emitting laser (VCSEL) in the ultraviolet A (UVA) range was demonstrated by using a thin-film transfer process based on laser lift-off (LLO) and spin-coating of a flexible substrate. The lasing wavelength is 376.5 nm with a linewidth of 0.6 nm and threshold energy of 98.4 nJ/pulse, corresponding to a threshold energy density of 13.9 mJ/cm2. The flexible substrate in this study is directly formed by spin-coating of photosensitive epoxy resin, which is much simplified and cost-effective, and a 2-in. wafer scale GaN-based membrane can be successfully transferred to a flexible substrate through this method. Such flexible UVA VCSELs are promising for the development of next-generation flexible and wearable technologies.

17.
Chemistry ; 30(3): e202302997, 2024 Jan 11.
Artigo em Inglês | MEDLINE | ID: mdl-37823329

RESUMO

The oxygen reduction reaction (ORR) is the key reaction in metal air and fuel cells. Among the catalysts that promote ORR, carbon-based metal-free catalysts are getting more attention because of their maximum atom utilization, effective active sites and satisfactory catalytic activity and stability. However, the pyrolysis synthesis of these carbons resulted in disordered porosities and uncontrolled catalytic sites, which hindered us in realizing the catalysts' design, the optimization of catalyst performance and the elucidation of structure-property relationship at the molecular level. Covalent organic frameworks (COFs) constructed with designable building blocks have been employed as metal-free electrocatalysts for the ORR due to their controlled skeletons, tailored pores size and environments, as well as well-defined location and kinds of catalytic sites. In this Concept article, the development of metal-free COFs for the ORR is summarized, and different strategies including skeletons regulation, linkages engineering and edge-sites modulation to improve the catalytic selectivity and activity are discussed. Furthermore, this Concept provides prospectives for designing and constructing powerful electrocatalysts based on the catalytic COFs.

18.
J Magn Reson Imaging ; 59(1): 340-349, 2024 01.
Artigo em Inglês | MEDLINE | ID: mdl-37183874

RESUMO

BACKGROUND: Global brain health has gained increasing attention recently. Imaging markers of brain frailty have been related to functional outcomes in previous studies on anterior circulation; however, little data are available on imaging markers and posterior circulation. PURPOSE: To investigate the impact of brain frailty on functional outcomes in patients with acute perforating artery infarction (PAI) of the posterior circulation. STUDY TYPE: Prospective. POPULATION: One hundred patients (60.78 ± 9.51 years, 72% men) with acute posterior circulation PAI (determined by diffusion-weighted magnetic resonance imaging (MRI)/time-of-flight MR angiography). FIELD STRENGTH/SEQUENCE: T1- and T2-weighted fast spin echo, T2-weighted fluid-attenuated inversion recovery, diffusion-weighted echo planar, gradient echo (susceptibility-weight imaging), and 3D time-of-flight MR angiography sequences at 3.0 T. ASSESSMENT: Periventricular and deep white matter hyperintensities (WMH), enlarged perivascular spaces (EPVS) in the basal ganglia and centrum semiovale area, lacunes, cerebral microbleeds (CMB), and total brain frailty score by calculating the above imaging characters were rated visually by three radiologists with 9, 10, and 11 years of experience and one neuroradiologist with 12. Infarction volume was assessed using baseline diffusion-weighted imaging (DWI) data obtained within 24 hours of symptom onset. A modified Rankin Scale (mRS) score >1 on day 90 defined an adverse functional outcome. Associations between the imaging markers of brain frailty and functional outcomes were assessed. STATISTICAL TESTS: Fisher's exact test, Mann-Whitney U test, and multivariable binary logistic regression. A P value <0.05 was considered statistically significant. RESULTS: Adverse prognoses (mRS > 1) were observed in 34 (34%) patients. Infarction volume, periventricular WMH, deep WMH, basal ganglia EPVS, CMB, and the brain frailty score were significantly associated with adverse functional outcomes. An increased brain frailty score was significantly associated with unfavorable mRS score on day 90 (odds ratio 1.773, 95% confidence interval 1.237-2.541). DATA CONCLUSION: Advanced MRI imaging markers of brain frailty, individually or combined as a total brain frailty score, were associated with worse functional outcomes after acute posterior circulation PAI. LEVEL OF EVIDENCE: 3 TECHNICAL EFFICACY: Stage 3.


Assuntos
Fragilidade , Masculino , Humanos , Feminino , Estudos Prospectivos , Fragilidade/diagnóstico por imagem , Imageamento por Ressonância Magnética , Encéfalo/diagnóstico por imagem , Artérias , Infarto
19.
FASEB J ; 37(2): e22728, 2023 02.
Artigo em Inglês | MEDLINE | ID: mdl-36607259

RESUMO

The incidence of androgen alopecia (AGA), also known as seborrheic alopecia, has surged in recent years, and onset is occurring at younger ages. Dermal papilla cells (DPCs) are key to maintaining hair cycling, and apoptosis-driven processes in DPCs are closely related to hair follicle regeneration. Circular RNAs (circRNAs) are widely present in the human body and are closely related to the occurrence and development of many diseases. Currently, the biological functions of circRNAs in AGA are largely unknown. Whole-transcriptome sequencing was used to screen differential circRNA expression profiles between AGA patients and non-AGA patients. We found that hsa_circ_0002980 (circAGK) was significantly highly expressed in the AGA group. CircAGK promoted DPC apoptosis in the presence of high dihydrotestosterone (DHT) (15 nmol/L). By regulating the miR-3180-5p/BAX axis, circAGK promotes DPC apoptosis in a high DHT environment in vitro and inhibits hair growth in AGA mice in vivo, indicating that circAGK is a potential target for the clinical treatment of AGA.


Assuntos
Di-Hidrotestosterona , MicroRNAs , Humanos , Camundongos , Animais , Di-Hidrotestosterona/farmacologia , Di-Hidrotestosterona/metabolismo , Proteína X Associada a bcl-2/metabolismo , Células Cultivadas , RNA Circular/genética , RNA Circular/metabolismo , Folículo Piloso/metabolismo , Alopecia/genética , Alopecia/metabolismo , Apoptose , MicroRNAs/genética , MicroRNAs/metabolismo
20.
Langmuir ; 40(28): 14384-14398, 2024 Jul 16.
Artigo em Inglês | MEDLINE | ID: mdl-38950117

RESUMO

Laser-assisted electrochemical machining (ECM) is an ideal manufacturing method for Inconel 718 (IN718) because of the method's high efficiency and good surface quality, and the basis for and key to laser-assisted ECM is its anodic electrochemical dissolution behavior. In this study, IN718 in a 10 wt % NaNO3 solution was subjected to innovative electrochemical testing and laser-assisted ECM experiments to investigate its corrosion properties and the passive film characteristics formed on its surface. The passivation-related behaviors and structures of the passive film were investigated based on open-circuit potentials, dynamic polarization, potentiostatic polarization, and electrochemical impedance spectroscopy. It was found that there was obvious active-passive-transpassive transition behavior, and the structure of the passive film in laser-assisted ECM exhibited pores and defects, resulting in weak corrosion resistance, compared with IN718 under ECM without laser irradiation. The chemical composition of the passive film was obtained by X-ray photoelectron spectroscopy. The results showed that the passive film was composed mainly of a mixture of NiO, Ni(OH)2, Cr2O3, CrO3, Fe2O3, α-Fe2O3, α-FeOOH, Nb2O5, NbO, MoO3, MoO2, and TiO2. The passive film formed by laser-assisted ECM was rich in NiO and TiO2 and lacked Cr2O3 and MoO3, which validated its pores and defect structures. A corresponding schematic model was also proposed to characterize the interface structure between the IN718 substrate and the passive film. Laser-assisted ECM tests were performed under different current densities and machining times, and the corrosion morphology of IN718 was identified. Corrosion pits and a loose product layer appeared on the machined surface at low current densities, and the dissolution mechanism was pitting. The quantity and depth of the corrosion pits dispersed on the machined surface clearly decreased as the current density increased. Finally, a quantitative corrosion model was established to characterize the dissolution behavior of IN718 in NaNO3 solution during laser-assisted ECM.

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