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1.
Plant Cell ; 35(8): 2736-2749, 2023 08 02.
Artigo em Inglês | MEDLINE | ID: mdl-37233025

RESUMO

Understanding gene regulatory networks is essential to elucidate developmental processes and environmental responses. Here, we studied regulation of a maize (Zea mays) transcription factor gene using designer transcription activator-like effectors (dTALes), which are synthetic Type III TALes of the bacterial genus Xanthomonas and serve as inducers of disease susceptibility gene transcription in host cells. The maize pathogen Xanthomonas vasicola pv. vasculorum was used to introduce 2 independent dTALes into maize cells to induced expression of the gene glossy3 (gl3), which encodes a MYB transcription factor involved in biosynthesis of cuticular wax. RNA-seq analysis of leaf samples identified, in addition to gl3, 146 genes altered in expression by the 2 dTALes. Nine of the 10 genes known to be involved in cuticular wax biosynthesis were upregulated by at least 1 of the 2 dTALes. A gene previously unknown to be associated with gl3, Zm00001d017418, which encodes aldehyde dehydrogenase, was also expressed in a dTALe-dependent manner. A chemically induced mutant and a CRISPR-Cas9 mutant of Zm00001d017418 both exhibited glossy leaf phenotypes, indicating that Zm00001d017418 is involved in biosynthesis of cuticular waxes. Bacterial protein delivery of dTALes proved to be a straightforward and practical approach for the analysis and discovery of pathway-specific genes in maize.


Assuntos
Fatores de Transcrição , Zea mays , Zea mays/genética , Zea mays/metabolismo , Fatores de Transcrição/genética , Fatores de Transcrição/metabolismo , Ativação Transcricional , Bactérias/metabolismo , Proteínas de Bactérias/genética , Proteínas de Bactérias/metabolismo , Regulação da Expressão Gênica de Plantas/genética , Ceras/metabolismo
2.
Chem Rev ; 123(16): 10206-10257, 2023 Aug 23.
Artigo em Inglês | MEDLINE | ID: mdl-37523660

RESUMO

Using compressive mechanical forces, such as pressure, to induce crystallographic phase transitions and mesostructural changes while modulating material properties in nanoparticles (NPs) is a unique way to discover new phase behaviors, create novel nanostructures, and study emerging properties that are difficult to achieve under conventional conditions. In recent decades, NPs of a plethora of chemical compositions, sizes, shapes, surface ligands, and self-assembled mesostructures have been studied under pressure by in-situ scattering and/or spectroscopy techniques. As a result, the fundamental knowledge of pressure-structure-property relationships has been significantly improved, leading to a better understanding of the design guidelines for nanomaterial synthesis. In the present review, we discuss experimental progress in NP high-pressure research conducted primarily over roughly the past four years on semiconductor NPs, metal and metal oxide NPs, and perovskite NPs. We focus on the pressure-induced behaviors of NPs at both the atomic- and mesoscales, inorganic NP property changes upon compression, and the structural and property transitions of perovskite NPs under pressure. We further discuss in depth progress on molecular modeling, including simulations of ligand behavior, phase-change chalcogenides, layered transition metal dichalcogenides, boron nitride, and inorganic and hybrid organic-inorganic perovskites NPs. These models now provide both mechanistic explanations of experimental observations and predictive guidelines for future experimental design. We conclude with a summary and our insights on future directions for exploration of nanomaterial phase transition, coupling, growth, and nanoelectronic and photonic properties.

3.
Nucleic Acids Res ; 51(1): 29-40, 2023 01 11.
Artigo em Inglês | MEDLINE | ID: mdl-36537218

RESUMO

Toehold-mediated strand displacement and its regulatory tools are fundamental for DNA nanotechnology. However, current regulatory tools all need to change the original sequence of reactants, making the regulation inconvenient and cumbersome. More importantly, the booming development of DNA nanotechnology will soon promote the production of packaged and batched devices or circuits with specified functions. Regarding standardized, packaged DNA nanodevices, access to personalized post-modification will greatly help users, whereas none of the current regulatory tools can provide such access, which has greatly constrained DNA nanodevices from becoming more powerful and practical. Herein, we developed a novel regulation tool named Cap which has two basic functions of subtle regulation of the reaction rate and erasability. Based on these functions, we further developed three advanced functions. Through integration of all functions of Cap and its distinct advantage of working independently, we finally realized personalized tailor-made post-modification on pre-fabricated DNA circuits. A pre-fabricated dual-output DNA circuit was successfully transformed into an equal-output circuit, a signal-antagonist circuit and a covariant circuit according to our requirements. Taken together, Cap is easy to design and generalizable for all strand displacement-based DNA nanodevices. We believe the Cap tool will be widely used in regulating reaction networks and personalized tailor-made post-modification of DNA nanodevices.


Assuntos
DNA , Nanotecnologia , DNA/genética , Recombinação Genética
4.
Small ; : e2405940, 2024 Aug 23.
Artigo em Inglês | MEDLINE | ID: mdl-39180267

RESUMO

Carbon superstructures with exquisite morphologies and functionalities show appealing prospects in energy realms, but the systematic tailoring of their microstructures remains a perplexing topic. Here, hydrangea-shaped heterodiatomic carbon superstructures (CHS) are designed using a solution phase manufacturing route, wherein machine learning workflow is applied to screen precursor-matched solvent for optimizing solvent-precursor interaction. Based on the established solubility parameter model and molecular growth kinetics simulation, ethanol as the optimal solvent stimulates thermodynamic solubilization and growth of polymeric intermediates to evoke CHS. Featured with surface-active motifs and consecutive charge transfer paths, CHS allows high accessibility of zincophilic sites and fast ion migration with low energy barriers. A anion-cation hybrid charge storage mechanism of CHS cathode is disclosed, which entails physical alternate uptake of Zn2+/CF3SO3 - ions at electroactive sites and chemical bipedal redox of Zn2+ ions with carbonyl/pyridine motifs. Such a beneficial electrochemistry contributes to all-round improvement in Zn-ion storage, involving excellent capacities (231 mAh g-1 at 0.5 A g-1; 132 mAh g-1 at 50 A g-1), high energy density (152 Wh kg-1), and long-lasting cyclability (100 000 cycles). This work expands the design versatilities of superstructure materials and will accelerate experimental procedures during carbon manufacturing through machine learning in the future.

5.
J Med Virol ; 96(7): e29808, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-39023086

RESUMO

To investigate the progress of disparities in human immunodeficiency virus/acquired immunodeficiency syndrome (HIV/AIDS), gonorrhea, and syphilis among children and adolescents aged 6-22 years in China during 2013-2021. A total of 614 325 cases data were extracted from the Chinese Information System for Infectious Diseases Control and Prevention during 2013-2021. Puberty health education data were drew from the Student Health Surveillance in 2021. Disparity patterns and average annual percentage changes (AAPCs) in sexually transmitted infections (STIs) incidence or new cases in China were examined using descriptive statistics and joinpoint regression. The incidence across 345 cities was stratified by gross domestic product (GDP). Between 2013 and 2021, there were 614 325 reported cases of HIV/AIDS, gonorrhea, and syphilis among children and adolescents aged 6-22, with an annual average incidence of 24.0967 per 100 000. The expansion of HIV/AIDS has halted, yet the surge in gonorrhea and syphilis remains notably pronounced. The ratio of male to female AIDS incidence increased from 2.75 (2.60, 2.90) to 7.13 (6.68, 7.62), but that of syphilis changed from 0.33 (0.32, 0.34) to 0.56 (0.55, 0.57). Students and out-of-school individuals aged 13-15 experienced a notably high increase in STI cases, surpassing other age groups, with an average annual percentage increase of 29.2% and 26.3%, respectively. Nonstudents consistently had a higher incidence rate than students, with an IRR reaching 31.80 (31.24, 32.37) in 2021. A noticeable clustering pattern of new cases emerged in the southeastern region of the Heihe-Tengchong line, extending inland from the coastal areas. Districts and counties with lower rates of puberty sexual health education tended to have higher average STI incidence rates. At the prefecture and city levels, there was a noticeable upward trend on average STI incidence rates in cities with per capita GDPs. Strategies to address those disparities include promoting equitable health education, and widespread sexual health education, particularly in areas with limited access to education and experiencing rapid economic development. The effectiveness of sexual health education intervention needs to be further evaluated in well-designed studies.


Assuntos
Gonorreia , Infecções Sexualmente Transmissíveis , Humanos , Adolescente , Masculino , Feminino , China/epidemiologia , Incidência , Criança , Adulto Jovem , Gonorreia/epidemiologia , Infecções Sexualmente Transmissíveis/epidemiologia , Infecções por HIV/epidemiologia , Sífilis/epidemiologia , Síndrome da Imunodeficiência Adquirida/epidemiologia , Monitoramento Epidemiológico
6.
Rheumatology (Oxford) ; 63(3): 826-836, 2024 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-37326830

RESUMO

OBJECTIVE: Sialylation of the crystallizable fragment (Fc) of ACPAs, which is catalysed by ß-galactoside α-2,6-sialyltransferase 1 (ST6GAL1) could attenuate inflammation of RA. In this study, we screened the transcription factor of ST6GAL1 and elucidated the mechanism of transcriptionally upregulating sialylation of ACPAs in B cells to explore its role in the progression of RA. METHODS: Transcription factors interacting with the P2 promoter of ST6GAL1 were screened by DNA pull-down and liquid chromatography with tandem mass spectrometry (LC-MS/MS), and verified by chromatin immunoprecipitation (ChIP), dual luciferase reporter assay and electrophoretic mobility shift assay (EMSA). The function of the CCCTC-binding factor (CTCF) on the expression of ST6GAL1 and the inflammatory effect of ACPAs were verified by knocking down and overexpressing CTCF in B cells. The CIA model was constructed from B cell-specific CTCF knockout mice to explore the effect of CTCF on arthritis progression. RESULTS: We observed that the levels of ST6GAL1 and ACPAs sialylation decreased in the serum of RA patients and were negatively correlated with DAS28 scores. Subsequently, CTCF was screened and verified as the transcription factor interacting with the P2 promoter of ST6GAL1, which enhances the sialylation of ACPAs, thus weakening the inflammatory activity of ACPAs. Furthermore, the above results were also verified in the CIA model constructed from B cell-specific CTCF knockout mice. CONCLUSION: CCCTC-binding factor is the specific transcription factor of ß-galactoside α-2,6-sialyltransferase 1 in B cells that upregulates the sialylation of ACPAs in RA and attenuates the disease progression.


Assuntos
Ácidos Aminossalicílicos , Artrite Reumatoide , Galactosídeos , Fatores de Transcrição , Animais , Camundongos , Humanos , Fator de Ligação a CCCTC , Anticorpos Antiproteína Citrulinada , Cromatografia Líquida , Espectrometria de Massas em Tandem , Camundongos Knockout , Sialiltransferases/genética
7.
Mol Pharm ; 21(7): 3434-3446, 2024 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-38781419

RESUMO

Chemodynamic therapy (CDT) is a novel antitumor strategy that employs Fenton or Fenton-like reactions to generate highly toxic hydroxyl radical (OH•) from hydrogen peroxide (H2O2) for inducing tumor cell death. However, the antitumor efficacy of the CDT strategy is harshly limited by the redox homeostasis of tumor cells; especially the OH • is easily scavenged by glutathione (GSH) and the intracellular H2O2 level is insufficient in the tumor cells. Herein, we propose the Mn2+-menadione (also known as vitamin K3, MK3) cascade biocatalysis strategy to disrupt the redox homeostasis of tumor cells and induce a OH• storm, resulting in enhanced CDT effect. A nanoliposome encapsulating Mn-MK3 (Mn-MK3@LP) was prepared for the treatment of hepatic tumors in this study. After Mn-MK3@LPs were taken up by tumor cells, menadione could facilitate the production of intracellular H2O2 via redox cycling, and further the cytotoxic OH • burst was induced by Mn2+-mediated Fenton-like reaction. Moreover, high-valent manganese ions were reduced by GSH and the depletion of GSH further disrupted the redox homeostasis of tumor cells, thus achieving synergistically enhanced CDT. Overall, both cellular and animal experiments confirmed that the Mn-MK3@LP cascade biocatalysis nanoliposome exhibited excellent biosafety and tumor suppression efficacy. This study may provide deep insights for developing novel CDT-based strategies for tumor therapy.


Assuntos
Glutationa , Peróxido de Hidrogênio , Radical Hidroxila , Vitamina K 3 , Animais , Radical Hidroxila/química , Radical Hidroxila/metabolismo , Humanos , Camundongos , Glutationa/metabolismo , Glutationa/química , Vitamina K 3/química , Vitamina K 3/farmacologia , Biocatálise , Linhagem Celular Tumoral , Manganês/química , Oxirredução/efeitos dos fármacos , Camundongos Endogâmicos BALB C , Lipossomos/química , Ensaios Antitumorais Modelo de Xenoenxerto , Neoplasias Hepáticas/tratamento farmacológico , Neoplasias Hepáticas/metabolismo , Camundongos Nus , Células Hep G2 , Antineoplásicos/farmacologia , Antineoplásicos/química , Nanopartículas/química , Ferro
8.
J Nanobiotechnology ; 22(1): 622, 2024 Oct 15.
Artigo em Inglês | MEDLINE | ID: mdl-39402673

RESUMO

Altering the mechanisms of tumor cell death and overcoming the limitations of traditional chemotherapy is pivotal to contemporary tumor treatment. Inducing ferroptosis, while circumventing safety concerns associated with ferrous vectors, through nonferrous ferroptosis is a promising but underexplored frontier in cancer therapy. Histidine phosphatase (LHPP) has emerged as a novel therapeutic target in treating hepatocellular carcinoma (HCC), but the precise mechanism of LHPP against HCC remains unclear. Herein, we explore the effects of upregulating LHPP expression on ferroptosis and tumor immunogenicity induction by simply delivering a miRNA-363-5p inhibitor (miR-363-5pi) via a previously optimized gemcitabine-oleic acid (GOA) prodrug. Efficient miRNA encapsulation was achieved through hydrogen bonding at an optimized GOA/miRNA molar feed ratio of 250:1, affording spherical nanoparticles with a uniform hydrodynamic size of 147.1 nm and a negative potential of -21.5 mV. The mechanism of this LHPP-ferroptosis crosstalk is disclosed to be an inhibited phosphorylation of the PI3K/Akt pathway, leading to a remarkable tumor inhibition rate of 88.2% in nude mice bearing Bel-7402 tumor xenografts via a combination of LHPP-triggered nonferrous ferroptosis and GOA-induced chemotherapy. The biocompatibility of GOA/miR-363-5pi is strongly supported by their non-hematologic toxicity and insignificant organ damage. In addition, the tumor immunogenic activation potential of GOA/miR-363-5pi was finally explored. Overall, this study is the first work that elucidates the precise mechanism of LHPP for treating HCC via ferroptosis induction and achieves the transformation of chemotherapy and gene therapy into ferroptosis activation with tumor cell immunogenicity, which lays a new therapeutic foundation for the clinical treatment of HCC.


Assuntos
Carcinoma Hepatocelular , Ferroptose , Neoplasias Hepáticas , Camundongos Nus , Animais , Carcinoma Hepatocelular/tratamento farmacológico , Neoplasias Hepáticas/tratamento farmacológico , Ferroptose/efeitos dos fármacos , Humanos , Camundongos , Linhagem Celular Tumoral , MicroRNAs/metabolismo , MicroRNAs/genética , Camundongos Endogâmicos BALB C , Nanopartículas/química , Pró-Fármacos/farmacologia , Pró-Fármacos/química , Pró-Fármacos/uso terapêutico , Desoxicitidina/análogos & derivados , Desoxicitidina/farmacologia , Desoxicitidina/uso terapêutico , Desoxicitidina/química , Gencitabina , Monoéster Fosfórico Hidrolases/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo , Ensaios Antitumorais Modelo de Xenoenxerto , Transdução de Sinais/efeitos dos fármacos , Pirofosfatase Inorgânica
9.
Ecotoxicol Environ Saf ; 283: 116966, 2024 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-39216218

RESUMO

Phthalates (PAEs) are synthetic compounds extensively employed in consumer products. Blood pressure (BP) in children can vary, the degree of visit-to-visit BP variability (VVV) is at least partially independent of BP. The interactions between PAEs exposure, pubertal-related genetic susceptibility and lifestyles on childhood VVV are not investigated. This study utilized data from a cohort collected from Oct 2017-2020 in Xiamen, China. Seven urine PAE metabolites were measured. The long-term VVV was characterized employing the standard deviation (SD) and average real variability. We constructed a genetic risk score (GRS) of pubertal-related genes and healthy lifestyle scores. Exposed to high levels of mono-2-ethyl-5-hydroxyhexyl phthalate (MEHHP) (OR=1.43, 95 %CI=1.07, 1.92) and mono-2-ethyl-5-oxohexyl phthalate (OR=1.36, 95 % CI=1.01, 1.83) was related to increased SBP-SD, and the OR for high SBP-SD related to high GRS was 1.38 (95 % CI=1.02, 1.85). Compared to participants who had low GRS and low MEHHP exposure, participants exhibiting high GRS and MEHHP levels were more likely to experience high SBP-SD (OR=2.00, P<0.05). Individuals exhibiting low GRS, low MEHHP levels, and adhering to healthy lifestyles were associated with the least probability of experiencing high SBP-SD (OR=0.31, P<0.05). Increased PAEs exposure could elevate childhood systolic VVV, and exacerbated the adverse impact of pubertal-related genetic susceptibility on the high VVV of SBP; however, healthy lifestyles might alleviate these adverse effects. Promoting healthy lifestyles and reducing PAEs exposure for preventing elevated BP variability among children is important, especially for individuals with greater genetic susceptibility to early pubertal onset. ENVIRONMENTAL IMPLICATION: Blood pressure (BP) in children can vary, as a noninvasive, inexpensive and applicable method, the extent of visit-to-visit variability (VVV) is at least partially independent of BP. The interactions between phthalates (PAEs) exposure, variants of puberty-related genes and lifestyles on VVV are not investigated. Increased childhood systolic VVV might be associated with PAEs exposure, with the associations more pronounced combined with pubertal genetic susceptibility. Yet, healthy habits could partly eliminate such adverse effects. Our study underscores the importance of advocating for healthy lifestyles and reducing exposure to PAEs, especially among individuals with high genetic susceptibility to early puberty onset.


Assuntos
Pressão Sanguínea , Exposição Ambiental , Interação Gene-Ambiente , Estilo de Vida , Ácidos Ftálicos , Humanos , Ácidos Ftálicos/urina , Criança , Pressão Sanguínea/efeitos dos fármacos , Pressão Sanguínea/genética , Masculino , Feminino , China , Poluentes Ambientais/urina , Polimorfismo Genético , Puberdade/efeitos dos fármacos , Puberdade/genética , Adolescente , Dietilexilftalato/toxicidade , Estudos de Coortes
10.
Environ Toxicol ; 39(5): 2817-2829, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38291708

RESUMO

INTRODUCTION: Allergic rhinitis (AR) is one of the leading allergic diseases worldwide. Allergen immunotherapy (AIT) induces persistent specific allergen tolerance to achieve remission of the symptoms in AR patients. We creatively conducted the intra-cervical lymphatic immunotherapy (ICLIT) for AR patients. However, the underlying molecular mechanism of immune cell response of AIT in AR remains elusive. METHOD: To investigate the transcriptome profile in AR patients who underwent ICLIT, we comprehensively investigated the transcriptional changes in B cells from peripheral blood mononuclear cells of AR patient by single-cell RNA sequencing. Immunoglobulins and relative key gene, which influences the B cell differentiation, was demonstrated. The biomarkers' association with different types of tumors was investigated. RESULTS: Naive B cells, germinal center B cells, activated memory B cells, and memory B cells constituted the B cells subsets. The expression of IGHE, IGHGs, IGHA, IGHD, and IGHM from memory B cells was validated. Pseudotime analysis further indicated the dynamic change from the expression of the immunoglobulins in the memory B cells, suggesting that ITGB1 may contribute to the differentiation procedure of memory B cells. The cell-cell communication among these immune cells demonstrated the significantly enhanced CD23, BTLA signaling after ICLIT in AR patient. ITGB1 was upregulated in 13 tumors and downregulated in six others. High ITGB1 expression was linked to poor prognosis in eight types of tumors. ITGB1 expression showed correlations with tumor mutation burden, tissue purity, and microsatellite instability in different types of tumors. DISCUSSION: ITGB1 was demonstrated as a potential biomarker for AR patients after ICLIT and is significant in identifying immune infiltration in tumor tissue and predicting tumor prognosis.


Assuntos
Neoplasias , Rinite Alérgica , Humanos , Leucócitos Mononucleares , Rinite Alérgica/genética , Rinite Alérgica/terapia , Rinite Alérgica/diagnóstico , Imunoglobulinas , Biomarcadores , Análise de Sequência de RNA
11.
Sensors (Basel) ; 24(15)2024 Aug 02.
Artigo em Inglês | MEDLINE | ID: mdl-39124064

RESUMO

Symbolic music understanding is a critical challenge in artificial intelligence. While traditional symbolic music representations like MIDI capture essential musical elements, they often lack the nuanced expression in music scores. Leveraging the advancements in multimodal pre-training, particularly in visual-language pre-training, we propose a groundbreaking approach: the Score Images as a Modality (SIM) model. This model integrates music score images alongside MIDI data for enhanced symbolic music understanding. We also introduce novel pre-training tasks, including masked bar-attribute modeling and score-MIDI matching. These tasks enable the SIM model to capture music structures and align visual and symbolic representations effectively. Additionally, we present a meticulously curated dataset of matched score images and MIDI representations optimized for training the SIM model. Through experimental validation, we demonstrate the efficacy of our approach in advancing symbolic music understanding.

12.
J Sci Food Agric ; 2024 Sep 19.
Artigo em Inglês | MEDLINE | ID: mdl-39297558

RESUMO

BACKGROUND: Gout poses a significant health threat. The use of Lactobacillus from the gut microbiota is one potential remedy. However, the intricate molecular mechanisms governing the impact of Lactobacillus on gout remain largely uncharted. In this study, a strain of Limosilactobacillus reuteri RE225 was separated from the gut of mice and colitis was treated with polypeptide intervention. RESULTS: Limosilactobacillus reuteri RE225 reduced foot tumefaction markedly in mice with gout and extended the pain threshold time in their feet. It also improved the health of gut microbiota. Intervention with L. reuteri RE225 also suppressed the TLR4/MyD88/NF-κB and nuclear factor erythroid 2-related factor 2 (Nrf2)/heme oxygenase-1 (HO-1) pathways in the mice, reduced the levels of pro-inflammatory cytokines - interleukin 1ß (IL-1ß), interleukin 6 (IL-6), and tumor necrosis factor-α (TNF-α) - and increased the level of the anti-inflammatory cytokine interleukin 10 (IL-10), thereby mitigating inflammation. CONCLUSION: This study provides a theoretical basis for the comprehensive development of Limosilactobacillus reuteri and new ideas for the non-pharmacological treatment of gout. © 2024 Society of Chemical Industry.

13.
Zhongguo Yi Liao Qi Xie Za Zhi ; 48(1): 88-93, 2024 Jan 30.
Artigo em Chinês | MEDLINE | ID: mdl-38384224

RESUMO

In recent years, China has made great progress in basic nanomedicine, nanotoxicology and nanobiology research. Nanotechnology has been continuously applied in biomaterial and medical device, more and more medical devices applying nanomaterials are developed and manufactured. In order to gain more comprehension and accurate understanding of the research and industrial development in nanobiomaterial medical devices, this study reviewed the common nanomaterial in medical devices and the regulatory situation of nanomaterial medical devices at home and abroad, and discussed the current challenges in biological evaluation of nanomaterial medical devices, with a view to providing ideas for the safety evaluation and research of related products.


Assuntos
Nanoestruturas , Nanotecnologia , Nanomedicina , Materiais Biocompatíveis , China
14.
BMC Biotechnol ; 23(1): 6, 2023 03 03.
Artigo em Inglês | MEDLINE | ID: mdl-36869335

RESUMO

BACKGROUND: Connective tissue growth factor (CTGF) plays a pivotal role in the pathogenesis of rheumatoid arthritis (RA) by facilitating angiogenesis and is a promising therapeutic target for RA treatment. Herein, we generated a fully human CTGF blocking monoclonal antibody (mAb) through phage display technology. RESULTS: A single-chain fragment variable (scFv) with a high affinity to human CTGF was isolated through screening a fully human phage display library. We carried out affinity maturation to elevate its affinity for CTGF and reconstructed it into a full-length IgG1 format for further optimization. Surface plasmon resonance (SPR) data showed that full-length antibody IgG mut-B2 bound to CTGF with a dissociation constant (KD) as low as 0.782 nM. In the collagen-induced arthritis (CIA) mice, IgG mut-B2 alleviated arthritis and decreased the level of pro-inflammatory cytokines in a dose-dependent manner. Furthermore, we confirmed that the TSP-1 domain of CTGF is essential for the interaction. Additionally, the results of Transwell assays, tube formation experiments, and chorioallantoic membrane (CAM) assays showed that IgG mut-B2 could effectively inhibit angiogenesis. CONCLUSION: The fully human mAb that antagonizes CTGF could effectively alleviate arthritis in CIA mice, and its mechanism is tightly associated with the TSP-1 domain of CTGF.


Assuntos
Artrite Experimental , Artrite Reumatoide , Humanos , Animais , Camundongos , Fator de Crescimento do Tecido Conjuntivo , Trombospondina 1 , Anticorpos Monoclonais , Imunoglobulina G
15.
Mol Carcinog ; 62(6): 731-742, 2023 06.
Artigo em Inglês | MEDLINE | ID: mdl-36929051

RESUMO

The underlying mechanisms of metastasis and recurrence of liver cancer remain largely unknown. Here, we found that Brother of the Regulator of Imprinted Sites (BORIS) variant SF2(C2/A4) was highly expressed in high metastatic potential hepatocellular carcinoma (HCC) cells and clinical tumor samples, related to the formation of satellite nodules. Its over expression promoted self-renewal, the expression of tumor stem cell markers, chemoresistance, wound healing rate, invasion and metastasis of HepG2 and Hep3B cells; reinforced epithelial-mesenchymal transition (EMT), decreased the expression of E-cadherin and increased N-cadherin and Vimentin. Subcellular localization experiment showed that BORIS SF2(C2/A4) was localized in nucleus and cytoplasm. Further double luciferase reporter gene experiment confirmed that it bound to TWIST1 gene promoter and significantly increased latter expression. BORIS SF2(C2/A4) knock down induced apoptosis of HCCLM3 and PLC/PRF/5 cells, and increased the protein content of cleaved caspase 3. Additionally, BORIS SF2(C2/A4) over expression increased the expression of fibroblast growth factor 2 (FGF2) in HepG2 and Hep3B cells. FGF2 expressed higher in HCC tumor tissues than in paired peri-tumor tissues, and its expression was positively correlated with BORIS SF2(C2/A4). Interestingly, high expression of FGF2 is also associated with the formation of satellite nodules. Moreover, using the medium from BORIS SF2(C2/A4) overexpressed cell lines to coculture hepatic stellate cell (HSCs) line LX-2, the latter could be activated and increased the expression of CD90 and PIGF, which is consistent with the effect of adding bFGF alone. These results indicate that BORIS SF2(C2/A4) plays a role in deterioration of liver cancer by regulating TWIST1 to induce EMT, and by FGF2 to activate HSCs.


Assuntos
Carcinoma Hepatocelular , Proteínas de Ligação a DNA , Neoplasias Hepáticas , Humanos , Carcinoma Hepatocelular/patologia , Linhagem Celular Tumoral , Transição Epitelial-Mesenquimal/genética , Fator 2 de Crescimento de Fibroblastos/genética , Fator 2 de Crescimento de Fibroblastos/metabolismo , Células Estreladas do Fígado/metabolismo , Células Estreladas do Fígado/patologia , Neoplasias Hepáticas/patologia , Fator de Crescimento Placentário/metabolismo , Proteínas de Ligação a DNA/genética
16.
Crit Rev Food Sci Nutr ; 63(25): 7811-7836, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-35317688

RESUMO

Airborne particulate matter (PM) exerts huge negative impacts on human health worldwide, not only targeting the respiratory system but more importantly inducing and aggravating associated chronic diseases like asthma, lung cancer, atherosclerosis, diabetes mellitus and Alzheimer diseases. Food-derived bioactive compounds like vitamins, dietary polyphenols, omega-3 polyunsaturated fatty acids and sulforaphane are feasible alternative therapeutic approaches against PM-mediated potential health damages, drawing great attention in recent years. In this review, the association between PM exposure and risks of developing chronic diseases, and the detailed mechanisms underlying the detrimental effects of PM will be discussed. Subsequently, principal food-derived bioactive compounds, with emphasize on the preventative or protective effects against PM, along with potential mechanisms will be elucidated. This comprehensive review will discuss and present current research findings to reveal the nutritional intervention as a preventative or therapeutic strategy against ambient air pollution, thereby lowering the risk of developing chronic diseases.


Assuntos
Poluentes Atmosféricos , Poluição do Ar , Asma , Humanos , Poluentes Atmosféricos/toxicidade , Poluentes Atmosféricos/análise , Poluição do Ar/análise , Material Particulado/toxicidade , Material Particulado/análise , Asma/induzido quimicamente , Asma/prevenção & controle , Doença Crônica
17.
Curr Genomics ; 24(6): 368-384, 2023 Dec 28.
Artigo em Inglês | MEDLINE | ID: mdl-38327651

RESUMO

Introduction: Hepatocellular carcinoma (HCC) has a high mortality rate, with curative resection being the primary treatment. However, HCC patients have a large possibility of recurrence within 5 years after curative resection. Methods: Thus, identifying biomarkers to predict recurrence is crucial. In our study, we analyzed data from CCLE, GEO, and TCGA, identifying eight oncogenes associated with HCC. Subsequently, the expression of 8 genes was tested in 5 cases of tumor tissues and the adjacent non-tumor tissues. Then ATP6AP1, PSMD14 and HSP90AB1 were selected to verify the expression in 63 cases of tumor tissues and the adjacent non-tumor tissues. The results showed that ATP6AP1, PSMD14, HSP90AB1 were generally highly expressed in tumor tissues. A five-year follow-up of the 63 clinical cases, combined with Kaplan-Meier Plotter's relapse-free survival (RFS) analysis, found a significant correlation between PSMD14 expression and recurrence in HCC patients. Subsequently, we analyzed the PSMD14 mutations and found that the PSMD14 gene mutations can lead to a shorter disease-free survival time for HCC patients. Results: The results of enrichment analysis indicated that the differentially expressed genes related to PSMD14 are mainly enriched in the signal release pathway. Conclusion: In conclusion, our research showed that PSMD14 might be related to recurrence in HCC patients, and the expression of PSMD14 in tumor tissue might be a potential prognostic biomarker after tumor resection in HCC patients.

18.
Adv Neonatal Care ; 23(6): 532-540, 2023 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-38038670

RESUMO

BACKGROUND: Although end-of-life care (EOLC) has been well-studied, the experience of neonatal intensive care unit (NICU) nurses in China, where little EOLC training is provided, requires further investigation. PURPOSE: To explore the lived experience of EOLC delivery among NICU nurses, to provide evidence to enhance nurses' EOLC skills and improve their overall quality. METHODS: This qualitative study adopted a phenomenological approach. A total of 11 NICU nurses participated in semistructured in-depth interviews between June and July 2022 at the First Affiliated Hospital of University of Science and Technology of China (USTC). Colaizzi's 7-step method was used to analyze the data. RESULTS: Five main themes were identified: (a) multiple emotions are experienced during EOLC delivery; (b) EOLC delivery is stressful from various sources for nurses; (c) expressing empathy and compassion is important; (d) ethical and clinical decision-making are key components of EOLC delivery; and (e) there are challenges in improving neonatal EOLC understanding and delivery. IMPLICATIONS FOR PRACTICE AND RESEARCH: The experience of EOLC among Chinese NICU nurses is multidimensional and intensive. Institutions or units must establish and implement related protocols and guidelines to address differences between clinical practice and ideal protocols for neonatal EOLC. Educational programs that consider nurses' personal and interpersonal factors, including local culture, must be developed. Neonatal nurses in Western countries encountering Chinese-born parents who have lost their infants can gain an understanding of parents' perceptions from this study. Future research should focus on developing and testing interventions to train and support NICU nurses working with end-of-life neonates.


Assuntos
Enfermeiros Neonatologistas , Assistência Terminal , Recém-Nascido , Lactente , Humanos , Unidades de Terapia Intensiva Neonatal , Enfermeiros Neonatologistas/psicologia , População do Leste Asiático , Assistência Terminal/psicologia , Emoções
19.
Arch Psychiatr Nurs ; 45: 113-123, 2023 08.
Artigo em Inglês | MEDLINE | ID: mdl-37544685

RESUMO

BACKGROUND: Resilience as a dynamic concept has already been described through various longitudinal studies. To better understand the changes in the resilience of caregivers over the course of care-providing, however, a scoping review can provide a clearer picture of their resilience process which, in turn, can be used to improve caregivers' well-being. OBJECTIVES: To provide a comprehensive overview of dynamic change in the resilience of caregivers while caring for the family to enhance understanding and potential for future research. METHODS: Following the methodological framework of Arksey and O'Malley, this scoping review was conducted using the Preferred Reporting Items for Systematic Reviews and the Meta-Analyses extension for Scoping Reviews (PRISMA-ScR) Checklist. Five electronic databases were searched for research published in English between January 2012 and May 2022, after which a manual search was performed. Key terms related to resilience and caregivers in longitudinal studies were included and screened for. Identified trajectories of patterns in resilience and factors associated with resilience process were categorized using content analysis. RESULTS: In total, 24 longitudinal studies met the eligibility criteria. Conceptually, our findings demonstrate three modes of change following healthcare challenges, each of which varies substantially. Methodologically, the results reveal three subcategories of assessment tools that can be used to impact caregivers' resilience when confronted with significant healthcare challenges. Consequentially, personal traits and environmental resources interacting with the resilience process will then lead to various outcomes in their resilience, including stability, growth, or decline. CONCLUSION: This review describes the change patterns of the resilience process, assessment instruments, and associated factors to offer a dynamic perspective for the investigation and intervention of psychological resilience. Major gaps nonetheless remain for future research regarding an operationalizing dynamic change in resilience.


Assuntos
Cuidadores , Resiliência Psicológica , Humanos , Atenção à Saúde
20.
Angew Chem Int Ed Engl ; 62(4): e202213208, 2023 Jan 23.
Artigo em Inglês | MEDLINE | ID: mdl-36445822

RESUMO

As a new type of inorganic-organic hybrid semiconductor, quantum-confined atomically precise metal nanoclusters (MNCs) have been widely applied in the fields of chemical sensing, optical imaging, biomedicine and catalysis. Herein, we successfully design and fabricate the first example of MNC-based spin valves (SVs) that exhibit remarkable magnetoresistance (MR) value up to 1.6 % even at room temperature (300 K). The concomitant photoresponse of MNC-based SVs unambiguously confirms that the spin-polarized electron transmission takes place across the MNC interlayer. Furthermore, the spin-dependent transport property of MNC-based SVs is largely varied by changing the atomic structure of MNCs. Both experimental proofs and quantum chemistry calculations reveal that the atomic structure-discriminative spin transport behavior is attributed to the distinct spin-orbit coupling (SOC) effect of MNCs.

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