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1.
Proc Natl Acad Sci U S A ; 121(17): e2321303121, 2024 Apr 23.
Artigo em Inglês | MEDLINE | ID: mdl-38640342

RESUMO

Understanding the transient dynamics of interlinked social-ecological systems (SES) is imperative for assessing sustainability in the Anthropocene. However, how to identify critical transitions in real-world SES remains a formidable challenge. In this study, we present an evolutionary framework to characterize these dynamics over an extended historical timeline. Our approach leverages multidecadal rates of change in socioeconomic data, paleoenvironmental, and cutting-edge sedimentary ancient DNA records from China's Yangtze River Delta, one of the most densely populated and intensively modified landscapes on Earth. Our analysis reveals two significant social-ecological transitions characterized by contrasting interactions and feedback spanning several centuries. Initially, the regional SES exhibited a loosely connected and ecologically sustainable regime. Nevertheless, starting in the 1950s, an increasingly interconnected regime emerged, ultimately resulting in the crossing of tipping points and an unprecedented acceleration in soil erosion, water eutrophication, and ecosystem degradation. Remarkably, the second transition occurring around the 2000s, featured a notable decoupling of socioeconomic development from ecoenvironmental degradation. This decoupling phenomenon signifies a more desirable reconfiguration of the regional SES, furnishing essential insights not only for the Yangtze River Basin but also for regions worldwide grappling with similar sustainability challenges. Our extensive multidecadal empirical investigation underscores the value of coevolutionary approaches in understanding and addressing social-ecological system dynamics.


Assuntos
Ecossistema , Rios , Eutrofização , Conservação dos Recursos Naturais/métodos
2.
Proc Natl Acad Sci U S A ; 121(21): e2318874121, 2024 May 21.
Artigo em Inglês | MEDLINE | ID: mdl-38753510

RESUMO

The single-pass transmembrane protein Stromal Interaction Molecule 1 (STIM1), located in the endoplasmic reticulum (ER) membrane, possesses two main functions: It senses the ER-Ca2+ concentration and directly binds to the store-operated Ca2+ channel Orai1 for its activation when Ca2+ recedes. At high resting ER-Ca2+ concentration, the ER-luminal STIM1 domain is kept monomeric but undergoes di/multimerization once stores are depleted. Luminal STIM1 multimerization is essential to unleash the STIM C-terminal binding site for Orai1 channels. However, structural basis of the luminal association sites has so far been elusive. Here, we employed molecular dynamics (MD) simulations and identified two essential di/multimerization segments, the α7 and the adjacent region near the α9-helix in the sterile alpha motif (SAM) domain. Based on MD results, we targeted the two STIM1 SAM domains by engineering point mutations. These mutations interfered with higher-order multimerization of ER-luminal fragments in biochemical assays and puncta formation in live-cell experiments upon Ca2+ store depletion. The STIM1 multimerization impeded mutants significantly reduced Ca2+ entry via Orai1, decreasing the Ca2+ oscillation frequency as well as store-operated Ca2+ entry. Combination of the ER-luminal STIM1 multimerization mutations with gain of function mutations and coexpression of Orai1 partially ameliorated functional defects. Our data point to a hydrophobicity-driven binding within the ER-luminal STIM1 multimer that needs to switch between resting monomeric and activated multimeric state. Altogether, these data reveal that interactions between SAM domains of STIM1 monomers are critical for multimerization and activation of the protein.


Assuntos
Proteínas de Neoplasias , Multimerização Proteica , Molécula 1 de Interação Estromal , Humanos , Sítios de Ligação , Cálcio/metabolismo , Retículo Endoplasmático/metabolismo , Células HEK293 , Simulação de Dinâmica Molecular , Proteínas de Neoplasias/metabolismo , Proteínas de Neoplasias/genética , Proteínas de Neoplasias/química , Proteína ORAI1/metabolismo , Proteína ORAI1/genética , Proteína ORAI1/química , Ligação Proteica , Domínios Proteicos , Molécula 1 de Interação Estromal/metabolismo , Molécula 1 de Interação Estromal/genética , Molécula 1 de Interação Estromal/química
3.
Trends Biochem Sci ; 46(5): 378-390, 2021 05.
Artigo em Inglês | MEDLINE | ID: mdl-33423940

RESUMO

Virion assembly is an important step in the life cycle of all viruses. For viruses of the Flavivirus genus, a group of enveloped positive-sense RNA viruses, the assembly step represents one of the least understood processes in the viral life cycle. While assembly is primarily driven by the viral structural proteins, recent studies suggest that several nonstructural proteins also play key roles in coordinating the assembly and packaging of the viral genome. This review focuses on describing recent advances in our understanding of flavivirus virion assembly, including the intermolecular interactions between the viral structural (capsid) and nonstructural proteins (NS2A and NS2B-NS3), host factors, as well as features of the viral genomic RNA required for efficient flavivirus virion assembly.


Assuntos
Flavivirus , RNA Viral/genética , Proteínas não Estruturais Virais/genética , Vírion , Montagem de Vírus
4.
PLoS Biol ; 20(12): e3001938, 2022 12.
Artigo em Inglês | MEDLINE | ID: mdl-36542658

RESUMO

Sustained attention (SA) and working memory (WM) are critical processes, but the brain networks supporting these abilities in development are unknown. We characterized the functional brain architecture of SA and WM in 9- to 11-year-old children and adults. First, we found that adult network predictors of SA generalized to predict individual differences and fluctuations in SA in youth. A WM model predicted WM performance both across and within children-and captured individual differences in later recognition memory-but underperformed in youth relative to adults. We next characterized functional connections differentially related to SA and WM in youth compared to adults. Results revealed 2 network configurations: a dominant architecture predicting performance in both age groups and a secondary architecture, more prominent for WM than SA, predicting performance in each age group differently. Thus, functional connectivity (FC) predicts SA and WM in youth, with networks predicting WM performance differing more between youths and adults than those predicting SA.


Assuntos
Imageamento por Ressonância Magnética , Memória de Curto Prazo , Criança , Adulto , Adolescente , Humanos , Imageamento por Ressonância Magnética/métodos , Encéfalo , Atenção , Mapeamento Encefálico/métodos
5.
Genomics ; 116(5): 110877, 2024 Jun 07.
Artigo em Inglês | MEDLINE | ID: mdl-38852876

RESUMO

Adenomyosis (ADS) is a common gynecological disorder, and its pathogenesis remains unclear. This study explores the functions of circRNAs in the eutopic endometrium of ADS and their diagnostic efficacy for ADS. High-throughput RNA sequencing was performed on 12 eutopic endometrial samples from ADS patients and 3 control endometrial samples. Additionally, circRNAs were analyzed in conjunction with clinical features. A competitive endogenous RNA network was established based on bioinformatics analysis, comprising 3 circRNAs, 1 miRNA, and 13 mRNAs. In the ADS group, the expression levels of hsa_circ_0008959 and SLC15A4 were significantly reduced, while hsa-miR-124-3p expression was increased. SLC15A4 was associated with cell proliferation and invasion. Decreased expression of hsa_circ_0008959 and SLC15A4, along with high VAS scores and elevated hsa-miR-124-3p levels, were identified as risk factors for ADS development. The combination of hsa_circ_0008959 and VAS scores demonstrated the highest diagnostic value for ADS.

6.
J Cogn Neurosci ; 36(3): 415-434, 2024 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-38060253

RESUMO

Nearly 50 years of research has focused on faces as a special visual category, especially during development. Yet it remains unclear how spatial patterns of neural similarity of faces and places relate to how information processing supports subsequent recognition of items from these categories. The current study uses representational similarity analysis and functional imaging data from 9- and 10-year-old youth during an emotional n-back task from the Adolescent Brain and Cognitive Development Study 3.0 data release to relate spatial patterns of neural similarity during working memory to subsequent out-of-scanner performance on a recognition memory task. Specifically, we examine how similarities in representations within face categories (neutral, happy, and fearful faces) and representations between visual categories (faces and places) relate to subsequent recognition memory of these visual categories. Although working memory performance was higher for faces than places, subsequent recognition memory was greater for places than faces. Representational similarity analysis revealed category-specific patterns in face-and place-sensitive brain regions (fusiform gyrus, parahippocampal gyrus) compared with a nonsensitive visual region (pericalcarine cortex). Similarity within face categories and dissimilarity between face and place categories in the parahippocampus was related to better recognition of places from the n-back task. Conversely, in the fusiform, similarity within face categories and their relative dissimilarity from places was associated with better recognition of new faces, but not old faces. These findings highlight how the representational distinctiveness of visual categories influence what information is subsequently prioritized in recognition memory during development.


Assuntos
Memória de Curto Prazo , Reconhecimento Psicológico , Adolescente , Humanos , Criança , Encéfalo , Córtex Cerebral , Emoções , Mapeamento Encefálico , Imageamento por Ressonância Magnética , Reconhecimento Visual de Modelos
7.
J Am Chem Soc ; 146(5): 2901-2906, 2024 Feb 07.
Artigo em Inglês | MEDLINE | ID: mdl-38271666

RESUMO

Macrocyclic arenes have emerged as pivotal scaffolds in supramolecular chemistry. Despite their significant contributions to molecular recognition and diverse applications, challenges persist in the development of macrocyclic arene-based crystalline materials, particularly in achieving porosity and addressing limitations in adsorption efficiency resulting from the small cavity sizes of existing macrocyclic arenes. In this study, we present the design and synthesis of a novel macrocyclic arene, clamparene (CLP), featuring a rigid backbone, easy synthesis, and a sizable cavity. CLP self-assembles into one-dimensional sub-nanotubes that further organize into a three-dimensional porous framework in the solid state. The crystalline solid of CLP exhibits potential as a porous crystalline adsorbent for various benzene-based contaminants with rapid adsorption kinetics, large uptake amounts, and good recyclability.

8.
Cancer Sci ; 115(1): 257-269, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-37986654

RESUMO

With the essential role of lipid transporting signaling in cancer-related immunity, apolipoprotein L3 (APOL3), a member of the apolipoprotein L gene family, demonstrated significant modulation ability in immunity. However, the expression profile and critical role of APOL3 in colorectal cancer (CRC) remain unclear. This study aimed to investigate the prognostic significance of APOL3 expression and its biological predictive value in CRC. The study enrolled multiple cohorts, consisting of 911 tumor microarray specimens of CRC patients from Zhongshan Hospital, 412 transcriptional data from The Cancer Genome Atlas, and 30 single-cell RNA sequencing (scRNA-seq) from internal and external CRC patients. APOL3 mRNA expression was directly acquired from public datasets, and APOL3 protein expression was detected using immunohistochemistry. Finally, the associations of APOL3 expression with clinical outcomes, immune context, and genomic and ferroptotic features were analyzed. Low APOL3 expression predicted poor prognosis and inferior responsiveness to 5-fluorouracil-based adjuvant chemotherapy (ACT) and targeted therapy. APOL3 fosters an immune-active microenvironment characterized by the promotion of ferroptosis, downregulation of macrophages, and upregulation of CD8+ T cell infiltration. Moreover, the expression of APOL3 in CD8+ T cells is intrinsically linked to ferroptosis and immune activation in CRC. In summary, APOL3 serves as an independent prognosticator and predictive biomarker for immunogenic ferroptosis, ACT, and targeted therapy in CRC. Furthermore, the APOL3 signaling activator could be a novel agent alone or in combination with current therapeutic strategies for CRC.


Assuntos
Neoplasias Colorretais , Ferroptose , Humanos , Ferroptose/genética , Prognóstico , Transporte Biológico , Linfócitos T CD8-Positivos , Neoplasias Colorretais/genética , Microambiente Tumoral
9.
J Virol ; 97(2): e0000923, 2023 02 28.
Artigo em Inglês | MEDLINE | ID: mdl-36744961

RESUMO

Mammalian orthoreovirus serotype 3 Dearing is an oncolytic virus currently undergoing multiple clinical trials as a potential cancer therapy. Previous clinical trials have emphasized the importance of prescreening patients for prognostic markers to improve therapeutic success. However, only generic cancer markers such as epidermal growth factor receptor (EGFR), Hras, Kras, Nras, Braf, and p53 are currently utilized, with limited benefit in predicting therapeutic efficacy. This study aimed to investigate the role of p38 mitogen-activated protein kinase (MAPK) signaling during reovirus infection. Using a panel of specific p38 MAPK inhibitors and an inactive inhibitor analogue, p38 MAPK signaling was found to be essential for establishment of reovirus infection by enhancing reovirus endocytosis, facilitating efficient reovirus uncoating at the endo-lysosomal stage, and augmenting postuncoating replication steps. Using a broad panel of human breast cancer cell lines, susceptibility to reovirus infection corresponded with virus binding and uncoating efficiency, which strongly correlated with status of the p38ß isoform. Together, results suggest p38ß isoform as a potential prognostic marker for early stages of reovirus infection that are crucial to successful reovirus infection. IMPORTANCE The use of Pelareorep (mammalian orthoreovirus) as a therapy for metastatic breast cancer has shown promising results in recent clinical trials. However, the selection of prognostic markers to stratify patients has had limited success due to the fact that these markers are upstream receptors and signaling pathways that are present in a high percentage of cancers. This study demonstrates that the mechanism of action of p38 MAPK signaling plays a key role in establishment of reovirus infection at both early entry and late replication steps. Using a panel of breast cancer cell lines, we found that the expression levels of the MAPK11 (p38ß) isoform are a strong determinant of reovirus uncoating and infection establishment. Our findings suggest that selecting prognostic markers that target key steps in reovirus replication may improve patient stratification during oncolytic reovirus therapy.


Assuntos
Neoplasias da Mama , Orthoreovirus Mamífero 3 , Infecções por Reoviridae , Internalização do Vírus , Proteínas Quinases p38 Ativadas por Mitógeno , Feminino , Humanos , Capsídeo/metabolismo , Proteínas do Capsídeo/genética , Proteínas do Capsídeo/metabolismo , Orthoreovirus Mamífero 3/fisiologia , Proteínas Quinases p38 Ativadas por Mitógeno/genética , Proteínas Quinases p38 Ativadas por Mitógeno/metabolismo , Replicação Viral , Linhagem Celular Tumoral
10.
J Virol ; 97(10): e0082823, 2023 10 31.
Artigo em Inglês | MEDLINE | ID: mdl-37747236

RESUMO

IMPORTANCE: Reoviruses infect many mammals and are widely studied as a model system for enteric viruses. However, most of our reovirus knowledge comes from laboratory strains maintained on immortalized L929 cells. Herein, we asked whether naturally circulating reoviruses possess the same genetic and phenotypic characteristics as laboratory strains. Naturally circulating reoviruses obtained from sewage were extremely diverse genetically. Moreover, sewage reoviruses exhibited poor fitness on L929 cells and relied heavily on gut proteases for viral uncoating and productive infection compared to laboratory strains. We then examined how naturally circulating reoviruses might adapt to cell culture conditions. Within three passages, virus isolates from the parental sewage population were selected, displaying improved fitness and intracellular uncoating in L929 cells. Remarkably, selected progeny clones were present at 0.01% of the parental population. Altogether, using reovirus as a model, our study demonstrates how the high genetic diversity of naturally circulating viruses results in rapid adaptation to new environments.


Assuntos
Adaptação Fisiológica , Aptidão Genética , Genoma Viral , Interações entre Hospedeiro e Microrganismos , Peptídeo Hidrolases , Reoviridae , Desenvelopamento do Vírus , Animais , Camundongos , Genoma Viral/genética , Genômica , Células L , Peptídeo Hidrolases/metabolismo , Reoviridae/classificação , Reoviridae/genética , Reoviridae/metabolismo , Inoculações Seriadas , Esgotos/virologia
11.
J Transl Med ; 22(1): 438, 2024 May 08.
Artigo em Inglês | MEDLINE | ID: mdl-38720336

RESUMO

BACKGROUND: Advanced unresectable gastric cancer (GC) patients were previously treated with chemotherapy alone as the first-line therapy. However, with the Food and Drug Administration's (FDA) 2022 approval of programmed cell death protein 1 (PD-1) inhibitor combined with chemotherapy as the first-li ne treatment for advanced unresectable GC, patients have significantly benefited. However, the significant costs and potential adverse effects necessitate precise patient selection. In recent years, the advent of deep learning (DL) has revolutionized the medical field, particularly in predicting tumor treatment responses. Our study utilizes DL to analyze pathological images, aiming to predict first-line PD-1 combined chemotherapy response for advanced-stage GC. METHODS: In this multicenter retrospective analysis, Hematoxylin and Eosin (H&E)-stained slides were collected from advanced GC patients across four medical centers. Treatment response was evaluated according to iRECIST 1.1 criteria after a comprehensive first-line PD-1 immunotherapy combined with chemotherapy. Three DL models were employed in an ensemble approach to create the immune checkpoint inhibitors Response Score (ICIsRS) as a novel histopathological biomarker derived from Whole Slide Images (WSIs). RESULTS: Analyzing 148,181 patches from 313 WSIs of 264 advanced GC patients, the ensemble model exhibited superior predictive accuracy, leading to the creation of ICIsNet. The model demonstrated robust performance across four testing datasets, achieving AUC values of 0.92, 0.95, 0.96, and 1 respectively. The boxplot, constructed from the ICIsRS, reveals statistically significant disparities between the well response and poor response (all p-values < = 0.001). CONCLUSION: ICIsRS, a DL-derived biomarker from WSIs, effectively predicts advanced GC patients' responses to PD-1 combined chemotherapy, offering a novel approach for personalized treatment planning and allowing for more individualized and potentially effective treatment strategies based on a patient's unique response situations.


Assuntos
Aprendizado Profundo , Inibidores de Checkpoint Imunológico , Receptor de Morte Celular Programada 1 , Neoplasias Gástricas , Humanos , Neoplasias Gástricas/tratamento farmacológico , Neoplasias Gástricas/patologia , Masculino , Feminino , Resultado do Tratamento , Pessoa de Meia-Idade , Inibidores de Checkpoint Imunológico/uso terapêutico , Receptor de Morte Celular Programada 1/antagonistas & inibidores , Idoso , Estudos Retrospectivos , Curva ROC , Adulto
12.
Opt Express ; 32(6): 10669-10678, 2024 Mar 11.
Artigo em Inglês | MEDLINE | ID: mdl-38571272

RESUMO

Many applications involve the phenomenon of a material absorbing electromagnetic radiation. By exploiting wave interference, the efficiency of absorption can be significantly enhanced. Here, we propose Friedrich-Wintgen bound states in the continuum (F-W BICs) based on borophene metamaterials to realize coherent perfect absorption with a dual-band absorption peak in commercially important communication bands. Metamaterials consist of borophene gratings and a borophene sheet that can simultaneously support a Fabry-Perot plasmon resonance and a guided plasmon mode. The formation and dynamic modulation of the F-W BIC can be achieved by adjusting the width or carrier density of the borophene grating, while the strong coupling leads to the anti-crossover behavior of the absorption spectrum. Due to the weak angular dispersion originating from the intrinsic flat-band characteristic of the deep sub-wavelength periodic structure, the proposed plasmonic system exhibits almost no change in wavelength and absorption at large incident angles (within 70 degrees). In addition, we employ the temporal coupled-mode theory including near- and far-field coupling to obtain strong critical coupling, successfully achieve coherent perfect absorption, and can realize the absorption switch by changing the phase difference between the two coherent beams. Our findings can offer theoretical support for absorber design and all-optical tuning.

13.
Langmuir ; 40(18): 9717-9724, 2024 May 07.
Artigo em Inglês | MEDLINE | ID: mdl-38712354

RESUMO

Connectivity isomerization of the same aromatic molecular core with different substitution positions profoundly affects electron transport pathways and single-molecule conductance. Herein, we designed and synthesized all connectivity isomers of a thiophene (TP) aromatic ring substituted by two dihydrobenzo[b]thiophene (BT) groups with ethynyl spacers (m,n-TP-BT, (m,n = 2,3; 2,4; 2,5; 3,4)), to systematically probe how connectivity contributes to single-molecule conductance. Single-molecule conductance measurements using a scanning tunneling microscopy break junction (STM-BJ) technique show ∼12-fold change in conductance values, which follow an order of 10-4.83 G0 (2,4-TP-BT) < 10-4.78 G0 (3,4-TP-BT) < 10-4.06 G0 (2,3-TP-BT) < 10-3.75 G0 (2,5-TP-BT). Electronic structure analysis and theoretical simulations show that the connectivity isomerization significantly changes electron delocalization and HOMO-LUMO energy gaps. Moreover, the connectivity-dependent molecular structures lead to different quantum interference (QI) effects in electron transport, e.g., a strong destructive QI near E = EF leads the smallest conductance value for 2,4-TP-BT. This work proves a clear relationship between the connectivity isomerization and single-molecule conductance of thiophene heterocyclic molecular junctions for the future design of molecular devices.

14.
Microb Ecol ; 87(1): 35, 2024 Jan 23.
Artigo em Inglês | MEDLINE | ID: mdl-38261068

RESUMO

Urease-producing bacteria (UPB) provide inorganic nitrogen for primary producers by hydrolyzing urea, and play an important role in marine nitrogen cycle. However, there is still an incomplete understanding of UPB and their ecological functions in the cultivation environment of the red macroalgae Gracilariopsis lemaneiformis. This study comprehensively analyzed the diversity of culturable UPB and explored their effects on urea uptake by G. lemaneiformis. A total of 34 isolates belonging to four main bacterial phyla i.e. (Proteobacteria, Bacteroidetes, Firmicutes, and Actinobacteria) were identified through 16S rRNA sequencing and were screened for UPB by urea agar chromogenic medium assay and ureC gene cloning. Our data revealed that only 8 strains contained urease. All of these UPB exhibited different urease activities, which were determined by the Berthelot reaction colorimetry assay. Additionally, the UPB strain (G13) isolated from G. lemaneiformis with higher urease activity was selected for co-culture with G. lemaneiformis to explore its role in promoting or inhibiting nitrogen uptake by macroalgae. The results showed a significant increase in urea consumption in the culture medium and the total cellular nitrogen in G. lemaneiformis in the UPB-co culture group compared to the sterile group. This suggests that the selected UPB strain positively influences nitrogen uptake by G. lemaneiformis. Similarly, isotopic assays revealed that the δ15N content of G. lemaneiformis was significantly higher in the UPB-co culture than in the control group, where δ15N-urea was the only nitrogen source in the culture medium. This indicates that the UPB helped G. lemaneiformis to absorb more nitrogen from urea. Moreover, the highest content of δ15N was found in G. lemaneiformis with epiphytic bacteria compared to sterilized (i.e. control), showing that epiphytic bacteria, along with UPB, have a compound effect in helping G. lemaneiformis absorb more nitrogen from urea. Taken together, these results provide unique insight into the ecological role of UPB and suggest that urease from macroalgae environment-associated bacteria might be an important player in marine nitrogen cycling.


Assuntos
Alga Marinha , Urease , RNA Ribossômico 16S/genética , Bactérias/genética , Nitrogênio , Ureia
15.
Nanotechnology ; 35(21)2024 Mar 04.
Artigo em Inglês | MEDLINE | ID: mdl-38368630

RESUMO

We observed a unique interpillar gap-related surface-enhanced Raman scattering (SERS) behavior ofp-aminothiophenol (PATP) molecules from periodic TiO2nanopillar arrays with three gap sizes of 191, 297 and 401 nm, which is completely different from that on Ag and Ni nanopillar arrays. Especially, the gap-size-dependent charge-transfer (CT) resonance enhancement from TiO2/Ni has been indicated through comparisons of variation trend of SERS intensities with inter-pillar gap size between TiO2/Ni and Ag/TiO2/Ni as well as Ni nanoarrays, and been confirmed by spectra of ultraviolet-visible absorption and photoluminescence. Results demonstrate that the CT resonance enhancement is more susceptible to the change of the gap size compared with the surface plasmon resonance (SPR) enhancement in TiO2/Ni nanoarrays. Hence, SPR and CT enhancement showing different variation trend and rate with the gap size that leads to a different relative contribution of CT resonance to the overall SERS enhancement as gap size changes, and consequently results in a unique gap-related SERS behavior for TiO2/Ni nanoarrays. The present study is not only helpful for investigating SERS mechanism for semiconductors but also providing a method to design and optimize periodic metal/semiconductor SERS substrates in a controllable way.

16.
Exp Lung Res ; 50(1): 1-14, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38234074

RESUMO

Purpose: Chronic obstructive pulmonary disease (COPD) is a common respiratory disorder. Pyroptosis represents a distinctive form of inflammatory cell death that is mediated through the activation of Caspase-1 and inflammasomes. CircRNAs have emerged as a novel class of biomolecules with implications in various human diseases. This study aims to investigate the circRNAs profile of in COPD progression and identify pivotal circRNAs associated with the development of this disease. Methods: he expression profiles of circRNAs in peripheral blood mononuclear cells of COPD patients were assessed by circRNA microarray. Furthermore, flag-labeled vectors were constructed to assess the potential protein-coding capacity of has-circ-0008833. 16HBE cells were stably transfected with lentivirus approach, and cell proliferation and death were assessed to clarify the functional roles of has-circ-0008833 and its encoded protein circ-0008833aa. Additionally, western blot analysis was furthered performed to determine the level of Caspase-1, IL-18, IL-1ß, NLRP3, ASC, and cleaved GSDMD regulated by has-circ-0008833 and circ-0008833-57aa. Results: Initially, we screened the expression profiles of human circRNAs in peripheral blood mononuclear cells of COPD patients, and found that has-circ-0008833 exhibited a significant increase in COPD mononuclear cells. Subsequently, we demonstrated that has-circ-0008833 carried an open reading frame (ORF), which encoded a functional protein, referred to as circ-0008833-57aa. By employing gain-of-function approaches, our results suggested that both circ-0008833 and circ-0008833-57aa inhibited proliferation, but accelerated the rate of 16HBE cell death. Finally, we discovered that circ-0008833 and circ-0008833-57aa promoted the expression of Caspase-1, IL-18, IL-1ß, NLRP3, ASC, and cleaved GSDMD in 16HBE cells. Conclusions: Upregulation of circ-0008833 might promote COPD progression by inducing pyroptosis of bronchial epithelial cells through the encoding of a 57-amino acid peptide.


Assuntos
MicroRNAs , Doença Pulmonar Obstrutiva Crônica , Masculino , Humanos , RNA Circular/genética , Proteína 3 que Contém Domínio de Pirina da Família NLR/genética , Proteína 3 que Contém Domínio de Pirina da Família NLR/metabolismo , Piroptose , Interleucina-18/metabolismo , Leucócitos Mononucleares , Células Epiteliais , Doença Pulmonar Obstrutiva Crônica/metabolismo , Caspases/metabolismo , MicroRNAs/genética
17.
Sleep Breath ; 28(1): 319-329, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-37726500

RESUMO

BACKGROUND: Exosomes are involved in cell-to-cell communication in numerous diseases including cardiovascular diseases, neurological diseases. Little attention has been dedicated to exosomal circular RNAs in obstructive sleep apnea (OSA)-related cardiovascular diseases. The aim of this study was to explore the role of exosomal circular RNA ZNF292 (circZNF292) on AC16 cells exposure to intermittent hypoxia (IH). METHODS: Exosome release inhibitor GW4869 was used to examine the effect of exosomes on IH-induced AC16 cells apoptosis. The expression of exosomal circZNF292 was detected by qRT-PCR in AC16 cells exposure to IH, and a luciferase reporter assay was conducted to confirm the connection between circZNF292 and miR-146a-5p. Exosomal circZNF292 was stably transfected with short hairpin RNAs (shRNAs) against circZNF292 and co-cultured with AC16 cells. The expression of miR-146a-5p and apoptosis-related protein was then measured to evaluate the effect of exosomal circZNF292. RESULTS: We found that IH contributed to the AC16 cells apoptosis, and the administration of GW4869 increased the apoptosis of cardiomyocytes when exposed to IH. The expression of exosomal circZNF292 decreased and miR-146a-5p increased significantly in AC16 cells exposed to IH compared to normoxic conditions. Bioinformatics analysis predicted a circZNF292/miR-146a-5p axis in IH-induced cardiomyocytes apoptosis. The dual-luciferase reporter system validated the direct interaction of circZNF292 and miR-146a-5p. Knockdown of circZNF292 increased the expressions of miR-146a-5p and accelerated the AC16 cardiomyocytes apoptosis. CONCLUSIONS: The findings of this study suggested a novel mechanism by which exosomes transmit intrinsic regulatory signals to the myocardium through the exosomal circZNF292/miR-146a-5p axis. This finding highlights the potential of targeting this pathway as a therapeutic approach for treating cardiovascular diseases associated with OSA.


Assuntos
Compostos de Anilina , Compostos de Benzilideno , Doenças Cardiovasculares , MicroRNAs , Apneia Obstrutiva do Sono , Humanos , MicroRNAs/genética , MicroRNAs/metabolismo , MicroRNAs/farmacologia , RNA Circular/genética , RNA Circular/metabolismo , RNA Circular/farmacologia , Miócitos Cardíacos/metabolismo , Doenças Cardiovasculares/metabolismo , Apoptose/genética , Hipóxia/genética , Hipóxia/metabolismo , Luciferases/metabolismo , Luciferases/farmacologia , Apneia Obstrutiva do Sono/metabolismo , Proteínas de Transporte , Proteínas do Tecido Nervoso/metabolismo , Proteínas do Tecido Nervoso/farmacologia
18.
J Prosthet Dent ; 2024 Jul 08.
Artigo em Inglês | MEDLINE | ID: mdl-38981805

RESUMO

STATEMENT OF PROBLEM: Although composite resin restorations have been widely used for dental restorations, the durability of the bond affects the rate of restoration failure. However, how multiple strategies for enhancing the resin-dentin bond affect durability is unclear. PURPOSE: The purpose of this systematic review and meta-analysis was to evaluate the impact of dentin conditioners on resin-dentin bond strength with different pretreatments before the application of adhesives. MATERIAL AND METHODS: The PubMed, Web of Science, EMBASE, and Cochrane Library databases were searched from 2013 to July 2023 for in vitro studies that evaluated the impact of dentin conditioners on resin-dentin bond strength. The meta-analysis was conducted using a random-effects model with pooled effect as standardized mean differences (α=.05). RESULTS: A total of 23 studies met the inclusion criteria for qualitative analysis, of which 15 were used for quantitative analysis. The results demonstrated that, under dry bonding conditions, selective extrafibrillar demineralization dentin conditioners significantly enhanced the immediate bond strength (P<.001). The long-term bond strength was limited by the sample size of the subgroup, but a significant effect was found after using selective extrafibrillar demineralization dentin conditioners (P<.001). However, metal salt-based dentin conditioners improved the immediate bond strength only under wet bonding conditions (P=.010). Notably, acid-based dentin conditioners significantly improved the long-term bond strength under both dry and wet bonding conditions (P<.001 and P=.006). CONCLUSIONS: The application of acid-based dentin conditioners significantly improved resin-dentin bond durability under both wet and dry bonding conditions. Furthermore, selective extrafibrillar demineralization dentin conditioners demonstrated remarkable effectiveness in improving resin-dentin bond durability under dry bonding conditions; however, more data are needed to support their use.

19.
Molecules ; 29(13)2024 Jul 03.
Artigo em Inglês | MEDLINE | ID: mdl-38999118

RESUMO

In this study, a liquid chromatographic method was developed for the fast determination of lincomycin, polymyxin and vancomycin in a preservation solution for transplants. A Kinetex EVO C18 (150 × 4.6 mm, 2.6 µm) column was utilized at 45 °C. Gradient elution was applied using a mixture of mobile phases A and B, both including 30 mM phosphate buffer at pH 2.0 and acetonitrile, at a ratio of 95:5 (v/v) for A and 50:50 (v/v) for B. A flow rate of 1.0 mL/min, an injection volume of 20 µL and UV detection at 210 nm were used. A degradation study treating the three antibiotics with 0.5 M hydrochloric acid, 0.5 M sodium hydroxide and 3% H2O2 indicated that the developed method was selective toward lincomycin, polymyxin, vancomycin and their degradation products. Other ingredients of the preservation solution, like those from the cell culture medium, did not interfere. The method was validated with good sensitivity, linearity, precision and accuracy. Furthermore, lincomycin, polymyxin and vancomycin were found to be stable in this preservation solution for 4 weeks when stored at -20 °C.


Assuntos
Lincomicina , Polimixinas , Vancomicina , Lincomicina/análise , Vancomicina/análise , Polimixinas/análise , Cromatografia Líquida/métodos , Soluções para Preservação de Órgãos , Antibacterianos/análise , Reprodutibilidade dos Testes , Cromatografia Líquida de Alta Pressão/métodos
20.
Aesthet Surg J ; 2024 May 26.
Artigo em Inglês | MEDLINE | ID: mdl-38796832

RESUMO

BACKGROUND: Keloids are excessive formations of scar tissue that develop at the site of a skin injury. Due to their invasive nature, they have a negative impact on the skin's appearance and are prone to recurrence, making them a challenging condition to treat in terms of skin aesthetics. OBJECTIVES: The objective of this article is to compare the long-term effects of dermatologic trephination with non-surgical treatments in scar repair and evaluate their clinical value. METHODS: A retrospective analysis was conducted on 48 patients who received keloids treatment in the Department of Dermatology and Thoracic Surgery of our hospital from January 2021 to October 2023, of which 24 patients received dermatologic trephination and 24 patients received non-surgical treatment. Outcome measures included scar appearance, scar healing time, pain and itching levels, and patient satisfaction. RESULTS: In the comparison of scar healing time, the healing time of patients using dermatologic trephination was significantly shorter than that of patients in the non-surgical group. In the evaluation of the degree of itching, the degree of itching in patients undergoing dermatologic trephination was significantly lower than that of patients in the non-surgical group. In the evaluation of satisfaction, the satisfaction of patients using dermatologic trephination was significantly higher than that of patients in the non-surgical group. CONCLUSIONS: This study demonstrates that trephination achieves more significant long-term results in keloid revision, including improved keloid appearance, itching and patient satisfaction.

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