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1.
RNA ; 29(8): 1288-1300, 2023 08.
Artigo em Inglês | MEDLINE | ID: mdl-37105714

RESUMO

Synthetic RNA oligonucleotides composed of canonical and modified ribonucleotides are highly effective for RNA antisense therapeutics and RNA-based genome engineering applications utilizing CRISPR-Cas9. Yet, synthesis of synthetic RNA using phosphoramidite chemistry is highly inefficient and expensive relative to DNA oligonucleotides, especially for relatively long RNA oligonucleotides. Thus, new biotechnologies are needed to significantly reduce costs, while increasing synthesis rates and yields of synthetic RNA. Here, we engineer human DNA polymerase theta (Polθ) variants and demonstrate their ability to synthesize long (95-200 nt) RNA oligonucleotides with canonical ribonucleotides and ribonucleotide analogs commonly used for stabilizing RNA for therapeutic and genome engineering applications. In contrast to natural promoter-dependent RNA polymerases, Polθ variants synthesize RNA by initiating from DNA or RNA primers, which enables the production of RNA without short abortive byproducts. Remarkably, Polθ variants show the lower capacity to misincorporate ribonucleotides compared to T7 RNA polymerase. Automation of this enzymatic RNA synthesis technology can potentially increase yields while reducing costs of synthetic RNA oligonucleotide production.


Assuntos
RNA Polimerases Dirigidas por DNA , RNA , Humanos , RNA/genética , RNA Polimerases Dirigidas por DNA/genética , DNA/genética , Ribonucleotídeos/genética , Oligonucleotídeos , DNA Polimerase teta
2.
Ecotoxicol Environ Saf ; 270: 115889, 2024 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-38150751

RESUMO

Silica nanoparticles (SiNPs) have been widely used in electronics, chemistry, and biomedicine. Human exposure to SiNPs and possible health effects have attracted much attention. The potential cardiovascular toxicity of SiNPs and their related mechanisms are still unclear. Therefore, in this study, we investigated the toxic effects of SiNPs on human umbilical vein endothelial cells (HUVECs). We found that SiNPs could induce HUVECs ferroptosis. The results showed that the level of intracellular divalent iron and lipid peroxidation increased, and mitochondrial cristae decreased. In addition, the pretreatment of the iron chelator deferoxamine mesylate (DFO) could alleviate the ferroptosis of cells. Interestingly, pretreatment of 3-methyladenine (3-MA), an autophagy/PI3K inhibitor could partially inhibit autophagy and reduce ferroptosis, which indicated that autophagy played an important role in cell ferroptosis. Additionally, after knocking down nuclear receptor coactivator 4 (NCOA4), Ferritin Heavy Chain 1 (FTH1) expression was up-regulated, and the levels of divalent iron and lipid peroxidation decreased, which suggested that NCOA4 mediated the ferroptosis of HUVECs induced by SiNPs. In conclusion, this study shows that SiNPs can induce cardiovascular toxicity in which there is ferroptosis. NCOA4-mediated ferritinophagy and resultant ferroptosis by SiNPs may play an important role. This study provides a new theoretical strategy for the treatment and prevention of cardiovascular diseases in the future.


Assuntos
Ferroptose , Nanopartículas , Humanos , Células Endoteliais da Veia Umbilical Humana/metabolismo , Dióxido de Silício/toxicidade , Fosfatidilinositol 3-Quinases/metabolismo , Ferro/metabolismo , Fatores de Transcrição/metabolismo , Nanopartículas/toxicidade , Autofagia , Coativadores de Receptor Nuclear/genética , Coativadores de Receptor Nuclear/metabolismo
3.
Environ Toxicol ; 39(3): 1175-1186, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-37860912

RESUMO

Magnetite nanoparticles (MNPs) have been extensively detected in the atmospheric environment and implicated as a prominent threat to atherosclerosis, a chronic vascular inflammatory disease. Due to globalization and economic development, the dramatic shift in diet from traditional to high-fat dietary patterns aggravated atherosclerosis progression induced by environmental factors. However, limited knowledge is available regarding vascular risks and underlying mechanisms of airborne MNPs in high-risk populations with high-fat dietary habits. Herein, we demonstrated that MNPs exerted a proatherogenic effect under high-fat dietary patterns, leading to aortic wall thickening, elastic fiber disorganization, macrophage infiltration, and local inflammation. Based on the correlation analysis between MNPs and PM group, we identified that MNPs might be a key PM component in atherogenic toxicity. MNPs exposure disturbed the dynamic process of lipid metabolism, manifested as aortic lipid accumulation, dyslipidemia, and hepatic lipid metabolism disorder, which was modulated by the JAK-STAT pathway. Overall, these findings provide new insight into understanding the cardiovascular risks and mechanisms of MNPs among high-risk populations.


Assuntos
Aterosclerose , Nanopartículas de Magnetita , Humanos , Metabolismo dos Lipídeos , Nanopartículas de Magnetita/toxicidade , Padrões Dietéticos , Janus Quinases , Transdução de Sinais , Fatores de Transcrição STAT
4.
Infect Immun ; 91(6): e0035722, 2023 Jun 15.
Artigo em Inglês | MEDLINE | ID: mdl-37212691

RESUMO

Osteomyelitis is difficult to cure, and the rapidly rising morbidity is a thorny problem accompanied by a large number of joint replacement applications. Staphylococcus aureus is the main pathogen of osteomyelitis. Circular RNAs (circRNAs), as emerging noncoding RNAs, play important roles in multiple physiopathological processes which could provide novel insights into osteomyelitis. However, little is known about the roles of circRNAs in the pathogenesis of osteomyelitis. Osteoclasts, considered bone sentinels, are the resident macrophages in bone and may play the immune defense roles in osteomyelitis. It has been reported that S. aureus can survive in osteoclasts, but the function of osteoclast circRNAs in response to intracellular S. aureus infection remains unclear. In this study, we investigated the profile of circRNAs in osteoclasts infected by intracellular S. aureus through high-throughput RNA sequencing. In total, 24 upregulated and 62 downregulated differentially expressed circRNAs were identified and subsequently analyzed to demonstrate their potential functions. On this basis, three circRNAs (chr4:130718154-130728164+, chr8:77409548-77413627-, and chr1:190871592-190899571-) were confirmed as potential novel biomarkers for the diagnosis of osteomyelitis through the murine model of osteomyelitis. Most importantly, we verified that the circRNA chr4:130718154-130728164+ named circPum1 could regulate the host autophagy to affect the intracellular infection of S. aureus through miR-767. In addition, circPum1 could serve as a promising serum biomarker in osteomyelitis patients caused by S. aureus infection. Taken together, this study provided the first global transcriptomic profile analysis of circRNAs in osteoclasts infected by intracellular S. aureus and first proposed a novel perspective for the pathogenesis and immunotherapy of S. aureus-induced osteomyelitis from the term of circRNAs.


Assuntos
MicroRNAs , Osteomielite , Humanos , Animais , Camundongos , RNA Circular/genética , RNA Circular/metabolismo , Osteoclastos/metabolismo , Transcriptoma , Staphylococcus aureus/genética , Staphylococcus aureus/metabolismo , Osteomielite/genética , MicroRNAs/genética , MicroRNAs/metabolismo
5.
Acc Chem Res ; 55(21): 3071-3079, 2022 11 01.
Artigo em Inglês | MEDLINE | ID: mdl-36251270

RESUMO

Reaction dynamics in the liquid-vapor interface is one of the crucial physical sciences but is still starving for in-depth exploration. It is challenging to selectively detect the interfacial species or the yields of chemical reaction therein, meanwhile shielding or reducing the interference from the vapor and liquid bulk. Mass spectrometry is a straightforward method but is also frustrated in such a selective detection. Using a liquid microjet in combination with a pulsed electron beam, a linear time-of-flight mass spectrometer, and a quadrupole mass filter, we recently innovated time-delayed mass spectrometry for investigations of the liquid-vapor interface. In this Account, we illustrate how this unique method succeeds in disentangling different sources, i.e., the vapor and liquid-vapor interface, of the ionic yields of the electron impacts with a liquid beam of alcohol in vacuum. These achievements are basically attributed to the application of an onion-peeling strategy in the ion detection. Concretely, the microsecond time scale of molecular volatilization can be resolved well by tuning the delay time between the nanosecond pulses of incident electron bunch and ion attractor. First, the specific orientation of the interfacial molecule, i.e., a well-known fact about the hydrophobic hydrocarbon groups pointing outside the liquid surface of alcohol, is validated again. More importantly, the dynamic features of time-delayed mass spectra, in particular, for the ionic yields from the liquid-vapor interface, are rationalized explicitly. Moreover, we demonstrate evidence of in situ molecular dimers in the liquid-vapor interface of 1-propanol. As the first example of electron-induced reaction in the liquid-vapor interface, dimethyl ether can be synthesized in the liquid methanol interface due to local interfacial acidification by high-energy electron impacts. On the contrary, the low energy electron can lead to local basicity through dissociative electron attachment (DEA). Besides the primary low-energy electrons, the low-energy secondary and inelastically scattered electrons in the higher-energy impacts of the primary electrons can also participate in the DEA process. In contrast to the gas- or solid-phase DEAs, that in the liquid-vapor interface shows distinct differences in both the types and efficiencies of anionic products. With these and efforts in the future, we develop a molecular-level understanding of how the chemical reactions happen in the liquid-vapor interface.


Assuntos
Elétrons , Metanol , Íons , Metanol/química , Ânions , Gases
6.
Eur Radiol ; 33(7): 4864-4874, 2023 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-36826500

RESUMO

OBJECTIVE: To investigate the feasibility of deep learning-based MRI (DL-MRI) in its application in shoulder imaging and compare its performance with conventional MR imaging (non-DL-MRI). METHODS: This retrospective study was approved by the local ethics committee. Seventy consecutive patients who had been examined with both DL-MRI and non-DL-MRI were enrolled for the image quality and lesion diagnosis comparison. Another 400 patients had been examined only with DL-MRI. Their images' quality was assessed by 20 radiologists using a satisfaction survey. The Kendall W test was performed to assess interobserver agreement. The Wilcoxon test was performed to compare the image quality. For lesion diagnosis, the interobserver and interstudy agreement were evaluated by kappa analysis. RESULTS: The scan time of DL-MRI (6 min 1 s) was nearly 50% decreased compared with that of non-DL-MRI (11 min 25 s). The image quality was higher in both PDWI (4.85 ± 0.31 for DL, and 4.73 ± 0.29 for non-DL) and T2WI (4.95 ± 0.2 for DL, and 4.74 ± 0.41 for non-DL) of DL-MRI. Good interobserver agreement was found for the image quality of all the MR sequences on both DL-MRI (Kendall W: 0.588~0.902) and non-DL-MRI (Kendall W: 0751~0.865). Both the SNRs and |CNR| were significantly higher in PDWI and T2WI of DL-MRI. High interobserver and interstudy agreements for the lesions in non-DL-MRI and DL-MRI (kappa value = 0.913 to 1.000) were observed. The results of the image quality satisfaction survey in 400 patients receiving DL-MRI in the shoulder obtained 5 scores among all the radiologists. CONCLUSION: Shoulder DL-MRI can greatly reduce the scan time, while improve imaging quality of PDWI and T2WI compared to non-DL-MRI. KEY POINTS: • Shoulder 2D DL-MRI can greatly reduce the whole scan time and improve imaging quality of both PDWI and T2WI compared to conventional parallel MRI. • Shoulder 2D DL-MRI could be a clinical routine with greatly improved work efficiency in the future.


Assuntos
Aprendizado Profundo , Ombro , Humanos , Ombro/diagnóstico por imagem , Estudos Retrospectivos , Imageamento por Ressonância Magnética/métodos , Espectroscopia de Ressonância Magnética , Algoritmos
7.
Chem Soc Rev ; 51(2): 720-760, 2022 Jan 24.
Artigo em Inglês | MEDLINE | ID: mdl-34985085

RESUMO

Photoresponsive nucleic acids attract growing interest as functional constituents in materials science. Integration of photoisomerizable units into DNA strands provides an ideal handle for the reversible reconfiguration of nucleic acid architectures by light irradiation, triggering changes in the chemical and structural properties of the nanostructures that can be exploited in the development of photoresponsive functional devices such as machines, origami structures and ion channels, as well as environmentally adaptable 'smart' materials including nanoparticle aggregates and hydrogels. Moreover, photoresponsive DNA components allow control over the composition of dynamic supramolecular ensembles that mimic native networks. Beyond this, the modification of nucleic acids with photosensitizer functionality enables these biopolymers to act as scaffolds for spatial organization of electron transfer reactions mimicking natural photosynthesis. This review provides a comprehensive overview of these exciting developments in the design of photoresponsive DNA materials, and showcases a range of applications in catalysis, sensing and drug delivery/release. The key challenges facing the development of the field in the coming years are addressed, and exciting emergent research directions are identified.


Assuntos
Nanopartículas , Nanoestruturas , Catálise , DNA , Sistemas de Liberação de Medicamentos
8.
Int J Mol Sci ; 24(19)2023 Oct 09.
Artigo em Inglês | MEDLINE | ID: mdl-37834477

RESUMO

ADP-ribosylation is a post-translational modification of proteins that plays a key role in various cellular processes, including DNA repair. Recently, significant progress has been made in understanding the mechanism and function of ADP-ribosylation in DNA repair. ADP-ribosylation can regulate the recruitment and activity of DNA repair proteins by facilitating protein-protein interactions and regulating protein conformations. Moreover, ADP-ribosylation can influence additional post-translational modifications (PTMs) of proteins involved in DNA repair, such as ubiquitination, methylation, acetylation, phosphorylation, and SUMOylation. The interaction between ADP-ribosylation and these additional PTMs can fine-tune the activity of DNA repair proteins and ensure the proper execution of the DNA repair process. In addition, PARP inhibitors have been developed as a promising cancer therapeutic strategy by exploiting the dependence of certain cancer types on the PARP-mediated DNA repair pathway. In this paper, we review the progress of ADP-ribosylation in DNA repair, discuss the crosstalk of ADP-ribosylation with additional PTMs in DNA repair, and summarize the progress of PARP inhibitors in cancer therapy.


Assuntos
Neoplasias , Poli(ADP-Ribose) Polimerases , Humanos , Poli(ADP-Ribose) Polimerases/metabolismo , Inibidores de Poli(ADP-Ribose) Polimerases/farmacologia , Inibidores de Poli(ADP-Ribose) Polimerases/uso terapêutico , ADP-Ribosilação , Reparo do DNA , Processamento de Proteína Pós-Traducional , Neoplasias/tratamento farmacológico , Neoplasias/genética , Proteínas/metabolismo
9.
Int J Mol Sci ; 24(12)2023 Jun 12.
Artigo em Inglês | MEDLINE | ID: mdl-37373165

RESUMO

The inflammatory system activated by uterine infection is associated with decreased fertility. Diseases can be detected in advance by identifying biomarkers of several uterine diseases. Escherichia coli is one of the most frequent bacteria that is involved in pathogenic processes in dairy goats. The purpose of this study was to investigate the effect of endotoxin on protein expression in goat endometrial epithelial cells. In this study, the LC-MS/MS approach was employed to investigate the proteome profile of goat endometrial epithelial cells. A total of 1180 proteins were identified in the goat Endometrial Epithelial Cells and LPS-treated goat Endometrial Epithelial Cell groups, of which, 313 differentially expressed proteins were accurately screened. The proteomic results were independently verified by WB, TEM and IF techniques, and the same conclusion was obtained. To conclude, this model is suitable for the further study of infertility caused by endometrial damage caused by endotoxin. These findings may provide useful information for the prevention and treatment of endometritis.


Assuntos
Endometrite , Endométrio , Cabras , Proteínas , Proteômica , Proteômica/métodos , Endometrite/diagnóstico , Espectrometria de Massa com Cromatografia Líquida , Feminino , Animais , Biomarcadores/análise , Endométrio/química , Células Epiteliais/química , Proteínas/análise , Células Cultivadas
10.
Int J Med Microbiol ; 312(7): 151568, 2022 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-36240531

RESUMO

Bone infection is a common and serious complication in the field of orthopedics, which frequently leads to excessive bone destruction and fracture nonunion. Staphylococcus aureus (S. aureus) infection affects bone cell function which, in turn, causes bone destruction. Bone is mainly regulated by osteoblasts and osteoclasts. Osteoclasts are the only cell type with bone resorptive function. Their over-activation is closely associated with excessive bone loss. Understanding how S. aureus changes the functional state of osteoclasts is the key to effective treatment. By reviewing the literature, this paper summarizes several mechanisms of bone destruction caused by S. aureus influencing osteoclasts, thereby stimulating new ideas for the treatment of bone infection.


Assuntos
Reabsorção Óssea , Infecções Estafilocócicas , Humanos , Osteoclastos/metabolismo , Staphylococcus aureus/fisiologia , Reabsorção Óssea/metabolismo , Diferenciação Celular , Infecções Estafilocócicas/metabolismo
11.
Cancer Cell Int ; 22(1): 78, 2022 Feb 12.
Artigo em Inglês | MEDLINE | ID: mdl-35151325

RESUMO

BACKGROUND: The role of circular RNAs (circRNAs) and microRNAs (miRNAs) in osteosarcoma (OS) development has not been fully elucidated. Further, the contribution of the immune response to OS progression is not well defined. However, it is known that circRNAs and miRNAs can serve as biomarkers for the diagnosis, prognosis, and therapy of many cancers. Thus, the aim of this study was to identify novel key serum biomarkers for the diagnosis and metastatic prediction of OS by analysis of immune cell infiltration and associated RNA molecules. METHODS: Human OS differentially expressed circRNAs (DEcircRNAs), differentially expressed miRNAs (DEmiRNAs), and differentially expressed mRNAs (DEmRNAs) were identified by analysis of microarray data downloaded from Gene Expression Omnibus (GEO) datasets. Further, characteristic patterns of OS-infiltrating immune cells were analyzed. On this basis, we identified statistically significant transcription factors. Moreover we performed pathway enrichment analysis, constructed protein-protein interaction networks, and devised competitive endogenous RNA (ceRNA) networks. Biological targets of the ceRNA networks were evaluated and potential OS biomarkers confirmed by RT-qPCR analysis of the patients' serum. RESULTS: Seven differentially expressed circRNAs, 166 differentially expressed miRNAs, and 175 differentially expressed mRNAs were identified. An evaluation of cellular OS infiltration identified the highest level of infiltration by M0 macrophages, M2 macrophages, and CD8+ T cells, with M0 macrophages and CD8+ T cells as the most prominent. Significant patterns of tumor-infiltrating immune cells were identified by principal component analysis. Moreover, 185 statistically significant transcription factors were associated with OS. Further, in association with immune cell infiltration, hsa-circ-0010220, hsa-miR-326, hsa-miR-338-3p, and FAM98A were identified as potential novel biomarkers for OS diagnosis. Of these, FAM98A had the most promise as a diagnostic marker for OS and OS metastasis. Most importantly, a novel diagnostic model consisting of these four biomarkers (hsa-circ-0010220, hsa-miR-326, hsa-miR-338-3p, and FAM98A) was established with a 0.928 AUC value. CONCLUSIONS: In summary, potential serum biomarkers for OS diagnosis and metastatic prediction were identified based on an analysis of immune cell infiltration. A novel diagnostic model consisting of these four promising serum biomarkers was established. Taken together, the results of this study provide a new perspective by which to understand immunotherapy of OS.

12.
J Org Chem ; 87(16): 10698-10709, 2022 08 19.
Artigo em Inglês | MEDLINE | ID: mdl-35930467

RESUMO

Employing a low loading of the terminal oxidant, a remote directing group-enabled radical relay strategy for benzylic direct C(sp3)-H alkoxylation with alcohols at room temperature is developed. Satisfactory site-selectivity, chemoselectivity, and reaction scope are achieved under simple and mild conditions, and no ligand or additive is required. Mechanistic studies, ready conversions of the directing group, and other benzylic functionalizations currently under development in our laboratory further indicate the promising potentials of this remote directing group-enabled radical relay strategy.


Assuntos
Etanol , Benzeno/química , Catálise , Temperatura
13.
Analyst ; 147(22): 4980-4985, 2022 Nov 07.
Artigo em Inglês | MEDLINE | ID: mdl-36197295

RESUMO

DNA methyltransferase (MTase) is an important regulatory enzyme in various biological processes. However, current methods for investigating MTase activity are still limited in terms of sensitivity and/or generality. Herein, we proposed a dual amplification fluorescence strategy for the ultrasensitive detection of DNA adenine methylation methyltransferase (Dam MTase) activity based on strand displacement amplification (SDA) coupled with rolling circle amplification (RCA). In this study, the hairpin probe could not be cleaved by Nt.AlwI nicking endonuclease (Nt.AlwI) in the presence of Dam MTase, and the subsequent SDA-RCA reaction was blocked, resulting in a weak fluorescence signal. Moreover, the blocking effect was more pronounced at a higher concentration of Dam MTase. This assay provides a very low detection limit (down to 0.0067 U ml-1), as well as good selectivity against other types of MTases (e.g., CpG methyltransferase (M.SssI MTase)). In addition, the analytical mode improves the generality and can be extended to the detection of other types of DNA MTases.


Assuntos
Técnicas Biossensoriais , Metilases de Modificação do DNA , Metilação de DNA , Espectrometria de Fluorescência/métodos , Metiltransferases/genética , DNA/genética , Técnicas Biossensoriais/métodos
14.
Nano Lett ; 21(17): 7388-7395, 2021 09 08.
Artigo em Inglês | MEDLINE | ID: mdl-34424703

RESUMO

Highly compact, filter-free multispectral photodetectors have important applications in biological imaging, face recognition, and remote sensing. In this work, we demonstrate room-temperature wavelength-selective multipixel photodetectors based on GaAs0.94Sb0.06 nanowire arrays grown by metalorganic vapor phase epitaxy, providing more than 10 light detection channels covering both visible and near-infrared ranges without using any optical filters. The nanowire array geometry-related tunable spectral photoresponse has been demonstrated both theoretically and experimentally and shown to be originated from the strong and tunable resonance modes that are supported in the GaAsSb array nanowires. High responsivity and detectivity (up to 44.9 A/W and 1.2 × 1012 cm √Hz/W at 1 V, respectively) were obtained from the array photodetectors, enabling high-resolution RGB color imaging by applying such a nanowire array based single pixel imager. The results indicate that our filter-free wavelength-selective GaAsSb nanowire array photodetectors are promising candidates for the development of future high-quality multispectral imagers.


Assuntos
Nanofios , Diagnóstico por Imagem
15.
Opt Express ; 29(21): 33548-33557, 2021 Oct 11.
Artigo em Inglês | MEDLINE | ID: mdl-34809165

RESUMO

Random lasers, which rely on random scattering events unlike traditional Fabry-Pérot cavities, are much simpler and cost-effective to fabricate. However, because of the chaotic fluctuations and instability of the lasing modes, controlling the lasing properties is challenging. In this study, we use random InP nanowire (NW) arrays that operate in the Anderson localization regime with stable modes as the random lasers. We show that by changing the design parameters of the NW arrays, such as filling factor, dimensions of the NWs, degree of randomness, and the size of the array, the properties of the lasing modes including the number of modes, lasing wavelengths, and lasing threshold can be controlled.

16.
Microb Pathog ; 158: 105051, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-34153417

RESUMO

As of April 1, 2021, more than 2.8 million people have died of SARS-CoV-2 infection. In addition, the mutation of virus strains that have accompanied the pandemic has brought more severe challenges to pandemic control. Host microRNAs (miRNAs) are widely involved in a variety of biological processes of coronavirus infection, including autophagy in SARS-CoV-2 infection. However, the mechanisms underlying miRNAs involved in autophagy in SARS-CoV-2 infection have not been fully elucidated. In this study, the miRNA and messenger RNA (mRNA) expression profiles of patients with SARS-CoV-2 infection were investigated based on raw data from Gene Expression Omnibus (GEO) datasets, and potential novel biomarkers of autophagy were revealed by bioinformatics analyses. We identified 32 differentially expressed miRNAs and 332 differentially expressed mRNAs in patients with SARS-CoV-2 infection. Cytokine receptor related pathways were the most enriched pathways for differentially expressed miRNAs identified by pathway analysis. Most importantly, an autophagy interaction network, which was associated with the pathological processes of SARS-CoV-2 infection, especially with the cytokine storm, was constructed. In this network, hsa-miR-340-3p, hsa-miR-652-3p, hsa-miR-4772-5p, hsa-miR-192-5p, TP53INP2, and CCR2 may be biomarkers that predict changes in mild SARS-CoV-2 infection. Some molecules, including hsa-miR-1291 and CXCR4, were considered potential targets to predict the emergence of severe symptoms in SARS-CoV-2 infection. To our knowledge, this study provided the first profile analysis of an autophagy interaction network in SARS-CoV-2 infection and revealed several novel autophagy-related biomarkers for understanding the pathogenesis of SARS-CoV-2 infection in vivo.


Assuntos
COVID-19 , MicroRNAs , Autofagia/genética , Biologia Computacional , Perfilação da Expressão Gênica , Redes Reguladoras de Genes , Humanos , MicroRNAs/genética , SARS-CoV-2
17.
Australas J Dermatol ; 62(2): e217-e222, 2021 May.
Artigo em Inglês | MEDLINE | ID: mdl-33326599

RESUMO

BACKGROUND: The aetiology and pathogenesis of vulvar lichen sclerosus (LS), a chronic inflammatory disease, is not completely clear. It has been found that local cellular immune abnormalities play an important role in the immune mechanism of LS, mainly characterised by abnormal numbers of Langerhans cells in the epidermis and abnormal numbers of dermal T lymphocytes. OBJECTIVE: To evaluate the densities of Langerhans cells and T-lymphocyte subpopulations in vulvar LS. METHODS: The density of Langerhans cells in the epidermis, and CD3+ , CD4+ and CD8+ T cells in the dermis of seven early-stage and eight late-stage cases of vulvar LS were detected with direct immunofluorescence, and compared with 15 normal controls. RESULTS: The density of Langerhans cells in the late-stage group was significantly higher than in the normal group (P = 0.001). The densities of CD3+ , CD4+ and CD8+ T lymphocytes in both the early- and late-stage (deeper dermis) groups were higher than in the normal group (P < 0.05). The ratio of CD4+ /CD8+ T lymphocytes in the early-stage and normal groups showed no significant difference (P = 0.151), while the late-stage (deeper dermis) groups decreased significantly compared with early-stage, late-stage (upper dermis) and normal groups (P < 0.001). CONCLUSION: The densities of Langerhans cells, CD3+ , CD4+ and CD8+ T cells, and the ratio of CD4+ /CD8+ T lymphocytes were different in different stages of LS, which supports the important role of cellular immunity in mechanisms of LS.


Assuntos
Células de Langerhans/patologia , Linfócitos T/patologia , Líquen Escleroso Vulvar/patologia , Adulto , Complexo CD3/metabolismo , Estudos de Casos e Controles , Contagem de Células , Derme/patologia , Feminino , Técnica Direta de Fluorescência para Anticorpo , Humanos , Pessoa de Meia-Idade , Adulto Jovem
18.
Environ Toxicol ; 36(7): 1389-1401, 2021 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-33764603

RESUMO

Silica nanoparticles (SiNPs) as one of the most productive nano-powder, has been extensively applied in various fields. There has been increasing concern about the adverse effects of SiNPs on the health of ecological organisms and human. The potential cardiovascular toxicity of SiNPs and involved mechanisms remain elusive. Hence, in this study, we investigated the cardiovascular toxicity of SiNPs (60 nm) and explored the underlying mechanisms using H9c2 cardiomyocytes. Results showed that SiNPs induced oxidative stress and activated the Nrf2/HO-1 antioxidant pathway. Autophagy was also activated by SiNPs. Interestingly, N-acetyl-L-cysteine (NAC)attenuated autophagy after inhibiting reactive oxygen species (ROS). Meanwhile, down-regulation of Nrf2 enhanced autophagy. In summary, these data indicated that SiNPs induce autophagy in H9c2 cardiomyocytes through oxidative stress, and the Nrf2/HO-1 pathway has a negative regulatory effect on autophagy. This study provides new evidence for the cardiovascular toxicity of SiNPs and provides a reference for the safe use of nanomaterials in the future.


Assuntos
Nanopartículas , Dióxido de Silício , Autofagia , Humanos , Fator 2 Relacionado a NF-E2/genética , Nanopartículas/toxicidade , Estresse Oxidativo , Espécies Reativas de Oxigênio , Transdução de Sinais , Dióxido de Silício/toxicidade
19.
Sensors (Basel) ; 21(16)2021 Aug 11.
Artigo em Inglês | MEDLINE | ID: mdl-34450862

RESUMO

Semiconductor nanowire arrays have been demonstrated as promising candidates for nanoscale optoelectronics applications due to their high detectivity as well as tunable photoresponse and bandgap over a wide spectral range. In the infrared (IR), where these attributes are more difficult to obtain, nanowires will play a major role in developing practical devices for detection, imaging and energy harvesting. Due to their geometry and periodic nature, vertical nanowire and nanopillar devices naturally lend themselves to waveguide and photonic crystal mode engineering leading to multifunctional materials and devices. In this paper, we computationally develop theoretical basis to enable better understanding of the fundamental electromagnetics, modes and couplings that govern these structures. Tuning the photonic response of a nanowire array is contingent on manipulating electromagnetic power flow through the lossy nanowires, which requires an intimate knowledge of the photonic crystal modes responsible for the power flow. Prior published work on establishing the fundamental physical modes involved has been based either on the modes of individual nanowires or numerically computed modes of 2D photonic crystals. We show that a unified description of the array key electromagnetic modes and their behavior is obtainable by taking into account modal interactions that are governed by the physics of exceptional points. Such models that describe the underlying physics of the photoresponse of nanowire arrays will facilitate the design and optimization of ensembles with requisite performance. Since nanowire arrays represent photonic crystal slabs, the essence of our results is applicable to arbitrary lossy photonic crystals in any frequency range.

20.
Psychol Health Med ; 26(10): 1248-1257, 2021 12.
Artigo em Inglês | MEDLINE | ID: mdl-32844666

RESUMO

Premature ovarian insufficiency (POI) is affecting about 1% women of reproductive age. However, current studies have primarily focused on women with the views of male partners greatly absent from the literature. We conduct this research to investigate the psychosocial effect of POI on male partners and their perceptions of the disease.52 male partners of POI patient (experiment group) and 52 controls (control group) were available for analysis. Anxiety, depression, and marital relationship were assessed for male partners in both groups. A questionnaire about perceptions of POI was completed by the experiment group. Male partners of POI patient experienced greater levels of anxiety (10.96 versus 4.88; P < 0.01) and depression (12.23 versus 5.19; P < 0.01) compared with controls. In addition, they experienced worse marital relationship in several aspects than their counterparts. The findings also demonstrate that most POI patient male partners had inadequate and inaccurate knowledge about their partners' disease, which may be the results of insufficient professional counseling from health-care practitioners. Moreover, their understanding level of the disease was correlated to anxiety (r = -0.64; P < 0.01), depression (r = -0.38; P < 0.01), and communication (r = 0.28; P < 0.05).The study highlights the need for health-care services, as well as support and professional information resources aimed at POI patients' male partners.


Assuntos
Insuficiência Ovariana Primária , Ansiedade/epidemiologia , Feminino , Humanos , Masculino
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