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1.
Bull Environ Contam Toxicol ; 111(5): 63, 2023 Oct 31.
Artigo em Inglês | MEDLINE | ID: mdl-37904061

RESUMO

The risk assessment of heavy metals (HMs) in sewage sludge (SS) is essential before land application. Six HMs in nineteen SS collected in the Yangtze River Delta were analyzed to assess risks to environment, ecosystem, and human health. HMs concentrations were ranked in the order of Zn > Cu > Cr > Ni > Pb > Cd, with Cu, Zn, and Ni in a total of 16% of samples exceeding the legal standard. Zn showed greatest extractability according to EDTA-extractable concentrations. HMs in 16% of SS samples posed heavy contamination to the environment with Zn as the major pollutant. HMs in 26% of samples posed ecological risk to the ecosystem and Cd was the highest risky HM. The probabilistic health risk assessment revealed that HMs posed carcinogenic risks to all populations, but non-carcinogenic risks only to children. This work will provide fundamental information for land application of SS in this area.


Assuntos
Metais Pesados , Poluentes do Solo , Criança , Humanos , Esgotos , Ecossistema , Monitoramento Ambiental , Rios , Cádmio , Poluentes do Solo/análise , Medição de Risco , Metais Pesados/análise , China
2.
Chemistry ; 28(40): e202200579, 2022 Jul 15.
Artigo em Inglês | MEDLINE | ID: mdl-35467772

RESUMO

Hybrid organic-inorganic perovskite (HOIP) have received tremendous scientific attention because of the phase transition and photovoltaic properties. However, achieving the special perovskite structure with both two-step dielectric response and luminescence characteristics is rarely reported. Herein, we report an organic-inorganic hybrid perovskite, [(BA)2 ⋅ PbI4 ] (Compound 1, BA=n-butylamine) by introducing flexible organic cations (HBA+ ), with direct mid-band gap as 2.28 eV. Interestingly, this material exhibits two-step reversible dielectric response at 350 K and 460 K (in heating process), respectively. Besides, the photoluminescence was found: it emits charming green light under 365 nm lamp (Photoluminescence quantum yield is 9.52 %). The outstanding two-step dielectric response and luminescence characteristics of this compound might pave the way for the application of dielectric and ferroelectric functional materials in temperature sensors and mechanical switches.

3.
J Am Chem Soc ; 142(10): 4756-4761, 2020 Mar 11.
Artigo em Inglês | MEDLINE | ID: mdl-32090555

RESUMO

Materials with circularly polarized luminescence (CPL) activity have immense potential applications in molecular switches, optical sensors, information storage, asymmetric photosynthesis, 3D optical displays, biological probe, and spintronic devices. However, the achiral architectures of most of the luminophores severely limit their practical needs. Within this context, molecular ferroelectrics with striking chemical variability and structure-property flexibility bring light to the assembly of CPL-active ferroelectric materials. Herein, we report organic-inorganic perovskite enantiomorphic ferroelectrics, (R)- and (S)-3-(fluoropyrrolidinium)MnBr3, undergoing a 222F2-type ferroelectric phase transition at 273 K. Their mirror relationships are verified by both single-crystal X-ray diffraction and vibrational circular dichroism (VCD). Furthermore, the corresponding Cotton effect for two chiral crystals was captured by mirror CPL activity. This may be assigned to the inducing interaction between the achiral luminescent perovskite framework and chiral organic components. As far as we know, this is the first molecular ferroelectric with CPL activity. Accordingly, this will inspire intriguing research in molecular ferroelectrics with CPL activity and holds great potential for the development of new optoelectronic devices.

4.
J Am Chem Soc ; 142(2): 1077-1082, 2020 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-31851495

RESUMO

Piezoelectric sensors that can work under various conditions with superior performance are highly desirable with the arrival of the Internet of Things. For practical applications, a large piezoelectric voltage coefficient g and a high Curie temperature Tc are critical to the performance of piezoelectric sensors. Here, we report a two-dimensional perovskite ferroelectric (4-aminotetrahydropyran)2PbBr4 [(ATHP)2PbBr4] with a saturated polarization of 5.6 µC cm-2, high Tc of 503 K [above that of BaTiO3 (BTO, 393 K)], and extremely large g33 of 660.3 × 10-3 V m N-1 [much beyond that of Pb(Zr,Ti)O3 (PZT) ceramics (20 to 40 × 10-3 V m N-1), more than 2 times higher than that of poly(vinylidene fluoride) (PVDF, about 286.7 × 10-3 V m N-1)]. Combined with the advantages of molecular ferroelectrics, such as light weight, easy and environmentally friendly processing, and mechanical flexibility, (ATHP)2PbBr4 would be a competitive candidate for next-generation smart piezoelectric sensors in flexible devices, soft robotics, and biomedical devices.

5.
Inorg Chem ; 59(7): 4720-4728, 2020 Apr 06.
Artigo em Inglês | MEDLINE | ID: mdl-32163278

RESUMO

Dual phase transition/switch materials are a critical cornerstone of information storage and sensing. However, they are difficult to design successfully, and compared with materials showing single-switchable phase transitions, the dual ones retain many challenges by far. Therefore, the significance of a general strategy is far greater than an accidental success. Here, an efficient strategy combining branchlike Et3R and trunklike benzylamine analogues successfully validates dual-switch implementation in the dielectric materials. This inevitable success is based on our treelike analogue mentioned above in which amines with multiple branches can achieve a temperature-induced phase change. Exactly, (BCDA)2ZnBr4 [BCDA = benzyl-(2-chloroethyl)dimethylammonium] proves the regularity and undergoes two reversible phase transitions at 295.4 and 340.8 K, respectively. Variable-temperature single-crystal X-ray diffraction revealed that the generation of double phase transitions is caused by progressive changes of treelike BCDA+ as the temperature rises. Because the permittivity ε' of (BCDA)2ZnBr4 abruptly changed near the phase-transition temperatures, such physical properties make it have latent applicability. In short, the success of our strategy will inspire researches to discover more interesting dual phase transition/switch materials.

6.
Inorg Chem ; 58(7): 4600-4608, 2019 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-30896161

RESUMO

With regard to the artificial molecular motor that was recognized with the 2016 Nobel Prize, this success proves the great scientific significance of rotary motor-type motion at the molecular level, which has been expected to play an invaluable role in the development of electronic information molecular materials. However, designing electronic information-critical high-temperature molecular motors has always been a huge challenge. Since we discovered [(CH3)3NCH2Cl]MnCl3, this cation rotation pattern with a motor-type motion structure has continued to attract our attention. Considering a strategy that combines molecular machines with dielectric theory, ( N, N-dimethylpiperidinium)CdCl3, the new dielectric molecular motor material that exhibits superior physical properties, could be considered to be an excellent dielectric switch based on its electric field and temperature. Crystal structure analyses reveal that the reversible phase transition is mainly induced by the unusual chair-to-rotator motion of cations. Because of the unprecedented leaping structural transition from P63/ mmc to P21/ c and the rotating motor-type motion structure, the material exhibits remarkable anisotropy and outstanding dielectric switching characteristics. These findings open a new avenue for the design and assembly of novel molecular motor materials in the field of electronic information.

7.
Inorg Chem ; 57(16): 10153-10159, 2018 Aug 20.
Artigo em Inglês | MEDLINE | ID: mdl-30070836

RESUMO

Due to having excellent properties of sensitive switchable physical and/or chemical response, simple preparation, and environmentally friendly processing, bistable switches (electric switching between "on" and "off" bistable states) have gradually developed into an ideal class of highly smart materials. However, most of them contain metals, especially heavy metals, which are highly toxic to the environment, and metal-free switch materials are rarely reported. Based on this issue, we successfully designed and synthesized organic ion crystals and realized thermal dielectric switching characteristics. Differential scanning calorimetry and dielectric measurements show that the large-size crystal (F-TEDA)(BF4)2 (1) can be regarded as an sensitive dielectric bistable switching between high (switch on) and low (switch off) dielectric states. Variable-temperature single crystal structure reveals one-half of the BF4- anions in the crystal undergoes order-disorder transition around 200 K, similar to the transition between flower buds and blooming flowers. This flower-style transition of BF(1)4-/BF(0.5)8- triggered the rapid switching performance; those properties establish the basis of their applications in excellent temperature-responsive electrical switches, especially lightweight devices.

8.
J Am Chem Soc ; 139(39): 13903-13908, 2017 10 04.
Artigo em Inglês | MEDLINE | ID: mdl-28866880

RESUMO

The classical organic ferroelectric, poly(vinylidene fluoride) (PVDF), has attracted much attention as a promising candidate for data storage applications compatible with all-organic electronics. However, it is the low crystallinity, the large coercive field, and the limited thermal stability of remanent polarization that severely hinder large-scale integration. In light of that, we show a molecular ferroelectric thin film of [Hdabco][ReO4] (dabco = 1,4-diazabicyclo[2.2.2]octane) (1), belonging to another class of typical organic ferroelectrics. Remarkably, it displays not only the highest Curie temperature of 499.6 K but also the fastest polarization switching of 100k Hz among all reported molecular ferroelectrics. Combined with the large remanent polarization values (∼9 µC/cm2), the low coercive voltages (∼10 V), and the unique multiaxial ferroelectric nature, 1 becomes a promising and viable alternative to PVDF for data storage applications in next-generation flexible devices, wearable devices, and bionics.

9.
J Am Chem Soc ; 139(31): 10897-10902, 2017 08 09.
Artigo em Inglês | MEDLINE | ID: mdl-28719192

RESUMO

With the flourishing development of (CH3NH3)PbI3, three-dimensional (3D) organic-inorganic perovskites with unique structure-property flexibility have become a worldwide focus. However, they still face great challenges in effectively inducing ferroelectricity. Despite the typical 3D perovskite structure and the ability of dabco (1,4-diazabicyclo[2.2.2]octane) to trigger phase transition, unfortunately [H2dabco]RbCl3 adopts a nonpolar crystal structure without ferroelectricity. Within the larger RbI3 framework, we assemble N-methyl-1,4-diazoniabicyclo[2.2.2]octane (MeHdabco) obtained by reducing the molecular symmetry of dabco into a new 3D organic-inorganic perovskite. As expected, MeHdabco bearing a molecular dipole moment turns out to be vital in the generation of polar crystal structure and ferroelectric phase transition occurring at 430 K. It is the first time that the dabco component has been successfully wrapped into a 3D cage to achieve ferroelectricity even through there is intensive research on dabco. This precise molecular design strategy based on the modification of molecular symmetry provides an efficient route to enrich the family of 3D organic-inorganic perovskite ferroelectrics. Intriguingly, the iodine-doped crystal can exhibit intense saffron yellow luminescence with a high quantum yield of 17.17% under UV excitation, extending its application in the field of ferroelectric luminescence and/or multifunctional devices.

10.
Phys Rev Lett ; 119(20): 207602, 2017 Nov 17.
Artigo em Inglês | MEDLINE | ID: mdl-29219370

RESUMO

Recently, a plastic crystal of quinuclidinium perrhenate (HQReO_{4}) was reported to have the feasibility of controlling the crystallographic orientation in the grown crystal, but the corresponding temperature window is only about 22 K (345-367 K). Such a narrow window and uncertain ferroelectricity at room temperature would extremely limit its application potential. In this report, we prepared a large area high-quality polycrystalline thin film of HQReO_{4} and for the first time observed ferroelectricity in the temperature range from 298 to 367 K. Density functional theory calculations revealed the origin of room-temperature ferroelectricity is ascribed to the collaborative flipping of HQ (protonated quinuclidine) and ReO_{4}^{-}, which is dynamically preferred in the presence of a N─H⋯O hydrogen bond. A local piezoresponse force microscopy measurement was also employed to study the mechanisms of multiaxial polarization rotation and domain dynamics. By extending the ferroelectric temperature window to room temperature and the extraordinary thin-film processability, HQReO_{4} would certainly become a suitable candidate for next generation ferroelectric materials.

11.
Inorg Chem ; 56(23): 14477-14485, 2017 Dec 04.
Artigo em Inglês | MEDLINE | ID: mdl-29131646

RESUMO

Switchable materials, due to their potential applications in the fields of sensors, photonic devices, digital processing, etc., have been developed drastically. However, they still face great challenges in effectively inducing multiple molecular switching. Herein organic-inorganic hybrid compounds, an emerging class of hydrosoluble optoelectronic-active materials, welcome a new member with smart unique optical/electrical (fluorescence/dielectric) dual switches (switching ON/OFF), that is, [C5H13NBr][Cd3Br7] (1) in the form of both a bulk crystal and an ultraflexible monodirectional thin film, which simultaneously exhibits fast dielectric/fluorescent dual switching triggered by an optical/thermal/electric signal with a high signal-to-noise ratio of 35 (the highest one in the known optical/dielectric dual molecular switches). Additionally, the exceptional stability/fatigue resistance as well as the fantastic extensibility/compactness of thin films (more than 10000 times folding over 90°), makes 1 an ideal candidate for single-molecule intelligent wearable devices and seamlessly integrated optoelectronic multiswitchable devices. This opens up a new route toward advanced light/electric high-performance switches/memories based on organic-inorganic hybrid compounds.

12.
J Clin Nurs ; 26(3-4): 369-378, 2017 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-27647779

RESUMO

AIMS AND OBJECTIVES: Our study was conducted to further investigate the model of social support and care for People Living with HIV/AIDS(PLHA), to explore their role in People Living with AIDS's quality of life (QOL) as reference for improving nursing policies for AIDS. BACKGROUND: Social support and care are the most important factors impacting the QOL of People Living with HIV/AIDS, but most studies conducted upon the influence of social support and QOL of People Living with HIV/AIDS are mainly based on cross-sectional design. DESIGN: Our study was a nonrandomised controlled community intervention study. METHODS: The participants diagnosed as People Living with HIV/AIDS at Beijing You An Hospital received a comprehensive social support care from December 2013 to December 2014. To evaluate the impact of social support and care model on People Living with HIV/AIDS, our study analysed the different dimension scores of social support scale and quality of life before and after the intervention. Correlation between the net benefit value of social support and that of QOL from various dimensions were analysed. RESULTS: There were significant differences in the score of objective support and usage of support (all p = 0·02) for social support. Net values of objective support score and usage of support were 0·25 and 0·19, respectively, after intervention. There were significant differences in physiological function, role physical, general health, vitality, social function, mental health, health transition and total score of quality of life (all p < 0·05). The canonical correlation analysis of net values of social support and QOL indicated that the first and second canonical correlation were statistically significant, with correlation coefficients of 0·53 (p = 0·00) and 0·21 (p = 0·04). CONCLUSION: Social support and care intervention model can effectively improve perceived subjective feeling on social support and QOL condition for People Living with HIV/AIDS. And strategies to improve social support and care intervention programmes are strongly encouraged. RELEVANCE TO CLINICAL PRACTICE: The method is simple and cost-effective and could be a way to improve the quality of life condition for People Living with HIV/AIDS.


Assuntos
Síndrome da Imunodeficiência Adquirida/psicologia , Serviços de Saúde Comunitária , Atenção à Saúde , Soropositividade para HIV/psicologia , Qualidade de Vida , Apoio Social , Adulto , Pequim , Estudos Transversais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Papel do Profissional de Enfermagem , Inquéritos e Questionários
13.
J Am Chem Soc ; 138(48): 15784-15789, 2016 12 07.
Artigo em Inglês | MEDLINE | ID: mdl-27934003

RESUMO

Molecular ferroelectrics are attracting much attention as valuable complements to conventional ceramic ferroelectrics owing to their solution processability and nontoxicity. Encouragingly, the recent discovery of a multiaxial molecular ferroelectric, tetraethylammonium perchlorate, is expected to be able to solve the problem that in the technologically relevant thin-film form uniaxial molecular ferroelectrics have been found to perform considerably more poorly than in bulk. However, it can show good polarization-electric field (P-E) hysteresis loops only at very low frequency, severely hampering practical applications such as ferroelectric random access memory. Here, we present a biaxial molecular ferroelectric thin film of [Hdabco]ClO4 (dabco = 1,4-diazabicyclo[2.2.2]octane) (1), where a perfect ferroelectric hysteresis loop can be observed even at 10 kHz. It is the first example of a molecular ferroelectric thin film whose polarization can be switched at such a high frequency. Moreover, using piezoresponse force microscopy, we clearly observed the coexistence of 180° and non-180° ferroelectric domains and provided direct experimental proof that 180° ferroelectric switching and non-180° ferroelastic switching are both realized; that is, a flexible alteration of the polarization axis direction can occur in the thin film by applying an electric field. These results open a new avenue for applications of molecular ferroelectrics and will inspire further exploration of high-performance multiaxial molecular ferroelectric thin films.

14.
Heliyon ; 10(1): e23694, 2024 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-38205329

RESUMO

The outcomes and prognosis of autoimmune diseases depend on early diagnosis and effective treatments. However, symptoms of early autoimmune diseases are often remarkably similar to many inflammatory diseases, leading to difficulty in precise diagnosis. Circular RNAs (circRNAs) belong to a novel class of endogenous RNAs, functioning as microRNA (miRNA) sponges or participating in protein coding. It has been shown in many studies that patients with autoimmune diseases have aberrant circRNA expression in liquid biopsy samples (such as plasma, saliva, and urine). Thus, circRNAs are potential biomarkers for the diagnosis and prognosis of autoimmune diseases. Moreover, overexpression and depletion of target circRNAs can be utilized as possible therapeutic approaches for treating autoimmune diseases. In this review, we summarized recent progress in the roles of circRNAs in the pathogenesis of autoimmune diseases, including rheumatoid arthritis, systemic lupus erythematosus, multiple sclerosis, and type 1 diabetes. We also discussed their potential as biomarkers and therapeutic targets.

15.
Front Immunol ; 15: 1438030, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-39206192

RESUMO

With the COVID-19 pandemic, the importance of vaccines has been widely recognized and has led to increased research and development efforts. Vaccines also play a crucial role in cancer treatment by activating the immune system to target and destroy cancer cells. However, enhancing the efficacy of cancer vaccines remains a challenge. Adjuvants, which enhance the immune response to antigens and improve vaccine effectiveness, have faced limitations in recent years, resulting in few novel adjuvants being identified. The advancement of artificial intelligence (AI) technology in drug development has provided a foundation for adjuvant screening and application, leading to a diversification of adjuvants. This article reviews the significant role of tumor vaccines in basic research and clinical treatment and explores the use of AI technology to screen novel adjuvants from databases. The findings of this review offer valuable insights for the development of new adjuvants for next-generation vaccines.


Assuntos
Adjuvantes Imunológicos , Inteligência Artificial , COVID-19 , Vacinas Anticâncer , Neoplasias , Humanos , Vacinas Anticâncer/imunologia , Vacinas Anticâncer/uso terapêutico , Neoplasias/imunologia , Neoplasias/terapia , COVID-19/prevenção & controle , COVID-19/imunologia , SARS-CoV-2/imunologia , Animais , Desenvolvimento de Vacinas , Desenvolvimento de Medicamentos
16.
Chem Commun (Camb) ; 58(11): 1712-1715, 2022 Feb 03.
Artigo em Inglês | MEDLINE | ID: mdl-35023514

RESUMO

Switchable nonlinear optical (NLO) materials have aroused broad interest on account of their captivating optical and electronic properties. We demonstrate a novel perovskite-type crystal with exceptional hydrogen bond interactions that are associated with the onset of reorientational motions of organic cations and thus induce the occurrence of two successive phase transitions to be a two-step NLO switch. This finding affords an alternative approach for the design and assembly of switchable NLO materials.

17.
Pest Manag Sci ; 78(4): 1740-1748, 2022 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-34997800

RESUMO

BACKGROUND: Insect chitinases play vital roles in postembryonic development, especially during the molting process, and are potential targets for the RNA interference (RNAi)-based insecticidal strategy. Systematic functional analyses of chitinase genes have already been conducted on numerous insect pests, but similar analyses have not been carried out on Diaphorina citri. RESULTS: Eleven chitinase/chitinase-like genes and one endo-ß-N-acetylglucosaminidase (ENGase) gene were identified in the Diaphorina citri genome using various bioinformatic tools. Transcriptomes of the integument and midgut from fifth-instar nymphs and freshly-emerged adults of Diaphorina citri were generated and sequenced. Potential functions of 12 chitinase/chitinase-like genes were examined during nymph-adult transitions. Four chitinase genes, including DcCht5, DcCht7, DcCht10-1 and DcCht10-2, were mainly expressed in the integument of fifth-instar nymphs. These four genes were also up-regulated significantly under 20-hydroxyecdysone (20E) treatments. RNAi-mediated knockdown of these four genes suggests that they are essential for nymph-adult transition. CONCLUSION: Our results demonstrated essential roles of the chitinase/chitinase-like genes during the nymph-adult transition in Diaphorina citri, which are potentially useful targets for controlling the Diaphorina citri pest. © 2022 Society of Chemical Industry.


Assuntos
Quitinases , Hemípteros , Animais , Quitinases/genética , Muda/genética , Ninfa/genética , Interferência de RNA
18.
Chin J Nat Med ; 20(1): 43-53, 2022 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-35101249

RESUMO

Bladder cancer is the most common malignancy of the urinary system. Compound Kushen Injection (CKI) is a Chinese medicinal preparation that has been widely used in the treatment of various types of cancers in the past two decades. However, the pharmacological effect of CKI on bladder cancer is not still completely understood. In the current study, network pharmacology combined with bioinformatics was used to elucidate the therapeutic mechanism and potential targets of CKI in bladder cancer. The mechanism by which CKI was effective against bladder cancer was further verified in vitro using human bladder cancer cell line T24. Network pharmacology analysis identified 35 active compounds and 268 target genes of CKI. Bioinformatics data indicated 5500 differentially expressed genes associated with bladder cancer. Common genes of CKI and bladder cancer suggested that CKI exerted anti-bladder cancer effects by regulating genes such as MMP-9, JUN, EGFR, and ERK1. Functional enrichment analysis indicated that CKI exerted therapeutic effects on bladder cancer by regulating certain biological processes, including cell proliferation, cell migration, and cell apoptosis. In addition, Kyoto Encyclopedia of Genes and Genomes enrichment analysis implicated pathways related to cancer, bladder cancer, and the PI3K-Akt signaling pathway. Consistently, cell experiments indicated that CKI inhibited the proliferation and migration of T24 cells, and induced their apoptosis. Moreover, RT-qPCR and Western blot results demonstrated that CKI was likely to treat bladder cancer by down-regulating the gene and protein expression of MMP-9, JUN, EGFR, and ERK1. CKI inhibited the proliferation and migration, and induced the apoptosis of T24 bladder cancer cells through multiple biological pathways and targets. CKI also exhibited significant effects on the regulation of key genes and proteins associated with bladder cancer. Overall, our findings provide solid evidence and deepen current understanding of the therapeutic effects of CKI for bladder cancer, and further support its clinical use.


Assuntos
Neoplasias da Bexiga Urinária , Biologia Computacional , Medicamentos de Ervas Chinesas , Humanos , Farmacologia em Rede , Fosfatidilinositol 3-Quinases , Neoplasias da Bexiga Urinária/tratamento farmacológico , Neoplasias da Bexiga Urinária/genética
19.
Cell Res ; 32(8): 715-728, 2022 08.
Artigo em Inglês | MEDLINE | ID: mdl-35661831

RESUMO

Vertebrate embryogenesis involves a conserved and fundamental process, called the maternal-to-zygotic transition (MZT), which marks the switch from a maternal factors-dominated state to a zygotic factors-driven state. Yet the precise mechanism underlying MZT remains largely unknown. Here we report that the RNA helicase Ddx3xb in zebrafish undergoes liquid-liquid phase separation (LLPS) via its N-terminal intrinsically disordered region (IDR), and an increase in ATP content promotes the condensation of Ddx3xb during MZT. Mutant form of Ddx3xb losing LLPS ability fails to rescue the developmental defect of Ddx3xb-deficient embryos. Interestingly, the IDR of either FUS or hnRNPA1 can functionally replace the N-terminal IDR in Ddx3xb. Phase separation of Ddx3xb facilitates the unwinding of 5' UTR structures of maternal mRNAs to enhance their translation. Our study reveals an unprecedent mechanism whereby the Ddx3xb phase separation regulates MZT by promoting maternal mRNA translation.


Assuntos
Peixe-Zebra , Zigoto , Animais , DNA Helicases , Desenvolvimento Embrionário/genética , Regulação da Expressão Gênica no Desenvolvimento , RNA Mensageiro Estocado/genética , Peixe-Zebra/genética , Proteínas de Peixe-Zebra/genética , Proteínas de Peixe-Zebra/metabolismo , Zigoto/metabolismo
20.
Front Genet ; 12: 765400, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34759961

RESUMO

Rationale: Severe asthma is a heterogeneous disease with multiple molecular mechanisms. Gene expression studies of asthmatic bronchial epithelial cells have provided biological insights and underscored possible pathological mechanisms; however, the molecular basis in severe asthma is still poorly understood. Objective: The objective of this study was to identify the features of asthma and uncover the molecular basis of severe asthma in distinct molecular phenotype. Methods: The k-means clustering and differentially expressed genes (DEGs) were performed in 129 asthma individuals in the Severe Asthma Research Program. The DEG profiles were analyzed by weighted gene co-expression network analysis (WGCNA), and the expression value of each gene module in each individual was annotated by gene set variation analysis (GSVA). Results: Expression analysis defined five stable asthma subtype (AS): 1) Phagocytosis-Th2, 2) Normal-like, 3) Neutrophils, 4) Mucin-Th2, and 5) Interferon-Th1 and 15 co-expressed gene modules. "Phagocytosis-Th2" enriched for receptor-mediated endocytosis, upregulation of Toll-like receptor signal, and myeloid leukocyte activation. "Normal-like" is most similar to normal samples. "Mucin-Th2" preferentially expressed genes involved in O-glycan biosynthesis and unfolded protein response. "Interferon-Th1" displayed upregulation of genes that regulate networks involved in cell cycle, IFN gamma response, and CD8 TCR. The dysregulation of neural signal, REDOX, apoptosis, and O-glycan process were related to the severity of asthma. In non-TH2 subtype (Neutrophils and Interferon-Th1) with severe asthma individuals, the neural signals and IL26-related co-expression module were dysregulated more significantly compared to that in non-severe asthma. These data infer differences in the molecular evolution of asthma subtypes and identify opportunities for therapeutic development. Conclusions: Asthma is a heterogeneous disease. The co-expression analysis provides new insights into the biological mechanisms related to its phenotypes and the severity.

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