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1.
J Transl Med ; 22(1): 561, 2024 Jun 12.
Artigo em Inglês | MEDLINE | ID: mdl-38867256

RESUMO

BACKGROUND: Fibrogenesis within ovarian endometrioma (endometrioma), mainly induced by transforming growth factor-ß (TGF-ß), is characterized by myofibroblast over-activation and excessive extracellular matrix (ECM) deposition, contributing to endometrioma-associated symptoms such as infertility by impairing ovarian reserve and oocyte quality. However, the precise molecular mechanisms that underpin the endometrioma- associated fibrosis progression induced by TGF-ß remain poorly understood. METHODS: The expression level of lysine acetyltransferase 14 (KAT14) was validated in endometrium biopsies from patients with endometrioma and healthy controls, and the transcription level of KAT14 was further confirmed by analyzing a published single-cell transcriptome (scRNA-seq) dataset of endometriosis. We used overexpression, knockout, and knockdown approaches in immortalized human endometrial stromal cells (HESCs) or human primary ectopic endometrial stromal cells (EcESCs) to determine the role of KAT14 in TGF-ß-induced fibrosis. Furthermore, an adeno-associated virus (AAV) carrying KAT14-shRNA was used in an endometriosis mice model to assess the role of KAT14 in vivo. RESULTS: KAT14 was upregulated in ectopic lesions from endometrioma patients and predominantly expressed in activated fibroblasts. In vitro studies showed that KAT14 overexpression significantly promoted a TGF-ß-induced profibrotic response in endometrial stromal cells, while KAT14 silencing showed adverse effects that could be rescued by KAT14 re-enhancement. In vivo, Kat14 knockdown ameliorated fibrosis in the ectopic lesions of the endometriosis mouse model. Mechanistically, we showed that KAT14 directly interacted with serum response factor (SRF) to promote the expression of α-smooth muscle actin (α-SMA) by increasing histone H4 acetylation at promoter regions; this is necessary for TGF-ß-induced ECM production and myofibroblast differentiation. In addition, the knockdown or pharmacological inhibition of SRF significantly attenuated KAT14-mediating profibrotic effects under TGF-ß treatment. Notably, the KAT14/SRF complex was abundant in endometrioma samples and positively correlated with α-SMA expression, further supporting the key role of KAT14/SRF complex in the progression of endometrioma-associated fibrogenesis. CONCLUSION: Our results shed light on KAT14 as a key effector of TGF-ß-induced ECM production and myofibroblast differentiation in EcESCs by promoting histone H4 acetylation via co-operating with SRF, representing a potential therapeutic target for endometrioma-associated fibrosis.


Assuntos
Endometriose , Fibrose , Fator de Resposta Sérica , Fator de Crescimento Transformador beta , Adulto , Animais , Feminino , Humanos , Camundongos , Endometriose/patologia , Endometriose/metabolismo , Endométrio/metabolismo , Endométrio/patologia , Histona Acetiltransferases/metabolismo , Miofibroblastos/metabolismo , Miofibroblastos/patologia , Fator de Resposta Sérica/metabolismo , Células Estromais/metabolismo , Células Estromais/patologia , Fator de Crescimento Transformador beta/metabolismo , Regulação para Cima/efeitos dos fármacos , Proteínas Adaptadoras de Transdução de Sinal/metabolismo
2.
EMBO Rep ; 23(11): e54686, 2022 11 07.
Artigo em Inglês | MEDLINE | ID: mdl-36094741

RESUMO

N6-methyladenosine (m6 A) and alternative polyadenylation (APA) are important regulators of gene expression in eukaryotes. Recently, it was found that m6 A is closely related to APA. However, the molecular mechanism of this new APA regulation remains elusive. Here, we show that YTHDC1, a nuclear m6 A reader, can suppress proximal APA sites and produce longer 3' UTR transcripts by binding to their upstream m6 A sites. YTHDC1 can directly interact with the 3' end processing factor FIP1L1 and interfere with its ability to recruit CPSF4. Binding to the m6 A sites can promote liquid-liquid phase separation of YTHDC1 and FIP1L1, which may play an important role in their interaction and APA regulation. Collectively, YTHDC1 as an m6 A "reader" links m6 A modification with pre-mRNA 3' end processing, providing a new mechanism for APA regulation.


Assuntos
Núcleo Celular , Poliadenilação , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Núcleo Celular/metabolismo , Adenosina/metabolismo , Regiões 3' não Traduzidas
3.
J Environ Manage ; 359: 121009, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38718600

RESUMO

Nitrification-denitrification process has failed to meet wastewater treatment standards. The completely autotrophic nitrite removal (CANON) process has a huge advantage in the field of low carbon/nitrogen wastewater nitrogen removal. However, slow start-up and system instability limit its applications. In this study, the time of the start-up CANON process was reduced by using bio-rope as loading materials. The establishing of graded dissolved oxygen improved the stability of the CANON process and enhanced the stratification effect between functional microorganisms. Microbial community structure and the abundance of nitrogen removal functional genes are also analyzed. The results showed that the CANON process was initiated within 75 days in the complete absence of anaerobic ammonium oxidizing bacteria (AnAOB) inoculation. The ammonium and nitrogen removal efficiencies of CANON process reached to 94.45% and 80.76% respectively. The results also showed that the relative abundance of nitrogen removal bacterial in the biofilm gradually increases with the dissolved oxygen content in the solution decreases. In contrast, the relative abundance of ammonia oxidizing bacteria was positively correlated with the dissolved oxygen content in the solution. The relative abundance of g__Candidatus_Brocadia in biofilm was 15.56%, and while g__Nitrosomonas was just 0.6613%. Metagenomic analysis showed that g__Candidatus_Brocadia also contributes 66.37% to the partial-nitrification functional gene Hao (K10535). This study presented a new idea for the cooperation between partial-nitrification and anammox, which improved the nitrogen removal system stability.


Assuntos
Processos Autotróficos , Nitritos , Nitrogênio , Águas Residuárias , Nitrogênio/metabolismo , Nitritos/metabolismo , Nitrificação , Desnitrificação , Bactérias/metabolismo , Bactérias/genética , Eliminação de Resíduos Líquidos/métodos , Biofilmes , Reatores Biológicos , Compostos de Amônio/metabolismo
4.
Int J Environ Health Res ; : 1-13, 2024 Feb 07.
Artigo em Inglês | MEDLINE | ID: mdl-38323408

RESUMO

Secular trends of mortality and disability-adjusted life years (DALY) in type 2 diabetes mellitus (T2DM) attributable to PM2.5 exposure in China remain unclear. This study applied the joinpoint regression analysis and age-period-cohort model to assess the secular trends. There was a slight alternation in age-standardized rate of mortality and DALY in the total population, while the changes were increased in males and decreased in females from 1990 to 2019. Meanwhile, the changes attributable to ambient particular matter pollution exposure (APE) increased significantly and reduced household air pollution from solid fuels exposure (HPE). Longitudinal age curves showed that T2DM mortality and DALY increased with age. Period rate ratios (RR) attributable to APE increased but fell to HPE. Similar trends were observed in the cohort RR. PM2.5 exposure is more harmful to males and older people. The type of air pollution responsible for T2DM has changed from HPE to APE.

5.
Langmuir ; 39(12): 4245-4256, 2023 03 28.
Artigo em Inglês | MEDLINE | ID: mdl-36913208

RESUMO

There are many treatments for nasopharyngeal carcinoma (NPC), but none of them are very effective. Radiotherapy is used extensively in NPC treatment, but radioresistance is a major problem. Graphene oxide (GO) has been previously studied in cancer treatment, and this study is aimed to explore its role in radiosensitization of NPC. Therefore, graphene oxide nanosheets were prepared, and the relationship between GO and radioresistance was explored. The GO nanosheets were synthesized by a modified Hummers' method. The morphologies of the GO nanosheets were characterized by field-emission environmental scanning electron microscopy (SEM) and transmission electron microscopy (TEM). The morphological changes and radiosensitivity of C666-1 and HK-1 cells with or without the GO nanosheets were observed by an inverted fluorescence microscopy and laser scanning confocal microscopy (LSCM). Colony formation assay and Western Blot were applied for analysis of NPC radiosensitivity. The as-synthesized GO nanosheets have lateral dimensions (sizes ∼1 µm) and exhibit a thin wrinkled two-dimensional lamellar structure with slight folds and crimped edges (thickness values ∼1 nm). C666-1 cells with the GO was significantly changed the morphology of cells postirradiation. The full field of view visualized by a microscope showed the shadow of dead cells or cell debris. The synthesized graphene oxide nanosheets inhibited cell proliferation, promoted cell apoptosis, and inhibited the expression of Bcl-2 in C666-1 and HK-1 cells but increased the level of Bax. The GO nanosheets could affect the cell apoptosis and reduce the pro-survival protein Bcl-2 related to the intrinsic mitochondrial pathway. The GO nanosheets could enhance radiosensitivity, which might be a radioactive material in NPC cells.


Assuntos
Grafite , Neoplasias Nasofaríngeas , Humanos , Grafite/farmacologia , Grafite/química , Microscopia Eletrônica de Transmissão , Carcinoma Nasofaríngeo/metabolismo , Carcinoma Nasofaríngeo/patologia , Neoplasias Nasofaríngeas/radioterapia , Neoplasias Nasofaríngeas/metabolismo , Neoplasias Nasofaríngeas/patologia
6.
Environ Health ; 21(1): 65, 2022 07 08.
Artigo em Inglês | MEDLINE | ID: mdl-35799180

RESUMO

BACKGROUND: Increasing evidence associates air pollution with thyroid dysfunction, whereas the potential relationship between exposure to ozone (O3) and Thyroid Nodules (TNs) is unclear. METHODS: This retrospective cohort study investigated the association between O3 exposure and TNs in Hunan province, enrolling 191,357 Chinese adults who lived in Hunan province from January 2009 to December 2019 and received voluntary medical examinations. Individual exposure levels to O3 from 2010 to 2019 were measured on account of participants' residential addresses at the district level. Associations of O3 exposure with the risk of incidental TNs were assessed by restricted cubic splines and surveyed as odds ratios after adjusting for demographic factors. RESULTS: In total, 81,900 adults were newly diagnosed with TNs during the study period. Age-standardized TNs detection rate in Hunan province increased from 25.9 to 46.3% between 2010 and 2019, with the greatest annual percent change being 8.1 [95% CI, 7.3-8.8]. A similar trend has been found in all tumor sizes, ages, and both sexes. O3 exposure presented a statistically significant dose-dependent positive correlation (greater than 0.036 ppm) with TNs. Similarly, long-term exposure to high levels of O3 (1-year average O3 concentrations exceeding 0.0417 ppm) was found positively associated with increased TSH levels. CONCLUSIONS: High-level O3 exposure in the long term was associated with an increase in TSH. Consequently, increased TSH was related to the increased risk of TNs. Being exposed to high-level O3 in the long term was related to the increased detection rates of TNs in Hunan province, which could be mediated by TSH.


Assuntos
Poluição do Ar , Exposição Ambiental , Ozônio , Nódulo da Glândula Tireoide , Adulto , Poluição do Ar/efeitos adversos , Exposição Ambiental/efeitos adversos , Feminino , Humanos , Masculino , Ozônio/efeitos adversos , Material Particulado/análise , Estudos Retrospectivos , Nódulo da Glândula Tireoide/induzido quimicamente , Nódulo da Glândula Tireoide/epidemiologia , Tireotropina
7.
Appl Opt ; 60(30): 9525-9529, 2021 Oct 20.
Artigo em Inglês | MEDLINE | ID: mdl-34807095

RESUMO

Metalens is a planar optical component that uses nanostructures with a thickness on the order of the wavelength to manipulate the wavefront of the incident light. A key problem, especially in color imaging and display applications, is the correction of chromatic aberration, which is an inherent effect caused by the dispersion of periodic lattices and resonance modes. However, the current achromatic metalenses either use the PB phase method that is only valid for circularly polarized light or nanostructures with complex cross sections that are difficult to manufacture. Here, we designed a broadband achromatic metalens for linearly polarized light from 450 to 800 nm. Rectangular titanium dioxide nanofins of various lengths and widths were applied to modulate the phase and dispersion of the incident light. The metalens can fulfill three target phases simultaneously by using an optimization method. The designed metalens has a stable focus from 450 to 800 nm with an average focusing efficiency of 64%. It can be potentially applied in microscopes, lithography machines, sensors, and displays.

8.
J Integr Plant Biol ; 63(7): 1273-1293, 2021 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-33559953

RESUMO

Biodiversity is not evenly distributed among related groups, raising questions about the factors contributing to such disparities. The sunflower family (Asteraceae, >26,000 species) is among the largest and most diverse plant families, but its species diversity is concentrated in a few subfamilies, providing an opportunity to study the factors affecting biodiversity. Phylotranscriptomic analyses here of 244 transcriptomes and genomes produced a phylogeny with strong support for the monophyly of Asteraceae and the monophyly of most subfamilies and tribes. This phylogeny provides a reference for detecting changes in diversification rates and possible factors affecting Asteraceae diversity, which include global climate shifts, whole-genome duplications (WGDs), and morphological evolution. The origin of Asteraceae was estimated at ~83 Mya, with most subfamilies having diverged before the Cretaceous-Paleocene boundary. Phylotranscriptomic analyses supported the existence of 41 WGDs in Asteraceae. Changes to herbaceousness and capitulescence with multiple flower-like capitula, often with distinct florets and scaly pappus/receptacular bracts, are associated with multiple upshifts in diversification rate. WGDs might have contributed to the survival of early Asteraceae by providing new genetic materials to support morphological transitions. The resulting competitive advantage for adapting to different niches would have increased biodiversity in Asteraceae.


Assuntos
Asteraceae/genética , Biodiversidade , Evolução Molecular , Duplicação Gênica/genética , Genoma de Planta/genética , Filogenia , Poliploidia , Transcriptoma/genética
9.
Gut ; 69(3): 513-522, 2020 03.
Artigo em Inglês | MEDLINE | ID: mdl-31900289

RESUMO

OBJECTIVE: Pre-eclampsia (PE) is one of the malignant metabolic diseases that complicate pregnancy. Gut dysbiosis has been identified for causing metabolic diseases, but the role of gut microbiome in the pathogenesis of PE remains unknown. DESIGN: We performed a case-control study to compare the faecal microbiome of PE and normotensive pregnant women by 16S ribosomal RNA (rRNA) sequencing. To address the causative relationship between gut dysbiosis and PE, we used faecal microbiota transplantation (FMT) in an antibiotic-treated mouse model. Finally, we determined the microbiome translocation and immune responses in human and mouse placental samples by 16S rRNA sequencing, quantitative PCR and in situ hybridisation. RESULTS: Patients with PE showed reduced bacterial diversity with obvious dysbiosis. Opportunistic pathogens, particularly Fusobacterium and Veillonella, were enriched, whereas beneficial bacteria, including Faecalibacterium and Akkermansia, were markedly depleted in the PE group. The abundances of these discriminative bacteria were correlated with blood pressure (BP), proteinuria, aminotransferase and creatinine levels. On successful colonisation, the gut microbiome from patients with PE triggered a dramatic, increased pregestational BP of recipient mice, which further increased after gestation. In addition, the PE-transplanted group showed increased proteinuria, embryonic resorption and lower fetal and placental weights. Their T regulatory/helper-17 balance in the small intestine and spleen was disturbed with more severe intestinal leakage. In the placenta of both patients with PE and PE-FMT mice, the total bacteria, Fusobacterium, and inflammatory cytokine levels were significantly increased. CONCLUSIONS: This study suggests that the gut microbiome of patients with PE is dysbiotic and contributes to disease pathogenesis.


Assuntos
Translocação Bacteriana , Disbiose/complicações , Microbioma Gastrointestinal , Placenta/imunologia , Placenta/microbiologia , Pré-Eclâmpsia/microbiologia , Animais , Pressão Sanguínea , Contagem de Linfócito CD4 , Estudos de Casos e Controles , Quimiocinas/genética , Creatinina/sangue , Citocinas/genética , Modelos Animais de Doenças , Disbiose/fisiopatologia , Faecalibacterium , Fezes/microbiologia , Feminino , Reabsorção do Feto/microbiologia , Fusobactérias , Humanos , Intestino Delgado/imunologia , Camundongos , Placenta/metabolismo , Pré-Eclâmpsia/fisiopatologia , Gravidez , Proteinúria/urina , RNA Mensageiro/metabolismo , Linfócitos T Reguladores , Células Th17 , Veillonella
10.
Reproduction ; 159(2): 171-180, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31786538

RESUMO

Small extracellular vesicles (sEVs) are important mediators of cell-to-cell communication involved in the successful establishment of a pregnancy. Human decidual stromal cells play a key role in regulating trophoblast invasion. Nevertheless, the regulatory functions of decidual stromal cells-derived sEVs in human trophoblast cells are still unclear. In this study, primary human decidual stromal cells were isolated, and immortalized human endometrial stromal cell line (HESCs) were decidualized into human decidual stromal cells (HDSCs) using hormonal cocktail containing medroxy progesterone 17-acetate (MPA), estrogen and cAMP analog. HDSC-sEVs were isolated from both primary human decidual stromal cells and immortal HDSCs, respectively, and identified by transmission electron microscopy and western blotting. EV uptake assay indicated that HDSC-sEVs could be uptaken by trophoblast cells. HDSC-sEVs could increase the invasiveness and the expression level of N-cadherin of trophoblast cells with elevated phosphorylation of SMAD2 and SMAD3 in the cells. Silencing of N-cadherin could block cell invasion induced by HDSC-sEVs, while knockdown of SMAD2 and SMAD3 could inhibit the upregulation of N-cadherin in trophoblast cells. Taken together, our results suggested a regulatory effect of HDSC-sEVs in the invasion of trophoblast cells, and HDSC-sEVs may be important mediators of trophoblasts during embryo implantation and placentation.

11.
Med Sci Monit ; 26: e918881, 2020 May 06.
Artigo em Inglês | MEDLINE | ID: mdl-32417848

RESUMO

BACKGROUND This retrospective study aimed to investigate the epidemiology of burns to the hand, including the causes, demographic data, management, and outcome in a single center in Southwest China between 2012 and 2017. MATERIAL AND METHODS A retrospective study included 470 patients with hand burns who were treated at a single hospital in Southwest China between 2012 and 2017. Demographic, injury-related, and clinical data were obtained from the clinical electronic data collection system. RESULTS In 470 patients, men were more commonly admitted to hospital with hand burns (73.62%). Children under 10 years (29.57%) were the main patient group. Hospital admissions occurred in the coldest months, from December to March (55.11%). In 60.21% of cases, hand burns occurred outside the workplace. Fire (40.42%), electricity (30.85%), and hot liquids (20.21%) were the main causes of hand burns. Data from 428 patients showed that burns with a larger total body surface area and deeper burns were associated with surgery and amputation. Burn depth was a risk factor for skin grafting, and lack of burn cooling before hospital admission increased the risk of amputation. Data from 117 patients with localized burns showed that full-thickness burns and lack of cooling before admission were associated with an increased hospital stay. CONCLUSIONS The findings suggest that in Southwest China, prevention programs for children aged 0-9 years, injuries occurring in winter and non-workplace sites, and fire burns were imperative.


Assuntos
Unidades de Queimados/estatística & dados numéricos , Queimaduras/fisiopatologia , Traumatismos da Mão/epidemiologia , Prevenção de Acidentes/métodos , Distribuição por Idade , Queimaduras/epidemiologia , China/epidemiologia , Feminino , Mãos , Hospitalização , Humanos , Tempo de Internação/estatística & dados numéricos , Masculino , Estudos Retrospectivos , Fatores de Risco , Transplante de Pele/métodos , Resultado do Tratamento
12.
Opt Lett ; 43(7): 1435-1438, 2018 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-29600998

RESUMO

Since few-mode fibers (FMFs) have great potential as the new transmission media for optical communications, the ability to distinguish different fiber modes is essential. Most of the traditional schemes do not yield phase information, or are limited by beam size and mechanical requirements. Here, a method is presented to analyze the mode distribution of FMFs. The fiber modes are mapped to different frequencies by using dynamic spatial phase masks. The complex amplitudes at these frequencies indicate the amplitudes and phases of the fiber modes. The method can extract not only the amplitude distribution, but also the phase distribution of the fiber modes, and no other assisted light is needed.

13.
Mol Biol Evol ; 33(11): 2820-2835, 2016 11.
Artigo em Inglês | MEDLINE | ID: mdl-27604225

RESUMO

Biodiversity results from multiple evolutionary mechanisms, including genetic variation and natural selection. Whole-genome duplications (WGDs), or polyploidizations, provide opportunities for large-scale genetic modifications. Many evolutionarily successful lineages, including angiosperms and vertebrates, are ancient polyploids, suggesting that WGDs are a driving force in evolution. However, this hypothesis is challenged by the observed lower speciation and higher extinction rates of recently formed polyploids than diploids. Asteraceae includes about 10% of angiosperm species, is thus undoubtedly one of the most successful lineages and paleopolyploidization was suggested early in this family using a small number of datasets. Here, we used genes from 64 new transcriptome datasets and others to reconstruct a robust Asteraceae phylogeny, covering 73 species from 18 tribes in six subfamilies. We estimated their divergence times and further identified multiple potential ancient WGDs within several tribes and shared by the Heliantheae alliance, core Asteraceae (Asteroideae-Mutisioideae), and also with the sister family Calyceraceae. For two of the WGD events, there were subsequent great increases in biodiversity; the older one proceeded the divergence of at least 10 subfamilies within 10 My, with great variation in morphology and physiology, whereas the other was followed by extremely high species richness in the Heliantheae alliance clade. Our results provide different evidence for several WGDs in Asteraceae and reveal distinct association among WGD events, dramatic changes in environment and species radiations, providing a possible scenario for polyploids to overcome the disadvantages of WGDs and to evolve into lineages with high biodiversity.


Assuntos
Asteraceae/genética , Duplicação Gênica , Biodiversidade , Evolução Biológica , Bases de Dados de Ácidos Nucleicos , Evolução Molecular , Variação Genética , Genoma de Planta , Modelos Genéticos , Filogenia , Poliploidia , Seleção Genética , Análise de Sequência de DNA/métodos , Transcriptoma
14.
Opt Express ; 25(13): 14023-14032, 2017 Jun 26.
Artigo em Inglês | MEDLINE | ID: mdl-28788987

RESUMO

A tomographic polarization analyzer is presented by polarization-mode-frequency mapping. Two orthogonal circularly polarized components of the unknown polarization state of light are converted to two orbital angular momentum (OAM) modes by a q-plate, and then the OAM modes are mapped to two frequencies by using time-varying spatial modulation. The polarization state of light can be retrieved by tomographic reconstruction of the temporal intensity signal collected by a photodetector. The time-varying spatial modulation can be achieved by either a programmable spatial device or a spinning object. Our method can directly measure the Jones matrix of light with high accuracy due to the high-volume time sampling.

15.
Med Res Rev ; 36(2): 193-220, 2016 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-26301869

RESUMO

Through positive selection, double-positive cells in the thymus differentiate into CD4(+) or CD8(+) T single-positive cells that subsequently develop into different types of effective T cells, such as T-helper and cytotoxic T lymphocyte cells, that play distinctive roles in the immune system. Development, differentiation, and function of thymocytes and CD4(+) and CD8(+) T cells are controlled by a multitude of secreted and intracellular factors, ranging from cytokine signaling modules to transcription factors and epigenetic modifiers. Members of the E26 transformation specific (Ets) family of transcription factors, in particular, are potent regulators of these CD4(+) or CD8(+) T-cell processes. In this review, we summarize and discuss the functions and underlying mechanisms of the Ets family members that have been characterized as involved in these processes. Ongoing research of these factors is expected to identify practical applications for the Ets family members as novel therapeutic targets for inflammation-related diseases.


Assuntos
Diferenciação Celular , Proteínas Proto-Oncogênicas c-ets/metabolismo , Subpopulações de Linfócitos T/citologia , Linfócitos T CD4-Positivos/citologia , Linfócitos T CD8-Positivos/citologia , Sobrevivência Celular , Humanos , Subpopulações de Linfócitos T/metabolismo , Timócitos/citologia , Timócitos/metabolismo
16.
Nature ; 462(7269): 87-9, 2009 Nov 05.
Artigo em Inglês | MEDLINE | ID: mdl-19890328

RESUMO

One of the most powerful features of plate tectonics is that the known plate motions give insight into both the locations and average recurrence interval of future large earthquakes on plate boundaries. Plate tectonics gives no insight, however, into where and when earthquakes will occur within plates, because the interiors of ideal plates should not deform. As a result, within plate interiors, assessments of earthquake hazards rely heavily on the assumption that the locations of small earthquakes shown by the short historical record reflect continuing deformation that will cause future large earthquakes. Here, however, we show that many of these recent earthquakes are probably aftershocks of large earthquakes that occurred hundreds of years ago. We present a simple model predicting that the length of aftershock sequences varies inversely with the rate at which faults are loaded. Aftershock sequences within the slowly deforming continents are predicted to be significantly longer than the decade typically observed at rapidly loaded plate boundaries. These predictions are in accord with observations. So the common practice of treating continental earthquakes as steady-state seismicity overestimates the hazard in presently active areas and underestimates it elsewhere.

17.
Int J Mol Sci ; 15(1): 1606-24, 2014 Jan 22.
Artigo em Inglês | MEDLINE | ID: mdl-24451141

RESUMO

Therapeutic modalities targeting vascular endothelial growth factor (VEGF) have been used to treat neovascularization and macular edema. However, anti-VEGF treatment alone may cause up-regulation of connective tissue growth factor (CTGF) in the retina, increasing the risk of fibrosis and tractional retinal detachment. Therefore, in this study, we employ a novel dual-target intervention that involves intravitreal injection of the VEGF inhibitor ranibizumab and a transfection reagent-treated non-viral vector carrying anti-CTGF short hairpin RNA (shRNA) driven by human RNA polymerase III promoter U6. The effects of the dual-target intervention on the expression of VEGF and CTGF and on microvessel ultrastructure were examined in retina of streptozocin-induced diabetic rats. CTGF was significantly up-regulated at week 8 after diabetic induction, whereas VEGF was not up-regulated until week 10. The high expression of both genes was maintained at week 12. Transmission electron microscopy also revealed progressive exacerbation of microvessel ultrastructure during the same period. In addition, ranibizumab significantly lowered VEGF but elevated CTGF mRNA, whereas CTGF shRNA significantly reduced the mRNA levels of both CTGF and VEGF in diabetic retinas. Importantly, dual-target intervention normalized the transcript levels of both target genes and ameliorated retinal microvessel ultrastructural damage better than either single-target intervention. These results suggest the advantages of dual-target over single-target interventions in diabetic retina and reveal a novel therapeutic modality for diabetic retinopathy.


Assuntos
Anticorpos Monoclonais Humanizados/uso terapêutico , Fator de Crescimento do Tecido Conjuntivo/metabolismo , Diabetes Mellitus Experimental/tratamento farmacológico , Retinopatia Diabética/tratamento farmacológico , Vasos Retinianos/efeitos dos fármacos , Animais , Anticorpos Monoclonais Humanizados/administração & dosagem , Anticorpos Monoclonais Humanizados/farmacologia , Fator de Crescimento do Tecido Conjuntivo/genética , Diabetes Mellitus Experimental/metabolismo , Retinopatia Diabética/metabolismo , Células HEK293 , Humanos , Injeções Intraoculares , Masculino , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , RNA Interferente Pequeno/genética , Ranibizumab , Ratos , Ratos Sprague-Dawley , Retina/efeitos dos fármacos , Retina/metabolismo , Retina/ultraestrutura , Vasos Retinianos/metabolismo , Vasos Retinianos/ultraestrutura , Fator A de Crescimento do Endotélio Vascular/genética , Fator A de Crescimento do Endotélio Vascular/metabolismo
18.
ACS Omega ; 9(15): 17097-17103, 2024 Apr 16.
Artigo em Inglês | MEDLINE | ID: mdl-38645313

RESUMO

In the present work, the thermoelectric properties of PbTe embedded with spherical Sb nanoscale inclusions were calculated in detail, following the idea that energy-selective carrier scattering can effectively increase the Seebeck coefficient. The quantitative relationships between such nanostructures in PbTe and thermoelectric properties indicated that interface potential barrier induced by Sb nanoinclusions results in a significant enhancement of the Seebeck coefficient, especially when around room temperature. Furthermore, the optimal parameters for boosting the thermoelectric performance of PbTe were found to be 4 nm-radius Sb nanoinclusions with high concentration.

19.
Heliyon ; 10(9): e29652, 2024 May 15.
Artigo em Inglês | MEDLINE | ID: mdl-38707449

RESUMO

Background: Current treatments for primary Sjögren's Syndrome (pSS) are with limited effect, partially due to the heterogeneity and uncleared mechanism. Methods: We got GSE40568 (Japan) and GSE40611 (USA), and analyzed them with WGCNA to find key Differentially expressed genes (DEGs) between pSS and healthy salivary glands (SG). Key pSS genes (KPGs) were further selected through 3 machine-learning methods. The expression of KPGs was validated via two other GEO datasets (GSE127952 and GSE154926). Infiltrated immune cells, ceRNA network, and potential compounds were explored. Results: Our study identified 376 DEGs from the pSS patients, with 186 genes located in the "plum2" module, showing the strongest correlation with clinical characteristics. SAMD9 and IFIT3 emerged as KPGs with excellent diagnostic potential. SAMD9 demonstrated close association with immune cell infiltration. We constructed a lncRNA-miRNA-mRNA network comprising 2 KPGs, 12 miRNAs, 124 lncRNAs, and potential therapeutic targets. Conclusion: In the investigation of pSS public datasets, our study revealed two potential critical mediators in the pathological process of pSS salivary glands, namely SAMD9 and IFIT3. Furthermore, we put forth a hypothesis regarding the ceRNA network and made predictions regarding potential therapeutic drugs targeting these two genes.

20.
J Colloid Interface Sci ; 671: 248-257, 2024 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-38810339

RESUMO

Composite solid electrolytes (CSEs) composed of polymer matrix and inorganic fillers show considerable potential for applications in all-solid-state lithium (Li) metal batteries. However, challenges such as fillers agglomeration and low lithium ion transference number (tLi+) remain significant obstacles to the practical application of CSEs. Herein, a general strategy of graft polymerization on the fillers surface to modulate the interface compatibility with the polymer matrix is proposed, and CSEs are prepared to verify the feasibility. The microstructure and composition of the surface coating of the fillers are analyzed, with subsequent studies of the fillers distribution within the CSEs confirming the improved interface compatibility. The enhancement of interface compatibility facilitates uniform dispersion of fillers, thereby greatly improving the utilization of fillers. CSEs exhibits high ionic conductivity (0.163 mS·cm-1 at 30 °C) and tLi+ (0.77), which gives the battery excellent rate performance and cycle stability. Therefore, chemical grafting of polymer onto the fillers surface to enhance the interface compatibility with the polymer matrix represents a promising strategy for the practical application of solid-state batteries.

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