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1.
Mar Environ Res ; 196: 106444, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38484649

RESUMO

To study the environmental responses of tropical cyclones (TCs) in continental shelf regions, TCs passing over the Yellow Sea and Bohai Sea (YBS) during 2002-2020 were investigated, with a special focus on how competition between ocean thermal structure and TC characteristics modulates ocean surface changes. The spatial distributions of the climatic mixed layer depth (MLD), accumulated wind forcing power index (WPi), accumulated sea surface temperature (SST) changes and accumulated chlorophyll (Chl-a) changes in the YBS were calculated. The linear regressions indicate that both the TC-induced SST cooling and TC-induced Chl-a increase are correlated with the TC wind speed rather than the translation speed, especially when the TC forcing depth (Zmixing) is greater than the MLD. Otherwise, both the changes in SST and Chl-a are correlated with the TC translation speed when Zmixing is shallower than the MLD. Further study has shown that whether TCs can break the MLD is also a key condition for oceanic responses. In the southern YBS, which has a deep-sea basin and MLD, the TC wind speed is the major factor affecting SST cooling and Chl-a increase, as TCs need more strength to reach the MLD. However, in the northern YBS, which has the shallowest sea basin and MLD, even weak TCs can easily break the MLD and reach the seabed; thus, ocean surface changes are associated mainly with the TC translation speed. The composite results reveal that both the maximum SST cooling center (1.64 °C) and the maximum Chl-a increasing center (0.14 log10(mg/m3)) are located on the right and behind the TC center, respectively. In addition, TC-induced SST cooling and Chl-a increase were initiated two days prior to TC passage and then reached their maximum values after 1 day. It takes approximately 7-8 days for the Chl-a concentration to recover, but it takes a much longer time (>15 days) for the SST to recover.


Assuntos
Tempestades Ciclônicas , Temperatura , Oceanos e Mares , Clorofila , Modelos Lineares
2.
JAMA Intern Med ; 184(3): 291-299, 2024 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-38285562

RESUMO

Importance: Electronic cigarettes (ECs) are often used by smokers as an aid to stopping smoking, but evidence is limited regarding their efficacy compared with nicotine replacement therapy (NRT), and no evidence is available on how their efficacy compares with that of varenicline. Objective: To evaluate whether ECs are superior to NRT and noninferior to varenicline in helping smokers quit. Design, Setting, and Participants: This was a randomized clinical trial conducted at 7 sites in China and including participants who were smoking at least 10 cigarettes per day and motivated to quit, not using stop-smoking medications or EC, and willing to use any of the study products. Participants were first recruited in May 2021, and data analysis was conducted in December 2022. Interventions: A cartridge-based EC (30 mg/mL nicotine salt for 2 weeks and 50 mg/mL after that), varenicline (0.5 mg, once a day for 3 days; 0.5 mg, twice a day for 4 days; and 1 mg, twice a day, after that), and 2 mg (for smokers of ≤20 cigarettes per day) or 4 mg (>20 cigarettes per day) nicotine chewing gum, all provided for 12 weeks and accompanied by minimal behavioral support (an invitation to join a self-help internet forum). Main Outcomes and Measures: The primary outcome was sustained abstinence from smoking at 6 months as validated by an expired-air carbon monoxide reading (<8 parts per million). Participants lost to follow-up were included as nonabstainers. Results: Of 1068 participants, 357 (33.5%) were female, and the mean (SD) age was 33.9 (3.1) years. A total of 409 (38.3%), 409 (38.3%), and 250 (23.4%) participants were randomized to the EC, varenicline, and NRT arms, respectively. The 6-month biochemically validated abstinence rates were 15.7% (n = 64), 14.2% (n = 58), and 8.8% (n = 22) in the EC, varenicline, and NRT study arms, respectively. The quit rate in the EC arm was noninferior to the varenicline arm (absolute risk reduction, 1.47%; 95% CI, -1.41% to 4.34%) and higher than in the NRT arm (odds ratio, 1.92; 95% CI, 1.15-3.21). Treatment adherence was similar in all study arms during the initial 3 months, but 257 participants (62.8%) in the EC arm were still using ECs at 6 months, with no further use in the 2 other study arms. The most common adverse reactions were throat irritation (32 [7.8%]) and mouth irritation (28 [6.9%]) in the EC arm, nausea (36 [8.8%]) in the varenicline arm, and throat irritation (20 [8.0%]) and mouth irritation (22 [8.8%]) in the NRT arm. No serious adverse events were recorded. Conclusions and Relevance: The results of this randomized clinical trial found that when all treatments were provided with minimal behavior support, the efficacy of EC was noninferior to varenicline and superior to nicotine chewing gum. Trial Registration: Chinese Clinical Trial Registry: ChiCTR2100048156.


Assuntos
Sistemas Eletrônicos de Liberação de Nicotina , Goma de Mascar de Nicotina , Abandono do Hábito de Fumar , Feminino , Humanos , Adulto , Masculino , Abandono do Hábito de Fumar/métodos , Vareniclina/uso terapêutico , Agonistas Nicotínicos/efeitos adversos , Dispositivos para o Abandono do Uso de Tabaco , Fumar
3.
Nano Lett ; 23(22): 10213-10220, 2023 Nov 22.
Artigo em Inglês | MEDLINE | ID: mdl-37910440

RESUMO

Strong spin-lattice coupling in van der Waals (vdW) magnets shows potential for innovative magneto-mechanical applications. Here, nanoscale and picosecond imaging by ultrafast electron microscopy reveal heterogeneous spin-mediated coherent acoustic phonon dynamics in a thin-film cavity of the vdW antiferromagnet FePS3. The harmonics of the interlayer shear acoustic modes are observed, in which the even and odd harmonics exhibit distinct nanoscopic dynamics. Corroborated by acoustic wave simulation, the role of defects in forming even harmonics is elucidated. Above the Néel temperature (TN), the interlayer shear acoustic harmonics are suppressed, while the in-plane traveling wave is predominantly excited. The dominant acoustic dynamics shifts from the out-of-plane shear to the in-plane traveling wave across TN, demonstrating that magnetic properties can influence phonon scattering pathways. The spatiotemporally resolved structural characterization provides valuable nanoscopic insights for interlayer-shear-mode-based acoustic cavities, opening up possibilities for magneto-mechanical applications of vdW magnets.

4.
Cell Mol Neurobiol ; 43(8): 4041-4058, 2023 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-37874455

RESUMO

The primary underlying contributor for cataract, a leading cause of vision impairment and blindness worldwide, is oxidative stress. Oxidative stress triggers protein damage, cell apoptosis, and subsequent cataract formation. The nuclear factor-erythroid 2-related factor 2 (Nrf2) serves as a principal redox transcriptional factor in the lens, offering a line of defense against oxidative stress. In response to oxidative challenges, Nrf2 dissociates from its inhibitor, Kelch-like ECH-associated protein 1 (Keap1), moves to the nucleus, and binds to the antioxidant response element (ARE) to activate the Nrf2-dependent antioxidant system. In parallel, oxidative stress also induces endoplasmic reticulum stress (ERS). Reactive oxygen species (ROS), generated during oxidative stress, can directly damage proteins, causing them to misfold. Initially, the unfolded protein response (UPR) activates to mitigate excessive misfolded proteins. Yet, under persistent or severe stress, the failure to rectify protein misfolding leads to an accumulation of these aberrant proteins, pushing the UPR towards an apoptotic pathway, further contributing to cataractogenesis. Importantly, there is a dynamic interaction between the Nrf2 antioxidant system and the ERS/UPR mechanism in the lens. This interplay, where ERS/UPR can modulate Nrf2 expression and vice versa, holds potential therapeutic implications for cataract prevention and treatment. This review explores the intricate crosstalk between these systems, aiming to illuminate strategies for future advancements in cataract prevention and intervention. The Nrf2-dependent antioxidant system communicates and cross-talks with the ERS/UPR pathway. Both mechanisms are proposed to play pivotal roles in the onset of cataract formation.


Assuntos
Antioxidantes , Catarata , Humanos , Antioxidantes/metabolismo , Proteína 1 Associada a ECH Semelhante a Kelch/metabolismo , Fator 2 Relacionado a NF-E2/metabolismo , Estresse do Retículo Endoplasmático/fisiologia , Estresse Oxidativo/fisiologia , Espécies Reativas de Oxigênio/metabolismo
5.
Nature ; 620(7976): 988-993, 2023 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-37532936

RESUMO

Understanding how microscopic spin configuration gives rise to exotic properties at the macroscopic length scale has long been pursued in magnetic materials1-5. One seminal example is the Einstein-de Haas effect in ferromagnets1,6,7, in which angular momentum of spins can be converted into mechanical rotation of an entire object. However, for antiferromagnets without net magnetic moment, how spin ordering couples to macroscopic movement remains elusive. Here we observed a seesaw-like rotation of reciprocal lattice peaks of an antiferromagnetic nanolayer film, whose gigahertz structural resonance exhibits more than an order-of-magnitude amplification after cooling below the Néel temperature. Using a suite of ultrafast diffraction and microscopy techniques, we directly visualize this spin-driven rotation in reciprocal space at the nanoscale. This motion corresponds to interlayer shear in real space, in which individual micro-patches of the film behave as coherent oscillators that are phase-locked and shear along the same in-plane axis. Using time-resolved optical polarimetry, we further show that the enhanced mechanical response strongly correlates with ultrafast demagnetization, which releases elastic energy stored in local strain gradients to drive the oscillators. Our work not only offers the first microscopic view of spin-mediated mechanical motion of an antiferromagnet but it also identifies a new route towards realizing high-frequency resonators8,9 up to the millimetre band, so the capability of controlling magnetic states on the ultrafast timescale10-13 can be readily transferred to engineering the mechanical properties of nanodevices.

7.
J Transl Med ; 21(1): 496, 2023 07 24.
Artigo em Inglês | MEDLINE | ID: mdl-37488572

RESUMO

BACKGROUND: Substantial studies have demonstrated that oxidative stress placenta and endothelial injury are considered to inextricably critical events in the pathogenesis of preeclampsia (PE). Systemic inflammatory response and endothelial dysfunction are induced by the circulating factors released from oxidative stress placentae. As a novel biomarker of oxidative stress, advanced oxidation protein products (AOPPs) levels are strongly correlated with PE characteristics. Nevertheless, the molecular mechanism underlying the effect of factors is still largely unknown. METHODS: With the exponential knowledge on the importance of placenta-derived extracellular vesicles (pEVs), we carried out lncRNA transcriptome profiling on small EVs (sEVs) secreted from AOPPs-treated trophoblast cells and identified upregulated lncRNA TDRKH-AS1 as a potentially causative factor for PE. We isolated and characterized sEVs from plasma and trophoblast cells by transmission electron microscopy (TEM), nanoparticle tracking analysis (NTA) and western blotting. The expression and correlation of lncRNA TDRKH-AS1 were evaluated using qRT-PCR in plasmatic sEVs and placentae from patients. Pregnant mice injected with TDRKH-AS1-riched trophoblast sEVs was performed to detect the TDRKH-AS1 function in vivo. To investigate the potential effect of sEVs-derived TDRKH-AS1 on endothelial function in vitro, transcriptome sequencing, scanning electron Microscopy (SEM), immunofluorescence, ELISA and western blotting were conducted in HUVECs. RNA pulldown, mass spectrometry, RNA immunoprecipitation (RIP), chromatin isolation by RNA purification (ChIRP) and coimmunoprecipitation (Co-IP) were used to reveal the latent mechanism of TDRKH-AS1 on endothelial injury. RESULTS: The expression level of TDRKH-AS1 was significantly increased in plasmatic sEVs and placentae from patients, and elevated TDRKH-AS1 in plasmatic sEVs was positively correlated with clinical severity of the patients. Moreover, pregnant mice injected with TDRKH-AS1-riched trophoblast sEVs exhibited a hallmark feature of PE with increased blood pressure and systemic inflammatory responses. Pyroptosis, an inflammatory form of programmed cell death, is involved in the development of PE. Indeed, our in vitro study indicated that sEVs-derived TDRKH-AS1 secreted from AOPPs-induced trophoblast elevated DDIT4 expression levels to trigger inflammatory response of pyroptosis in endothelial cells through interacting with PDIA4. CONCLUSIONS: Herein, results in the present study supported that TDRKH-AS1 in sEVs isolated from oxidative stress trophoblast may be implicated in the pathogenesis of PE via inducing pyroptosis and aggravating endothelial dysfunction.


Assuntos
Vesículas Extracelulares , Pré-Eclâmpsia , RNA Longo não Codificante , Feminino , Gravidez , Humanos , Animais , Camundongos , Células Endoteliais , Piroptose , Produtos da Oxidação Avançada de Proteínas , Trofoblastos , Proteínas de Ligação a RNA , Fatores de Transcrição , Isomerases de Dissulfetos de Proteínas
8.
Cell Host Microbe ; 31(5): 798-810.e7, 2023 05 10.
Artigo em Inglês | MEDLINE | ID: mdl-37054714

RESUMO

Rheumatoid arthritis (RA) is an autoimmune disorder that has been associated with the gut microbiota. However, whether and how the gut microbiota plays a pathogenic role in RA remains unexplored. Here, we observed that Fusobacterium nucleatum is enriched in RA patients and positively associated with RA severity. F. nucleatum similarly aggravates arthritis in a mouse model of collagen-induced arthritis (CIA). F. nucleatum outer membrane vesicles (OMVs) containing the virulence determinant FadA translocate into the joints, triggering local inflammatory responses. Specifically, FadA acts on synovial macrophages, resulting in the activation of the Rab5a GTPase involved in vesicle trafficking and inflammatory pathways and YB-1, a key regulator of inflammatory mediators. OMVs containing FadA and heightened Rab5a-YB-1 expression were observed in RA patients compared with controls. These findings suggest a causal role of F. nucleatum in aggravating RA and provide promising therapeutic targets for clinically ameliorating RA.


Assuntos
Artrite Reumatoide , Fusobacterium nucleatum , Animais , Camundongos , Fusobacterium nucleatum/metabolismo , Fatores de Virulência/metabolismo
10.
Nature ; 612(7939): 259-265, 2022 12.
Artigo em Inglês | MEDLINE | ID: mdl-36443603

RESUMO

The unique topology and physics of chiral superlattices make their self-assembly from nanoparticles highly sought after yet challenging in regard to (meta)materials1-3. Here we show that tetrahedral gold nanoparticles can transform from a perovskite-like, low-density phase with corner-to-corner connections into pinwheel assemblies with corner-to-edge connections and denser packing. Whereas corner-sharing assemblies are achiral, pinwheel superlattices become strongly mirror asymmetric on solid substrates as demonstrated by chirality measures. Liquid-phase transmission electron microscopy and computational models show that van der Waals and electrostatic interactions between nanoparticles control thermodynamic equilibrium. Variable corner-to-edge connections among tetrahedra enable fine-tuning of chirality. The domains of the bilayer superlattices show strong chiroptical activity as identified by photon-induced near-field electron microscopy and finite-difference time-domain simulations. The simplicity and versatility of substrate-supported chiral superlattices facilitate the manufacture of metastructured coatings with unusual optical, mechanical and electronic characteristics.


Assuntos
Ouro , Nanopartículas Metálicas , Eletrônica , Física
11.
Ophthalmol Ther ; 11(6): 2169-2182, 2022 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-36169874

RESUMO

INTRODUCTION: This study developed and validated a nomogram for predicting the risk of second surgery in patients with concomitant esotropia (CE) based on a cohort in Beijing. METHODS: In this retrospective cohort study, the inpatient and outpatient medical records of 419 patients with CE who underwent surgery at the Peking University First Hospital between January 1, 2005 and December 31, 2009 were collected. A total of 357 CE cases were included. For those cases 70% were randomly assigned to the training set (n = 234) and 30% to the validation set (n = 123). Demographic and clinical variables were ascertained at hospital admission and discharge and screened using multivariate Cox proportional hazards regression analysis to construct predictive models and generate a 1-, 4-, and 8-year overall survival nomogram. This nomogram provided an estimate of the risk of second surgery in patients with surgically treated CE. Internal validation was conducted using the concordance index (C-index) and calibration curve for the training and validation sets. RESULTS: Six independent prognostic factors were identified, namely age at surgery, age at onset, amblyopia, deviation angles, surgical amount, and deviation angles 1 week after surgery, and these were entered into the nomogram. The proposed nomogram showed favorable discrimination and accuracy in the training and validation sets. The C-indexes of the training and validation sets were 0.84 (95% CI 0.79-0.89) and 0.80 (95% CI 0.78-0.82), respectively. CONCLUSIONS: The proposed nomogram can serve as a predictive tool for prognostic evaluation of CE surgery.

12.
Front Oncol ; 12: 991051, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36119530

RESUMO

Pancreatic cancer (PC) is burdened with a low 5-year survival rate and high mortality due to a severe lack of early diagnosis methods and slow progress in treatment options. To improve clinical diagnosis and enhance the treatment effects, we applied metabolomics using ultra-high-performance liquid chromatography with a high-resolution mass spectrometer (UHPLC-HRMS) to identify and validate metabolite biomarkers from paired tissue samples of PC patients. Results showed that the metabolic reprogramming of PC mainly featured enhanced amino acid metabolism and inhibited sphingolipid metabolism, which satisfied the energy and biomass requirements for tumorigenesis and progression. The altered metabolism results were confirmed by the significantly changed gene expressions in PC tissues from an online database. A metabolites biomarker panel (six metabolites) was identified for the differential diagnosis between PC tumors and normal pancreatic tissues. The panel biomarker distinguished tumors from normal pancreatic tissues in the discovery group with an area under the curve (AUC) of 1.0 (95%CI, 1.000-1.000). The biomarker panel cutoff was 0.776. In the validation group, an AUC of 0.9000 (95%CI = 0.782-1.000) using the same cutoff, successfully validated the biomarker signature. Moreover, this metabolites panel biomarker had a great capability to predict the overall survival (OS) of PC. Taken together, this metabolomics method identifies and validates metabolite biomarkers that can diagnose the onsite progression and prognosis of PC precisely and sensitively in a clinical setting. It may also help clinicians choose proper therapeutic interventions for different PC patients and improve the survival of PC patients.

13.
Front Mol Biosci ; 9: 841223, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35252357

RESUMO

Graves' disease (GD) is an autoimmune thyroid disease (AITD), which is one of the most common organ-specific autoimmune disorders with an increasing prevalence worldwide. But the etiology of GD is still unclear. A growing number of studies show correlations between gut microbiota and GD. The dysbiosis of gut microbiota may be the reason for the development of GD by modulating the immune system. Metabolites act as mediators or modulators between gut microbiota and thyroid. The purpose of this review is to summarize the correlations between gut microbiota, microbial metabolites and GD. Challenges in the future study are also discussed. The combination of microbiome and metabolome may provide new insight for the study and put forward the diagnosis, treatment, prevention of GD in the future.

14.
Front Pharmacol ; 13: 785105, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35185560

RESUMO

Many reports have shown that patients with Hp-associated chronic gastritis exhibit anxiety and poor sleep quality. However, less is known about the effects and specific manifestations of Hp-associated chronic gastritis on autonomous activity and sleep quality in animals. Here, we investigated the effect of Helicobacter pylori (Hp)-associated chronic gastritis on autonomous activity and sleep quality in mice. To do this, a Hp-associated chronic gastritis mouse model was first established, then analyzed for autonomous activity, relative to controls, for 15 min using an autonomous activity tester. Next, sleep quality of mice was detected by sodium pentobarbital-induced sleep experiment and results compared between groups. The results showed that male mice in the model group exhibited higher activity counts but lower forelimb lift counts, relative to those in the control group, although there were no significant differences (all p > .05). Conversely, female mice in the model group recorded lower activity counts, albeit at no significant difference (p > .05), and significantly lower counts of forelimb lift (p < .05), relative to those in the control group. Notably, male mice in the model group had longer sleep latency and shorter sleep duration than those in the control group, albeit at no significant differences (all p > .05). On the other hand, female mice in the model group recorded significantly longer sleep latency as well as shorter sleep duration compared to those in the control group (all p < .01). We conclude that Hp-associated chronic gastritis exerts certain effects on autonomous activity and sleep quality of mice in a gender-dependent manner. Notably, female mice with Hp-associated chronic gastritis had lower activity and forelimb lift counts, as well as prolonged sleep latency, and shortened sleep duration. These effects were all statistically significant except for activity counts.

15.
J Food Sci ; 87(1): 339-352, 2022 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-34954823

RESUMO

Sweet potato starch industry produce generous high soluble solid wastewater containing various biochemicals such as proteins. The wastewater could be spray dried into a product called yellow powder (YP). Proteins in the YP were recovered and profiled in this study. The extraction conditions were optimized on dependent variables of YP material-water ratio, pH, and temperature using response surface methodology (RSM). Maximum protein yield (61.2%) using RSM were observed at a material-water ratio of 50 (mg/L), pH 9.5, and extraction temperature of 30℃. Subsequently, a total of 25 proteins were identified by proteomic analysis, which mainly were sporamins, ß-amylase, starch phosphorylase, polyphenol oxidase, and superoxide dismutase. The extraction and profiling of proteins from YP would contribute to a comprehensive utilization and added value of the wastewater produced by sweet potato starch processing industry. PRACTICAL APPLICATION: This study reported the recovery (61.2%) of proteins and protein profile of yellow powder (byproducts) from sweet potato starch wastewater. These information could contribute to the valorization a yellow powder into high-value ingredients.


Assuntos
Ipomoea batatas , Pós , Proteômica , Amido , Águas Residuárias
16.
Clin Anat ; 35(2): 211-221, 2022 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-34851529

RESUMO

While blended learning has been growing in popularity in recent years, the effectiveness of this procedure remains controversial. In this report, we assess the effectiveness of blended learning of embryology within international medical students. The participants were international medical students taking embryology in the Bachelor of Medicine and Bachelor of Surgery program. The blended learning group (BLG) consisted of students (n = 43) in the 2018-2019 academic year, taught with blended learning model via a customized small private online course (SPOC). The control traditional teaching group (TTG) consisted students (n = 48) in the 2017-2018 academic year, taught with traditional teaching model. Academic performance, including mean scores and passing ratios on the final exam of two groups were compared and analyzed with a t-test. In addition, a questionnaire directed toward evaluating student's perceptions with the blended learning was administered to students in BLG. The majority of students in BLG actively participated in online self-study activities and discussion in face-to-face class sessions. The mean score and passing ratio were significantly greater than those of students in TTG (p < 0.01). Results from the questionnaire revealed that the majority of BLG students felt that this method was beneficial for their learning of human embryology. The blended learning model, that integrates SPOC with face-to-face class lectures proved a more effective means for the teaching of embryology than the traditional lecture-based teaching model. This blended learning method may serve as a feasible model that can be readily applied for use in other medical courses.


Assuntos
Desempenho Acadêmico , Estudantes de Medicina , Currículo , Avaliação Educacional , Humanos , Aprendizagem Baseada em Problemas , Ensino
17.
Oxid Med Cell Longev ; 2021: 3259238, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34721757

RESUMO

Acetaminophen (APAP) hepatotoxicity is the leading cause of acute liver failure in the western world. Oridonin (OD), which is the major active ingredient of the traditional Chinese medicine Rabdosia rubescens, reportedly exerts anti-inflammatory and antioxidative effects. Here, we first find that OD protects against APAP-induced hepatotoxicity. The results of hepatic tissue-associated RNA-seq and metabolomics showed that the protective effects of OD were dependent upon urea cycle regulation. And such regulation of OD is gut microbiota partly dependent, as demonstrated by fecal microbiota transplantation (FMT). Furthermore, using 16S rRNA sequencing, we determined that OD significantly enriched intestinal Bacteroides vulgatus, which activated the nuclear factor erythroid 2-related factor 2 (Nrf2) pathway to regulate redox homeostasis against APAP by urea cycle. In conclusion, our study suggests that the Bacteroides vulgatus-urea cycle-Nrf2 axis may be a potential target for reducing APAP-induced liver injury, which is altered by OD.


Assuntos
Bacteroides/efeitos dos fármacos , Doença Hepática Induzida por Substâncias e Drogas/prevenção & controle , Diterpenos do Tipo Caurano/farmacologia , Microbioma Gastrointestinal/efeitos dos fármacos , Fígado/efeitos dos fármacos , Ureia/metabolismo , Acetaminofen , Animais , Bacteroides/genética , Bacteroides/metabolismo , Doença Hepática Induzida por Substâncias e Drogas/metabolismo , Doença Hepática Induzida por Substâncias e Drogas/microbiologia , Doença Hepática Induzida por Substâncias e Drogas/patologia , Modelos Animais de Doenças , Disbiose , Transplante de Microbiota Fecal , Fígado/metabolismo , Masculino , Metaboloma , Camundongos Endogâmicos C57BL , Camundongos Knockout , Fator 2 Relacionado a NF-E2/genética , Fator 2 Relacionado a NF-E2/metabolismo
18.
Nano Lett ; 21(13): 5842-5849, 2021 07 14.
Artigo em Inglês | MEDLINE | ID: mdl-34153185

RESUMO

Hybrids of graphene and metal plasmonic nanostructures are promising building blocks for applications in optoelectronics, surface-enhanced scattering, biosensing, and quantum information. An understanding of the coupling mechanism in these hybrid systems is of vital importance to its applications. Previous efforts in this field mainly focused on spectroscopic studies of strong coupling within the hybrids with no spatial resolution. Here we report direct imaging of the local plasmonic coupling between single Au nanocapsules and graphene step edges at the nanometer scale by photon-induced near-field electron microscopy in an ultrafast electron microscope for the first time. The proximity of a step in the graphene to the nanocapsule causes asymmetric surface charge density at the ends of the nanocapsules. Computational electromagnetic simulations confirm the experimental observations. The results reported here indicate that this hybrid system could be used to manipulate the localized electromagnetic field on the nanoscale, enabling promising future plasmonic devices.


Assuntos
Grafite , Nanoestruturas , Microscopia de Força Atômica , Microscopia Eletrônica , Nanotecnologia
19.
Mol Ther Nucleic Acids ; 22: 684-695, 2020 Dec 04.
Artigo em Inglês | MEDLINE | ID: mdl-33230466

RESUMO

Preeclampsia is believed to be caused by impaired placentation with insufficient trophoblast invasion, leading to impaired uterine spiral artery remodeling and angiogenesis. However, the underlying molecular mechanism remains unknown. We recently carried out transcriptome profiling of placental long noncoding RNAs (lncRNAs) and identified 383 differentially expressed lncRNAs in early-onset severe preeclampsia. Here, we are reporting our identification of lncRNA INHBA-AS1 as a potential causal factor of preeclampsia and its downstream pathways that may be involved in placentation. We found that INHBA-AS1 was upregulated in patients and positively correlated with clinical severity. We systematically searched for potential INHBA-AS1-binding transcription factors and their targets in databases and found that the targets were enriched with differentially expressed genes in the placentae of patients. We further demonstrated that the lncRNA INHBA-AS1 inhibited the invasion and migration of trophoblast cells through restraining the transcription factor CENPB from binding to the promoter of TNF receptor-associated factor 1 (TRAF1). Therefore, we have identified the dysregulated pathway "INHBA-AS1-CENPB-TRAF1" as a contributor to the pathogenesis of preeclampsia through prohibiting the proliferation, invasion, and migration of trophoblasts during placentation.

20.
Cell Death Dis ; 11(7): 583, 2020 07 27.
Artigo em Inglês | MEDLINE | ID: mdl-32719429

RESUMO

Accumulating evidence suggests that the pathogenesis of preeclampsia involves poor placentation caused by insufficient trophoblast invasion and impaired uterine spiral artery remodeling, yet the underlying molecular mechanism remains unclear. We carried out transcriptome profiling on placentae from preeclamptic patients and normal subjects, and identified about four hundred long non-coding RNAs differentially expressed in placentae of patients with early-onset severe preeclampsia. Here, we report our identification of lncRNA SH3PXD2A-AS1 as a potential causal factor for this disease and its downstream pathways involved in placentation. We found that expression level of SH3PXD2A-AS1 in the placentae is positively correlated with clinical severity of the patients. We demonstrated that SH3PXD2A-AS1 inhibited invasion and migration through recruiting CCCTC-binding factor (CTCF) to the promoters of SH3PXD2A and CCR7 to inhibit their transcription. Therefore, we conclude that the upregulation of lncRNA SH3PXD2A-AS1 may contribute to the pathogenesis of preeclampsia through prohibiting trophoblast invasion during placentation.


Assuntos
Movimento Celular/genética , Placenta/patologia , Pré-Eclâmpsia/genética , RNA Longo não Codificante/metabolismo , Trofoblastos/metabolismo , Trofoblastos/patologia , Adulto , Fator de Ligação a CCCTC/metabolismo , Pontos de Checagem do Ciclo Celular/genética , Morte Celular/genética , Linhagem Celular , Proliferação de Células/genética , Feminino , Humanos , Pré-Eclâmpsia/patologia , Gravidez , Regiões Promotoras Genéticas/genética , Ligação Proteica , RNA Longo não Codificante/genética , Receptores CCR7/metabolismo , Frações Subcelulares/metabolismo , Transcrição Gênica , Regulação para Cima/genética
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