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1.
Diabetologia ; 2021 Feb 11.
Artigo em Inglês | MEDLINE | ID: mdl-33569632

RESUMO

AIMS/HYPOTHESIS: Failure of pancreatic and duodenal homeobox factor 1 (PDX1) to localise in the nucleus of islet beta cells under high-fat diet (HFD) conditions may be an early functional defect that contributes to beta cell failure in type 2 diabetes; however, the mechanism of PDX1 intracellular mislocalisation is unclear. Stress granules (SGs) are membrane-less cytoplasmic structures formed under stress that impair nucleocytoplasmic transport by sequestering nucleocytoplasmic transport factors and components of the nuclear pore complex. In this study, we investigated the stimulators that trigger SG formation in islet beta cells and the effects of SGs on PDX1 localisation and beta cell function. METHODS: The effect of palmitic acid (PA) on nucleocytoplasmic transport was investigated by using two reporters, S-tdTomato and S-GFP. SG assembly in rat insulinoma cell line INS1 cells, human islets under PA stress, and the pancreas of diet-induced obese mice was analysed using immunofluorescence and immunoblotting. SG protein components were identified through mass spectrometry. SG formation was blocked by specific inhibitors or genetic deletion of essential SG proteins, and then PDX1 localisation and beta cell function were investigated in vitro and in vivo. RESULTS: We showed that saturated fatty acids (SFAs) are endogenous stressors that disrupted nucleocytoplasmic transport and stimulated SG formation in pancreatic beta cells. Using mass spectrometry approaches, we revealed that several nucleocytoplasmic transport factors and PDX1 were localised to SGs after SFA treatment, which inhibited glucose-induced insulin secretion. Furthermore, we found that SFAs induced SG formation in a phosphoinositide 3-kinase (PI3K)/eukaryotic translation initiation factor 2α (EIF2α) dependent manner. Disruption of SG assembly by PI3K/EIF2α inhibitors or genetic deletion of T cell restricted intracellular antigen 1 (TIA1) in pancreatic beta cells effectively suppressed PA-induced PDX1 mislocalisation and ameliorated HFD-mediated beta cell dysfunction. CONCLUSIONS/INTERPRETATION: Our findings suggest a link between SG formation and beta cell dysfunction in the presence of SFAs. Preventing SG formation may be a potential therapeutic strategy for treating obesity and type 2 diabetes.

2.
Int J Cancer ; 2021 Jan 31.
Artigo em Inglês | MEDLINE | ID: mdl-33521941

RESUMO

China has made rapid progress in reducing the incidence of HBV infection in the past three decades, along with a rapidly changing lifestyle and aging population. We aimed to develop and validate an up-to-date liver cancer risk prediction model with routinely available predictors and evaluate its applicability for screening guidance. Using data from the China Kadoorie Biobank, we included 486 285 participants in this analysis. Fifteen risk factors were included in the model. Flexible parametric survival models were used to estimate the 10-year absolute risk of liver cancer. Decision curve analysis was performed to evaluate the net benefit of the model to quantify clinical utility. A total of 2706 participants occurred liver cancer over the 4 814 320 person-years of follow-up. Excellent discrimination of the model was observed in both development and validation datasets, with c-statistics (95% CI) of 0.80 (0.79-0.81) and 0.80 (0.78-0.82) respectively, as well as excellent calibration of observed and predicted risks. Decision curve analysis revealed that use of the model in selecting participants for screening improved benefit at a threshold of 2% 10-year risk, compared to current guideline of screening all HBsAg carriers. Our model was more sensitive than current guideline for cancer screening (28.17% vs 25.96%). We developed and validated a CKB-PLR (Prediction for Liver cancer Risk Based on the China Kadoorie Biobank Study) model to predict the absolute risk of liver cancer for both HBsAg seropositive and seronegative populations. Application of the model is beneficial for precisely identifying the high-risk groups among the general population.

3.
Exp Lung Res ; : 1-13, 2021 Feb 16.
Artigo em Inglês | MEDLINE | ID: mdl-33590796

RESUMO

Background Asthma is a chronic inflammatory heterogeneous respiratory disease. Previous studies showed that the lncRNA NEAT1 (nuclear paraspeckle assembly transcript 1) might play an important role in the pathogenesis of asthma, but its potential mechanism in airway smooth muscle cell (ASMC) inflammation remains largely unknown and needs further investigation. Methods We performed cellular immunofluorescence to identify the features of ASMCs and detected the expression levels of lncRNA NEAT1, miR-139, TNF-α, IL-6, IL-8 and IL-1ß by quantitative real-time PCR (Q-PCR) and ELISA. Western blotting (WB) was used to measure the protein expression of the related genes, and bioinformatics as well as dual luciferase assays were used to validate the interaction between lncRNA NEAT1 and miR-139 and the interaction between miR-139 and the 3'-UTR of JAK3. Results The expression of lncRNA NEAT1 was increased in the ASMCs of asthma patients, but miR-139 was decreased. Overexpression of lncRNA NEAT1 promoted the expression of the inflammatory cytokines such as TNF-α, IL-6, IL-8 and IL-1ß in ASMCs. LncRNA NEAT1 was able to target miR-139 to activate the JAK3/STAT5 signaling pathway and induced the expression of these inflammatory cytokines in ASMCs. Overexpression of miR-139 or suppression of the JAK3/STAT5 signaling pathway reversed the inflammatory effect of lncRNA NEAT1. Conclusion LncRNA NEAT1 played a pivotal role in ASMC inflammation and exerted its function through the miR-139/JAK3/STAT5 signaling network.

4.
Am J Trop Med Hyg ; 2021 Feb 16.
Artigo em Inglês | MEDLINE | ID: mdl-33591933

RESUMO

Knowledge of the clinical progress of severe fever with thrombocytopenia syndrome (SFTS) and the associated predictors of mortality is important for providing appropriate treatment in severe cases. A multihospital retrospective study was conducted in three SFTS-endemic cities, in 2018. Of the 208 SFTS-confirmed cases, there were 189 survivors and 19 deaths. The median age was 64 years; 104 (50.0%) patients were men, and 188 (90.4%) were farmers. Furthermore, 203 (97.6%) patients reported fever and 70 (33.7%) reported fatigue. Most fatal cases had complications including multiple-organ failure, central nervous syndrome (CNS) abnormalities, and disseminated intravascular coagulation. During the fever phase, alanine transaminase, aspartate aminotransferase (AST), blood urea nitrogen (BUN), creatinine, D-dimer, glucose, hydroxybutyrate dehydrogenase, lactate dehydrogenase (LDH), procalcitonin, prothrombin time, and uric acid levels were higher in fatal than in nonfatal cases (P < 0.05). Creatine kinase (CK), CK-MB (CKMB), AST, and LDH levels were significantly lower in nonfatal than in fatal cases (P < 0.05). Central nervous syndrome abnormalities (odds ratio [OR] = 20.9, 95% CI: 4.3, 100), body temperature ≥ 38.5°C (OR = 23.2, 95% CI: 3.4, 158), BUN levels ≥ 6.4 mmol/L (OR = 9.9, 95% CI: 2.2, 44), CKMB levels ≥ 100 U/L (OR = 33.2, 95% CI: 5.8, 192), and LDH levels ≥ 1,000 U/L (OR = 8.3, 95% CI: 1.9, 37) were predictors of mortality. Our findings reveal that the presence of specific complications and laboratory parameters may serve as predictors of mortality and aid in early identification of severe SFTS cases in clinical practice.

5.
Nano Lett ; 21(4): 1722-1728, 2021 Feb 24.
Artigo em Inglês | MEDLINE | ID: mdl-33528254

RESUMO

Gram-negative bacteria, which possess an impermeable outer membrane, are responsible for many untreatable infections. The lack of development of new relevant antibiotics for over 50 years has increased threats. Peptides are regarded as the most promising alternatives to antibiotics. However, since the activities of existing peptides are not yet comparable to those of current antibiotics, there is an urgent need to improve their antibacterial efficiencies. Herein, we conjugate peptides onto one-dimensional rod-like tobacco mosaic virus (TMV). The peptides on the obtained nanoparticles (peptide-TMV) are hundreds of times superior to free peptides in combating Gram-negative bacteria. Through morphology and gene detection of Escherichia coli, it was revealed that following peptide-TMV application, the high osmotic pressure related to membrane damage and the generated reactive oxygen species cause Escherichia coli's death. In addition, peptide-TMV causes a downregulation of biofilm-related genes, inhibiting biofilm formation. This work paves the way to combat Gram-negative bacteria-related infection.

6.
Pain Res Manag ; 2021: 8857948, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33613794

RESUMO

Purpose: Medical cannabis for patients with chronic noncancer pain (CNCP) has been the focus of numerous health care recommendations. We conducted a systematic review to identify and summarize the currently available evidence-based recommendations. Methods: We searched MEDLINE, EMBASE, PsycINFO, the Cochrane database of systematic reviews, and websites for clinical guidelines and recommendations. We summarized the type of the publications, developers, approach of health care recommendation development, year and country of publication, and conditions that were addressed. We categorized the direction and strength of each recommendation. Results: We identified 12 eligible publications. Publication years ranged from 2007 to 2019; four (33.3%) of them were published in 2018. Canada ranked first for the number of publications (n = 4, 33.3%). Most (n = 11, 92%) of the included recommendations were based on both a systematic review of the best evidence and expert consensus. All the included publications provided a recommendation supporting medical cannabis for CNCP in general and for the specific conditions of neuropathic pain, chronic pain in people living with Human Immunodeficiency Virus (HIV), and chronic abdominal pain, with detailed information sharing and comprehensive consideration of a patient's own values and preferences. Conclusion: Clinicians can attend to the guidance currently offered, being aware that only weak recommendations are available for medical cannabis in patients with CNCP, as a third- or fourth-line therapy. Detailed discussions with patients regarding the benefits in reducing pain and potential adverse effects are required before its prescription.

7.
PLoS One ; 16(1): e0245430, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33444389

RESUMO

Reducing the water content of oily sludge is essential for the disposal of it. Despite conditioning and solid-liquid separation, the water content of oily sludge generally exceeds 65%. A large amount of this water exists in the form of emulsified and bound water, reducing the efficiency of water removal during the natural semi-drying process of oily sludge. To shorten the time required for natural semi-drying, this study applied an orthogonal test to screen an oily sludge modified material (OSM). The effect and mechanism of OSM on the natural semi-drying of oily sludge were studied using a thermal gravimetric analyzer (TGA), scanning electron microscope (SEM), surface tension measurement, and microscopic observations. The results show that when the ambient temperature exceeded 10°C, the OSM increased in mass by 8-10%, and the time required for the natural semi-drying of oily sludge was shortened from 15 days to less than 5 days. OSM can rupture the emulsion, reduce the surface tension, convert the emulsion and bound water in the oily sludge into free water, and accelerate the rate of water migration, diffusion, and natural evaporation from the inside of the oily sludge to the surface and air. The research results show that changing the form of water can speed up the drying of oily sludge, creating positive economic benefits in the process of oily sludge reduction and recycling.

8.
Gene ; 767: 145287, 2021 Jan 30.
Artigo em Inglês | MEDLINE | ID: mdl-33181258

RESUMO

BACKGROUND: Chronic respiratory diseases have become a non-negligible cause of death globally. Although smoking and environmental exposures are primary risk factors for chronic respiratory diseases, genetic factors also play an important role in determining individual's susceptibility to diseases. Here we performed integrated gene-based and pathway analyses to systematically illuminate the heritable characteristics of chronic respiratory diseases. METHODS: UK (United Kingdom) Biobank is a very large, population-based prospective study with over 500,000 participants, established to allow detailed investigations of the genetic and nongenetic determinants of the diseases. Utilizing the GWAS-summarized data downloaded from UK Biobank, we conducted gene-based analysis to obtain associations of susceptibility genes with asthma, chronic obstructive pulmonary disease(COPD) and pneumonia using FUSION and MAGMA software. Across the identified susceptibility regions, functional annotation integrating multiple functional data sources was performed to explore potential regulatory mechanisms with INQUISIT algorithm. To further detect the biological process involved in the development of chronic respiratory diseases, we undertook pathway enrichment analysis with the R package (clusterProfiler). RESULTS: A total of 195 susceptibility genes were identified significantly associated with chronic respiratory diseases (Pbonferroni < 0.05), and 24/195 located out of known susceptibility regions (e.g. WDPCP in 2p15). Within the identified susceptibility regions, functional annotation revealed an aggregation of credible variants in promoter-like and enhancer-like histone modification regions and such regulatory mechanisms were specific to lung tissues. Furthermore, 110 genes with INQUISIT score ≥1 may influence diseases susceptibility through exerting effects on coding sequences, proximal promoter and distal enhancer regulations. Pathway enrichment results showed that these genes were enriched in immune-related processes and nicotinic acetylcholine receptors pathways. CONCLUSIONS: This study implemented an integrated gene-based and pathway strategy to explore the underlying biological mechanisms and our findings may serve as promising targets for future clinical treatments of chronic respiratory diseases.


Assuntos
Predisposição Genética para Doença/genética , Estudo de Associação Genômica Ampla/métodos , Transtornos Respiratórios/genética , Asma/genética , Bancos de Espécimes Biológicos , Doença Crônica/epidemiologia , Bases de Dados Genéticas , Feminino , Humanos , Pulmão/fisiopatologia , Masculino , Polimorfismo de Nucleotídeo Único/genética , Estudos Prospectivos , Doença Pulmonar Obstrutiva Crônica/genética , Fumar/genética , Reino Unido
9.
Huan Jing Ke Xue ; 42(1): 242-250, 2021 Jan 08.
Artigo em Chinês | MEDLINE | ID: mdl-33372476

RESUMO

Connected rivers are a common engineering method to ensure the ecological health of urban water. However, for the lakes with serious cyanobacteria blooms, the algal particles are carried by the outflow of the lake and will have a significant impact on water quality. The location at which the Liangxi river meets Meiliang Bay of Lake Taihu was selected to explore the influence of the eutrophic lake on the connected rivers, and high-frequency monitoring was conducted in summer for three consecutive years to analyze the changes in the flux of cyanobacterial bloom particles in rivers and their impact on river water quality. The results show that:① The improvement of the algal cyanobacteria bloom in Meiliang Bay and the operation of the pressure-controlled algae well at the entrance of the river significantly reduced the concentration of chlorophyll a and the flux of algae particles in the Liangxi River. The average value of the concentration of chlorophyll a and the flux of algae particles in the river in summer 2019 were 54.34 µg·L-1 and 84.7 t·d-1, respectively, and significantly lower than those of 2017; ② Water diversion had a significant effect on improving the water quality of the receiving water. Except for DTP, the nitrogen and phosphorus concentrations of the remaining forms of the Liangxi River showed a downward trend from 2017 to 2019, indicating that the water quality of the Liangxi river improved after water transfer; ③ A large amount of cyanobacterial blooms entering the channel significantly increased the particulate nitrogen and phosphorus content of the water. From 2017 to 2019, the nitrogen and phosphorus in the Liangxi River were mainly PN and PP, accounting for 62.5% and 70.8% of TN and TP, respectively; ④ The water quality of the Beijing-Hangzhou Grand Canal and other connected rivers has not been affected by the algal particles in Meiliang Bay. In August 2019, the chlorophyll a content in the canal water decreased by 65% compared with that of June, indicating that cyanobacterial bloom particles have not accumulated in the Grand Canal; ⑤ On the premise that the cyanobacteria bloom in the lake has not been effectively improved, the algae particles carried by the water diversion will have an impact on the water quality and landscape of the local reach connecting the river.


Assuntos
Lagos , Rios , Pequim , China , Clorofila A , Monitoramento Ambiental , Eutrofização , Nitrogênio/análise , Fósforo/análise , Qualidade da Água
10.
Dev Cell ; 56(3): 366-382.e9, 2021 Feb 08.
Artigo em Inglês | MEDLINE | ID: mdl-33378662

RESUMO

The development of mouse embryos can be partially recapitulated by combining embryonic stem cells (ESCs), trophoblast stem cells (TS), and extra-embryonic endoderm (XEN) stem cells to generate embryo-like structures called ETX embryos. Although ETX embryos transcriptionally capture the mouse gastrula, their ability to recapitulate complex morphogenic events such as gastrulation is limited, possibly due to the limited potential of XEN cells. To address this, we generated ESCs transiently expressing transcription factor Gata4, which drives the extra-embryonic endoderm fate, and combined them with ESCs and TS cells to generate induced ETX embryos (iETX embryos). We show that iETX embryos establish a robust anterior signaling center that migrates unilaterally to break embryo symmetry. Furthermore, iETX embryos gastrulate generating embryonic and extra-embryonic mesoderm and definitive endoderm. Our findings reveal that replacement of XEN cells with ESCs transiently expressing Gata4 endows iETX embryos with greater developmental potential, thus enabling the study of the establishment of anterior-posterior patterning and gastrulation in an in vitro system.

11.
Artigo em Inglês | MEDLINE | ID: mdl-33255768

RESUMO

The outbreak of Coronavirus Disease 2019 (COVID-19) posed a powerful threat to human life. The preventive behaviors of individuals (e.g., home quarantine, disinfection, and wearing masks) play a key role in preserving and controlling the disease. In this case, as a motivational psychological system oriented toward avoiding infection, the behavioral immune system (BIS) may be activated and link to preventive behaviors. This study investigated the mechanisms through which emotional and cognitive processes resulted by BIS have promoted preventive behaviors in relation to COVID-19. We collected data on 22,005 active Sina Weibo users from 31 December 2019 to 8 February 2020 to measure their emotions (including disgust, happiness, and fear), cultural values (individualism and collectivism), moral concern (including purity vice, fairness vice, and authority virtue), and behavioral intentions (including isolation intention, protection intention, and aid intention) using Text Mind software and related dictionaries. Multiple regression and mediation analyses were performed to explore the relationships among variables. The results showed seven complete mediation paths (such as disgust-purity vice-protection intention). Each of these paths describes the effects of cognitive processes caused by BIS on preventive behaviors. We inferred that there may be path mechanisms such as disgust-cognitive processes-preventive behaviors. Using these results, policy makers can take appropriate measures to intervene in preventive behaviors (e.g., by posting disgusting images on social media to evoke disgust). The results can be used to explain differences in preventive behaviors among populations even in the face of similar thread levels. Furthermore, our research provides empirical evidence for the hypothesis of pathogen prevalence.

12.
Redox Biol ; 38: 101813, 2020 Nov 25.
Artigo em Inglês | MEDLINE | ID: mdl-33279869

RESUMO

Diabetic kidney disease is known as a major cause of chronic kidney disease and end stage renal disease. Polysulfides, a class of chemical agents with a chain of sulfur atoms, are found to confer renal protective effects in acute kidney injury. However, whether a polysulfide donor, sodium tetrasulfide (Na2S4), confers protective effects against diabetic nephropathy remains unclear. Our results showed that Na2S4 treatment ameliorated renal dysfunctional and histological damage in diabetic kidneys through inhibiting the overproduction of inflammation cytokine and reactive oxygen species (ROS), as well as attenuating renal fibrosis and renal cell apoptosis. Additionally, the upregulated phosphorylation and acetylation levels of p65 nuclear factor κB (p65 NF-κB) and signal transducer and activator of transcription 3 (STAT3) in diabetic nephropathy were abrogated by Na2S4 in a sirtuin-1 (SIRT1)-dependent manner. In renal tubular epithelial cells, Na2S4 directly sulfhydrated SIRT1 at two conserved CXXC domains (Cys371/374; Cys395/398), then induced dephosphorylation and deacetylation of its targeted proteins including p65 NF-κB and STAT3, thereby reducing high glucose (HG)-caused oxidative stress, cell apoptosis, inflammation response and epithelial-to-mesenchymal transition (EMT) progression. Most importantly, inactivation of SIRT1 by a specific inhibitor EX-527, small interfering RNA (siRNA), a de-sulfhydration reagent dithiothreitol (DTT), or mutation of Cys371/374 and Cys395/398 sites at SIRT1 abolished the protective effects of Na2S4 on diabetic kidney insulting. These results reveal that polysulfides may attenuate diabetic renal lesions via inactivation of p65 NF-κB and STAT3 phosphorylation/acetylation through sulfhydrating SIRT1.

13.
Thromb Res ; 198: 72-78, 2020 Nov 28.
Artigo em Inglês | MEDLINE | ID: mdl-33290885

RESUMO

INTRODUCTION: Thrombotic thrombocytopenic purpura (TTP) requires prompt initiation of therapeutic plasma exchange (TPE) to avoid significant morbidity and mortality. ADAMTS13 activity testing defines TTP, however, at most institutions this is a send-out test and therapy is often initiated prior to measurement availability. We describe our experience looking at absolute immature platelet counts (A-IPC) in patients suspected with TTP at presentation and in response to therapy. MATERIALS AND METHODS: Forty-eight patients treated for suspected TTP with A-IPC measure on admission and during hospitalization met inclusion criteria. Of these patients, sixteen had new-onset TTP (ADAMTS13 < 10%), ten were relapsing patients (first diagnosis prior to study period), and 22 were classified as non-TTP (ADAMTS13 ≥ 10%). RESULTS: Patients with ADAMTS13 deficiency (TTP) had A-IPC different from those without deficiency. A-IPC of 1-2 × 109/L at presentation had high sensitivity and specificity with a negative predictive value of 95.5 to 100%. Two-to-three-fold increases in A-IPC from count prior to TPE initiation was limited to ADAMTS13 deficient patients who was the group responding to therapy. Increases were higher in patients with new disease onset compared to relapsing patients (p = 0.018). Likewise, relapsing patients' A-IPC appeared dependent upon platelet count at time of relapse. A-IPC predicted and correlated with ADAMTS13 deficiency in new-onset TTP (p = 0.0002). CONCLUSIONS: Only patients with A-IPC-fold increases responded to TPE with platelet count normalization. Our results represent a proof of concept that A-IPC measurements can supplement ADAMTS13 testing and determine response to TPE. Future studies are needed to establish ways to apply these findings in the setting of suspected TTP.

14.
Nano Lett ; 2020 Dec 02.
Artigo em Inglês | MEDLINE | ID: mdl-33264014

RESUMO

Multiferroic tunnel junctions (MFTJs) have aroused significant interest due to their functional properties useful for nonvolatile memory devices. So far, however, all of the existing MFTJs have been based on perovskite-oxide heterostructures limited by a relatively high resistance-area (RA) product unfavorable for practical applications. Here, using first-principles calculations, we explore spin-dependent transport properties of van der Waals (vdW) MFTJs which consist of two-dimensional (2D) ferromagnetic FenGeTe2 (n = 3, 4, 5) electrodes and 2D ferroelectric In2Se3 barrier layers. We demonstrate that such FemGeTe2/In2Se3/FenGeTe2 (m, n = 3, 4, 5; m ≠ n) MFTJs exhibit multiple nonvolatile resistance states associated with different polarization orientation of the ferroelectric In2Se3 layer and magnetization alignment of the two ferromagnetic FenGeTe2 layers. We find a remarkably low RA product (less than 1 Ω·µm2) which makes the proposed vdW MFTJs superior to the conventional MFTJs in terms of their promise for nonvolatile memory applications.

15.
Cell Cycle ; : 1-12, 2020 Dec 03.
Artigo em Inglês | MEDLINE | ID: mdl-33269647

RESUMO

Store-operated Ca2+ entry (SOCE) plays an important role in regulating Ca2+ influx, which participates in tumor cell survival and motility. We aim to elucidate the role of SOCE in the behavior of C6 glioma cells. Lentiviral vector inserted with the Orai1-targeting shRNA was used to inhibit SOCE in C6 glioma cells. The down-regulation of Orai1 was confirmed by western blot. The ability of shOrai1 or SOCE inhibitor (SKF96365) in regulating SOCE inhibition was evaluated by measuring Ca2+ concentration. Additionally, its effect on cell behavior was assessed using methyl thiazolyl tetrazolium (MTT) assay, wound healing assay, transwell assay, and adhesion assay. Focal adhesions were visualized by immunofluorescence assay. Further, the expression of proline-rich tyrosine kinase 2 (Pyk2) and phosphorylated Pyk2 (p-Pyk2) was analyzed using western blot. Both, SKF96365 treatment and the Orai1 down-regulation inhibited SOCE by perturbing Ca2+ influx. The inhibitory effects of shOrai1 on C6 cell proliferation, migration, and invasion were similar to that of SKF96365. Moreover, Orai1 inhibition enhanced C6 cell adhesion by increasing the size of focal adhesion plaques. The down-regulation of Pyk2 was observed in both SKF96365-treated and Orai1-silenced C6 cells. Additionally, Orai1 inhibition blocked AKT/mTOR, NFAT, and NF-κB pathways. The silencing of Orai1 inhibited the C6 glioma cell migration, invasion and contributed to focal adhesion.

16.
Science ; 370(6522)2020 Dec 11.
Artigo em Inglês | MEDLINE | ID: mdl-33303584

RESUMO

Embryo polarization is critical for mouse development; however, neither the regulatory clock nor the molecular trigger that it activates is known. Here, we show that the embryo polarization clock reflects the onset of zygotic genome activation, and we identify three factors required to trigger polarization. Advancing the timing of transcription factor AP-2 gamma (Tfap2c) and TEA domain transcription factor 4 (Tead4) expression in the presence of activated Ras homolog family member A (RhoA) induces precocious polarization as well as subsequent cell fate specification and morphogenesis. Tfap2c and Tead4 induce expression of actin regulators that control the recruitment of apical proteins on the membrane, whereas RhoA regulates their lateral mobility, allowing the emergence of the apical domain. Thus, Tfap2c, Tead4, and RhoA are regulators for the onset of polarization and cell fate segregation in the mouse.

17.
Cell ; 183(6): 1467-1478, 2020 Dec 10.
Artigo em Inglês | MEDLINE | ID: mdl-33306953

RESUMO

Early embryogenesis is a conserved and self-organized process. In the mammalian embryo, the potential for self-organization is manifested in its extraordinary developmental plasticity, allowing a correctly patterned embryo to arise despite experimental perturbation. The underlying mechanisms enabling such regulative development have long been a topic of study. In this Review, we summarize our current understanding of the self-organizing principles behind the regulative nature of the early mammalian embryo. We argue that geometrical constraints, feedback between mechanical and biochemical factors, and cellular heterogeneity are all required to ensure the developmental plasticity of mammalian embryo development.

18.
Phytochem Anal ; 2020 Dec 16.
Artigo em Inglês | MEDLINE | ID: mdl-33331092

RESUMO

INTRODUCTION: The structural annotation of target relies on high-resolution mass spectrometry (HRMS) information resulting in dubious identities in most cases. The accurate annotation of isomeric structures is still challenging to be confirmed with significant bottleneck. OBJECTIVE: This study focused on the improvement of structural annotation of candidate structures via four pairs of isomeric flavanone-7-O-diglucosides and their basic flavanone aglycones commonly detected in citrus products. METHOD: An integrated liquid chromatography coupled with high-resolution mass spectrometry (LC-HRMS) approach merging retention time, accurate mass, tandem mass spectrometry (MS/MS) information (diagnostic ions), ion ratio at selected collision energy was established successfully. RESULTS: Feasibility of this approach was validated confidently in biological samples with relative standard deviation (RSD) of ion ratio range from 3.91 to 12.28%. Differences of fragmentation patterns of citrus flavanones were illustrated reasonably. MS/MS fragments of (S)-hesperetin and (S)-isosakuranetin were complicated and showed typical radical ion [1,2 A - H]•- (m/z 164) in negative ESI mode due to the methoxyl group on B-ring, which showed huge difference with (R)-hesperetin and (R)-isosakuranetin. CONCLUSION: This study integrated multiple levels to boost the confidence of structural annotation relied on LC-HRMS, and provided important values in practice for precise identification of citrus flavanones in biological matrices.

19.
BMC Public Health ; 20(1): 1707, 2020 Nov 16.
Artigo em Inglês | MEDLINE | ID: mdl-33198699

RESUMO

BACKGROUND: Despite worldwide calls for precautionary measures to combat COVID-19, the public's preventive intention still varies significantly among different regions. Exploring the influencing factors of the public's preventive intention is very important to curtail the spread of COVID-19. Previous studies have found that fear can effectively improve the public's preventive intention, but they ignore the impact of differences in cultural values. The present study examines the combined effect of fear and collectivism on the public's preventive intention towards COVID-19 through the analysis of social media big data. METHODS: The Sina microblog posts of 108,914 active users from Chinese mainland 31 provinces were downloaded. The data was retrieved from January 11 to February 21, 2020. Afterwards, we conducted a province-level analysis of the contents of downloaded posts. Three lexicons were applied to automatically recognise the scores of fear, collectivism, and preventive intention of 31 provinces. After that, a multiple regression model was established to examine the combined effect of fear and collectivism on the public's preventive intention towards COVID-19. The simple slope test and the Johnson-Neyman technique were used to test the interaction of fear and collectivism on preventive intention. RESULTS: The study reveals that: (a) both fear and collectivism can positively predict people's preventive intention and (b) there is an interaction of fear and collectivism on people's preventive intention, where fear and collectivism reduce each other's positive influence on people's preventive intention. CONCLUSION: The promotion of fear on people's preventive intention may be limited and conditional, and values of collectivism can well compensate for the promotion of fear on preventive intention. These results provide scientific inspiration on how to enhance the public's preventive intention towards COVID-19 effectively.


Assuntos
Infecções por Coronavirus/prevenção & controle , Infecções por Coronavirus/psicologia , Medo/psicologia , Intenção , Pandemias/prevenção & controle , Pneumonia Viral/prevenção & controle , Pneumonia Viral/psicologia , Valores Sociais , Big Data , China/epidemiologia , Infecções por Coronavirus/epidemiologia , Humanos , Pneumonia Viral/epidemiologia , Mídias Sociais
20.
Sci Total Environ ; : 143532, 2020 Nov 16.
Artigo em Inglês | MEDLINE | ID: mdl-33250260

RESUMO

Terrestrial evapotranspiration (ETa) reflects the complex interactions of climate, vegetation, soil and terrain and is a critical component in water and energy cycles. However, the manner in which climate change and vegetation greening influence ETa remains poorly understood, especially in alpine regions. Drawing on the Global Land Evaporation Amsterdam Model (GLEAM) ETa data, the interannual variability of ETa and its ties to precipitation (P), potential evaporation (ETp) and vegetation (NDVI) were analysed. The Budyko framework was implemented over the period of 1982 to 2015 to quantify the response of ETa to climate change's direct (P and ETp) and indirect (NDVI) impacts. The ETa, P, ETp and NDVI all showed significant increasing trends from 1981 to 2015 with rates of 1.52 mm yr-1, 3.18 mm yr-1, 0.89 mm yr-1 and 4.0 × 10-4 yr-1, respectively. At the regional level, the positive contribution of increases in P and NDVI offset the negative contribution of ETp to the change in ETa (∆ETa). The positive ∆ETa between 1982 and 2001 was strongly linked with the concomitant increase in NDVI. Increases in vegetation contributing to a positive ∆ETa differed among landscape types: for shrub, meadow and steppe they occurred during both periods, for alpine vegetation between 1982 and 2001, and for desert between 2002 and 2015. Climate change directly contributed to a rise in ETa, with P as the dominant factor affecting forested lands during both periods, and alpine vegetation between 2002 and 2015. Moreover, ETp was a dominant factor for the desert between 1982 and 2001, where the variation of P was not significant. The contributions of factors having an impact on ∆ETa are modulated by both the sensitivity of impact factors acting on ETa as well as the magnitudes of factor changes. The greening of vegetation can influence ETa by increasing vegetation transpiration and rainfall interception in forest, brush and meadow landscapes. These findings can help in developing a better understanding of the interaction of ecosystems and hydrology in alpine regions.

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