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1.
J Sci Food Agric ; 102(1): 350-359, 2022 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-34143449

RESUMO

BACKGROUND: The contribution of bacteria to fermented tea is not clear and the associated research is relatively limited. To reveal the role of microorganisms in fermented tea processing, the microbial community and metabolites of Fuzhuan brick tea (FBT), a Chinese traditional fermented tea, were revealed via high-throughput sequencing and liquid chromatography-mass spectrometry (LC-MS). RESULTS: In FBT, bacterial communities had a higher abundance and diversity, Lactococcus and Bacillus were the main bacteria, and Eurotium was the predominant fungus. The predictive metabolic function indicated the pathways of cellular growth, environmental information, genetics and material metabolism of bacterial communities were abundant, whereas the fungal community predictive metabolic function was almost saprotroph. Using LC-MS, 1143 and 536 metabolites were defined in positive and negative ion mode, respectively. There were essential correlations between bacterial populations and metabolites, such that Bacillus was correlated significantly with 44 metabolites (P < 0.05) and Enterococcus was significantly associated with 15 metabolites (P < 0.05). Some of the main active components were significantly correlated with the bacteria, such as Enterococcus, Lactococcus and Carnobacterium. CONCLUSION: Not only Eurotium, but also the bacteria were involved in the changes of metabolomics profile in fermented FBT. The present study assists in providing new insights into metabolomics profile generation in fermented tea. The present research lays a foundation for controlling the FBT fermentation by artificial inoculation to improve quality. © 2021 Society of Chemical Industry.


Assuntos
Bactérias/metabolismo , Camellia sinensis/microbiologia , Bactérias/química , Bactérias/classificação , Bactérias/genética , Camellia sinensis/metabolismo , Cromatografia Líquida , Fermentação , Fungos/química , Fungos/classificação , Fungos/genética , Fungos/metabolismo , Sequenciamento de Nucleotídeos em Larga Escala , Espectrometria de Massas , Metabolômica , Chá/química
2.
Front Immunol ; 12: 750969, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34858407

RESUMO

The COVID-19 is an infectious disease caused by SARS-CoV-2 infection. A large number of clinical studies found high-level expression of pro-inflammatory cytokines in patients infected with SARS-CoV-2, which fuels the rapid development of the disease. However, the specific molecular mechanism is still unclear. In this study, we found that SARS-CoV-2 Nsp5 can induce the expression of cytokines IL-1ß, IL-6, TNF-α, and IL-2 in Calu-3 and THP1 cells. Further research found that Nsp5 enhances cytokine expression through activating the NF-κB signaling pathway. Subsequently, we investigated the upstream effectors of the NF-κB signal pathway on Nsp5 overexpression and discovered that Nsp5 increases the protein level of MAVS. Moreover, Nsp5 can promote the SUMOylation of MAVS to increase its stability and lead to increasing levels of MAVS protein, finally triggering activation of NF-κB signaling. The knockdown of MAVS and the inhibitor of SUMOylation treatment can attenuate Nsp5-mediated NF-κB activation and cytokine induction. We identified a novel role of SARS-CoV-2 Nsp5 to enhance cytokine production by activating the NF-κB signaling pathway.

3.
Nanomaterials (Basel) ; 11(12)2021 Dec 06.
Artigo em Inglês | MEDLINE | ID: mdl-34947661

RESUMO

The application of moth-eye nanostructured polymer film on the flexible polyethylene terephthalate (PET) substrate is an effective way to improve its antireflection (AR) performance. However, many factors affect the AR properties of the moth-eye structure in the actual manufacturing process. Moreover, the antireflection research based on PET substrate has been relatively lacking compared with the silicon substrate. In this paper, we simulate and analyze the AR performance of the moth-eye nanostructured polymer film on PET substrate by using the finite-difference time-domain method within the wavelength range of 400-1100 nm. Simulation results show that the parabola-shaped moth-eye structure (PSMS) can suppress the Fresnel reflection significantly. Moreover, the height and filling ratios are the dominant factors that affect the AR performance of PSMS. Additionally, the base diameter, residual layer thickness, and the refractive index of PSMS polymer film also affect the reflectivity of PET slightly. As a result, an optimal PSMS with base diameter of 400 nm, height of 300 nm, and the hexagonal close-packed arrangement is appropriate, and the solar-weighted reflectivity of PET can be suppressed to 0.21%, which shows a prominent advantage over the bare PET (≈6%). Therefore, this research has promising potential for improving the optical performance of optoelectronic devices by using nanostructured polymer materials.

4.
PLoS One ; 16(12): e0261971, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34965271

RESUMO

MicroRNAs (miRNAs) are important molecules that mediate virus-host interactions, mainly by regulating gene expression via gene silencing. Here, we demonstrated that HIV-1 infection upregulated miR-210-5p in HIV-1-inoculated cell lines and in the serum of HIV-1-infected individuals. Luciferase reporter assays and western blotting confirmed that a target protein of miR-210-5p, TGIF2, is regulated by HIV-1 infection. Furthermore, HIV-1 Vpr protein induced miR-210-5p expression. The use of a miR-210-5p inhibitor and TGIF2 overexpression showed that Vpr upregulated miR-210-5p and thereby downregulated TGIF2, which might be one of the mechanisms used by Vpr to induce G2 arrest. Moreover, we identified a transcription factor, NF-κB p50, which upregulated miR-210-5p in response to Vpr protein. In conclusion, we identified a mechanism whereby miR-210-5p, which is induced upon HIV-1 infection, targets TGIF2. This pathway was initiated by Vpr protein activating NF-κB p50, which promoted G2 arrest. These alterations orchestrated by miRNA provide new evidence on how HIV-1 interacts with its host during infection and increase our understanding of the mechanism by which Vpr regulates the cell cycle.

5.
Small ; : e2104301, 2021 Nov 25.
Artigo em Inglês | MEDLINE | ID: mdl-34825484

RESUMO

The fabrication of discrete nanostructures with both plasmonic circular dichroism (PCD) and chiral features is still a challenge. Here, gold nanoarrows (GNAs) with both chiroptical responses and chiral morphologies are achieved by using L-selenocystine (L-SeCys2 ) as a chiral inducer. While L-SeCys2 generates GNAs with a weak PCD signal, the irradiated L-SeCys2 (irr-L-SeCys2 ) leads to GNAs with featured helical grooves (HeliGNAs) accompanying with a strong PCD signal. It is revealed that when L-SeCys2 is photo-irradiated, the emergence of selenyl radicals plays an important role in the formation of HeliGNAs and enhancement of the chiroptical signal. In comparison with L-SeCys2 and the other kinds of sulfur-containing amino acids, the formation mechanism of helical grooves on the surface of GNAs is proposed. Both HeliGNAs and GNAs are used to discriminate amino acids by utilizing surface enhanced Raman scattering (SERS) effect. In the presence of either GNAs or HeliGNAs as the substrate, Fmoc-L-Phe shows more significant SERS than Fmoc-D-Phe. This study may advance the design of discrete plasmonic nanomaterials with both chiral morphology and potential applications in discrimination of chiral molecules.

6.
Mediators Inflamm ; 2021: 9059601, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34776789

RESUMO

The inflammatory storm in the early stage and immunosuppression in the late stage are responsible for the high mortality rates and multiple organ dysfunction in sepsis. In recent years, studies have found that the body's cholinergic system can spontaneously and dynamically regulate inflammation and immunity in sepsis according to the needs of the body. Firstly, the vagus nerve senses and regulates local or systemic inflammation by means of the Cholinergic Anti-inflammatory Pathway (CAP) and activation of α7-nicotinic acetylcholine receptors (α7nAChRs); thus, α7nAChRs play important roles for the central nervous system (CNS) to modulate peripheral inflammation; secondly, the activation of muscarinic acetylcholine receptors 1 (M1AChRs) in the forebrain can affect the neurons of the Medullary Visceral Zone (MVZ), the core of CAP, to regulate systemic inflammation and immunity. Based on the critical role of these two cholinergic receptor systems in sepsis, it is necessary to collect and analyze the related findings in recent years to provide ideas for further research studies and clinical applications. By consulting the related literature, we draw some conclusions: MVZ is the primary center for the nervous system to regulate inflammation and immunity. It coordinates not only the sympathetic system and vagus system but also the autonomic nervous system and neuroendocrine system to regulate inflammation and immunity; α7nAChRs are widely expressed in immune cells, neurons, and muscle cells; the activation of α7nAChRs can suppress local and systemic inflammation; the expression of α7nAChRs represents the acute or chronic inflammatory state to a certain extent; M1AChRs are mainly expressed in the advanced centers of the brain and regulate systemic inflammation; neuroinflammation of the MVZ, hypothalamus, and forebrain induced by sepsis not only leads to their dysfunctions but also underlies the regulatory dysfunction on systemic inflammation and immunity. Correcting the neuroinflammation of these regulatory centers and adjusting the function of α7nAChRs and M1AChRs may be two key strategies for the treatment of sepsis in the future.

7.
Dig Dis Sci ; 2021 Nov 19.
Artigo em Inglês | MEDLINE | ID: mdl-34797444

RESUMO

BACKGROUND: Slow transit constipation (STC) is caused by intestinal peristalsis dysfunction and is closely associated with disturbance of the intestinal microecological balance. Bacillus subtilis plays a positive role in the treatment of STC, but its mechanism needs to be further explored. AIMS: The purpose of the present study was to explore the effects and mechanism of B. subtilis on the pathophysiology of STC. METHODS: A STC mouse model was established with compound diphenoxylate, following which B. subtilis was used to treat STC. The effects and possible mechanism of B. subtilis on STC were investigated by assessing intestinal motility, histology of the colon, release of 5-HT in enterochromaffin cells (ECs) and the TGR5/TRPA1 pathway. Moreover, LC-MS targeted metabolomics was used to analyze the regulation of Bacillus subtilis on bile acid metabolisms in STC mice. RESULTS: Bacillus subtilis significantly increased 24 h defecations, fecal moisture and intestinal transport rate of STC mice, improved pathological damage of the colon and showed protective effects on the intestinal tract. The release of 5-HT from ECs and the bile acid receptor TGR5/TRPA1 pathway were significantly increased in STC mice treated with B. subtilis. In addition, the metabolomics results showed that the bile acid contents of STC mice were significantly decreased, and B. subtilis could increase the bile acid composition and content of STC mice. CONCLUSION: Bacillus subtilis regulates intestinal peristalsis of STC by promoting the release of 5-HT from ECs through bile acid metabolism and its receptor TGR5 pathway and plays a positive role in the treatment of STC.

8.
Am J Cardiol ; 2021 Nov 10.
Artigo em Inglês | MEDLINE | ID: mdl-34774286

RESUMO

There remains a lack of prognosis models for patients with chronic thromboembolic pulmonary hypertension (CTEPH). This study aims to develop a nomogram predicting 3-, 5-, and 7-year survival in patients with CTEPH and verify the prognostic model. Patients with CTEPH diagnosed in Fuwai Hospital were enrolled consecutively between May 2013 and May 2019. Among them, 70% were randomly split into a training set and the other 30% as a validation set for external validation. Cox proportional hazards model was used to identify the potential survival-related factors which were candidate variables for the establishment of nomogram and the final model was internally validated by the bootstrap method. A total of 350 patients were included in the final analysis and the median follow-up period of the whole cohort was 51.2 months. Multivariate analysis of Cox proportional hazards regression showed body mass index, mean right atrial pressure, N-terminal pro-brain natriuretic peptide (per 500 ng/ml increase in concentration), presence of anemia, and main treatment choice were the independent risk factors of mortality. The nomogram demonstrated good discrimination with the corrected C-index of 0.82 in the training set, and the C-index of 0.80 (95% CI: 0.70 to 0.91) in the external validation set. The calibration plots also showed a good agreement between predicted and actual survival in both training and validation sets. In conclusion, we developed an easy-to-use nomogram with good apparent performance using 5 readily available variables, which may help physicians to identify CTEPH patients at high risk for poor prognosis and implement medical interventions.

9.
Dev Neurobiol ; 2021 Nov 14.
Artigo em Inglês | MEDLINE | ID: mdl-34779143

RESUMO

Interferon regulatory factor-7 (IRF7) is an essential regulator of both innate and adaptive immunity. It is also expressed in the otic vesicle of zebrafish embryos. However, any role for irf7 in hair cell development was uncharacterized. Does it work as a potential deaf gene to regulate hair cell development? We used whole-mount in situ hybridization (WISH) assay and morpholino-mediated gene knockdown method to investigate the role of irf7 in the development of otic vesicle hair cells during zebrafish embryogenesis. We performed RNA sequencing to gain a detailed insight into the molecules/genes which are altered upon downregulation of irf7. Compared to the wild-type siblings, knockdown of irf7 resulted in severe developmental retardation in zebrafish embryos as well as loss of neuromasts and damage to hair cells at an early stage (within 3 days post fertilization). Co-injection of zebrafish irf7 mRNA could partially rescued the defects of the morphants. atp1b2b mRNA injection can also partially rescue the phenotype induced by irf7 gene deficiency. Loss of hair cells in irf7-morphants does not result from cell apoptosis. Gene expression profiles show that, compared to wild-type, knockdown of irf7 can lead to 2,053 and 2,678 genes being upregulated and downregulated, respectively. Among them, 18 genes were annotated to HC development or posterior lateral line (PLL) development. All results suggest irf7 plays an essential role in hair cell development in zebrafish, indicating that irf7 may be a member of deafness gene family. This article is protected by copyright. All rights reserved.

10.
Front Oncol ; 11: 754975, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34660324

RESUMO

Background: Whether muscle strength and physical performance should be components of sarcopenia remains controversial. This study evaluated the skeletal muscle index derived from computed tomography images at the 12th thoracic vertebra level (T12 SMI), handgrip strength, performance status, and their combination for predicting overall survival in patients with advanced non-small cell lung cancer. Methods: Chest computed tomography, handgrip strength measurement, and bioelectrical impedance analysis were performed. Sarcopenia was defined based on the T12 SMI alone or the T12 SMI, handgrip, and/or physical performance (i.e. Asian Working Group for Sarcopenia [AWGS]-defined sarcopenia or severe sarcopenia). Results: Overall, 639 participants were included; 488 (76.4%) died. At baseline, 160 (25.0%), 141 (22.1%), and 42 (6.6%) patients had computed tomography-defined sarcopenia, AWGS-defined sarcopenia, and AWGS-defined severe sarcopenia, respectively. Chest computed tomography-defined sarcopenia (hazard ratio [HR], 2.00; 95% confidence interval [CI], 1.65-2.43), AWGS-defined sarcopenia (HR, 2.00; 95% CI, 1.59-2.49), and AWGS-defined severe sarcopenia (HR, 3.01; 95% CI, 2.21-4.09) were more strongly associated with poor prognosis than a performance status score ≥2 (HR, 1.37; 95% CI, 1.10-1.73). Conclusions: Adding handgrip strength and the performance status score to chest computed tomography-defined sarcopenia improved its prognostic ability. Oncological sarcopenia research should focus on muscle mass, strength, and function.

11.
Environ Sci Technol ; 55(21): 14720-14731, 2021 11 02.
Artigo em Inglês | MEDLINE | ID: mdl-34636548

RESUMO

Quantitative structure-activity relationship (QSAR) modeling can be used to predict the toxicity of ionic liquids (ILs), but most QSAR models have been constructed by arbitrarily selecting one machine learning method and ignored the overall interactions between ILs and biological systems, such as proteins. In order to obtain more reliable and interpretable QSAR models and reveal the related molecular mechanism, we performed a systematic analysis of acetylcholinesterase (AChE) inhibition by 153 ILs using machine learning and molecular modeling. Our results showed that more reliable and stable QSAR models (R2 > 0.85 for both cross-validation and external validation) were obtained by combining the results from multiple machine learning approaches. In addition, molecular docking results revealed that the cations and organic anions of ILs bound to specific amino acid residues of AChE through noncovalent interactions such as π interactions and hydrogen bonds. The calculation results of binding free energy showed that an electrostatic interaction (ΔEele < -285 kJ/mol) was the main driving force for the binding of ILs to AChE. The overall findings from this investigation demonstrate that a systematic approach is much more convincing. Future research in this direction will help design the next generation of biosafe ILs.


Assuntos
Acetilcolinesterase , Líquidos Iônicos , Acetilcolinesterase/metabolismo , Ânions , Aprendizado de Máquina , Simulação de Acoplamento Molecular , Relação Quantitativa Estrutura-Atividade
12.
J Biomed Opt ; 26(10)2021 10.
Artigo em Inglês | MEDLINE | ID: mdl-34655182

RESUMO

SIGNIFICANCE: Fourier ptychography microscopy (FPM) is a computational optical imaging technology that employs angularly varying illuminations and a phase retrieval algorithm to achieve a wide field of view and high-resolution imaging simultaneously. In the FPM, LED position error will reduce the quality of the reconstructed high-resolution image. To correct the LED positions, current methods consider each of the LED positions as independent and use an optimization algorithm to get each of the positions. When the positional misalignment is large or the search position falls into a local optimal value, the current methods may lack stability and accuracy. AIM: We improve the model of the LED position and propose an accurate and stable two-step correction scheme (tcFPM) to calibrate the LED position error. APPROACH: The improved LED positions model combines the overall offset, which represents the relative deviation of the LED array and the optical axis, with the slight deviation of each LED's independent position. In the tcFPM, the overall offset of the LED array is corrected at first, which obtains an approximate value of the overall offset of the LED array. Then the position of each LED is precisely adjusted, which obtains the slight offset of each LED. RESULTS: This LED position error model is more in line with the actual situation. The simulation and experimental results show that the method has high accuracy in correcting the LED position. Furthermore, the reconstruction process of tcFPM is more stable and significantly improves the quality of the reconstruction results, which is compared with some LED position error correction methods. CONCLUSIONS: An LED position error correction technology is proposed, which has a stable iterative process and improves the reconstruction accuracy of complex amplitude.


Assuntos
Algoritmos , Microscopia , Calibragem , Análise de Fourier , Iluminação
13.
Cancer Cell Int ; 21(1): 556, 2021 Oct 24.
Artigo em Inglês | MEDLINE | ID: mdl-34689774

RESUMO

BACKGROUND: Brain metastasis is an important cause of increased mortality in patients with non-small cell lung cancer (NSCLC). In brain metastasis, the blood-brain barrier (BBB) is frequently impaired, forming blood-tumor barrier (BTB). The efficacy of chemotherapy is usually very poor. However, the characteristics of BTB and the impacts of BTB on chemotherapeutic drug delivery remain unclear. The present study investigated the structure of BTB, as well as the distribution of routine clinical chemotherapeutic drugs in both brain and peripheral tumors. METHODS: Bioluminescent image was used to monitor the tumor load after intracranial injection of lung cancer Lewis cells in mice. The permeability of BBB and BTB was measured by fluorescent tracers of evans blue and fluorescein sodium. Transmission electron microscopy (TEM), immunohistochemistry and immunofluorescence were performed to analyze structural differences between BBB and BTB. The concentrations of chemotherapeutic drugs (gemcitabine, paclitaxel and pemetrexed) in tissues were assayed by liquid chromatography with tandem mass spectrometry (LC-MS/MS). RESULTS: Brain metastases exhibited increased BTB permeability compared with normal BBB detected by fluorescence tracers. TEM showed abnormal blood vessels, damaged endothelial cells, thick basement membranes, impaired intercellular endothelial tight junctions, as well as increased fenestrae and pinocytotic vesicles in metastatic lesions. Immunohistochemistry and immunofluorescence revealed that astrocytes were distributed surrounded the blood vessels both in normal brain and the tumor border, but no astrocytes were found in the inner metastatic lesions. By LC-MS/MS analysis, gemcitabine showed higher permeability in brain metastases. CONCLUSIONS: Brain metastases of lung cancer disrupted the structure of BBB, and this disruption was heterogeneous. Chemotherapeutic drugs can cross the BTB of brain metastases of lung cancer but have difficulty crossing the normal BBB. Among the three commonly used chemotherapy drugs, gemcitabine has the highest distribution in brain metastases. The permeability of chemotherapeutic agents is related to their molecular weight and liposolubility.

14.
Artigo em Inglês | MEDLINE | ID: mdl-34705198

RESUMO

The long-term prognosis of patients with chronic thromboembolic pulmonary hypertension (CTEPH) receiving different treatments is deserved to be analyzed in modern era of CTEPH treatment. From 2013 to 2019, a total of 364 patients diagnosed with CTEPH were retrospectively included, 14 patients were lost during follow-up. Among 350 patients included in the final analysis: 123 underwent pulmonary endarterectomy (PEA), 121 received balloon pulmonary angioplasty (BPA), and 106 treated with targeted drug alone. The median period of follow-up was 51.2 months, the estimated survival at 1-, 3-, 5- and 7-year was 97.1%, 93.3%, 86.9%, and 82.0% for the whole cohort; 100%, 99.20%, 96.5% and 92.5% in PEA group; 98.4%, 97.4%, 95.3% and 89.3% in BPA group;92.5%, 81.9%, 70.1% and 66.8% in patients who received targeted drug alone. In comparing with targeted treatment along, results of multivariate Cox analysis after adjusting the confounders showed that receiving PEA decreased the risk of death by 83% (HR [hazard ratio] 0.17, 95% CI [Confidence interval] 0.07-0.44) and receiving BPA decreased the risk of death by 89% (HR 0.11, 95% CI 0.04-0.29). In conclusion, the estimated survival of CTEPH patients at 1-, 3-, 5- and 7-year was 97.1%, 93.3%, 86.9%, and 82.0% respectively. The intervention of revascularization, including PEA and BPA, were preferred than treating with targeted drug alone in the view of long-term prognosis of CTEPH.

15.
IEEE Trans Med Imaging ; PP2021 Oct 28.
Artigo em Inglês | MEDLINE | ID: mdl-34710042

RESUMO

Uniquely capable of simultaneous imaging of the hemoglobin concentration, blood oxygenation, and flow speed at the microvascular level in vivo, multi-parametric photoacoustic microscopy (PAM) has shown considerable impact in biomedicine. However, the multi-parametric PAM acquisition requires dense sampling and thus a high laser pulse repetition rate (up to MHz), which sets a strict limit on the applicable pulse energy due to safety considerations. A similar limitation is shared by high-speed PAM, which also uses lasers with high pulse repetition rates. To achieve high quantitative accuracy besides good structural visualization at low levels of laser fluence in PAM, we have developed a new, sparse coding-based two-step denoising technique. In the setting of intravital brain imaging, we demonstrated that this unsupervised learning approach enabled the reduction of the laser fluence in PAM by 5 times without compromise of the image quality (structural similarity index measure or SSIM: >0.92) and the quantitative accuracy (errors: <4.9%). Offering a significant relaxation in the requirement of PAM on laser fluence while maintaining the quality of structural imaging and accuracy of quantitative measurements, this sparse coding-based approach is expected to facilitate the application and clinical translation of multi-parametric PAM and high-speed PAM, which have a tight photon budget due to either safety considerations or laser source limitations.

16.
Small ; 17(42): e2103136, 2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-34523802

RESUMO

Powering device for miniaturized electronics is highly desired with well-maintained capacity and high-rate performance. Though Ni-Zn microbattery can meet the demand to some extent with intrinsic fast kinetic, it still suffers irreversible structure degradation due to the repeated lattice strain. Herein, a stable Ni-Zn microbattery with ultrahigh-rate performance is rationally constructed through in situ electrochemical approaches, including the reconstruction of nanoporous nickel and the introduction of epitaxial Zn(OH)2 nanophase. With the enhanced ionic adsorption effect, the superior reactivity of the superficial nickel-based nanostructure is well stabilized. Based on facile miniaturization and electrochemical techniques, the fabricated nickel microelectrode exhibits 63.8% capacity retention when the current density is 500 times folded, and the modified hydroxides contribute to the great stability of the porous structure (92% capacity retention after 10 000 cycles). Furthermore, when the constructed Ni-Zn microbattery is measured in a practical metric, excellent power density (320.17 mW cm-2 ) and stable fast-charging performance (over 90% capacity retention in 3500 cycles) are obtained. This surface reconstruction strategy for nanostructure provides a new direction for the optimization of electrode structure and enriches high-performance output units for integrated microelectronics.

17.
Thromb Res ; 207: 16-24, 2021 Sep 05.
Artigo em Inglês | MEDLINE | ID: mdl-34507265

RESUMO

AIMS/HYPOTHESIS: An association between obesity and deep vein thrombosis (DVT) has been revealed by observational studies, but it is not clear if the observed associations are causal, caused by confounding bias or reverse causation. METHODS: We performed a two-sample Mendelian Randomization (MR) study by obtaining exposure and outcome data from separate published studies. We utilized data from Genetic Investigation of Anthropometric Traits (GIANT, 339,224 participants) consortium and FinnGen project (FinnGen, 1785 DVT case and 84,462 control participants) to determine the causal effect of BMI on DVT. RESULTS: All three MR methods provided a positive association between BMI and DVT. Using IVW, we found evidence of causal relationships between BMI and DVT. BMI is positively associated with DVT (IVW odds ratio [OR] per SD increase in BMI = 1.67 [95% CI, 1.16-2.40]; P = 0.006). MR Egger and weighted median regression also showed directionally similar estimates (MR-Egger OR per SD increase in BMI, 2.50 [95% CI, 1.07-5.84], P = 0.034; weighted median OR per SD increase in BMI, 2.02 [95% CI, 1.10-3.71], P = 0.023). Both funnel plots and MR-Egger intercepts suggest no directional pleiotropic effects observed between BMI and DVT. CONCLUSIONS/INTERPRETATION: Our findings provide evidence of significant causal association between BMI and DVT in agreement with observational studies. Taking measures to reduce the proportion of obesity may help reduce the incidence of DVT.

18.
Pregnancy Hypertens ; 26: 17-23, 2021 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-34428710

RESUMO

AIMS: The aim of this study was to apply the Mendelian randomization (MR) design to explore the potential causal association between COVID-19 and the risk of hypertension disorders in pregnancy. METHODS: Our primary genetic instrument comprised 8 single-nucleotide polymorphisms (SNPs) associated with COVID-19 at genome-wide significance. Data on the associations between the SNPs and the risk of hypertension disorders in pregnancy were obtained from study based on a very large cohort of European population. The random-effects inverse-variance weighted method was conducted for the main analyses, with a complementary analysis of the weighted median and MR-Egger approaches. RESULTS: Using IVW, we found that genetically predicted COVID-19 was significantly positively associated with hypertension disorders in pregnancy, with an odds ratio (OR) of 1.111 [95% confidence interval (CI) 1.042-1.184; P = 0.001]. Weighted median regression also showed directionally similar estimates [OR 1.098 (95% CI, 1.013-1.190), P = 0.023]. Both funnel plots and MR-Egger intercepts suggest no directional pleiotropic effects observed. CONCLUSIONS: Our findings provide direct evidence that there is a shared genetic predisposition so that patients infected with COVID-19 may be causally associated with increased risk of hypertension disorders in pregnancy.

19.
J Alzheimers Dis ; 83(1): 423-433, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34334397

RESUMO

BACKGROUND: Histopathologic studies have demonstrated differential amyloid-ß (Aß) burden between cortical sulci and gyri in Alzheimer's disease (AD), with sulci having a greater Aß burden. OBJECTIVE: To characterize Aß deposition in the sulci and gyri of the cerebral cortex in vivo among subjects with normal cognition (NC), mild cognitive impairment (MCI), and AD, and to evaluate if these differences could improve discrimination between diagnostic groups. METHODS: T1-weighted 3T MR and florbetapir (amyloid) positron emission tomography (PET) data were obtained from the Alzheimer's Disease Neuroimaging Initiative (ADNI). T1 images were segmented and the cortex was separated into sulci/gyri based on pial surface curvature measurements. T1 images were registered to PET images and regional standardized uptake value ratios (SUVr) were calculated. A linear mixed effects model was used to analyze the relationship between clinical variables and amyloid PET SUVr measurements in the sulci/gyri. Receiver operating characteristic (ROC) analysis was performed to define amyloid positivity. Logistic models were used to evaluate predictive performance of clinical diagnosis using amyloid PET SUVr measurements in sulci/gyri. RESULTS: 719 subjects were included: 272 NC, 315 MCI, and 132 AD. Gyral and sulcal Aß increased with worsening cognition, however there was a greater increase in gyral Aß. Females had a greater gyral and sulcal Aß burden. Focusing on sulcal and gyral Aß did not improve predictive power for diagnostic groups. CONCLUSION: While there were significant differences in Aß deposition in cerebral sulci and gyri across the AD spectrum, these differences did not translate into improved prediction of diagnosis. Females were found to have greater gyral and sulcal Aß burden.

20.
IEEE Trans Med Imaging ; PP2021 Aug 13.
Artigo em Inglês | MEDLINE | ID: mdl-34388091

RESUMO

Photoacoustic microscopy (PAM) leverages the optical absorption contrast of blood hemoglobin for high-resolution, multi-parametric imaging of the microvasculature in vivo. However, to quantify the blood flow speed, dense spatial sampling is required to assess blood flow-induced loss of correlation of sequentially acquired A-line signals, resulting in increased laser pulse repetition rate and consequently optical fluence. To address this issue, we have developed a sparse modeling approach for blood flow quantification based on downsampled PAM data. Evaluation of its performance both in vitro and in vivo shows that this sparse modeling method can accurately recover the substantially downsampled data (up to 8 times) for correlation-based blood flow analysis, with a relative error of 12.7 ± 6.1 % across 10 datasets in vitro and 12.7 ± 12.1 % in vivo for data downsampled 8 times. Reconstruction with the proposed method is on par with recovery using compressive sensing, which exhibits an error of 12.0 ± 7.9 % in vitro and 33.86 ± 26.18 % in vivo for data downsampled 8 times. Both methods outperform bicubic interpolation, which shows an error of 15.95 ± 9.85 % in vitro and 110.7 ± 87.1 % in vivo for data downsampled 8 times.

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