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1.
Sci Total Environ ; 804: 150054, 2022 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-34509839

RESUMO

The deep-sea mussel Gigantidas platifrons is a representative species that relies on nutrition provided by chemoautotrophic endosymbiotic bacteria to survive in both hydrothermal vent and methane seep environments. However, vent and seep habitats have distinct geochemical features, with vents being more harsh than seeps because of abundant toxic chemical substances, particularly hydrogen sulfide (H2S). Until now, the adaptive strategies of G. platifrons in a heterogeneous environment and their sulfide detoxification mechanisms are still unclear. Herein, we conducted 16S rDNA sequencing and metatranscriptome sequencing of G. platifrons collected from a methane seep at Formosa Ridge in the South China Sea and a hydrothermal vent at Iheya North Knoll in the Mid-Okinawa Trough to provide a model for understanding environmental adaption and sulfide detoxification mechanisms, and a three-day laboratory controlled Na2S stress experiment to test the transcriptomic responses under sulfide stress. The results revealed the active detoxification of sulfide in G. platifrons gills. First, epibiotic Campylobacterota bacteria were more abundant in vent mussels and contributed to environmental adaptation by active oxidation of extracellular H2S. Notably, a key sulfide-oxidizing gene, sulfide:quinone oxidoreductase (sqr), derived from the methanotrophic endosymbiont, was significantly upregulated in vent mussels, indicating the oxidization of intracellular sulfide by the endosymbiont. In addition, transcriptomic comparison further suggested that genes involved in oxidative phosphorylation and mitochondrial sulfide oxidization pathway played important roles in the sulfide tolerance of the host mussels. Moreover, transcriptomic analysis of Na2S stressed mussels confirmed the upregulation of oxidative phosphorylation and sulfide oxidization genes in response to sulfide exposure. Overall, this study provided a systematic transcriptional analysis of both the active bacterial community members and the host mussels, suggesting that the epibionts, endosymbionts, and mussel host collaborated on sulfide detoxification from extracellular to intracellular space to adapt to harsh H2S-rich environments.


Assuntos
Sulfeto de Hidrogênio , Fontes Hidrotermais , Mytilidae , Animais , Bactérias , Simbiose
2.
Comput Biol Med ; 139: 105000, 2021 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-34741905

RESUMO

Diabetic retinopathy (DR), as an important complication of diabetes, is the primary cause of blindness in adults. Automatic DR detection poses a challenge which is crucial for early DR screening. Currently, the vast majority of DR is diagnosed through fundus images, where the microaneurysm (MA) has been widely used as the most distinguishable marker. Research works on automatic DR detection have traditionally utilized manually designed operators, while a few recent researchers have explored deep learning techniques for this topic. But due to issues such as the extremely small size of microaneurysms, low resolution of fundus pictures, and insufficient imaging depth, the DR detection problem is quite challenging and remains unsolved. To address these issues, this research proposes a new deep learning model (Magnified Adaptive Feature Pyramid Network, MAFP-Net) for DR detection, which conducts super-resolution on low quality fundus images and integrates an improved feature pyramid structure while utilizing a standard two-stage detection network as the backbone. Our proposed detection model needs no pre-segmented patches to train the CNN network. When tested on the E-ophtha-MA dataset, the sensitivity value of our method reached as high as 83.5% at false positives per image (FPI) of 8 and the F1 value achieved 0.676, exceeding all those of the state-of-the-art algorithms as well as the human performance of experienced physicians. Similar results were achieved on another public dataset of IDRiD.

3.
Opt Express ; 29(21): 33456-33466, 2021 Oct 11.
Artigo em Inglês | MEDLINE | ID: mdl-34809157

RESUMO

Strong absorption of the full spectrum of sunlight at high temperatures is desired for photothermal devices and thermophotovoltaics. Here, we experimentally demonstrate a thin-film broadband absorber consisting of a vanadium nitride (VN) film and a SiO2 anti-reflective layer. Owing to the intrinsic high loss of VN, the fabricated absorber exhibits high absorption over 90% in the wide range of 400-1360 nm. To further enhance the near-infrared absorption, we also propose a metamaterial absorber by depositing patterned VN square patches on the thin-film absorber. An average absorption of 90.4% over the range of 400-2500 nm is achieved due to the excitation of broad electric dipole resonance. Both thin-film and metamaterial absorbers are demonstrated to possess excellent incident angle tolerances (up to 60°) and superior thermal stability at 800 ℃. The proposed refractory VN absorbers may be potentially used for solar energy harvesting, thermal emission, and photodetection.

4.
Theranostics ; 11(19): 9358-9375, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34646375

RESUMO

Rationale: Atherosclerosis plaque rupture (PR) is the pathological basis and chief culprit of most acute cardiovascular events and death. Given the complex and important role of macrophage apoptosis and autophagy in affecting plaque stability, an important unanswered question include is whether, and how, immunity-related GTPase family M protein (IRGM) and its mouse orthologue IRGM1 affect macrophage survival and atherosclerotic plaque stability. Methods: To investigate whether serum IRGM of ST-segment elevation myocardial infarction (STEMI) patients is related to plaque morphology, we divided 85 STEMI patients into those with and without plaque rupture (PR and non-PR, respectively) based on OCT image analysis, and quantified the patients' serum IRGM levels. Next, we engineered Irgm1 deficient mice (Irgm1 +/-) and chimera mice with Irgm1 deficiency in the bone marrow on an ApoE -/- background, which were then fed a high-fat diet for 16 weeks. Pathological staining was used to detect necrotic plaque cores, ratios of neutral lipids and cholesterol crystal, as well as collagen fiber contents in these mice to characterize plaque stability. In addition, immunofluorescence, immunohistochemical staining and western blot were used to detect the apoptosis of macrophages in the plaques. In vitro, THP-1 and RAW264.7 cells were stimulated with ox-LDL to mimic the in vivo environment, and IRGM/IRGM1 expression were modified by specific siRNA (knockdown) or IRGM plasmid (knocked-in). The effect of IRGM/Irgm1 on autophagy and apoptosis of macrophages induced by ox-LDL was then evaluated. In addition, we introduced inhibitors of the JNK/p38/ERK signaling pathway to verify the specific mechanism by which Irgm1 regulates RAW264.7 cell apoptosis. Results: The serum IRGM levels of PR patients is significantly higher than that of non-PR patients and healthy volunteers, which may be an effective predictor of PR. On a high-fat diet, Irgm1-deficient mice exhibit reduced necrotic plaque cores, as well as neutral lipid and cholesterol crystal ratios, with increased collagen fiber content. Additionally, macrophage apoptosis is inhibited in the plaques of Irgm1-deficient mice. In vitro, IRGM/Irgm1 deficiency rapidly inhibits ox-LDL-induced macrophage autophagy while inhibiting ox-LDL-induced macrophage apoptosis in late stages. Additionally, IRGM/Irgm1 deficiency suppresses reactive oxygen species (ROS) production in macrophages, while removal of ROS effectively inhibits macrophage apoptosis induced by IRGM overexpression. We further show that Irgm1 can affect macrophage apoptosis by regulating JNK/p38/ERK phosphorylation in the MAPK signaling pathway. Conclusions: Serum IRGM may be related to the process of PR in STEMI patients, and IRGM/Irgm1 deficiency increases plaque stability. In addition, IRGM/Irgm1 deficiency suppresses macrophage apoptosis by inhibiting ROS generation and MAPK signaling transduction. Cumulatively, these results suggest that targeting IRGM may represent a new treatment strategy for the prevention and treatment of acute cardiovascular deaths caused by PR.

5.
Sci Rep ; 11(1): 19883, 2021 Oct 06.
Artigo em Inglês | MEDLINE | ID: mdl-34615940

RESUMO

To investigate the mechanism of 25 hydroxyvitamin D (25(OH)D) deficiency in children with biliary atresia (BA) and its effect on liver fibrosis. The serum vitamin D and 25(OH)D, and expression of 25 hydroxylase (CYP2R1 and CYP27A1) in the liver of BA patients were detected and compared with those in the control group. We investigated the effect of differential expression of CYP2R1 in hepatocytes on the expression of genes related to liver fibrosis in primary hepatic stellate cells (HSCs) of BA and animal models of cholestasis. The ratio of 25(OH)D/vitamin D in the BA group was significantly lower than that in the control group. The mRNA and protein expression of CYP2R1 and CYP27A1 in liver tissue of the BA group was significantly lower than that in the control group. Exogenous active vitamin D (calcitriol) inhibited the proliferation and migration of primary HSCs isolated from BA patients, and reduced the expression of fibrosis-related genes in vitro. Downregulation of expression of CYP2R1 in hepatocytes increased expression of transforming growth factor (TGF)-ß1, collagen (Col)-1α1 and tissue inhibitor of metalloproteinase (TIMP)-1, and decreased the expression of matrix metalloproteinase (MMP)-2 in cocultured primary HSCs of BA. Upregulation of expression of CYP2R1 in mice with bile duct ligation significantly increased the level of 25(OH)D, decreased the expression of TGF-ß1, Col-1α1 and TIMP-1, and increased the expression of MMP-2. Children with BA have impaired vitamin D activation due to CYP2R1 deficiency. The dysactivation of vitamin D can promote the proliferation and activation of HSCs and participate in the development of hepatic fibrosis in BA.

6.
Nanoscale Res Lett ; 16(1): 157, 2021 Oct 19.
Artigo em Inglês | MEDLINE | ID: mdl-34665335

RESUMO

We demonstrate terahertz dielectric metasurfaces with anisotropic multipoles within the framework of the generalized Huygens principle, in which the interference among these multipoles achieves giant phase shift with broadened bandwidth and high transmission coefficients. More importantly, owing to the anisotropic design, various phase delays between π/2 and 3π/2 are obtained, which convert the incident linearly polarized terahertz wave into right/left-handed circularly polarized light, elliptically polarized light and cross-polarized light. Both simulation and experimental results verify complete terahertz polarization control with the ellipticity ranging from 1 to - 1, which paves a way for polarization-related applications of terahertz meta-devices.

7.
Org Lett ; 23(21): 8229-8234, 2021 Nov 05.
Artigo em Inglês | MEDLINE | ID: mdl-34623158

RESUMO

An iridium-catalyzed redox-neutral C-2 and C-3 dual C-H functionalization of indoles with nitrones has been developed, furnishing a range of 7H-indolo[2,3-c]quinolines with high efficiency and regioselectivity under mild reaction conditions. Notably, sequential multiple C-H bond cleavage and C-C bond formation constitute the key events of this process, in which nitrone serves as a building block and an oxidant. Distinct from the previous methods toward 7H-indolo[2,3-c]quinolines, this newly developed reaction features readily available substrates, operational simplicity, broad scope, good to high efficiency, and excellent regioselectivity.

8.
Am J Hum Genet ; 108(10): 1891-1906, 2021 10 07.
Artigo em Inglês | MEDLINE | ID: mdl-34551312

RESUMO

The success of personalized genomic medicine depends on our ability to assess the pathogenicity of rare human variants, including the important class of missense variation. There are many challenges in training accurate computational systems, e.g., in finding the balance between quantity, quality, and bias in the variant sets used as training examples and avoiding predictive features that can accentuate the effects of bias. Here, we describe VARITY, which judiciously exploits a larger reservoir of training examples with uncertain accuracy and representativity. To limit circularity and bias, VARITY excludes features informed by variant annotation and protein identity. To provide a rationale for each prediction, we quantified the contribution of features and feature combinations to the pathogenicity inference of each variant. VARITY outperformed all previous computational methods evaluated, identifying at least 10% more pathogenic variants at thresholds achieving high (90% precision) stringency.


Assuntos
Algoritmos , Biologia Computacional/normas , Doença/etiologia , Mutação de Sentido Incorreto , Predisposição Genética para Doença , Humanos , Fenótipo , Medicina de Precisão , Software
9.
Am J Hum Genet ; 108(7): 1283-1300, 2021 07 01.
Artigo em Inglês | MEDLINE | ID: mdl-34214447

RESUMO

Most rare clinical missense variants cannot currently be classified as pathogenic or benign. Deficiency in human 5,10-methylenetetrahydrofolate reductase (MTHFR), the most common inherited disorder of folate metabolism, is caused primarily by rare missense variants. Further complicating variant interpretation, variant impacts often depend on environment. An important example of this phenomenon is the MTHFR variant p.Ala222Val (c.665C>T), which is carried by half of all humans and has a phenotypic impact that depends on dietary folate. Here we describe the results of 98,336 variant functional-impact assays, covering nearly all possible MTHFR amino acid substitutions in four folinate environments, each in the presence and absence of p.Ala222Val. The resulting atlas of MTHFR variant effects reveals many complex dependencies on both folinate and p.Ala222Val. MTHFR atlas scores can distinguish pathogenic from benign variants and, among individuals with severe MTHFR deficiency, correlate with age of disease onset. Providing a powerful tool for understanding structure-function relationships, the atlas suggests a role for a disordered loop in retaining cofactor at the active site and identifies variants that enable escape of inhibition by S-adenosylmethionine. Thus, a model based on eight MTHFR variant effect maps illustrates how shifting landscapes of environment- and genetic-background-dependent missense variation can inform our clinical, structural, and functional understanding of MTHFR deficiency.


Assuntos
Metilenotetra-Hidrofolato Redutase (NADPH2)/genética , Mutação de Sentido Incorreto , Substituição de Aminoácidos , Análise Mutacional de DNA , Diploide , Biblioteca Gênica , Genótipo , Humanos , Metilenotetra-Hidrofolato Redutase (NADPH2)/deficiência , Metilenotetra-Hidrofolato Redutase (NADPH2)/fisiologia , Saccharomyces cerevisiae/genética
10.
Front Pediatr ; 9: 625451, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34079779

RESUMO

Objectives: Biliary atresia (BA) is a rare neonatal liver disease of which the early diagnosis remains a challenge for clinicians. Our center has established a nomogram diagnostic model based on clinical characteristics and liver function characteristics. We aim to develop and validate a nomogram that includes additional ultrasound and finds hepatobiliary abnormality with better BA early screening performance. Methods: In this single-center, retrospective cohort analysis, 1,001 neonatal obstructive jaundice (NOJ) patients between 2012 and 2015 were enrolled. Multivariable analysis was used to identify clinical characteristics, laboratory liver function characteristics, and ultrasonic features that may early screen BA. A nomogram was developed to predict the probability of BA using multiple logistic regression analysis. This nomogram was subsequently validated using another cohort of 501 NOJ patients between 2015 and 2017. Calibration curve analysis and decision curve analyses were performed to evaluate and interpret the nomogram's clinical benefits. Results: Gender, direct bilirubin (DB), alkaline phosphatase (ALP), gamma-glutamyl transpeptidase (GGT), fasting gallbladder visibility, fasting gallbladder filling, and common bile duct visibility were found to have profound statistical significance between the BA and non-BA groups (P < 0.05). The significant features were used to build the nomogram. The area under the receiver operating characteristic (ROC) curve (AUC) value of the novel nomogram (0.87) was superior to those of the former nomogram (0.83) and GGT alone (0.81) in the prediction of BA. The calibration curve revealed a close resemblance between the predicted and actual BA probabilities. Also, the net benefit from the decision curve analysis (DCA) of the nomogram (0.54) was superior to those of the former nomogram (0.49) and GGT alone (0.45) at 80% of threshold possibility. Conclusions: The nomogram has demonstrated better performance for BA screening by including additional information of the US finding, holding a promising future as a non-invasive method for BA patients.

11.
Plant Dis ; 2021 Jun 23.
Artigo em Inglês | MEDLINE | ID: mdl-34161123

RESUMO

Polygonatum odoratum (Mill.) Druce is used in traditional Chinese medicine and also consumed as a vegetable. In July of 2020, a root rot was observed on P. odoratum in a commercial field located in Benxi city (41º23'32" N, 124º04'27" E), Liaoning province of China. About 35% diseased plants in the field exhibited poor vigor, were stunted, and had yellow or brown leaves. Affected plants wilted and died. Roots of the plants were poorly developed, had brown lesions, and later rotted. To determine the causal agent, symptomatic roots with typical lesions were cut into small pieces, surface sterilized in 2% sodium hypochlorite (NaOCl) for 3 min, rinsed three times in sterile water, and plated onto PDA medium. After 5 days of incubation at 26°C, whitish-pink to red colonies growing from the root samples were observed and transferred to carnation leaf agar (CLA). Ten single conidia isolates obtained from the colonies on CLA were incubated at 26°C for 10 days. Abundant macroconidia were formed in sporodochia on CLA. Macroconidia were falcate, slender, distinctively curved in the bottom half of the apical cell, had 3 to 5 septa, and 33.1 - 46.3 × 5.0 - 7.2 µm (n=50). Chlamydospores formed in chains or single, measuring 13.8 to 14.5 µm in diameter. Microconidia were not observed on CLA. Morphologically, the isolates were identified as Fusarium acuminatum (Leslie and Summerell, 2006). To confirm the species identity, the partial translation elongation factor 1 alpha (TEF1-α) gene and rDNA internal transcribed spacer (ITS) region of isolate YZ5-2 were amplified and sequenced (O'Donnell et al. 2015; White et al.1990). BLASTn analysis of both TEF sequence (MW423623) and ITS sequence (MW423626), revealed 100% (696/692 bp) and 99.64% (563/602 bp) sequence identity with F. acuminatum LC546967 and MF509746, respectively. Pathogenicity tests were carried out in the greenhouse. A conidial suspension (2 × 106 conidia per ml) of the isolate YZ5-2 was prepared from 7-day-old cultures grown in potato dextrose broth (PDB) o n a shaker (140 rpm) at 26±1°C. Five 12-liter pots were filled with sterilized field soil and each pot was drenched with 300ml of conidial suspension. Five control pots with sterilized field soil and 300 ml PDB were also included. Roots of 20 healthy P. odoratum plants were surface disinfected in 2% NaOCl for 3 min, and rinsed with sterilized water. Prior to planting, 2-3 pinholes (1.5× 1.0 mm) were made using a toothpick on the root surface of each plant, and they were then planted in each pot (2 plants per pot). All ten pots were maintained in a greenhouse at 22-26°C for 40 days. Plants grown in the pots inoculated with the conidial suspension were stunted, had yellowed leaves and were wilted. The roots of the affected plants were rotted. Disease symptoms were similar to those observed in field. Non-inoculated control plants had no symptoms. F. acuminatum was reisolated from inoculated plants and was identical to the original isolate. The experiment was repeated twice with similar results. To our knowledge, this is the first report of root rot of P. odoratum caused by F. acuminatum in China. The disease has since been observed on P. odoratum in fields in Liaoyang and Qingyuan city in Liaoning Province of China, and it has become an important threat to P. odoratum production in China.

12.
Anal Methods ; 13(22): 2459-2465, 2021 06 14.
Artigo em Inglês | MEDLINE | ID: mdl-34028478

RESUMO

Chemiluminescence (CL) is a dominant technology in clinical diagnosis. In order to meet the increasing demand for the sensitive and simultaneous detection of chemiluminescence from multiple samples, the development of multiplex analysis on a single chip is highly desired. However, most chemiluminescence detection systems for multiple samples are still simple lens-based optical imaging systems, and a compromise must always be made between a large aperture (required by the weak chemiluminescence) and a large field of view (required by the size of the sample array). In this paper, we report a fiber bundle-based chemiluminescence detection system for the simultaneous and efficient detection of multiple chemiluminescent samples. In this system, one side of the fiber bundle is directly coupled to the optically active surface of a charge-coupled device (CCD), while the other end is divided into many sub-bundles that are aligned above the samples in a chemiluminescence array to collect their chemiluminescence. Taking advantage of the large numerical aperture and high transmittance of optical fibers, this system shows about a 50 times increase in chemiluminescence collection efficiency over the lens-based imaging system. Moreover, it shows no vignetting effect that is inevitable in a lens-based imaging system with a large field of view. This work provides a promising method for multiple sample chemiluminescence detection, and should find application in bioassays.


Assuntos
Luminescência , Medições Luminescentes , Bioensaio , Diagnóstico por Imagem , Fibras Ópticas
13.
Pediatr Surg Int ; 37(8): 1089-1097, 2021 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-34013444

RESUMO

OBJECTIVE: Biliary atresia (BA) is a neonatal liver disease and requires Kasai portoenterostomy. Many patients develop postoperative cholangitis, resulting in a poor prognosis. The preventive strategy of antibiotics is empirical and lacks a standard regimen. We aimed to analyze the effect of different durations of prophylactic intravenous antibiotics against post-Kasai cholangitis. STUDY DESIGN: A single-center, open-labeled, randomized clinical trial was performed from June 2016 to August 2017. One hundred and eighty BA patients were recruited and randomized into a short-term (n = 90) and a long-term (n = 90) treatment group, and prophylactic intravenous antibiotics were used for 7 versus 14 days, respectively. The primary outcome was the overall cholangitis incidence within 6-months post-Kasai portoenterostomy. The secondary outcomes included cholangitis incidence within 1 and 3 months post-Kasai portoenterostomy, the onset and average episodes of cholangitis, jaundice clearance rate, native liver survival rate, and adverse events within 6-months post-Kasai portoenterostomy. RESULTS: The cholangitis incidence within 6-months post-Kasai in the short-term group was similar to the long-term group (62% vs. 70%, p = 0.27) with intention-to-treat and pre-protocol analysis. There was no significant difference in jaundice clearance rate or native liver survival rate between the two groups. However, the percentage of early onset (61% vs. 38%, p = 0.02) and average episodes (2.4 ± 0.2 vs. 1.8 ± 0.1 episodes, p = 0.01) of cholangitis were lower in the long-term group. CONCLUSION: Long-term intravenous antibiotics can be replaced by the short-term regimen in the general protection against post-Kasai cholangitis.


Assuntos
Antibioticoprofilaxia/métodos , Atresia Biliar/tratamento farmacológico , Colangite/prevenção & controle , Administração Intravenosa , Atresia Biliar/epidemiologia , Colangite/epidemiologia , Colangite/etiologia , Feminino , Humanos , Incidência , Lactente , Recém-Nascido , Icterícia/etiologia , Masculino , Portoenterostomia Hepática/métodos , Período Pós-Operatório
14.
BMC Musculoskelet Disord ; 22(1): 425, 2021 May 07.
Artigo em Inglês | MEDLINE | ID: mdl-33962594

RESUMO

BACKGROUND: We aimed to determine the efficacy and safety of multiple doses of intravenous tranexamic acid (IV-TXA) on perioperative blood loss in patients with rheumatoid arthritis (RA) who had undergone primary unilateral total knee arthroplasty (TKA). METHODS: For this single-center, single-blind randomized controlled clinical trial, 10 male and 87 female participants with RA, aged 50-75 years, who underwent unilateral primary TKA were recruited. The patients received one dose of 1 g IV-TXA 10 min before skin incision, followed by articular injection of 1.5 g tranexamic acid after cavity suture during the surgery. The patients were randomly assigned (1:1) into two groups and received an additional single dose of IV-TXA (1 g) for 3 h (group A) or three doses of IV-TXA (1 g) for 3, 6, and 12 h (group B) postoperatively. Primary outcomes were total blood loss (TBL), hidden blood loss (HBL), and maximum hemoglobin (Hb) level decrease. Secondary outcomes were transfusion rate and D-dimer levels. All parameters were measured postoperatively during inpatient hospital stay. RESULTS: The mean TBL, HBL, and maximum Hb level decrease in group B (506.1 ± 227.0 mL, 471.6 ± 224.0 mL, and 17.5 ± 7.7 g/L, respectively) were significantly lower than those in group A (608.8 ± 244.8 mL, P = 0.035; 574.0 ± 242.3 mL, P = 0.033; and 23.42 ± 9.2 g/L, P = 0.001, respectively). No episode of transfusion occurred. The D-dimer level was lower in group B than in group A on postoperative day 1 (P <  0.001), and the incidence of thromboembolic events was similar between the groups (P > 0.05). CONCLUSION: In patients with RA, three doses of postoperative IV-TXA further facilitated HBL and Hb level decrease without increasing the incidence of adverse events in a short period after TKA. TRIAL REGISTRATION: The trial was registered in the Chinese Clinical Trial Registry ( ChiCTR1900025013 ).


Assuntos
Antifibrinolíticos , Artrite Reumatoide , Artroplastia do Joelho , Ácido Tranexâmico , Administração Intravenosa , Idoso , Antifibrinolíticos/efeitos adversos , Artrite Reumatoide/diagnóstico , Artrite Reumatoide/tratamento farmacológico , Artrite Reumatoide/cirurgia , Artroplastia do Joelho/efeitos adversos , Perda Sanguínea Cirúrgica/prevenção & controle , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Método Simples-Cego , Ácido Tranexâmico/efeitos adversos
15.
Org Lett ; 23(8): 2895-2899, 2021 04 16.
Artigo em Inglês | MEDLINE | ID: mdl-33783223

RESUMO

A visible-light photoredox-catalyzed reductive α-aminomethyl carboxylation of styrenes with sodium glycinates and CO2 has been developed to synthesize a series of α,α-disubstituted γ-amino acids and γ-lactams with high efficiency and regioselectivity. Notably, CO2 released from the decarboxylation step can be reused for the subsequent carboxylation. Distinct from the previous reactions with the same type of substrates leading to simple decarboxylation and olefin hydroalkylation, this process involves additional CO2 sequestration, thus leading to olefin α-aminomethyl carboxylation. These findings not only provide new access to α,α-disubstituted γ-amino acids and γ-lactams but also serve as a proof of concept for CO2 reutilization in decarboxylation reactions.


Assuntos
Aminoácidos/química , Dióxido de Carbono/química , Lactamas/química , Estirenos/química , Alcenos/química , Ácidos Carboxílicos/química , Catálise , Estrutura Molecular , Sódio/química
16.
Cell Death Dis ; 12(1): 88, 2021 01 18.
Artigo em Inglês | MEDLINE | ID: mdl-33462182

RESUMO

Inducing autophagy and inhibiting apoptosis may provide a therapeutic treatment for atherosclerosis (AS). For the treatment of progressive AS, arsenic trioxide (ATO) has been used to coat vascular stents. However, the effect of ATO on autophagy of macrophages is still unknown. Therefore, the aims of this study were to characterize the effects and the mechanism of actions of ATO on autophagy in macrophages. Our results showed that ATO-induced activation of autophagy was an earlier event than ATO-induced inhibition of the expression of apoptosis markers in macrophages and foam cells. Nuclear transcription factor EB (TFEB) prevents atherosclerosis by activating macrophage autophagy and promoting lysosomal biogenesis. Here, we report that ATO triggered the nuclear translocation of TFEB, which in turn promoted autophagy and autophagosome-lysosome fusion. Both the latter events were prevented by TFEB knockdown. Moreover, ATO decreased the p-AKT and p-mTOR in the PI3K/AKT/mTOR signaling pathway, thus inducing autophagy. Correspondingly, treatment with the autophagy inhibitor 3-methyladenine (3-MA) abolished the autophagy-inducing effects of ATO. Meanwhile, PI3K inhibitor (LY294002) and mTOR inhibitor (rapamycin) cooperated with ATO to induce autophagy. Furthermore, reactive oxygen species (ROS) were generated in macrophages after treatment with ATO. The ROS scavenger N-acetyl-1-cysteine (NAC) abolished ATO-induced nuclear translocation of TFEB, as well as changes in key molecules of the AKT/mTOR signaling pathway and downstream autophagy. More importantly, ATO promoted autophagy in the aorta of ApoE-/- mice and reduced atherosclerotic lesions in early AS, which were reversed by 3-MA treatment. In summary, our data indicated that ATO promoted ROS induction, which resulted in nuclear translocation of TFEB and inhibition of the PI3K/AKT/mTOR pathway. These actions ultimately promoted macrophage autophagy and reduced atherosclerotic lesions at early stages. These findings may provide a new perspective for the clinical treatment of early-stage atherosclerosis and should be further studied.


Assuntos
Trióxido de Arsênio/farmacologia , Macrófagos/efeitos dos fármacos , Proteínas Proto-Oncogênicas c-akt/metabolismo , Espécies Reativas de Oxigênio/metabolismo , Serina-Treonina Quinases TOR/metabolismo , Animais , Apoptose/efeitos dos fármacos , Aterosclerose/tratamento farmacológico , Aterosclerose/patologia , Autofagia/efeitos dos fármacos , Núcleo Celular/metabolismo , Humanos , Macrófagos/metabolismo , Macrófagos/patologia , Masculino , Camundongos , Células RAW 264.7 , Transdução de Sinais/efeitos dos fármacos , Células THP-1 , Transfecção
17.
Curr Eye Res ; 46(8): 1171-1177, 2021 08.
Artigo em Inglês | MEDLINE | ID: mdl-33390025

RESUMO

PURPOSE: To investigate the change and recovery of choroid thickness after short-term application of 1% atropine gel and its influencing factors in 6-7-year-old children. MATERIALS AND METHODS: 71 right eyes of 71 children were enrolled and divided into myopia and control group. 1% atropine gel was administered twice a day for one week and then stopped. Spherical equivalent (SE), accommodative amplitude (AA), keratometry (K), axial length (AL), and choroidal thickness (CT) were obtained at baseline and 1st, 4th, and 8th weeks. CT was measured at subfovea and 1 mm, 2 mm, and 3 mm temporal, superior, nasal, and inferior from the fovea using spectral-domain optical coherence tomography. RESULTS: In both groups, all CTs increased following the change in SE, AA, and AL after administration of 1% atropine for one week. They gradually recovered to baseline levels seven weeks after withdrawal. The change (Δ) in CT at 3 mm superior from the fovea was significantly higher in the myopia group than in the control group. In both groups, ΔCT at subfovea had no significant correlation with SE, AA, and AL, both at baseline and one week. However, ΔCT at subfovea was negatively correlated with ΔAL in the control group. CONCLUSIONS: One-week application of 1% atropine gel may increase CT in 6-7-year-old Chinese children. Meanwhile, the recovery process after withdrawal lasts seven weeks. During the recovery process, the changes in structural parameters (AL, CT) and functional parameters (AA, SE) in both groups occurred synchronously. The SE, AA, and AL at baseline may not predict the extent of atropine's effect on CT.

18.
Physiol Plant ; 171(4): 714-727, 2021 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-33094482

RESUMO

Cation/H+ -exchanger (CHX) perform diverse functions in plants, including being a part of the protective mechanisms to cope with salt stress. GmCHX1 has been previously identified as the causal gene in a major salt-tolerance quantitative trait locus (QTL) in soybean, but little is known about another close paralog, GmCHX20a, found in the same QTL. In this study, GmCHX20a was characterized along with GmCHX1. The expression patterns of the two genes and the direction of Na+ flux directed by overexpression of these two transporters are different, suggesting that they are functionally distinct. The ectopic expression of GmCHX20a led to an increase in salt sensitivity and osmotic tolerance, which was consistent with its role in increasing Na+ uptake into the root. Although this seems counter-intuitive, it may in fact be part of the mechanism by which soybean could counter act the effects of osmotic stress, which is commonly manifested in the initial stage of salinity stress. On the other hand, GmCHX1 from salt-tolerant soybean was shown to protect plants via Na+ exclusion under salt stress. Taken together these results suggest that GmCHX20a and GmCHX1 might work complementally through a concerted effort to address both osmotic stress and ionic stress as a result of elevated salinity.


Assuntos
Tolerância ao Sal , Soja , Cátions , Membrana Celular , Proteínas de Plantas/genética , Salinidade , Estresse Salino , Tolerância ao Sal/genética , Soja/genética
19.
J Cell Physiol ; 236(3): 2058-2069, 2021 03.
Artigo em Inglês | MEDLINE | ID: mdl-32783191

RESUMO

The long noncoding RNA antisense noncoding RNA in the INK4 locus (ANRIL) plays a critical role in the development of atherosclerosis. However, the precise effect of ANRIL on endothelial dysfunction remains unclear. In this study, we investigated ANRIL expression in patients with coronary artery disease and elucidated the molecular mechanism underlying its effect. ANRIL expression was detected in the blood plasma of 111 patients. We analysed the correlation between ANRIL and endothelial dysfunction markers. We also examined the effect of ANRIL on the regulation of endothelial dysfunction. ANRIL levels were increased in patients with acute coronary syndrome. The expression of ANRIL is associated with the inflammatory cytokines monocyte chemoattractant protein-1 and interleukin-10, which are secreted in response to endothelial dysfunction. Knockdown of ANRIL significantly promoted cell proliferation and tubule formation and inhibited inflammatory activation and apoptosis of human umbilical vein endothelial cells (HUVEC). ANRIL-mediated inhibition of let-7b regulates HUVEC dysfunction by targeting the TGF-ßR1/Smad signalling pathway. This study highlights a new therapeutic strategy for preventing endothelial dysfunction associated with cardiovascular disease.


Assuntos
Células Endoteliais da Veia Umbilical Humana/metabolismo , Células Endoteliais da Veia Umbilical Humana/patologia , MicroRNAs/metabolismo , RNA Longo não Codificante/metabolismo , Receptor do Fator de Crescimento Transformador beta Tipo I/metabolismo , Transdução de Sinais , Síndrome Coronariana Aguda/genética , Sequência de Bases , Biomarcadores/metabolismo , Humanos , Inflamação/genética , Inflamação/patologia , Modelos Biológicos , RNA Longo não Codificante/genética , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Transdução de Sinais/genética , Proteínas Smad/metabolismo , Regulação para Cima/genética
20.
Orthop Surg ; 13(1): 126-133, 2021 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-33295133

RESUMO

OBJECTIVE: To identify the efficacy and safety of multiple doses of intravenous tranexamic acid (IV-TXA) following primary total knee arthroplasty (TKA) with a tourniquet. METHODS: This is a single-blind randomized controlled study that recruited osteoarthritis patients who had undergone primary unilateral TKA from May 2019 to May 2020 at our medical center. A total of 300 patients were randomly divided into three groups to receive: one dose (1 g) of IV-TXA before skin incision combined with one dose (1.5 g) of intra-articular tranexamic acid(IA-TXA) followed by a single dose of IV-TXA (1 g) for 3 h (group A); two doses of IV-TXA (1 g) for 3 and 6 h (group B); or three doses of IV-TXA (1 g) for 3, 6, and 12 h (group C) postoperatively. TKA with a tourniquet was performed by the same surgical team. The primary outcomes were total blood cell loss (TBL), hidden blood loss (HBL), maximum hemoglobin (Hb) drop, and transfusion rate. Secondary outcomes were levels of C-reactive protein (CRP) and D-dimer, and the incidence of postoperative complications. One-way analysis of variance, subgroup analysis, and multivariate correlation analysis were used to calculate the differences among the three groups. RESULTS: The study included 56 male and 244 female patients aged 60-80 years. The mean TBL, the mean HBL, and the maximum Hb drop in group C (471.2 ± 190.6 mL, 428.4 ± 190.3 mL, and 21.2 ± 3.8 g/L, respectively) were significantly lower than those in groups B (563.4 ± 224.6 mL, P = 0.030; 519.9 ± 226.4 mL, P = 0.033; and 23.2 ± 4.1 g/L, P = 0.001, respectively), and A (651.6 ± 254.1 mL, P < 0.001; 607.1 ± 254.3 mL, P < 0.001; and 25.1 ± 4.3 g/L, P < 0.001, respectively). No transfusions were required. The postoperative acute inflammatory reaction was less problematic for patients in Group C, and the incidence of thromboembolic events was similar among the groups (P > 0.05). In addition, there were positive correlations between the HBL and the tourniquet inflation time (r = 0.844, P < 0.001). Similarly, the level of CRP on POD1 (r = 0.393, P < 0.001) and POD3 (r = 0.149, P = 0.010), and the level of D-dimer on POD1 (r = 0.382, P < 0.001) were positively correlated with the HBL. CONCLUSION: Three doses of postoperative IV-TXA decreased blood loss and diminished the postoperative inflammatory and fibrinolytic response more than a single dose or two doses in elderly patients following TKA without increasing the incidence of adverse events.

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