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1.
J Hazard Mater ; 443(Pt A): 130151, 2023 02 05.
Artigo em Inglês | MEDLINE | ID: mdl-36270187

RESUMO

Pyrite-mediated arsenopyrite oxidation is an important process affecting arsenic (As) mobility. The iron sulfides-induced reactive oxidation species (ROS) can exert significant influence on As transformation. However, the impact of pyrite-arsenopyrite association on ROS production and its contribution to As transformation were rarely estimated. Here, ROS formation and the redox conversion of As during the interaction between pyrite and arsenopyrite as function of O2, pH and pyrite surface oxidation were investigated. Pyrite promoted arsenopyrite oxidation and As(III) oxidation due to heterogeneous electron transfer. The electron transfer from arsenopyrite facilitated O2 reduction on pyrite surface with increasing ROS formation. Hydroxyl radical (HO˙), superoxide (O2•)- and hydrogen peroxide (H2O2) were the main reactive species for As(III) oxidation. Iron (hydr)oxides produced from pyrite surface oxidation provided fast electron transfer channels for efficient O2 reduction as evidenced by electrochemical experiment, further verifying the promoted effect of surface-oxidized pyrite (SOP) on arsenopyrite dissolution. However, total As and As(V) obviously decreased during SOP-mediated arsenopyrite oxidation. Iron (hydr)oxides retained appreciable As through adsorption to limit its mobility, and decreased HO˙ production to inhibit As(III) oxidation via decomposing H2O2. This work furthers our understanding of arsenic transformation in the environment which has important implications for mitigating arsenic pollution.


Assuntos
Arsênio , Espécies Reativas de Oxigênio , Peróxido de Hidrogênio , Sulfetos , Ferro , Oxirredução , Óxidos
2.
Phytomedicine ; 108: 154514, 2022 Oct 28.
Artigo em Inglês | MEDLINE | ID: mdl-36334390

RESUMO

BACKGROUND: A wave of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Omicron variant rapidly resulted in a steep increase in the infected population and an overloaded healthcare system. Effective medications for Omicron are currently limited. The previous observational study supports the efficacy and safety of Reyanning (RYN) mixture in the treatment of coronavirus disease 2019 (COVID-19). PURPOSE: To evaluate the efficacy of RYN in asymptomatic and mildly infected patients with SARS-CoV-2 infection. STUDY DESIGN AND METHODS: This study was a prospective, open-label, randomized controlled trial. We consecutively recruited 2830 patients from Shanghai New International Expo Center mobile cabin hospital and randomized them in a 1:1 ratio to receive RYN plus standard care or receive standard care alone. The primary outcomes were the negative conversion of nucleic acid. Secondary outcomes included the hospital duration, new-onset symptoms, proportion of disease progression, and the viral load measured by the cycle threshold (Ct) value. RESULTS: A total of 1393 patients in the intervention group and 1407 patients in the control group completed the study. The negative conversion time of nucleic acid was significantly shortened in the intervention group (median: 6 d vs. 7 d, Hazard ratio: 0.768, 95CI %: 0.713-0.828, p < 0.0001). The negative conversion rate of nucleic acid was significantly higher in the intervention group (Day 3: 32.4% vs. 18.3%; Day7: 65.3% vs. 55.2%, p < 0.001). The hospitalization duration was significantly shortened in the intervention group (median: 8 d vs. 9 d, Hazard ratio: 0.759, 95% CI: 0.704-0.818, p < 0.0001). The proportion of new-onset fever (2.4% vs. 4.1%, p = 0.012), coughing (12.2% vs. 14.8%, p = 0.046), and expectoration (6.0% vs. 8.0%, p = 0.032) in the intervention group was significantly lower. RYN treatment increased Ct values and reduced the viral load. No disease progression and serious adverse events were reported during the study. CONCLUSION: RYN is a safe and effective treatment that can accelerate virus clearance and promote disease recovery in asymptomatic and mild Omicron infections.

3.
J Affect Disord ; 322: 2-8, 2022 Nov 05.
Artigo em Inglês | MEDLINE | ID: mdl-36343783

RESUMO

BACKGROUND: The study explored the differences in nightmare, insomnia, depression, anxiety, and cognitive deficits among adolescents and the chain mediating effects of insomnia, depression, and anxiety on the relationship between nightmares and cognitive deficits in adolescents. METHODS: An online survey was used to collect demographic data of 6014 adolescents and assess nightmare, insomnia, depression, anxiety, and cognitive deficits using the Chinese Version of Nightmare Distress Questionnaire, Insomnia Severity Index, Patient Health Questionnaire 9, Generalized Anxiety Disorder 7, and Perceived Deficits Questionnaire-Depression. Spearman correlation analysis and the SPSS function "PROCESS macro" were used for correlation and mediation analyses, respectively. RESULTS: Female adolescents, senior high school, and poor academic performance had higher nightmare, insomnia, and cognitive deficit scores; those living in the city had higher depression and anxiety scores. Cognitive deficits were positively correlated with nightmares, insomnia, depression, and anxiety. Further, insomnia, depression, and anxiety had a chain mediating effect between nightmares and cognitive deficits in adolescents. Nightmares indirectly affect cognition deficits by affecting insomnia and then depression and anxiety symptoms. LIMITATIONS: As this was a cross-sectional study, the causal relationship between the variables could not be determined. Moreover, reporting bias and volunteer bias might be present. CONCLUSIONS: These findings suggest that clinicians should identify adolescents with frequent nightmares early and provide timely treatment to minimize negative outcomes and possibly limit the chronicity of nightmare disorder. It is significant to maintain the physical and mental health development of adolescents to reduce the risk of insomnia, depression, anxiety, and cognitive deficits.

4.
Artigo em Inglês | MEDLINE | ID: mdl-36346499

RESUMO

PURPOSE: Cross-sequence magnetic resonance image (MRI) registration and segmentation are two essential steps in a variety of medical image analysis tasks. And have attracted considerable research interest. However, they remain challenging due to domain shifts between different sequences. This study is aiming at proposing a novel method via disentangled representations, latent shape image learning (LSIL), for cross-sequence image registration and segmentation. METHODS: Images from different sequences were firstly decomposed into a shared domain-invariant shape space and a domain-specific appearance space via an unsupervised image-to-image translation approach. A latent shape image learning model is then built on the disentangled shape representations to generate latent shape images. A series of experiments including cross-sequence image registration and segmentation were performed to qualitatively and quantitatively verify the validity of our method. Dice similarity coefficient (DSC) and 95th percentile Hausdorff distance (HD95) were adopted as our evaluation metrics. RESULTS: The performance of our method was evaluated based on 2 datasets total of 50 MRIs. The experimental results showed the superiority of the proposed framework over the state-of-the-art cross-sequence registration and segmentation approaches. The proposed method shows the mean DSCs of 0.711 and 0.867, respectively, in cross-sequence registration and segmentation. CONCLUSION: We proposed a novel method based on representation disentangling to solve the cross-sequence registration and segmentation problem. Experimental results prove the feasibility and generalization of the generated latent shape images. The proposed method demonstrates significant potential for use in clinical environments of missing sequences. The source code is available at https://github.com/wujiong-hub/LSIL .

5.
World J Pediatr ; 2022 Nov 17.
Artigo em Inglês | MEDLINE | ID: mdl-36385369

RESUMO

BACKGROUND: The impact of stressful life events (SLEs) in early childhood is often ignored. We aimed to examine longitudinal associations between SLEs and psychosocial and general health in preschool children. METHODS: Twelve SLEs occurring before the age of 24 months were assessed and categorized by frequency (no events, 1-2 SLEs, and > 2 SLEs) and overall tension (no events, low, and high) (n = 1431). Psychosocial and general health were measured three times at the age of 24, 36 and 45 months. The associations were examined by logistic regression models using generalized estimating equations to handle repeated measurements. RESULTS: Half (48.4%) of the families experienced SLEs, and 23.8% perceived high-tension SLEs before the children were aged 24 months. Gender differences were observed in the association between SLEs and psychosocial health. Compared to girls without SLEs, girls who experienced > 2 SLEs [OR = 3.31, 95% confidence interval (CI) 2.05-5.35] or high-tension SLEs (OR = 3.01, 95% CI 2.07-4.39) had higher odds of psychosocial problems from 24 to 45 months. The odds ratios in boys were 2.10 (95% CI 1.36-3.24) and 1.47 (95% CI 1.06-2.03), respectively. Moreover, only girls' risk of psychosocial problems increased after experiencing 1-2 SLEs (OR = 2.15, 95% CI 1.54-3.00) or low-tension SLEs (OR = 1.90, 95% CI 1.31-2.74). Regarding general health, children who experienced > 2 SLEs (OR = 1.96, 95% CI 1.21-3.18) and high-tension SLEs (OR = 1.60, 95% CI 1.12-2.28) had higher odds of poor general health from 24 to 45 months. CONCLUSIONS: The findings emphasized that young children's psychosocial and general health can be impacted by experiencing SLEs in early childhood. Attention and adequate support for families experiencing SLEs are needed to minimize the potential negative effect of SLEs on child health, particularly in girls.

6.
Artigo em Inglês | MEDLINE | ID: mdl-36394543

RESUMO

Li3VO4 (LVO) is considered as a novel alternative anode material for lithium-ion batteries (LIBs) due to its high capacity and good safety. However, the inferior electronic conductivity impedes its further application. Here, nanofibers (nLICVO/NC) with In/Ce co-doped Li3VO4 strengthened by nitrogen-modified carbon are prepared. Density functional theory calculations demonstrate that In/Ce co-doping can substantially reduce the LVO band gap and achieve orders of magnitude increase (from 2.79 × 10-4 to 1.38 × 10-2 S cm-1) in the electronic conductivity of LVO. Moreover, the carbon-based nanofibers incorporated with 5LICVO nanoparticles can not only buffer the structural strain but also form a good framework for electron transport. This 5LICVO/NC material delivers high reversible capacities of 386.3 and 277.9 mA h g-1 at 0.1 and 5 A g-1, respectively. Furthermore, high discharge capacities of 335 and 259.5 mA h g-1 can be retained after 1200 and 4000 cycles at 0.5 and 1.6 A g-1, respectively (with the corresponding capacity retention of 98.4 and 78.7%, respectively). When the 5LICVO/NC anode assembles with commercial LiNi1/3Co1/3Mn1/3O2 (NCM111) into a full cell, a high discharge capacity of 191.9 mA h g-1 can be retained after 600 cycles at 1 A g-1, implying an inspiring potential for practical application in high-efficiency LIBs.

7.
Front Public Health ; 10: 1015811, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36353283

RESUMO

Objective: To evaluate determinants of prolonged viral RNA shedding in hospitalized patients with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Omicron variant infection. Materials and methods: Hospitalized patients tested SARS-CoV-2 positive by nasopharyngeal real-time reverse transcriptase-polymerase chain reaction (RT-PCR) were included in the single-center, retrospective study. Patients were divided into 2 groups according to the timing of viral clearance (≤ 8 days, "early clearance" and ≥15 days, "late clearance"). Results: 4,084 patients were included in the study (1,023 late clearance, 3,061 early clearance), with median age of 50 years and a higher proportion (61.4%) of male. Univariate analyses showed that comorbidities (including hypertension, diabetes, and coronary heart disease), receiving vaccine, the number of vaccinations, cycle threshold (Ct) open reading frame 1ab (ORF 1ab), and nucleocapsid protein (N) gene values on admission were associated with late viral clearance. In the multivariable analysis, the number of vaccinations (P = 0.010) and Ct ORF 1ab gene (P < 0.001) values on admission were significantly associated with late viral clearance. Generalized Estimating Equations (GEE) analysis showed that the Ct value of ORF 1ab gene and N gene remained unchanged within 3 days, and showed progressively higher values with increasing days during late viral RNA clearance. Conclusion: The number of vaccinations and Ct values of ORF 1ab gene were independently associated with a prolonged SARS-CoV-2 RNA shedding.


Assuntos
COVID-19 , SARS-CoV-2 , Humanos , Masculino , Pessoa de Meia-Idade , SARS-CoV-2/genética , Eliminação de Partículas Virais , Reação em Cadeia da Polimerase Via Transcriptase Reversa , RNA Viral/análise , Estudos Retrospectivos , COVID-19/epidemiologia , China/epidemiologia
8.
Plant Physiol Biochem ; 193: 139-152, 2022 Dec 15.
Artigo em Inglês | MEDLINE | ID: mdl-36356545

RESUMO

High salinity and drought stresses often cause plants to produce ROS, including hydrogen peroxide (H2O2) and superoxide (O2-), which interfere with plant growth and affect crop yield. The transcription factors of the MYB family are involved in responses to biotic and abiotic stresses. Here, we isolated the R2R3-MYB transcription factor gene SlMYB50 and found that silencing of SlMYB50 increased resistance to PEG 6000, mannitol and salt. In addition, the resistance of transgenic tomatoes increased under high salt and drought stress. After stress treatment, the relative water content, chlorophyll content (critical for carbon fixation) and root vitality of the SlMYB50-RNAi lines were higher than those of the wild-type (WT). The opposite was true the water loss rate, relative conductivity, and MDA (as a sign of cell wall disruption). Under drought stress conditions, SlMYB50-silenced lines exhibited less H2O2 and less O2- accumulation, as well as higher CAT enzyme activity, than were exhibited by the WT. Notably, after stress treatment, the expression levels of chlorophyll-synthesis-related, flavonoid-synthesis-related, carotenoid-related, antioxidant-enzyme-related and ABA-biosynthesis-related genes were all upregulated in SlMYB50-silenced lines compared to those of WT. A dual-luciferase reporter system was used to verify that SlMYB50 could bind to the CHS1 promoter. In summary, this study identified essential roles for SlMYB50 in regulating drought and salt tolerance.


Assuntos
Secas , Lycopersicon esculentum , Lycopersicon esculentum/metabolismo , Regulação da Expressão Gênica de Plantas , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo , Peróxido de Hidrogênio/metabolismo , Plantas Geneticamente Modificadas/metabolismo , Estresse Salino/genética , Estresse Fisiológico/genética , Clorofila , Água/metabolismo
9.
Eur Radiol ; 2022 Nov 18.
Artigo em Inglês | MEDLINE | ID: mdl-36396791

RESUMO

OBJECTIVE: To investigate the utility of an automatic deep learning (DL) method for segmentation of T2 maps in patients with idiopathic inflammatory myopathy (IIM) against healthy controls, and also the association of quantitative T2 values in patients with laboratory and pulmonary findings. METHODS: Structural MRI and T2 mapping of bilateral thigh muscles from patients with IIM and healthy volunteers were segmented using dedicated software based on a pre-trained convolutional neural network. Incremental and federated learning were implemented for continuous adaptation and improvement. Muscle T2 values derived from DL segmentation were compared between patients and healthy controls, and T2 values of patients were further analyzed with serum muscle enzymes, and interstitial lung disease (ILD) which was diagnosed and graded based on chest HRCT. RESULTS: Overall, 64 patients (27 patients with dermatomyositis, 29 with polymyositis, and 8 with antisynthetase syndrome (ASS)) and 10 healthy controls were included. By using DL-based muscle segmentation, T2 values generated from T2 maps accurately differentiated patients from those of controls (p < 0.001) with a cutoff value of 36.4 ms (sensitivity 96.9%, and specificity 100%). In patients with IIM, muscle T2 values positively correlated with all the serum muscle enzymes (all p < 0.05). ILD score of patients with ASS was markedly higher than that of those without ASS (p = 0.011), while dissociation between the severity of muscular involvement and ILD was observed (p = 0.080). CONCLUSION: Automatic DL could be used to segment thigh muscles and help quantitatively assess muscular inflammation of IIM through T2 mapping. KEY POINTS: • Muscle T2 mapping automatically segmented by deep learning can differentiate IIM from healthy controls. • T2 value, an indicator of active muscle inflammation, positively correlates with serum muscle enzymes. • T2 mapping can detect muscle disease in patients with normal muscle enzyme levels.

10.
Sci Rep ; 12(1): 18844, 2022 Nov 07.
Artigo em Inglês | MEDLINE | ID: mdl-36344629

RESUMO

To observe the efficacy and safety of solifenacin and/or mirabegron as a medical expulsive therapy (MET) in patients with double-J stent-related overactive bladder (OAB) symptoms. A total of 219 patients with double-J stent-related OAB symptoms were prospectively randomized into two groups. One-hundred and nine cases in the combination group accepted mirabegron and solifenacin therapy and 110 cases as control only accepted solifenacin therapy. The lower urinary tract symptoms and overactive bladder questionnaire (OAB-q) health-related quality of life (HRQol) and symptom bother score between two groups were compared at the 1st, 2nd and 4th week ends. All of 219 patients were randomly assigned to two groups, of which 109 patients were included in the combination group and 110 in the solifenacin group. The incidences of LUTS, including urgency, frequent urination, and incontinence episodes, in the 2nd week (44.9% vs. 64.5%, P = 0.028; 48.6% vs. 62.7%, P = 0.036; and 40.4% vs. 56.4%, P = 0.018) and the 4th week (14.7% vs. 30.9%, P = 0.004; 16.5% vs. 33.6%, P = 0.003; and 11.9% vs. 26.4%, P = 0.007) after combination treatment were significantly lower than those in the solifenacin group. The incidence of drug-related adverse events in the solifenacin group was higher than that in the combination group, but there was no statistically significant difference (P > 0.05). In terms of secondary variables, the OAB-q HRQol score in the combination group was statistically superior in comparison with that in the solifenacin group between the second and fourth week (77.9 vs. 76.4, P = 0.020; and 87.9 vs. 85.6, P = 0.001). The OAB-q symptom bother score was higher in the solifenacin group than in the combination group (37.6 vs. 36.4, P = 0.016; and 26.2 vs. 24.8, P = 0.003). Combination therapy of solifenacin and mirabegron demonstrated significant improvements over solifenacin monotherapy in reducing OAB symptoms associated with double-J stents, and providing a higher quality of life without increasing bothersome adverse effects.


Assuntos
Succinato de Solifenacina , Bexiga Urinária Hiperativa , Humanos , Succinato de Solifenacina/efeitos adversos , Bexiga Urinária Hiperativa/tratamento farmacológico , Bexiga Urinária Hiperativa/diagnóstico , Estudos Prospectivos , Qualidade de Vida , Resultado do Tratamento , Quimioterapia Combinada , Acetanilidas/efeitos adversos , Stents , Antagonistas Muscarínicos/uso terapêutico
11.
Nutrients ; 14(21)2022 Oct 26.
Artigo em Inglês | MEDLINE | ID: mdl-36364768

RESUMO

Endothelial cells (ECs) line the inner surface of blood vessels and play a substantial role in vascular biology. Endothelial dysfunction (ED) is strongly correlated with the initiation and progression of many vascular diseases. Regulated cell death, such as ferroptosis, is one of the multiple mechanisms that lead to ED. Ferroptosis is an iron-dependent programmed cell death associated with various vascular diseases, such as cardiovascular, cerebrovascular, and pulmonary vascular diseases. This review summarized ferroptosis of ECs in vascular diseases and discussed potential therapeutic strategies for treating ferroptosis of ECs. In addition to lipid peroxidation inhibitors and iron chelators, a growing body of evidence showed that clinical drugs, natural products, and intervention of noncoding RNAs may also inhibit ferroptosis of ECs.


Assuntos
Ferroptose , Doenças Vasculares , Humanos , Células Endoteliais/metabolismo , Peroxidação de Lipídeos , Ferro/metabolismo , Doenças Vasculares/metabolismo
12.
Healthcare (Basel) ; 10(11)2022 Nov 18.
Artigo em Inglês | MEDLINE | ID: mdl-36421631

RESUMO

Effectively identifying high-risk patients with de novo hypertensive disorder of pregnancy (HDP) is required to enable timely intervention and to reduce adverse maternal and perinatal outcomes. Electronic medical record of pregnant women with de novo HDP were extracted from a birth cohort in Beijing, China. The adverse outcomes included maternal and fetal morbidities, mortality, or any other adverse complications. A multitude of machine learning statistical methods were employed to develop two prediction models, one for maternal complications and the other for perinatal deteriorations. The maternal model using the random forest algorithm produced an AUC of 0.984 (95% CI (0.978, 0.991)). The strongest predictors variables selected by the model were platelet count, fetal head/abdominal circumference ratio, and gestational age at the diagnosis of de novo HDP; The perinatal model using the boosted tree algorithm yielded an AUC of 0.925 (95% CI (0.907, 0.945]). The strongest predictor variables chosen were gestational age at the diagnosis of de novo HDP, fetal femur length, and fetal head/abdominal circumference ratio. These prediction models can help identify de novo HDP patients at increased risk of complications who might need intense maternal or perinatal care.

13.
Chem Sci ; 13(37): 11126-11131, 2022 Sep 28.
Artigo em Inglês | MEDLINE | ID: mdl-36320467

RESUMO

The separation of acetylene from ethylene is a crucial process in the petrochemical industry, because even traces of acetylene impurities can poison the catalysts of ethylene polymerization. Herein, we synthesize a new family of 3D porous aromatic frameworks (PAFs), non-functionalized PAF-28, carbene-functionalized PAF-28 (cPAF-28) and imidazolium-functionalized PAF-28 (iPAF-28), via Sonogashira coupling reactions. These PAFs show high porosity and good thermal stability. Both cPAF-28 and iPAF-28 are proved to be good candidates for C2H2 adsorption, demonstrated by C2H2/C2H4 selectivity of 12.2 and 15.4, and C2H2 capacity of 48 cm3 g-1 and 57 cm3 g-1, which are significantly higher than those of non-functionalized PAF-28 (1.8, 37 cm3 g-1). Furthermore, the cPAF-28 and iPAF-28 display good breakthrough performance and remarkable recyclability for the separation of the C2H2/C2H4 gas mixture. In addition, the C2H2/C2H4 adsorption sites are revealed by DFT calculations. This work sheds a new light on gas molecular recognition by tailoring the pore chemistry of PAFs.

14.
Plant Mol Biol ; 2022 Oct 08.
Artigo em Inglês | MEDLINE | ID: mdl-36207656

RESUMO

KEY MESSAGE: 1. Purple flowering stalk (Brassica campestris L. ssp. chinensis L. var. purpurea Bailey) is a crop with the high-level anthocyanin. 2. Increased abundance of LBGs promoted the synthesis of anthocyanin. 3. TTG2 (WRKY) interacted with TTG1 (WD40), probably regulating anthocyanin accumulation by shaping a MBWW complex. Brassica crops are a class of nutrient-rich vegetables. Here, two Brassica Crops-Flowering Stalk cultivars, purple flowering stalk (Brassica campestris L. var. purpurea Bailey) and pakchoi (Brassica campestris ssp. chinensis var. communis) were investigated. HPLC-ESI-MS/MS analysis demonstrated that Cy 3-p-coumaroylsophoroside-5-malonylglucoside and Cy 3-diferuloylsophoroside-5-malonylglucoside were identified as the major anthocyanin in peel of purple flowering stalk. The transcript level of structural genes including C4H, CHS, F3H, DFR, ANS and UFGT, and regulatory genes such as TT8, TTG1, Bra004162, Bra001917 and TTG2 in peel of purple flowering stalk were significantly higher than that in peel of pakchoi. In addition, the TTG2(WRKY) interacted only with TTG1(WD40) and the interaction between TT8 (bHLH) and TTG1/Bra004162(MYB)/Bra001917(MYB) were identified. Else, the WD40-WRKY complex (TTG1-TTG2) could activate the transcript of TT12. Our study laid a foundation for the research on the anthocyanin accumulation in Brassica crops.

15.
J Control Release ; 351: 656-666, 2022 11.
Artigo em Inglês | MEDLINE | ID: mdl-36183971

RESUMO

Adrenergic nerves, which are innervated in the tumor, regulate tumor initiation, angiogenesis, and the establishment of the tumor immunosuppressive microenvironment. The study aimed to evaluate the effectiveness of propranolol liposomes (Lipo pro) in inhibiting adrenergic nerve signaling in cancer therapy. Lipo pro significantly regulated the distribution of tumor microenvironment adrenergic nerves, tumor blood vessels, and immunosuppressive microenvironment. Furthermore, it displayed considerable therapeutic effects on prostatic cancer, pancreatic ductal adenocarcinoma, and melanoma. The combination therapeutic regimen, in which Lipo pro was the primary treatment and was supplemented by chemotherapy, showed significant advantages over any single treatment, effectively restraining tumor growth in situ and metastasis, thereby prolonging the survival of mice. This study established a proof-of-concept by targeting tumor adrenergic nerve signaling for cancer therapy.


Assuntos
Carcinoma Ductal Pancreático , Neoplasias Pancreáticas , Camundongos , Animais , Lipossomos , Microambiente Tumoral , Neoplasias Pancreáticas/patologia , Carcinoma Ductal Pancreático/patologia , Adrenérgicos/uso terapêutico , Linhagem Celular Tumoral
16.
Front Public Health ; 10: 1004117, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36211676

RESUMO

Coronavirus Disease 2019 (COVID-19) is currently a global pandemic, and early screening is one of the key factors for COVID-19 control and treatment. Here, we developed and validated chest CT-based imaging biomarkers for COVID-19 patient screening from two independent hospitals with 419 patients. We identified the vasculature-like signals from CT images and found that, compared to healthy and community acquired pneumonia (CAP) patients, COVID-19 patients display a significantly higher abundance of these signals. Furthermore, unsupervised feature learning led to the discovery of clinical-relevant imaging biomarkers from the vasculature-like signals for accurate and sensitive COVID-19 screening that have been double-blindly validated in an independent hospital (sensitivity: 0.941, specificity: 0.920, AUC: 0.971, accuracy 0.931, F1 score: 0.929). Our findings could open a new avenue to assist screening of COVID-19 patients.


Assuntos
COVID-19 , Aprendizado Profundo , Biomarcadores , Humanos , SARS-CoV-2 , Tomografia Computadorizada por Raios X/métodos
17.
Pharmacotherapy ; 2022 Oct 20.
Artigo em Inglês | MEDLINE | ID: mdl-36263704

RESUMO

STUDY OBJECTIVE: East Asians have a higher risk of bleeding than Europeans when treated with ticagrelor. This study aimed to explore genetic indicators related to the high bleeding propensity in East Asian patients with acute coronary syndrome (ACS) using ticagrelor. DESIGN: A multicenter prospective cohort study. SETTING: Four sub center hospitals participating the study. PATIENTS: Between March 2018 and July 2021, 208 patients with ACS were administered ticagrelor and underwent genetic testing. INVERTENTION: Patients were enrolled and followed up for bleeding events for 12 months. Single-nucleotide polymorphisms (SNPs) were detected using whole-exome sequencing. SNPs significantly associated with cumulative bleeding events within 1-, 6-, and 12-month follow-ups were selected (p < 0.01). Among these, SNPs showing a difference of ≥2 fold in their distribution frequency among East Asians and Europeans were selected. MEASUREMENTS AND MAIN RESULTS: Among all patients, 96.60% received ticagrelor plus aspirin or cilostazol, and 42.3% suffered from bleeding events during 12-month follow-up. Furthermore, 22 SNPs of 15 genes were found to have a significant association with cumulative bleeding events within 1-, 6-, and 12-month follow-ups. Among these SNPs, FIG4 rs2295837 (A>T) variant had the strongest association with bleeding events within 1 month (p = 1.28 × 10-4 ), with an increased risk of bleeding in T allele carriers (odds ratio [OR]: 3.07, 95% confidence interval [CI]: 1.68-5.63). PROK2 rs3796224 (C>T) variant was most strongly associated with cumulative bleeding events within 6 months (p = 4.57 × 10-4 ) with an increased risk of bleeding in T allele carriers (OR: 2.16, 95% CI: 1.20-3.89). Moreover, HRNR rs6662450 (C>T) variant showed the strongest relation with cumulative bleeding events within 12 months (p = 4.86 × 10-4 ) with a reduced risk of bleeding in T allele carriers (OR: 0.48, 95% CI: 0.24-0.95). CONCLUSION: Fifteen genes, including PROK2, HRNR, and FIG4, were potential biomarkers of high bleeding propensity in East Asian patients with ACS using ticagrelor.

18.
Genes (Basel) ; 13(10)2022 10 15.
Artigo em Inglês | MEDLINE | ID: mdl-36292752

RESUMO

(1) Background: The purpose of this study was to evaluate the effect of gene polymorphisms on prothrombin time (PT) and activated partial thromboplastin time (APTT) in a healthy Chinese population. (2) Methods: A total of 403 healthy volunteers from a series of novel oral anticoagulants (NOACs) bioequivalence trials in China were included. Coagulation tests for PT and APTT were performed in the central lab at Peking University First Hospital. Whole-exome sequencing (WES) and genome-wide association analysis were performed. (3) Results: In the correlation analysis of PT, 105 SNPs from 84 genes reached the genome-wide significance threshold (p < 1 × 10-5). Zinc Finger Protein 594 (ZNF594) rs184838268 (p = 4.50 × 10-19) was most significantly related to PT, and Actinin Alpha 1 (ACTN1) was found to interact most with other candidate genes. Significant associations with previously reported candidate genes Aurora Kinase B (AURKB), Complement C5(C5), Clock Circadian Regulator (CLOCK), and Histone Deacetylase 9(HDAC9) were detected in our dataset (p < 1 × 10-5). PiggyBac Transposable Element Derived 2(PGBD2) rs75935520 (p = 4.49 × 10-6), Bromodomain Adjacent To Zinc Finger Domain 2A(BAZ2A) rs199970765 (p = 5.69 × 10-6) and Protogenin (PRTG) rs80064850 (p = 8.69 × 10-6) were significantly correlated with APTT (p < 1 × 10-5). The heritability values of PT and APTT were 0.83 and 0.64, respectively; (4) Conclusion: The PT and APTT of healthy populations are affected by genetic polymorphisms. ZNF594 and ACTN1 variants could be novel genetic markers of PT, while PRTG polymorphisms might be associated with APTT levels. The findings could be attributed to ethnic differences, and need further investigation.


Assuntos
Actinina , Estudo de Associação Genômica Ampla , Humanos , Tempo de Tromboplastina Parcial , Tempo de Protrombina , Aurora Quinase B , Administração Oral , Marcadores Genéticos , Elementos de DNA Transponíveis , Anticoagulantes , Testes de Coagulação Sanguínea , Polimorfismo Genético , Complemento C5 , Histona Desacetilases , Proteínas Cromossômicas não Histona
19.
Artigo em Inglês | MEDLINE | ID: mdl-36304738

RESUMO

Federated learning (FL) has emerged with increasing popularity in the medical image analysis field. In collaborative model training, it provides a privacy-preserving scheme by keeping data localized. In FL frameworks, instead of collecting data from clients, the server learns a global model by aggregating local training models from clients and broadcasts the updated model. However, in the situation where data is not identically and independently distributed (non-i.i.d), the model aggregation requires frequent message passing, which may face the communication bottleneck. In this paper, we propose a communication-efficient FL framework based on the adaptive server-client model transmission. The local model in the client will only be uploaded to the server under the conditions of (1) a probability threshold and (2) an informative model updating threshold. Our framework also tackles the data heterogeneity in federated networks by involving a proximal term. We evaluate our approach on a simulated multi-site medical image dataset for diabetic retinopathy (DR) rating. We demonstrate that our framework not only maintains the accuracy on non-i.i.d dataset but also provides a significant reduction in communication cost compared to other FL algorithms.

20.
Nat Commun ; 13(1): 6361, 2022 Oct 26.
Artigo em Inglês | MEDLINE | ID: mdl-36289208

RESUMO

Biosynthesis of the flavonoid naringenin in plants and bacteria is commonly catalysed by a type III polyketide synthase (PKS) using one p-coumaroyl-CoA and three malonyl-CoA molecules as substrates. Here, we report a fungal non-ribosomal peptide synthetase -polyketide synthase (NRPS-PKS) hybrid FnsA for the naringenin formation. Feeding experiments with isotope-labelled precursors demonstrate that FnsA accepts not only p-coumaric acid (p-CA), but also p-hydroxybenzoic acid (p-HBA) as starter units, with three or four malonyl-CoA molecules for elongation, respectively. In vitro assays and MS/MS analysis prove that both p-CA and p-HBA are firstly activated by the adenylation domain of FnsA. Phylogenetic analysis reveals that the PKS portion of FnsA shares high sequence homology with type I PKSs. Refactoring the biosynthetic pathway in yeast with the involvement of fnsA provides an alternative approach for the production of flavonoids such as isorhamnetin and acacetin.


Assuntos
Flavonoides , Policetídeo Sintases , Policetídeo Sintases/genética , Policetídeo Sintases/metabolismo , Filogenia , Espectrometria de Massas em Tandem , Peptídeo Sintases/metabolismo , Malonil Coenzima A , Catálise
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