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1.
Bioinformatics ; 39(10)2023 10 03.
Artigo em Inglês | MEDLINE | ID: mdl-37851379

RESUMO

MOTIVATION: Gene regulatory networks (GRNs) are a way of describing the interaction between genes, which contribute to revealing the different biological mechanisms in the cell. Reconstructing GRNs based on gene expression data has been a central computational problem in systems biology. However, due to the high dimensionality and non-linearity of large-scale GRNs, accurately and efficiently inferring GRNs is still a challenging task. RESULTS: In this article, we propose a new approach, iLSGRN, to reconstruct large-scale GRNs from steady-state and time-series gene expression data based on non-linear ordinary differential equations. Firstly, the regulatory gene recognition algorithm calculates the Maximal Information Coefficient between genes and excludes redundant regulatory relationships to achieve dimensionality reduction. Then, the feature fusion algorithm constructs a model leveraging the feature importance derived from XGBoost (eXtreme Gradient Boosting) and RF (Random Forest) models, which can effectively train the non-linear ordinary differential equations model of GRNs and improve the accuracy and stability of the inference algorithm. The extensive experiments on different scale datasets show that our method makes sensible improvement compared with the state-of-the-art methods. Furthermore, we perform cross-validation experiments on the real gene datasets to validate the robustness and effectiveness of the proposed method. AVAILABILITY AND IMPLEMENTATION: The proposed method is written in the Python language, and is available at: https://github.com/lab319/iLSGRN.


Assuntos
Algoritmos , Redes Reguladoras de Genes , Biologia de Sistemas , Algoritmo Florestas Aleatórias , Fatores de Tempo , Biologia Computacional/métodos
2.
Angew Chem Int Ed Engl ; 63(24): e202404952, 2024 Jun 10.
Artigo em Inglês | MEDLINE | ID: mdl-38588012

RESUMO

The vast bulk of polystyrene (PS), a major type of plastic polymers, ends up in landfills, which takes up to thousands of years to decompose in nature. Chemical recycling promises to enable lower-energy pathways and minimal environmental impacts compared with traditional incineration and mechanical recycling. Herein, we demonstrated that methanol as a hydrogen supplier assisted the depolymerization of PS (denoted as PS-MAD) into alkylbenzenes over a heterogeneous catalyst composed of Ru nanoparticles on SiO2. PS-MAD achieved a high yield of liquid products which accounted for 93.2 wt % of virgin PS at 280 °C for 6 h with the production rate of 118.1 mmolcarbon gcatal. -1 h-1. The major components were valuable alkylbenzenes (monocyclic aromatics and diphenyl alkanes), the sum of which occupied 84.3 wt % of liquid products. According to mechanistic studies, methanol decomposition dominates the hydrogen supply during PS-MAD, thereby restraining PS aromatization which generates by-products of fused polycyclic arenes and polyphenylenes.

3.
Rapid Commun Mass Spectrom ; 37(21): e9634, 2023 Nov 15.
Artigo em Inglês | MEDLINE | ID: mdl-37799030

RESUMO

RATIONALE: Cooking oil fumes contain numerous hazardous and carcinogenic chemicals, posing potential threats to human health. However, the sources of these species remain ambiguous, impeding health risk assessment, pollution control and mechanism research. METHODS: To address this issue, the thermal oxidation of three common unsaturated fatty acids (UFAs), namely oleic, linoleic and linolenic acids, present in vegetable oils was investigated. The volatile and semi-volatile products were comprehensively characterized by online synchrotron radiation photoionization mass spectrometry (SR-PIMS) with two modes, which were validated and complemented using offline gas chromatography (GC)/MS methods. Tunable SR-PIMS combined with photoionization efficiency curve simulation enabled the recognition of isomers/isobars in gaseous fumes. RESULTS: SR-PIMS revealed over 100 products, including aldehydes, alkenes, furans, aromatic hydrocarbons, etc., such as small molecules of formaldehyde, acetaldehyde, acrolein, ethylene and furan, which are not readily detected by conventional GC/MS; and some unreported fractions, e.g. ketene, 4-ethylcyclohexene and cycloundecene(E), were also observed. Furthermore, real-time monitoring of product emissions during the thermal oxidation of the three UFAs via SR-PIMS revealed that linolenic acid may be the major source of acrolein. CONCLUSION: SR-PIMS has been demonstrated as a powerful technique for online investigation of cooking oil fumes. This study achieved comprehensive characterization of volatile and semi-volatile products from the thermal oxidation of oleic, linoleic and linolenic acids, facilitating the traceability of species in cooking fumes and aiding in exploring the thermal reactions of different vegetable oils.


Assuntos
Acroleína , Ácidos Linolênicos , Humanos , Acroleína/análise , Ácidos Graxos/química , Síncrotrons , Óleos de Plantas , Ácidos Graxos Insaturados , Espectrometria de Massas
4.
Angew Chem Int Ed Engl ; 62(32): e202304352, 2023 Aug 07.
Artigo em Inglês | MEDLINE | ID: mdl-37219500

RESUMO

Photocatalysis has emerged as an ideal method for the direct activation and conversion of methane under mild conditions. In this reaction, methyl radical (⋅CH3 ) was deemed a key intermediate that affected the yields and selectivity of the products. However, direct observation of ⋅CH3 and other intermediates is still challenging. Here, a rectangular photocatalytic reactor coupled with in situ synchrotron radiation photoionization mass spectrometry (SR-PIMS) was developed to detect reactive intermediates within several hundred microseconds during photocatalytic methane oxidation over Ag-ZnO. Gas phase ⋅CH3 generated by photogenerated holes (O- ) was directly observed, and its formation was demonstrated to be significantly enhanced by coadsorbed oxygen molecules. Methoxy radical (CH3 O⋅) and formaldehyde (HCHO) were confirmed to be key C1 intermediates in photocatalytic methane overoxidation to CO2 . The gas-phase self-coupling reaction of ⋅CH3 contributes to the formation of ethane, which indicates the key role of ⋅CH3 desorption in the highly selective synthesis of ethane. Based on the observed intermediates, the reaction network initiated from ⋅CH3 of photocatalytic methane oxidation could be clearly illustrated, which is helpful for studying the photocatalytic methane conversion processes.

5.
Phys Chem Chem Phys ; 23(36): 20388-20397, 2021 Sep 22.
Artigo em Inglês | MEDLINE | ID: mdl-34491254

RESUMO

We study the absorption of self-propelled particles into a finite-size dense porous medium, which is mimicked by an obstacle array. We find that, depending on the competition of the propelling strength versus the repulsive barrier formed by obstacles and the contrast between the characteristic time scales of permeation and propelling persistence, the absorption process exhibits three distinct types of behavior. In Type I and II behavior, the propelling strength is not large enough to surmount the barrier, and hence particles transport in the medium by barrier-hopping dynamics. The initial permeation of particles toward the medium center is phenomenologically similar to a normal slow diffusion process. But, surprisingly, after the initial permeation process, a concentrated nucleus of particle aggregates forms and grows at the medium center in Type I, due to the long propelling persistence. Such an abnormal "nucleation" phenomenon does not appear in Type II, in which the propelling persistence is low. When the propelling strength is very high (Type III), particles transport smoothly in the medium, hence the initial slow diffusion process disappears and small particle clusters form and merge randomly in the medium. Our results provide a foundation for applications of active objects in a complex environment and also suggest the possible usage of a porous medium, for example, in the selection or sorting of active matter.

6.
BMC Cancer ; 20(1): 1026, 2020 Oct 23.
Artigo em Inglês | MEDLINE | ID: mdl-33097010

RESUMO

BACKGROUND: Circular RNAs (circRNAs) have emerged as a novel category of non-coding RNA, which exhibit a pivotal effect on regulating gene expression and biological functions, yet how circRNAs function in osteosarcoma (OSA) still demands further investigation. This study aimed at probing into the function of hsa_circ_0000282 in OSA. METHODS: The expressions of circ_0000282 and miR-192 in OSA tissues and cell lines were examined by quantitative real-time polymerase chain reaction (qRT-PCR), and the correlation between the expression level of circ_0000282 and clinicopathological features of OSA patients was analyzed. The expressions of X-linked inhibitor of apoptosis protein (XIAP), B-cell lymphoma-2 (Bcl-2) and Bcl-2 associated X protein (Bax) in OSA cells were assayed by Western blot. The proliferation and apoptosis of OSA cells were examined by CCK-8, BrdU and flow cytometry, respectively. Bioinformatics analysis, dual-luciferase reporter gene assay and RIP experiments were employed to predict and validate the targeting relationships between circ_0000282 and miR-192, and between miR-192 and XIAP, respectively. RESULTS: Circ_0000282 was highly expressed in OSA tissues and cell lines, which represented positive correlation with Enneking stage of OSA patients and negative correlation with tumor differentiation degree. In vitro experiments confirmed that overexpression of circ_0000282 markedly facilitated OSA cell proliferation and repressed cancer cell apoptosis in comparison to control group. Besides, knockdown of circ_0000282 repressed OSA cell proliferation and promoted apoptosis. Additionally, the binding relationships between circ_0000282 and miR-192, and between miR-192 and XIAP were validated. Circ_0000282 indirectly up-regulated XIAP expression by adsorbing miR-192, thereby playing a role in promoting cancer in OSA. CONCLUSION: Circ_0000282 was a novel oncogenic circRNA in OSA. Circ_0000282/miR-192/XIAP axis regulated OSA cell proliferation apoptosis with competitive endogenous RNA mechanism.


Assuntos
Neoplasias Ósseas/patologia , MicroRNAs/genética , Osteossarcoma/patologia , RNA Circular/genética , Proteínas Inibidoras de Apoptose Ligadas ao Cromossomo X/genética , Neoplasias Ósseas/genética , Neoplasias Ósseas/metabolismo , Linhagem Celular Tumoral , Proliferação de Células , Sobrevivência Celular , Regulação Neoplásica da Expressão Gênica , Humanos , Estadiamento de Neoplasias , Osteossarcoma/genética , Osteossarcoma/metabolismo , Proteínas Proto-Oncogênicas c-bcl-2/metabolismo , Proteínas Inibidoras de Apoptose Ligadas ao Cromossomo X/metabolismo , Proteína X Associada a bcl-2/metabolismo
7.
Chemistry ; 24(63): 16766-16769, 2018 Nov 13.
Artigo em Inglês | MEDLINE | ID: mdl-30203453

RESUMO

Uranyl-organic frameworks (UOFs) have recently been the object of many research endeavors due to the unique coordination mode of uranyl ions and their attractive physicochemical properties. Here, a new (3,4)-connected UOF (U-IHEP-4) assembled from uranyl and porphyrin ligand tetrakis(4-carboxyphenyl)porphyrin (H4TCPP) is reported, which represents the first case of actinide porphyrinic MOFs. Adsorption experiments in DMF solution demonstrated that U-IHEP-4 selectively adsorbs positively charged dyes, which is in line with its negatively charged framework and large pore volume ratio (90 %). Remarkably, U-IHEP-4 exhibited high catalytic activity for the dehydrogenation of N-heterocycles to synthesize the corresponding aromatic heterocycles and it can be used as an efficient heterogeneous catalyst.

8.
Analyst ; 143(12): 2790-2798, 2018 Jun 11.
Artigo em Inglês | MEDLINE | ID: mdl-29790507

RESUMO

A novel detector for liquid chromatography (LC) for the determination of dithiocarbamate (DTC) fungicides is presented with a miniaturized dielectric barrier discharge-microplasma molecular emission spectrometer and an online microwave-assisted hydrolysis reactor. DTCs in the sample/standard solutions together with SnCl2 were pumped to the reactor to be converted to CS2 with high efficiency, which was then separated from the liquid phase and transformed for the detection of the specific molecular emission at 257.49 nm by the spectrometer. Under optimized conditions, the performance of this new detector was evaluated by its determination of different types of DTC including mancozeb, thiram, zineb, propineb, and metiram, and the limit of detection (LOD) values were found to be in the range 0.1-1.0 µg mL-1. The results from 20 test vegetable and fruit samples determined with the proposed method agreed well with those obtained using the standard headspace gas chromatography-electron capture detector (GC-ECD) method. Preliminary experimental results showed that the proposed method provided slightly higher LOD values than those obtained using GC-ECD. Most importantly, the new LC detector could detect each DTC chemical, whereas the traditional method could not distinguish between analytes of different subclasses of DTC.

9.
Molecules ; 19(7): 9675-88, 2014 Jul 07.
Artigo em Inglês | MEDLINE | ID: mdl-25004074

RESUMO

Red radish (Raphanus L.) pickles are popular appetizers or spices in Asian-style cuisine. However, tons of radish brines are generated as wastes from industrial radish pickle production. In this study, we evaluated the dynamic changes in colour properties, phenolics, anthocyanin profiles, phenolic acid composition, flavonoids, and antioxidant properties in radish brines during lactic acid fermentation. The results showed that five flavonoids detected were four anthocyanins and one kaempferol derivative, including pelargonidin-3-digluoside-5-glucoside derivatives acylated with p-coumaric acid, ferulic acid, p-coumaric and manolic acids, or ferulic and malonic acids. Amounts ranged from 15.5-19.3 µg/mL in total monomeric anthocyanins, and kaempferol-3,7-diglycoside (15-30 µg/mL). 4-Hydroxy-benzoic, gentisic, vanillic, syringic, p-coumaric, ferulic, sinapic and salicylic acids were detected in amounts that varied from 70.2-92.2 µg/mL, whereas the total phenolic content was 206-220 µg/mL. The change in colour of the brine was associated with the accumulation of lactic acid and anthocyanins. The ORAC and Fe2+ chelation capacity of radish brines generally decreased, whereas the reducing power measured as FRAP values was increased during the fermentation from day 5 to day 14. This study provided information on the phytochemicals and the antioxidative activities of red radish fermentation waste that might lead to further utilization as nutraceuticals or natural colorants.


Assuntos
Antioxidantes/química , Fermentação , Ácido Láctico/química , Compostos Fitoquímicos/química , Raphanus/química , Sais/química , Antocianinas , Antioxidantes/farmacologia , Flavonoides , Concentração de Íons de Hidrogênio , Hidroxibenzoatos , Fenóis , Compostos Fitoquímicos/farmacologia , Pigmentos Biológicos/química , Sais/farmacologia
10.
Biomed Res Int ; 2024: 6640796, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38884020

RESUMO

Diabetes has a significant global prevalence. Chronic hyperglycemia affects multiple organs and tissues, including bones. A large number of diabetic patients develop osteoporosis; however, the precise relationship between diabetes and osteoporosis remains incompletely elucidated. The activation of the AGE-RAGE signaling pathway hinders the differentiation of osteoblasts and weakens the process of bone formation due to the presence of advanced glycation end products. High glucose environment can induce ferroptosis of osteoblasts and then develop osteoporosis. Hyperglycemia also suppresses the secretion of sex hormones, and the reduction of testosterone is difficult to effectively maintain bone mineral density. As diabetes therapy, thiazolidinediones control blood glucose by activating PPAR-γ. Activated PPAR-γ can promote osteoclast differentiation and regulate osteoblast function, triggering osteoporosis. The effects of metformin and insulin on bone are currently controversial. Currently, there are no appropriate tools available for assessing the risk of fractures in diabetic patients, despite the fact that the occurrence of osteoporotic fractures is considerably greater in diabetic individuals compared to those without diabetes. Further improving the inclusion criteria of FRAX risk factors and clarifying the early occurrence of osteoporosis sites unique to diabetic patients may be an effective way to diagnose and treat diabetic osteoporosis and reduce the risk of fracture occurrence.


Assuntos
Osteoporose , Humanos , Osteoporose/metabolismo , Fatores de Risco , Fraturas por Osteoporose/metabolismo , Fraturas Ósseas/metabolismo , Redes e Vias Metabólicas , Diabetes Mellitus/metabolismo , Densidade Óssea , Osteoblastos/metabolismo , Transdução de Sinais
11.
Sci Rep ; 14(1): 10321, 2024 May 06.
Artigo em Inglês | MEDLINE | ID: mdl-38710790

RESUMO

The wide application of rotating machinery has boosted the development of electricity and aviation, however, long-term operation can lead to a variety of faults. The use of different measures to deal with corresponding malfunctions is the key to generating benefits, so it is significant to carry out the fault diagnosis of rotating machinery. In this work, a test bench for single-span rotor bearings was established, three faults, including spindle bending, spindle crack without end loading and spindle crack with end loading, are experimental analyzed with basic mechanical response. Moreover, a diagnosis is performed using a convolutional neural network, according to the differences in mechanical responses of the three faults obtained from experiments. For three faults, the change in the properties of spindle itself results in different axis trajectories and spectra. Compared with spindle bending fault, spindle crack fault not only cause 1×, 2×, 3× frequency component excitation, also 4×, 5× frequency component excitation. Additionally, the classification accuracy of the training set and the test set under machine learning for the three types of working conditions is 100%. This indicates that the network can significantly identify signal features so as to make effective fault classification.

12.
Sci Adv ; 10(26): eado4390, 2024 Jun 28.
Artigo em Inglês | MEDLINE | ID: mdl-38941471

RESUMO

Light-driven oxidative coupling of methane (OCM) for multi-carbon (C2+) product evolution is a promising approach toward the sustainable production of value-added chemicals, yet remains challenging due to its low intrinsic activity. Here, we demonstrate the integration of bismuth oxide (BiOx) and gold (Au) on titanium dioxide (TiO2) substrate to achieve a high conversion rate, product selectivity, and catalytic durability toward photocatalytic OCM through rational catalytic site engineering. Mechanistic investigations reveal that the lattice oxygen in BiOx is effectively activated as the localized oxidant to promote methane dissociation, while Au governs the methyl transfer to avoid undesirable overoxidation and promote carbon─carbon coupling. The optimal Au/BiOx-TiO2 hybrid delivers a conversion rate of 20.8 millimoles per gram per hour with C2+ product selectivity high to 97% in the flow reactor. More specifically, the veritable participation of lattice oxygen during OCM is chemically looped by introduced dioxygen via the Mars-van Krevelen mechanism, endowing superior catalyst stability.

13.
Int J Surg ; 2024 May 23.
Artigo em Inglês | MEDLINE | ID: mdl-38781043

RESUMO

BACKGROUND: The aim of this study is to assess the diagnostic accuracy of intraoperative frozen section (FS) in determining the pathological subtypes among patients diagnosed with cT1N0M0 invasive lung adenocarcinoma. MATERIALS AND METHODS: This was a prospective, multi-center (7 centers in China) clinical trial of Eastern Cooperative Thoracic Oncology Projects (ECTOP-1015). Patients with cT1N0M0 invasive lung adenocarcinoma were enrolled in the study. Pathological images obtained from FS and final pathology (FP) were reviewed by at least two pathologists. The primary endpoint was the concordance between FS and FP diagnoses. The inter-observer agreement for identifying pathological subtypes on FS was evaluated among three pathologists. RESULTS: A total of 935 patients were enrolled. The best sensitivity of diagnosing the predominant subtype was 78.2% in the evaluation of acinar pattern. Presence of acinar pattern diagnosed by FS was an independent factor for the concordance between FS and FP (P=0.007, 95% CI: 2.332-4.736). Patients with tumor size >2 cm measured by pathology showed a better concordance rate for the predominant subtype (81.6% vs 74.6%, P=0.023). The presence of radiological ground glass opacity (GGO) component did not affect the diagnosis accuracy of FS for predominant subtype (concordance rate: 76.4% vs 75.2%, P=0.687). Patients with GGO component showed better accuracy of the identification in the presence of LPA (82.1% vs 71.0%, P= 0.026). Substantial agreement between the FS diagnosis from 3 pathologists for the predominant pathological pattern was revealed with κ = 0.846. CONCLUSIONS: This is the largest prospective trial evaluating FS diagnosing pathological subtype in cT1N0M0 invasive lung adenocarcinoma. A favorable concordance in the assessment of the pathological subtypes between FS and FP was observed, indicating the feasibility of utilizing accurate intraoperative pathological diagnoses from FS in guiding surgical strategies. And combination of radiology could improve the precision of FS.

14.
J Am Soc Mass Spectrom ; 34(12): 2680-2690, 2023 Dec 06.
Artigo em Inglês | MEDLINE | ID: mdl-37983183

RESUMO

Cooking oil fumes are an intricate and dynamic mixture containing a variety of poisonous and hazardous substances, and their real-time study remains challenging. Based on tunable synchrotron radiation photoionization mass spectrometry (SR-PIMS), isomeric/isobaric compounds in the gaseous oil fumes from oleic acid thermal oxidation were determined in real time and distinguished by photoionization efficiency (PIE) curve simulation combined with multiple linear regression (MLR) analysis. A series of common carcinogens such as formaldehyde, acetaldehyde, acrolein, and several unreported chemicals including diethyl ether and formylcyclohexane were successfully characterized. Moreover, time-resolved profiles of certain components in gaseous oil fumes were monitored for 55 h. Distinct evolutionary processes were observed, indicating the consumption and formation of parent molecules, intermediates, and final products.

15.
Sci Bull (Beijing) ; 68(17): 1886-1893, 2023 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-37544879

RESUMO

Inspiration from natural enzymes enabling creationary catalyst design is appealing yet remains extremely challenging for selective methane (CH4) oxidation. This study presents the construction of a biomimetic catalyst platform for CH4 oxidation, which is constructed by incorporating Fe-porphyrin into a robust metal-organic framework, UiO-66, furnished with saturated monocarboxylic fatty acid bearing different long alkyl chains. The catalysts demonstrate the high efficiency in the CH4 to methanol (CH3OH) conversion at 50 °C. Moreover, the selectivity to CH3OH can be effectively regulated and promoted through a fine-tuned microenvironment by hydrophobic modification around the Fe-porphyrin. The long-chain fatty acids anchored on the Zr-oxo cluster of UiO-66 can not only tune the electronic state of the Fe sites to improve CH4 adsorption, but also restrict the amount of H2O2 around the Fe sites to reduce the overoxidation. This behavior resembles the microenvironment regulation in methane monooxygenase, resulting in high CH3OH selectivity.

16.
Adv Healthc Mater ; 12(4): e2202317, 2023 02.
Artigo em Inglês | MEDLINE | ID: mdl-36349826

RESUMO

In the process of bone tissue regeneration, regulation of osteogenesis-angiogenesis coupling is of great importance. Therefore, dimethyloxallyl glycine (DMOG) is loaded by nanoscale zeolitic imidazolate frameworks-8 (ZIF-8) to obtain a drug-loading system that can promote osteogenesis-angiogenesis coupling. Characterization of the drug-loading nanoparticles (DMOG@ZIF-8) reveals that DMOG is successfully loaded into ZIF-8 by two different methods, and the DMOG@ZIF-8 is prepared using the one-pot method (OD@ZIF-8) achieves higher loading efficiency and longer release time than those prepared using the post-loading method (PD@ZIF-8). In vitro studies found that DMOG@ZIF-8 significantly enhances the migration, tube formation, and angiogenesis-related protein secretion of human umbilical vein endothelial cells as well as the extracellular matrix mineralization, alkaline phosphatase activity, and osteogenesis-related protein secretion of bone marrow mesenchymal stem cells. Moreover, OD@ZIF-8 nanoparticles are more efficient than PD@ZIF-8 nanoparticles in induction of osteogenesis-angiogenesis coupling. Then, in vivo cranial critical defect model shows that the addition of OD@ZIF-8 significantly promotes vascularized bone formation as indicated by the results including microcomputed tomographic, histological and immunofluorescence staining, and so on. Taken together, loading ZIF-8 with DMOG may be a promising solution for critical-sized bone defect reconstruction and the one-pot method is preferred in the preparation of such drug-loading system.


Assuntos
Zeolitas , Humanos , Zeolitas/farmacologia , Células Endoteliais , Regeneração Óssea , Osteogênese
17.
Pulm Pharmacol Ther ; 25(1): 99-103, 2012 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-22210005

RESUMO

RATIONALE: Neutrophil elastases (NE) play an important role in the pathogenesis of acute lung injury (ALI). NE activities are significantly increased in serums and lungs of patients or animals with ALI. Intravenous infusion (IV) of Sivelestat, an NE inhibitor, can reduce ALI. Through inhalation, drugs reach lungs directly and in high concentration. We hypothesized that inhaled Sivelestat would alleviate oleic acid (OA)-induced ALI in rats. METHODS: Rats were anesthetized and mechanically ventilated, and then ALI was induced by OA injection. One hour later, the animals were randomized to receive either Sivelestat (3 mg/kg/h) or saline inhalation. The effect of Sivelestat IV (3 mg/kg/h) was also investigated. All animals were ventilated and observed for 6 h. RESULTS: OA injection increased NE activities in lung tissues and serums. The increase of NE activities in lung tissues and serums markedly reduced by 77%, and 29%, respectively, by the inhalation of Sivelestat; and 53.8%, and 80%, respectively, by Sivelestat IV. Additionally, inhaled Sivelestat resulted in ameliorated lung injury by reducing edema and infiltration of neutrophils in the lung, improved oxygenation and survival. CONCLUSIONS: An over increased NE activity in lungs may play a vital effect in the pathogenesis of OA-induced ALI in rats. Topical application of nebulized Sivelestat, an NE inhibitor, may reduce OA-induced ALI in rats. Sivelestat inhalation can be developed as a novel treatment for ALI.


Assuntos
Lesão Pulmonar Aguda/induzido quimicamente , Lesão Pulmonar Aguda/tratamento farmacológico , Glicina/análogos & derivados , Elastase de Leucócito/antagonistas & inibidores , Ácido Oleico , Proteínas Secretadas Inibidoras de Proteinases/farmacologia , Sulfonamidas/farmacologia , Lesão Pulmonar Aguda/enzimologia , Administração por Inalação , Albuminas/análise , Albuminas/metabolismo , Animais , Gasometria , Líquido da Lavagem Broncoalveolar/química , Líquido da Lavagem Broncoalveolar/citologia , Contagem de Células , Água Extravascular Pulmonar/efeitos dos fármacos , Feminino , Glicina/administração & dosagem , Glicina/farmacologia , Injeções Intravenosas , Contagem de Leucócitos , Elastase de Leucócito/metabolismo , Ovalbumina/administração & dosagem , Ovalbumina/toxicidade , Peroxidase/metabolismo , Proteínas Secretadas Inibidoras de Proteinases/administração & dosagem , Ratos , Ratos Sprague-Dawley , Soroalbumina Bovina/administração & dosagem , Soroalbumina Bovina/toxicidade , Sulfonamidas/administração & dosagem , Análise de Sobrevida
18.
Molecules ; 17(11): 12910-24, 2012 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-23117431

RESUMO

Phenolic acids are potent antioxidants, yet the quantitative structure-activity relationships of phenolic acids remain unclear. The purpose of this study was to establish 3D-QSAR models able to predict phenolic acids with high DPPH• scavenging activity and understand their structure-activity relationships. The model has been established by using a training set of compounds with cross-validated q2 = 0.638/0.855, non-cross-validated r2 = 0.984/0.986, standard error of estimate = 0.236/0.216, and F = 139.126/208.320 for the best CoMFA/CoMSIA models. The predictive ability of the models was validated with the correlation coefficient r2(pred) = 0.971/0.996 (>0.6) for each model. Additionally, the contour map results suggested that structural characteristics of phenolics acids favorable for the high DPPH• scavenging activity might include: (1) bulky and/or electron-donating substituent groups on the phenol ring; (2) electron-donating groups at the meta-position and/or hydrophobic groups at the meta-/ortho-position; (3) hydrogen-bond donor/electron-donating groups at the ortho-position. The results have been confirmed based on structural analyses of phenolic acids and their DPPH• scavenging data from eight recent publications. The findings may provide deeper insight into the antioxidant mechanisms and provide useful information for selecting phenolic acids for free radical scavenging properties.


Assuntos
Compostos de Bifenilo/química , Sequestradores de Radicais Livres/química , Radicais Livres/química , Hidroxibenzoatos/química , Picratos/química , Relação Quantitativa Estrutura-Atividade , Simulação por Computador , Análise de Alimentos , Sequestradores de Radicais Livres/análise , Ligação de Hidrogênio , Hidroxibenzoatos/análise , Modelos Químicos , Modelos Moleculares , Estrutura Molecular
19.
Front Surg ; 9: 987500, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36211299

RESUMO

Objective: Vertebral augmentation techniques are widely used to treat osteoporotic vertebral compression fractures (OVCFs). Superior analgesic effects and shortened bed rest time means patients recover quickly, but prolonged unscheduled hospitalization can increase medical expenses and the risk of bed rest complications. The aim of this study was to investigate the reasons for prolonged hospitalization after vertebral augmentation surgery and to determine the relative risk factors. Methods: A single-center retrospective study was conducted to enroll patients with OVCFs and accepted vertebral augmentation surgery from January 2017 to December 2017. Clinical information was collected from the Hospital Information System (HIS). The criterion of delayed discharge was postoperative hospitalization more than 3 days. Telephone interviews and medical history evaluations were conducted to confirm the exact reason for retention. The risk factors were analyzed by multiple logistic regression. Results: Overall, 1,442 patients were included, and 191 (13.2%) stayed in the hospital for more than 3 days postoperatively. The reasons for delayed discharge were psychological factors (37.2%), residual pain (32.5%), cardiopulmonary complications (15.7%), nonspecific symptoms (8.4%), incision abnormalities (2.6%), thrombosis (2.1%), and postanesthesia reactions (1.6%). The multiple logistic model was significant; age (OR 1.028; 95% CI 1.009-1.046), preoperative stay (OR 1.192; 95% CI 1.095-1.298), operation type (OR 1.494; 95% CI 1.019-2.189), and the number of surgical segments (OR 2.238; 95% CI 1.512-3.312) showed statistical significance. In contrast, gender (P > 0.1) and chronic comorbidities (P > 0.1) were not predictors in this model. Conclusion: Overall, 13.2% of OVCF patients who underwent vertebral augmentation surgery were not discharged within 3 days postoperatively, and several predictors were found. Preoperative communication and comprehensive evaluations are calling for more attention; physicians should adopt an appropriate medical process to enhance rehabilitation in geriatric orthopedics.

20.
Front Oncol ; 12: 778545, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35280757

RESUMO

Background: PARP inhibitors have been approved as targeted therapy for BRCA-deficient metastatic ovarian cancer (OC). Fanconi anemia complementation group A (FANCA), one of the homologous recombination repair pathway genes, is a susceptibility gene to breast cancer and OC. Therefore, it is interesting to investigate whether germline FANCA-mutated relapsed epithelial OC could achieve clinical benefit from the treatment of PARP inhibitor. Case Presentation: A 49-year-old female patient without a family history of cancer was diagnosed with epithelial OC. This patient underwent surgical resection plus platinum-based treatment twice in 2016 and 2018, successively. After the second relapse in July 2019, the patient underwent another radical resection. The next-generation sequencing analysis results revealed a germline FANCA mutation in the tumor tissue. Subsequently, the third-line treatment of liposomal doxorubicin hydrochloride plus lobaplatin was administrated for five cycles with the patient's consent. Then, oral niraparib (200 mg daily) was given for maintenance treatment. During the follow-up, no evidence of tumor recurrence was observed. Currently, the survival with no evidence of disease has already exceeded 21 months, and the treatment is still going on. Conclusions: This case highlighted that OC patients harboring pathogenic gene alterations in the homologous recombination pathway might achieve clinical benefit from PARP inhibitors, which should be confirmed in further studies.

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