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1.
Artigo em Inglês | MEDLINE | ID: mdl-36131178

RESUMO

This prevalence of coronavirus disease 2019 (COVID-19) has become one of the most serious public health crises. Tree-based machine learning methods, with the advantages of high efficiency, and strong interpretability, have been widely used in predicting diseases. A data-driven interpretable ensemble framework based on tree models was designed to forecast daily new cases of COVID-19 in the USA and to determine the important factors related to COVID-19. Based on a hyperparametric optimization technique, we developed three machine learning algorithms based on decision trees, including random forest (RF), eXtreme Gradient Boosting (XGBoost), and Light Gradient Boosting Machine (LightGBM), and three linear ensemble models were used to integrate these outcomes for better prediction accuracy. Finally, the SHapley Additive explanation (SHAP) value was used to obtain the feature importance ranking. Our outcomes demonstrated that, among the three basic machine learners, the prediction accuracy was the following in descending order: LightGBM, XGBoost, and RF. The optimized LAD ensemble was the most precise prediction model that reduced the prediction error of the best base learner (LightGBM) by approximately 3.111%, while vaccination, wearing masks, less mobility, and government interventions had positive effects on the control and prevention of COVID-19.

2.
Front Endocrinol (Lausanne) ; 13: 967739, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36133311

RESUMO

In recent years, the incidence of infertility has been increasing gradually, while the natural rate of population growth is declining or even at zero growth. China is observed to enter a depth of aging society, leading to more severe infertility. Infertility patients face many predicaments, and many unreasonable behaviors existed in seeking medical diagnosis and treatment, of which the main influencing factor is economic condition. In China, Beijing has taken the lead in providing medical insurance for 16 assisted reproductive technology items. Assuming that all infertile couples with the option of assisted reproduction are treated, there would be a huge market gap. The reimbursement rate can be adjusted based on some factors within the affordable range of the medical insurance fund. Progress on infertility coverage in other countries was also reviewed. This paper cited the data of medical insurance funds in China in the recent 4 years as a reference. Based on the data, it is not currently able to cover all the costs of infertility diagnosis and treatment during the research period, but it is feasible to access selective reimbursement and subsidies for those in particular need as well as to develop some commercial insurances. There is a big gap in the application of assisted reproductive technology between China and developed countries. More comprehensive and constructive policies should be formulated countrywide to standardize the market. Assisted reproduction-related technologies and acceleration of the domestic medical apparatus and instrument replacement should be improved to reduce the cost.


Assuntos
Infertilidade , Seguro , China/epidemiologia , Estudos de Viabilidade , Humanos , Infertilidade/epidemiologia , Infertilidade/terapia , Técnicas de Reprodução Assistida
3.
Curr Issues Mol Biol ; 44(9): 4100-4117, 2022 Sep 07.
Artigo em Inglês | MEDLINE | ID: mdl-36135193

RESUMO

This study aimed to explore the possible relationship between the expression of Micro RNA-214 (miR-214) and the pathogenesis and recovery in mice with post-traumatic osteoarthritis (PTOA). In this study, 40 male C57BL/6 mice were randomly divided into five groups: model control (MC) group, model (M) group, rehabilitation control (RC) group, model + rehabilitation (M + R) group, and model + convalescent (M + C) group. Four weeks of high-intensity treadmill exercise (HITE) and 4 weeks of moderate-intensity treadmill exercise (MITE) were implemented for PTOA modeling and rehabilitation, respectively. In vitro, 10% elongation mechanical strain was used for IL-1ß stimulated chondrocytes. We found that compared with the MC group, there was a significant increase in the aspect of inflammation and catabolism while a dramatic fall in miR-214 expression was observed in the M group. After the 4 weeks of MITE, the level of inflammation and metabolism, as well as miR-214 expression, was partially reversed in the M + R group compared with the M + C group. The expression of miR-214 decreased dramatically after chondrocyte stimulation by IL-1ß and then increased significantly after 10% strain was applied to IL-1ß-treated cells. These results suggest that a suitable mechanical load can increase the expression of miR-214, and that miR-214 may play a chondroprotective effect in the development of OA.

4.
Front Endocrinol (Lausanne) ; 13: 986841, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36120457

RESUMO

Objective: This study aims to outline the clinical characteristics of pediatric NAFLD, as well as establish and validate a prediction model for the disease. Materials and methods: The retrospective study enrolled 3216 children with obesity from January 2003 to May 2021. They were divided into obese without NAFLD, nonalcoholic fatty liver (NAFL), and nonalcoholic steatohepatitis (NASH) groups. Clinical data were retrieved, and gender and chronologic characteristics were compared between groups. Data from the training set (3036) were assessed using univariate analyses and stepwise multivariate logistic regression, by which a nomogram was developed to estimate the probability of NAFLD. Another 180 cases received additional liver hydrogen proton magnetic resonance spectroscopy (1H-MRS) as a validation set. Results: The prevalence of NAFLD was higher in males than in females and has increased over the last 19 years. In total, 1915 cases were NAFLD, and the peak onset age was 10-12 years old. Hyperuricemia ranked first in childhood NAFLD comorbidities, followed by dyslipidemia, hypertension, metabolic syndrome (MetS), and dysglycemia. The AUROC of the eight-parameter nomogram, including waist-to-height ratio (WHtR), hip circumference (HC), triglyceride glucose-waist circumference (TyG-WC), alanine aminotransferase (ALT), high-density lipoprotein cholesterol (HDL-C), apolipoprotein A1(ApoA1), insulin sensitivity index [ISI (composite)], and gender, for predicting NAFLD was 0.913 (sensitivity 80.70%, specificity 90.10%). Calibration curves demonstrated a great calibration ability of the model. Conclusion and relevance: NAFLD is the most common complication in children with obesity. The nomogram based on anthropometric and laboratory indicators performed well in predicting NAFLD. This can be used as a quick screening tool to assess pediatric NAFLD in children with obesity.


Assuntos
Hepatopatia Gordurosa não Alcoólica , Alanina Transaminase , Apolipoproteína A-I , Criança , Colesterol , Feminino , Glucose , Humanos , Lipoproteínas HDL , Masculino , Hepatopatia Gordurosa não Alcoólica/complicações , Hepatopatia Gordurosa não Alcoólica/diagnóstico , Hepatopatia Gordurosa não Alcoólica/epidemiologia , Obesidade/complicações , Estudos Retrospectivos , Triglicerídeos
5.
Biomolecules ; 12(9)2022 Sep 17.
Artigo em Inglês | MEDLINE | ID: mdl-36139156

RESUMO

Human-adipose-derived mesenchymal stem cells (hADMSCs) are adult stem cells and are relatively easy to access compared to other sources of mesenchymal stem cells (MSCs). They have shown immunomodulation properties as well as effects in improving tissue regeneration. To better stimulate and preserve the therapeutic properties of hADMSCs, biomaterials for cell delivery have been studied extensively. To date, hyaluronic acid (HA)-based materials have been most widely adopted by researchers around the world. PGmatrix is a new peptide-based hydrogel that has shown superior functional properties in 3D cell cultures. Here, we reported the in vitro and in vivo functional effects of PGmatrix on hADMSCs in comparison with HA and HA-based Hystem hydrogels. Our results showed that PGmatrix was far superior in maintaining hADMSC viability during prolonged incubation and stimulated expression of SSEA4 (stage-specific embryonic antigen-4) in hADMSCs. hADMSCs encapsulated in PGmatrix secreted more immune-responsive proteins than those in HA or Hystem, though similar VEGF-A and TGFß1 release levels were observed in all three hydrogels. In vivo studies revealed that hADMSCs encapsulated with PGmatrix showed improved skin wound healing in diabetic-induced mice at an early stage, suggesting possible anti-inflammatory effects, though similar re-epithelialization and collagen density were observed among PGmatrix and HA or Hystem hydrogels by day 21.

6.
Comput Methods Programs Biomed ; 226: 107114, 2022 Sep 08.
Artigo em Inglês | MEDLINE | ID: mdl-36116399

RESUMO

BACKGROUND AND OBJECTIVE: Accurate extraction of the coronary artery centerline is crucial in the processes of coronary artery reconstruction, coronary artery stenosis or lesion detection, and surgical navigation. Furthermore, in clinical medicine, the complex background of angiography, low signal-to-noise ratio, and complex vascular structure make coronary artery centerline extraction challenging. In this study, a direct centerline extraction method is proposed that automatically and accurately extracts vascular centerlines from X-ray coronary angiography images based on deep learning and conventional methods. METHODS: In this study, a coronary artery centerline extraction method is proposed that comprises two parts: the preliminary centerline extraction network based on U-Net with a residual network, called C-UNet, and the multifactor centerline reconnection algorithm based on the geometric characteristics of blood vessels. RESULTS: The qualitative and quantitative results demonstrate the effectiveness of the presented method. In this study, three widely used evaluation indices were adopted to evaluate the performance of the method: precision, recall, and F1_Score. The experimental results show that this method can accurately extract coronary artery centerlines. CONCLUSIONS: The proposed centerline extraction method accurately extracts centerlines from X-ray coronary angiography images and improves both the accuracy and continuity of centerline extraction.

7.
Cortex ; 155: 287-306, 2022 Aug 17.
Artigo em Inglês | MEDLINE | ID: mdl-36075141

RESUMO

Language processing requires the integration of diverse sources of information across multiple levels of processing. A range of psycholinguistic properties have been documented in previous studies as having influence on brain activation during language processing. However, most of those studies have used factorial designs to probe the effect of one or two individual properties using highly controlled stimuli and experimental paradigms. Little is known about the neural correlates of psycholinguistic properties in more naturalistic discourse, especially during language production. The aim of our study is to explore the above issues in a rich fMRI dataset in which participants both listened to recorded passages of discourse and produced their own narrative discourse in response to prompts. Specifically, we measured 13 psycholinguistic properties of the discourse comprehended or produced by the participants, and we used principal components analysis (PCA) to address covariation in these properties and extract a smaller set of latent language characteristics. These latent components indexed vocabulary complexity, sensory-motor and emotional language content, discourse coherence and speech quantity. A parametric approach was adopted to study the effects of these psycholinguistic variables on brain activation during comprehension and production. We found that the pattern of effects across the cortex was somewhat convergent across comprehension and production. However, the degree of convergence varied across language properties, being strongest for the component indexing sensory-motor language content. We report the full, unthresholded effect maps for each psycholinguistic variable, as well as mapping how these effects change along a large-scale cortical gradient of brain function. We believe that our findings provide a valuable starting point for future, confirmatory studies of discourse processing.

8.
Adv Drug Deliv Rev ; 189: 114529, 2022 Sep 05.
Artigo em Inglês | MEDLINE | ID: mdl-36064031
9.
Front Immunol ; 13: 973601, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36105816

RESUMO

Background: As the forefront of nanomedicine, bionic nanotechnology has been widely used for drug delivery in order to obtain better efficacy but less toxicity for cancer treatments. With the rise of immunotherapy, the combination of nanotechnology and immunotherapy will play a greater potential of anti-tumor therapy. Due to its advantage of homologous targeting and antigen library from source cells, cancer cell membrane (CCM)-wrapped nanoparticles (CCNPs) has become an emerging topic in the field of immunotherapy. Key scientific concepts of review: CCNP strategies include targeting or modulating the tumor immune microenvironment and combination therapy with immune checkpoint inhibitors and cancer vaccines. This review summarizes the current developments in CCNPs for cancer immunotherapy and provides insight into the challenges of transferring this technology from the laboratory to the clinic as well as the potential future of this technology. Conclusion: This review described CCNPs have enormous potential in cancer immunotherapy, but there are still challenges in terms of translating their effects in vitro to the clinical setting. We believe that these challenges can be addressed in the future with a focus on individualized treatment with CCNPs as well as CCNPs combined with other effective treatments.


Assuntos
Vacinas Anticâncer , Nanopartículas , Neoplasias , Vacinas Anticâncer/uso terapêutico , Membrana Celular , Humanos , Fatores Imunológicos , Imunoterapia , Microambiente Tumoral
10.
Drugs Aging ; 2022 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-36107399

RESUMO

BACKGROUND AND OBJECTIVE: Prescribing cascades occur when a drug is prescribed to manage side effects of another drug, typically when a side effect is misinterpreted as a new condition. A consensus list of clinically important prescribing cascades that adversely affect older persons' health (i.e., where risks of the prescribing cascade usually exceed benefits) was developed to help identify, prevent, and manage prescribing cascades. METHODS: Three rounds of a modified Delphi process were conducted with a multidisciplinary panel of 38 clinicians from six countries with expertise in geriatric pharmacotherapy. The clinical importance of 139 prescribing cascades was assessed in Round 1. Cascades highly rated by ≥ 70% of panelists were included in subsequent rounds. Factors influencing ratings in Rounds 1 and 3 were categorized. After three Delphi rounds, highly rated prescribing cascades were reviewed by the study team to determine the final list of clinically important cascades consistent with potentially inappropriate prescribing. RESULTS: After three rounds, 13 prescribing cascades were highly rated by panelists. Following a study team review, the final tool includes nine clinically important prescribing cascades consistent with potentially inappropriate prescribing. Panelists reported that their ratings were influenced by many factors (e.g., how commonly they encountered the medications involved and the cascade itself, the severity of side effects, availability of alternatives). The relative importance of these factors in determining clinical importance varied by panelist. CONCLUSIONS: A nine-item consensus-based list of clinically important prescribing cascades, representing potentially inappropriate prescribing, was developed. Panelists' decisions about what constituted a clinically important prescribing cascade were multi-factorial. This tool not only raises awareness about these cascades but will also help clinicians recognize these and other important prescribing cascades. This list contributes to the prevention and management of polypharmacy and medication-related harm in older people.

11.
J Environ Public Health ; 2022: 5901718, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36120145

RESUMO

The ecological problems faced by China's environmental protection are becoming more and more serious. Serious haze occurs frequently in some areas. Water pollution, soil pollution, and other new types of pollution are still relatively prominent problems. Therefore, rural architectural planning and landscape optimization design should be based on the premise of ecological environmental protection. This paper puts forward the evaluation of rural architectural planning and landscape in the context of ecological environment protection and uses the analytic hierarchy process to analyze and obtain the evaluation results. This method has a comprehensive and scientific powerful evaluation function. The experimental results of this paper show that after the evaluation of the analytic hierarchy process, it is found that the comprehensive score of the architectural planning and landscape of village A is not very high. The highest weight is 0.3210, the landscape diversity score of street A is 1.28, and the landscape diversity score of street D is 1.76. This is the highest score, indicating that the architectural planning and landscape of the village cannot meet the needs of contemporary ecological environmental protection. Aiming at the problems existing in the landscape, the corresponding measures are also given at the end of the experiment, which has certain significance for the landscape optimization design.


Assuntos
Conservação dos Recursos Naturais , Ecossistema
12.
Cancer Discov ; 2022 Sep 19.
Artigo em Inglês | MEDLINE | ID: mdl-36122307

RESUMO

IDH wild-type glioblastoma (GBM) has a dismal prognosis. A better understanding of tumor evolution holds the key to developing more effective treatment. Here we study glioblastoma's natural evolutionary trajectory by using rare, multifocal samples. We sequenced 61,062 single cells from eight multifocal IDH wild-type primary GBMs and defined a natural evolution signature (NES) of the tumor. We show that the NES significantly associates with the activation of transcription factors that regulate brain development, including MYBL2 and FOSL2. Hypoxia is involved in inducing NES-transition potentially via activation of the HIF1A-FOSL2 axis. High NES tumor cells could recruit and polarize bone marrow-derived macrophages through activation of the FOSL2-ANXA1-FPR1/3 axis. These polarized macrophages can efficiently suppress T cell activity and accelerate NES-transition in tumor cells. Moreover, The polarized macrophages could upregulate CCL2 to induce tumor cell migration.

13.
J Control Release ; 2022 Sep 16.
Artigo em Inglês | MEDLINE | ID: mdl-36122895

RESUMO

Photodynamic therapy (PDT) can produce a large amount of reactive oxygen species (ROS) in the radiation field to kill tumor cells. However, the sustainable anti-tumor efficacy of PDT is limited due to the hypoxic microenvironment of tumor. In this study, classic PDT agent indocyanine green (ICG) and hypoxia-activated chemotherapeutic drug tirapazamine (TPZ) were loaded on mesoporous polydopamine (PDA) to construct PDA@ICG-TPZ nanoparticles (PIT). Then, PIT was camouflaged with cyclic arginine-glycine-aspartate (cRGD) modified tumor cell membranes to obtain the engineered membrane-coated nanoreactor (cRGD-mPIT). The nanoreactor cRGD-mPIT could achieve the dual-targeting ability via tumor cell membrane mediated homologous targeting and cRGD mediated active targeting. With the enhanced tumor-targeting and penetrating delivery system, PIT could efficiently accumulate in hypoxic tumor cells and the loaded drugs were quickly released in response to near-infrared (NIR) laser. The nanoreactor might produce cytotoxic ROS under NIR and further enhance hypoxia within tumor to activate TPZ, which efficiently inhibited hypoxic tumor by synergistic photodynamic-chemotherapy. Mechanically, hypoxia-inhibitory factor-1α (HIF-1α) was down-regulated by the synergistic therapy. Accordingly, the cRGD-mPIT nanoreactor with sustainable and cascade anti-tumor effects and satisfied biosafety might be a promising strategy in hypoxic tumor therapy.

14.
Adv Healthc Mater ; : e2200955, 2022 Sep 19.
Artigo em Inglês | MEDLINE | ID: mdl-36123781

RESUMO

Osteosarcoma is a rare malignant bone-originating tumor that usually occurs in young people. Programmed cell death 1 ligand 1 (PD-L1), an immune checkpoint protein, is highly expressed in osteosarcoma tissues. Several recent studies have indicated that the tumor-related role of PD-L1 in tumors, especially non-plasma membrane (NPM)-localized PD-L1, is not limited to immune regulation in osteosarcoma. Here, we combined mass spectrometry analysis with RNA-seq examination to identify the intracellular binding partners of PD-L1 and elucidate the underlying mechanism of its action. We found that NPM-localized PD-L1 interacted with Insulin-like growth factor binding protein-3 (IGFBP3) to promote osteosarcoma tumor growth by activating mTOR signaling. This interaction was enforced after phosphoglyceratekinase1 (PGK1)-mediated PD-L1 phosphorylation. Based on these findings, we designed a phosphorylation-mimicking peptide from PD-L1 and encapsulated it with a Cyclic RGD (cRGD)-modified red blood cell membrane (RBCM) vesicle (Peptide@cRGD-M). The Peptide@cRGD-M precisely delivered the PD-L1-derived phosphorylation-mimicking peptide into osteosarcoma lesions and significantly promoted its therapeutic effect on the tumor. Therefore, our investigation not only highlighted the function of NPM-localized PD-L1 but also used an engineering approach to synthesize a small molecular peptide capable of inhibiting osteosarcoma growth. This article is protected by copyright. All rights reserved.

15.
PLoS One ; 17(9): e0273785, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36103478

RESUMO

Thousand-grain weight is a key indicator of crop yield and an important parameter for evaluating cultivation measures. Existing methods based on image analysis are convenient but lack a counting algorithm that is suitable for multiple types of grains. This research develops an application program based on an Android device to quickly calculate the number of grains. We explore the short axis measurement method of the grains with morphological thought, and determine the relationship between the general corrosion threshold and the short axis. To solve the problem of calculating the number of grains in the connected area, the study proposes a corrosion algorithm based on the short axis and an improved corner point method. After testing a variety of crop grains and equipment, it was found that the method has high universality, supports grain counting with white paper as the background, and has high accuracy and calculation efficiency. The average accuracy rate is 97.9%, and the average time is less than 0.7 seconds. In addition, the difference between the average accuracy for various mobile phones and multiple crops is small. This research proposes a grain counting algorithm with a wide range of applications to meet the requirements of nonglare use in the field. The algorithm provides a fast, accurate, low-cost tool for counting grains of wheat, corn, mung bean, soybean, peanut, rapeseed, etc., which is less constrained by space and power conditions. The algorithm is highly adaptable and can provide a reference for the study of grain counting.


Assuntos
Grão Comestível , Triticum , Algoritmos , Processamento de Imagem Assistida por Computador , Zea mays
16.
Drug Deliv ; 29(1): 2995-3008, 2022 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-36104946

RESUMO

To increase the antitumor drug concentration in the liver tumor site and improve the therapeutic effects, a functionalized liposome (PPP-LIP) with tumor targetability and enhanced internalization after matrix metalloproteinase-2 (MMP2)-triggered cell-penetrating peptide (TATp) exposure was modified with myrcludex B (a synthetic HBV preS-derived lipopeptide endowed with compelling liver tropism) for liver tumor-specific delivery. After intravenous administration, PPP-LIP was mediated by myrcludex B to reach the hepatocyte surface. The MMP2-overexpressing tumor microenvironment deprotected PEG, exposing it to TATp, facilitating tumor penetration and subsequent efficient destruction of tumor cells. In live imaging of small animals and cellular uptake, PPP-LIP was taken up much more than typical unmodified liposomes in the ICR mouse liver and liver tumor cells. Hydroxycamptothecin (HCPT)-loaded PPP-LIP showed a better antitumor effect than commercially available HCPT injections among MTT, three-dimensional (3 D) tumor ball, and tumor-bearing nude mouse experiments. Our findings indicated that PPP-LIP nanocarriers could be a promising tumor-targeted medication delivery strategy for treating liver cancers with elevated MMP2 expression.


Assuntos
Carcinoma Hepatocelular , Neoplasias Hepáticas , Animais , Carcinoma Hepatocelular/tratamento farmacológico , Hepatócitos , Lipossomos , Neoplasias Hepáticas/tratamento farmacológico , Metaloproteinase 2 da Matriz , Camundongos , Camundongos Endogâmicos ICR , Microambiente Tumoral
17.
Artigo em Inglês | MEDLINE | ID: mdl-36124014

RESUMO

Ischemic stroke is a common cause of permanent disability worldwide. Magnoflorine has been discovered to have good antioxidation, immune regulation, and cardiovascular system protection functions. However, whether magnoflorine treatment protects against cerebral ischemic stroke and the mechanism of such protection remains unknown. Here, we investigated the effect of magnoflorine on the development of ischemic stroke disorder in rats. A middle cerebral artery occlusion (MCAO) model followed by 24 h reperfusion after 90 min ischemia was used. The rats were treated with magnoflorine (10 mg/kg or 20 mg/kg) for 15 consecutive days. The neurological deficit scores, cerebral infarct volume, and brain water content were measured. The neuronal density was determined using Nissl and NeuN staining. The oxidative stress levels were determined using commercial kits. Immunofluorescence staining of LC3 and western blot assay for LC3 and p62 were used to assess autophagy. Magnoflorine treatment significantly reduced the cerebral infarct volume and brain water content and improved the neurological deficit scores in the rat MCAO model. In addition, magnoflorine ameliorated neuronal injury and neuron density in the cortex of rats. Magnoflorine also prevented oxidative damage following ischemia, reflected by the decrement of nitric oxide and malondialdehyde and the increase of glutathione (GSH) and GSH peroxidase. Moreover, the fluorescence intensity of LC3 and the ratio of LC3-II to LC3-I were remarkably downregulated in ischemic rat administration of magnoflorine. Finally, the expression levels of p62, sirtuin 1 (Sirt1), and phosphorylated-adenosine monophosphate-activated protein kinase (AMPK) were upregulated with magnoflorine. Magnoflorine attenuated the cerebral ischemia-induced neuronal damage, which was possibly associated with antioxidative stress, suppression of autophagy, and activation of the Sirt1/AMPK pathway in the rats.

18.
Acta Pharmacol Sin ; 2022 Sep 20.
Artigo em Inglês | MEDLINE | ID: mdl-36127507

RESUMO

Aversive emotion of opioid withdrawal generates motivational state leading to compulsive drug seeking and taking. Kappa opioid receptor (KOR) and its endogenous ligand dynorphin have been shown to participate in the regulation of aversive emotion. In the present study, we investigated the role of dynorphin/KOR system in the aversive emotion following opioid withdrawal in acute morphine-dependent mice. We found that blockade of KORs before pairing by intracerebroventricular injection of KOR antagonist norBNI (20, 40 µg) attenuated the development of morphine withdrawal-induced conditioned place aversion (CPA) behavior. We further found that morphine withdrawal increased dynorphin A expression in the dorsal hippocampus, but not in the amygdala, prefrontal cortex, nucleus accumbens, and thalamus. Microinjection of norBNI (20 µg) into the dorsal hippocampus significantly decreased morphine withdrawal-induced CPA behavior. We further found that p38 MAPK was significantly activated in the dorsal hippocampus after morphine withdrawal, and the activation of p38 MAPK was blocked by pretreatment with norBNI. Accordingly, microinjection of p38 MAPK inhibitor SB203580 (5 µg) into the dorsal hippocampus significantly decreased morphine withdrawal-produced CPA behavior. This study demonstrates that upregulation of dynorphin/KOR system in the dorsal hippocampus plays a critical role in the formation of aversive emotion associated with morphine withdrawal, suggesting that KOR antagonists may have therapeutic value for the treatment of opioid withdrawal-induced mood-related disorders.

19.
Phys Chem Chem Phys ; 2022 Sep 21.
Artigo em Inglês | MEDLINE | ID: mdl-36128880

RESUMO

It has been generally recognized that the α-agostic interaction (M⋯H-C) in transition metal carbene compounds LnMCHR (R = H, Me etc.) can be interpreted with a double metal-carbon bonding model. This bonding model involves the reorganization of the σ component, which can be illustrated in terms of three-center two-electron (3c-2e) M-H-C covalent bond as in transition metal alkyl compounds. Herein, we propose an alternative partial triple metal-carbon bonding model to elucidate the agostic interaction in LnMCHR. Apart from the well-defined σ and π bonds, there exists a seemingly weak but decisive third force, namely the πCHR→dM bonding between an occupied π-like symmetric CHR orbital and a vacant metal d orbital, which is the true origin of the α-agostic effect. This partial triple bonding model is authenticated on both Fischer- and Schrock-type carbenes by an ab initio valence bond (VB) method or the block-localized wavefunction (BLW) method, which has the capability to quantify this notable π bonding and further demonstrate its geometric, energetic and spectral impacts on agostic transition metal carbene compounds. We also show that ancillary ligands can modulate the πCHR→dM bonding through electronic and steric effects.

20.
Chemistry ; 2022 Sep 11.
Artigo em Inglês | MEDLINE | ID: mdl-36089553

RESUMO

A visible-light mediated chemoselective transfer hydrogenation of α-aryl imino esters was demonstrated. The methodology has allowed the efficient and practical preparation of α-amino acid esters. The mechanism of the reaction was probed by DFT calculations and deuteration experiments, indicated deuterium was introduced into amino acid esters efficiently (up to 99% D ratio), enabling a feasible way to obtain deuterated amino acids using D 2 O as a cheap deuterium source.

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