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1.
Front Genet ; 13: 909267, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35692842

RESUMO

Shimao City is considered an important political and religious center during the Late Neolithic Longshan period of the Middle Yellow River basin. The genetic history and population dynamics among the Shimao and other ancient populations, especially the Taosi-related populations, remain unknown. Here, we sequenced 172 complete mitochondrial genomes, ranging from the Yangshao to Longshan period, from individuals related to the Shimao culture in northern Shaanxi Province and Taosi culture in southern Shanxi Province, Middle Yellow River basin. Our results show that the populations inhabiting Shimao City had close genetic connections with an earlier population in the Middle Neolithic Yangshao period of northern Shaanxi Province, revealing a mostly local origin for the Shimao Society. In addition, among the populations in other regions of the Yellow River basin, the Shimao-related populations had the closest maternal affinity with the contemporaneous Taosi populations from the Longshan period. The Shimao-related populations also shared more affinity with present-day northern Han populations than with the minorities and southern Han in China. Our study provides a new perspective on the genetic origins and structure of the Shimao people and the population dynamics in the Middle Yellow River basin during the Neolithic period.

2.
Magn Reson Imaging ; 91: 69-80, 2022 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-35643335

RESUMO

PURPOSE: To develop a motion-resolved and free-breathing liver magnetic resonance fingerprinting (MRF) protocol. METHODS: The deformation maps were obtained from the first singular image of MRF data. The reconstruction method enforced the consistency of the MRF data with the deformation maps by adding the deformation maps to the encoding matrix. A sliding window reconstruction was inherently assumed, with a window size of 60 repetition times (TRs) and a step size of 30 TRs. L1 wavelet regularization was applied to reduce the undersampling artifact. MRF was tested on four healthy volunteers with parameters: 13 s/slice, 0.39 s/frame, and 33 time frames/slice. RESULTS: For measuring the accuracy of the deformation map, the typical normalized root mean square error (NRMSE) of the first singular image after motion correction was 0.19. In the sagittal scan, the liver T1 and T2 were 808.7±96.8 ms and 52.7±11.6 ms, respectively. They agreed with our previously reported values, i.e., T1 = 759 ms and T2 = 51 ms at 3 T, using free-breathing liver MRF. Compared to breath-hold MRF, the NRMSEs for T1 and T2 maps (without considering vessel pixels) from the proposed method were 0.13 and 0.18, respectively. CONCLUSION: We demonstrated a motion-resolved MRF with a nominal frame rate of 2.5 Hz for free-breathing liver imaging.


Assuntos
Fígado , Imageamento por Ressonância Magnética , Humanos , Processamento de Imagem Assistida por Computador , Fígado/diagnóstico por imagem , Espectroscopia de Ressonância Magnética , Movimento (Física) , Imagens de Fantasmas
3.
Curr Med Sci ; 2022 Jun 21.
Artigo em Inglês | MEDLINE | ID: mdl-35727418

RESUMO

OBJECTIVE: Cholesteryl esters (CEs) are composed of various fatty acyl chains attached to the hydroxyl groups of cholesterol, and abnormalities in their metabolism are related to many diseases. This study aimed to develop an ultrahigh-performance liquid chromatography-quadrupole exactive mass spectrometry (UPLC-Q-Exactive MS) method to identify the CEs in plasma. METHODS: First, the MS fragmentation patterns were investigated using seven commercial CE standards. Then, the CEs in plasma were characterized through the accurate mass data of precursor ions and characteristic product ions. A strategy of step-by-step m/z scans in a narrow range was proposed to identify more trace CEs by the full-scan data-dependent MS/MS (ddMS2) mode. RESULTS: A total of 50 CE species consisting of 55 regioisomers were identified in human plasma. Among them, two species were reported for the first time. CONCLUSION: This study is the most comprehensive identification of CE species in human plasma to date. These results will contribute to the in-depth profiling of CEs in human plasma and provide guidance for animal model selection when studying lipid-related diseases.

4.
J Appl Clin Med Phys ; : e13695, 2022 Jun 20.
Artigo em Inglês | MEDLINE | ID: mdl-35723875

RESUMO

PURPOSE: The detection of abdominal free fluid or hemoperitoneum can provide critical information for clinical diagnosis and treatment, particularly in emergencies. This study investigates the use of deep learning (DL) for identifying peritoneal free fluid in ultrasonography (US) images of the abdominal cavity, which can help inexperienced physicians or non-professional people in diagnosis. It focuses specifically on first-response scenarios involving focused assessment with sonography for trauma (FAST) technique. METHODS: A total of 2985 US images were collected from ascites patients treated from 1 January 2016 to 31 December 2017 at the Shenzhen Second People's Hospital. The data were categorized as Ascites-1, Ascites-2, or Ascites-3, based on the surrounding anatomy. A uniform standard for regions of interest (ROIs) and the lack of obstruction from acoustic shadow was used to classify positive samples. These images were then divided into training (90%) and test (10%) datasets to evaluate the performance of a U-net model, utilizing an encoder-decoder architecture and contracting and expansive paths, developed as part of the study. RESULTS: Test results produced sensitivity and specificity values of 94.38% and 68.13%, respectively, in the diagnosis of Ascites-1 US images, with an average Dice coefficient of 0.65 (standard deviation [SD] = 0.21). Similarly, the sensitivity and specificity for Ascites-2 were 97.12% and 86.33%, respectively, with an average Dice coefficient of 0.79 (SD = 0.14). The accuracy and area under the curve (AUC) were 81.25% and 0.76 for Ascites-1 and 91.73% and 0.91 for Ascites-2. CONCLUSION: The results produced by the U-net demonstrate the viability of DL for automated ascites diagnosis. This suggests the proposed technique could be highly valuable for improving FAST-based preliminary diagnoses, particularly in emergency scenarios.

5.
Comput Intell Neurosci ; 2022: 1026494, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35707202

RESUMO

In this study, magnetic resonance imaging (MRI) was used to evaluate the relapse features of patients with Rolandic meningioma after the microsurgery. 53 patients with Rolandic meningioma were selected as the research objects, and they were divided into the relapse group (n = 16) and nonrelapse group (n = 37) according to whether patients had a relapse during the follow-up period. Differences in quality of life, 1H-MRS index, vascular density, and cell proliferation between the two groups were assessed as well as imaging differences between the two groups were analyzed using MRI. The results showed that the patients' quality-of-life scores in the two groups increased notably after the surgical treatment (P < 0.05). Compared with the nonrelapse group, the proportion of irregular boundary and uneven enhancement of focal tissue in the relapse group was signally increased (P < 0.05). Compared with the nonrelapse group, cell proliferation index, vascular density and imaging index, mean tumor diameter, mean transit time (MTT), time to peak (TTP), fractional anisotropy (FA), choline (Cho)/N-acetylaspartic acid (NAA), Cho/creatine (Cr), lactic acid (Lac)/Cr, and the maximum value of relative cerebral blood volume (rCBVmax) in the relapse group were obviously increased (P < 0.05). However, the apparent dispersion coefficient, NAA/Cr, and Lac/NAA values decreased greatly (P < 0.05). To sum up, the microsurgical treatment helped improve the quality of life of patients with Rolandic meningioma, and MR imaging could be used to determine the relapse of Rolandic meningioma after microsurgical treatment.


Assuntos
Neoplasias Meníngeas , Meningioma , Ácido Aspártico , Colina , Creatina , Humanos , Imageamento por Ressonância Magnética , Espectroscopia de Ressonância Magnética/métodos , Neoplasias Meníngeas/diagnóstico por imagem , Neoplasias Meníngeas/cirurgia , Meningioma/diagnóstico por imagem , Meningioma/cirurgia , Recidiva Local de Neoplasia/diagnóstico por imagem , Qualidade de Vida
6.
J Med Chem ; 65(11): 7415-7437, 2022 Jun 09.
Artigo em Inglês | MEDLINE | ID: mdl-35594541

RESUMO

Despite significant efficacy, one of the major limitations of small-molecule Bruton's tyrosine kinase (BTK) agents is the presence of clinically acquired resistance, which remains a major clinical challenge. This Perspective focuses on medicinal chemistry strategies for the development of BTK small-molecule inhibitors against resistance, including the structure-based design of BTK inhibitors targeting point mutations, e.g., (i) developing noncovalent inhibitors from covalent inhibitors, (ii) avoiding steric hindrance from mutated residues, (iii) making interactions with the mutated residue, (iv) modifying the solvent-accessible region, and (v) developing new scaffolds. Additionally, a comparative analysis of multi-inhibitions of BTK is presented based on cross-comparisons between 2916 unique BTK ligands and 283 other kinases that cover 7108 dual/multiple inhibitions. Finally, targeting the BTK allosteric site and uding proteolysis-targeting chimera (PROTAC) as two potential strategies are addressed briefly, while also illustrating the possibilities and challenges to find novel ligands of BTK.


Assuntos
Química Farmacêutica , Inibidores de Proteínas Quinases , Tirosina Quinase da Agamaglobulinemia , Ligantes , Inibidores de Proteínas Quinases/química , Inibidores de Proteínas Quinases/farmacologia , Inibidores de Proteínas Quinases/uso terapêutico
7.
Spectrochim Acta A Mol Biomol Spectrosc ; 279: 121408, 2022 May 20.
Artigo em Inglês | MEDLINE | ID: mdl-35617839

RESUMO

Polyvinyl pyrrolidone (PVP), playing roles as a templating agent, can be applied to prepare blue-emitting copper nanoclusters (Cu NCs@PVP) on the basis of a rapid chemical reduction synthesis method. The Cu NCs@PVP displayed a blue emission wavelength at 430 nm and the corresponding quantum yield (QY) could reach 10.4%. Subsequently, the as-synthesized Cu NCs@PVP were used for the trace analysis of furaltadone based on the inner filter effect (IFE) between Cu NCs@PVP and furaltadone, which caused the fluorescence to be effectively quenched. Additionally, this proposed determination platform based on the Cu NCs@PVP for furaltadone sensing possessed an excellent linear range from 0.5 to 100 µM with a lower detection limit of 0.045 µM (S/N = 3). Meanwhile, the Cu NCs@PVP also could be applied for the sensing of temperature. Furthermore, the practicability of the sensing platform has been successfully verified by measuring furaltadone in real samples, affirming its potential to increase fields for the determination of furaltadone.

8.
ACS Appl Mater Interfaces ; 14(22): 26014-26023, 2022 Jun 08.
Artigo em Inglês | MEDLINE | ID: mdl-35608943

RESUMO

Although numerous studies on polymeric protective films to stabilize lithium (Li)-metal electrodes have been reported, the construction of self-healing polymers that enables the long-term operation of Li-metal batteries (LMBs) at relatively low temperatures has rarely been demonstrated. Herein, a highly stretchable, autonomous self-healable, and ionic-conducting polymer network (SHIPN) is synthesized as an efficient protective film for LMBs. The network backbone, synthesized from copolymerization of poly(ethylene glycol)-mono-methacrylate (PEGMMA) and 2-[[(butylamino)carbonyl]oxy]ethyl acrylate (BCOE), is chemically cross-linked via diisocyanate. With SHIPN-modified electrodes, enhanced electrochemical performance can be achieved in Li/Cu, Li/Li, and Li/LiFePO4 (Li/LFP) cells. The SHIPN@Li/LFP cell delivers a capacity retention of 85.6% after 500 cycles at 5 °C, resulting from the low-temperature self-healability of SHIPN. In full cells with a high-mass-loading LFP cathode (∼17 mg cm-2), the capacity retention is at least 300% higher than that with a bare Li electrode. Further physical characterizations of electrodes confirm the effect of SHIPN in enhancing the interfacial stability and suppressing Li dendrite growth. Our results will provide insights into rationally designing soft and hybrid materials toward stable LMBs at different temperatures.

9.
BMC Musculoskelet Disord ; 23(1): 509, 2022 May 30.
Artigo em Inglês | MEDLINE | ID: mdl-35637476

RESUMO

BACKGROUND: Low back pain (LBP) is associated with lumbar disc degeneration (LDD) and fatty infiltration of paraspinal muscles. However, there are some controversies about the relationship between LDD and fatty infiltration of paraspinal muscles, and the causation of them is also not clear. Thus, we investigated whether the degree of LDD was associated with fatty infiltration of paraspinal muscles and preliminarily explored the underlying mechanism. METHODS: A retrospective study was conducted on 109 patients with chronic LBP. The degree of LDD was assessed by the Pfirrmann classification. Total muscle cross-sectional area, L4 vertebral body endplate area, and fat cross-sectional area at axial T2-weighted MRI were measured. Multifidus and lumbar disc specimens were taken from eight individuals undergoing discectomy for disc herniation. Gene and protein expression levels of TNF were quantified through qPCR assays and ELISA, respectively. RESULTS: The relative cross-sectional area, total muscle cross-sectional area, and muscle cross-sectional area asymmetry were not related to LDD. Pfirrmann grades correlated strongly with fatty infiltration of the multifidus and moderately with fatty infiltration of the erector spinae and the psoas muscles. Linear regression analysis suggested that Pfirrmann grades were most associated with fatty infiltration of the multifidus. Compared with II-degree degeneration discs (mild-degeneration group), fatty infiltration of the multifidus in IV-degree degeneration discs (severe-degeneration group) significantly increased, accompanied by increased mRNA expression of TNF. Meanwhile, the protein expression levels of TNF (pg/g protein) in discs (16.62 ± 4.33) and multifidus (13.10 ± 2.76) of the severe-degeneration group were higher than those in the mild-degeneration group (disc: 9.75 ± 2.18; multifidus: 7.84 ± 2.43). However, the mRNA expression of TNF in the multifidus was not significantly different between the two groups. CONCLUSIONS: The results suggest that LDD is associated with fatty infiltration of the multifidus. The possible underlying mechanism is that LDD induces fatty infiltration by inflammation. Furthermore, compared with the erector spinae and the psoas muscles, fatty infiltration of the multifidus shows an optimal correlation with LDD, which may contribute to further understanding of LDD pathology.


Assuntos
Degeneração do Disco Intervertebral , Deslocamento do Disco Intervertebral , Dor Lombar , Humanos , Degeneração do Disco Intervertebral/patologia , Deslocamento do Disco Intervertebral/complicações , Dor Lombar/etiologia , Dor Lombar/patologia , Músculos Paraespinais/diagnóstico por imagem , Músculos Paraespinais/patologia , RNA Mensageiro , Estudos Retrospectivos
10.
Front Genet ; 13: 853471, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35547245

RESUMO

The role of N6-methyladenosine (m6A)-associated long-stranded non-coding RNA (lncRNA) in pancreatic cancer is unclear. Therefore, we analysed the characteristics and tumour microenvironment in pancreatic cancer and determined the value of m6A-related lncRNAs for prognosis and drug target prediction. An m6A-lncRNA co-expression network was constructed using The Cancer Genome Atlas database to screen m6A-related lncRNAs. Prognosis-related lncRNAs were screened using univariate Cox regression; patients were divided into high- and low-risk groups and randomised into training and test groups. In the training group, least absolute shrinkage and selection operator (LASSO) was used for regression analysis and to construct a prognostic model, which was validated in the test group. Tumor mutational burden (TMB), immune evasion, and immune function of risk genes were analysed using R; drug sensitivity and potential drugs were examined using the Genomics of Drug Sensitivity in Cancer database. We screened 129 m6A-related lncRNAs; 17 prognosis-related m6A-related lncRNAs were obtained using multivariate analysis and three m6A-related lncRNAs (AC092171.5, MEG9, and AC002091.1) were screened using LASSO regression. Survival rates were significantly higher (p < 0.05) in the low-risk than in the high-risk group. Risk score was an independent predictor affecting survival (p < 0.001), with the highest risk score being obtained by calculating the c-index. The TMB significantly differed between the high- and low-risk groups (p < 0.05). In the high- and low-risk groups, mutations were detected in 61 of 70 samples and 49 of 71 samples, respectively, with KRAS, TP53, and SMAD4 showing the highest mutation frequencies in both groups. A lower survival rate was observed in patients with a high versus low TMB. Immune function HLA, Cytolytic activity, and Inflammation-promoting, T cell co-inhibition, Check-point, and T cell co-stimulation significantly differed in different subgroups (p < 0.05). Immune evasion scores were significantly higher in the high-risk group than in the low-risk group. Eight sensitive drugs were screened: ABT.888, ATRA, AP.24534, AG.014699, ABT.263, axitinib, A.443654, and A.770041. We screened m6A-related lncRNAs using bioinformatics, constructed a prognosis-related model, explored TMB and immune function differences in pancreatic cancer, and identified potential therapeutic agents, providing a foundation for further studies of pancreatic cancer diagnosis and treatment.

11.
Med Biol Eng Comput ; 2022 May 06.
Artigo em Inglês | MEDLINE | ID: mdl-35522357

RESUMO

The dynamic functional connectivity analysis provides valuable information for understanding functional brain activity underlying different cognitive processes. Modeling spatio-temporal dynamics in functional brain networks is critical for underlying the functional mechanism of autism spectrum disorder (ASD). In our study, we propose a machine learning approach for the classification of neurological disorders while providing an interpretable framework, which thoroughly captures spatio-temporal features in resting-state functional magnetic resonance imaging (rs-fMRI) data. Specifically, we first transform rs-fMRI time-series into temporal multi-graph using the sliding window technique. A temporal multi-graph clustering is then designed to eliminate the inconsistency of the temporal multi-graph series. Then, a graph structure-aware LSTM (GSA-LSTM) is further proposed to capture the spatio-temporal embedding for temporal graphs. Furthermore, The proposed GSA-LSTM can not only capture discriminative features for prediction but also impute the incomplete graphs for the temporal multi-graph series. Extensive experiments on the autism brain imaging data exchange (ABIDE) dataset demonstrate that the proposed dynamic brain network embedding learning outperforms the state-of-the-art brain network classification models. Furthermore, the obtained clustering results are consistent with the previous neuroimaging-derived evidence of biomarkers for autism spectrum disorder (ASD).

12.
Molecules ; 27(9)2022 Apr 24.
Artigo em Inglês | MEDLINE | ID: mdl-35566098

RESUMO

Shikonin is the main component of root extracts from the Chinese herbal medicine Lithospermum erythrorhizon, which is commonly used for the treatment of various diseases including cancer. Previous research showed that shikonin suppressed pancreatic cancer growth; nevertheless, its molecular targets and mechanisms have not been elucidated. This study aimed to investigate the interaction and regulatory mechanisms of shikonin on its potential target p21-activated kinase 1 (PAK1). Through a labchip-based screening method, shikonin was identified as a potential bioactive PAK1 inhibitor. Molecular docking technology was used to detect the interaction sites of shikonin and PAK1 kinase. Western blot was performed to validate the mechanism. MTT and flow cytometry were practiced to investigate the effect of shikonin against pancreatic cancer cells. The results show that shikonin significantly inhibited the activity of PAK1 kinase with IC50 value of 7.252 ± 0.054 µM. Molecular docking studies showed that shikonin binds to the ATP-binding pocket of the PAK1 kinase domain. Moreover, shikonin inhibited PAK1 activation and its downstream signaling pathway proteins, while reducing proliferation and inducing apoptosis of pancreatic cancer cells. Further studies showed that the treatment of shikonin sensitized pancreatic cancer cells to chemotherapeutic drugs. These results suggest that shikonin, a potential natural inhibitor targeting PAK1 kinase, has promising potent applications in the treatment of pancreatic cancer and chemotherapy sensitization.


Assuntos
Naftoquinonas , Neoplasias Pancreáticas , Apoptose , Linhagem Celular Tumoral , Proliferação de Células , Humanos , Simulação de Acoplamento Molecular , Naftoquinonas/farmacologia , Neoplasias Pancreáticas/tratamento farmacológico , Quinases Ativadas por p21
13.
Front Public Health ; 10: 836113, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35570903

RESUMO

Objectives: This study aims to evaluate the direct effects of work stress, health status and presenteeism on task performance, and further explore the mediating effects of health status and presenteeism, hoping to provide theoretical basis for improving the performance of medical staff. Methods: A cross-sectional study was conducted among medical staff in Jilin Province, Northeast China. The Challenge and Hindrance-Related Self-Reported Stress scale, Short Form-8 Health Survey scale, Stanford Presenteeism Scale and Task Performance Scale were adopted to assess the work stress, health status, presenteeism and task performance of medical staff. Results: A total of 4,347 questionnaires were distributed among medical staff, and 4261 were valid, for an effective rate of 98.02%. The mean scores for work stress, health status, presenteeism and task performance were 2.05 ± 0.84, 4.18 ± 0.68, 2.15 ± 0.79 and 4.49 ± 0.64, respectively. The ANOVA results showed that there were significant differences in the task performance scores between different genders, ages, marital statuses, professional titles, departments and work years (P < 0.05). Work stress (ß = -0.136, P < 0.001) and presenteeism (ß = -0.171, P < 0.001) were negative predictors of task performance. Health status (ß = 0.10; P < 0.001) was positive predictor of task performance. Health status (ß = -0.070; P < -0.001) and presenteeism (ß = -0.064; P < 0.001) mediated the relationship between work stress and task performance (P < 0.001). Presenteeism mediated the relationship between health status and task performance (ß = 0.07; P < 0.001). Conclusion: Work stress and presenteeism had significant negative impact on the task performance of medical staff; health status had a significant positive effect on task performance. Meanwhile, health status and presenteeism played a mediating role in the relationship between work stress and task performance, and presenteeism played a mediating role in the relationship between health status and task performance. Reasonable assignment of tasks can reduce the work stress, but to improve the performance of medical staff, we should pay more attention on improving health, such as making health-related safeguard measures, raising awareness, building a platform, etc.


Assuntos
COVID-19 , Estresse Ocupacional , COVID-19/epidemiologia , China/epidemiologia , Estudos Transversais , Feminino , Nível de Saúde , Humanos , Masculino , Corpo Clínico , Estresse Ocupacional/epidemiologia , Pandemias , Presenteísmo , Análise e Desempenho de Tarefas
14.
Front Nutr ; 9: 850971, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35600830

RESUMO

Purpose: Gallbladder carcinoma (GBC) is the most common malignancy of the biliary tract, with a 5-year survival rate of 5%. The prognostic models to predict the prognosis of patients with GBC remain controversial. Therefore, to construct a prognosis prediction of GBC, a retrospective cohort study was carried out to investigate the prognostic nutritional index and histological grade in the long-term outcome of patients with GBC after radical surgery (RS). Methods: A retrospective study of a total of 198 patients with GBC who underwent surgical treatment were enrolled. The hematological indicators, imageological data, and perioperative clinical data were acquired for statistical analysis and poor prognosis model construction. Results: Prognostic nutrition index (PNI) < 45.88, maximum tumor diameter (MTD) > 2.24 cm, and jaundice (JD) were all associated with a poor prognosis in multivariate logistic regression analysis. The prognosis prediction model was based on the three risk factors, which indicated a superior predictive ability in the primary cohort [area under the curve (AUC) = 0.951] and validation cohort (AUC = 0.888). In multivariate Cox regression analysis, poorly differentiation (PD) was associated with poor 3-year survival. In addition, Kaplan-Meier (KM) survival analysis suggested that GBC patients with high-risk scores and PD had a better prognosis after RS (p < 0.05), but there was no significant difference in prognosis for patients with non-poorly differentiation (NPD) or low-risk scores after RS (p > 0.05). Conclusion: Our prediction model for GBC patients with prognosis evaluation is accurate and effective. For patients with PD and high-risk scores, RS is highly recommended; a simple cholecystectomy can also be considered for acceptance for patients with NPD or low-risk score. The significant findings provide a new therapeutic strategy for the clinical treatment of GBC.

15.
Neuron ; 110(12): 1993-2008.e6, 2022 Jun 15.
Artigo em Inglês | MEDLINE | ID: mdl-35443154

RESUMO

Empathic pain has attracted the interest of a substantial number of researchers studying the social transfer of pain in the sociological, psychological, and neuroscience fields. However, the neural mechanism of empathic pain remains elusive. Here, we establish a long-term observational pain model in mice and find that glutamatergic projection from the insular cortex (IC) to the basolateral amygdala (BLA) is critical for the formation of observational pain. The selective activation or inhibition of the IC-BLA projection pathway strengthens or weakens the intensity of observational pain, respectively. The synaptic molecules are screened, and the upregulated synaptotagmin-2 and RIM3 are identified as key signals in controlling the increased synaptic glutamate transmission from the IC to the BLA. Together, these results reveal the molecular and synaptic mechanisms of a previously unidentified neural pathway that regulates observational pain in mice.


Assuntos
Complexo Nuclear Basolateral da Amígdala , Animais , Complexo Nuclear Basolateral da Amígdala/fisiologia , Córtex Cerebral/fisiologia , Ácido Glutâmico/fisiologia , Camundongos , Dor , Sinapses
16.
Transplant Proc ; 54(3): 638-644, 2022 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-35428510

RESUMO

BACKGROUND: Tacrolimus is a common immunosuppressive for transplantation. The enzyme encoded by the CYP3A5 gene can regulate the metabolism of tacrolimus, and the polymorphism of the CYP3A5 gene regulates the enzyme function. However, its characteristics in Chinese kidney transplant recipients remain unclear. METHODS: A computer-based database retrieval included Pubmed, Web of Science, Embase, China National Knowledge Infrastructure, China Biology Medicine Disc, and WanFang databases between January 2010 and December 2020. Search terms included "CYP3A5," "polymorphism," and "renal transplantation." Literature included in this study had sample sizes >130. Genetic testing data of CYP3A5*1/*1, *1/*3, *3/*3 genes were analyzed using a statistical method of meta-analysis to explore the mutation rate of CYP3A5 in Chinese and foreign populations. RESULTS: The frequency of the A allele in the CYP3A5 gene was 23% in all transplant recipients from the 28 included studies. The frequency in Chinese renal transplant recipients was 29%, and it was 30% in renal transplant recipients from other Asian countries but significantly higher than that in Western renal transplant recipients (14%). In subgroup analysis, the frequencies of the A allele in renal transplant recipients in different parts of China were comparable. CONCLUSIONS: We found that there were significant differences in CYP3A5 gene polymorphism between Asians and Westerners. There was no significant difference in the frequency of the A allele in CYP3A5 gene among Chinese renal transplant recipients from different parts of China.


Assuntos
Citocromo P-450 CYP3A , Transplante de Rim , /genética , Citocromo P-450 CYP3A/genética , Citocromo P-450 CYP3A/metabolismo , Genótipo , Humanos , Imunossupressores/uso terapêutico , Transplante de Rim/efeitos adversos , Transplante de Rim/métodos , Polimorfismo de Nucleotídeo Único , Tacrolimo
17.
ACS Nano ; 2022 Apr 22.
Artigo em Inglês | MEDLINE | ID: mdl-35451839

RESUMO

The key to controlling the spread of the coronavirus disease 2019 (COVID-19) and reducing mortality is highly dependent on the safe and effective use of vaccines for the general population. Current COVID-19 vaccination practices (intramuscular injection of solution-based vaccines) are limited by heavy reliance on medical professionals, poor compliance, and laborious vaccination recording procedures, resulting in a waste of health resources and low vaccination coverage, etc. In this study, we developed a smart mushroom-inspired imprintable and lightly detachable (MILD) microneedle platform for the effective and convenient delivery of multidose COVID-19 vaccines and decentralized vaccine information storage. The mushroom-like structure allows the MILD system to be easily pressed into the skin and detached from the patch base, acting as a "tattoo" to record the vaccine counts in situ without any storage equipment, offering quick accessibility and effortless readout, saving a great deal of valuable time and energy for both patients and health professionals. After loading inactivated SARS-CoV-2 virus-based vaccines, MILD system induced a high level of antibodies against the SARS-CoV-2 receptor-binding domain (RBD) in vivo without eliciting systemic toxicity and local damage. Collectively, this smart delivery platform serves as a promising carrier to improve COVID-19 vaccination efficacy through its dual capabilities of vaccine delivery and in situ data storage, thus exhibiting great potential for helping to contain the COVID-19 pandemic or a resurgence.

18.
Front Plant Sci ; 13: 860577, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35463452

RESUMO

Steroidal glycoalkaloids (SGAs) are cholesterol-derived molecules that contribute to the pathogen defense in tomato but are toxic and considered to be antinutritional compounds to humans. APETALA2/Ethylene Responsive Factor (AP2/ERF) family transcription factors (TFs) play an indispensable role in various biological processes, such as plant growth and development, fruit ripening, biotic and abiotic stresses responses, and SGA biosynthesis. In this study, we identified 176 AP2/ERF genes that were domesticated or improved SlAP2/ERF in the tomato variome (Solanum lycopersicum) within either domestication or improvement sweeps, respectively. According to the RNA-sequencing data, 93 of the ERF genes with high transcriptional level (Transcripts Per Million, TPM > 1) belong to six clusters. Weighted gene co-expression network analysis (WGCNA) and metabolite-based genome-wide association study (mGWAS) analyses revealed that the expression level of the Solyc04g071770 (SlERF.D6) gene in the cluster six gradually increased as the fruit matured. Transient transformation verified that the overexpression of SlERF.D6 significantly promoted fruit ripening and regulated the expression of multiple genes in the SGA synthesis pathway, thereby affecting the SGA content of the fruit. Virus-induced gene silencing (VIGS) showed that the silencing of SlERF.D6 delayed fruit ripening and influenced the content of SGAs. Our data provide new insights into AP2/ERF TFs in tomato, offer a candidate TF for fruit development and steroidal glycoalkaloids, and provide new resources for tomato breeding and improvement.

19.
Microbes Infect ; : 104980, 2022 Apr 14.
Artigo em Inglês | MEDLINE | ID: mdl-35430372

RESUMO

Propionibacterium acnes infection in intervertebral discs (IVDs) is a newly identified cause of low back pain (LBP). In the present study, we aimed to determine whether the nerve growth factor (NGF), a critical pro-algesic factor, is involved in P. acnes-induced LBP. After co-culturing with P. acnes, nucleus pulposus cells (NPCs) produced NGF, which was upregulated after inoculation of P. acnes into IVDs of rats. In addition, administration of P. acnes into rat IVDs leads to significant mechanical allodynia and cold hyperreflexia, and significant upregulation of the pain-related factors, including substance P (SP), calcitonin gene-related peptide (CGRP), and Transient Receptor Potential Vanilloid1 (TRPV1), in rat dorsal root ganglia (DRG), suggesting that P. acnes-inoculated rats had obvious discogenic LBP. However, inhibition of NGF bioactivity significantly ameliorated P. acnes-induced discogenic LBP, suggesting that P. acnes induced LBP via NGF. Finally, an in vitro mechanism study demonstrated that P. acnes stimulated NPCs to secrete NGF via TLR-2 receptor and NF-κB p65/JNK pathway, or ROS-related pathway. Therefore, P. acnes had a strong association with LBP by stimulating NPCs to secrete NGF via the TLR2-NF- κB/JNK or ROS-related pathway. These findings propose a novel potential therapeutic strategy for LBP.

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