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BACKGROUND: The traditional suturing method for cyclodialysis cleft usually requires an incision in the sclera for direct suturing, resulting in greater damage and a high risk of postoperative complications. The purpose of this work is to propose a newly intrascleral double continuous suture repair technique for the treatment of cyclodialysis clefts. METHODS: Seven patients with cyclodialysis cleft underwent microinvasive intrascleral double continuous suture repair surgery to restore the attachment of the detached ciliary body to the sclera without scleral incision. All operations were performed by the same surgeon. Preoperative and postoperative visual acuity (VA), intraocular pressure (IOP), slit lamp and corneal examination results, ultrasound biomicroscopy (UBM) and optical coherence tomography (OCT) results were recorded. RESULTS: Closure of the cyclodialysis cleft was achieved in 7 eyes and no obvious complications occurred after the operation. Intraocular pressure increased from preoperatively 6.8 ± 1.35 mmHg (range: 4.8-8.0 mmHg) to postoperatively 12.5 ± 4.0 mmHg (range: 8.0-20.0 mmHg) (paired sample T test, P < 0.01). Best-corrected Snellen visual acuity improved from preoperatively range 20/2000-20/63 to range 20/200-20/25 at final follow-up. CONCLUSION: In short, intrascleral double continuous suture repair surgical is safe and effective in treating cyclodialysis cleft, with minimal surgical trauma.
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Background: Our study aimed to develop a nomogram incorporating cytokeratin fragment antigen 21-1 (CYFRA21-1) to assist in differentiating between patients with intrahepatic cholangiocarcinoma (ICC) and hepatocellular carcinoma (HCC). Methods: A total of 487 patients who were diagnosed with ICC and HCC at Qilu Hospital of Shandong University were included in this study. The patients were divided into a training cohort and a validation cohort based on whether the data collection was retrospective or prospective. Univariate and multivariate analyses were employed to select variables for the nomogram. The discrimination and calibration of the nomogram were evaluated using the area under the receiver operating characteristic curve (AUC) and calibration plots. Decision curve analysis (DCA) was used to assess the nomogram's net benefits at various threshold probabilities. Results: Six variables, including CYFRA21-1, were incorporated to establish the nomogram. Its satisfactory discriminative ability was indicated by the AUC (0.972 for the training cohort, 0.994 for the validation cohort), sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) values. The Hosmer-Lemeshow test and the calibration plots demonstrated favorable consistency between the nomogram predictions and the actual observations. Moreover, DCA revealed the clinical utility and superior discriminative ability of the nomogram compared to the model without CYFRA21-1 and the model consisting of the logarithm of alpha-fetoprotein (Log AFP) and the logarithm of carbohydrate antigen 19-9 (Log CA19-9). Additionally, the AUC values suggested that the discriminative ability of Log CYFRA21-1 was greater than that of the other variables used as diagnostic biomarkers. Conclusions: This study developed and validated a nomogram including CYFRA21-1, which can aid clinicians in the differential diagnosis of ICC and HCC patients.
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Wheat yellow mosaic virus (WYMV) causes severe viral wheat disease in Asia. The WYMV P1 protein encoded by RNA2 has viral suppressor of RNA silencing (VSR) activity to facilitate virus infection, however, VSR activity has not been identified for P2 protein encoded by RNA2. In this study, P2 protein exhibited strong VSR activity in Nicotiana benthamiana at the four-leaf stage, and point mutants P70A and G230A lost VSR activity. Protein P2 interacted with calmodulin (CaM) protein, a gene-silencing associated protein, while point mutants P70A and G230A did not interact with it. Competitive bimolecular fluorescence complementation and competitive co-immunoprecipitation experiments showed that P2 interfered with the interaction between CaM and calmodulin-binding transcription activator 3 (CAMTA3), but the point mutants P70A and G230A could not. Mechanical inoculation of wheat with in vitro transcripts of WYMV infectious cDNA clone further confirmed that VSR-deficient mutants P70A and G230A decreased WYMV infection in wheat plants compared with the wild type. In addition, RNA silencing, temperature, ubiquitination and autophagy had significant effects on accumulation of P2 protein in N. benthamiana leaves. In conclusion, WYMV P2 plays a VSR role in N. benthamiana and promotes virus infection by interfering with calmodulin-related antiviral RNAi defense.
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The physiological and genotypic characteristics of Mangrovibacter (MGB) remain largely unexplored, including their distribution and abundance within ecosystems. M. phragmitis (MPH) ASIOC01 was successfully isolated from activated sludge (AS), which was pre-enriched by adding 1,3-dichloro-2-propanol and 3-chloro-1,2-propanediol as carbon sources. The new isolate, MPH ASIOC01, exhibited resilience in a medium containing sodium chloride concentration up to 11% (with optimal growth observed at 3%) and effectively utilizing glycerol as their sole carbon source. However, species delimitation of MGBs remains challenging due to high 16S rRNA sequence similarity (greater than 99% ANI) among different MGBs. In contrast, among the housekeeping gene discrepancies, the tryptophan synthase beta chain gene can serve as a robust marker for fast species delimitation among MGBs. Furthermore, the complete genome of MPH ASIOC01 was fully sequenced and circlized as a single contig using the PacBio HiFi sequencing method. Comparative genomics revealed genes potentially associated with various phenotypic features of MGBs, such as nitrogen-fixing, phosphate-solubilizing, cellulose-digesting, Cr-reducing, and salt tolerance. Computational analysis suggested that MPH ASIOC01 may have undergone horizontal gene transfer events, possibly contributing unique traits such as antibiotic resistance. Finally, our findings also disclosed that the introduction of MPH ASIOC01 into AS can assist in the remediation of wastewater chemical oxygen demand, which was evaluated using gas chromatograph-mass spectrometry. To the best of our knowledge, this study offers the most comprehensive understanding of the phenotypic and genotypic features of MGBs to date.
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[This corrects the article DOI: 10.3389/fncel.2022.878673.].
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[This retracts the article DOI: 10.1021/acsomega.3c01296.].
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BACKGROUND: Emodin, a natural anthraquinone derivative found in various Chinese medicinal herbs, has been proved to be an effective therapeutic agent in the treatment of many diseases. However, its effect on lung injury after intestinal ischemia/reperfusion injury remains unknown. This research was designed to investigate whether emodin protects against intestinal ischemia/reperfusion-induced lung injury and to elucidate the underlying molecular mechanisms in vivo and in vitro. METHODS: Intestinal ischemia/reperfusion injury was induced by occluding the superior mesenteric artery in mice, and mouse lung epithelial-12 cells were subjected to oxygen-glucose deprivation and reoxygenation to establish an in vitro model. RESULTS: Our data indicated that emodin treatment reduced intestinal ischemia/reperfusion-induced oxidative stress, inflammation and apoptosis in lung tissues and alleviated lung injury. However, the protective effects of emodin on intestinal ischemia/reperfusion-induced lung injury were reversed by the protein kinase B inhibitor triciribine or the heme oxygenase-1 inhibitor tin protoporphyrin IX. The protein kinase inhibitor triciribine also downregulated the expression of heme oxygenase-1. CONCLUSION: In conclusion, our data suggest that emodin treatment protects against intestinal ischemia/reperfusion-induced lung injury by enhancing heme oxygenase-1 expression via activation of the PI3K/protein kinase pathway. Emodin may act as a potential therapeutic agent for the prevention and treatment of lung injury induced by intestinal ischemia/reperfusion.
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Emodina , Heme Oxigenase-1 , Fosfatidilinositol 3-Quinases , Proteínas Proto-Oncogênicas c-akt , Traumatismo por Reperfusão , Transdução de Sinais , Regulação para Cima , Animais , Emodina/farmacologia , Emodina/uso terapêutico , Traumatismo por Reperfusão/prevenção & controle , Traumatismo por Reperfusão/metabolismo , Traumatismo por Reperfusão/etiologia , Traumatismo por Reperfusão/tratamento farmacológico , Camundongos , Proteínas Proto-Oncogênicas c-akt/metabolismo , Heme Oxigenase-1/metabolismo , Masculino , Fosfatidilinositol 3-Quinases/metabolismo , Transdução de Sinais/efeitos dos fármacos , Regulação para Cima/efeitos dos fármacos , Intestinos/irrigação sanguínea , Intestinos/patologia , Intestinos/efeitos dos fármacos , Camundongos Endogâmicos C57BL , Lesão Pulmonar/etiologia , Lesão Pulmonar/prevenção & controle , Lesão Pulmonar/metabolismo , Lesão Pulmonar/tratamento farmacológico , Lesão Pulmonar/patologia , Modelos Animais de Doenças , Estresse Oxidativo/efeitos dos fármacos , Proteínas de MembranaRESUMO
Herein, we report an extensive phytochemical study on the whole plant of Drymaria cordata, which led to the isolation of ten new orbitides, named drymariamides A-J (1-10). Compounds 2, 3, and 5 incorporate rare residues of noncanonical amino acids of kynurenine (Kyn) or 3a-hydroxypyrroloindoline (HPI). Their structures with absolute configurations were elucidated by a combination of spectroscopic analysis, advanced Marfey's method, X-ray diffraction, and electronic circular dichroism analysis. Compounds 1-10 exhibited antiadipogenic effects in 3T3-L1 adipocytes, and the most potent compound 7 showed an EC50 value of 1.17 ± 0.19 µM.
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Células 3T3-L1 , Aminoácidos , Peptídeos Cíclicos , Animais , Camundongos , Aminoácidos/química , Estrutura Molecular , Peptídeos Cíclicos/química , Peptídeos Cíclicos/farmacologia , Adipogenia/efeitos dos fármacos , Adipócitos/efeitos dos fármacos , Adipócitos/metabolismoRESUMO
Traffic cyclic loading is the key factor that leads to the deterioration of the long-term service behavior of subgrade. A series of cyclic triaxial tests was carried out by the large-scale dynamic and static triaxial apparatus (LSDSTA) to study the dynamic behaviors of coal gangue subgrade filler (CGSF) under multi-step cyclic loading using the morphological characteristics of hysteretic curves (MCHC). MCHC was quantitatively characterized by four parameters, i.e., the unclosed degree (εphl), inclination of long axis degree (khl), area (Shl) and fullness degree (αhl). With the increase of dynamic strain, εphl increases exponentially. khl of the coal gangue sample first decreases and then shows an increasing trend with the increasing dynamic strain. The values of Shl are close to each other, and the energy dissipation in the sample is small. However, with the increase of dynamic strain, the specimen failure degree is increased, Shl increases exponentially, and the damping ratio increases. With the increase of dynamic strain, αhl increases approximately linearly. Confining pressure has a certain effect on the four parameters. There parameters can be recommended and used for quantitative analysis the dynamic behaviors of subgrade filler under traffic cyclic loading.
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Potassium (K+) plays crucial roles in both plant development and immunity. However, the function of K+ in plant-virus interactions remains largely unknown. Here, we utilized Barley yellow striate mosaic virus (BYSMV), an insect-transmitted plant cytorhabdovirus, to investigate the interplay between viral infection and plant K+ homeostasis. The BYSMV accessory P9 protein exhibits viroporin activity by enhancing membrane permeability in Escherichia coli. Additionally, P9 increases K+ uptake in yeast (Saccharomyces cerevisiae) cells, which is disrupted by a point mutation of Glycine 14 to Threonine (P9G14T). Furthermore, BYSMV P9 forms oligomers and targets to both the viral envelope and the plant membrane. Based on the recombinant BYSMV-green fluorescent protein (BYGFP) virus, a P9-deleted mutant (BYGFPΔP9) was rescued and demonstrated infectivity within individual plant cells of Nicotiana benthamiana and insect vectors. However, BYGFPΔP9 failed to infect barley plants after transmission by insect vectors. Furthermore, infection of barley plants was severely impaired for BYGFP-P9G14T lacking P9 K+ channel activity. In vitro assays demonstrate that K+ facilitates virion disassembly and the release of genome RNA for viral mRNA transcription. Altogether, our results show that the K+ channel activity of viroporins is conserved in plant cytorhabdoviruses and plays crucial roles in insect-mediated virus transmission.
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Croton laui (Euphorbiaceae) is a traditional medicinal plant used by the Li ethnic group in China to treat headaches, stomachaches, and diphtheria. To understand the pharmacological basis of its medicinal use, an extensive investigation of the ethanolic extract of the bark of C. laui was performed. After repeated chromatography, twenty-four undescribed labdane-type diterpenoids, lauinoids A-X (1-24), and five known analogs (25-29) were isolated. Their structures and absolute configurations were established using a combination of spectroscopic analyses, electronic circular dichroism, nuclear magnetic resonance calculations, and single-crystal X-ray diffraction. Among them, compounds 1-3 exhibited an 11(12 â 13)-abeo-16-nor-labdane skeleton, which originated putatively from 9 through a plausible pathway that involves a semipinacol rearrangement process. Compounds 11 and 12 belong to the rare class of 14,15-dinor-labdane diterpenoids. Compounds 18 and 28 exhibited substantial inhibitory effects by suppressing lipopolysaccharide-induced NO production in RAW 264.7 macrophages, with IC50 values of 3.37 ± 0.23 and 5.82 ± 0.28 µM, respectively. This study has greatly expanded the chemical diversity of labdane diterpenoids from C. laui and will guide future research on this ethnomedicinal plant.
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Anti-Inflamatórios , Croton , Diterpenos , Diterpenos/farmacologia , Diterpenos/química , Diterpenos/isolamento & purificação , Croton/química , Camundongos , Animais , Células RAW 264.7 , Anti-Inflamatórios/farmacologia , Anti-Inflamatórios/química , Anti-Inflamatórios/isolamento & purificação , Lipopolissacarídeos/farmacologia , Lipopolissacarídeos/antagonistas & inibidores , Estrutura Molecular , Relação Estrutura-Atividade , Óxido Nítrico/biossíntese , Óxido Nítrico/antagonistas & inibidores , Conformação Molecular , Relação Dose-Resposta a DrogaRESUMO
BACKGROUND: Inguinal hernia in adults is a common and frequent disease in surgery, prone to occur in the elderly or in those with a weak abdominal wall. Despite its prevalence, Molecular mechanisms underlying inguinal hernia formation are unclear. OBJECTIVE: This study aims to identify potential gene markers for inguinal hernia and available drugs. METHODS: Pubmed2Ensembl text mining was used to identify genes related to "inguinal hernia" keywords. The GeneCodis system was used to specify GO biological process terms and KEGG pathways defined in the Kyoto Encyclopedia of Genes and Genomes (KEGG). The STRING tool was used to construct protein-protein interaction networks, which were then visualized using Cytoscape.CytoHubba and Molecular Complex Detection were utilized to analyze the module (MCODE). A GO and KEGG analysis of gene modules was conducted using the DAVID platform database. Hub genes are those that are concentrated in prominent modules. The druggene interaction database was also used to identify potential drugs for inguinal hernia patients based on their interactions between the hub genes. Finally, a Mendelian randomization study was conducted based on genome-wide association studies to determine whether hub genes cause inguinal hernias. RESULTS: The identification of 96 genes associated with inguinal hernia was carried out using text mining techniques. It was constructed using PPI networks with 80 nodes and 476 edges, and the sequence of the genes was performed using CytoHubba. MCODE analysis identified three gene modules. Three modules contain 37 genes clustered as hub candidate genes associated with inguinal hernia patients. The PI3K-Akt, MAPK, AGE-RAGE, and HIF-1 pathways were found to be enriched in signaling pathways. Sixteen of the 37 genes were found to be targetable by 30 existing drugs. The relationship between hub genes and inguinal hernia was examined using Mendelian randomization. The research revealed nine genes that may be connected with inguinal hernia, such as POMC, CD40LG, TFRC, VWF, LOX, IGF2, BRCA1, TNF, and HGF in the plasma. By inverse variance weighting, ALB was associated with an increased risk of inguinal hernia with an OR of 1.203 (OR [95%] = 1,04 [1.012 to 1.089], p = 0.008). CONCLUSION: We identified potential hub genes for inguinal hernia, predicted potential drugs for inguinal hernia, and reverse-validated potential genes by Mendelian randomization. This may provide further insights into asymptomatic pre-diagnostic methods and contribute to studies to understand the molecular mechanisms of risk genes associated with inguinal hernia.
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PCDD/Fs are dioxins produced by waste incineration and pose risks to human health. We aimed to detail the health risks of airborne and soil PCDD/Fs near a municipal solid-waste incinerator (MSWI) for the surrounding population and develop a new model that improves upon existing methods. Thus, we conducted field sampling and then investigated a MSWI in the Pearl River Delta (2016-2018). Our results showed that the carcinogenic and non-carcinogenic risk values of PCDD/Fs exposed to residents in nearby areas were acceptable, with hazard index (HI) values lower than 1.0 and a total carcinogenic risk lower than 1.0E-6. Notably, the results raised concerns regarding higher non-carcinogenic risks in children than in adults. Comparative analysis of the frequency accumulation diagram, accumulated probability risk, and the absolute value of error (δ) between the 95% confidence interval (CI) and the 90% CI of the Monte Carlo stochastic simulation-triangular fuzzy number (MCSS-TFN) and the MCSS model, respectively, demonstrated that the MCSS-TFN exhibited less uncertainty than the MCSS model, regardless of the health risk value of PCDD/Fs in ambient air or in soil. This observation underscores the superiority of the MCSS-TFN model over other models in assessing the health risks associated with PCDD/Fs in situations with limited data. Our new method overcomes the limited dataset size and high uncertainty in assessing the health risks of dioxin substances, providing a more comprehensive understanding of their associated health risks than MCSS models.
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Poluentes Atmosféricos , Dioxinas , Dibenzodioxinas Policloradas , Adulto , Criança , Humanos , Resíduos Sólidos , Monitoramento Ambiental/métodos , Dibenzodioxinas Policloradas/toxicidade , Dibenzodioxinas Policloradas/análise , Dibenzofuranos , Poluentes Atmosféricos/análise , Incineração , Dioxinas/toxicidade , Medição de Risco , Dibenzofuranos Policlorados/análise , SoloRESUMO
PURPOSE: To evaluate the incidence, associated factors, and outcome of persistent subretinal fluid (SRF) after vitrectomy for macular hole-associated retinal detachment (MHRD). METHODS: A total of 158 eyes from 156 patients with MHRD who achieved macular hole closure after primary vitrectomy were included in the analysis; persistent SRF was defined as the presence of SRF for more than 1 month after first surgery. Preoperative and postoperative parameters were analyzed for their relationship with SRF development. RESULTS: Persistent SRF was observed in 19 eyes (12.0% of 158) postoperatively. Seven eyes (36.8% of 19) with persistent SRF eventually displayed complete absorption during follow-up. Univariate analysis revealed that eyes with persistent SRF were statistically associated with internal limiting membrane inverted flap, duration of symptoms, tamponade (perfluoropropane/silicone oil: 14/5 vs. 35/104, P < 0.001), and MHRD subtype (Type 1/Type 2/Type 3: 15/4/0 vs. 60/40/39, P = 0.003). In multivariate analysis, only internal limiting membrane inverted flap (odds ratio, 15.778, 95% confidence interval, 3.170-78.523; P = 0.001) was positively associated with persistent SRF. There were no significant differences in best-corrected visual acuity improvement ( P = 0.425) between the SRF involved foveal and without involved foveal groups and no significant differences between the SRF complete absorption and incomplete absorption groups. CONCLUSION: Absorption of persistent SRF may be more difficult in MHRD eyes than in ordinary rhegmatogenous retinal detachment eyes. The internal limiting membrane inverted flap in MHRD was associated with a greater likelihood of persistent SRF. The location and incomplete absorption of persistent SRF did not seem to be associated with the final visual outcome.
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Tamponamento Interno , Descolamento Retiniano , Perfurações Retinianas , Líquido Sub-Retiniano , Tomografia de Coerência Óptica , Acuidade Visual , Vitrectomia , Humanos , Vitrectomia/métodos , Descolamento Retiniano/cirurgia , Descolamento Retiniano/diagnóstico , Descolamento Retiniano/etiologia , Masculino , Feminino , Perfurações Retinianas/cirurgia , Perfurações Retinianas/diagnóstico , Perfurações Retinianas/etiologia , Estudos Retrospectivos , Idoso , Pessoa de Meia-Idade , Tamponamento Interno/métodos , Tomografia de Coerência Óptica/métodos , Complicações Pós-Operatórias , Seguimentos , Fluorocarbonos/administração & dosagem , IncidênciaRESUMO
BACKGROUND: This study aimed to investigate the combined pathological risk factors (PRFs) to stratify low-risk (pT1-3N1) stage III colon cancer (CC), providing a basis for individualized treatment in the future. PATIENTS AND METHODS: PRFs for low-risk stage III CC were identified using COX model. Low-risk stage III CC was risk-grouped combining with PRFs, and survival analysis were performed using Kaplan-Meier. The Surveillance, Epidemiology, and End Results (SEER) databases was used for external validation. RESULTS: Nine hundred sixty-two stage III CC patients were included with 634 (65.9%) as low risk and 328 (34.1%) as high risk. Poor differentiation (OS: P = 0.048; DFS: P = 0.011), perineural invasion (OS: P = 0.003; DFS: P < 0.001) and tumor deposits (OS: P = 0.012; DFS: P = 0.003) were identified as PRFs. The prognosis of low-risk CC combined with 2 PRFs (OS: HR = 3.871, 95%CI, 2.004-7.479, P < 0.001; DFS: HR = 3.479, 95%CI, 2.158-5.610, P < 0.001) or 3 PRFs (OS: HR = 5.915, 95%CI, 1.953-17.420, P = 0.002; DFS: HR = 5.915, 95%CI, 2.623-13.335, P < 0.001) was similar to that of high-risk CC (OS: HR = 3.927, 95%CI, 2.317-6.656, P < 0.001; DFS: HR = 4.132, 95%CI, 2.858-5.974, P < 0.001). In the SEER database, 18,547 CC patients were enrolled with 10,023 (54.0%) as low risk and 8524 (46.0%) as high risk. Low-risk CC combined with 2 PRFs (OS: HR = 1.857, 95%CI, 1.613-2.139, P < 0.001) was similar to that of high-risk CC without PRFs (HR = 1.876, 95%CI, 1.731-2.033, P < 0.001). CONCLUSION: Combined PRFs improved the risk stratification of low-risk stage III CC, which could reduce the incidence of undertreatment and guide adjuvant chemotherapy.
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Neoplasias do Colo , Humanos , Estadiamento de Neoplasias , Neoplasias do Colo/patologia , Prognóstico , Fatores de Risco , Quimioterapia Adjuvante , Medição de Risco , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêuticoRESUMO
The proteins were mainly derived from Protaetia brevitarsis larval extracts obtained using two empty intestine methods (traditional static method: TSM or salt immersion stress method: SISM) and extraction solvents (water: W or 50 % water-ethanol: W:E), and the proteins were used as objects to investigate the effect of emptying intestine methods on hypolipidemic peptides. The results revealed that the F-2 fractions of protein hydrolysate had stronger in vitro hypolipidemic activity, with the peptides obtained by SISM possessing a stronger cholesterol micelle solubility inhibition rate, especially in SISM-W:E-P. Moreover, a total of 106 peptides were tentatively identified, among which SISM identified more peptides with an amino acid number < 8. Meanwhile, five novel peptides (YPPFH, YPGFGK, KYPF, SPLPGPR and VPPP) exhibited good hypolipidemic activity in vitro and in vivo, among which YPPFH, VPPP and KYPF had strong inhibitory activities on pancreatic lipase (PL) and cholesteryl esterase (CE), and KYPF, SPLPGPR and VPPP could significantly reduce the TG content in Caenorhabditis elegans. Thus, P. brevitarsis can be developed as a naturally derived hypolipidemic component for the development and application in functional foods.
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Besouros , Hidrolisados de Proteína , Animais , Larva/química , Hidrolisados de Proteína/farmacologia , Hidrolisados de Proteína/metabolismo , Besouros/química , Peptídeos/farmacologia , Peptídeos/metabolismo , Água/metabolismo , Proteínas de Insetos/farmacologia , Proteínas de Insetos/metabolismoRESUMO
Background: There are currently five different kinds of transcranial magnetic stimulation (TMS) motor mapping algorithms available, from ordinary point-based algorithms to advanced field-based algorithms. However, there have been only a limited number of comparison studies conducted, and they have not yet examined all of the currently available algorithms. This deficiency impedes the judicious selection of algorithms for application in both clinical and basic neuroscience, and hinders the potential promotion of a potential superior algorithm. Considering the influence of algorithm complexity, further investigation is needed to examine the differences between fMRI peaks and TMS cortical hotspots that were identified previously. Methods: Twelve healthy participants underwent TMS motor mapping and a finger-tapping task during fMRI. The motor cortex TMS mapping results were estimated by five algorithms, and fMRI activation results were obtained. For each algorithm, the prediction error was defined as the distance between the measured scalp hotspot and optimized coil position, which was determined by the maximum electric field strength in the estimated motor cortex. Additionally, the study identified the minimum number of stimuli required for stable mapping. Finally, the location difference between the TMS mapping cortical hotspot and the fMRI activation peak was analyzed. Results: The projection yielded the lowest prediction error (5.27 ± 4.24 mm) among the point-based algorithms and the association algorithm yielded the lowest (6.66 ± 3.48 mm) among field-based estimation algorithms. The projection algorithm required fewer stimuli, possibly resulting from its suitability for the grid-based mapping data collection method. The TMS cortical hotspots from all algorithms consistently deviated from the fMRI activation peak (20.52 ± 8.46 mm for five algorithms). Conclusion: The association algorithm might be a superior choice for clinical applications and basic neuroscience research, due to its lower prediction error and higher estimation sensitivity in the deep cortical structure, especially for the sulcus. It also has potential applicability in various other TMS domains, including language area mapping and more. Otherwise, our results provide further evidence that TMS motor mapping intrinsically differs from fMRI motor mapping.
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BACKGROUND: Synthesis of neural imaging information from many studies is valuable for identifying stable cortical targets for non-invasive brain stimulation (NIBS). Typically, these targets are specified in Montreal Neurological Institute (MNI) standard brain space. However, in practical NIBS applications, localizing MNI cortical targets often relies on the International 10-20 system or heuristic scalp approaches, which often lacks precision or applies only to specific targets. OBJECTIVE/HYPOTHESIS: We aim to establish a probabilistic mapping from any cortical target in MNI space to continuous proportional coordinate (CPC) standard scalp space (MNI2CPC) and assess the performance of this mapping for NIBS targeting. METHODS: The MNI2CPC mapping was calculated based on a large MRI dataset (n = 114). Its targeting error was evaluated via cross-individual validation using a leave-one-out approach, as well as through independent validation across race (n = 27) and across patient (n = 58) cohorts. RESULTS: The cross-individual validation demonstrated targeting errors of 4.03 ± 0.69 mm on the scalp and 3.30 ± 0.59 mm in the cortex. For independent cohorts, targeting errors were 4.71 ± 0.81 mm (scalp) and 3.85 ± 0.64 mm (cortex) across race, and 4.66 ± 0.77 mm (scalp) and 3.77 ± 0.61 mm (cortex) across patient. We publish a free online tool to enable querying of the CPC coordinate for any given MNI cortical target. The resulting CPC coordinates enable rapid and accurate manual localization on the scalp in a user-friendly manner. CONCLUSIONS: The MNI2CPC mapping developed in this study allows for manual localization of any MNI cortical target, which improves the accessibility and ease of application of NIBS in diverse settings.
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Mapeamento Encefálico , Couro Cabeludo , Humanos , Mapeamento Encefálico/métodos , Encéfalo/diagnóstico por imagem , Encéfalo/fisiologia , Técnicas Estereotáxicas , Imageamento por Ressonância Magnética , Estimulação Magnética Transcraniana/métodosRESUMO
Excessive productions of inflammatory cytokines and free radicals are involved in spinal cord injury (SCI). Fibroblast growth factor 5 (FGF5) is associated with inflammatory response and oxidative damage, and we herein intend to determine its function in SCI. Lentivirus was instilled to overexpress or knockdown FGF5 expression in mice. Compound C or H89 2HCl were used to suppress AMP-activated protein kinase (AMPK) or protein kinase A (PKA), respectively. FGF5 level was significantly decreased during SCI. FGF5 overexpression mitigated, while FGF5 silence further facilitated inflammatory response, oxidative damage and SCI. Mechanically, FGF5 activated AMPK to attenuate SCI in a cAMP/PKA-dependent manner, while inhibiting AMPK or PKA with pharmacological methods significantly abolished the neuroprotective effects of FGF5 against SCI. More importantly, serum FGF5 level was decreased in SCI patients, and elevated serum FGF5 level often indicate better prognosis. Our study identifies FGF5 as an effective therapeutic and prognostic target for SCI.
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Proteínas Quinases Ativadas por AMP , Fator 5 de Crescimento de Fibroblastos , Estresse Oxidativo , Traumatismos da Medula Espinal , Animais , Humanos , Camundongos , Proteínas Quinases Ativadas por AMP/metabolismo , Fator 5 de Crescimento de Fibroblastos/genética , Fator 5 de Crescimento de Fibroblastos/metabolismo , Medula Espinal/metabolismo , Traumatismos da Medula Espinal/metabolismo , Camundongos Knockout , Masculino , Feminino , Adulto , Pessoa de Meia-IdadeRESUMO
This study utilizes digital image correlation (DIC) technology to measure the far-field displacements and strains of rock specimens during the entire loading and unloading. Through analyzing the distributions of strain, displacement and their variations per unit length at different stages, the variations of both length and migration velocity of the fracture process zone (FPZ) were studied, and the crack propagation was also investigated. In addition, the entire path of crack propagation was observed by scanning electron microscope (SEM). The results reveal that (1) the fractured ligament can be divided into three zones based on the displacement variation per unit length: intact zone, crack propagation zone, and FPZ. (2) The FPZ length reaches its maximum at the peak load and then decreases, and the minimum length even is only 1/3-1/2 of the maximum length. The FPZ migration velocity is - 48 to 1460 m/s. FPZ's microscale features are intergranular microcracks, transgranular microcracks, cleavage, and debris on fracture surface and around main crack propagation path. (3) The crack propagation length during peak load to peak-post 90% accounts for more than 1/3-1/4 of the entire post-peak length. Crack propagation is alternating fast and slow, i.e., the velocity of crack propagation varies regularly in the range of 24-700 m/s. The region of crack initial propagation is more severely damaged compared to other propagation regions.