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A linear self-reference spectral interferometry has been proposed to measure the distribution of polarization-maintaining photonic crystal fiber (PM-PCF) birefringence over a wide wavelength range combined with the soliton self-frequency shift and birefringence effect. The birefringence of PM-PCF is measured experimentally over the range of 800-970 nm, which is larger than 5×10-4 and shows a segmented change trend. The air micropore structure has a significant effect on the characteristics of PM-PCF, which makes it have a highly nonlinear coefficient, and at the same time, changes the dispersion and birefringence distributions of the PM-PCF. The distribution of PM-PCF birefringence, measured by experiment, provides a new dimension for the design of PM-PCF, which is helpful for a detailed fiber model and an iterative optimization of fiber structure.
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The measurement of the spatial attitude of the tube sheet is the basis for automated shield assembly. This paper presents an image processing method for measuring the surface grooves of the tube sheet. The measurement process consists of two processes: target detection and target coordinate measurement. The environmental factors that affect the recognition rate are analyzed and effective recognition coefficients are defined to further improve the method's ability to resist interference from external factors.
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A position-deviation-compensation demodulation method is proposed to improve the channel adaptability of Fabry-Perot (F-P) sensor in a multi-channel optical fiber F-P sensing system. By combining the envelope peak position (EPP) retrieval process and the position compensation process, the proposed method enables the accurate demodulation of F-P sensors in all channels. Thereinto, the EPP retrieval process uses the phase information to recover the EPP with high precision; the position compensation process compensates the position deviation by an optical-path-based model, which is established to illustrate the principle of the position deviation between different channels. We carried out the pressure experiment to verify the effectiveness of the proposed method. The experiment results showed that the demodulation errors of all channels are no more than 0.13 kPa, which demonstrated that our approach is reliable for improving the channel adaptability of F-P sensors.
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The rapid development and increase of antibiotic resistance are global phenomena resulting from the extensive use of antibiotics in human clinics and animal feeding operations. Antibiotics can promote the occurrence of antibiotic resistance genes (ARGs), which can be transferred horizontally to humans and animals through water and the food chain. In this study, the presence and abundance of ARGs in livestock waste was monitored by quantitative PCR. A diverse set of bacteria and tetracycline resistance genes encoding ribosomal protection proteins (RPPs) from three livestock farms and a river were analyzed through denaturing gradient gel electrophoresis (DGGE). The abundance of sul(I) was 103 to 105 orders of magnitude higher than that of sul(II). Among 11 tet-ARGs, the most abundant was tet(O). The results regarding bacterial diversity indicated that the presence of antibiotics might have an evident impact on bacterial diversity at every site, particularly at the investigated swine producer. The effect of livestock waste on the bacterial diversity of soil was stronger than that of water. Furthermore, a sequencing analysis showed that tet(M) exhibited two genotypes, while the other RPPs-encoding genes exhibited at least three genotypes. This study showed that various ARGs and RPPs-encoding genes are particularly widespread among livestock.
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Resistência Microbiana a Medicamentos/genética , Proteínas Ribossômicas/genética , Microbiologia do Solo , Microbiologia da Água , Animais , Bactérias/efeitos dos fármacos , Bactérias/genética , Bovinos , Eletroforese em Gel de Gradiente Desnaturante , Fazendas , Genes Bacterianos , Gado/microbiologia , Filogenia , Reação em Cadeia da Polimerase/métodos , Rios/microbiologia , Suínos , Resistência a Tetraciclina/genéticaRESUMO
The current first-line treatment for atherosclerotic cardiovascular disease (ASCVD) involves the reduction of a patient's low-density lipoprotein cholesterol (LDL-C) levels through the use of lipid-lowering drugs. However, even when other risk factors such as hypertension and diabetes are effectively managed, there remains a residual cardiovascular risk in these patients despite achieving target LDL-C levels with statins and new lipid-lowering medications. This risk was previously believed to be associated with lipid components other than LDL, such as triglycerides. However, recent studies have unveiled the crucial role of remnant cholesterol (RC) in atherosclerosis, not just triglycerides. The metabolized product of triglyceride-rich lipoproteins is referred to as triglyceride-rich remnant lipoprotein particles, and its cholesterol component is known as RC. Numerous pieces of evidence from epidemiological investigations and genetic studies demonstrate that RC plays a significant role in predicting the incidence of ASCVD. As a novel marker for atherosclerosis prediction, when LDL-C is appropriately controlled, RC should be prioritized for attention and intervention among individuals at high risk of ASCVD. Therefore, reducing RC levels through the use of various lipid-lowering drugs may yield long-term benefits. Nevertheless, routine testing of RC in clinical practice remains controversial, necessitating further research on the treatment of elevated RC levels to evaluate the advantages of reducing RC in patients at high risk of ASCVD.
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Aterosclerose , Colesterol , Humanos , Aterosclerose/sangue , Colesterol/sangue , Colesterol/metabolismo , Triglicerídeos/sangue , Fatores de Risco , Biomarcadores/sangue , LDL-Colesterol/sangue , Lipoproteínas/sangue , Lipoproteínas/metabolismo , Doenças Cardiovasculares/sangue , Doenças Cardiovasculares/etiologia , Doenças Cardiovasculares/prevenção & controleRESUMO
BACKGROUND: Studies have shown that vagus nerve-mediated inflammatory reflex could inhibit cytokine production and inflammation in sepsis animals. OBJECTIVES: This study aimed to explore the efficacy of transcutaneous auricular vagus nerve stimulation (taVNS) on inflammation and disease severity of sepsis patients. METHODS: A randomized, double-blind, sham-controlled pilot study was performed. Twenty sepsis patients were randomly assigned to receive taVNS or sham stimulation for five consecutive days. Stimulation effect was assessed with serum cytokine levels, Acute Physiology and Chronic Health Evaluation (APACHE) â ¡ score, and Sequential Organ Failure Assessment (SOFA) score at baseline and on Day 3, Day 5, and Day 7. RESULTS: TaVNS was well tolerated in the study population. Patients receiving taVNS experienced significant reductions in serum TNF-α and IL-1ß levels and increases in IL-4 and IL-10 levels. SOFA scores decreased on Day 5 and Day 7 compared with baseline in the taVNS group. However, no changes were found in sham stimulation group. The changes of cytokine from Day 7 to Day 1 were greater with taVNS than sham stimulation. No differences in the APACHE â ¡ score and SOFA score were observed between the two groups. CONCLUSIONS: TaVNS resulted in significantly lower serum pro-inflammatory cytokines and higher serum anti-inflammatory cytokines in sepsis patients.
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Sepse , Estimulação do Nervo Vago , Animais , Humanos , Projetos Piloto , Estimulação do Nervo Vago/métodos , Citocinas , Nervo Vago/fisiologia , Sepse/terapia , Sepse/etiologiaRESUMO
Background: Pinus yunnanensis is a major silvicultural species in Southwest China. Currently, large areas of twisted-trunk Pinus yunnanensis stands severely restrict its productivity. Different categories of rhizosphere microbes evolve alongside plants and environments and play an important role in the growth and ecological fitness of their host plant. However, the diversity and structure of the rhizosphere microbial communities between P. yunnanensis with two different trunk types-straight and twisted-remain unclear. Methods: We collected the rhizosphere soil of 5 trees with the straight and 5 trees with the twisted trunk type in each of three sites in Yunnan province. We assessed and compared the diversity and structure of the rhizosphere microbial communities between P. yunnanensis with two different trunk types by Illumina sequencing of 16S rRNA genes and internal transcribed spacer (ITS) regions. Results: The available phosphorus in soil differed significantly between P. yunnanensis with straight and twisted trunks. Available potassium had a significant effect on fungi. Chloroflexi dominated the rhizosphere soils of the straight trunk type, while Proteobacteria was predominant in the rhizosphere soils of the twisted trunk type. Trunk types significantly explained 6.79% of the variance in bacterial communities. Conclusion: This study revealed the composition and diversity of bacterial and fungal groups in the rhizosphere soil of P. yunnanensis with straight and twisted trunk types, providing proper microbial information for different plant phenotypes.
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PURPOSE: Previous studies proved the benefits of electroacupuncture (EA) on heart in ischemia reperfusion injury and chronic heart failure. However, the role of EA on sepsis-induced cardiac dysfunction has rarely been elucidated before. In this study, we aimed to investigate the effects of EA on cardiac dysfunction in a rat model of sepsis and to speculate the underlying mechanisms. METHODS: Sepsis was induced by cecum ligation and puncture in anesthetized rats. EA at the acupoint "Neiguan (PC6)" was applied 0.5 h after the induction of sepsis for 20 min. Heart rate variability was obtained immediately after EA to evaluate autonomic balance. Echocardiography was performed at 6 h and 24 h after sepsis induction in vivo. Measurements of hemodynamics, blood gases, cytokines and biochemistry were collected at 24 h. Cardiac tissue underwent immunofluorescence staining to determine the expression of α7 nicotinic acetylcholine receptor (α7nAChR) on macrophages. RESULTS: EA increased vagus nerve activity, prevented the development of hyperlactatemia, attenuated the decline of left ventricle ejection fraction, suppressed systemic and cardiac inflammation and alleviated the histopathological manifestations of heart in sepsis rats. Furthermore, the cardiac tissue from EA treated rats showed increased expressions of α7nAChR on macrophages. The cardio-protective and anti-inflammatory effects of EA were partly or completely prevented in rats with vagotomy. CONCLUSION: EA at PC6 attenuates left ventricle dysfunction and decreases inflammation in sepsis-induced cardiac dysfunction. The cardio-protective effects of EA are mediated through vagus nerve mediated cholinergic pathway.
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Eletroacupuntura , Cardiopatias , Sepse , Ratos , Animais , Ratos Sprague-Dawley , Receptor Nicotínico de Acetilcolina alfa7/metabolismo , Nervo Vago/metabolismo , Nervo Vago/patologia , Inflamação/patologia , Punções , Ceco/patologiaRESUMO
'Locked nucleic acids' (LNAs) are sugar modified nucleic acids containing the 2'-O-4'C-methylene-ß-D-ribofuranoses. The substitution of RNAs with LNAs leads to an enhanced thermostability. Aptamers are nucleic acids, which are selected for specific target binding from a large library pool by the 'SELEX' method. Introduction of modified nucleic acids into aptamers can improve their stability. The stem region of a ricin A chain RNA aptamer was substituted by locked nucleic acids. Different constructs of the LNA-substituted aptamers were examined for their thermostability, binding activity, folding and RNase sensitivity as compared to the natural RNA counterpart. The LNA-modified aptamers were active in target binding, while the loop regions and the adjacent stem nucleotides remained unsubstituted. The thermostability and RNase resistance of LNA substituted aptamers were enhanced as compared to the native RNA aptamer. This study supports the approach to substitute the aptamer stem region by LNAs and to leave the loop region unmodified, which is responsible for ligand binding. Thus, LNAs possess an encouraging potential for the development of new stabilized nucleic acids and will promote future diagnostic and therapeutic applications.
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Aptâmeros de Nucleotídeos/química , Oligonucleotídeos/química , Ricina/química , Sequência de Bases , Guanosina/química , Conformação de Ácido Nucleico , Técnica de Seleção de AptâmerosRESUMO
ABSTRACT: Vagus nerve stimulation has been shown to exert anti-inflammation activities in sepsis. However, surgical implantation of stimulation devices is performed under general anesthesia, which limits its clinical application. Auricular vagus nerve stimulation (AVNS) is a minimal invasive technique that delivers electrical currents to the auricular branch of the vagus nerve. The purpose of this study was to determine the effects of AVNS on systemic inflammation, lung injury, neutrophil infiltration, and neutrophil extracellular traps (NETs) formation in the lung. In a LPS challenge lung-injury mice model, AVNS was applied to bilateral ears. Twelve hours after LPS administration, samples of blood, bronchoalveolar lavage fluid (BALF), and lung tissues were processed for investigations. We found that the treatment with AVNS significantly attenuated histopathological changes and neutrophil infiltration in the lung tissue, inhibited inflammatory cytokine elevations in serum and BALF, and decreased protein concentrations in BALF. Besides, AVNS decreased leukocyte and neutrophil accounts in BALF. Furthermore, colocalization of citrullination of histone H3 and myeloperoxidase expressions (highly specific marker of NETs) was reduced in AVNS mice. In conclusion, AVNS reduced systemic inflammation, attenuated lung edema, and inhibited neutrophil infiltration and NETs formation in the lung in LPS mice.
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Lesão Pulmonar Aguda/prevenção & controle , Armadilhas Extracelulares/fisiologia , Infiltração de Neutrófilos/fisiologia , Neutrófilos/fisiologia , Estimulação do Nervo Vago , Lesão Pulmonar Aguda/etiologia , Lesão Pulmonar Aguda/metabolismo , Animais , Líquido da Lavagem Broncoalveolar/química , Citocinas/metabolismo , Modelos Animais de Doenças , Histonas/metabolismo , Lipopolissacarídeos , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Peroxidase/metabolismoRESUMO
Objectives: To evaluate the safety and efficacy of balloon-occluded retrograde transvenous obliteration (BRTO) using lauromacrogol sclerosant foam for gastric varices (GVs) with gastrorenal venous shunts. Methods: Data of GV patients treated with BRTO using lauromacrogol sclerosant foam in 2016-2020 were retrospectively analyzed along with procedural success rate, complications, and follow-up efficacy. Results: A total of 31 patients were treated with BRTO. The sclerosant foam was prepared by mixing iodinated oil, lauromacrogol, and air at a 1:2:3 ratio. The BRTO procedure was successfully completed in 93.5% of patients. One patient was allergic to the lauromacrogol injection. A mild postoperative fever occurred in three patients. One patient experienced grand mal seizures after the procedure. There was no significant difference in the median Child-Turcotte-Pugh scores before versus after BRTO. Complete GV resolution was observed in 93.1% of patients. One patient underwent endoscopic treatment for the development of high-risk esophageal varices. Another patient underwent transjugular intrahepatic portosystemic shunt placement for the aggravation of ascites. Conclusions: Lauromacrogol sclerosant foam is safe and effective in patients undergoing BRTO for GV.
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BACKGROUND: The thrombodynamic ratio (TDR) as a composite thromboelastography (TEG) parameter, has been proven to be valuable in multiple diseases. However, the association between TDR and mortality in sepsis has not been studied. METHODS: One hundred forty-one patients were enrolled in this retrospectively study. TEG was performed immediately at admission. Two cox proportional hazards models were developed for the prediction of 28-day mortality. The C statistic, continuous net reclassification index (cNRI) and integrated discriminatory index (IDI) were calculated to compare the discrimination performance of clinical models with and without the TDR value. The integrated calibration index (ICI) and E50 were calculated to compare the calibration. RESULTS: Patients with lower TDR were more likely to have organ impairments and increased 28-day mortality. The TDR value improved discrimination performance in both Model 1 (C statistic, 0.745 vs 0.735; cNRI 19.4%, p = 0.044; IDI 5.6%, p = 0.012) and Model 2 (C statistic, 0.761 vs 0.751; IDI, 5.1%, p = 0.012). Compared to the calibration curve of Model 1 without TDR, addition of TDR displayed better calibration (ICI, 0.023; E50, 0.021). CONCLUSION: TDR value significantly predicts 28-day mortality in patients with sepsis and could improve the discrimination and calibration performance of clinical prediction models.
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Sepse , Hospitalização , Humanos , Prognóstico , Modelos de Riscos Proporcionais , Estudos Retrospectivos , Sepse/diagnósticoRESUMO
Organ failure resulting from excessive inflammation is the leading cause of death in the early phase of acute pancreatitis (AP). The autonomic nervous system was reported to be involved in AP, and the vagus nerve could exert anti-inflammatory effects through α7 nicotinic acetylcholine receptor (α7nAChR) signaling. Acupuncture has been widely used in traditional Asian medicine, and recent studies suggested the inflammation modulating effect of electroacupuncture (EA) might be mediated by the autonomic nervous system. In this study, we aimed to investigate the effects of EA in AP animal models. Two independent AP mouse models were used, namely, caerulein hyperstimulation and pancreatic duct ligation. We found that EA at Zusanli acupoint increased vagus nerve activity, suppressed systemic inflammation, and alleviated the histopathological manifestations and leukocyte infiltrations of the pancreas. Induction of AP resulted in a remarkable decrease in the frequency of α7nAchR+ macrophages in the pancreas, while EA counteracted this phenomenon. The anti-inflammatory, pancreatic protective and upregulation of α7nAchR effects of EA were reduced in mice with vagotomy. Moreover, the therapeutic effects of EA were attenuated in mice treated with methyllycaconitine citrate, a selective α7nAChR antagonist. Taken together, EA could modulate inflammation, thereby exerting protective effects in AP. The mechanism may include activating the vagus nerve through the cholinergic anti-inflammatory pathway.
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Risk classification plays a crucial role in clinical management and therapy decisions in children with neuroblastoma. Risk assessment is currently based on patient criteria and molecular factors in single tumor biopsies at diagnosis. Growing evidence of extensive neuroblastoma intratumor heterogeneity drives the need for novel diagnostics to assess molecular profiles more comprehensively in spatial resolution to better predict risk for tumor progression and therapy resistance. We present a pilot study investigating the feasibility and potential of matrix-assisted laser desorption/ionization mass spectrometry imaging (MALDI-MSI) to identify spatial peptide heterogeneity in neuroblastoma tissues of divergent current risk classification: high versus low/intermediate risk. Univariate (receiver operating characteristic analysis) and multivariate (segmentation, principal component analysis) statistical strategies identified spatially discriminative risk-associated MALDI-based peptide signatures. The AHNAK nucleoprotein and collapsin response mediator protein 1 (CRMP1) were identified as proteins associated with these peptide signatures, and their differential expression in the neuroblastomas of divergent risk was immunohistochemically validated. This proof-of-concept study demonstrates that MALDI-MSI combined with univariate and multivariate analysis strategies can identify spatially discriminative risk-associated peptide signatures in neuroblastoma tissues. These results suggest a promising new analytical strategy improving risk classification and providing new biological insights into neuroblastoma intratumor heterogeneity.
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Protectin D1 (PD1), a DHA-derived lipid mediator, has recently been shown to possess anti-inflammatory and pro-resolving properties. To date, little is known about the effect of PD1 on lipopolysaccharide (LPS)-induced acute lung injury (ALI) in mice. The aim of the present study was to investigate the therapeutic effects of PD1 on LPS-induced ALI and its potential mechanisms of action. ALI was induced via an intraperitoneal injection of LPS, where PD1 (2 ng/mouse) was administered intravenously 30 min after LPS challenge. Mice were sacrificed 24 h after modeling. Lung histopathological changes were assessed using hematoxylin and eosin staining and myeloperoxidase (MPO) activity was tested using immunohistochemistry. Tumor necrosis-α and interleukin-6 levels in the bronchoalveolar lavage fluid (BALF) and serum were measured using ELISA. To detect neutrophil extracellular traps produced by infiltrated neutrophils in the lung tissue, immunofluorescence staining was performed using anti-MPO and anti-histone H3 antibodies. The results indicated that PD1 significantly attenuated histological damage and neutrophil infiltration in lung tissue, reduced the lung wet/dry weight ratio, protein concentration and proinflammatory cytokine levels in BALF and decreased proinflammatory cytokine levels in serum. Moreover, neutrophil citrullinated histone H3 (CitH3) expression was also reduced after PD1 administration. In conclusion, PD1 attenuated LPS-induced ALI in mice via inhibition of neutrophil extracellular trap formation in lung tissue. Therefore, PD1 administration may serve to be a new strategy for treating ALI.
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BACKGROUND: Docosahexaenoic acid-derived protectin D1 (PD1) was identified critical in the resolution of inflammation in vivo, where it modulates the innate immune response and stimulates resolution. Acute pancreatitis (AP) is characterized by local pancreatic inflammation with mild forms whereas systemic inflammation with severe forms. Herein we investigate the impact of PD1 in murine models of pancreatitis. METHODS: Three independent AP models, which induced in male mice via intraperitoneal injection of caerulein, L-arginine or pancreatic duct ligation, were used to confirm the protective effect of PD1. Infiltrationsof neutrophils and macrophages in pancreas were detected by flow cytometry and immunohistochemistry. In vitro and in vivo neutrophil extracellular traps formation was detected by immunofluorescence staining. Expression of peptidylarginine deiminase 4 (PAD4) in activated neutrophils was evaluated by western blotting. RESULTS: Systemic treatment with PD1 reduced serum activities of amylase and lipase, blunted the concentrations of tumor necrosis factor-α and interleukin-6 in serum and protected against pancreas histologic damage in three AP models. PD1 also prolonged the survival in the pancreatic duct ligation model. Moreover, pancreatic infiltrationofneutrophils and neutrophil CitH3 expression were reduced after PD1 administration. In vitro studies revealed PD1 decreased supernatant cell-free DNA and CitH3 levels and downregulated PAD4 expression in mouse bone-marrow derived neutrophils. However, in the caerulein mice pretreated with GSK484 hydrochloride, an inhibitor of PAD4, PD1 treatment showed no more protective effect. CONCLUSIONS: PD1 ameliorates AP by decreasing early infiltration of neutrophils into the pancreas and neutrophil extracellular traps formation through PAD4. These results supply the foundation to consider PD1 as a therapy for AP.
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Ácidos Docosa-Hexaenoicos/uso terapêutico , Armadilhas Extracelulares/efeitos dos fármacos , Neutrófilos/efeitos dos fármacos , Pancreatite/tratamento farmacológico , Animais , Modelos Animais de Doenças , Ácidos Docosa-Hexaenoicos/farmacologia , Armadilhas Extracelulares/imunologia , Macrófagos/imunologia , Masculino , Camundongos Endogâmicos ICR , Neutrófilos/imunologia , Pâncreas/efeitos dos fármacos , Pâncreas/imunologia , Pâncreas/patologia , Pancreatite/imunologia , Pancreatite/patologia , Proteína-Arginina Desiminase do Tipo 4/imunologiaRESUMO
Olive (Olea europaea.L) is an economically important oleaginous crop and its fruit cold-pressed oil is used for edible oil all over the world. The basic region-leucine zipper (bZIP) family is one of the largest transcription factors families among eukaryotic organisms; its members play vital roles in environmental signaling, stress response, plant growth, seed maturation, and fruit development. However, a comprehensive report on the bZIP gene family in olive is lacking. In this study, 103 OebZIP genes from the olive genome were identified and divided into 12 subfamilies according to their genetic relationship with 78 bZIPs of A. thaliana. Most OebZIP genes are clustered in the subgroup that has a similar gene structure and conserved motif distribution. According to the characteristics of the leucine zipper region, the dimerization characteristics of 103 OebZIP proteins were predicted. Gene duplication analyses revealed that 22 OebZIP genes were involved in the expansion of the bZIP family. To evaluate the expression patterns of OebZIP genes, RNA-seq data available in public databases were analyzed. The highly expressed OebZIP genes and several lipid synthesis genes (LPGs) in fruits of two varieties with different oil contents during the fast oil accumulation stage were examined via qRT-PCR. By comparing the dynamic changes of oil accumulation, OebZIP1, OebZIP7, OebZIP22, and OebZIP99 were shown to have a close relationship with fruit development and lipid synthesis. Additionally, some OebZIP had a significant positive correlation with various LPG genes. This study gives insights into the structural features, evolutionary patterns, and expression analysis, laying a foundation to further reveal the function of the 103 OebZIP genes in olive.
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Fatores de Transcrição de Zíper de Leucina Básica/genética , Regulação da Expressão Gênica de Plantas/genética , Genes de Plantas , Olea/genética , Proteínas de Plantas/genética , Fatores de Transcrição de Zíper de Leucina Básica/biossíntese , Fatores de Transcrição de Zíper de Leucina Básica/química , Fatores de Transcrição de Zíper de Leucina Básica/classificação , Mapeamento Cromossômico , Cromossomos de Plantas/genética , Sequência Conservada , Dimerização , Evolução Molecular , Frutas/crescimento & desenvolvimento , Duplicação Gênica , Lipídeos/biossíntese , Olea/metabolismo , Azeite de Oliva/metabolismo , Filogenia , Proteínas de Plantas/biossíntese , Proteínas de Plantas/química , Proteínas de Plantas/classificação , RNA-SeqRESUMO
Background: Vagus nerve stimulation (VNS) is effective in reducing inflammation in various diseases, such as rheumatoid arthritis, colitis and acute kidney injury. The anti-inflammatory effect of vagus nerve in these diseases necessitates the interactions of neural activation and α7 nicotinic acetylcholine receptors (α7nAChRs) on splenic macrophages. In this study, we aimed to investigate the effect of VNS on severity in experimental acute pancreatitis (AP). Methods: Two independent AP models were used, which induced in ICR mice with caerulein or pancreatic duct ligation (PDL). Thirty minutes after modeling, the left cervical carotid sheath containing the vagus nerve was electrically stimulated for 2 min. Plasma lipase and amylase activities, TNF-α levels and pancreas histologic damage were evaluated. In caerulein mice, the percentages of α7nAChR+ macrophage in pancreas and spleen were assessed by flow cytometry. Furthermore, splenectomy and adoptive transfer of VNS-conditioned α7nAChR splenocytes were performed in caerulein mice to evaluate the role of spleen in the protective effect of VNS. Results: VNS reduced plasma lipase and amylase activities, blunted the concentrations of TNF-α and protected against pancreas histologic damage in two AP models. Survival rates were improved in the PDL model after VNS. In caerulein AP mice, VNS increased the percentages of α7nAChR+ macrophages in pancreas and spleen. Adoptive transfer of VNS-treated α7nAChR splenocytes provided protection against pancreatitis in recipient mice. However, splenectomy did not abolish the protective effect of VNS. Conclusions: VNS reduces disease severity and attenuates inflammation in AP mice. This effect is independent of spleen and is probably related to α7nAChR on macrophage.
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Pancreatite/patologia , Estimulação do Nervo Vago , Doença Aguda , Transferência Adotiva , Animais , Biomarcadores , Ceruletídeo/efeitos adversos , Modelos Animais de Doenças , Potenciais Evocados , Imuno-Histoquímica , Masculino , Camundongos , Pancreatite/etiologia , Pancreatite/mortalidade , Pancreatite/terapia , Índice de Gravidade de Doença , Taxa de Sobrevida , Estimulação do Nervo Vago/métodosRESUMO
With regard to relapse and survival, early-stage high-grade serous ovarian (HGSOC) patients comprise a heterogeneous group and there is no clear consensus on first-line treatment. Currently, no prognostic markers are available for risk assessment by standard targeted immunohistochemistry and novel approaches are urgently required. Here, we applied MALDI-imaging mass spectrometry (MALDI-IMS), a new method to identify distinct mass profiles including protein signatures on paraffin-embedded tissue sections. In search of prognostic biomarker candidates, we compared proteomic profiles of primary tumor sections from early-stage HGSOC patients with either recurrent (RD) or non-recurrent disease (N = 4; each group) as a proof of concept study. In total, MALDI-IMS analysis resulted in 7537 spectra from the malignant tumor areas. Using receiver operating characteristic (ROC) analysis, 151 peptides were able to discriminate between patients with RD and non-RD (AUC > 0.6 or < 0.4; p < 0.01), and 13 of them could be annotated to proteins. Strongest expression levels of specific peptides linked to Keratin type1 and Collagen alpha-2(I) were observed and associated with poor prognosis (AUC > 0.7). These results confirm that in using IMS, we could identify new candidates to predict clinical outcome and treatment extent for patients with early-stage HGSOC.
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PURPOSE: Precise histological classification of epithelial ovarian cancer (EOC) has immanent diagnostic and therapeutic consequences, but remains challenging in histological routine. The aim of this pilot study is to examine the potential of matrix-assisted laser desorption/ionization (MALDI) imaging mass spectrometry in combination with machine learning methods to classify EOC histological subtypes from tissue microarray. EXPERIMENTAL DESIGN: Formalin-fixed-paraffin-embedded tissue of 20 patients with ovarian clear-cell, 14 low-grade serous, 19 high-grade serous ovarian carcinomas, and 14 serous borderline tumors are analyzed using MALDI-Imaging. Classifications are computed by linear discriminant analysis (LDA), support vector machines with linear (SVM-lin) and radial basis function kernels (SVM-rbf), a neural network (NN), and a convolutional neural network (CNN). RESULTS: MALDI-Imaging and machine learning methods result in classification of EOC histotypes with mean accuracy of 80% for LDA, 80% SVM-lin, 74% SVM-rbf, 83% NN, and 85% CNN. Based on sensitivity (69-100%) and specificity (90-99%), CCN and NN are most suited to EOC classification. CONCLUSION AND CLINICAL RELEVANCE: The pilot study demonstrates the potential of MALDI-Imaging derived proteomic classifiers in combination with machine learning algorithms to discriminate EOC histotypes. Applications may support the development of new prognostic parameters in the assessment of EOC.