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BACKGROUND AND AIMS: Metabolic dysfunction-associated steatohepatitis (MASH)-related fibrosis is reversible. However, the dynamic morphology change in fibrosis regression remains unclear. We aim to explore the morphological characteristics of fibrosis regression in advanced MASH patients. METHODS: Clinical and histological data of 79 biopsy-proved MASH patients with advanced fibrosis (F3-F4) were reviewed. The second harmonic generation/two-photon excitation fluorescence (SHG/TPEF) image technology was used to quantitatively identify the R (regressive) septa from P (progressive) septa and PS (perisinusoidal) fibrosis. Non-invasive tests were used to compare the fibrosis level with and without R septa groups. Transcriptomics was used to explore hub genes and the underlying mechanism of the formation of R septa. RESULTS: The R septa were different from the P septa and PS fibrosis in detail collagen quantitation identified by SHG/TPEF technology. The R septa were found in MASH fibrosis-regressed patients, which met the definition of the "Beijing classification". Therefore, patients were divided into two groups according to septa morphology: with R septa (n = 10, 12.7%), and without R septa (n = 69, 87.3%). Patients with R septa had lower values in most non-invasive tests, especially for liver stiffness assessed by TE (12.3 vs. 19.4 kPa, p = 0.010) and FAST (FibroScan®-AST) score (0.43 vs. 0.70, p = 0.003). Transcriptomics analysis showed that the expressions of five hub fibrogenic genes, including Col3A1, BGN, Col4A1, THBS2, and Col4A2 in the R septa group, were significantly lower. CONCLUSIONS: The R septa can be differentiated from the P septa and PS fibrosis by quantitative assessment of SHG/TPEF, and it represents a tendency of fibrosis regression in MASH patients. TRIAL REGISTRATION: NCT03386890, 29/12/2017.
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The ion association of salts aqueous solutions have long captivated the attention of researchers within the field of physical chemistry. In this paper, we have performed a comprehensive analysis of ion interactions in sodium sulfate (Na2SO4) aqueous solutions using a combination of high-resolution techniques, including excess (ERS) and two-dimensional correlation (2DCRS) Raman spectroscopy in conjunction with molecular dynamics (MD) calculations. The Raman spectrum shows that two inflection points in the Raman shift of the O-H vibration are observed with the increase in Na2SO4 concentration. Simultaneously, a new peak of the SO42- vibration appears at first inflection point, representing the formation of ion association. Further analysis based on ERS and 2CRS reveals that these two inflection points correspond respectively to the formation of ion pairs (CIPs) and small ion clusters. Importantly, MD simulations confirm the above experimental results. Our study provides evidence for ion association and clustering in aqueous in salt ion aqueous solutions.
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RATIONALE: Desmoid tumor (DT) is a rare soft tissue tumor that can occur anywhere in the body. Abdominal wall DT presents unique clinical challenges due to its distinctive manifestations, treatment modalities, and the lack of biomarkers for diagnosis and recurrence prediction, making clinical decisions exceedingly complex. PATIENT CONCERNS: A 32-year-old female who underwent radical resection combined with patch reinforcement for rectus abdominis DT, successfully alleviating abdominal discomfort, with no recurrence during the 6-month follow-up after surgery. DIAGNOSES: Based on the imaging studies and medical history, the patient underwent radical surgical resection. Histopathology reveals that the tumor cells predominantly composed of proliferative fibroblasts with local collagen deposition. The lesional cells show positive staining for ß-catenin, indicating a diagnosis of DT. INTERVENTIONS: The patient underwent radical surgical resection with patch reinforcement to repair the abdominal wall defect. Pathology confirmed negative margins, achieving an R0 resection, and genetic testing identified a T41A mutation in CTNNB1. Consequently, no additional adjuvant therapy was administered postoperatively. OUTCOMES: The patient was discharged with the incision healing well after 3 days postoperation. Upon reexamination 6 months later, no recurrence or adverse complications were observed. LESSONS: Abdominal wall DT treatment requires personalized plans from multidisciplinary team discussions. Genetic testing plays a crucial role in identifying novel biomarkers for abdominal wall DT. We have once again demonstrated the significant clinical significance of CTNNB1 mutations in the diagnosis and progression of abdominal wall DT. Additionally, genes such as CCND1, CYP3A4, SLIT1, RRM1, STIM1, ESR2, UGT1A1, among others, may also be closely associated with the progression of abdominal wall DT. Future research should delve deeper into and systematically evaluate the precise impact of these genetic mutations on treatment selection and prognosis for abdominal wall DT, in order to better guide patient management and treatment decisions.
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Fibromatose Agressiva , Reto do Abdome , Humanos , Feminino , Adulto , Fibromatose Agressiva/cirurgia , Fibromatose Agressiva/diagnóstico , Fibromatose Agressiva/genética , Fibromatose Agressiva/patologia , Reto do Abdome/cirurgia , beta Catenina/genética , Neoplasias Abdominais/cirurgia , Neoplasias Abdominais/genética , Neoplasias Abdominais/diagnóstico , Neoplasias Abdominais/patologiaRESUMO
ABSTRACT: Glycoprotein Ibα (GPIbα), the ligand-binding subunit of platelet GPIb-IX complex, interacts with von Willebrand factor (VWF) exposed at the injured vessel wall, initiating platelet adhesion, activation, hemostasis, and thrombus formation. The cytoplasmic tail of GPIbα interacts with 14-3-3ζ, regulating the VWF-GPIbα-elicited signal transduction and VWF binding function of GPIbα. However, we unexpectedly found that the GPIbα-14-3-3ζ association, beyond VWF-dependent function, is essential for general platelet activation. We found that the myristoylated peptide of GPIbα C-terminus MPαC, a potential GPIbα inhibitor, by itself induced platelet aggregation, integrin αIIbß3 activation, granule secretion, and phosphatidylserine (PS) exposure. Conversely, the deletion of the cytoplasmic tail of GPIbα in mouse platelets (10aa-/-) decreased platelet aggregation, integrin αIIbß3 activation, granule secretion, and PS exposure induced by various physiological agonists. Phosphoproteome-based kinase activity profiling revealed significantly upregulated protein kinase C (PKC) activity in MPαC-treated platelets. MPαC-induced platelet activation was abolished by the pan-PKC inhibitor and PKCα deletion. Decreased PKC activity was observed in both resting and agonist-stimulated 10aa-/- platelets. GPIbα regulates PKCα activity by sequestering 14-3-3ζ from PKCα. In vivo, the deletion of the GPIbα cytoplasmic tail impaired mouse hemostasis and thrombus formation and protected against platelet-dependent pulmonary thromboembolism. Therefore, our findings demonstrate an essential role for the GPIbα cytoplasmic tail in regulating platelet general activation and thrombus formation beyond the VWF-GPIbα axis.
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Plaquetas , Ativação Plaquetária , Complexo Glicoproteico GPIb-IX de Plaquetas , Complexo Glicoproteico GPIb-IX de Plaquetas/metabolismo , Animais , Camundongos , Humanos , Plaquetas/metabolismo , Proteínas 14-3-3/metabolismo , Fator de von Willebrand/metabolismo , Trombose/metabolismo , Transdução de Sinais , Complexo Glicoproteico GPIIb-IIIa de Plaquetas/metabolismo , Camundongos Knockout , Agregação PlaquetáriaAssuntos
Seio Cavernoso , Malformações Vasculares do Sistema Nervoso Central , Humanos , Malformações Vasculares do Sistema Nervoso Central/diagnóstico por imagem , Malformações Vasculares do Sistema Nervoso Central/complicações , Seio Cavernoso/diagnóstico por imagem , Masculino , Feminino , Pessoa de Meia-IdadeRESUMO
Marine macroalgae are increasingly recognized for their significant biological and economic potential. The key to unlocking this potential lies in the efficient degradation of all carbohydrates from the macroalgae biomass. However, a variety of polysaccharides (alginate, cellulose, fucoidan, and laminarin), are difficult to degrade simultaneously in a short time. In this study, the brown alga Saccharina japonica was found to be rapidly and thoroughly degraded by the marine bacterium Agarivorans albus B2Z047. This strain harbors a broad spectrum of carbohydrate-active enzymes capable of degrading various polysaccharides, making it uniquely equipped to efficiently break down both fresh and dried kelp, achieving a hydrolysis rate of up to 52%. A transcriptomic analysis elucidated the presence of pivotal enzyme genes implicated in the degradation pathways of alginate, cellulose, fucoidan, and laminarin. This discovery highlights the bacterium's capability for the efficient and comprehensive conversion of kelp biomass, indicating its significant potential in biotechnological applications for macroalgae resource utilization.
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Phaeophyceae , Polissacarídeos , Alga Marinha , Alga Marinha/metabolismo , Phaeophyceae/metabolismo , Polissacarídeos/metabolismo , Hidrólise , Biomassa , Glucanos/metabolismo , Flavobacteriaceae/metabolismo , Kelp/metabolismoRESUMO
Aim: This study aimed to examine the association of liver enzymes, including alanine aminotransferase (ALT), aspartate aminotransferase (AST), and gamma-glutamyl-transferase (GGT), with type 2 diabetes (T2D) risk, particularly their dose-response relationship. Methods: This cross-sectional study enrolled participants aged >20 years old who underwent physical examination at our local hospital from November 2022 to May 2023. A generalized additive model (GAM) was fit to assess the dose-response relationship between liver enzymes and T2D risk. Furthermore, data from the UK Biobank (n=217,533) and National Health and Nutrition Examination Survey (NHANES 2011-2018; n= 15,528) were analyzed to evaluate whether the dose-response relationship between liver enzymes and T2D differed by population differences. Results: A total of 14,100 participants were included (1,155 individuals with T2D and 12,945 individuals without diabetes) in the analysis. GAM revealed a non-linear relationship between liver enzymes and T2D risk (P non-linear < 0.001). Specifically, T2D risk increased with increasing ALT and GGT levels (range, <50 IU/L) and then plateaued when ALT and GGT levels were >50 IU/L. Elevated AST within a certain range (range, <35 IU/L) decreased the risk of T2D, whereas mildly elevated AST (>35 IU/L) became a risk factor for T2D. The UK Biobank and NHANES data analysis also showed a similar non-linear pattern between liver enzymes and T2D incidence. Conclusion: Liver enzymes were non-linearly associated with T2D risk in different populations, including China, the UK, and the US. Elevated ALT and GGT levels, within a certain range, could increase T2D risk. More attention should be given to liver enzyme levels for early lifestyle intervention and early T2D prevention. Further studies are necessary to explore the mechanism of the non-linear association between liver enzymes and T2D risk.
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Diabetes Mellitus Tipo 2 , Humanos , Adulto Jovem , Adulto , Diabetes Mellitus Tipo 2/epidemiologia , Inquéritos Nutricionais , Estudos Transversais , Alanina Transaminase , FígadoRESUMO
BACKGROUND: Observational studies have demonstrated an association between white blood cells (WBC) subtypes and type 2 diabetes (T2D) risk. However, it is unknown whether this relationship is causal. We used Mendelian randomization (MR) to investigate the causal effect of WBC subtypes on T2D and glycemic traits. METHODS: The summary data for neutrophil, lymphocyte, monocyte, eosinophil, and basophil counts were extracted from a recent genome-wide association study (n = 173,480). The DIAGRAM and MAGIC consortia offered summary data pertaining to T2D and glycemic characteristics, including fasting glucose (FG) (n = 133,010), glycosylated hemoglobin (HbA1c) (n = 46,368), and homeostatic model assessment-estimated insulin resistance (HOMA-IR) (n = 37,037). A series of MR analyses (univariable MR, multivariable MR, and reverse MR) were used to investigate the causal association of different WBC subtypes with T2D and glycemic traits. RESULTS: Using the inverse-variance weighted method, we found one standard deviation increases in genetically determined neutrophil [odd ratio (OR): 1.086, 95% confidence interval (CI): 0.877-1.345], lymphocyte [0.878 (0.766-1.006)], monocyte [1.010 (0.906-1.127)], eosinophil [0.995 (0.867-1.142)], and basophil [0.960 (0.763-1.207)] were not causally associated with T2D risk. These findings were consistent with the results of three pleiotropy robust methods (MR-Egger, weighted median, and mode-based estimator) and multivariable MR analyses. Reverse MR analysis provided no evidence for the reverse causation of T2D on WBC subtypes. The null causal effects of WBC subtypes on FG, HbA1c, and HOMA-IR were also identified. CONCLUSIONS: WBCs play no causal role in the development of insulin resistance and T2D. The observed association between these factors may be explained by residual confounding.
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Diabetes Mellitus Tipo 2 , Resistência à Insulina , Humanos , Diabetes Mellitus Tipo 2/complicações , Hemoglobinas Glicadas/genética , Resistência à Insulina/genética , Análise da Randomização Mendeliana , Estudo de Associação Genômica Ampla , Glucose , BasófilosRESUMO
BACKGROUND: Krascheninnikovia ceratoides, a perennial halophytic semi-shrub belonging to the genus Krascheninnikovia (Amarathaceae), possesses noteworthy ecological, nutritional, and economic relevance. This species is primarily distributed across arid, semi-arid, and saline-alkaline regions of the Eurasian continent, encompassing Inner Mongolia, Xinjiang, Qinghai, Gansu, Ningxia, and Tibet. RESULTS: We reported the comprehensive chloroplast (cp) genome of K. ceratoides, characterized by a circular conformation spanning 151,968 bp with a GC content of 36.60%. The cp genome encompassed a large single copy (LSC, 84,029 bp), a small single copy (SSC, 19,043 bp), and a pair of inverted repeats (IRs) regions (24,448 bp each). This genome harbored 128 genes and encompassed 150 simple sequence repeats (SSRs). Through comparative analyses involving cp genomes from other Cyclolobeae (Amarathaceae) taxa, we observed that the K. ceratoides cp genome exhibited high conservation, with minor divergence events in protein-coding genes (PCGs) accD, matK, ndhF, ndhK, ycf1, and ycf2. Phylogenetic reconstructions delineated K. ceratoides as the sister taxon to Atriplex, Chenopodium, Dysphania, and Suaeda, thus constituting a robust clade. Intriguingly, nucleotide substitution ratios (Ka/Ks) between K. ceratoides and Dysphania species for ycf1 and ycf2 genes surpassed 1.0, indicating the presence of positive selection pressure on these loci. CONCLUSIONS: The findings of this study augment the genomic repository for the Amarathaceae family and furnish crucial molecular instruments for subsequent investigations into the ecological adaptation mechanisms of K. ceratoides within desert ecosystems.
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Chenopodiaceae , Genoma de Cloroplastos , Códon , Genoma de Cloroplastos/genética , Filogenia , Resistência à Seca , Ecossistema , Chenopodiaceae/genéticaRESUMO
V2O5·nH2O is a promising cathode material for zinc-ion batteries. One of the synthesis methods of V2O5·nH2O is in situ self-transformation. In this communication, we focus on the influence of the electrolyte environment during in situ self-transformation (from VO2 to V2O5·nH2O). 2 M ZnSO4 and 2 M Zn(OTf)2 were used as different electrolytes to produce VOH-1 and VOH-2. VOH-1 expands in volume along the electric field to form a porous surface structure and shows low crystallinity along the (0 0 1) plane, while VOH-2 exhibits the opposite. These advantages enable the assembled batteries with VOH-1 to maintain excellent cycling performance at a rate of 2 A g-1 with a capacity of 500 mA h g-1 and stable cycling for 1800 cycles.
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Aim: Multiple studies have investigated the association between alanine aminotransferase (ALT) and diabetes mellitus (DM); however, only a few studies have specifically examined the relationship between ALT and diabetic kidney disease (DKD). This study aimed to investigate the relationship between ALT and DKD using clinical data. Methods: A cross-sectional study was conducted on 668 individuals that included non-DM (N=281), DM without DKD (N=160), and DKD (N=227) patients. A generalized additive model (GAM) was used to examine the dose-response relationship between ALT and DKD risk. We also analyzed the data from the US National Health and Nutrition Examination Survey (NHANES) 2015-2018 using the same statistical methods; 4481, 1110, and 671 individuals were included in the non-DM, DM without DKD, and DKD groups, respectively. Results: The changes in ALT activity among the non-DM, DM without DKD, and DKD groups showed a similar pattern in both our clinical data and the NHANES dataset. ALT activity increases with the onset of DM, whereas ALT activity decreases when DM progresses to DKD. The GAM revealed a nonlinear U-shaped relationship between ALT and DKD risk in the two datasets, and the lowest range of ALT was 40-50 IU/L. Both lower (<40 IU/L) and higher (>50 IU/L) ALT activity were found to be positively associated with DKD risk. Conclusion: A U-shaped nonlinear association between ALT and DKD was found in our clinical data and NHANES data. DKD risk was increased by both lower or higher ALT activity. To confirm the causality of nonlinear relationship, larger prospective studies or Mendelian randomization analysis are required.
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Thrombocytopenia is a critical complication after radiation therapy and exposure. Dysfunction of megakaryocyte development and platelet production are key pathophysiological stages in ionizing radiation (IR)-induced thrombocytopenia. Protein kinase C (PKC) plays an important role in regulating megakaryocyte development and platelet production. However, it remains unclear how PKC regulates IR-induced megakaryocyte apoptosis. In this study, we found that pretreatment of PKC pan-inhibitor Go6983 delayed IR-induced megakaryocyte apoptosis, and inhibited IR-induced mitochondrial membrane potential and ROS production in CMK cells. Moreover, suppressing PKC activation inhibited cleaved caspase3 expression and reduced p38 phosphorylation levels, and IR-induced PKC activation might be regulated by p53. In vivo experiments confirmed that Go6983 promoted platelet count recovery after 21 days of 3 Gy total body irradiation. Furthermore, Go6983 reduced megakaryocyte apoptosis, increased the number of megakaryocyte and polyploid formation in bone marrow, and improved the survival rate of 6 Gy total body irradiation. In conclusion, our results provided a potential therapeutic target for IR-induced thrombocytopenia.
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Megacariócitos , Trombocitopenia , Humanos , Proteína Quinase C/metabolismo , Proteína Quinase C/uso terapêutico , Raios X , Trombocitopenia/etiologia , Trombopoese , Apoptose , PlaquetasRESUMO
H2O2 is widely used in the treatment of refractory organic pollutants.However, due to its explosive and corrosive chemical characteristics, H2O2 will bring great safety risks and troubles in transportation.So we chose sodium percarbonate(SPC) to be used in catalytic wet peroxide oxidation enhanced by swirl flow(SF-CWPO) and we designed carbon nanotubes with Ni single atom sites(Ni-NCNTs/AC) to activate SPC to treat an m-cresol wastewater containing Si.Meanwhile, artificial intelligence which used Artificial neural network (ANN) was used to optimize the conditions.Under the conditions of pH = 9.27, reaction time of 8.91 min, m-cresol concentration is 59.09 mg L-1, SPC dosage is 2.80 g L-1 and Na2SiO3·9H2O dosage is 77.27 mg L-1, the degradation rate of total organic carbon(TOC) and m-cresol reaches 94.37% and 100%, respectively.Finally, the applicability of Ni-NCNTs/AC-SPC-SF-CWPO technology was evaluated in a wastewater system of a sewage treatment enterprise and Fourier transform ion cyclotron resonance mass spectrum(FT-ICR MS) analysis and chemical oxygen demand(COD) analysis showed the great ability of Ni-NCNTs/AC-SPC-SF-CWPO technology to treat wastewater.It is believed that this paper is of great significance to the design and construction of the in-depth research and industrial application of SF-CWPO.
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Nanotubos de Carbono , Poluentes Químicos da Água , Peróxido de Hidrogênio , Águas Residuárias , Silício , Inteligência Artificial , Peróxidos , Oxirredução , CatáliseRESUMO
As the promotive/complementary mechanism of the microbe-soil-tobacco (Nicotiana tabacum L.) interaction remains unclear and the contribution of this triple interaction to tobacco growth is not predictable, the effects of intercropping on soil nutrients, enzymatic activity, microbial community composition, plant growth, and plant quality were studied, and the regulatory mechanism of intercropping on plant productivity and soil microenvironment (fertility and microorganisms) were evaluated. The results showed that the soil organic matter (OM), available nitrogen (AN), available phosphorus (AP), available potassium (AK), the urease activity (UE) and sucrase activity (SC), the diversity, abundance, and total and unique operational taxonomic units (OTUs) of bacteria and fungi as well as plant biomass in T1 (intercropping onion), T2 (intercropping endive), and T3 (intercropping lettuce) treatments were significantly higher than those of the controls (monocropping tobacco). Although the dominant bacteria and fungi at the phylum level were the same for each treatment, LEfSe analysis showed that significant differences in community structure composition and the distribution proportion of each dominant community were different. Proteobacteria, Acidobacteria, and Firmicutes of bacteria and Ascomycota and Basidiomycetes of fungi in T1, T2, and T3 treatments were higher than those of the controls. Redundancy analysis (RDA) suggested a close relation between soil characteristic parameters and microbial taxa. The correlation analysis between the soil characteristic parameters and the plant showed that the plant biomass was closely related to soil characteristic parameters. In conclusion, the flue-cured tobacco intercropping not only increased plant biomass and improved chemical quality but also significantly increased rhizospheric soil nutrient and enzymatic activities, optimizing the microbial community composition and diversity of rhizosphere soil. The current study highlighted the importance of microbe-soil-tobacco interactions in maintaining plant productivity and provided the potential fertilization practices in flue-cured tobacco production to maintain ecological sustainability.
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Iron-loaded zeolite (Fe-zeolite) has shown great potential as an efficient catalyst for degrading organic pollutants with high concentrations in the catalytic wet peroxide oxidation (CWPO) process under mild conditions. Here, 0.4 wt% Lanthanum (La) was added in the 1.0 wt% Fe-ZSM-5 by two-step impregnation method for an enhanced H2O2 utilization efficiency. For a systematical comparison, the CWPO process at 55 °C, where m-cresol with a high concentration of 1000 mg/L as a substrate, was studied over Fe-ZSM-5 and Fe-La-ZSM-5 catalysts. Compared with Fe-ZSM-5, Fe-La-ZSM-5 showed 15% higher H2O2 utilization efficiency with comparable total organic carbon (TOC) removal at around 40%, meanwhile with a 15% reduced metal leaching. Transmission electron microscopy (TEM) with elemental mapping (EDS), surface acidity analysis by Fourier transform infrared (FT-IR) and NH3-temperature programmed desorption (NH3-TPD), redox property analysis by Raman spectroscopy and H2-temperature-programmed reduction (H2-TPR) of both catalysts revealed, that the La doped Fe-ZSM-5 can provide an altered surface acidity, a more uniform and evenly dispersed surface Fe species with a promoted reducibility, which effectively promoted the accurate decomposition of H2O2 into the reactive â¢OH radicals, enhanced the H2O2 utilization efficiency, and increased the catalyst stability. Also, more than 90% conversion was maintained during the continuous experiment for more than 10 consecutive test days under 55 °C without pH adjustment, showing a promising possibility of the Fe-La-ZSM-5 for a practical wastewater treatment process.
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Peróxidos , Zeolitas , Peróxido de Hidrogênio/química , Lantânio , Zeolitas/química , Espectroscopia de Infravermelho com Transformada de Fourier , Catálise , OxirreduçãoRESUMO
A method of energy-transfer resonance of lycopene used to enhance stimulated Raman scattering (SRS) of a weak vibration C-O mode in tetrahydrofuran (THF) was developed in this study. Only C-H SRS was observed in pure THF at high energies. When lycopene was added, the C-O SRS located at 915â cm-1 of the weak vibration mode in THF was observed. The maximum SRS enhancement of the C-O mode was achieved when the concentration was 3.72 × 10-6â mol/L because of the resonance enhancement of the solute, which transferred the excess vibrational energy to the solvent. Moreover, the pulse width compression phenomenon of the C-H vibration in the presence of C-O SRS was obtained.
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Ring skeleton vibrations of aromatic series are dominant in Raman spectroscopy compared with the C-H stretching vibrations. When a laser-induced plasma (LIP) was generated in a mixed solution of naphthalene and benzene, an anomalous enhancement was observed in stimulated Raman scattering (SRS) of aromatic C-H stretching vibrations of naphthalene (3055â cm-1). However, SRS of C-H stretching vibrations of benzene at 3060â cm-1 disappeared. The LIP produced electrons and cations, and the transient production of ionized material contributed to the enhancement of SRS of C-H vibrations of naphthalene. Density functional theory calculations showed that the C-H Raman activity of the naphthalene molecules in (naphthalene-benzene)+ heterodimer was significantly enhanced compared with neutral naphthalene. In addition, SRS pulse durations were better compressed in pure benzene and naphthalene due to the self-focusing effect.
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OBJECTIVES: Cyclic thrombocytopenia (CTP) is a rare blood disorder characterized by periodic fluctuations in platelet counts. CTP usually appears in pre-menopausal women, and these fluctuations of platelets are in phase with the menstrual cycle. CTP is a heterogeneous disease, and the pathogenic mechanism is still unclear. Therefore, it harbors great significance for exploring the association of fluctuations in platelet counts with hormonal-cycle. MATERIALS: Firstly, we washed human platelets from healthy volunteers following the Declaration of Helsinki. Flow cytometer was employed to measure the mitochondrial inner transmembrane potential (ΔΨm) depolarization, PS exposure, P-selectin expression, and GPIIb/IIIa activation in platelets. In addition, western blot detected the related protein expression. The corresponding assay kit measured the caspase-3 and PDE3A activity. Finally, flow cytometry determined mouse platelets labeled with calcein. RESULTS: We find a reverse relationship between the platelet count and serum estradiol (E2) level in a CTP patient. We demonstrated that E2 induces platelet apoptosis in vitro and platelet clearance in vivo. We further discovered that E2 activates phosphodiesterase 3A, which inhibits protein kinase A (PKA), leading to PKA-mediated platelet apoptosis. Activation of PKA protected platelets from E2-induced thrombocytopenia and elevated the number of mice circulatory platelets. CONCLUSIONS: We find that E2 induces platelet apoptosis and clearance through PDE3A-mediated PKA inhibition. Activation of PKA rescues E2-induced thrombocytopenia in mice. Thus, our study reveals a pathogenesis of E2-related CTP and suggests promising therapeutic strategies for the disease.
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Estradiol , Trombocitopenia , Humanos , Feminino , Animais , Camundongos , Estradiol/metabolismo , Plaquetas/metabolismo , Contagem de Plaquetas , ApoptoseRESUMO
In situ and on-site analysis of trace components, such as methanol and ethyl acetate, in distilled spirits poses significant challenges. In this study, we have proposed a simple, yet effective and rapid approach that combines Raman spectroscopy with Raman integrating sphere technology to accurately detect trace constituents in distilled spirits. An external standard method to effectively separate overlapping Raman peaks from different substances are developed. Experimental results demonstrate that with an exposure time of 180 s under normal temperature and pressure, the detection limits for methanol, acetic acid, and ethyl acetate in proportioned distilled spirits are below 0.1 g/L. Importantly, the detection limit of methanol and acetic acid remains unaffected by the concentration of distilled spirits and the types of trace substances. Notably, the concentration of trace solute exhibits a highly linear relationship with its corresponding Raman intensity, offering a reliable probe for identifying unknown components in distilled spirits.
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Bebidas Alcoólicas , Metanol , Metanol/análise , Bebidas Alcoólicas/análise , Análise Espectral Raman , Ácido Acético/análiseRESUMO
Objectives: This study is designed to analyze the potential influencing factors of hyperlipidemia, and to explore the relationship between liver function indicators such as gamma-glutamyltransferase (GGT) and hyperlipidemia. Methods: Data were derived from 7599 outpatients who visited the Department of Endocrinology of the First Hospital of Jilin University (2017-2019). A multinomial regression model is used to identify related factors of hyperlipidemia and the decision tree method is used to explore the general rules in hyperlipidemia patients and non-hyperlipidemia patients on these factors. Results: The average of age, body mass index (BMI), systolic blood pressure (SBP), diastolic blood pressure, aspartate aminotransferase, alanine aminotransferase (ALT), GGT and glycosylated hemoglobin (HbA1c) in the hyperlipidemia group are higher than those in the non-hyperlipidemia group. In multiple regression analysis, SBP, BMI, fasting plasma glucose, 2-h postprandial blood glucose, HbA1c, ALT, GGT are associated with triglyceride. For people with HbA1c less than 6.0%, controlling GGT within 30â IU/L reduces the prevalence of hypertriglyceridemia by 4%, and for people with metabolic syndrome with impaired glucose tolerance controlling GGT within 20â IU/L reduces the prevalence of hypertriglyceridemia by 11%. Conclusions: Even when GGT is in the normal range, the prevalence of hypertriglyceridemia increases with its gradual increase. Controlling GGT in people with normoglycemia and impaired glucose tolerance can reduce the risk of hyperlipidemia.