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Parkinson's disease (PD) is a common neurodegenerative disease with complex pathogenesis and no effective treatment. Recent studies have shown that dysbiosis of the oral microflora is closely related to the development of PD. The abnormally distributed oral microflora of PD patients cause degenerative damage and necrosis of dopamine neurons by releasing their own components and metabolites, intervening in the oral-gut-brain axis, crossing the biofilm, inducing iron dysregulation, activating inter-microflora interactions, and through the mediation of saliva,ultimately influencing the development of the disease. This article reviews the structure of oral microflora in patients with PD, the mechanism of development of PD caused by oral microflora, and the potential value of targeting oral microflora in developing a new strategy for PD prevention, diagnosis and treatment.
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Dust storms have great impacts on air quality and climate. Dust can influence cloud microphysical properties and determine their radiative forcing and precipitation. Asian dust storms (ADS) are important sources of global aerosol. However, the physiochemical characteristics of dust from ADS at a single particle level are less understood, and the exact particles that can serve as ice nucleating particles (INPs) remain unclear. Here, we present the physicochemical properties and ice nucleation ability of dust particles collected in Beijing during two major ADS in March 2021. The particles from two ADS were classified into Illite, Kaolinite, Feldspar, Quartz, Chlorite, Mixed-dust, and Non-dust particles, which contributed 28.6 % ± 3.3 %, 20.0 % ± 3.9 %, 12.3 % ± 2.3 %, 11.1 % ± 2.8 %, 9.8 % ± 0.8 %, 13.7 % ± 1.8 %, and 4.4 % ± 1.7 % in number, respectively. On average, the ADS particles formed ice crystals via deposition ice nucleation from relative humidity with respect to ice (RHice) of 112 % ± 1 % at 250 K to 154 % ± 15 % RHice at 205 K. Part of the samples also formed ice via immersion freezing between 230 K and 250 K. Among the 149 identified INPs, Clay-like particles (Chlorite, Illite, and Kaolinite) contributed 71.1 % ± 6.2 % in number and followed by Mixed-dust-like particles (16.9 % ± 8.7 %) and Feldspar-like particles (10.4 % ± 6.3 %). Enrichment factor of each particle type in INPs is calculated as the ratio of its number fractions in INPs and the aerosol population. It ranges from 0.6 ± 0.7 to 1.3 ± 2.2. The contribution of each particle type to INP was correlated with its fraction in the population. These results imply that each particle type can serve as INP. Clay-like particles are the dominant INPs during the ADS. We conducted ice nucleation kinetic analysis and provided parameterizations of heterogeneous ice nucleation rate coefficient and contact angle for ADS. These parameterizations can be used in the modeling study to evaluate the impact of ADS in atmospheric ice crystal formation in clouds.
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Objectives: The purpose of this study was to analyze the effects of lamotrigine on peripheral blood cytokines and depression in patients with epilepsy and to explore the possible mechanism by which lamotrigine regulates depression in patients with epilepsy. Methods: 50 healthy people, 72 patients treated with lamotrigine (LTG group) and 72 patients treated with valproate were enrolled (VPA group). Cytokine levels in the peripheral blood of the subjects were measured and their level of depression was scored according to the self-rating Depression Scale (SDS), Hamilton Depression Scale (HAMD) and Chinese version of Epilepsy Depression Scale (c-NDDI-E). The cytokine levels and depression scale scores were compared between the three groups. The correlation between cytokine levels and depression scale scores was analyzed. Results: The levels of IL-1ß, IL-2, IL-6, and TNF-α and the SDS, HAMD, and c-NDDI-E scores in healthy group was lower than that in epileptic group. After 6 months of treatment, the difference valule of IL-1ßãIL-6ãTNF-αãSDS and HAMD before and after treatment in LTG group significantly higher than that in VPA group. Correlation analysis showed that the SDS scores were correlated with the levels of IL-1ß and TNF-α, and the HAMD scores were correlated with the levels of TNF-α. Multiple linear regression analysis showed that the HAMD scores were correlated with the levels of TNF-α. Conclusion: Lamotrigine can inhibit peripheral blood inflammation and improve depression in epileptic patients. Lamotrigine improved depressive mood in epileptic patients, which may be related to reduced TNF-α levels.
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Composite insulators have been widely used in power grids due to their excellent electrical-external-insulation performance. Long-term operation at high voltage levels accelerates the aging of composite insulators; however, there is a scarcity of research on aged composite insulators operating at 500 kV for over ten years. In this paper, the mechanical, electrical, and microscopic properties were tested on different sheds along a 500 kV composite insulator that had been running for 18 years. Additionally, the results were compared with a new insulator and the standards for live insulator operation. The results showed that the aging of the high-voltage end of composite insulators was the most serious. The results of the physical properties test indicated that the insulator's hardness was compliant but its tensile strength and break elongation did not meet standards. Under wet conditions, the pollution flashover voltage decreases by about 50% compared to the new insulator. Combined with the microscopic test results, the shed skeleton structure could be damaged and the filler might be lost during the aging process of polydimethylsiloxane (PDMS). The hardness of the insulator would increase by the precipitation of inorganic silicon; however, inorganic silicon might destroy the hydrophobicity and other properties of insulator sheds. These results can provide theoretical references for insulator life prediction and operation protection.
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Superhydrophobic coatings are increasingly recognized as a promising approach to enhancing power generation efficiency and prolonging the operational lifespan of wind turbines. In this research, a durable superhydrophobic perfluoroalkoxy alkane (PFA) coating was developed and specifically designed for spray application onto the surface of wind turbine blades. The PFA coating features a micronano hierarchical structure, exhibiting a high water contact angle of 167.0° and a low sliding angle of 1.7°. The optimal PFA coating exhibits stability and maintains a superhydrophobic performance during mechanical and chemical tests. The findings of this study establish a positive association between the surface energy of the coating and its effectiveness in anti-icing. The delayed icing time for the PFA-coated surface is 46.83 times longer than that of an uncoated surface, and the ice adhesion strength is only 1.875 kPa. Additionally, the PFA coating demonstrates remarkably high ice suppression efficiencies of 94.7 and 99.5% in anti-icing experiments at ambient temperatures of -6 and -10 °C, respectively. It is anticipated that this stable superhydrophobic PFA coating will be a candidate for anti-icing applications in wind turbine blades.
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OBJECTIVE: To analyze the correlation between the level of 25(OH)D in peripheral blood and cognitive function in patients with epilepsy, and to find the biomarkers of epilepsy complicated with cognitive dysfunction. METHODS: 68 patients with epilepsy and 30 healthy subjects were included in this study. The 25(OH)D level in peripheral blood of all subjects was detected and the score of the Montreal Cognitive Assessment Scale was performed. The patients with epilepsy were divided into a cognitively normal group (36 cases) and a cognitively impaired group (32 cases) according to the scale score. The inter-group scale score and 25(OH)D level were compared, and the correlation was analyzed. RESULTS: The levels of 25(OH)D and MOCA in epileptic group were significantly lower than those in healthy control group. The 25(OH)D and MOCA of the cognitively impaired group were significantly lower than those of the cognitively normal group. Logistic regression analysis indicated that serum 25(OH)D level was an independent risk factor for epilepsy combined with cognitive impairment (OR = 0.704, P = 0.014). The area under ROC curve of serum 25(OH)D for diagnosis of epilepsy combined with cognitive impairment was 0.924 (95 %CI 0.866,0.981), the critical value was 34.50 nmol/L, the sensitivity was 0.778, and the specificity was 0.906. CONCLUSION: Decreased levels of vitamin D are associated with cognitive impairment associated with epilepsy, and it may be a biomarker for early screening of cognitive impairment.
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In Brief: The mechanisms that determine the length of pregnancy remain undetermined. Here, we review what has been previously published on the topic and incorporate new data to describe a molecular model in which placental stress and fetal signaling ultimately lead to labor onset in uncomplicated pregnancies. Abstract: The mechanisms that govern the length of human pregnancy have not been determined, while preterm birth remains the leading cause of death and disability in newborns worldwide. Here, we review recent data to generate a novel hypothesis about how the pregnancy clock may function to initiate human labor in uncomplicated pregnancies. In this model, placental stress induced by the growing fetus drives placental production of NFKB, which is then activated by exosomes containing platelet-activating factor and complement 4-binding protein-A from the mature fetus, to drive pro-labor genes in the placenta. A better understanding of the clock that triggers labor may lead to new, more effective therapies to prevent spontaneous preterm birth.
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Placenta , Humanos , Feminino , Gravidez , Placenta/metabolismo , Placenta/fisiologia , Relógios Biológicos , Nascimento Prematuro/metabolismo , Início do Trabalho de Parto/fisiologiaRESUMO
Ulcerative colitis (UC) is an inflammatory bowel disease with an increasing prevalence year over year, and the medications used to treat patients with UC clinically have severe side effects. Oyster peptides (OPs) have anti-inflammatory and antioxidant properties as functional foods that can alleviate a wide range of inflammatory conditions. However, the application of oyster peptides in ulcerative colitis is not well studied. In this work, an animal model of acute colitis was established using 3% dextran sulfate sodium (DSS), and the impact of OP therapy on colitis in mice was examined. Supplementing with OPs prevented DSS-induced colitis from worsening, reduced the expression of oxidative stress and inflammatory markers, and restored the intestinal barrier damage caused by DSS-induced colitis in mice. The 16S rDNA results showed that the OP treatment improved the gut microbiota structure of the UC mice, including increasing microbial diversity, increasing beneficial bacteria, and decreasing harmful bacteria. In the UC mice, the OP therapy decreased the relative abundance of Family_XIII_AD3011_group and Prevotella_9 and increased the relative abundance of Alistipes. In conclusion, OP treatment can inhibit the TLR4/NF-κB pathway and improve the intestinal microbiota in UC mice, which in turn alleviates DSS-induced colitis, providing a reference for the treatment of clinical UC patients.
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Colite Ulcerativa , Microbioma Gastrointestinal , Peptídeos , Transdução de Sinais , Animais , Masculino , Camundongos , Anti-Inflamatórios/farmacologia , Colite Ulcerativa/induzido quimicamente , Colite Ulcerativa/tratamento farmacológico , Colite Ulcerativa/microbiologia , Sulfato de Dextrana , Modelos Animais de Doenças , Microbioma Gastrointestinal/efeitos dos fármacos , Camundongos Endogâmicos C57BL , NF-kappa B/metabolismo , Ostreidae , Estresse Oxidativo/efeitos dos fármacos , Peptídeos/farmacologia , Transdução de Sinais/efeitos dos fármacos , Receptor 4 Toll-Like/metabolismoRESUMO
2-(2-Phenylethyl)chromones (PECs) are the primary constituents responsible for the promising pharmacological activities and unique fragrance of agarwood. However, the O-methyltransferases (OMTs) involved in the formation of diverse methylated PECs have not been reported. In this study, we identified one Mg2+-dependent caffeoyl-CoA-OMT subfamily enzyme (AsOMT1) and three caffeic acid-OMT subfamily enzymes (AsOMT2-4) from NaCl-treated Aquilaria sinensis calli. AsOMT1 not only converts caffeoyl-CoA to feruloyl-CoA but also performs nonregioselective methylation at either the 6-OH or 7-OH position of 6,7-dihydroxy-PEC. On the other hand, AsOMT2-4 preferentially utilizes PECs as substrates to produce structurally diverse methylated PECs. Additionally, AsOMT2-4 also accepts nonPEC-type substrates such as caffeic acid and apigenin to generate methylated products. Protein structure prediction and site-directed mutagenesis revealed that residues of L313 and I318 in AsOMT3, as well as S292 and F313 in AsOMT4 determine the distinct regioselectivity of these two OMTs toward apigenin. These findings provide important biochemical evidence of the remarkable structural diversity of PECs in agarwood.
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Metiltransferases , Proteínas de Plantas , Thymelaeaceae , Metiltransferases/genética , Metiltransferases/química , Metiltransferases/metabolismo , Thymelaeaceae/enzimologia , Thymelaeaceae/química , Thymelaeaceae/genética , Proteínas de Plantas/genética , Proteínas de Plantas/química , Proteínas de Plantas/metabolismo , Madeira/química , Especificidade por Substrato , Ácidos Cafeicos/química , Ácidos Cafeicos/metabolismo , Metilação , FlavonoidesRESUMO
BACKGROUND: Community-acquired pneumonia (CAP) patients with chronic obstructive pulmonary disease (COPD) have higher disease severity and mortality compared to those without COPD. However, deep investigation into microbiome distribution of lower respiratory tract of CAP with or without COPD was unknown. METHODS: So we used metagenomic next generation sequencing (mNGS) to explore the microbiome differences between the two groups. RESULTS: Thirty-six CAP without COPD and 11 CAP with COPD cases were retrieved. Bronchoalveolar lavage fluid (BALF) was collected and analyzed using untargeted mNGS and bioinformatic analysis. mNGS revealed that CAP with COPD group was abundant with Streptococcus, Prevotella, Bordetella at genus level and Cutibacterium acnes, Rothia mucilaginosa, Bordetella genomosp. 6 at species level. While CAP without COPD group was abundant with Ralstonia, Prevotella, Streptococcus at genus level and Ralstonia pickettii, Rothia mucilaginosa, Prevotella melaninogenica at species level. Meanwhile, both alpha and beta microbiome diversity was similar between groups. Linear discriminant analysis found that pa-raburkholderia, corynebacterium tuberculostearicum and staphylococcus hominis were more enriched in CAP without COPD group while the abundance of streptococcus intermedius, streptococcus constellatus, streptococcus milleri, fusarium was higher in CAP with COPD group. CONCLUSIONS: These findings revealed that concomitant COPD have an mild impact on lower airway microbiome of CAP patients.
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Líquido da Lavagem Broncoalveolar , Infecções Comunitárias Adquiridas , Metagenômica , Microbiota , Doença Pulmonar Obstrutiva Crônica , Humanos , Doença Pulmonar Obstrutiva Crônica/microbiologia , Líquido da Lavagem Broncoalveolar/microbiologia , Infecções Comunitárias Adquiridas/microbiologia , Masculino , Estudos Retrospectivos , Idoso , Feminino , Microbiota/genética , Pessoa de Meia-Idade , Metagenômica/métodos , Sequenciamento de Nucleotídeos em Larga Escala , Pneumonia/microbiologia , Idoso de 80 Anos ou maisRESUMO
BACKGROUND: Acute Liver Failure (ALF) is a critical medical condition with rapid development, often caused by viral infections, hepatotoxic drug abuse, or other severe liver diseases. Timely and accurate prediction of ALF occurrence is clinically crucial. However, predicting ALF poses challenges due to the diverse physiological differences among patients and the dynamic nature of the disease. OBJECTIVE: This study introduces a deep learning approach that combines fully connected and convolutional neural networks for effective ALF prediction. The goal is to overcome limitations of traditional machine learning methods and enhance predictive model performance and generalization. METHODS: The proposed model integrates a fully connected neural network for handling basic patient features and a convolutional neural network dedicated to capturing temporal patterns in patient data. The combination allows automatic learning of complex patterns and abstract features present in highly dynamic medical data associated with ALF. RESULTS: The model's effectiveness is demonstrated through comprehensive experiments and performance evaluations. It outperforms traditional machine learning methods, achieving 94.8% accuracy and superior generalization capabilities. CONCLUSIONS: The study highlights the potential of deep learning in ALF prediction, emphasizing the importance of considering individualized medical factors. Future research should focus on improving model robustness, addressing imbalanced data, and further exploring personalized features for enhanced predictive accuracy in real-world clinical scenarios.
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Aprendizado Profundo , Falência Hepática Aguda , Redes Neurais de Computação , Humanos , Masculino , FemininoRESUMO
OBJECTIVE: Pregnant women are at increased risk of coronavirus disease 2019 (COVID-19). This could be explained through the prism of physiologic and immunologic changes in pregnancy. In addition, certain immunological reactions originate in the placenta in response to viral infections.This study aimed to investigate whether severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2) can infect the human placenta and discuss its implications in the pathogenesis of adverse pregnancy outcomes. STUDY DESIGN: We conducted a retrospective cohort study in which we collected placental specimens from pregnant women who had a laboratory-confirmed SARS-CoV-2 infection. We performed RNA in situ hybridization assay on formalin-fixed paraffin-embedded tissues to establish the in vivo evidence for placental infectivity by this corona virus. In addition, we infected trophoblast isolated from uninfected term human placenta with SARS-CoV-2 variants to further provide in vitro evidence for such an infectivity. RESULTS: There was a total of 21 cases enrolled, which included 5 cases of spontaneous preterm birth (SPTB) and 2 intrauterine fetal demises (IUFDs). Positive staining of positive-sense strand of SARS-CoV-2 virions was detected in 15 placentas including 4 SPTB and both IUFDs. In vitro infection assay demonstrated that SARS-CoV-2 virions were highly capable of infecting both cytotrophoblast and syncytiotrophoblast. CONCLUSION: This study implies that placental SARS-CoV-2 infection may be associated with an increased risk of adverse obstetrical outcomes. KEY POINTS: · SARS-CoV-2 can effectively infect human placenta.. · Such infectivity is confirmed by in vitro experiments.. · Placental SARS-CoV-2 corelates with adverse obstetrical outcomes..
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Constructing Z-scheme heterojunctions incorporating an exquisite hollow structure is an effective performance regulation strategy for the realization of high quantum efficiency and a strong redox ability over photocatalysts. Herein, we report the delicate design and preparation of a core-shell hollow CdS@CoTiO3 Z-scheme heterojunction with a CdS nanoparticle (NP)-constructed outer shell supported on a CoTiO3 nanorod (NR) inner shell. The in situ growth synthetic method led to a tightly connected interface for the heterojunction between CdS and CoTiO3, which shortened the transport distance of photoinduced charges from the interface to the surface. The promoted charge carrier separation efficiency and the retained strong redox capacity caused by the Z-scheme photoinduced charge-transfer mechanism were mainly responsible for the boosted photocatalytic performance. Additionally, the well-designed core-shell structure afforded a larger interfacial area by the multiple direction contact between CdS and CoTiO3, ensuring sufficient channels for efficient charge transfer, and thus further boosting the photocatalytic activity. As an efficient photocatalyst, the optimized CdS@CoTiO3 nanohybrids displayed excellent 2,4-dichlorophenol (2,4-DCP) and tetracycline (TC) degradation efficiencies of 91.3% and 91.8%, respectively. This study presents a Z-scheme heterojunction based on ecofriendly CoTiO3, which could be valuable for the development of metal perovskite photocatalysts for application in environmental remediation, and also demonstrated the tremendous potential of integrating a Z-scheme heterojunction with the morphology design of photocatalyts.
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To analyse the risk factors affecting wound healing and infection after spinal meningioma resection surgery. The surgical incision healing of 137 patients who underwent spinal meningioma resection at our hospital from January 2021 to January 2024 was analysed. The data collected included physical examination findings, haematological and biochemical measurements, and various scales assessed upon admission and after surgery. These data were then analysed. The surgical wound healing, infection and postoperative complications were statistically analysed. Multiple logistic regression analysis method was used to conduct risk factor analysis on corresponding indicators; the odds ratio and p value of 95% confidence interval were calculated. Factors such as age and smoking history were significantly negatively correlated with wound healing after meningioma resection (odds ratio < 1.000, p < 0.05), while preoperative albumin and platelet count were significantly positively correlated with wound healing (odds ratio > 1.000, p < 0.05). Age, WHO Meningioma Grading, preoperative albumin and preoperative platelet were significantly negatively correlated with wound infection after meningioma resection (odds ratio < 1.000, p < 0.05). The history of virus infection and history of neurological disorders were significantly positively correlated with wound infection (odds ratio > 1.000, p < 0.05). The influence of each factor is different. Age, smoking history, WHO Meningioma Grading, preoperative albumin, preoperative platelets, history of virus infection and history of neurological disorders had the greatest influence on wound healing and infection after meningioma resection.
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Neoplasias Meníngeas , Meningioma , Ferida Cirúrgica , Viroses , Infecção dos Ferimentos , Humanos , Meningioma/cirurgia , Estudos Retrospectivos , Fatores de Risco , Cicatrização , Neoplasias Meníngeas/cirurgia , AlbuminasRESUMO
OBJECTIVE: By analysing the difference in TNF-α levels in the peripheral blood of patients with medial temporal lobe epilepsy (mTLE) with or without hippocampal sclerosis and the correlation between TNF-α and N-acetylaspartate levels in the hippocampus, we explored the relationship between TNF-α and the degree of damage to hippocampal sclerosis neurons in medial temporal lobe epilepsy. METHODS: This is a prospective, population-based study. A total of 71 Patients with medial temporal lobe epilepsy diagnosed by clinical seizures, video-EEG, epileptic sequence MRI, and other imaging examinations were recruited from October 2020 to July 2022 in the Department of Neurology, Affiliated Hospital of Xuzhou Medical University. Twenty age-matched healthy subjects were selected as the control group. The patients were divided into two groups: the medial temporal epilepsy with hippocampal sclerosis group (positive group, mTLE-HS-P group) and the medial temporal epilepsy without hippocampal sclerosis group (negative group, mTLE-HS-N group). The levels of IL-1ß, IL-5, IL-6, IL-8, IL-17, IFN-γ and TNF-α in the peripheral blood of the patients in the three groups were detected by multimicrosphere flow immunofluorescence assay. The level of N-acetylaspartate (NAA) in the hippocampus was measured by 1H-MRS. The differences in cytokine levels among the three groups were analysed, and the correlation between cytokine and NAA levels was analysed. RESULTS: The level of TNF-α in the peripheral blood of the patients in the mTLE-HS-P group was significantly higher than that of the patients in the mTLE-HS-N and healthy control groups, and the level of TNF-α in the patients in the mTLE-HS-N group was significantly higher than that of the patients in the healthy control group. The NAA level in mTLE-HS-P group patients was significantly lower than that of mTLE-HS-N patients and healthy controls, but there was no significant difference between mTLE-HS-N patients and healthy controls (P > 0.05). Spearman correlation analysis showed that TNF-α level (rs = -0.437, P < 0.05) and the longest duration of a single seizure (rs = -0.398, P < 0.05) were negatively correlated with NAA level. Logistic regression analysis showed that there was no significant correlation between the longest duration of a single seizure and hippocampal sclerosis, but TNF-α level was closely related to hippocampal sclerosis in patients with mTLE (OR = 1.315, 95 % CI 1.084-1.595, P = 0.005). CONCLUSION: The level of TNF-α in the peripheral blood of patients with medial temporal lobe epilepsy with hippocampal sclerosis was higher, and it was correlated with NAA and hippocampal sclerosis. The high expression of TNF-α may be of important value in the evaluation of hippocampal sclerosis patients.
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Ácido Aspártico , Epilepsia do Lobo Temporal , Esclerose Hipocampal , Fator de Necrose Tumoral alfa , Adulto , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Adulto Jovem , Ácido Aspártico/análogos & derivados , Ácido Aspártico/análise , Biomarcadores/sangue , Epilepsia do Lobo Temporal/sangue , Epilepsia do Lobo Temporal/patologia , Esclerose Hipocampal/diagnóstico , Imageamento por Ressonância Magnética , Estudos Prospectivos , Fator de Necrose Tumoral alfa/sangueRESUMO
Ulcerative colitis (UC) is a recurrent intestinal disease with an increasing incidence worldwide that seriously affects the life of patients. Turtle peptide (TP) is a bioactive peptide extracted from turtles that has anti-inflammatory, antioxidant and anti-aging properties. However, studies investigating the effect of TP on the progression of UC are lacking. The aim of this study was to investigate effects and underlying mechanisms of TP and its derivative peptide GPAGPIGPV (GP-9) in alleviating UC in mice. The results showed that 500 mg/kg TP treatment significantly ameliorated colitis symptoms and oxidative stress in UC mice. TP alleviated intestinal barrier damage in UC mice by promoting mucosal repair and increasing the expression of tight junction proteins (ZO1, occludin and claudin-1). TP also modulated the composition of the gut microbiota by increasing the abundance of the beneficial bacteria Anaerotignum, Prevotellaceae_UCG-001, Alistipes, and Lachno-spiraceae_NK4A136_group and decreasing the abundance of the harmful bacteria Prevotella_9 and Parasutterella. Furthermore, we characterized the peptide composition of TP and found that GP-9 ameliorated the symptoms of dextran sodium sulfate (DSS)-induced colitis in mice by inhibiting the TLR4/NF-κB signaling pathway. In conclusion, TP and its derivative peptides ameliorated DSS-induced ulcerative colitis by inhibiting the expression of inflammatory factors and modulating the composition of the intestinal microbiota; this study provides a theoretical basis for the application of TP and its derivative peptides for their anti-inflammatory activity.
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Anti-Inflamatórios , Colite Ulcerativa , Sulfato de Dextrana , Microbioma Gastrointestinal , Camundongos Endogâmicos C57BL , Peptídeos , Tartarugas , Animais , Colite Ulcerativa/tratamento farmacológico , Colite Ulcerativa/induzido quimicamente , Colite Ulcerativa/patologia , Colite Ulcerativa/imunologia , Microbioma Gastrointestinal/efeitos dos fármacos , Camundongos , Peptídeos/uso terapêutico , Peptídeos/farmacologia , Anti-Inflamatórios/uso terapêutico , Anti-Inflamatórios/farmacologia , Tartarugas/microbiologia , Tartarugas/imunologia , Masculino , Receptor 4 Toll-Like/metabolismo , NF-kappa B/metabolismo , Modelos Animais de Doenças , Mucosa Intestinal/efeitos dos fármacos , Mucosa Intestinal/patologia , Mucosa Intestinal/metabolismo , Mucosa Intestinal/microbiologia , Colo/patologia , Colo/efeitos dos fármacos , Humanos , Estresse Oxidativo/efeitos dos fármacos , Transdução de Sinais/efeitos dos fármacosRESUMO
Repair of bone defects exceeding a critical size has been always a big challenge in clinical practice. Tissue engineering has exhibited great potential to effectively repair the defects with less adverse effect than traditional bone grafts, during which how to induce vascularized bone formation has been recognized as a critical issue. Therefore, recently many studies have been launched to attempt to promote osteogenesis-angiogenesis coupling. This review summarized comprehensively and explored in depth current efforts to ameliorate the coupling of osteogenesis and angiogenesis from four aspects, namely the optimization of scaffold components, modification of scaffold structures, loading strategies for bioactive substances, and employment tricks for appropriate cells. Especially, the advantages and the possible reasons for every strategy, as well as the challenges, were elaborated. Furthermore, some promising research directions were proposed based on an in-depth analysis of the current research. This paper will hopefully spark new ideas and approaches for more efficiently boosting new vascularized bone formations.
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Osso e Ossos , Neovascularização Fisiológica , Osteogênese , Engenharia Tecidual , Alicerces Teciduais , Osteogênese/efeitos dos fármacos , Humanos , Neovascularização Fisiológica/efeitos dos fármacos , Animais , Alicerces Teciduais/química , AngiogêneseRESUMO
BACKGROUND: A more secure and efficacious therapy than has been developed so far is imperative for patients suffering from recurrent trigeminal neuralgia (TN). Despite numerous reports on the use of enhanced percutaneous balloon compression (PBC) techniques, such as altering compression duration and balloon pressure, none have yielded satisfactory outcomes. With these issues in mind, we have employed the PBC double-compression technique for the first time. This technique involves initially inflating a balloon to expand the adhesive tissue in Meckel's lumen, followed by emptying of the contrast medium and subsequent slight catheter adjustment for further compression. The total duration of compression remains unchanged and may even be shortened. OBJECTIVES: The objective of this study was to assess the clinical effectiveness of the PBC double-compression technique in patients with recurrent TN and to analyze the technique's efficacy, subsequent duration of patients' facial numbness, and other complications. STUDY DESIGN: Retrospective study. SETTING: A single-center study. METHODS: Retrospective analysis was conducted on clinical data from 125 patients with postoperative recurrent TN who underwent double compression of the PBC and 65 patients who underwent single compression of the PBC between August 2017 and April 2022. The Barrow Neurological Institute Pain Intensity (BNI-P) score was utilized to quantify the severity of pain, while the Barrow Neurological Institute Facial Numbness (BNI-N) score was employed to separately evaluate the extent of postoperative pain relief and facial numbness. RESULTS: The BNI-P and BNI-N scores before and after PBC treatment are presented herein. At T0, there was no significant difference in the BNI-P scores between the single-compression group and the double-compression group; however, at T1-T4, the BNI-P scores of the double-compression group were lower than those of the single-compression group (P < 0.05). There was no significant difference in BNI-P scores between the 2 groups at T5. At T1-T4, the BNI-N score of the double-compression group was significantly lower than that of the single-compression group (P < 0.05). However, there was no significant difference in BNI-N score between the double and single compression groups at T5. In the single-compression group, one patient (1.5%) experienced insignificant pain relief on postoperative day one, while 2 patients (3.1%) suffered from pain recurrence during the 1-4-year follow-up period. Similarly, in the double-compression group, one patient (0.8%) had inadequate pain relief on postoperative day one, and 3 patients (2.4%) experienced pain recurrence during the same follow-up period. The remaining patients did not require further surgical intervention but continued to rely on regular oral analgesia. In the single-compression group, masticatory muscle weakness was observed in 50 cases (76.9%), while in the double-compression group, it was observed in 92 cases (73.6%). Perioral herpes affected 4 patients (7.1%) and 6 patients (4.8%) in the single- and double-compression groups, respectively. Facial hematoma occurred in 7 cases (10.8%) and 13 cases (10.4%) of the single- and double-compression groups, respectively; each group included one patient suffered who from diplopia. Notably, none of the patients in this study reported any instances of corneal anesthesia, anesthesia pain, aseptic meningitis, cerebrospinal fluid leakage, subarachnoid hemorrhage, carotid-cavernous fistula, or mortality. LIMITATIONS: This was a single-center retrospective study with a small sample size and relatively short follow-up time. Therefore, further evaluation of the long-term efficacy of PBC for postoperative recurrent TN is needed from multiple centers with larger sample sizes and longer follow-up periods. CONCLUSIONS: The double PBC method boasts a high cure rate, a low recurrence rate, and minimal complications, rendering the option appropriate for patients with recurrent TN and thus deserving of clinical promotion.
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Neuralgia do Trigêmeo , Humanos , Neuralgia do Trigêmeo/cirurgia , Estudos Retrospectivos , Hipestesia , Dor , Manejo da DorRESUMO
OBJECTIVE: To investigate the prognostic utility of radiomics features extracted from 18F-fluorodeoxyglucose (FDG) PET/CT combined with clinical factors and metabolic parameters in predicting progression-free survival (PFS) and overall survival (OS) in individuals diagnosed with extranodal nasal-type NK/T cell lymphoma (ENKTCL). MATERIALS AND METHODS: A total of 126 adults with ENKTCL who underwent 18F-FDG PET/CT examination before treatment were retrospectively included and randomly divided into training (n = 88) and validation cohorts (n = 38) at a ratio of 7:3. Least absolute shrinkage and selection operation Cox regression analysis was used to select the best radiomics features and calculate each patient's radiomics scores (RadPFS and RadOS). Kaplan-Meier curve and Log-rank test were used to compare survival between patient groups risk-stratified by the radiomics scores. Various models to predict PFS and OS were constructed, including clinical, metabolic, clinical + metabolic, and clinical + metabolic + radiomics models. The discriminative ability of each model was evaluated using Harrell's C index. The performance of each model in predicting PFS and OS for 1-, 3-, and 5-years was evaluated using the time-dependent receiver operating characteristic (ROC) curve. RESULTS: Kaplan-Meier curve analysis demonstrated that the radiomics scores effectively identified high- and low-risk patients (all P < 0.05). Multivariable Cox analysis showed that the Ann Arbor stage, maximum standardized uptake value (SUVmax), and RadPFS were independent risk factors associated with PFS. Further, ß2-microglobulin, Eastern Cooperative Oncology Group performance status score, SUVmax, and RadOS were independent risk factors for OS. The clinical + metabolic + radiomics model exhibited the greatest discriminative ability for both PFS (Harrell's C-index: 0.805 in the validation cohort) and OS (Harrell's C-index: 0.833 in the validation cohort). The time-dependent ROC analysis indicated that the clinical + metabolic + radiomics model had the best predictive performance. CONCLUSION: The PET/CT-based clinical + metabolic + radiomics model can enhance prognostication among patients with ENKTCL and may be a non-invasive and efficient risk stratification tool for clinical practice.
Assuntos
Linfoma de Células T , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada , Adulto , Humanos , Fluordesoxiglucose F18 , Prognóstico , Estudos Retrospectivos , RadiômicaRESUMO
L-Tryptophan hydroxylation catalyzed by tryptophan hydroxylase (TPH) presents a promising method for synthesizing 5-hydroxytryptophan (5-HTP), yet the limited activity of wild-type human TPH2 restricts its application. A high-activity mutant, MT10 (H318E/H323E), was developed through semi-rational active site saturation testing (CAST) of wild-type TPH2, exhibiting a 2.85-fold increase in kcat/Km over the wild type, thus enhancing catalytic efficiency. Two biotransformation systems were developed, including an in vitro one-pot system and a Whole-Cell Catalysis System (WCCS). In the WCCS, MT10 achieved a conversion rate of only 31.5 % within 32 h. In the one-pot reaction, MT10 converted 50 mM L-tryptophan to 44.5 mM 5-HTP within 8 h, achieving an 89 % conversion rate, outperforming the M1 (NΔ143/CΔ26) variant. Molecular dynamics simulations indicated enhanced interactions of MT10 with the substrate, suggesting improved binding affinity and system stability. This study offers an effective approach for the efficient production of 5-HTP.