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BACKGROUND: Pneumococcus is a common cause of pneumonia, meningitis, and other serious infections in children. The previous study has proved that the 13-valent pneumococcal conjugate vaccine (PCV13) has sufficient immunogenicity in children. The data on long-term persistence of immunity will help the follow-up development work of pneumococcal vaccines. METHODS: Children who received the full vaccination course of the tested PCV13 in the previous clinical trial were enrolled again, and these who received other pneumococcal vaccines, or were infected with one or more serotypes of S. pneumoniae corresponding to PCV13 before enrollment were excluded. Participants were divided into four groups by age which is same as that of previous trial. The study lasted for 5 years, during which we measured pneumococcal antibodies of 13 serotypes included in PCV13 at particular points in time. Geometric mean concentrations (GMCs) and seropositive rates (the rate of IgG concentration ≥0.35 µg/mL) of antibodies against 13 serotypes were calculated. RESULTS: For the participants aged 2 months, five years after primary vaccination, except for serotypes 3 and 4, seropositive rates were 100%. GMCs of IgG antibodies against 13 serotypes ranged from 0.733 to 15.160 µg/mL. All of the participants aged 7-11 months had the serotype-specific IgG concentration ≥0.35 µg/mL four years after primary vaccination with the exception of serotypes 3, 4, 6 A and 9 V. IgG GMCs were 0.753-11.031 µg/mL. All participants aged 12-23 months and 2-5 years old had the serotype-specific IgG concentration ≥0.35 µg/mL three or two years after primary vaccination respectively, except for serotype 3. IgG GMCs ranged from 0.815 to 13.111 µg/mL, and 0.684 to 12.282 µg/mL respectively. CONCLUSION: PCV13 was applied to the population aged 2 months and 7 months - 5 years old with a good immune persistence, providing more extensive evidence of long-term efficacy for that vaccine. TRIAL REGISTRATION: The trial was registered with ClinicalTrials.gov, number NCT06210737.
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Anticorpos Antibacterianos , Imunoglobulina G , Infecções Pneumocócicas , Vacinas Pneumocócicas , Sorogrupo , Streptococcus pneumoniae , Humanos , Vacinas Pneumocócicas/imunologia , Vacinas Pneumocócicas/administração & dosagem , Lactente , Anticorpos Antibacterianos/sangue , Anticorpos Antibacterianos/imunologia , Pré-Escolar , Streptococcus pneumoniae/imunologia , Streptococcus pneumoniae/classificação , Feminino , Masculino , Infecções Pneumocócicas/prevenção & controle , Infecções Pneumocócicas/imunologia , Imunoglobulina G/sangue , Imunoglobulina G/imunologia , Vacinas Conjugadas/imunologia , Vacinas Conjugadas/administração & dosagem , Vacinação/métodosRESUMO
Background: Identifying the factors influencing mental health of mothers at critical stages of childrearing is significant for the implementation of effective promotion policies and counselling activities. Objective: This study aimed to investigate the relationships between children's feeding difficulties, marital quality, parenting quality and maternal mental health risks amidst Chinese mothers with high and low social support using a multi-group structural equation modelling approach. Participants: A cross-sectional study was conducted in Wenzhou, China and a total of 772 mothers with children aged 0-3 were surveyed by using purposive sampling. Findings: Results showed that of the 772 participants, 23.6 % reported anxiety, 50.1 % reported depression, 91.2 % reported insomnia, and 24 % reported feeding difficulties. The joint occurrence of multiple forms of mental problems is the most commonly reported features of mental health risks among mothers. The positive association between feeding difficulties of children and mental health risks of mothers was mediated by marital quality and parenting quality. In addition, feeding difficulties were not related to mental health risks in high social support group but all the relationships were significant in low social support group. Conclusions: These findings highlight the importance of the specific interventions to enhance social support, marital quality and parenting quality for improving mental health of mothers of children with feeding difficulties.
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The bioactive peptides derived from yak milk cheese exhibited cholesterol-lowering properties. However, there was limited research on their inhibitory effects on cholesterol esterase (CE) and elucidation of their potential inhibitory mechanisms. In this study, we identified CE-inhibiting peptides through virtual screening and in vitro assays. Additionally, molecular docking and molecular dynamics studies were conducted to explore the mechanisms. The results indicated that peptides RK7 (RPKHPIK), KQ7 (KVLPVPQ), QP13 (QEPVLGPVRGPFP), TL9 (TPVVVPPFL), VN10 (VYPFPGPIPN), LQ10 (LPPTVMFPPQ), and SN12 (SLVYPFPGPIPN) possessed molecular weights of less than 1.5 kDa and a high proportion of hydrophobic amino acids, demonstrating notable inhibitory effects on CE. Molecular docking and dynamics revealed that peptides RK7, KQ7, QP13, and VN10 bound to key amino acid residues Arg423, His435, and Ser422 of CE through hydrogen bonds, hydrophobic interactions, salt bridges, and π-π stacking, occupying the substrate-binding site and exerting inhibitory effects on CE. The four peptides were further synthesized to verify their CE-inhibitory effects in vitro. RK7, KQ7, QP13, and VN10 exhibited inhibitory activity on CE with IC50 values of 8.16 × 10-7 mol/L, 8.10 × 10-7 mol/L, 4.63 × 10-7 mol/L, and 7.97 × 10-7 mol/L; RK7, KQ7, QP13, and VN10 were effective in inhibiting CE after simulated gastrointestinal digestion, especially with a significant increase in the inhibitory activity of KQ7 and RK7, respectively. Our findings suggested that bioactive peptides from yak milk cheese represented a novel class of potential CE inhibitors.
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Objectives: This study compiled a Social Support Needs Questionnaire (SSNQ) for the left-behind older adults in rural China and assessed its psychometric properties. Methods: The formation of the SSNQ included three stages. First, item pool was established based on literature analysis. Second, through expert consultation, the 1-version questionnaire items were determined. Third, pre-survey with 901 cases of rural left-behind older adults was used to develop and test final-version of the Social Support Needs Questionnaire (SSNQ). Results: The Cronbach's α of the SSNQ was 0.914, ranging from 0.815 to 0.886 for each factor. The item-content validity index ranged from 0.875 to 1.00, and the scale-content validity index was 0.969. Conclusions: The SSNQ prepared by this study can be used as an evaluation tool for the social support needs of left-behind older adults in rural China, providing a basis for further establishment of the social support system.
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AIM: To study functional brain abnormalities in patients with hypertensive retinopathy (HR) and to discuss the pathophysiological mechanisms of HR by fractional amplitude of low-frequency fluctuations (fALFFs) method. METHODS: Twenty HR patients and 20 healthy controls (HCs) were respectively recruited. The age, gender, and educational background characteristics of the two groups were similar. After functional magnetic resonance imaging (fMRI) scanning, the subjects' spontaneous brain activity was evaluated with the fALFF method. Receiver operating characteristic (ROC) curve analysis was used to classify the data. Further, we used Pearson's correlation analysis to explore the relationship between fALFF values in specific brain regions and clinical behaviors in patients with HR. RESULTS: The brain areas of the HR group with lower fALFF values than HCs were the right orbital part of the middle frontal gyrus (RO-MFG) and right lingual gyrus. In contrast, the values of fALFFs in the left middle temporal gyrus (MTG), left superior temporal pole (STP), left middle frontal gyrus (MFG), left superior marginal gyrus (SMG), left superior parietal lobule (SPL), and right supplementary motor area (SMA) were higher in the HR group. The results of a t-test showed that the average values of fALFFs were statistically significantly different in the HR group and HC group (P<0.001). The fALFF values of the left middle frontal gyrus in HR patients were positively correlated with anxiety scores (r=0.9232; P<0.0001) and depression scores (r=0.9682; P<0.0001). CONCLUSION: fALFF values in multiple brain regions of HR patients are abnormal, suggesting that these brain regions in HR patients may be dysfunctional, which may help to reveal the pathophysiological mechanisms of HR.
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Drought is one of the most severe environmental factors limiting plant growth and crop yield, necessitating the identification of genes that enhance drought resistance for crop improvement. Through screening an ethyl methyl sulfonate-mutagenized rice mutant library, we isolated the PEG tolerance mutant 97-1 (ptm97-1), which displays enhanced resistance to osmotic and drought stress, and increased yield under drought conditions. A point mutation in OsMATE6 was identified as being associated with the drought-resistant phenotype of ptm97-1. The role of OsMATE6 in conferring drought resistance was confirmed by additional OsMATE6 knockout mutants. OsMATE6 is expressed in guard cells, shoots and roots and the OsMATE6-GFP fusion protein predominantly localizes to the plasma membrane. Our ABA efflux assays suggest that OsMATE6 functions as an ABA efflux transporter; mutant protoplasts exhibited a slower ABA release rate compared to the wild type. We hypothesize that OsMATE6 regulates ABA levels in guard cells, influencing stomatal closure and enhancing drought resistance. Notably, OsMATE6 knockout mutants demonstrated greater yields under field drought conditions compared to wild-type plants, highlighting OsMATE6 as a promising candidate for improving crop drought resistance.
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Acute pancreatitis, a common exocrine inflammatory disease affecting the pancreas, is characterized by intense abdominal pain and multiple organ dysfunction. However, the alterations in retinal blood vessels among individuals with acute pancreatitis remain poorly understood. This study employed optical coherence tomography angiography (OCTA) to examine the superficial and deep retinal blood vessels in patients with pancreatitis. Sixteen patients diagnosed with pancreatitis (32 eyes) and 16 healthy controls (32 eyes) were recruited from the First Affiliated Hospital of Nanchang University for participation in the study. Various ophthalmic parameters, such as visual acuity, intraocular pressure, and OCTA image for retina consisting of the superficial retinal layer (SRL) and the deep retinal layer (DRL), were recorded for each eye. The study observed the superficial and deep retinal microvascular ring (MIR), macrovascular ring (MAR), and total microvessels (TMI) were observed. Changes in retinal vascular density in the macula through annular partitioning (C1-C6), hemispheric quadrant partitioning (SR, SL, IL, and IR), and early diabetic retinopathy treatment studies (ETDRS) partitioning methods (R, S, L, and I). Correlation analysis was employed to investigate the relationship between retinal capillary density and clinical indicators. Our study revealed that in the superficial retinal layer, the vascular density of TMI, MIR, MAR, SR, IR, S, C2, C3 regions were significantly decreased in patients group compared with the normal group. For the deep retinal layer, the vascular density of MIR, SR, S, C1, C2 regions also reduced in patient group. The ROC analysis demonstrated that OCTA possesses significant diagnostic performance for pancreatitis. In conclusion, patients with pancreatitis may have retinal microvascular dysfunction, and OCTA can be a valuable tool for detecting alterations in ocular microcirculation in pancreatitis patients in clinical practice.
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Pancreatite , Vasos Retinianos , Tomografia de Coerência Óptica , Adulto , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos de Casos e Controles , Relevância Clínica , Microvasos/diagnóstico por imagem , Microvasos/patologia , Microvasos/fisiopatologia , Pancreatite/complicações , Pancreatite/patologia , Pancreatite/fisiopatologia , Vasos Retinianos/diagnóstico por imagem , Vasos Retinianos/patologia , Tomografia de Coerência Óptica/métodos , Acuidade VisualRESUMO
Ataxia-telangiectasia mutated (ATM) was first discovered in patients with AT (ataxia telangiectasia), which is characteristic with cerebellar degeneration, immunodeficiency, being susceptible to malignant tumors and sensitive to radiation. ATM kinase could detect DNA double-strand breaks and play a vital role in the DNA damage response. Inhibiting the function of ATM could sensitize tumor cells to both ionizing radiation (IR) and chemotherapy, as well as improve the chemoresistance and radioresistance observed in some patients. As such, ATM is a novel and important target for the cancer therapy. We reviewed ATM inhibitors reported in the last two decades, focusing on their development process, structure-activity relationships, inhibitory efficacy, pharmacokinetics and pharmacodynamics characteristics in the preclinical and clinical studies. We summarized the clinical value of ATM inhibitors in tumors and some neurodegenerative diseases, as well as the main challenges to the development of the drugs, providing directions and references for the future development of ATM inhibitors.
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Antineoplásicos , Proteínas Mutadas de Ataxia Telangiectasia , Inibidores de Proteínas Quinases , Humanos , Proteínas Mutadas de Ataxia Telangiectasia/antagonistas & inibidores , Proteínas Mutadas de Ataxia Telangiectasia/metabolismo , Inibidores de Proteínas Quinases/farmacologia , Inibidores de Proteínas Quinases/química , Antineoplásicos/farmacologia , Antineoplásicos/química , Relação Estrutura-Atividade , Animais , Neoplasias/tratamento farmacológico , Neoplasias/patologia , Estrutura MolecularRESUMO
The average content of casein in yak milk is 40.2 g/L. Casein can be degraded by enzymatic digestion or food processing to produce abundant degradation peptides. International researchers have studied the degradation peptides of yak milk casein by using multiple techniques and methods, such as in vitro activity tests, cellular experiments, proteomics, bioinformatics, etc., and found that the degradation peptides have a wide range of functional activities that are beneficial to the human body, such as angiotensin-converting enzyme (ACE) inhibitory, antioxidant, anti-inflammatory, antidiabetic, antimicrobial, anticancer, and immunomodulatory activities, etc., and it has been proved that the types and strengths of functional activities are closely related to the structural characteristics of the peptides. This paper describes the characteristics of yak milk proteins, the functional activities, and mechanism of action of degraded peptides. Based on the types of functional activities of yak milk casein degradation peptides, we classified and elucidated the effects of structural factors, such as peptide molecular weight, peptide length, amino acid sequence, physicochemical properties, electrical charge, hydrophobicity, spatial conformation, chain length, and the type of enzyme on these activities. It reveals the great potential of yak milk casein degradation peptides as functional active peptide resources and as auxiliary treatments for diseases. It also provides important insights for analyzing yak casein degradation peptide activity and exploring high-value utilization.
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Caseínas , Leite , Peptídeos , Caseínas/química , Caseínas/metabolismo , Animais , Leite/química , Bovinos , Peptídeos/química , Peptídeos/farmacologia , Peptídeos/metabolismo , Humanos , Antioxidantes/química , Antioxidantes/farmacologia , Sequência de Aminoácidos , Inibidores da Enzima Conversora de Angiotensina/química , Inibidores da Enzima Conversora de Angiotensina/farmacologia , Inibidores da Enzima Conversora de Angiotensina/metabolismo , ProteóliseRESUMO
BACKGROUND: Yunaconitine (YAC) is a hidden toxin that greatly threatens the life safety of patients who are prescribed herbal medicines containing Aconitum species; however, its underlying mechanism remains unclear. OBJECTIVE: The objective of this study is to elucidate the functions of P-glycoprotein (P-gp) in regulating the efficacy, toxicity, and pharmacokinetics of YAC. METHODS: The efflux function of P-gp on YAC was explored by using Caco-2 monolayers in combination with the P-gp inhibitor verapamil. The impact of P-gp on regulating the analgesic and anti-inflammatory effects, acute toxicity, tissue distribution, and pharmacokinetics of YAC was determined via male Mdr1a gene knocked-out mice and wild-type FVB mice. RESULTS: The presence of verapamil significantly decreased the efflux ratio of YAC from 20.41 to 1.07 in Caco- 2 monolayers (P < 0.05). Moreover, oral administration of 0.07 and 0.14 mg/kg YAC resulted in a notable decrease in writhing times in Mdr1a-/- mice by 23.53% and 49.27%, respectively, compared to wild-type FVB mice (P < 0.05). Additionally, the deficiency of P-gp remarkably decreased the half-lethal dose (LD50) of YAC from 2.13 to 0.24 mg/kg (P < 0.05). Moreover, the concentrations of YAC in the tissues of Mdr1a-/- mice were statistically higher than those in wild-type FVB mice (P < 0.05). Particularly, the brain accumulation of YAC in Mdr1a-/- mice significantly increased by 12- and 19-fold, respectively, after oral administration for 30 and 120 min, when compared to wild-type FVB mice (P < 0.05). There were no significant differences in the pharmacokinetic characteristics of YAC between Mdr1a-/- and wild-type FVB mice. CONCLUSION: YAC is a sensitive substrate of P-gp. The absence of P-gp enhances the analgesic effect and toxicity of YAC by upregulating its brain accumulation. Co-administration with a P-gp inhibitor may lead to severe YAC poisoning.
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BACKGROUND: Surgical therapy is the most optimal treatment for hepatocellular carcinoma (HCC) combined with bile duct tumor thrombus (BDTT) patients. However, whether to perform bile duct resection (BDR) is still controversial. The purpose of this multicenter research is to compare the effect of BDR on the prognosis of extrahepatic BDTT patients. METHODS: We collected the data of 111 HCC patients combined with extrahepatic BDTT who underwent radical hepatectomy from June 1, 2004 to December 31, 2021. Those patients had either received hepatectomy with extrahepatic bile duct resection (BDR group) or hepatectomy without bile duct resection (NBDR group). Inverse probability of treatment weighting (IPTW) was used to reduce the potential bias between two groups and balance the influence of confounding factors in baseline data. Then compare the prognosis between the two groups of patients. Cox regression model was used for univariate and multivariate analysis to further determine the independent risk factors that influence the prognosis of HCC-BDTT patients. RESULTS: There were 38 patients in the BDR group and 73 patients in the NBDR group. Before and after IPTW, there were no statistical significance in OS, RFS and intraoperative median blood loss between the two groups (all P > 0.05). Before IPTW, the median postoperative hospital stay in the NBDR group was shorter (P = 0.046) and the grade of postoperative complications was lower than BDR group (P = 0.014). After IPTW, there was no difference in postoperative hospital stay between the two groups (P > 0.05). The complication grade in the NBDR group was still lower than that in the BDR group (P = 0.046). The univariate analysis showed that TNM stage and portal vein tumor thrombus (PVTT) were significantly correlated with OS (both P < 0.05). Preoperative AFP level, TNM stage and prognostic nutritional index (PNI) were significantly correlated with postoperative RFS (all P < 0.05). Multivariate analysis showed that tumor TNM stage was an independent risk factor for the OS rate (P = 0.014). TNM stage, PNI and AFP were independent predictors of RFS after radical hepatectomy (all P < 0.05). CONCLUSIONS: For HCC-BDTT patients, hepatocellular carcinoma resection combined with choledochotomy to remove the tumor thrombus may benefit more.
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Ductos Biliares Extra-Hepáticos , Carcinoma Hepatocelular , Hepatectomia , Neoplasias Hepáticas , Humanos , Carcinoma Hepatocelular/cirurgia , Carcinoma Hepatocelular/patologia , Carcinoma Hepatocelular/mortalidade , Carcinoma Hepatocelular/complicações , Masculino , Feminino , Neoplasias Hepáticas/cirurgia , Neoplasias Hepáticas/patologia , Neoplasias Hepáticas/mortalidade , Neoplasias Hepáticas/complicações , Pessoa de Meia-Idade , Prognóstico , Ductos Biliares Extra-Hepáticos/cirurgia , Ductos Biliares Extra-Hepáticos/patologia , Trombose/cirurgia , Trombose/etiologia , Trombose/patologia , Estudos Retrospectivos , Neoplasias dos Ductos Biliares/cirurgia , Neoplasias dos Ductos Biliares/patologia , Neoplasias dos Ductos Biliares/complicações , Neoplasias dos Ductos Biliares/mortalidade , Idoso , AdultoRESUMO
BACKGROUND: The accuracy of traditional knee MR imaging in diagnosing anterior cruciate ligament tears, especially partial tears, is relatively low, which may lead to misdiagnosis and missed diagnosis. This study aimed to assess the diagnostic performance of a novel imaging method, high-resolution oblique coronal MRI at an optimal flexed-knee Angle, for ACL tears. METHODS: 50 healthy volunteers were scanned with a scan-assisted device for the optimal flexion angle of ACL. For 92 knee trauma patients selected strictly according to inclusion and exclusion criteria, conventional extended-knee scans (control group) and high-resolution oblique coronal scans based on the optimal flexed-knee angle (experimental group) were conducted. Two observers rated ACL visibility blindly on a 5-point scale. Arthroscopy-defined outcomes determined diagnostic metrics for each method and sensitivity, specificity, positive predictive value, negative predictive value and accuracy were calculated. RESULTS: The average optimal flexion angle for healthy volunteers was approximately 30° (30.3° ± 5.0°). Imaging demonstrated complete visualization of the ACL in 96.7% of images in the experimental group versus 12.0% in the control group. The diagnostic indicators of the experimental group surpassed those of the control group: sensitivity (94.9% vs. 76.3%), specificity (97.0% vs. 81.8%), positive predictive value (98.2% vs. 88.2%), negative predictive value(91.4% vs. 65.9%), and accuracy (95.7% vs. 78.3%). ROC analysis indicated superior diagnostic performance in the experimental group, with an AUC of 0.945 compared with 0.776 for the control group (p < 0.0001). CONCLUSIONS: High-resolution oblique coronal imaging at the optimal 30° flexed-knee angle improved ACL visualization and diagnostic performance compared with conventional techniques.
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Lesões do Ligamento Cruzado Anterior , Imageamento por Ressonância Magnética , Humanos , Lesões do Ligamento Cruzado Anterior/diagnóstico por imagem , Imageamento por Ressonância Magnética/métodos , Feminino , Masculino , Adulto , Adulto Jovem , Pessoa de Meia-Idade , Articulação do Joelho/diagnóstico por imagem , Adolescente , Artroscopia/métodosRESUMO
BACKGROUND: Cardiac iron overload and ferroptosis greatly contribute to the poor prognosis of myocardial infarction (MI). Iron chelator is one of the most promising strategies for scavenging excessive iron and alleviating cardiac dysfunction post MI. However, various side effects of existing chemical iron chelators restrict their clinical application, which calls for a more viable and safer approach to protect against iron injury in ischemic hearts. RESULTS: In this study, we isolated macrophage-derived extracellular vesicles (EVs) and identified macrophage-derived EVs as a novel endogenous biological chelator for iron. The administration of macrophage-derived EVs effectively reduced iron overload in hypoxia-treated cardiomyocytes and hearts post MI. Moreover, the oxidative stress and ferroptosis induced by excessive iron were considerably suppressed by application of macrophage-derived EVs. Mechanistically, transferrin receptor (TfR), which was inherited from macrophage to the surface of EVs, endowed EVs with the ability to bind to transferrin and remove excess protein-bound iron. EVs with TfR deficiency exhibited a loss of function in preventing MI-induced iron overload and protecting the heart from MI injury. Furthermore, the iron-chelating EVs were ultimately captured and processed by macrophages in the liver. CONCLUSIONS: These results highlight the potential of macrophage-derived EVs as a powerful endogenous candidate for iron chelation therapy, offering a novel and promising therapeutic approach to protect against iron overload-induced injury in MI and other cardiovascular diseases.
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Vesículas Extracelulares , Quelantes de Ferro , Sobrecarga de Ferro , Macrófagos , Camundongos Endogâmicos C57BL , Infarto do Miocárdio , Receptores da Transferrina , Infarto do Miocárdio/metabolismo , Animais , Vesículas Extracelulares/metabolismo , Sobrecarga de Ferro/metabolismo , Macrófagos/metabolismo , Macrófagos/efeitos dos fármacos , Camundongos , Quelantes de Ferro/farmacologia , Quelantes de Ferro/uso terapêutico , Receptores da Transferrina/metabolismo , Masculino , Ferro/metabolismo , Miócitos Cardíacos/metabolismo , Ferroptose/efeitos dos fármacos , Estresse Oxidativo/efeitos dos fármacos , Transferrina/metabolismo , HumanosRESUMO
Compared to conventional nucleic acid detection methods, label-free single nucleotide polymorphism (SNP) detection presents challenging due to the necessity of discerning single base mismatches, especially in the field of enzyme-free detection. In this study, we introduce a novel bulged-type DNA duplex probe designed to significantly amplify single-base differences. This probe is integrated with programmable DNA-based nanostructures to develop a sensitive, label-free biosensor for nonenzymatic SNP detection. The duplex probe with one bulge could selectively identify wild-typed DNA (WT) and mutant-type DNA (MT) based on a competitive strand displacement reaction mechanism. The hyperbranched HCR (HHCR) by incorporating of hairpin DNA into the DNA tetrahedron and surface-tethering on the portable screen printing electrode (SPCE) significantly favor the formation of negatively charged DNA nanostructure. We harnessed strong repulsion of DNA nanostructure towards the electroactive [Fe(CN)6]³â»/4â» in combination with electrochemical technique to create a label-free biosensor. This simple, enzyme-free and label-free biosensor could detect MT with a detection limit of 56 aM, even in multiple sequence backgrounds. The study served as the proof-of-concept for the integration of enzyme-free competitive mechanism and label-free strategy, which can be extended as a powerful tool to various fields.
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Técnicas Biossensoriais , DNA , Técnicas Eletroquímicas , Polimorfismo de Nucleotídeo Único , Técnicas Biossensoriais/métodos , Técnicas Eletroquímicas/métodos , DNA/genética , DNA/química , Limite de Detecção , Nanoestruturas/química , Humanos , Sondas de DNA/química , Sondas de DNA/genéticaRESUMO
There are two main types of carbon nanotubes (CNTs): metallic and semiconducting. Naturally grown CNTs are randomly distributed, posing challenges in distinguishing between the two types. Here, a novel approach for nanoscale high-resolution imaging and identification of CNTs was introduced by incorporating the heterodyne technique into high-harmonic electrostatic force microscopy (HH-EFM) on an atomic force microscopy (AFM) platform. In the developed heterodyne HH-EFM, a more localized high-order gradient of tip-sample nonlinear interaction force is used as signal channels, resulting in an improved spatial resolution, compared to the conventional HH-EFM. Furthermore, the heterodyne HH-EFM also has the capability to visualize material carrier density and assess qualitative carrier transport performance. Our work not only presents a new approach to identifying/exploring electrical properties of low-dimensional nanomaterials but also provides a solution for optimizing resolution in long-range interaction-based functional AFM technologies.
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Organohalides are widespread pollutants that pose significant environmental hazards due to their high degree of halogenation and elevated redox potentials, making them resistant to natural attenuation. Traditional bioremediation approaches, primarily relying on bioaugmentation and biostimulation, often fall short of achieving complete detoxification. Furthermore, the emergence of complex halogenated pollutants, such as per- and polyfluoroalkyl substances (PFASs), further complicates remediation efforts. Therefore, there is a pressing need to reconsider novel approaches for more efficient remediation of these recalcitrant pollutants. This review proposes novel redox-potential-mediated hybrid bioprocesses, tailored to the physicochemical properties of pollutants and their environmental contexts, to achieve complete detoxification of organohalides. The possible scenarios for the proposed bioremediation approaches are further discussed. In anaerobic environments, such as sediment and groundwater, microbial reductive dehalogenation coupled with fermentation and methanogenesis can convert organohalides into carbon dioxide and methane. In environments with anaerobic-aerobic alternation, such as paddy soil and wetlands, a synergistic process involving reduction and oxidation can facilitate the complete mineralization of highly halogenated organic compounds. Future research should focus on in-depth exploration of microbial consortia, the application of ecological principles-guided strategies, and the development of bioinspired-designed techniques. This paper contributes to the academic discourse by proposing innovative remediation strategies tailored to the complexities of organohalide pollution.
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Biodegradação Ambiental , Oxirredução , Poluentes Ambientais/metabolismo , Hidrocarbonetos Halogenados/metabolismo , Hidrocarbonetos Halogenados/química , Anaerobiose , Metano/metabolismo , Halogenação , Bactérias/metabolismo , Bactérias/genéticaRESUMO
ß2 adrenergic receptor (ß2AR) is a G-protein-coupled receptor involved in cardiac protection. In chronic heart failure (CHF), persistent sympathetic nervous system activation occurs, resulting in prolonged ß2AR activation and subsequent receptor desensitization and downregulation. Notoginsenoside R1 (NGR1) has the functions of enhancing myocardial energy metabolism and mitigating myocardial fibrosis. The mechanisms of NGR1 against ischemic heart failure are unclear. A left anterior descending (LAD) artery ligation procedure was performed on C57BL/6â¯J mice for four weeks. From the 4th week onwards, they were treated with various doses (3, 10, 30â¯mg/kg/day) of NGR1. Subsequently, the impacts of NGR1 on ischemic heart failure were evaluated by assessing cardiac function, morphological changes in cardiac tissue, and the expression of atrial natriuretic peptide (ANP) and beta-myosin heavy chain (ß-MHC). H9c2 cells were protected by NGR1 when exposed to OGD/R conditions. H9c2 cells were likewise protected from OGD/R damage by NGR1. Furthermore, NGR1 increased ß2AR levels and decreased ß2AR ubiquitination. Mechanistic studies revealed that NGR1 enhanced MDM2 protein stability and increased the expression of MDM2 and ß-arrestin2 while inhibiting their interaction. Additionally, under conditions produced by OGD/R, the protective benefits of NGR1 on H9c2 cells were attenuated upon administration of the MDM2 inhibitor SP141. According to these findings, NGR1 impedes the interplay between ß-arrestin2 and MDM2, thereby preventing the ubiquitination and degradation of ß2AR to improve CHF.
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Ginsenosídeos , Insuficiência Cardíaca , Isquemia Miocárdica , Proteínas Proto-Oncogênicas c-mdm2 , Receptores Adrenérgicos beta 2 , Ubiquitinação , beta-Arrestina 2 , Animais , Masculino , Camundongos , Ratos , beta-Arrestina 2/metabolismo , Linhagem Celular , Modelos Animais de Doenças , Ginsenosídeos/farmacologia , Insuficiência Cardíaca/tratamento farmacológico , Insuficiência Cardíaca/metabolismo , Camundongos Endogâmicos C57BL , Isquemia Miocárdica/metabolismo , Isquemia Miocárdica/tratamento farmacológico , Proteínas Proto-Oncogênicas c-mdm2/metabolismo , Receptores Adrenérgicos beta 2/metabolismo , Ubiquitinação/efeitos dos fármacosRESUMO
BACKGROUND: DNA methylation is an important epigenetic modification that plays a crucial role in the development and progression of various tumors. However, the association between methylationdriven genes and diagnosis, prognosis, and immune characteristics of head and neck squamous cell carcinoma (HNSCC) remains unclear. METHODS: We obtained transcriptome, methylation, and clinical data from HNSCC patients in TCGA database, and used MethylMix algorithm to identify methylation-driven genes. A methylation driven gene-related risk model was constructed using Lasso regression analysis, and validated using data from GEO database. Immune infiltration and immune function analysis of the expression profiles were conducted using ssGSEA. Differences in immune checkpoint-related genes were analyzed, and the efficacy of immunotherapy was evaluated using TCIA database. Finally, a series of cell functional experiments were conducted to validate the results. RESULTS: Five methylation-driven genes were identified and utilized to construct a prognostic risk model. Based on the median risk score, all patients were categorized into high-risk and low-risk groups. The K-M analysis revealed that patients in the high-risk group have a worse prognosis. Additionally, the risk model demonstrated better prognostic predictive value as indicated by ROC analysis. GSEA enrichment analysis indicated that gene sets in the high and low-risk groups were primarily enriched in pathways associated with tumor immunity and metabolism. Our subsequent investigations showed that high-risk patients exhibited more immunosuppressive phenotypes, while low-risk patients were more likely to respond positively to immunotherapy. CONCLUSION: These findings of our research have the potential to improve patient stratification, guide treatment decisions, and advance the development of personalized therapies for HNSCC.
Assuntos
Metilação de DNA , Regulação Neoplásica da Expressão Gênica , Neoplasias de Cabeça e Pescoço , Carcinoma de Células Escamosas de Cabeça e Pescoço , Transcriptoma , Humanos , Metilação de DNA/genética , Carcinoma de Células Escamosas de Cabeça e Pescoço/genética , Carcinoma de Células Escamosas de Cabeça e Pescoço/imunologia , Prognóstico , Transcriptoma/genética , Neoplasias de Cabeça e Pescoço/genética , Neoplasias de Cabeça e Pescoço/imunologia , Neoplasias de Cabeça e Pescoço/diagnóstico , Biomarcadores Tumorais/genética , Masculino , Feminino , Imunoterapia , Perfilação da Expressão Gênica , Epigênese Genética , Bases de Dados GenéticasRESUMO
Gut microbiota acts as a critical regulator in the development of nonalcoholic fatty liver disease (NAFLD), making probiotics a promise therapeutic strategy. Studies are needed to identify beneficial Bacteroides strains against NAFLD. Bacteroides ovatus (B. ovatus) may also exhibit therapy effect on NAFLD. The aim of this work was to evaluate the effect of B. ovatus on NAFLD and examine the mechanism. C57BL/6â¯J male mice were randomly divided into three groups: a control group (NCD) that received control standard diet, a model group (M) with high-fat and high-cholesterol (HFHC) diet, and M_Bo group that was fed HFFC supplemented with B. ovatus. Treatment with B. ovatus could reduce body weight, prevent hepatic steatohepatitis and liver injury. Mechanistically, B. ovatus induced changes of gut microbial diversity and composition, characterized by a decreased Firmicutes/Bacteroidetes (F/B) ratio in M_Bo group mice, a lower abundance of Proteobacteria, Verrucomicrobiota at phylum level and Ruminococcus_torques_group, Ruminococcus_gauvreauii_group, Erysipelatoclostridium at genus level, simultaneously a remarkablely higher fecal abundance of Lachnospiraceae_NK4A136_group, norank_f__Oscillospiraceae, Colidextribacter. Compared with M group, mice treated with B. ovatus showed an markedly altered fecal short chain fatty acids (SCFAs), a decline in serum levels of lipopolysaccharide (LPS), CD163, IL-1ß, TNF-α, reduced macrophages in livers. Additionally, B. ovatus treatment caused downregulation of genes involved in denovo lipogenesis (such as Srebfl, Acaca, Scd1, Fasn), which was accompanied by the upregulation of genes related with fatty acid oxidation (such as Ppara). In conclusion, this study provides evidence that B. ovatus could ameliorate NAFLD by modulating the gut-liver axis.
Assuntos
Bacteroides , Dieta Hiperlipídica , Microbioma Gastrointestinal , Fígado , Camundongos Endogâmicos C57BL , Hepatopatia Gordurosa não Alcoólica , Probióticos , Hepatopatia Gordurosa não Alcoólica/metabolismo , Hepatopatia Gordurosa não Alcoólica/tratamento farmacológico , Hepatopatia Gordurosa não Alcoólica/prevenção & controle , Hepatopatia Gordurosa não Alcoólica/microbiologia , Animais , Masculino , Microbioma Gastrointestinal/efeitos dos fármacos , Dieta Hiperlipídica/efeitos adversos , Fígado/efeitos dos fármacos , Fígado/metabolismo , Bacteroides/efeitos dos fármacos , Probióticos/farmacologia , Camundongos , Colesterol na Dieta/efeitos adversosRESUMO
Cinnamomum camphora chvar. borneol, a rare camphor tree variant recently identified in China, is distinguished by its high concentration of D-borneol, also known as " plant gold" due to its significant value. The essential oil extracted from this variant,rich in monoterpenes and sesquiterpenes, demonstrates a broad spectrum of pharmacological activities, including analgesic, antiinflammatory, antioxidant, cognition-enhancing, anti-bacterial, and insecticidal effects. These properties, underscored by extensive research, highlight the oil's potential in the biomedical, chemical, and food sectors as a valuable commodity. Nonetheless, the safety profile of this valuable oil remains poorly characterized, with its chemical composition and therapeutic efficacy subject to variations in the factors like geographic origin, harvesting timing, part used for extraction, and processing techniques. Such variability poses challenges to its clinical application and hampers the efficient exploitation of this resource. This review synthesizes current studies on C. camphora chvar. borneol essential oil and provides a detailed examination of its chemical and pharmacological profiles. In this study, we discuss existing research gaps and propose strategies for advancing its clinical use and industrial application, aiming to provide a foundational reference for future investigations and the resolution of its commercial and therapeutic challenges.