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1.
Adv Mater ; : e2311264, 2024 Feb 08.
Artigo em Inglês | MEDLINE | ID: mdl-38330187

RESUMO

Cavernous nerve injury (CNI), resulting in erectile dysfunction (ED), poses a significant threat to the quality of life for men. Strategies utilizing conductive hydrogels have demonstrated promising results for the treatment of peripheral nerves with a large diameter (>2 mm). However, integrating convenient minimally invasive operation, antiswelling and immunomodulatory conductive hydrogels for treating small-diameter injured cavernous nerves remains a great challenge. Here, a sprayable adhesive conductive hydrogel (GACM) composed of gelatin, adenine, carbon nanotubes, and mesaconate designed for cavernous nerve repair is developed. Multiple hydrogen bonds provide GACM with excellent adhesive and antiswelling properties, enabling it to establish a conformal electrical bridge with the damaged nerve and aiding in the regeneration process. Additionally, mesaconate-loaded GACM suppresses the release of inflammatory factors by macrophages and promotes the migration and proliferation of Schwann cells. In vivo tests demonstrate that the GACM hydrogel repairs the cavernous nerve and restores erectile function and fertility. Furthermore, the feasibility of sprayable GACM in minimally invasive robotic surgery in beagles is validated. Given the benefits of therapeutic effectiveness and clinical convenience, the research suggests a promising future for sprayable GACM materials as advanced solutions for minimally invasive nerve repair.

3.
J Vis Exp ; (203)2024 Jan 26.
Artigo em Inglês | MEDLINE | ID: mdl-38345262

RESUMO

The lethality of liver cancer and the resistance to chemical drugs have forced the search for effective prescriptions of traditional herbs for liver cancer. Animal models that are repeatable, easy to manipulate, and highly mimic the pathophysiological processes of liver cancer are the prerequisite for the successful screening of effective drug candidates. Meanwhile, reliable drug efficacy evaluation indicators and means are also the guarantee of anti-liver cancer drug research and development. Sanleng Jiashen formula, a representative prescription of traditional Chinese medicine containing Sparganium stoloni erum, Buch. -Ham. (Sanleng), Panax ginseng C. A. Mey. (ginseng), Rheum officinale Baill. (rhubarb), and Ligusticum chuanxiong Hort. (Chuanxiong), is prescribed to nourish the liver and clear heat, remove toxins, and promote blood circulation to treat liver cancer. This experimental protocol describes the preparation of lyophilized Sanleng Jiashen formula and the establishment process of in-situ liver cancer in BALB/c-nu mice. Histopathological staining, immunohistochemical detection of cancer markers, in vivo imaging of mice, and chick embryo chorioallantoic membrane test were used to explore the inhibition and anti-angiogenesis effect of Sanleng Jiashen formula on malignant proliferation of liver cancer tissue. The data show that the Sanleng Jiashen formula can effectively resist the malignant proliferation of liver cancer tissue, which is manifested by reduced tumor mass volume, improved pathological damage, and lower levels of the cancer marker ki67. The superior inhibition of angiogenesis also suggests that the Sanleng Jiashen formula may have the potential to treat and prevent the progression and deterioration of liver cancer. The whole experimental scheme shows a comprehensive process of traditional Chinese medicine components in the treatment of mouse liver cancer, which provides a reference for the establishment and optimization of a liver cancer model, as well as the research and development of drugs to prevent and treat liver cancer.


Assuntos
Carcinoma Hepatocelular , Medicamentos de Ervas Chinesas , Neoplasias Hepáticas , Embrião de Galinha , Camundongos , Animais , Camundongos Endogâmicos BALB C , Medicamentos de Ervas Chinesas/farmacologia , Medicamentos de Ervas Chinesas/uso terapêutico , Medicina Tradicional Chinesa , Carcinoma Hepatocelular/tratamento farmacológico , Neoplasias Hepáticas/tratamento farmacológico
4.
Immunity ; 57(2): 271-286.e13, 2024 Feb 13.
Artigo em Inglês | MEDLINE | ID: mdl-38301652

RESUMO

The immune system encodes information about the severity of a pathogenic threat in the quantity and type of memory cells it forms. This encoding emerges from lymphocyte decisions to maintain or lose self-renewal and memory potential during a challenge. By tracking CD8+ T cells at the single-cell and clonal lineage level using time-resolved transcriptomics, quantitative live imaging, and an acute infection model, we find that T cells will maintain or lose memory potential early after antigen recognition. However, following pathogen clearance, T cells may regain memory potential if initially lost. Mechanistically, this flexibility is implemented by a stochastic cis-epigenetic switch that tunably and reversibly silences the memory regulator, TCF1, in response to stimulation. Mathematical modeling shows how this flexibility allows memory T cell numbers to scale robustly with pathogen virulence and immune response magnitudes. We propose that flexibility and stochasticity in cellular decisions ensure optimal immune responses against diverse threats.


Assuntos
Linfócitos T CD8-Positivos , Células T de Memória , Epigênese Genética , Células Clonais , Memória Imunológica , Diferenciação Celular
5.
J Ethnopharmacol ; 325: 117840, 2024 Feb 03.
Artigo em Inglês | MEDLINE | ID: mdl-38316219

RESUMO

ETHNOPHARMACOLOGICAL RELEVANCE: Lysimachiae Herba (LH), called Jinqiancao in Chinese, is a commonly used traditional Chinese medicine in clinical practice. Doctors in the Qing Dynasty recorded that it tastes bitter, sour, and slightly cold, and it belongs to the liver, gallbladder, kidney, and bladder meridians. It has the effects of removing dampness and jaundice, eliminating gallstones, and reducing blood stasis. Because of its potent pharmacological effects, it is extensively utilized in the treatment of hepatobiliary and urinary system stones, jaundice, hepatitis, and cholecystitis. Although LH is included in "Sichuan authentic Chinese herbal medicine records", the quality of it from different origins still lacks reliable evaluation methods, which is difficult to reflect the high quality of LH from Sichuan. AIMS OF THE STUDY: This study aimed to establish a fingerprint-activity relationship model between the fingerprint of LH and its protective effect on cholestatic liver injury, and to evaluate the quality of LH from Sichuan and Guizhou by multivariate statistical analysis. MATERIALS AND METHODS: 20 batches of LH samples were collected from Sichuan and Guizhou. Characteristic fingerprints of samples were established by UHPLC-Triple TOF-MS/MS and the chemical pattern recognition analysis was carried out by HCA. Then, a rat model of cholestatic liver injury was established by intragastric administration of ANIT. Combined with the common peak information of fingerprint and pharmacodynamic index results, GCA and BCA were used to screen the efficacy markers. Finally, based on UHPLC-QTRAP-MS/MS, the content of efficacy markers was simultaneously determined, and the overall quality of LH from two origins was evaluated by PCA and TOPSIS. RESULTS: In the fingerprint of 20 batches of LH, 15 common peaks were identified in the negative ion mode, and the similarity was between 0.887 and 0.981. Pharmacological results showed that, compared with the control group, the content of AST, ALT, ALP, TBA, TBIL, and MDA in serum increased, and the content of GSH and SOD activity decreased after 48 h of ANIT administration. In addition, compared to the model group, different doses of LH from the two origins could decrease the serum levels of AST, ALT, ALP, TBA, TBIL, and MDA, raise the levels of GSH and SOD activity, reduce the infiltration range of inflammatory cells, and improve the cholestatic liver injury in rats. Among them, the pharmacodynamic indices of the SCHD group were significantly better. GCA and BCA showed that a total of 7 constituents related to the efficacy were screened, which were proanthocyanidin B1, ferulic acid, hyperoside, astragalin, nicotiflorin, afzelin, and kaempferol. Besides, the content of 7 active constituents in samples from Sichuan was higher than that from Guizhou, indicating that the quality of samples from Sichuan may be better, consistent with the result of the pharmacological experiment. CONCLUSION: The quality and efficacy of LH from different origins were stable, and all of them had protective effects on cholestatic liver injury in rats. The method established in this study is accurate and reliable, and it can be used to comprehensively evaluate the internal quality of LH.

6.
Bone Joint Res ; 13(2): 66-82, 2024 Feb 05.
Artigo em Inglês | MEDLINE | ID: mdl-38310924

RESUMO

Aims: This study aimed to explore the biological and clinical importance of dysregulated key genes in osteoarthritis (OA) patients at the cartilage level to find potential biomarkers and targets for diagnosing and treating OA. Methods: Six sets of gene expression profiles were obtained from the Gene Expression Omnibus database. Differential expression analysis, weighted gene coexpression network analysis (WGCNA), and multiple machine-learning algorithms were used to screen crucial genes in osteoarthritic cartilage, and genome enrichment and functional annotation analyses were used to decipher the related categories of gene function. Single-sample gene set enrichment analysis was performed to analyze immune cell infiltration. Correlation analysis was used to explore the relationship among the hub genes and immune cells, as well as markers related to articular cartilage degradation and bone mineralization. Results: A total of 46 genes were obtained from the intersection of significantly upregulated genes in osteoarthritic cartilage and the key module genes screened by WGCNA. Functional annotation analysis revealed that these genes were closely related to pathological responses associated with OA, such as inflammation and immunity. Four key dysregulated genes (cartilage acidic protein 1 (CRTAC1), iodothyronine deiodinase 2 (DIO2), angiopoietin-related protein 2 (ANGPTL2), and MAGE family member D1 (MAGED1)) were identified after using machine-learning algorithms. These genes had high diagnostic value in both the training cohort and external validation cohort (receiver operating characteristic > 0.8). The upregulated expression of these hub genes in osteoarthritic cartilage signified higher levels of immune infiltration as well as the expression of metalloproteinases and mineralization markers, suggesting harmful biological alterations and indicating that these hub genes play an important role in the pathogenesis of OA. A competing endogenous RNA network was constructed to reveal the underlying post-transcriptional regulatory mechanisms. Conclusion: The current study explores and validates a dysregulated key gene set in osteoarthritic cartilage that is capable of accurately diagnosing OA and characterizing the biological alterations in osteoarthritic cartilage; this may become a promising indicator in clinical decision-making. This study indicates that dysregulated key genes play an important role in the development and progression of OA, and may be potential therapeutic targets.

7.
Front Cell Infect Microbiol ; 14: 1289231, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38318165

RESUMO

Background: Pulmonary trichomoniasis is considered a neglected disease due to failures in recognizing it, stemming from insensitive microbial methods and a lack of specific clinical features. This study aims to analyze the clinical implications of trichomonads detected in bronchoalveolar lavage fluid (BALF) by metagenomic next-generation sequencing (mNGS). Methods: This multicenter retrospective study included patients diagnosed with pneumonia, admitted to three tertiary hospitals in China from July 2018 to September 2022, with trichomonads detected in BALF through mNGS. The analysis covered demographics, comorbidities, symptoms, laboratory findings, mNGS results, clinical treatment, and outcomes of these patients. Results: A total of 17 patients were enrolled, comprising 14 males and 3 females. Trichomonas tenax and Trichomonas vaginalis were detected by mNGS in BALF samples of 15 and 2 patients, respectively. Patients were categorized into two groups based on the presence of risk factors for trichomonad infection, including immunocompromised conditions, uncontrolled diabetes mellitus, oral/periodontal diseases, and aspiration. Among 11 patients with risk factors (Case 1-11), 4 received nitromidazoles as part of comprehensive treatment, achieving a 100% treatment success rate. The remaining 7 patients, who did not receive nitromidazoles, had only one achieving relief after broad-spectrum antimicrobial therapy, resulting in a 14.3% treatment success rate. For the 6 patients without any risk factors for trichomonad infection (Case 12-17), none received nitromidazoles during hospitalization. However, 4 out of these 6 patients (66.7%) eventually recovered. Conclusion: mNGS proves to be an efficient tool for detecting trichomonads in BALF samples. Comprehensive analysis of clinical features and laboratory indicators is essential to distinguish between infection and colonization of trichomonads. Pulmonary trichomoniasis should not be overlooked when trichomonads are detected in BALF from patients with risk factors.


Assuntos
Sequenciamento de Nucleotídeos em Larga Escala , Tricomoníase , Feminino , Masculino , Humanos , Estudos Retrospectivos , Líquido da Lavagem Broncoalveolar , Fatores de Risco , Metagenômica , Tricomoníase/diagnóstico , Sensibilidade e Especificidade
8.
Mol Neurobiol ; 2024 Feb 06.
Artigo em Inglês | MEDLINE | ID: mdl-38321351

RESUMO

Brain-derived estrogen (BDE2) is gaining attention as an endogenous neurotransmitter. Recent research has revealed that selectively removing the aromatase gene, the pivotal enzyme responsible for BDE2 synthesis, in forebrain neurons or astrocytes can lead to synaptic loss and cognitive impairment. It is worth noting that remote ischemia post-conditioning (RIP), a non-invasive technique, has been shown to activate natural protective mechanisms against severe ischemic events. The aim of our study was to investigate whether RIP triggers aromatase-BDE2 signaling, shedding light on its neuroprotective mechanisms after global cerebral ischemia (GCI) in ovariectomized rats. Our findings are as follows: (1) RIP was effective in mitigating ischemic damage in hippocampal CA1 neurons and improved cognitive function after GCI. This was partially due to increased Aro-BDE2 signaling in CA1 neurons. (2) RIP intervention efficiently enhanced pro-survival kinase pathways, such as AKT, ERK1/2, CREB, and suppressed CaMKIIα signaling in CA1 astrocytes induced by GCI. Remarkably, inhibiting CaMKIIα activity led to elevated Aro-BDE2 levels and replicated the benefits of RIP. (3) We also identified the positive mediation of Cav1.2, an LVGCC calcium channel, on CaMKIIα-Aro/BDE2 pathway response to RIP intervention. (4) Significantly, either RIP or CaMKIIα inhibition was found to alleviate reactive astrogliosis, which was accompanied by increased pro-survival A2-astrocyte protein S100A10 and decreased pro-death A1-astrocyte marker C3 levels. In summary, our study provides compelling evidence that Aro-BDE2 signaling is a critical target for the reparative effects of RIP following ischemic insult. This effect may be mediated through the CaV1.2-CaMKIIα signaling pathway, in collaboration with astrocyte-neuron interactions, thereby maintaining calcium homeostasis in the neuronal microenvironment and reducing neuronal damage after ischemia.

9.
Int J Lab Hematol ; 2024 Feb 07.
Artigo em Inglês | MEDLINE | ID: mdl-38323755

RESUMO

INTRODUCTION: Ethylenediaminetetraacetic acid (EDTA)-dependent platelet aggregation (PA) can cause medical errors. Currently, there is no reliable method for completely solving this problem. This study aims to solve this problem that has plagued clinical practice for many years by using oscillation method. METHODS: Sixty-one EDTA-PA samples were collected, divided, and disaggregated using the oscillation method at various times and speeds. The samples were analyzed using routine blood tests and blood smears. RESULTS: Platelet counts (PLT) were increased significantly after oscillation. PLT in the 3000 rpm for 0.5 min group was significantly higher than that in the 500 rpm for 0.5 min group (p < 0. 01). After 3000 rpm oscillation, the PLT gradually increased with time, while compared with the 10-min group, the PLT in the 13-min group showed no significant differences. The effective disaggregation rates in the EDTA-PA samples using the oscillation method and sodium citrate anticoagulant were 96.72% and 65.57%, respectively. There were no significant changes in white blood cell (WBC) or red blood cell (RBC) counts or morphology after the use of the oscillation method. CONCLUSION: The oscillation method effectively depolymerized EDTA-PA without adverse effects on WBC and RBC. The implementation of this technique promises to resolve the issue of EDTA-PA.

10.
Heart Rhythm O2 ; 5(1): 34-40, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-38312199

RESUMO

Background: Long-term rhythm monitoring to detect atrial fibrillation (AF) following a cryptogenic stroke (CS) is well established. However, the burden of organized atrial arrhythmias in this population is not well defined. Objective: The purpose of this study was to assess the incidence and risk factors for organized atrial arrhythmias in patients with CS. Methods: We evaluated all patients with CS who received an insertable cardiac monitor (ICM) between October 2014 and April 2020. All ICM transmissions categorized as AF, tachycardia, or bradycardia were reviewed. We evaluated the time to detection of organized AF and the combination of either organized atrial arrhythmia or AF. Results: A total of 195 CS patients with ICMs were included (51% men; mean age 66 ± 12 years; mean CHA2DS2-VASC score 4.6). Over mean follow-up of 18.9 ± 11.2 months, organized atrial arrhythmias lasting ≥30 seconds were detected in 45 patients (23%), of whom 62% did not have AF. Seventeen patients had both organized atrial arrhythmia and AF, and another 21 patients had AF only. Compared to those with normal left atrial size, patients with left atrial enlargement had a higher adjusted risk for development of atrial arrhythmias (mild left atrial enlargement: hazard ratio 1.99; 95% confidence interval 1.06-3.75; moderate/severe left atrial enlargement: hazard ratio 3.06; 95% confidence interval 1.58-5.92). Conclusion: Organized atrial arrhythmias lasting ≥30 seconds are detected in nearly one-fourth of CS patients. Two-thirds of these patients did not have AF. Further studies are required to evaluate the impact of organized atrial arrhythmias on recurrent stroke risk.

11.
Heliyon ; 10(2): e24405, 2024 Jan 30.
Artigo em Inglês | MEDLINE | ID: mdl-38312643

RESUMO

Objective: The lung is a common organ for colon cancer metastasis, and the objective of this experiment was to explore the protective effect of berberine on lung tissue or alveolar epithelial cells induced by colon cancer. Methods: Thirty-six BALB/c nude mice were used to establish a xenograft model of colon cancer with the HT29 cell line and were treated with berberine and probiotics. Human bronchial epithelial BEAS-2B cells were induced by conditioned medium (CM) from the colon cancer cell lines HT29 and RKO and were treated with berberine. Lung tissues were collected to detect the changes in the microbiota using 16S rDNA sequencing and the expression of inflammatory cytokines. The expression of E-cadherin and N-cadherin in BEAS-2B cells was detected by cellular immunofluorescence. The changes in cell proliferation were detected by the CCK-8 assay. Western blotting was used to detect E-cadherin, N-cadherin, collagen I, fibronectin, PDGF-ß, and RAD51 expression in BEAS-2B cells. Results: The richness and evenness of the microbiota in the lung tissues of mice with colon cancer were significantly lower than those of the control group. Berberine significantly increased the abundances of Bacteroidetes, Bacteroidia, Bacteroidales, Lactobacillaceae, Lactobacillus and Acinetobacter in the lung tissue of mice with colon cancer, with reduced abundances of Actinobacteria, Bacillales, Staphylococcaceae and Staphylococcus. Berberine or probiotics significantly increased the alpha diversity of the lung microbiota. Compared with probiotics, berberine significantly enhanced the abundance of microbiota involved in the metabolism of lysosomes, flavone and flavonol biosynthesis, glycosaminoglycan degradation, and glycosphingolipid biosynthesis-ganglio. Berberine increased IL-6 and IL-10 and decreased IL-17 and IFN-γ expression in lung tissue (P > 0.05), but berberine-probiotics significantly decreased IL-17 and IFN-γ and increased IL-10 expression (P < 0.05). Colon cancer cells could not induce BEAS-2B proliferation but decreased the expression of the epithelial marker E-cadherin and altered the expression of extracellular matrix-related proteins (collagen I, fibronectin, and PDGF-ß), which were reversed by berberine. Berberine increased RAD51 expression in BEAS-2B cells, which had been decreased by HT29 and RKO CM treatment. Conclusion: Berberine can selectively regulate the abundance of some microbiomes of lung tissue in colon cancer, improve the inflammatory response in lung tissue, and antagonize the cancerous stimulation of colon cancer cells to lung tissue cells by regulating the bronchial epithelial cell phenotype, extracellular matrix remodelling and the expression of the repair gene RAD51.

12.
PeerJ ; 12: e16866, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38313027

RESUMO

Objective: The objective of this study was to appraise the prognostic impact of lymph nodes in patients diagnosed with pT1c33N0M0 non-small cell lung cancer (NSCLC) and to delve into the prognostic significance of lymph nodes located at the N1 lymph node station in this patient cohort. Methods: A retrospective analysis of clinical data was conducted for 255 patients diagnosed with pT1c33N0M0 NSCLC. Lymph nodes were tabulated and categorized into three groups (0-10 nodes, 11-16 nodes, >16 nodes). Clinical data among these three groups of pT1c33N0M0 NSCLC patients were compared. We conducted both univariate and multivariate analyses to pinpoint the factors that impact the prognosis of patients with pT1c33N0M0 non-small cell lung cancer (NSCLC). Additionally, we employed receiver operating characteristic (ROC) curve analysis to pinpoint the optimal lymph node criteria at the N1 station for prognostic prediction in pT1c33N0M0 NSCLC patients. Results: Within the cohort of 255 individuals afflicted with pT1c33N0M0 non-small cell lung cancer (NSCLC), a comprehensive tally of 3,902 lymph nodes was diligently established, yielding an average of 15.3 nodes for each patient. Multivariate analysis demonstrated that tumor size, T stage, and lymph nodes were independent factors significantly impacting the prognosis of pT1c33N0M0 NSCLC patients (P < 0.05). ROC curve analysis revealed an area under the curve of 0.6982 for predicting prognosis using N1 station in pT1c33N0M0 NSCLC patients. The maximum Youden index was observed at an N1 station of 2.7 nodes. Patients with N1 station ≥ three nodes had significantly better prognoses compared to those with < 3 nodes (both P < 0.05). Conclusion: Lymph nodes serve as an independent prognostic factor for pT1c33N0M0 NSCLC patients. Detecting at least three or more lymph nodes at the N1 station is associated with a more favourable prognosis in pT1c33N0M0 NSCLC patients.


Assuntos
Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , Humanos , Carcinoma Pulmonar de Células não Pequenas/complicações , Estudos Retrospectivos , Neoplasias Pulmonares/complicações , Prognóstico , Estadiamento de Neoplasias , Metástase Linfática/patologia , Linfonodos/patologia
13.
Front Microbiol ; 15: 1334703, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38314433

RESUMO

Microbial communities, demonstrating dynamic changes in cadavers and the surroundings, provide invaluable insights for forensic investigations. Conventional methodologies for microbiome sequencing data analysis face obstacles due to subjectivity and inefficiency. Artificial Intelligence (AI) presents an efficient and accurate tool, with the ability to autonomously process and analyze high-throughput data, and assimilate multi-omics data, encompassing metagenomics, transcriptomics, and proteomics. This facilitates accurate and efficient estimation of the postmortem interval (PMI), detection of crime location, and elucidation of microbial functionalities. This review presents an overview of microorganisms from cadavers and crime scenes, emphasizes the importance of microbiome, and summarizes the application of AI in high-throughput microbiome data processing in forensic microbiology.

14.
Front Nutr ; 11: 1310155, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38298422

RESUMO

Introduction: In recent years, the relationship between circadian rhythm and overweight and obesity has attracted the attention of many scholars. Methods: To evaluate association between the duration of sleep and the regularity of breakfast and overweight. A total of 1,178 students from Qingdao University were selected by stratified cluster sampling. There were 601 males (24.69 ± 0.80 years old) and 569 females (24.54 ± 0.70 years old). We used body mass index (BMI), waist circumference (WC), and waist-to-hip ratio (WHR) to define overweight levels. Chi-square test, Pearson correlation test, and logistic regression were applied to test association among overweight, sleep duration, sleep onset time, and breakfast regularity. Pittsburgh sleep quality index was used to assess the overall sleep quality of the study subjects. Mediation effect and Sobel test were used to analyze the effect of sleep duration on breakfast regularity and overweight. Results: Only 34.1% of the population ate breakfast every day, and eating breakfast 1-3 times per week was associated with a higher risk of overweight (BMI: OR = 2.183, 95%CI: 1.369,3,481; WC: OR = 2.101, 95%CI: 1.232,3,583; WHR: OR = 2.108, 95%CI: 1.331,3,337). The effects of all types of Usual Breakfast Consumption Frequency on overweight were fully mediated by sleep duration (p < 0.05). In particular, the subjects exercised outdoors more than five times per week slept longer (p < 0.05). Conclusion: Short sleep duration may be the main reason for irregular breakfast leading to overweight. Adequate outdoor exercise is essential for weight maintenance.

15.
Front Psychol ; 15: 1290310, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38298521

RESUMO

Background: Sleep problems in preschoolers are becoming increasingly prominent, and the association between sleep status and anxiety symptoms has attracted growing attention. However, studies investigating the relationship between bedtime and nighttime sleep duration in preschoolers and their anxiety symptoms remain scant. We used the large sample data from the Longhua Cohort Study of Children in Shenzhen, China (LCCS) to analyze the association between bedtime and sleep in preschoolers and their anxiety symptoms. Methods: A cross-sectional study of 69,138 preschoolers in Longhua District, Shenzhen, China was conducted in 2022. Data on sociodemographic characteristics of families, bedtime, nighttime sleep duration of preschoolers, and their anxiety symptoms (measured by the Spence Preschool Children Anxiety Scale) were collected through a structured questionnaire completed by the parents. Using binary logistic regression models, the relationship between bedtime, nighttime sleep duration, and childhood anxiety symptoms was examined. Results: The bedtimes of preschoolers were concentrated between 21:01-22:00 (52.41%). Among the preschoolers, 38.70% had bedtimes later than 22:00, and 75.49% had insufficient nighttime sleep duration. The positive screening rate for anxiety symptoms among preschoolers was 3.50%. After adjusting for confounding factors using binary logistic regression models, compared with preschoolers with bedtime ≤21:00, The OR (95%CI) values of anxiety in preschoolers with bedtime ≥23:01, 22:01-23:00 and 21:01-22:00 were 2.86 (2.21-3.69), 1.51 (1.27-1.79) and 1.48 (1.26-1.76), respectively. Compared with those with sufficient nighttime sleep duration, the OR (95%CI) of children with nighttime sleep duration less than 9 h was 1.36 (1.23-1.51). Conclusion: An association exists between bedtime and nighttime sleep duration in preschoolers and their anxiety symptoms. Preschoolers with 21:00 for bedtime and a nighttime sleep duration of 10 h may have lower anxiety symptoms. These findings support the importance of adequate sleep for preventing anxiety symptoms in children.

16.
Science ; : eadj2609, 2024 Feb 02.
Artigo em Inglês | MEDLINE | ID: mdl-38305684

RESUMO

Insects rely on a family of seven-transmembrane proteins called gustatory receptors (GRs) to encode different taste modalities such as sweet and bitter. Here we report structures of Drosophila sweet taste receptors GR43a and GR64a in the apo and sugar-bound states. Both GRs form tetrameric sugar-gated cation channels, composed of one central pore domain (PD) and four peripheral ligand-binding domains (LBDs). Whereas GR43a is specifically activated by the monosaccharide fructose that binds to a narrow pocket in LBD, disaccharides sucrose and maltose selectively activate GR64a by binding to a larger and flatter pocket in LBD. Sugar binding to LBD induces local conformational changes, which are subsequently transferred to PD to cause channel opening. Our studies have revealed structural basis for sugar recognition and activation of GRs.

17.
J Environ Manage ; 353: 120155, 2024 Feb 27.
Artigo em Inglês | MEDLINE | ID: mdl-38308987

RESUMO

Dimethylsulfide (DMS) is a major organic sulfide in aquatic ecosystems and an infochemical that is considered as a key predictor of changes in energy and material fluxes and stocks. It is largely unknown how DMS changes and affects the food webs and material cycles in eutrophicated freshwater. In this study, field monitoring and literature surveys were conducted to analyze the effects of eutrophication on DMS concentrations. Daphnia-zebrafish microcosms were then used to investigate the effects of DMS concentrations on carbon transfer. The results demonstrated that the concentration of DMS was increased by eutrophication related indicators (chlorophyll and phosphorus). Eutrophication driven DMS altered carbon transfer in the freshwater food chain. Low concentrations (0.1-1 nM) of DMS promoted the predation of daphnia by zebrafish compared to the 0.01 nM DMS, which further stimulated the total carbon transfer from daphnia to zebrafish and altered the dissolved organic carbon (DOC) distribution in water. High concentrations (10-100 nM) of DMS did not alter zebrafish predation on daphnia and carbon transfer. DOC excreted by zebrafish altered carbon emission potential, and DMS in water showed a unimodal relationship with the carbon emission potential, peaking at 0.40 nM DMS. Keeping the DMS in water at 1.82 nM may maintain a lower carbon emission potential. These results improved the understanding of the effects of eutrophication on DMS, demonstrated the ecological role of DMS on freshwater fish and the carbon cycle, estimated the effects of DMS on the carbon emission potential of fish, and offered new insights into the management of eutrophication.


Assuntos
Carbono , Cadeia Alimentar , Animais , Ecossistema , Peixe-Zebra , Água Doce , Sulfetos , Eutrofização , Água
18.
Bioorg Chem ; 144: 107169, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38330722

RESUMO

Four undescribed compounds including one aromatic glucoside derivative, cordyceglycoside A (1), one new isoleucine derivative inner salt, cordycepisosalt A (2), a rare four-membered lactam, cinerealactam B (3), and one sesquiterpene derivative, cordycepsetp A (4), together with six known compounds were isolated from Cordyceps militaris. The structures including absolute configurations of these new compounds, were unambiguously elucidated by spectroscopic data analysis and single crystal X-ray diffraction. Biological evaluation of compounds 1-4 showed that 3 displays anti-renal fibrotic activities in TGF-ß1 induced NRK-52e cells. Furthermore, DARTS coupled with LC-MS/MS analysis was used to identify candidate target proteins for 3. Subsequently, C1qbp knockdown using siRNA allowed us to validate the target protein of 3.


Assuntos
Cordyceps , Cordyceps/química , Cordyceps/metabolismo , Cromatografia Líquida , Espectrometria de Massas em Tandem , Análise Espectral , Fibrose
19.
Proc Natl Acad Sci U S A ; 121(8): e2319364121, 2024 Feb 20.
Artigo em Inglês | MEDLINE | ID: mdl-38359296

RESUMO

Clonal hematopoiesis (CH) represents the clonal expansion of hematopoietic stem cells and their progeny driven by somatic mutations. Accurate risk assessment of CH is critical for disease prevention and clinical decision-making. The size of CH has been showed to associate with higher disease risk, yet, factors influencing the size of CH are unknown. In addition, the characteristics of CH in long-lived individuals are not well documented. Here, we report an in-depth analysis of CH in longevous (≥90 y old) and common (60~89 y old) elderly groups. Utilizing targeted deep sequencing, we found that the development of CH is closely related to age and the expression of aging biomarkers. The longevous elderly group exhibited a significantly higher incidence of CH and significantly higher frequency of TET2 and ASXL1 mutations, suggesting that certain CH could be beneficial to prolong life. Intriguingly, the size of CH neither correlates significantly to age, in the range of 60 to 110 y old, nor to the expression of aging biomarkers. Instead, we identified a strong correlation between large CH size and the number of mutations per individual. These findings provide a risk assessment biomarker for CH and also suggest that the evolution of the CH is influenced by factor(s) in addition to age.


Assuntos
Hematopoiese Clonal , Hematopoese , Humanos , Idoso , Hematopoiese Clonal/genética , Hematopoese/genética , Envelhecimento/genética , Mutação , Biomarcadores
20.
Int J Surg Case Rep ; 116: 109358, 2024 Feb 07.
Artigo em Inglês | MEDLINE | ID: mdl-38364752

RESUMO

INTRODUCTION AND IMPORTANCE: Congenital hepatoblastoma is an exceedingly rare neoplasm, predominantly documented as isolated instances, with contentious aspects surrounding its therapeutic approaches and prognostic implications. This study aims to comprehensively summarize and evaluate the management experience of congenital hepatoblastoma (CHB). CASE PRESENTATION: This cohort comprised five infants diagnosed with hepatoblastoma, confirmed through pathological examination, and with an onset of symptoms before 28 days of age. They were enrolled between November 2019 and May 2022. The treatment course they underwent has been summarized, and their prognosis has been subject to analysis. CLINICAL DISCUSSION: Distinguishing congenital hepatoblastoma from other medical conditions is typically necessary. Given the patient's tender age, the approach to treatment demands comprehensive assessment, particularly in cases involving unique tumor locations or substantial tumor sizes. The selection of treatment modalities, encompassing preoperative neoadjuvant chemotherapy and surgical techniques, becomes of paramount importance. Furthermore, determining the treatment's endpoint poses a notable challenge and often necessitates a comprehensive evaluation. CONCLUSION: For pediatric patients afflicted with CHB, the application of preoperative neoadjuvant chemotherapy mitigates surgical risks, while the incorporation of surgical procedures followed by postoperative chemotherapy significantly enhances the overall prognosis. Additionally, AFP-L3% levels may serve as a valuable adjunctive marker signifying the conclusion of treatment.

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