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1.
Nat Commun ; 15(1): 3221, 2024 Apr 15.
Artigo em Inglês | MEDLINE | ID: mdl-38622129

RESUMO

The hippocampus creates a cognitive map of the external environment by encoding spatial and self-motion-related information. However, it is unclear whether hippocampal neurons could also incorporate internal cognitive states reflecting an animal's exploratory intention, which is not driven by rewards or unexpected sensory stimuli. In this study, a subgroup of CA1 neurons was found to encode both spatial information and animals' investigatory intentions in male mice. These neurons became active before the initiation of exploration behaviors at specific locations and were nearly silent when the same fields were traversed without exploration. Interestingly, this neuronal activity could not be explained by object features, rewards, or mismatches in environmental cues. Inhibition of the lateral entorhinal cortex decreased the activity of these cells during exploration. Our findings demonstrate that hippocampal neurons may bridge external and internal signals, indicating a potential connection between spatial representation and intentional states in the construction of internal navigation systems.


Assuntos
Intenção , Navegação Espacial , Masculino , Camundongos , Animais , Percepção Espacial/fisiologia , Hipocampo/fisiologia , Córtex Entorrinal , Sinais (Psicologia) , Navegação Espacial/fisiologia
2.
Environ Int ; 186: 108655, 2024 Apr 14.
Artigo em Inglês | MEDLINE | ID: mdl-38626494

RESUMO

The rhizosphere is one of the key determinants of plant health and productivity. Mixtures of pesticides are commonly used in intensified agriculture. However, the combined mechanisms underlying their impacts on soil microbiota remain unknown. The present study revealed that the rhizosphere microbiota was more sensitive to azoxystrobin and oxytetracycline, two commonly used pesticides, than was the microbiota present in bulk soil. Moreover, the rhizosphere microbiota enhanced network complexity and stability and increased carbohydrate metabolism and xenobiotic biodegradation as well as the expression of metabolic genes involved in defence against pesticide stress. Co-exposure to azoxystrobin and oxytetracycline had antagonistic effects on Arabidopsis thaliana growth and soil microbial variation by recruiting organic-degrading bacteria and regulating ABC transporters to reduce pesticide uptake. Our study explored the composition and function of soil microorganisms through amplicon sequencing and metagenomic approaches, providing comprehensive insights into the synergistic effect of plants and rhizosphere microbiota on pesticides and contributing to our understanding of the ecological risks associated with pesticide use.

3.
Europace ; 26(4)2024 Mar 30.
Artigo em Inglês | MEDLINE | ID: mdl-38584395

RESUMO

AIMS: A few studies have reported the effect and safety of pulsed field ablation (PFA) catheters for ablating atrial fibrillation (AF), which were mainly based on basket-shaped or flower-shaped designs. However, the clinical application of a circular-shaped multi-electrode catheter with magnetic sensors is very limited. To study the efficacy and safety of a PFA system in patients with paroxysmal AF using a circular-shaped multi-electrode catheter equipped with magnetic sensors for pulmonary vein isolation (PVI). METHODS AND RESULTS: A novel proprietary bipolar PFA system was used for PVI, which utilized a circular-shaped multi-electrode catheter with magnetic sensors and allowed for three-dimensional model reconstruction, mapping, and ablation in one map. To evaluate the efficacy, efficiency, and safety of this PFA system, a prospective, multi-centre, single-armed, pre-market clinical study was performed. From July 2021 to December 2022, 151 patients with paroxysmal AF were included and underwent PVI. The study examined procedure time, immediate success rate, procedural success rate at 12 months, and relevant complications. In all 151 patients, all the pulmonary veins were acutely isolated using the studied system. Pulsed field ablation delivery was 78.4 ± 41.8 times and 31.3 ± 16.7 ms per patient. Skin-to-skin procedure time was 74.2 ± 29.8 min, and fluoroscopy time was 13.1 ± 7.6 min. The initial 11 (7.2%) cases underwent procedures with deep sedation anaesthesia, and the following cases underwent local anaesthesia. In the initial 11 cases, 4 cases (36.4%) presented transient vagal responses, and the rest were all successfully preventatively treated with atropine injection and rapid fluid infusion. No severe complications were found during or after the procedure. During follow-up, 3 cases experienced atrial flutter, and 11 cases had AF recurrence. The estimated 12-month Kaplan-Meier of freedom from arrhythmia was 88.4%. CONCLUSION: The PFA system, comprised of a circular PFA catheter with magnetic sensors, could rapidly achieve PVI under three-dimensional guidance and demonstrated excellent safety with comparable effects.


Assuntos
Fibrilação Atrial , Ablação por Cateter , Veias Pulmonares , Humanos , Veias Pulmonares/cirurgia , Resultado do Tratamento , Estudos Prospectivos , Fibrilação Atrial/diagnóstico , Fibrilação Atrial/cirurgia , Cateteres , Ablação por Cateter/efeitos adversos , Ablação por Cateter/métodos , Fenômenos Magnéticos , Recidiva
4.
Molecules ; 29(7)2024 Mar 27.
Artigo em Inglês | MEDLINE | ID: mdl-38611777

RESUMO

Iridoid components have been reported to have significant neuroprotective effects. However, it is not yet clear whether the efficacy and mechanisms of iridoid components with similar structures are also similar. This study aimed to compare the neuroprotective effects and mechanisms of eight iridoid components (catalpol (CAT), genipin (GE), geniposide (GEN), geniposidic acid (GPA), aucubin (AU), ajugol (AJU), rehmannioside C (RC), and rehmannioside D (RD)) based on corticosterone (CORT)-induced injury in PC12 cells. PC12 cells were randomly divided into a normal control group (NC), model group (M), positive drug group (FLX), and eight iridoid administration groups. Firstly, PC12 cells were induced with CORT to simulate neuronal injury. Then, the MTT method and flow cytometry were applied to evaluate the protective effects of eight iridoid components on PC12 cell damage. Thirdly, a cell metabolomics study based on ultra-performance liquid chromatography-quadrupole-time-of-flight mass spectrometry (UPLC-Q/TOF-MS) was performed to explore changes in relevant biomarkers and metabolic pathways following the intervention of administration. The MTT assay and flow cytometry analysis showed that the eight iridoid components can improve cell viability, inhibit cell apoptosis, reduce intracellular ROS levels, and elevate MMP levels. In the PCA score plots, the sample points of the treatment groups showed a trend towards approaching the NC group. Among them, AU, AJU, and RC had a weaker effect. There were 38 metabolites (19 metabolites each in positive and negative ion modes, respectively) identified as potential biomarkers during the experiment, among which 23 metabolites were common biomarkers of the eight iridoid groups. Pathway enrichment analysis revealed that the eight iridoid components regulated the metabolism mainly in relation to D-glutamine and D-glutamate metabolism, arginine biosynthesis, the TCA cycle, purine metabolism, and glutathione metabolism. In conclusion, the eight iridoid components could reverse an imbalanced metabolic state by regulating amino acid neurotransmitters, interfering with amino acid metabolism and energy metabolism, and harmonizing the level of oxidized substances to exhibit neuroprotective effects.


Assuntos
Glucosídeos Iridoides , Glicosídeos Iridoides , Fármacos Neuroprotetores , Piranos , Animais , Ratos , Fármacos Neuroprotetores/farmacologia , Metabolômica , Iridoides/farmacologia , Aminoácidos , Biomarcadores
6.
BMC Cancer ; 24(1): 359, 2024 Mar 20.
Artigo em Inglês | MEDLINE | ID: mdl-38509485

RESUMO

BACKGROUND: Papillary thyroid carcinoma (PTC) is the most frequent histological type of thyroid carcinoma. Although an increasing number of diagnostic methods have recently been developed, the diagnosis of a few nodules is still unsatisfactory. Therefore, the present study aimed to develop and validate a comprehensive prediction model to optimize the diagnosis of PTC. METHODS: A total of 152 thyroid nodules that were evaluated by postoperative pathological examination were included in the development and validation cohorts recruited from two centres between August 2019 and February 2022. Patient data, including general information, cytopathology, imprinted gene detection, and ultrasound features, were obtained to establish a prediction model for PTC. Multivariate logistic regression analysis with a bidirectional elimination approach was performed to identify the predictors and develop the model. RESULTS: A comprehensive prediction model with predictors, such as component, microcalcification, imprinted gene detection, and cytopathology, was developed. The area under the curve (AUC), sensitivity, specificity, and accuracy of the developed model were 0.98, 97.0%, 89.5%, and 94.4%, respectively. The prediction model also showed satisfactory performance in both internal and external validations. Moreover, the novel method (imprinted gene detection) was demonstrated to play a role in improving the diagnosis of PTC. CONCLUSION: The present study developed and validated a comprehensive prediction model for PTC, and a visualized nomogram based on the prediction model was provided for clinical application. The prediction model with imprinted gene detection effectively improves the diagnosis of PTCs that are undetermined by the current means.


Assuntos
Carcinoma Papilar , Neoplasias da Glândula Tireoide , Nódulo da Glândula Tireoide , Humanos , Câncer Papilífero da Tireoide/diagnóstico , Câncer Papilífero da Tireoide/genética , Carcinoma Papilar/diagnóstico , Carcinoma Papilar/genética , Carcinoma Papilar/patologia , Neoplasias da Glândula Tireoide/diagnóstico , Neoplasias da Glândula Tireoide/genética , Neoplasias da Glândula Tireoide/patologia , Nódulo da Glândula Tireoide/patologia , Nomogramas , Estudos Retrospectivos
7.
J Gastrointest Oncol ; 15(1): 1-11, 2024 Feb 29.
Artigo em Inglês | MEDLINE | ID: mdl-38482217

RESUMO

Background: The prognosis for esophageal cancer (EC), a common malignant tumor, is poor. The new oral small-molecule tyrosine kinase inhibitor apatinib has shown an excellent therapeutic effect on treating EC. Camrelizumab is a humanized programmed death 1 (PD-1) inhibitor with high affinity. Immune checkpoint inhibitors combined with chemotherapy have become the standard first-line treatment for advanced EC. The new combination strategy of anti-angiogenic therapy combined with immunotherapy has great application prospects in the treatment of tumors. We aimed to assess camrelizumab in combination with apatinib as a new combination regimen for advanced or metastatic esophageal squamous cell carcinoma (ESCC). Methods: In this study, we recruited patients with an Eastern Cooperative Oncology Group (ECOG) performance status ≤2, with pathologically confirmed unresectable, locally advanced, locally recurrent, or metastatic ESCC. Each patient received an intravenous infusion of camrelizumab 200 mg and oral administration of apatinib 250 mg once a day, every 21 days, as a cycle until disease progression, intolerance, or death. The primary endpoint was the objective response rate (ORR), while the Kaplan-Meier method and LIFETEST procedure were used to estimate survival functions for overall survival (OS) and progression-free survival (PFS). The National Cancer Institute Common Terminology Criteria for Adverse Events, version 4.03, was used to evaluate adverse events. Results: Between December 1, 2019 and July 31, 2022, 35 patients were enrolled, with 29 patients in the efficacy and safety analysis. The ORR was 34.5%, and the disease control rate (DCR) reached 82.8%. Median OS was 13.8 months (95% CI: 11.2-16.2), and the estimated 6-, 9-, and 12-month OS rates were 85.5% (95% CI: 65.7-94.3%), 80.9% (95% CI: 60.3-91.5%), and 67.0% (95% CI: 43.8-82.4%), respectively. Median PFS was 9.5 months (95% CI: 7.0-13.6). The most prominent grade ≥3 adverse events associated with treatments were alanine aminotransferase (ALT) increase (10.3%), hypertension (10.3%), and reactive cutaneous capillary endothelial proliferation (CCEP) (6.9%), and no deaths occurred due to adverse events. Conclusions: Among patients with advanced or metastatic ESCC, camrelizumab combined with apatinib showed a reasonable remission rate and survival benefit with a manageable safety profile.

8.
Anal Chem ; 96(10): 4103-4110, 2024 Mar 12.
Artigo em Inglês | MEDLINE | ID: mdl-38427614

RESUMO

Pancreatic ductal adenocarcinoma (PDAC) is an aggressive malignancy with a 5 year survival rate less than 12%. This malignancy is closely related to the unique tumor microenvironment (TME), which is characterized by a hypovascular and hyperdense extracellular matrix, making it difficult for drugs to permeate the tumor center. Near-infrared fluorescence (NIRF) imaging, which has high sensitivity and resolution, may improve the survival rate of PDAC patients. In this study, we first used JS-K (O2-(2,4-dinitrophenyl) 1-[(4-ethoxycarbonyl) piperazine-1-yl] diazene-1-ium-1,2-diolate) to specifically dilate blood vessels within the TME of PDAC patients and subsequently injected IR820-PEG-MNPs (IPM NPs) to diagnose and treat orthotopic PDAC. We found that JS-K promoted the accumulation of IPM NPs in orthotopic Pan02 tumor-bearing mice and was able to increase the tumor signal-to-background ratio (SBR) in the orthotopic PDAC area by 41.5%. In addition, surgical navigation in orthotopic Pan02 tumor-bearing mice and complete tumor resection based on fluorescence imaging were achieved with a detection sensitivity of 81.0%. Moreover, we verified the feasibility of the combination of laparoscopy and photothermal ablation (PTA) for the treatment of PDAC. Finally, we demonstrated that IPM NPs had greater affinity for human PDAC tissues than for normal pancreatic tissues ex vivo, preliminarily highlighting the potential for clinical translation of these NPs. In conclusion, we developed and validated a novel sequential delivery strategy that promotes the accumulation of nanoagents in the tumor area and can be used for the diagnosis and treatment of PDAC.


Assuntos
Carcinoma Ductal Pancreático , Neoplasias Pancreáticas , Humanos , Camundongos , Animais , Melaninas , Medicina de Precisão , Neoplasias Pancreáticas/diagnóstico por imagem , Neoplasias Pancreáticas/tratamento farmacológico , Carcinoma Ductal Pancreático/diagnóstico por imagem , Carcinoma Ductal Pancreático/tratamento farmacológico , Imagem Óptica/métodos , Linhagem Celular Tumoral , Microambiente Tumoral
9.
ACS Synth Biol ; 13(4): 1303-1311, 2024 Apr 19.
Artigo em Inglês | MEDLINE | ID: mdl-38529630

RESUMO

In this study, we proposed a biological approach to efficiently produce pseudouridine (Ψ) from glucose and uracil in vivo using engineered Escherichia coli. By screening host strains and core enzymes, E. coli MG1655 overexpressing Ψ monophosphate (ΨMP) glycosidase and ΨMP phosphatase was obtained, which displayed the highest Ψ concentration. Then, optimization of the RBS sequences, enhancement of ribose 5-phosphate supply in the cells, and overexpression of the membrane transport protein UraA were investigated. Finally, fed-batch fermentation of Ψ in a 5 L fermentor can reach 27.5 g/L with a yield of 89.2 mol % toward uracil and 25.6 mol % toward glucose within 48 h, both of which are the highest to date. In addition, the Ψ product with a high purity of 99.8% can be purified from the fermentation broth after crystallization. This work provides an efficient and environmentally friendly protocol for allowing for the possibility of Ψ bioproduction on an industrial scale.


Assuntos
Proteínas de Escherichia coli , Escherichia coli , Escherichia coli/metabolismo , Pseudouridina/metabolismo , Glucose/metabolismo , Uracila/metabolismo , Reatores Biológicos , Fermentação , Engenharia Metabólica , Proteínas de Membrana Transportadoras/metabolismo , Proteínas de Escherichia coli/metabolismo
10.
Science ; 383(6684): eadi3332, 2024 Feb 16.
Artigo em Inglês | MEDLINE | ID: mdl-38359126

RESUMO

The identification of mechanisms to store glucose carbon in the form of glycogen rather than fat in hepatocytes has important implications for the prevention of nonalcoholic fatty liver disease (NAFLD) and other chronic metabolic diseases. In this work, we show that glycogenesis uses its intermediate metabolite uridine diphosphate glucose (UDPG) to antagonize lipogenesis, thus steering both mouse and human hepatocytes toward storing glucose carbon as glycogen. The underlying mechanism involves transport of UDPG to the Golgi apparatus, where it binds to site-1 protease (S1P) and inhibits S1P-mediated cleavage of sterol regulatory element-binding proteins (SREBPs), thereby inhibiting lipogenesis in hepatocytes. Consistent with this mechanism, UDPG administration is effective at treating NAFLD in a mouse model and human organoids. These findings indicate a potential opportunity to ameliorate disordered fat metabolism in the liver.


Assuntos
Lipogênese , Glicogênio Hepático , Fígado , Hepatopatia Gordurosa não Alcoólica , Pró-Proteína Convertases , Serina Endopeptidases , Uridina Difosfato Glucose , Animais , Humanos , Camundongos , Carbono/metabolismo , Glucose/metabolismo , Hepatócitos/metabolismo , Fígado/metabolismo , Glicogênio Hepático/metabolismo , Hepatopatia Gordurosa não Alcoólica/tratamento farmacológico , Hepatopatia Gordurosa não Alcoólica/metabolismo , Pró-Proteína Convertases/metabolismo , Proteína de Ligação a Elemento Regulador de Esterol 1/genética , Proteína de Ligação a Elemento Regulador de Esterol 1/metabolismo , Uridina Difosfato Glucose/administração & dosagem , Uridina Difosfato Glucose/metabolismo , Masculino , Camundongos Endogâmicos C57BL , Células HEK293
11.
Sci China Life Sci ; 2024 Feb 07.
Artigo em Inglês | MEDLINE | ID: mdl-38332216

RESUMO

Fulminant myocarditis is an acute diffuse inflammatory disease of myocardium. It is characterized by acute onset, rapid progress and high risk of death. Its pathogenesis involves excessive immune activation of the innate immune system and formation of inflammatory storm. According to China's practical experience, the adoption of the "life support-based comprehensive treatment regimen" (with mechanical circulation support and immunomodulation therapy as the core) can significantly improve the survival rate and long-term prognosis. Special emphasis is placed on very early identification,very early diagnosis,very early prediction and very early treatment.

12.
Langmuir ; 40(13): 6862-6868, 2024 Apr 02.
Artigo em Inglês | MEDLINE | ID: mdl-38385757

RESUMO

We report on a synthesis protocol, experimental characterization, and theoretical modeling of active pulsatile Belousov-Zhabotinsky (BZ) hydrogels. Our two-step synthesis technique allows independent optimization of the geometry, the chemical, and the mechanical properties of BZ gels. We identify the role of the surrounding medium chemistry and gel radius for the occurrence of BZ gel oscillations, quantified by the Damköhler number, which is the ratio of chemical reaction to diffusion rates. Tuning the BZ gel size to maximize its chemomechanical oscillation amplitude, we find that its oscillatory strain amplitude is limited by the time scale of gel swelling relative to the chemical oscillation period. Our experimental findings are in good agreement with a Vanag-Epstein model of BZ chemistry and a Tanaka Fillmore theory of gel swelling dynamics.

13.
J Hazard Mater ; 468: 133865, 2024 Apr 15.
Artigo em Inglês | MEDLINE | ID: mdl-38412801

RESUMO

Measurements of radon exhalation rate using traditional methods can be affected by back-diffusion or differential pressure in the accumulation chamber, resulting in deviations between the measured and the true values. To obtain an accurate radon exhalation rate for evaluation of radon-risk regions, two novel approaches of measurements based on traditional methods were proposed. Repeated experiments were implemented on a self-designed stainless cylindrical vessel filled with uranium tailings sand. The measured radon exhalation rates on average were 0.51 ± 0.02 and 0.52 ± 0.02 Bq m-2 s-1 for the two proposed methods, with 0.02% and 0.04%, respectively, deviations from the theoretical value. In addition, numerical techniques were employed to interpret the defects of traditional methods and mechanisms of proposed approaches to measure accurate values. Two novel approaches have significantly reduced the impact of back diffusion and differential pressure inside the chamber and consumed less time.

14.
Appl Environ Microbiol ; 90(3): e0224223, 2024 Mar 20.
Artigo em Inglês | MEDLINE | ID: mdl-38358247

RESUMO

The extensive accumulation of polyethylene terephthalate (PET) has become a critical environmental issue. PET hydrolases can break down PET into its building blocks. Recently, we identified a glacial PET hydrolase GlacPETase sharing less than 31% amino acid identity with any known PET hydrolases. In this study, the crystal structure of GlacPETase was determined at 1.8 Å resolution, revealing unique structural features including a distinctive N-terminal disulfide bond and a specific salt bridge network. Site-directed mutagenesis demonstrated that the disruption of the N-terminal disulfide bond did not reduce GlacPETase's thermostability or its catalytic activity on PET. However, mutations in the salt bridges resulted in changes in melting temperature ranging from -8°C to +2°C and the activity on PET ranging from 17.5% to 145.5% compared to the wild type. Molecular dynamics simulations revealed that these salt bridges stabilized the GlacPETase's structure by maintaining their surrounding structure. Phylogenetic analysis indicated that GlacPETase represented a distinct branch within PET hydrolases-like proteins, with the salt bridges and disulfide bonds in this branch being relatively conserved. This research contributed to the improvement of our comprehension of the structural mechanisms that dictate the thermostability of PET hydrolases, highlighting the diverse characteristics and adaptability observed within PET hydrolases.IMPORTANCEThe pervasive problem of polyethylene terephthalate (PET) pollution in various terrestrial and marine environments is widely acknowledged and continues to escalate. PET hydrolases, such as GlacPETase in this study, offered a solution for breaking down PET. Its unique origin and less than 31% identity with any known PET hydrolases have driven us to resolve its structure. Here, we report the correlation between its unique structure and biochemical properties, focusing on an N-terminal disulfide bond and specific salt bridges. Through site-directed mutagenesis experiments and molecular dynamics simulations, the roles of the N-terminal disulfide bond and salt bridges were elucidated in GlacPETase. This research enhanced our understanding of the role of salt bridges in the thermostability of PET hydrolases, providing a valuable reference for the future engineering of PET hydrolases.


Assuntos
Hidrolases , Polietilenotereftalatos , Polietilenotereftalatos/metabolismo , Filogenia , Estabilidade Enzimática , Hidrolases/metabolismo , Dissulfetos , Temperatura
15.
Arch Gerontol Geriatr ; 120: 105336, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38301318

RESUMO

OBJECTIVES: The causal relationship between intrinsic capacity and frailty in older adults, as well as the underlying temporal mechanisms, remained poorly understood. The study aimed to investigate the causal association between intrinsic capacity and frailty while exploring the potential mediating role of self-perception of aging. MEASUREMENTS: A survey was conducted with a sample of 429 participants who completed measures of intrinsic capacity, self-perception of aging, and frailty at baseline and were followed for one year. The relationships between these variables were assessed using an autoregressive cross-lagged model. RESULTS: The study found reciprocal associations between intrinsic capacity and frailty (p < 0.01). Furthermore, the results indicated that self-perception of aging partially mediated the effect of frailty at baseline (T1) on intrinsic capacity at one-year follow-up (T2) (ß = -0.02, confidence interval: [-0.055, -0.004]). However, the reverse causation was not observed. CONCLUSIONS AND IMPLICATIONS: This study demonstrates a bidirectional causal relationship between intrinsic capacity and frailty in older adults. Self-perception of aging plays a significant mediating role in this relationship. Older adults with a worse level of frailty should be made aware of the potentially vicious cycle related to self-perception of aging, which can negatively affect their intrinsic capacity. Maintaining a positive self-perception of aging may help preserve physical and psychological reserves, maintain intrinsic capacity, and slow the decline of frailty.


Assuntos
Fragilidade , Humanos , Idoso , Idoso Fragilizado/psicologia , Envelhecimento/psicologia , Autoimagem , Inquéritos e Questionários , Estudos Longitudinais
16.
Zhongguo Zhong Yao Za Zhi ; 49(2): 389-402, 2024 Jan.
Artigo em Chinês | MEDLINE | ID: mdl-38403315

RESUMO

Ultra-high-performance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry(UPLC-Q/TOF-MS) was employed to examine the impact of Coptidis Rhizoma(CR) and its processed products on the metabolism in the rat model of oral ulcer due to excess heat and to compare the effectiveness of CR and its three products. Male SD rats were randomly allocated to the sham-operation(Sham), model(M, oral ulcer due to excess heat), CR, wine/Zingiberis Rhizoma Recens/Euodiae Fructus processed CR(wCR/zCR/eCR), and Huanglian Shangqing Tablets(HST) groups. Except the Sham group, the other groups were administrated with Codonopsis Radix-Astragali Radix decoction by gavage for two consecutive weeks. The anal temperature and water consumption of rats were monitored throughout the modeling period of excess heat. Following the completion of the modeling, oral ulcer was modeled with acetic acid. Hematoxylin-eosin(HE) staining was employed to observe the mucosal pathological changes in oral ulcer. A colorimetric assay was employed to determine the serum level of glutathione peroxidase(GSH-Px). Enzyme-linked immunosorbent assay(ELISA) was conducted to determine the levels of tumor necrosis factor-alpha(TNF-α), interleukin-6(IL-6), interleukin-1ß(IL-1ß), superoxide dismutase(SOD), and malondialdehyde(MDA) in the serum. The non-targeted metabolomics analysis based on UPLC-Q/TOF-MS was conducted on the serum samples. Metabolic profiles were then built, and the potential biomarkers were screened by principal component analysis(PCA) and orthogonal partial least squares discriminant analysis(OPLS-DA). The Mev software was used to establish a heat map and conduct cluster analysis on the quantitative results of the markers. The online databases including MBRole, KEGG, and MetaboAnalyst were used for pathway enrichment analysis and metabolic network building. The experimental results showed that the modeling led to pathological damage to the oral mucosa, elevated serum levels of TNF-α, IL-6, IL-1ß, and MDA, and lowered levels of SOD and GSH-Px in rats. The drug administration recovered all the indices to varying extents, and wCR exhibited the best performance. Non-targeted metabolomics identified 48 differential metabolites including 27 metabolites in the positive ion mode and 21 metabolites in the negative ion mode. Five enriched pathways were common, including glycerophospholipid metabolism, linoleic acid metabolism, and tyrosine metabolism. Conclusively, CR and its three processed products could alleviate the inflammation and oxidative stress injury in rats suffering from oral ulcers due to excess heat by regulating lipid and amino acid metabolism. Notably, wCR demonstrated the most significant therapeutic effect.


Assuntos
Medicamentos de Ervas Chinesas , Úlceras Orais , Ratos , Masculino , Animais , Medicamentos de Ervas Chinesas/farmacologia , Úlceras Orais/tratamento farmacológico , Interleucina-6 , Temperatura Alta , Fator de Necrose Tumoral alfa , Ratos Sprague-Dawley , Metabolômica/métodos , Cromatografia Líquida de Alta Pressão , Superóxido Dismutase , Biomarcadores
17.
Light Sci Appl ; 13(1): 48, 2024 Feb 14.
Artigo em Inglês | MEDLINE | ID: mdl-38355692

RESUMO

Endowing flexible and adaptable fiber devices with light-emitting capabilities has the potential to revolutionize the current design philosophy of intelligent, wearable interactive devices. However, significant challenges remain in developing fiber devices when it comes to achieving uniform and customizable light effects while utilizing lightweight hardware. Here, we introduce a mass-produced, wearable, and interactive photochromic fiber that provides uniform multicolored light control. We designed independent waveguides inside the fiber to maintain total internal reflection of light as it traverses the fiber. The impact of excessive light leakage on the overall illuminance can be reduced by utilizing the saturable absorption effect of fluorescent materials to ensure light emission uniformity along the transmission direction. In addition, we coupled various fluorescent composite materials inside the fiber to achieve artificially controllable spectral radiation of multiple color systems in a single fiber. We prepared fibers on mass-produced kilometer-long using the thermal drawing method. The fibers can be directly integrated into daily wearable devices or clothing in various patterns and combined with other signal input components to control and display patterns as needed. This work provides a new perspective and inspiration to the existing field of fiber display interaction, paving the way for future human-machine integration.

18.
Sci Robot ; 9(87): eadh2479, 2024 Feb 21.
Artigo em Inglês | MEDLINE | ID: mdl-38381840

RESUMO

Cerebral aneurysms and brain tumors are leading life-threatening diseases worldwide. By deliberately occluding the target lesion to reduce the blood supply, embolization has been widely used clinically to treat cerebral aneurysms and brain tumors. Conventional embolization is usually performed by threading a catheter through blood vessels to the target lesion, which is often limited by the poor steerability of the catheter in complex neurovascular networks, especially in submillimeter regions. Here, we propose magnetic soft microfiberbots with high steerability, reliable maneuverability, and multimodal shape reconfigurability to perform robotic embolization in submillimeter regions via a remote, untethered, and magnetically controllable manner. Magnetic soft microfiberbots were fabricated by thermal drawing magnetic soft composite into microfibers, followed by magnetizing and molding procedures to endow a helical magnetic polarity. By controlling magnetic fields, magnetic soft microfiberbots exhibit reversible elongated/aggregated shape morphing and helical propulsion in flow conditions, allowing for controllable navigation through complex vasculature and robotic embolization in submillimeter regions. We performed in vitro embolization of aneurysm and tumor in neurovascular phantoms and in vivo embolization of a rabbit femoral artery model under real-time fluoroscopy. These studies demonstrate the potential clinical value of our work, paving the way for a robotic embolization scheme in robotic settings.


Assuntos
Neoplasias Encefálicas , Aneurisma Intracraniano , Procedimentos Cirúrgicos Robóticos , Robótica , Animais , Coelhos , Procedimentos Cirúrgicos Robóticos/métodos , Aneurisma Intracraniano/terapia , Fenômenos Magnéticos
19.
Chemphyschem ; 25(7): e202400005, 2024 Apr 02.
Artigo em Inglês | MEDLINE | ID: mdl-38259129

RESUMO

Two complexes of dihydroxylammonium 5,5'-bistetrazole-1,1'-diolate (TKX-50) were employed to evaluate the aromaticity of their tetrazole rings via deep analysis such as the electronic structure, the ZZ component of the natural chemical shielding tensor (NICSZZ) and component orbitals, localized orbital locator purely contributed by σ-orbitals (LOL-σ) and localized orbital locator purely contributed by π-orbitals (LOL-π), the anisotropy of the induced current density (AICD) and the ZZ component of iso-chemical shielding surface (ICSSZZ) of these tetrazole rings thereof. The conclusion shows: that all tetrazole rings and bi-tetrazole rings in complexes have strong σ and a comparable strength π double aromaticity; all these magnetic shields almost symmetrically increase from the central axis to the tetrazole ring atoms; tetrazole rings in complex II show a little stronger dual aromaticity than that in complex I mainly due to the different orientation of the fragment 2 encompassing two hydroxylamine groups resulting in different effects on the contributions of σ orbitals and π orbitals to total aromaticity of tetrazole rings thereof; the difference in aromaticity is fundamentally caused by the atoms O with stronger electron-withdrawing than atom N in fragment 2 interact with bi-tetrazole ring through O in complex I but through N in complex II.

20.
Sci Rep ; 14(1): 945, 2024 Jan 10.
Artigo em Inglês | MEDLINE | ID: mdl-38200028

RESUMO

With the rapid development of AI and big data mining technologies, computerized medical decision-making has become increasingly prominent. The aim of high-utility pattern mining (HUPM) is to discover meaningful patterns in medical databases that contribute to maximizing the utility from the perspective of diagnosis. However, HUPM pays less attention to the interpretability and explainability of these patterns in medical decision-making scenarios. This paper proposes a novel algorithm called the Improved fuzzy high-utility pattern mining (IF-HUPM) to address this problem. First, the paper applies a fuzzy preprocessing method to divide the fuzzy intervals of a medical quantitative data set, which enhances the fuzziness and interpretability of the data. Next, in the process of IF-HUPM, both fuzzy tree and list structures are employed to calculate fuzzy high-utility values. By combining the characteristics of the one-stage and two-stage algorithms of HUPM, an adaptive-phase Fuzzy HUPM hybrid frame is proposed. The experimental results demonstrate that the proposed IF-HUPM algorithm enhances both accuracy and efficiency and the mining process requires less time and space on average.

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