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1.
Behav Sci (Basel) ; 14(3)2024 Feb 22.
Artigo em Inglês | MEDLINE | ID: mdl-38540467

RESUMO

BACKGROUND: Regular physical activity is an effective means to enhance university students' subjective well-being. However, current research needs to understand how physical activity enhances the subjective well-being of Chinese university students. Therefore, the study investigated the mechanism of physical activity's impact on university students' subjective well-being and the mediating roles of cognitive reappraisal and resilience in this mechanism. METHODS: The physical activity scale, subjective well-being scale, cognitive reappraisal scale and resilience scale were used to investigate 1350 university students, and the relationship between physical activity, cognitive reappraisal, resilience and university students' subjective well-being was verified through correlation analysis, regression analysis and a Bootstrap method. RESULTS: (1) There is a significant positive correlation between physical activity, cognitive reappraisal, resilience and university students' subjective well-being (p < 0.01); (2) physical activity, cognitive reappraisal and resilience all have a significant positive effects on university students' subjective well-being (p < 0.01); (3) cognitive reappraisal and resilience have significant mediating roles in the process of physical activity affecting university students' well-being, with mediating-effect values of 0.052 and 0.285; (4) the chain-mediating role of cognitive reappraisal and resilience in the process of physical activity affecting university students' well-being is significant, with the chain-mediating effect value of 0.062. CONCLUSION: Promoting university students' participation in physical activity not only directly enhances university students' subjective well-being but also indirectly improves university students' subjective well-being through cognitive reappraisal and resilience.

3.
medRxiv ; 2024 Jan 22.
Artigo em Inglês | MEDLINE | ID: mdl-38260271

RESUMO

While whole genome sequencing (WGS) of cell-free DNA (cfDNA) holds enormous promise for molecular residual disease (MRD) detection, its performance is limited by WGS error rate. Here we introduce AccuScan, an efficient cfDNA WGS technology that enables genome-wide error correction at single read level, achieving an error rate of 4.2×10 -7 , which is about two orders of magnitude lower than a read-centric de-noising method. When applied to MRD detection, AccuScan demonstrated analytical sensitivity down to 10 -6 circulating tumor allele fraction at 99% sample level specificity. In colorectal cancer, AccuScan showed 90% landmark sensitivity for predicting relapse. It also showed robust MRD performance with esophageal cancer using samples collected as early as 1 week after surgery, and predictive value for immunotherapy monitoring with melanoma patients. Overall, AccuScan provides a highly accurate WGS solution for MRD, empowering circulating tumor DNA detection at parts per million range without high sample input nor personalized reagents. One Sentence Summary: AccuScan showed remarkable ultra-low limit of detection with a short turnaround time, low sample requirement and a simple workflow for MRD detection.

4.
J Transl Med ; 21(1): 824, 2023 Nov 17.
Artigo em Inglês | MEDLINE | ID: mdl-37978537

RESUMO

BACKGROUND: The morbidity of cancer keeps growing worldwide, and among that, the colorectal cancer (CRC) has jumped to third. Existing early screening tests for CRC are limited. The aim of this study was to develop a diagnostic strategy for CRC by plasma metabolomics. METHODS: A targeted amino acids metabolomics method was developed to quantify 32 plasma amino acids in 130 CRC patients and 216 healthy volunteers, to identify potential biomarkers for CRC, and an independent sample cohort comprising 116 CRC subjects, 33 precancerosiss patients and 195 healthy volunteers was further used to validate the diagnostic model. Amino acids-related genes were retrieved from Gene Expression Omnibus and Molecular Signatures Database and analyzed. RESULTS: Three were chosen out of the 32 plasma amino acids examined. The tryptophan / sarcosine / glutamic acid -based receiver operating characteristic (ROC) curve showed the area under the curve (AUC) of 0.955 (specificity 83.3% and sensitivity 96.8%) for all participants, and the logistic regression model were used to distinguish between early stage (I and II) of CRC and precancerosiss patients, which showed superiority to the commonly used carcinoembryonic antigen. The GO and KEGG enrichment analysis proved many alterations in amino acids metabolic pathways in tumorigenesis. CONCLUSION: This altered plasma amino acid profile could effectively distinguish CRC patients from precancerosiss patients and healthy volunteers with high accuracy. Prognostic tests based on the tryptophan/sarcosine/glutamic acid biomarkers in the large population could assess the clinical significance of CRC early detection and intervention.


Assuntos
Aminoácidos , Neoplasias Colorretais , Humanos , Triptofano , Sarcosina , Biomarcadores Tumorais/genética , Metabolômica , Neoplasias Colorretais/diagnóstico , Neoplasias Colorretais/genética , Neoplasias Colorretais/metabolismo , Glutamatos
5.
Cell Rep ; 42(11): 113362, 2023 11 28.
Artigo em Inglês | MEDLINE | ID: mdl-37938970

RESUMO

Upregulation of FGL1 helps tumors escape from immune surveillance, and therapeutic antibodies targeting FGL1 have potential as another immune checkpoint inhibitor. However, the underlying mechanism of high FGL1 protein level in cancers is not well defined. Here, we report that FBXO38 interacts with and ubiquitylates FGL1 to negatively regulate its stability and to mediate cancer immune response. Depletion of FBXO38 markedly augments FGL1 abundance, not only suppressing CD8+ T cell infiltration and enhancing immune evasion of tumor but also increasing inflammation in mice. Importantly, we observe a negative correlation of FBXO38 with FGL1 and IL-6 in non-small cell lung cancer specimens. FGL1 and IL-6 levels positively correlate with TNM (tumor, lymph node, metastasis) stages, while FBXO38 and the infiltrating CD8+ T cells negatively correlate with TNM stages. Our study identifies a mechanism regulating FGL1 stability and a target to enhance the immunotherapy and suggests that the combination of anti-FGL1 and anti-IL-6 is a potential therapeutic strategy for cancer immunotherapy.


Assuntos
Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , Animais , Camundongos , Linfócitos T CD8-Positivos , Inflamação , Interleucina-6 , Ubiquitinação
6.
J Alzheimers Dis ; 95(4): 1709-1722, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37718803

RESUMO

BACKGROUND: Alzheimer's disease (AD) is the leading cause of dementia, with its prevalence increasing as the global population ages. AD is a multifactorial and intricate neurodegenerative disease with pathological changes varying from person to person. Because the mechanism of AD is highly controversial, effective treatments remain a distant prospect. Currently, one of the most promising hypotheses posits mitochondrial dysfunction as an early event in AD diagnosis and a potential therapeutic target. OBJECTIVE: Here, we adopted a systems medicine strategy to explore the mitochondria-related mechanisms of AD. Then, its implications for discovering nutrients combatting the disease were demonstrated. METHODS: We employed conditional mutual information (CMI) to construct AD gene dependency networks. Furthermore, the GeneRank algorithm was applied to prioritize the gene importance of AD patients and identify potential anti-AD nutrients targeting crucial genes. RESULTS: The results suggested that two highly interconnected networks of mitochondrial ribosomal proteins (MRPs) play an important role in the regulation of AD pathology. The close association between mitochondrial ribosome dysfunction and AD was identified. Additionally, we proposed seven nutrients with potential preventive and ameliorative effects on AD, five of which have been supported by experimental reports. CONCLUSIONS: Our study explored the important regulatory role of MRP genes in AD, which has significant implications for AD prevention and treatment.

7.
Nutrients ; 15(15)2023 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-37571354

RESUMO

PURPOSE: The purpose of this study was to investigate the association between moderate to vigorous physical activity (MVPA), sedentary behavior, fruit and vegetable intake, and the risk of sarcopenia among older Chinese adults. METHODS: This cross-sectional study enrolled 5418 older Chinese adults who participated in the Study on Global Aging and Adult Health (SAGE). Participants reported information about their physical activity, sedentary behavior, and dietary habits (fruit and vegetable intake). Sarcopenia was defined as the presence of low skeletal muscle mass and either a slow gait speed or weak handgrip strength. A multiple logistic regression model was employed to determine the relationship between MVPA, sedentary behavior, fruit and vegetable intake, and the risk of sarcopenia. RESULTS: Only 32.63% of participants met all three recommendations (for MVPA, sedentary behavior, and fruit and vegetable intake). Compared with meeting none of the recommendations, meeting all three recommendations was associated with a lower risk of sarcopenia (OR = 0.63, 95% CI = 0.41-0.98). Moreover, meeting the recommendation for sufficient fruit and vegetable intake (OR = 0.69, 95% CI = 0.58-0.83), MVPA and fruit/vegetable intake (OR = 0.67, 95% CI = 0.52-0.86), and sedentary behavior and fruit/vegetable intake (OR = 0.69, 95% CI = 0.48-0.98) was associated with a lower risk of sarcopenia. CONCLUSION: Our findings indicate that in this large representative sample of older Chinese adults, meeting lifestyle recommendations for MVPA, sedentary behavior, and fruit and vegetable intake protected against sarcopenia.


Assuntos
Sarcopenia , Verduras , Humanos , Adulto , Pessoa de Meia-Idade , Idoso , Frutas , Sarcopenia/epidemiologia , Sarcopenia/prevenção & controle , Estudos Transversais , Força da Mão , Comportamento Sedentário , População do Leste Asiático , Exercício Físico/fisiologia
8.
Eur Geriatr Med ; 14(5): 1059-1064, 2023 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-37392358

RESUMO

PURPOSE: We aimed to determine the best machine learning (ML) regression model for predicting grip strength in adults above 65 years using various independent variables, such as body composition, blood pressure, and physical performance. METHODS: The data comprised 107,290 participants, of whom 33.3% were male and 66.7% were female in Korean National Fitness Award Data from 2009 to 2019. The dependent variable was grip strength, which was calculated as the mean of right and left grip strength values. RESULTS: The results showed that the CatBoost Regressor had the lowest mean squared error (M [Formula: see text] SE:16.659 ± 0.549) and highest R2 value (M [Formula: see text] SE:0.719 ± 0.009) among the seven prediction models tested. The importance of independent variables in facilitating model learning was also determined, with the Figure-of-8 walk test being the most significant. These findings suggest that walking ability and grip strength are closely related, and the Figure-of- 8 walk test is a reasonable indicator of grip strength in older adults. CONCLUSION: The findings of this study can be used to develop more accurate predictive models of grip strength in older adults.

9.
ACS Appl Mater Interfaces ; 15(30): 36190-36200, 2023 Aug 02.
Artigo em Inglês | MEDLINE | ID: mdl-37463433

RESUMO

The use of bismuth (Bi) as an anode material in nickel-metal batteries has gained significant attention due to its highly reversible redox reaction and suitable operating conditions. However, the cycling stability and flexibility of nickel-bismuth (Ni//Bi) batteries need to be further improved. This paper employs a facile electrodeposition technique to prepare Bi nanosheets uniformly grown on a porous carbon cloth (PCC), denoted as Bi-PCC electrodes. The Bi-PCC electrode portrays a specific surface area and good wettability that enable fast charge transfer and ion transport channels. Consequently, the Bi-PCC electrode demonstrates a high specific capacity of up to 297.1 mAh g-1 at 2 A g-1, with a capacity retention of up to 71.5% at 2-40 A g-1 and an impressive capacity retention of 79.9% after 1000 cycles at 2-40 A g-1. More importantly, the flexible rechargeable Ni//Bi battery (denoted as Ni(OH)2-PCC//Bi-PCC) with Bi-PCC as the anode and Ni(OH)2-PCC as the cathode has excellent electrochemical performance. The Ni(OH)2-PCC//Bi-PCC battery boasts a remarkable capacity retention of 93.6% after 3000 cycles at 10 A g-1. Further, the cell presents a maximum energy density of 73.1 Wh kg-1 and an impressive power density of 11.9 kW kg-1.

10.
J Transl Med ; 21(1): 421, 2023 06 29.
Artigo em Inglês | MEDLINE | ID: mdl-37386465

RESUMO

BACKGROUND: We aimed to evaluate whether extracellular vesicles (EV)-derived microRNAs (miRNAs) can be used as biomarkers for advanced adenoma (AA) and colorectal cancer (CRC). METHODS: We detected the changes in the plasma EV-delivered miRNA profiles in healthy donor (HD), AA patient, and I-II stage CRC patient groups using miRNA deep sequencing assay. We performed the TaqMan miRNA assay using 173 plasma samples (two independent cohorts) from HDs, AA patients, and CRC patients to identify the candidate miRNA(s). The accuracy of candidate miRNA(s) in diagnosing AA and CRC was determined using the area under the receiver-operating characteristic curve (AUC) values. Logistic regression analysis was performed to evaluate the association of candidate miRNA(s) as an independent factor for the diagnosis of AA and CRC. The role of candidate miRNA(s) in the malignant progression of CRC was explored using functional assays. RESULTS: We screened and identified four prospective EV-delivered miRNAs, including miR-185-5p, which were significantly upregulated or downregulated in AA vs. HD and CRC vs. AA groups. In two independent cohorts, miR-185-5p was the best potential biomarker with the AUCs of 0.737 (Cohort I) and 0.720 (Cohort II) for AA vs. HD diagnosis, 0.887 (Cohort I) and 0.803 (Cohort II) for CRC vs. HD diagnosis, and 0.700 (Cohort I) and 0.631 (Cohort II) for CRC vs. AA diagnosis. Finally, we demonstrated that the upregulated expression of miR-185-5p promoted the malignant progression of CRC. CONCLUSION: EV-delivered miR-185-5p in the plasma of patients is a promising diagnostic biomarker for colorectal AA and CRC. Trial registration The study protocol was approved by the Ethics Committee of Changzheng Hospital, Naval Medical University, China (Ethics No. 2022SL005, Registration No. of China Clinical Trial Registration Center: ChiCTR220061592).


Assuntos
Adenoma , Neoplasias Colorretais , Vesículas Extracelulares , MicroRNAs , Humanos , Estudos Prospectivos , MicroRNAs/genética , Adenoma/diagnóstico , Adenoma/genética , Neoplasias Colorretais/diagnóstico , Neoplasias Colorretais/genética
11.
Opt Express ; 31(12): 19754-19765, 2023 Jun 05.
Artigo em Inglês | MEDLINE | ID: mdl-37381384

RESUMO

We report a sub-terahertz scattering-type scanning near-field microscope (sub-THz s-SNOM) which uses a 6 mm long metallic tip driven by a quartz tuning fork as the near-field probe. Under continuous-wave illumination by a 94 GHz Gunn diode oscillator, terahertz near-field images are obtained by demodulating the scattered wave at both the fundamental and the second harmonic of the tuning fork oscillation frequency together with the atomic-force-microscope (AFM) image. The terahertz near-field image of a gold grating with a period of 2.3 µm obtained at the fundamental modulation frequency agrees well with the AFM image. The experimental relationship between the signal demodulated at the fundamental frequency and the tip-sample distance is well fitted with the coupled dipole model indicating that the scattered signal from the long probe is mainly contributed by the near-field interaction between the tip and the sample. This near-filed probe scheme using quartz tuning fork can adjust the tip length flexibly to match the wavelength over the entire terahertz frequency range and allows for operation in cryogenic environment.

12.
Front Genet ; 14: 1202409, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37303949

RESUMO

Spatially resolved transcriptomics (SRT) provides an unprecedented opportunity to investigate the complex and heterogeneous tissue organization. However, it is challenging for a single model to learn an effective representation within and across spatial contexts. To solve the issue, we develop a novel ensemble model, AE-GCN (autoencoder-assisted graph convolutional neural network), which combines the autoencoder (AE) and graph convolutional neural network (GCN), to identify accurate and fine-grained spatial domains. AE-GCN transfers the AE-specific representations to the corresponding GCN-specific layers and unifies these two types of deep neural networks for spatial clustering via the clustering-aware contrastive mechanism. In this way, AE-GCN accommodates the strengths of both AE and GCN for learning an effective representation. We validate the effectiveness of AE-GCN on spatial domain identification and data denoising using multiple SRT datasets generated from ST, 10x Visium, and Slide-seqV2 platforms. Particularly, in cancer datasets, AE-GCN identifies disease-related spatial domains, which reveal more heterogeneity than histological annotations, and facilitates the discovery of novel differentially expressed genes of high prognostic relevance. These results demonstrate the capacity of AE-GCN to unveil complex spatial patterns from SRT data.

13.
Health Sci Rep ; 6(6): e1307, 2023 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-37313533

RESUMO

Background and Aims: The annual incidence of early-onset colorectal cancer (EOCRC) is increasing at an alarming rate. The prognosis of EOCRC remains controversial, and whether the early onset is a risk factor for colorectal cancer remains unclear. Methods: We searched four electronic bibliographic databases from database inception to April 25, 2022 for studies that included both early- and later-onset patients and performed a prognostic analysis. Random-effects models were used to summarize the prognostic information extracted by the investigators, including overall survival (OS), cancer-special survival (CSS), and disease-free survival (DFS). Network meta-analysis (NMA) was used to compare patients' long-term prognoses in different age subgroups. Results: After 694 reports were screened, 13 studies were included in the final analysis, with a total of 448,781 CRC cases. In the meta-analysis of the 5-year OS, EOCRC had a better prognosis compared to LOCRC (hazard ratio [HR] 0.87, 95% confidence interval [CI], 0.74-0.99; relative risk [RR] 0.83, 95% CI, 0.78-0.89). No difference in prognosis was found between the two groups in terms of 5-year CSS (RR 0.99, 95% CI, 0.93-1.05), 5-year DFS (RR 0.90, 95% CI, 0.74-1.09), and short-term OS. In the NMA, patients aged <30 years had the worst outcome (surface under the cumulative ranking curve [SUCRA], 15.8%) in 5-year OS; consistent results were observed in the analysis of 5-year CSS (<30 years, SUCRA 4.5%), but the difference was not statistically significant. Conclusion: Although patients with early-onset CRC had better OS than those with later-onset CRC, there was no difference in the CSS. Meanwhile, the trend for survival was worse in younger patients, especially in those ages 18-29 years. Thus, more attention should be paid to early diagnosis and treatment of EOCRC. Systematic Review and Meta­Analysis Registration: The systematic review and Meta-analysis protocol was registered with PROSPERO (registration number CRD42022334697).

14.
Chem Sci ; 14(25): 7016-7025, 2023 Jun 28.
Artigo em Inglês | MEDLINE | ID: mdl-37389262

RESUMO

The dark-colored viologen radical cations are unstable in air and easily fade, thus greatly limiting their applications. If a suitable substituent is introduced into the structure, it will have the dual function of chromism and luminescence, which will broaden its application field. Here, Vio1·2Cl and Vio2·2Br were synthesized by introducing aromatic acetophenone and naphthophenone substituents into the viologen structure. The keto group (-CH2CO-) on the substituents is prone to isomerize into the enol structure (-CH[double bond, length as m-dash]COH-) in organic solvents, especially in DMSO, resulting in a larger conjugated system to stabilize the molecular structure and enhance fluorescence. The time-dependent fluorescence spectrum shows obvious keto-to-enol isomerization-induced fluorescence enhancement. The quantum yield also increased significantly (T = 1 day, ΦVio1 = 25.81%, ΦVio2 = 41.44%; T = 7 days, ΦVio1 = 31.48%, and ΦVio2 = 54.40%) in DMSO. The NMR and ESI-MS data at different times further confirmed that the fluorescence enhancement was caused by isomerization, and no other fluorescent impurities were produced in solution. DFT calculations show that the enol form is almost coplanar throughout the molecular structure, which is conducive to stabilizing the structure and enhancing fluorescence. The fluorescence emission peaks of the keto and enol structures of Vio12+ and Vio22+ were at 416-417 nm and 563-582 nm, respectively. The fluorescence relative oscillator strength of Vio12+ and Vio22+ enol structures is significantly higher than that of keto structures (f value changes from 1.53 to 2.63 for Vio12+ and from 1.62 to 2.81 for Vio22+), indicating stronger fluorescence emission of the enol structure. The calculated results are in good agreement with the experimental results. Vio1·2Cl and Vio2·2Br are the first examples of isomerization-induced fluorescence enhancement of viologen derivatives, which shows strong solvatofluorochromism under UV light, making up for the disadvantage that it is easy for a viologen radical to fade in air, and providing a new strategy for designing and synthesizing viologen materials with strong fluorescence.

15.
Opt Express ; 31(6): 10720-10731, 2023 Mar 13.
Artigo em Inglês | MEDLINE | ID: mdl-37157613

RESUMO

To satisfy the demand for broadband and high-sensitivity terahertz detectors, we designed and verified a broadband terahertz detector built with antenna-coupled AlGaN/GaN high-electron-mobility transistors (HEMTs). Eighteen pairs of dipole antennas with different center frequency from 0.24 to 7.4 THz are arrayed into a bow-tie pattern. The corresponding eighteen transistors have common a source and a drain but different gated channels coupled by the corresponding antennas. The photocurrents generated by each gated channel are combined in the drain as the output port. With incoherent terahertz radiation from a hot blackbody in a Fourier-transform spectrometer (FTS), the detector exhibits a continuous response spectrum from 0.2 to 2.0 THz at 298 K and from 0.2 to 4.0 THz at 77 K, respectively. The results agree well with simulations taking into account the silicon lens, antenna and blackbody radiation law. The sensitivity is characterized under coherent terahertz irradiation, the average noise-equivalent power (NEP) is about 188 p W/H z at 298 K and 19 p W/H z at 77 K from 0.2 to 1.1 THz, respectively. A maximum optical responsivity of 0.56 A/W and a minimum NEP of 7.0 p W/H z at 0.74 THz are achieved at 77 K. The blackbody response spectrum is divided by the blackbody radiation intensity to obtain a performance spectrum, which is calibrated by measuring coherence performance from 0.2 to 1.1 THz to evaluate detector performance at frequencies above 1.1 THz. At 298 K, the NEP is about 1.7 n W/H z at 2.0 THz. At 77 K, the NEP is about 3 n W/H z at 4.0 THz. For further improvements in sensitivity and bandwidth, high-bandwidth coupling components, smaller series resistance, smaller gate lengths and high-mobility materials need to be considered.

16.
Brief Bioinform ; 24(4)2023 07 20.
Artigo em Inglês | MEDLINE | ID: mdl-37253698

RESUMO

Spatially resolved transcriptomics (SRT) enable the comprehensive characterization of transcriptomic profiles in the context of tissue microenvironments. Unveiling spatial transcriptional heterogeneity needs to effectively incorporate spatial information accounting for the substantial spatial correlation of expression measurements. Here, we develop a computational method, SpaSRL (spatially aware self-representation learning), which flexibly enhances and decodes spatial transcriptional signals to simultaneously achieve spatial domain detection and spatial functional genes identification. This novel tunable spatially aware strategy of SpaSRL not only balances spatial and transcriptional coherence for the two tasks, but also can transfer spatial correlation constraint between them based on a unified model. In addition, this joint analysis by SpaSRL deciphers accurate and fine-grained tissue structures and ensures the effective extraction of biologically informative genes underlying spatial architecture. We verified the superiority of SpaSRL on spatial domain detection, spatial functional genes identification and data denoising using multiple SRT datasets obtained by different platforms and tissue sections. Our results illustrate SpaSRL's utility in flexible integration of spatial information and novel discovery of biological insights from spatial transcriptomic datasets.


Assuntos
Perfilação da Expressão Gênica , Aprendizagem , Transcriptoma
17.
J Ethnopharmacol ; 314: 116478, 2023 Oct 05.
Artigo em Inglês | MEDLINE | ID: mdl-37121449

RESUMO

ETHNOPHARMACOLOGICAL RELEVANCE: Salvia miltiorrhiza Bunge is a widely used traditional Chinese medicine with anticholinesterase, antitumor, and anti-inflammatory. Total Tanshinones (TTN), the most significant active ingredient of Salvia miltiorrhiza Bunge, exerts anti-inflammatory activity. However, the protective mechanism of total Tanshinones on acute lung injury (ALI) still needs to be explored. AIM OF THIS STUDY: In this study, the underlying mechanisms of TTN to treat with ALI were investigated in vitro and in vivo. MATERIALS AND METHODS: Cell experiments established an in vitro model of LPS-induced J774A.1 and MH-S macrophages to verify the mechanism. The levels of inflammatory cytokines (TNF-α, IL-6 and IL-1ß) were estimated by ELISA. The changes of ROS, Ca2+ and NO were detected by flow cytometry. The expression levels of proteins related to the NLRP3 inflammasome were determined by Western blotting. The effect of TTN on NLRP3 inflammasome activation was examined by immunofluorescence analysis of caspase-1 p20. Male BALB/c mice were selected to establish the ALI model. The experiment was randomly divided into six groups: control, LPS, LPS + si-NC, LPA + si-Nek7, LPS + TTN, and DEX. Pathological alterations were explored by H&E staining. The expression levels of proteins related to the NLRP3 inflammasome were analyzed by Western blotting. RESULTS: TTN decreased pro-inflammatory cytokines levels like TNF-α, IL-6, IL-1ß, NO, and ROS in alveolar macrophages. TTN bound to NIMA-related kinase 7 (NEK7), a new therapeutic protein to modulate NLRP3 inflammasome and PLCγ2-PIP2 signaling pathway. In ALI mice, LPS enhanced IL-1ß levels in the serum, lung tissues, and bronchoalveolar lavage fluid (BALF),which were reversed by TTN. TTN decreased cleaved-caspase-1 and NLRP3 expressions in lung tissues. When Nek7 was knocked down in mice by siRNA, the syndrome of ALI in mice was significantly suppressed, of which the effect was similar to that of TTN. CONCLUSIONS: This research demonstrates that TTN alleviated ALI by binding to NEK7 in vitro and in vivo to modulate NLRP3 inflammasome activation and PLCγ2-PIP2 signaling pathways.


Assuntos
Lesão Pulmonar Aguda , Inflamassomos , Masculino , Camundongos , Animais , Inflamassomos/metabolismo , Proteína 3 que Contém Domínio de Pirina da Família NLR/metabolismo , Fator de Necrose Tumoral alfa/farmacologia , Interleucina-6 , Lipopolissacarídeos/farmacologia , Fosfolipase C gama/metabolismo , Espécies Reativas de Oxigênio/metabolismo , Lesão Pulmonar Aguda/induzido quimicamente , Lesão Pulmonar Aguda/tratamento farmacológico , Lesão Pulmonar Aguda/prevenção & controle , Transdução de Sinais , Citocinas/farmacologia , Anti-Inflamatórios/efeitos adversos , Caspases/metabolismo , Camundongos Endogâmicos C57BL
18.
Front Oncol ; 13: 1109464, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36910607

RESUMO

Main point: Our retrospective analysis of a large number of cases found in patients with primary colorectal cancer (CRC) carrying positive HBsAg inhibited the occurrence of synchronous liver metastases (SLM). However, liver cirrhosis caused by non-HBV factors promoted the occurrence of SLM. Objectives: This study aimed to investigate the effect of HBV on the occurrence of synchronous liver metastases (SLM) of colorectal cancer (CRC). Methods: Univariate and multivariate analyses were used to analyze the influence of clinical parameters on the occurrence of SLM. Results: A total of 6, 020 patients with primary CRC were included in our study, of which 449 patients carrying HBsAg(+) accounted for 7.46%. 44 cases of SLM occurred in the HBsAg(+) group, accounting for 9.80%, which was much lower than 13.6% (758/5571) in the HBsAg(-) group (X=5.214, P=0.022). Among CRC patients with HBsAg(-), the incidence of SLM was 24.9% and 14.9% in the group with high APRI and FIB-4 levels, respectively, which were significantly higher than that in the compared groups (12.3% and 12.5%, all P<0.05). Compared with the control group, female patients, late-onset patients, and HBV-infective patients had lower risks of SLM (HR=0.737, 95%CI: 0.614-0.883, P<0.001; HR=0.752, 95%CI: 0.603-0.943, P=0.013; HR=0.682, 95%CI: 0.473-0.961, P=0.034). Conclusions: The carriage of HBsAg(+) status inhibited the occurrence of SLM from CRC. HBV-causing liver cirrhosis did not further influence the occurrence of SLM, whereas non-HBV-factor cirrhosis promoted the occurrence of SLM. Nevertheless, this still required prospective data validation.

19.
Nanomaterials (Basel) ; 13(5)2023 Feb 27.
Artigo em Inglês | MEDLINE | ID: mdl-36903766

RESUMO

The integrated structure of graphene single-electron transistor and nanostrip electrometer was prepared using the semiconductor fabrication process. Through the electrical performance test of the large sample number, qualified devices were selected from low-yield samples, which exhibited an obvious Coulomb blockade effect. The results show that the device can deplete the electrons in the quantum dot structure at low temperatures, thus, accurately controlling the number of electrons captured by the quantum dot. At the same time, the nanostrip electrometer coupled with the quantum dot can be used to detect the quantum dot signal, that is, the change in the number of electrons in the quantum dot, because of its quantized conductivity characteristics.

20.
Front Oncol ; 13: 1001819, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36998438

RESUMO

Background: Diversion colitis (DC) is nonspecific inflammation of the distal intestinal mucosa following disruption of colonic continuity with colonic dysfunction. The colonscopic score is a good tool for differentiating the severity of patients with DC. At present, no studies have analyzed the pathogenesis of DC from the perspective of the diversity and and differences of intestinal flora. Methods: Retrospective study: Clinical information were collected from patients with low rectal cancer admitted to the Department of Anorectal Surgery, Changzheng Hospital, from April 2017 to April 2019. These patients underwent laparoscopic low anterior resection (LAR) combined with terminal ileum enterostomy (dual-chamber). We used chi-square test to comparethe clinical baseline information, clinical symptoms, and colonscopic characteristics between different severity of DC. Propsective oberservational study: We recruited 40 patients with laparoscopic anterior low resection combined with terminal ileum enterostomy and they were further classified into mild group and severe group according to the scores of colonscopic examinations for DC. 16s-rDNA sequencing was carried out to analyze the diversity and and differences of intestinal flora in the intestinal lavage fluid of the two groups. Results: In retrospective study, we found that age, BMI, history of diabetes, and symptoms associated with the stoma state were the independent risk factors that affect DC severity (P<0.05). Meanwhile, age, BMI, history of diabetes and colonscopic score were found to be independent risk factors affecting the severity of diarrhea after ileostomy closure surgery(P<0.05), which was consistent with our results of differentiating the severity of DC under endoscopy; In propsective oberservational study, 40 patients with low rectal cancer recruited by sample size calculation, 23 were in the mild group and 17 in the severe group. The results of 16s-rDNA sequencing showed that intestinal flora with high enrichment values primarily consisted of Bifidobacteriales and Prevotella in mild group, whereas that in the severe group consisted of Providencia and Dorea. The functional predictions on such two types of intestinal flora were mainly focused on lipid synthesis, glycan synthesis, metabolism, and amino acid metabolism pathways. Conclusion: After ileostomy closure surgery, a series of severe clinical symptoms might appear in DC patients. There are significant differences in local and systemic inflammatory responses, composition of intestinal flora between DC patients with different colonscopic scores, which provide a basis for the clinical interventional treatment for DC in patients with permanent stoma.

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