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1.
Oxid Med Cell Longev ; 2022: 6766787, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35571245

RESUMO

Background: Fructose-1,6-bisphosphatase 2 (FBP2), known as a rate-limiting enzyme in gluconeogenesis, is a tumor suppressor downregulated in various cancers. However, the role of FBP2 in oral squamous cell carcinoma (OSCC) remains largely unclear. Methods: The level of FBP2 in OSCC tissues and matched adjacent normal tissues was determined by western blot and RT-qPCR assays. In addition, analysis of FBP2 function in OSCC cells was assessed using both gain-of-function and loss-of-function studies. Results: In this study, we found that the expression of FBP2 was remarkably downregulated in OSCC tissues and OSCC cells. Overexpression of FBP2 suppressed the viability, proliferation, migration, and glycolysis of OSCC cells, whereas FBP2 knockdown exhibited the opposite results. Moreover, downregulation of FBP2 promoted the growth and glycolysis of OSCC cells in nude mice in a xenograft model. Specifically, FBP2 colocalizes with the c-Myc transcription factor in the nucleus. Significantly, inhibitory effects of FBP2 overexpression on the viability, proliferation, migration, and glycolysis of OSCC cells were reversed by c-Myc overexpression. Conclusion: Collectively, FBP2 could suppress the proliferation, migration and glycolysis in OSCC cells through downregulation of c-Myc. Our study revealed a FBP2-c-Myc signaling axis that regulates OSCC glycolysis and may provide a potential intervention strategy for OSCC treatment.

2.
Front Cell Dev Biol ; 10: 885440, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35573682

RESUMO

Monatomic ions play critical biological roles including maintaining the cellular osmotic pressure, transmitting signals, and catalyzing redox reactions as cofactors in enzymes. The ability to visualize monatomic ion concentration, and dynamic changes in the concentration, is essential to understanding their many biological functions. A growing number of genetically encodable and synthetic indicators enable the visualization and detection of monatomic ions in biological systems. With this review, we aim to provide a survey of the current landscape of reported indicators. We hope this review will be a useful guide to researchers who are interested in using indicators for biological applications and to tool developers seeking opportunities to create new and improved indicators.

3.
Front Plant Sci ; 13: 825492, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35574144

RESUMO

Nitrogen (N) deposition significantly affects the growth and the function of invasive clonal plants. However, the effects of heterogeneous N supply with different frequencies on the growth and the potential contribution of clonal integration in invasion plants are still unclear, especially in the complex environment considering ramet damage. To address this question, apical and basal ramets of the clonal invader Hydrocotyle vulgaris were connected or disconnected, N was added to the basal ramets with a high frequency, a low frequency, or no supply, and the total N quantity was the same for the different frequency. Furthermore, 8 aphids were placed on the apical ramets, and 30% of each leaf was cut off to cause damage. The connection between ramets significantly increased the biomass, total carbon (C), and total N of the basal and apical ramets. Higher frequency N supply significantly increased the biomass, total C, and total N of the basal ramets and the entire clonal fragment biomass. The damage had no significant effect on the growth of basal and apical ramets. Especially, under the high N frequency and ramet damage condition, the connection between ramets more significantly increased the biomass, total C, and total N of the apical ramets and the entire clonal fragment biomass. In addition, the uptake rates of 15 NH 4 + and 15 NO 3 - in H. vulgaris had no significant difference, and N supply increased the uptake rates of 15 NH 4 + and 15 NO 3 - of the basal ramets. Our results suggest that both higher frequency N supply and clonal integration are beneficial to the growth of H. vulgaris. Moreover, the heterogeneous N supply with high frequency and ramet damage increases the benefits of clonal integration in H. vulgaris. These findings improve our understanding of the response of clonal invader H. vulgaris to nitrogen deposition and ramet damage.

4.
J Clin Lab Anal ; : e24484, 2022 May 13.
Artigo em Inglês | MEDLINE | ID: mdl-35561269

RESUMO

PURPOSE: Immunotherapy is changing head and neck squamous cell carcinoma (HNSCC) treatment pattern. According to the Chinese Society of Clinical Oncology (CSCO) guidelines, immunotherapy has been deemed as first-line recommendation for recurrent/metastatic HNSCC, marking that advanced HNSCC has officially entered the era of immunotherapy. Long non-coding RNAs (lncRNAs) impact every step of cancer immunity. Therefore, reliable immune-lncRNAs able to accurately predict the immune landscape and survival of HNSCC are crucial to clinical management. METHODS: In the current study, we downloaded the transcriptomic and clinical data of HNSCC from The Cancer Genome Atlas and identified differentially expressed immune-related lncRNAs (DEir-lncRNAs). Further then, Cox and least absolute shrinkage and selection operator (LASSO) regression analyses were performed to identify proper DEir-lncRNAs to construct optimal risk model. Low-risk and high-risk groups were classified based on the optimal cut-off value generated by the areas under curve for receiver operating characteristic curves (AUC), and Kaplan-Meier survival curves were utilized to validate the prediction model. We then evaluated the model based on the clinical factors, immune cell infiltration, and chemotherapeutic and immunotherapeutic efficacy between two groups. RESULTS: In our study, we identified 256 Deir-lncRNAs in HNSCC. A total of 18 Deir-lncRNA pairs (consisting of 35 Deir-lncRNAs) were used to construct a risk model significantly associated with survival of HNSCC. Cox proportional hazard regression analysis confirmed that our risk model could be served as an independent prognostic indicator. Besides, HNSCC patients with low-risk score significantly enriched of CD8+ T cell, and corelated with high chemosensitivity and immunotherapeutic sensitivity. CONCLUSION: Our risk model could be served as a promising clinical prediction indicator, effective discoursing of the immune cell infiltration of HNSCC patients, and distinguishing patients who could benefit from chemotherapy and immunotherapy.

5.
Cancer Med ; 2022 May 14.
Artigo em Inglês | MEDLINE | ID: mdl-35567376

RESUMO

BACKGROUND: Pyroptosis plays an essential function in carcinogenesis and the antitumor immune response. Herein, we constructed a pyroptosis-related long noncoding RNA (prLncRNA) signature to predict therapeutic effects and outcomes for head and neck squamous cell carcinoma (HNSCC) patients. METHODS: Patients obtained from the TCGA-HNSC project were divided randomly into the training as well as the validation sets at a ratio of 7:3. A novel prognostic prLncRNA signature was constructed from the results of the training set using the least absolute shrinkage and selection operation. The medium value was used as the basis for categorizing all HNSCC patients into a low- or high-risk cohort. Cox regression and Kaplan-Meier (KM) survival analyses were executed to estimate the prognostic value. We also evaluated the functional enrichment, tumor microenvironment, immune cell infiltration, and the sensitivity to chemotherapy and immunotherapy between the high- and low-risk cohorts. RESULTS: Nineteen prognostic prlncRNAs were identified to establish the prognostic signature. Multivariate Cox regression and KM survival analyses confirmed that this prlncRNA signature might serve as an independent prognostic indicator of patient survival, which was subsequently confirmed using a validating dataset. Multiple ROC curves indicated the prlncRNA signature presented a more predictive power than clinicopathological factors (age, sex, tumor grade, and tumor stage). GO, KEGG, and GSEA enrichment analysis disclosed several immune-related pathways which appeared to be enhanced in the low-risk cohort. ESTIMATE, CIBERSORT, and ssGSEA algorithms indicated considerable differences in the tumor microenvironment and immune cell infiltration in the low- and high-risk cohorts. Furthermore, the low-risk cohort was predicted to achieve a better response to immunotherapeutic drugs, while in contrast, the high-risk cohort would be more sensitive to chemotherapy drugs. CONCLUSIONS: Our findings robustly demonstrate that our constructed prlncRNA signature could serve as an efficient indicator of prognosis, immunotherapy response, and chemosensitivity for HNSCC patients.

6.
J Clin Lab Anal ; : e24480, 2022 May 06.
Artigo em Inglês | MEDLINE | ID: mdl-35522142

RESUMO

BACKGROUND: Previous studies have determined that necroptosis-related genes are potential biomarkers in head and neck squamous cell carcinoma (HNSCC). Herein, we established a novel risk model based on necroptosis-related lncRNAs (nrlncRNAs) to predict the prognosis of HNSCC patients. METHODS: Transcriptome and related information were obtained from TCGA database, and an nrlncRNA signature was established based on univariate Cox analysis and least absolute shrinkage and selection operator Cox regression. Kaplan-Meier analysis and time-dependent receiver operating characteristic (ROC) analysis were used to evaluate the model, and a nomogram for survival prediction was established. Gene set enrichment analysis, immune analysis, drug sensitivity analysis, correlation with N6-methylandenosin (m6A), and tumor stemness analysis were performed. Furthermore, the entire set was divided into two clusters for further discussion. RESULTS: A novel signature was established with six nrlncRNAs. The areas under the ROC curves (AUCs) for 1-, 3-, and 5-year overall survival (OS) were 0.699, 0.686, and 0.645, respectively. Patients in low-risk group and cluster 2 had a better prognosis, more immune cell infiltration, higher immune function activity, and higher immune scores; however, patients in high-risk group and cluster 1 were more sensitive to chemotherapy. Moreover, the risk score had negative correlation with m6A-related gene expression and tumor stemness. CONCLUSION: According to this study, we constructed a novel signature with nrlncRNA pairs to predict the survival of HNSCC patients and guide immunotherapy and chemotherapy. This may possibly promote the development of individualized and precise treatment for HNSCC patients.

7.
J Clin Epidemiol ; 2022 May 07.
Artigo em Inglês | MEDLINE | ID: mdl-35537604

RESUMO

OBJECTIVE: Nutritional screening tools should be sensitive, simple, and easy to use. Differing opinions among clinicians concern the simplicity of the three tools - the Global Leadership Initiative on Malnutrition (GLIM) criteria, Nutritional Risk Screening 2002 (NRS-2002) and Patient Generated Subjective Global Assessment (PG-SGA). For each tool, we estimate prediction of overall survival (OS) in tumor staging, sensitivity, specificity. NRS-2002 is favored by clinicians because it is simple to use. We compare its sensitivity and specificity with GLIM and PG-SGA STUDY DESIGN AND SETTING: This is an analysis of data from 1358 adult colorectal cancer patients recruited in a multicenter from July 2013 to July 2018. RESULTS: In Kaplan-Meier Models, each tool was found to be significantly predictive of overall survival - NRS-2002 (1.28), GLIM (1.49) and PG-SGA (1.42). Use of any tool improved prediction of survival at tumor staging. NRS-2002 has superior specificity (0.90) to diagnose patients without nutritional deficits (GLIM 0.62, PG-SGA 0.82). CONCLUSION: This study provides evidence for the superiority of NRS-2002 accurately identify colorectal cancer patients without nutritional limitations. Compared with the complexity of the other tools, NRS-2002 is simplest to use in routine nutritional screening. in busy clinical practice.

8.
Oxid Med Cell Longev ; 2022: 9148246, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35528525

RESUMO

Current evidences indicate that both inflammation and oxidative stress contribute to the pathogenesis of sepsis-associated skeletal muscle atrophy. However, the interaction between inflammation and oxidative stress has not been completely understood in sepsis-associated skeletal muscle atrophy. Here in the present study, a murine model of sepsis has been established by cecal ligation and puncture (CLP) with wild-type and interleukin- (IL-) 6 knockout (KO) mice. Our results suggested that IL-6 KO largely attenuated skeletal muscle atrophy as reflected by reduced protein degradation, increased cross-sectional area (CSA) of myofibers, and improved muscle contractile function (all P < 0.05). In addition, we observed that IL-6 KO promoted the expression of peroxisome proliferator-activated receptor γ coactivator-1alpha (PGC-1α) and inhibited CLP-induced mitochondrial reactive oxygen species (ROS) production in skeletal muscles (all P < 0.05). However, the knockdown of PGC-1α abolished the protective effects of IL-6 KO in CLP-induced skeletal muscle atrophy and reversed the changes in mitochondrial ROS production (all P < 0.05). Ex vivo experiments found that exogenous IL-6 inhibited PGC-1α expression, promoted mitochondrial ROS production, and induced proteolysis in C2C12 cells (all P < 0.05). Together, these results suggested that IL-6 deficiency attenuated skeletal muscle atrophy by inhibiting mitochondrial ROS production through the upregulation of PGC-1α expression in septic mice.


Assuntos
Interleucina-6 , Doenças Musculares , Sepse , Animais , Inflamação/patologia , Interleucina-6/deficiência , Camundongos , Músculo Esquelético/metabolismo , Atrofia Muscular/metabolismo , Doenças Musculares/metabolismo , Coativador 1-alfa do Receptor gama Ativado por Proliferador de Peroxissomo/metabolismo , Espécies Reativas de Oxigênio/metabolismo , Sepse/patologia , Fatores de Transcrição/metabolismo , Regulação para Cima
9.
J Orthop Surg Res ; 17(1): 259, 2022 May 12.
Artigo em Inglês | MEDLINE | ID: mdl-35551637

RESUMO

BACKGROUND: Periacetabular malignant tumor seriously endangers the life and health of patients. Hemipelvic replacement provides a good method for patients who want complete resection of the tumor while retaining or restoring the function of the affected limb. OBJECTIVE: To investigate the performance and clinical application of the new adjustable modular hemipelvic prosthesis and to compare the effects of three kinds of hemipelvic prosthesis. METHODS: In this study, 23 patients, with an average age of 44.6 years (21-75 years), were collected, who received hemipelvic replacement with new adjustable, modular, and screw-rod system hemipelvic prosthesis. Preoperative preparation was conducted on them, and operative complications were recorded. Postoperative functional follow-up was performed regularly. RESULTS: The average operation time was 319 min (170-480 min), and the average blood loss was 2813 ml (1000 mL-8000 ml). The incidence of complications was 47.8%, and type A (wound-related complications) had the highest incidence (34.8%). Postoperative dislocation occurred in 3 cases (13.0%), and no dislocation occurred in the new adjustable modular hemipelvic prosthesis group. The average MSTS score of the patients was 18.6 (10-23), and the average Harris score was 73.7 (53-87). CONCLUSIONS: The new adjustable modular hemipelvic prosthesis has the feasibility of reconstruction and good functional outcome, making it ideal for periacetabular tumors. Furthermore, preoperative tumor-feeding artery embolization and abdominal aortic balloon implantation may be an effective choice to reduce intraoperative blood loss and facilitate the operation of tumor resection.

10.
Int J Mol Sci ; 23(9)2022 Apr 21.
Artigo em Inglês | MEDLINE | ID: mdl-35562990

RESUMO

Sleep and wakefulness are basic behavioral states that require coordination between several brain regions, and they involve multiple neurochemical systems, including neuropeptides. Neuropeptides are a group of peptides produced by neurons and neuroendocrine cells of the central nervous system. Like traditional neurotransmitters, neuropeptides can bind to specific surface receptors and subsequently regulate neuronal activities. For example, orexin is a crucial component for the maintenance of wakefulness and the suppression of rapid eye movement (REM) sleep. In addition to orexin, melanin-concentrating hormone, and galanin may promote REM sleep. These results suggest that neuropeptides play an important role in sleep-wake regulation. These neuropeptides can be divided into three categories according to their effects on sleep-wake behaviors in rodents and humans. (i) Galanin, melanin-concentrating hormone, and vasoactive intestinal polypeptide are sleep-promoting peptides. It is also noticeable that vasoactive intestinal polypeptide particularly increases REM sleep. (ii) Orexin and neuropeptide S have been shown to induce wakefulness. (iii) Neuropeptide Y and substance P may have a bidirectional function as they can produce both arousal and sleep-inducing effects. This review will introduce the distribution of various neuropeptides in the brain and summarize the roles of different neuropeptides in sleep-wake regulation. We aim to lay the foundation for future studies to uncover the mechanisms that underlie the initiation, maintenance, and end of sleep-wake states.

11.
BMC Surg ; 22(1): 186, 2022 May 14.
Artigo em Inglês | MEDLINE | ID: mdl-35568886

RESUMO

BACKGROUNDS: High level of anion gap (AG) was associated with organic acidosis. This study aimed to explore the relationship between delta AG (ΔAG = AGmax - AGmin) during first 3 days after intensive care unit (ICU) admission and hospital mortality for patients admitted in the cardiothoracic surgery recovery unit (CSRU). METHODS: In this retrospective cohort study, we identified patients from the open access database called Multiparameter Intelligent Monitoring in Intensive Care III (MIMIC III). A logistic regression model was established to predict hospital mortality by adjusting confounding factors using a stepwise backward elimination method. We conducted receiver operating characteristic (ROC) curves to compare the diagnostic performance of acid-base variables. Cox regression model and Kaplan Meier curve were applied to predict patients' 90-day overall survival (OS). RESULTS: A total of 2,860 patients were identified. ΔAG was an independent predictive factor of hospital mortality (OR = 1.24 per 1 mEq/L increase, 95% CI: 1.11-1.39, p < 0.001). The area under curve (AUC) values of ΔAG suggested a good diagnostic accuracy (AUC = 0.769). We established the following formula to estimate patients' hospital mortality: Logit(P) = - 15.69 + 0.21ΔAG + 0.13age-0.21BE + 2.69AKF. After calculating Youden index, patients with ΔAG ≥ 7 was considered at high risk (OR = 4.23, 95% CI: 1.22-14.63, p = 0.023). Kaplan Meier curve demonstrated that patients with ΔAG ≥ 7 had a poorer 90-day OS (Adjusted HR = 3.20, 95% CI: 1.81-5.65, p < 0.001). CONCLUSION: ΔAG is a prognostic factor of hospital mortality and 90-day OS. More prospective studies are needed to verify and update our findings.

12.
BMC Cancer ; 22(1): 550, 2022 May 16.
Artigo em Inglês | MEDLINE | ID: mdl-35578198

RESUMO

BACKGROUND: Homologous recombination deficiency (HRD) is a molecular biomarker for administrating PARP inhibitor (PARPi) or platinum-based (Pt) chemotherapy. The most well-studied mechanism of causing HRD is pathogenic BRCA1/2 mutations, while HRD phenotype is also present in patients without BRCA1/2 alterations, suggesting other unknown factors. METHODS: The targeted next-generation sequencing (GeneseeqPrime® HRD) was used to evaluate the HRD scores of 199 patients (Cohort I). In Cohort II, a total of 85 Pt-chemotherapy-treated high-grade serous ovarian cancer (HGSOC) patients were included for investigating the role of HRD score in predicting treatment efficacy. The concurrent genomic features analyzed along HRD score evaluation were studied in a third cohort with 416 solid tumor patients (Cohort III). RESULTS: An HRD score ≥ 38 was predefined as HRD-positive by analyzing Cohort I (range: 0-107). Over 95% of the BRCA1/2-deficient cases of Cohort I were HRD-positive under this threshold. In Cohort II, Pt-sensitive patients have significantly higher HRD scores than Pt-resistant patients (median: 54 vs. 34, p = 0.031) and a significantly longer PFS was observed in HRD-positive patients (median: 548 vs. 343 days, p = 0.003). Furthermore, TP53, NCOR1, and PTK2 alterations were enriched in HRD-positive patients. In Cohort III, impaired homologous recombination repair pathway was more frequently observed in HRD-positive patients without BRCA1/2 pathogenic mutations. The alteration enrichment of TP53, NCOR1, and PTK2 observed in Cohort II was also validated by the ovarian subgroup in Cohort III. CONCLUSIONS: Using an in-house HRD evaluation method, our findings show that overall HRR gene mutations account for a significant part of HRD in the absence of BRCA1/2 aberrations, and suggest that HRD positive status might be a predictive biomarker of Pt-chemotherapy.

13.
Acupunct Med ; : 9645284221085579, 2022 May 17.
Artigo em Inglês | MEDLINE | ID: mdl-35579008

RESUMO

OBJECTIVE: To visualize and compare the sensory and autonomic innervation of the local tissues at the sites of different traditional acupuncture points in the rat forehead and face by histochemical examination. METHODS: GB14 (Yangbai), ST2 (Sibai) and ST6 (Jiache) were selected as the representative traditional acupuncture points in this study, and the local tissues at these sites were dissected in rats after perfusion followed by double or triple fluorescent histochemical staining. Here, calcitonin gene-related peptide (CGRP), tyrosine hydroxylase (TH) and vesicular acetylcholine transporter (VAChT) were used to label the sensory, sympathetic and parasympathetic nerve fibers, respectively. RESULTS: The CGRP+ sensory, TH+ sympathetic and VAChT+ parasympathetic nerve fibers were simultaneously demonstrated in the local tissues at GB14, ST2 and ST6. Although the three kinds of nerve fibers ran in parallel or intermingled with each other, by the analysis from the view of three-dimensional reconstruction, it was clear that each of them distributed in an independent pattern to their corresponding target tissues including the blood vessels, hair follicles, arrector pili and subcutaneous muscles, as well as sebaceous glands. CONCLUSION: Our study demonstrated the sensory and autonomic innervation of the local tissues at GB14, ST2 and ST6, providing neurochemical evidence indicating that the CGRP+ sensory, TH+ sympathetic and VAChT+ parasympathetic nerve fibers form a neural network at these point locations that may respond to acupuncture stimulation.

14.
J Colloid Interface Sci ; 622: 390-401, 2022 Apr 22.
Artigo em Inglês | MEDLINE | ID: mdl-35525142

RESUMO

Two well-defined CoFe bimetal oxides are prepared from Prussian blue analogues (PBAs) as precursors with designable structures, which are further explored for phosphate removal. A speed-controlled coordination strategy is used to fabricate two CoFe PBA microcrystals with different morphologies, then two regular CoFe oxides are obtained via an intermediate-temperature calcination. CoFeS, a slow-speed coordination product with truncated microcube structure, contains less coordinated water and Fe3+ in its framework, but can create more mesopores and Fe3+ in its oxidative product of CoFeST300. CoFeST300 has been demonstrated to have higher adsorption capacity and affinity for phosphate adsorption compared to that of the fast-speed coordination product, due to its more Fe3+ as effective adsorption sites via ligand exchange. Besides, the inner-sphere complexation mechanism makes CoFeST300 high selectivity for phosphate removal compared to other co-existing anions. The application performance of CoFeST300 is examined by multiple continuous treatment of actual sewage, and the result of all effluent concentrations below 0.5 mg P/L verifies a promising potential of the fabricated adsorbent for phosphorus removal. Thus, design or regulation of the precursors is an efficiency method to fabricate an ideal metal oxide for phosphate adsorption.

15.
Thorac Cancer ; 13(10): 1505-1512, 2022 May.
Artigo em Inglês | MEDLINE | ID: mdl-35394114

RESUMO

BACKGROUND: The treatment options for epidermal growth factor receptor (EGFR)-mutated non-small cell lung cancer (NSCLC) with brain metastases (BMs) include EGFR-tyrosine kinase inhibitors (TKIs), stereotactic radiosurgery (SRS), whole-brain radiotherapy, brain surgery, and antiangiogenesis therapy. As treatment options evolve, redefining optimal treatment strategies to improve survival are crucial. METHODS: A total of 150 EGFR-mutant NSCLC patients with BMs who received first- or second-generation EGFR-TKIs as first-line treatment between January 2012 and October 2019 were included in this analysis. RESULTS: After multivariate analysis, patients with the graded prognostic assessment for lung cancer using molecular markers (Lung-mol GPA) ≥3 (hazard ratio [HR]: 0.538, 95% confidence interval [CI]: 0.35-0.83), who received afatinib or erlotinib as first-line treatment (HR: 0.521, 95% CI: 0.33-0.82), underwent SRS therapy (HR: 0.531, 95% CI: 0.32-0.87), or were sequentially treated with osimertinib (HR: 0.400, 95% CI: 0.23-0.71) were associated with improved overall survival (OS). Furthermore, SRS plus EGFR-TKI provided more OS benefits in patients with Lung-mol GPA ≥3 compared with EGFR-TKI alone in our patient cohort (44.9 vs. 26.7 months, p = 0.005). The OS in patients who received sequential osimertinib therapy was significantly longer than those without osimertinib treatment (43.5 vs. 24.3 months, p < 0.001), regardless of T790 mutation status (positive vs. negative vs. unknown: 40.4 vs. 54.6 vs.43.4 months, p = 0.227). CONCLUSIONS: The study demonstrated that EGFR-mutant NSCLC patients with BMs could be precisely treated with SRS according to Lung-mol GPA ≥3. Sequential osimertinib was associated with prolonged survival, regardless of T790M status.

16.
Nat Commun ; 13(1): 1850, 2022 Apr 06.
Artigo em Inglês | MEDLINE | ID: mdl-35387971

RESUMO

Genetically-encoded biosensors based on a single fluorescent protein are widely used to visualize analyte levels or enzymatic activities in cells, though usually to monitor relative changes rather than absolute values. We report photochromism-enabled absolute quantification (PEAQ) biosensing, a method that leverages the photochromic properties of biosensors to provide an absolute measure of the analyte concentration or activity. We develop proof-of-concept photochromic variants of the popular GCaMP family of Ca2+ biosensors, and show that these can be used to resolve dynamic changes in the absolute Ca2+ concentration in live cells. We also develop intermittent quantification, a technique that combines absolute aquisitions with fast fluorescence acquisitions to deliver fast but fully quantitative measurements. We also show how the photochromism-based measurements can be expanded to situations where the absolute illumination intensities are unknown. In principle, PEAQ biosensing can be applied to other biosensors with photochromic properties, thereby expanding the possibilities for fully quantitative measurements in complex and dynamic systems.


Assuntos
Técnicas Biossensoriais , Técnicas Biossensoriais/métodos , Transferência Ressonante de Energia de Fluorescência , Corantes Fluorescentes , Ionóforos , Luz , Proteínas
17.
Front Med (Lausanne) ; 9: 860733, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35391883

RESUMO

Background: The aim of study is to investigate the influence of pulmonary function on the prognosis in patients with advanced non-small cell lung cancer (NSCLC) receiving immune checkpoint inhibitors (ICI). Patients and Methods: Data were collected retrospectively from 151 patients with stage IV NSCLC who received ICI and completed spirometry before ICI therapy in Taipei Veterans General Hospital between January 2016 and December 2020. The co-primary end points were overall survival (OS) and progression-free survival (PFS) between groups divided by 80% predicted FEV1 since ICI therapy started; the secondary outcomes were objective response rate. Results: Among 151 patients enrolled to this study, 67.5% of patients were men, 75.5% were adenocarcinoma, 24.5% had known targetable driver mutation, 33.8% received first-line ICI, and 62.8% received ICI monotherapy. The objective response rate was 24.5% and disease control rate was 54.3%. In multivariable analysis, patient with reduced FEV1 had inferior PFS (FEV1 < 80% vs. FEV1 ≥ 80%, adjusted HR = 1.80, P = 0.006) and OS (FEV1 < 80% vs. FEV1 ≥ 80%, adjusted HR = 2.50, P < 0.001). Median PFS and OS in the preserved FEV1 group (≥80% predicted FEV1) compared to the reduced FEV1 group (<80% predicted FEV1) were 5.4 vs. 2.9 months (HR = 1.76, P = 0.003) and 34.9 vs. 11.1 months (HR = 2.44, P < 0.001), respectively. The other independent prognostic factors of OS include stage IVA disease (adjusted HR = 0.57, P = 0.037), initial liver metastasis (adjusted HR = 2.00, P = 0.049), ICI monotherapy (adjusted HR = 1.73, P = 0.042) and ICI related pneumonitis (adjusted HR = 3 .44, P = 0.025). Conclusions: Reduced FEV1 is strongly associated with inferior clinical outcomes in patients with advanced NSCLC treated with ICI.

18.
Environ Sci Technol ; 56(10): 6699-6709, 2022 May 17.
Artigo em Inglês | MEDLINE | ID: mdl-35475353

RESUMO

The water shortage crisis, characterized by organic micropollutants (OMPs), urgently requires new materials and methods to deal with it. Although heteroatom doping has been developed into an effective method to modify carbon nanomaterials for various heterogeneous adsorption and catalytic oxidation systems, the active source regulated by intrinsic electron and spin structures is still obscure. Here, a series of nonmetallic element-doped (such as P, S, and Se) covalent triazine frameworks (CTFs) were constructed and applied to remove organic pollutants using the adsorption-photocatalysis process. The external mass transfer model (EMTM) and the homogeneous surface diffusion model (HSDM) were employed to describe the adsorption process. It was found that sulfur-doped CTF (S-CTF-1) showed a 25.6-fold increase in saturated adsorption capacity (554.7 µmol/g) and a 169.0-fold surge in photocatalytic kinetics (5.07 h-1), respectively, compared with the pristine CTF-1. A positive correlation between electron accumulation at the active site (N1 atom) and adsorption energy was further demonstrated with experimental results and theoretical calculations. Meanwhile, the photocatalytic degradation rates were greatly enhanced by forming a built-in electric field driven by spin polarization. In addition, S-CTF-1 still maintained a 98.3% removal of 2,2',4,4'-tetrahydroxybenzophenone (BP-2) micropollutants and 97.6% regeneration after six-cycle sequencing batch treatment in real water matrices. This work established a relation between electron and spin structures for adsorption and photocatalysis, paving a new way to design modified carbon nanomaterials to control OMPs.

19.
Global Spine J ; : 21925682221094265, 2022 Apr 09.
Artigo em Inglês | MEDLINE | ID: mdl-35403474

RESUMO

STUDY DESIGN: Retrospective cohort study. OBJECTIVES: This study aimed to explore the effect of preoperative cervical spondylosis on the heterotopic ossification (HO) formation in different locations after cervical disc replacement (CDR). METHODS: The degree of preoperative cervical spondylosis was evaluated radiologically, including the intervertebral disc, uncovertebral joints, facet joints and ligaments. The effects of cervical spondylosis on the HO formation after CDR were analyzed according to the location of HO. Multivariate logistic regression was performed to identify the independent factors. RESULTS: 149 patients with a total of 196 arthroplasty segments were involved in this study. HO, anterior HO (AHO), and posterior HO (PHO) developed in 59.69%, 22.96%, and 41.84% levels, respectively. The significant factors in univariate analysis for PHO after CDR included the disc height loss, anterior osteophytes, preoperative uncovertebral joint osteophytes and facet joint degeneration. The incidence of adjacent segment degeneration (ASD) was significantly higher in the PHO group compared to that without PHO at the last follow-up (P = .003). The disc height loss in high-grade HO was significantly more than that in low-grade group (P = .039). Multivariate analysis identified disc height loss was the only independent factor for PHO (P = .009). No significant degenerative factors related to the formation of AHO were found. CONCLUSIONS: Preoperative cervical spondylosis predominantly affected the HO formation in the posterior disc space after CDR. The disc height loss was an independent risk factor for PHO formation. Rigorous criteria for the extent of preoperative disc height loss should be used when selecting appropriate candidates for CDR.

20.
JMIR Mhealth Uhealth ; 10(4): e32435, 2022 04 08.
Artigo em Inglês | MEDLINE | ID: mdl-35394447

RESUMO

BACKGROUND: The prevalence of obesity in children and adolescents remains a global public health issue. Wearable devices may offer new opportunities for prevention and intervention in obesity. Previous systematic reviews have only examined the effect of the wearable device interventions on preventing and treating obesity in adults. However, no systematic review has provided an evaluation of wearable devices as physical activity interventions for preventing and treating obesity in children and adolescents. OBJECTIVE: The purpose of this review and meta-analysis was to evaluate the effectiveness of wearable devices as physical activity interventions on obesity-related anthropometric outcomes in children and adolescents. METHODS: Research articles retrieved from PubMed, EMBASE, Cochrane Library, Scopus, and EBSCO from inception to February 1, 2021, were reviewed. The search was designed to identify studies utilizing wearable devices for preventing and treating obesity in children and adolescents. The included studies were evaluated for risk of bias following the Cochrane recommendation. Meta-analyses were conducted to evaluate the effectiveness of wearable devices as physical activity interventions on body weight, body fat, BMI z-score (BMI-Z), BMI, and waist circumference. Subgroup analyses were performed to determine whether the characteristics of the interventions had an impact on the effect size. RESULTS: A total of 12 randomized controlled trials (3227 participants) were selected for meta-analysis. Compared with the control group, wearable device interventions had statistically significant beneficial effects on BMI (mean difference [MD] -0.23; 95% CI -0.43 to -0.03; P=.03; I2=2%), BMI-Z (MD -0.07; 95% CI -0.13 to -0.01; P=.01; I2=81%), body weight (MD -1.08; 95% CI -2.16 to -0.00; P=.05; I2=58%), and body fat (MD -0.72; 95% CI -1.19 to -0.25; P=.003; I2=5%). However, no statistically significant effect was found on waist circumference (MD 0.55; 95% CI -0.21 to 1.32; P=.16; I2=0%). The subgroup analysis showed that for participants with overweight or obesity (MD -0.75; 95% CI -1.18 to -0.31; P<.01; I2=0%), in the short-term (MD -0.62; 95% CI -1.03 to -0.21; P<.01; I2=0%), wearable-based interventions (MD -0.56; 95% CI -0.95 to -0.18; P<.01; I2=0%) generally resulted in greater intervention effect size on BMI. CONCLUSIONS: Evidence from this meta-analysis shows that wearable devices as physical activity interventions may be useful for preventing and treating obesity in children and adolescents. Future research is needed to identify the most effective physical activity indicators of wearable devices to prevent and treat obesity in children and adolescents.


Assuntos
Obesidade Pediátrica , Dispositivos Eletrônicos Vestíveis , Adolescente , Adulto , Peso Corporal , Criança , Exercício Físico , Humanos , Sobrepeso/terapia , Obesidade Pediátrica/prevenção & controle
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