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1.
J Clin Pharmacol ; 2022 Sep 09.
Artigo em Inglês | MEDLINE | ID: mdl-36083133

RESUMO

Immune checkpoint inhibitors (ICIs) have been established as the cornerstone for advanced non-small cell lung cancer, while thyroid adverse events (AEs) associated with ICIs have not been systematically documented. Therefore, we performed a meta-analysis to evaluate the effect of ICI applications on the thyroid of patients with non-small cell lung cancer. We performed a systematic search of PubMed, the Cochrane Library, Web of Science, and Embase for eligible randomized controlled trials up to November 2021. Clinical trials reporting thyroid AEs including hypothyroidism, hyperthyroidism, and thyroiditis were enrolled. The I2  statistic was also calculated to quantify the heterogeneity. Data were evaluated as risk ratio (RR) and corresponding 95%CIs. A total of 10 randomized clinical trials involving 6154 patients were included in this meta-analysis. ICI application was found to have a statistically significant higher risk of all grade hypothyroidism (RR, 7.03; P < .0001), hyperthyroidism (RR, 4.88; P < .0001), and thyroiditis (RR, 6.58; P = .0014) compared with the chemotherapy group. Moreover, we demonstrated that second-line therapy significantly increased the risk of all-grade hypothyroidism (RR, 7.03 [95%CI, 4.69-10.55]) and hyperthyroidism (RR, 4.88 [95%CI, 3.11-7.65]). Our meta-analysis manifested that regimens with ICIs may significantly increase all grades of hypothyroidism, hyperthyroidism, and thyroiditis. ICIs may certainly induce the occurrence and exacerbation of endocrine AEs compared with chemotherapy. This article is protected by copyright. All rights reserved.

2.
J Phys Chem Lett ; : 8641-8647, 2022 Sep 09.
Artigo em Inglês | MEDLINE | ID: mdl-36083282

RESUMO

Biomicroparticles such as proteins, bacterium, and cells are known to be viscoelastic, which significantly affects their performance in microfluidic applications. However, the exact effects and the quantitative study of cellular viscoelastic creep within different applications remain unclear. In this study, the cellular-deforming evolution within a filter unit was studied using a multiphysics numerical model. A general cellular creep deformation process of viscoelastic particle trapping in pores was revealed. Two featured variables, namely, the maximum surface displacement and the volumetric strain, were identified and determined to quantitatively describe the evolution. The effects of flow conditions and physical characteristics of the microparticles were studied. Furthermore, a Giardia concentration experiment was conducted using an integrated hydraulic filtration system with a porous membrane. The experimental results agreed well with the numerical analysis, indicating that, compared to pure elastic particles, it is more difficult to release cellular material matters including cells, chemical synthetic particles, and microbes from trapping due to their time-accumulated creep deformation.

3.
Clin Exp Nephrol ; 2022 Sep 09.
Artigo em Inglês | MEDLINE | ID: mdl-36083528

RESUMO

OBJECTIVE: We retrospectively analyzed risk factors on in-hospital mortality in CRRT-therapy patients with open cardiac surgery (CS)-induced acute kidney injury (AKI), to provide the clinical basis for predicting and lowering the in-hospital mortality after CS. METHODS: 84 CS-AKI patients with CRRT were divided into survival and death groups according to discharge status, and the perioperative data were analyzed with R version 4.0.2. RESULTS: There were significant differences between the two groups, including: urea nitrogen, Sequential Organ Failure Assessment (SOFA) score and vasoactive-inotropic score (VIS) on the first day after operation; VIS just before CRRT; SOFA score and negative balance of blood volume 24 h after CRRT; the incidence rate of bleeding, severe infection and MODS after operation; and the interval between AKI and CRRT. Univariate logistic regression analysis showed that SOFA score and VIS on the first day after operation; VIS just before CRRT; VIS and negative balance of blood volume 24 h after CRRT; the incidence rate of bleeding, infection and multiple organ dysfunction syndrome (MODS) after operation; bootstrap resampling analysis showed that SOFA score and VIS 24 h after CRRT, as well as the incidence of bleeding after operation were the independent risk factors. CONCLUSION: Maintaining stable hemodynamics and active prevention of bleeding are expected to decrease the in-hospital mortality.

4.
Genet Res (Camb) ; 2022: 3483498, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36072012

RESUMO

Objective: To screen the cell differentiation trajectory-related genes and build a cell differentiation trajectory-related signature for predicting the prognosis of lung adenocarcinoma (LUAD). Methods: LUAD single cell mRNA expression profile, TCGA-LUAD transcriptome data were obtained from GEO and TCGA databases. Single-cell RNA-seq data were used for cell clustering and pseudotime analysis after dimensionality reduction analysis, and the cell differentiation trajectory-related genes were acquired after differential expression analysis conducted between the main branches. Then, the consensus clustering analysis was carried out on TCGA-LUAD samples, and the GSEA analysis was performed, then the differences on the expression levels of immune checkpoint genes and immunotherapy response were compared among clusters. The prognostic model was constructed, and the GSE42127 dataset was used to validate. A nomogram evaluation model was used to predict prognosis. Results: Two subsets with distinct differentiation states were found after cell differentiation trajectory analysis. TCGA-LUAD samples were divided into two cell differentiation trajectory-related gene-based clusters, GSEA found that cluster 1 was significantly related to 20 pathways, cluster 2 was significantly enriched in three pathways, and it was also shown that clusters could better predict immune checkpoint gene expression and immunotherapy response. A six cell differentiation-related genes-based prognostic signature was constructed, and the patients in the high-risk group had poorer prognosis than those in the low-risk group. Moreover, a nomogram was constructed based on the prognostic signature and clinicopathological features, and this nomogram had strong predictive performance and high accuracy. Conclusion: The cell differentiation-related signature and the prognostic nomogram could accurately predict survival.


Assuntos
Adenocarcinoma de Pulmão , Neoplasias Pulmonares , Adenocarcinoma de Pulmão/genética , Adenocarcinoma de Pulmão/patologia , Diferenciação Celular/genética , Regulação Neoplásica da Expressão Gênica , Humanos , Neoplasias Pulmonares/diagnóstico , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/metabolismo , Prognóstico
5.
Front Physiol ; 13: 909209, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36051916

RESUMO

The prevalence rates of obesity and its complications have increased dramatically worldwide. Obesity can lead to low-grade chronic systemic inflammation, which predisposes individuals to an increased risk of morbidity and mortality. Although obesity has received considerable interest in recent years, the essential role of obesity in asthma development has not been explored. Asthma is a common chronic inflammatory airway disease caused by various environmental allergens. Obesity is a critical risk factor for asthma exacerbation due to systemic inflammation, and obesity-related asthma is listed as an asthma phenotype. A suitable model can contribute to the understanding of the in-depth mechanisms of obese asthma. However, stable models for simulating clinical phenotypes and the impact of modeling on immune response vary across studies. Given that inflammation is one of the central mechanisms in asthma pathogenesis, this review will discuss immune responses in the airways of obese asthmatic mice on the basis of diverse modeling protocols.

6.
J Vasc Surg ; 2022 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-36058432

RESUMO

OBJECTIVES: To investigate the risk factors of distal stent graft induced new entry (dSINE) after thoracic endovascular aortic repair (TEVAR) in patients with uncomplicated type B aortic dissection (TBAD) and report the outcomes of using tapered stent graft and dSINE reintervention. METHODS: Between January 2010 and December 2018, 226 patients with uncomplicated TBAD after TEVAR were analyzed retrospectively. The global features of the thoracic aorta and the local features of the proximal and distal landing zones were evaluated and compared between with or without dSINE group. The multivariate Cox model was used to identify the independent risk factors for dSINE. The cumulative incidences of reintervention were estimated using competing risk models. RESULTS: After a median follow-up of 4.6 years, 16 (7.1%) patients developed dSINE. Multivariable Cox regression analysis demonstrated that type III aortic arch, decreased angle, increased distal oversizing and distal mismatch ratio were significant risk factors for dSINE. Among patients with tapered stent grafts, 5 with ≤ 4 mm taper showed dSINE, however, no dSINE was seen in the > 4 mm taper group (P = .024). Reintervention was performed for 43.8% (7/16) of patients with dSINE. The mean time from initial detection of dSINE to reintervention was 6.43 ± 4.62 months. The competing risk analyses showed that the cumulative incidences of reintervention at 1, 3, and 5 years were 25.0%, 37.5%, and 43.5%, respectively, in the dSINE group. CONCLUSIONS: Type III aortic arch, excessive distal oversizing and mismatch ratio, and severe angulation were associated with dSINE in patients with uncomplicated TBAD. The use of a tapered stent graft with > 4 mm taper may help prevent dSINE in patients with a high taper ratio. Aggressive reintervention was associated with favorable long-term outcomes in patients with progressive dSINE.

7.
Psychol Med ; : 1-14, 2022 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-36047042

RESUMO

Aberrations in how people form expectations about rewards and how they respond to receiving rewards are thought to underlie major depressive disorder (MDD). However, the underlying mechanism linking the appetitive reward system, specifically anticipation and outcome, is still not fully understood. To examine the neural correlates of monetary anticipation and outcome in currently depressed subjects with MDD, we performed two separate voxel-wise meta-analyses of functional neuroimaging studies using the monetary incentive delay task. During reward anticipation, the depressed patients exhibited an increased response in the bilateral middle cingulate cortex (MCC) extending to the anterior cingulate cortex, the medial prefrontal cortex, the left inferior frontal gyrus (IFG), and the postcentral gyrus, but a reduced response in the mesolimbic circuit, including the left striatum, insula, amygdala, right cerebellum, striatum, and IFG, compared to controls. During the outcome stage, MDD showed higher activity in the left inferior temporal gyrus, and lower activity in the mesocortical pathway, including the bilateral MCC, left caudate nucleus, precentral gyrus, thalamus, cerebellum, right striatum, insula, IFG, middle frontal gyrus, and temporal pole. Our findings suggest that cMDD may be characterised by state-dependent hyper-responsivity in cortical regions during the anticipation phase, and hypo-responsivity of the mesocortico-limbic circuit across the two phases of the reward response. Our study showed dissociable neural circuit responses to monetary stimuli during reward anticipation and outcome, which help to understand the dysfunction in different aspects of reward processing, particularly motivational v. hedonic deficits in depression.

8.
J Oleo Sci ; 2022 Sep 09.
Artigo em Inglês | MEDLINE | ID: mdl-36089399

RESUMO

Renal tissue plays a crucial function in maintaining homeostasis, making it vulnerable to xenobiotic toxicity. Pueraria montana has more beneficial potential against the various diseases and has long history used as a traditional Chinese medicine. But its effect against the renal cancer not scrutinize. The goal of this study is to see if Pueraria montana can protect rats from developing kidney tumors caused by diethylnitrosamine (DEN) and ferric nitrite (Fe-NTA). Wistar rats was selected for the current study and DEN (use as an inducer) and Fe-NTA (promoter) for induction the renal cancer. For 22 weeks, the rats were given oral Pueraria montana (12.5, 25, and 50 mg/kg) treatment. At regular intervals, the body weight and food intake were calculated. The rats were macroscopically evaluated for identification of cancer in the renal tissue. The renal tumor makers, renal parameters, antioxidant enzymes, phase I and II enzymes, inflammatory cytokines and mediators were estimated at end of the experimental study. Pueraria montana treated rats displayed the suppression of renal tumors, incidence of the tumors along with suppression of tumor percentage. Pueraria montana treated rats significantly (p < 0.001) increased body weight and suppressed the renal weight and food intake. It also reduced the level of renal tumor marker ornithine decarboxylase (ODC) and [3H] thymidine incorporation along with suppression of renal parameter such as uric acid, blood urea nitrogen (BUN) and urea and creatinine. Pueraria montana treatment significantly (p < 0.001) altered the level of phase enzymes and antioxidant. Pueraria montana treatment significantly (p < 0.001) repressed the level of tumor necrosis factor-α (TNF-α), interleukin-1ß (IL-1ß), interleukin-6 (IL-6) and improved the level of interleukin-10 (IL-10). Pueraria montana treatment suppressed the level of prostaglandin (PGE2), cyclooxygenase-2 (COX-2), nuclear kappa B factor (NF-κB) and transforming growth factor beta 1 (TGF-ß1). Pueraria montana suppressed the inflammatory necrosis, size the bowman capsules in the renal histopathology. Pueraria montana exhibited the chemoprotective effect via dual mechanism such as suppression of inflammatory reaction and oxidative stress.

9.
Small ; : e2203619, 2022 Sep 09.
Artigo em Inglês | MEDLINE | ID: mdl-36084239

RESUMO

Diabetic infectious micromilieu (DIM) leads to a critical failure rate of osseointegration by virtue of two main peculiarities: high levels of topical glucose and inevitable infection. To tackle the daunting issue, a bioheterojunction-engineered orthopedic polyetheretherketone (PEEK) implant consisting of copper sulfide/graphene oxide (CuS/GO) bioheterojunctions (bioHJs) and glucose oxidase (GOx) is conceived and developed for DIM enhanced disinfection and boosted osseointegration. Under hyperglycemic micromilieu, GOx can convert surrounding glucose into hydrogen peroxide (H2 O2 ). Then, upon infectious micromilieu, the bioHJs enable the catalyzation of H2 O2 to highly germicidal hydroxyl radical (·OH). As a result, the engineered implants massacre pathogenic bacteria through DIM twin-engine powered photo-chemodynamic therapy in vitro and in vivo. In addition, the engineered implants considerably facilitate cell viability and osteogenic activity of osteoblasts under a hyperglycemic microenvironment via synergistic induction of copper ions (Cu2+ ) and GO. In vivo studies using bone defect models of diabetic rats at 4 and 8 weeks further authenticate that bioHJ-engineering PEEK implants substantially elevate their osseointegration through biofilm elimination and vascularization, as well as macrophage reprogramming. Altogether, the present study puts forward a tactic that arms orthopedic implants with DIM twin-engine powered antibacterial and formidable osteogenic capacities for diabetic stalled osseointegration.

10.
J Leukoc Biol ; 2022 Sep 08.
Artigo em Inglês | MEDLINE | ID: mdl-36073781

RESUMO

The role of distinct immune cell types in modulating cancer progression has recently gained attention. The immune context is indicated by the abundance of immune infiltration based on quantified lymphocytes in the core of tumors (CT) and invasive tumor margin (IM). Novel immune biomarkers could potentially complement tumor-node-metastasis (TNM) classification for non-small cell lung cancers (NSCLCs), thereby improving prognostic accuracy. This study evaluated the prognostic value of a newly established immunologic score (neo-IS) in patients with NSCLC. We detected 10 immune biomarkers, including CD45RO, CD3, CD8, CD68, CD163, CD66b, FoxP3, PD-1, PD-L1, and TIM-3, in 350 patients with NSCLC from 2 cohorts using immunohistochemistry (IHC). The 3- and 5-year survival and overall survival (OS) rates were evaluated. An immunologic prediction model specifically for NSCLC patients, the neo-immunologic score (neo-ISNSCLC ), was constructed using a Cox proportional hazards regression model. In the discovery cohort (n = 250), the establishment of neo-ISNSCLC was based on 4 immune biomarkers: CD3+IM , CD8+CT , FoxP3+IM , and PD-1+IM . Significant prognostic differences were found upon comparing low-ISNSCLC patients and high-ISNSCLC patients. The OS rate in the high-ISNSCLC group was significantly longer than that in the low-ISNSCLC group (67.5 months vs. 51.2 months, p < 0.001). The neo-ISNSCLC was validated in the validation cohort (n = 100), and the results were confirmed. Multivariate analyses indicated that neo-ISNSCLC was an independent indicator of prognosis in patients with NSCLC. Finally, we combined neo-ISNSCLC with clinicopathologic factors to establish a tumor-node-metastasis-immune (TNM-I) staging system for clinical use, which showed better prediction accuracy than the TNM stage.

11.
Sensors (Basel) ; 22(17)2022 Aug 29.
Artigo em Inglês | MEDLINE | ID: mdl-36080952

RESUMO

Obtaining surface albedo data with high spatial and temporal resolution is essential for measuring the factors, effects, and change mechanisms of regional land-atmosphere interactions in deserts. In order to obtain surface albedo data with higher accuracy and better applicability in deserts, we used MODIS and OLI as data sources, and calculated the daily surface albedo data, with a spatial resolution of 30 m, of Guaizi Lake at the northern edge of the Badain Jaran Desert in 2016, using the Spatial and Temporal Non-Local Filter-based Fusion Model (STNLFFM) and topographical correction model (C model). We then compared the results of STNLFFM and C + STNLFFM for fusion accuracy, and for spatial and temporal distribution differences in surface albedo over different underlying surfaces. The results indicated that, compared with STNLFFM surface albedo and MODIS surface albedo, the relative error of C + STNLFFM surface albedo decreased by 2.34% and 3.57%, respectively. C + STNLFFM can improve poor applicability of MODIS in winter, and better responds to the changes in the measured value over a short time range. After the correction of the C model, the spatial difference in surface albedo over different underlying surfaces was enhanced, and the spatial differences in surface albedo between shifting dunes and semi-shifting dunes, fixed dunes and saline-alkali land, and the Gobi and saline-alkali land were significant. C + STNLFFM maintained the spatial and temporal distribution characteristics of STNLFFM surface albedo, but the increase in regional aerosol concentration and thickness caused by frequent dust storms weakened the spatial difference in surface albedo over different underlying surfaces in March, which led to the overcorrection of the C model.

12.
Transl Lung Cancer Res ; 11(8): 1591-1605, 2022 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-36090636

RESUMO

Background: Representative prognostic data by clinical characteristics for lung cancer is not yet available in China. This study aimed to calculate the survival of lung cancer patients with different pathological evaluations, explore their predictive effects and provide information for prognosis improvement. Methods: In this multicenter cohort study, primary lung cancer patients diagnosed in 17 hospitals at three distinct levels in China between 2011-2013 were enrolled and followed up till 2020. Overall survival and lung cancer specific survival were calculated by Kaplan-Meier method. Cox proportional hazards model was applied to assess the effects of predictors of lung cancer survival. Results: Of all the 7,311 patients, the 5-year overall and lung cancer specific survival rates were 37.0% and 41.6%, respectively. For lung cancer patients at stages I, II, III, and IV, the 5-year overall survival rates were 76.9%, 56.1%, 32.6%, and 21.4%, respectively; the lung cancer specific survival rates were 82.3%, 59.7%, 37.2%, and 26.4%, respectively. Differences of survival for each stage remained significant between histological classifications (P<0.01). The 5-year overall survival rates for patients with squamous cell carcinoma, adenocarcinoma (AC), and small cell carcinoma were 36.9%, 43.3% and 27.9%, respectively; the corresponding disease-specific rates were 41.5%, 48.6% and 31.0%, respectively. Such differences were non-statistically significant at advanced stages (P=0.09). After multivariate adjustments, stage and classification remained independent predictors for the survival of lung cancer. Conclusions: The prognosis of lung cancer varied with the pathological stages and histological classifications, and had room for improvement. Stage was the strongest predictor, so efforts on early detection and treatment are needed.

13.
PeerJ ; 10: e13899, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36061757

RESUMO

Background: Owing to intermittent/acute exposure to hypobaric hypoxia, highland miners may often suffer, the physiological characteristics between highland and lowland miners, however, are rarely reported. The objective of this study was to compare the physiological characteristics of coal miners working at disparate altitudes. Methods: Twenty-three male coal mining workers acclimating to high altitude for 30 ± 6 days in Tibet (highland group; approx. 4500 m above sea level; 628.39 millibar), and 22 male coal mining workers in Hebei (lowland group; less than 100 m above sea level; 1021.82 millibar) were recruited. Tests were conducted to compare ventilatory parameters, circulation parameters, resting metabolic rate (RMR), and heart rate variability (HRV) indices between the two groups in resting state. Results: Ventilation volume per minute (VE) of the highland group was markedly raised compared to that of the lowland group (11.70 ± 1.57 vs. 8.94 ± 1.97 L/min, p = 0.000). In the meanwhile, O2 intake per heart beat (VO2/HR) was strikingly decreased (3.54 ± 0.54 vs. 4.36 ± 0.69 ml/beat, p = 0.000). Resting metabolic rate relevant to body surface area (RMR/BSA) was found no significant difference between the two groups. Evident reduction in standard deviation of NN intervals (SDNN) and remarkable increase in ratio of low- and high- frequency bands (LF/HF) were manifest in highland miners compared to that of lowland ones (110.82 ± 33.34 vs. 141.44 ± 40.38, p = 0.008 and 858.86 ± 699.24 vs. 371.33 ± 171.46, p = 0.003; respectively). Conclusions: These results implicate that long-term intermittent exposure to high altitude can lead miners to an intensified respiration, a compromised circulation and a profound sympathetic-parasympathetic imbalance, whereas the RMR in highland miners does not distinctly decline.

14.
Opt Lett ; 47(17): 4291-4294, 2022 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-36048636

RESUMO

Metasurfaces have exhibited powerful capabilities in the modulation of electromagnetic waves. Here, we demonstrate the polarization-selective full-space complex amplitude modulations of incident electromagnetic waves using all-dielectric metasurfaces. This is done via ingeniously designed subwavelength-scale super-pixels. As a proof of concept, we design two metasurfaces working in transmission and reflection spaces: one generates two independent vortex beams and the other generates two pairs of foci of arbitrary intensity ratios. The proposed full-space complex amplitude modulation provides more choices for the manipulation of electromagnetic waves.

15.
Pharmacol Res ; 184: 106422, 2022 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-36058431

RESUMO

Targeting cardiomyocyte plasticity has emerged as a new strategy for promoting heart repair after myocardial infarction. However, the precise mechanistic network underlying heart regeneration is not completely understood. As noncoding RNAs, circular RNAs (circRNAs) play essential roles in regulating cardiac physiology and pathology. The present study aimed to investigate the potential roles of circMdc1 in cardiac repair after injury and elucidate its underlying mechanisms. Here, we identified that circMdc1 levels were upregulated in postnatal mouse hearts but downregulated in the regenerative myocardium. The expression of circMdc1 in cardiomyocytes is sensitive to oxidative stress, which was attenuated by N-acetyl-cysteine. Enforced circMdc1 expression inhibited cardiomyocyte proliferation, while circMdc1 silencing led to cardiomyocyte cell cycle re-entry. In vivo, the cardiac-specific adeno-associated virus-mediated knockdown of circMdc1 promoted cardiac regeneration and heart repair accompanied by improved heart function. Conversely, circMdc1 overexpression blunted the regenerative capacity of neonatal hearts after apex resection. Moreover, circMdc1 was able to block the translation of its host gene Mdc1 specifically by binding to PABP, affecting DNA damage and the chromosome stability of cardiomyocytes. Furthermore, overexpression of Mdc1 caused damaged mouse hearts to regenerate and repair after myocardial infarction in vivo. Oxidative stress-sensitive circMdc1 plays an important role in cardiac regeneration and heart repair after injury by regulating DNA damage and chromosome stability in cardiomyocytes by blocking the translation of the host gene Mdc1.

16.
Front Pharmacol ; 13: 958146, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36091786

RESUMO

DNA methylation is one of the most essential epigenetic mechanisms to regulate gene expression. DNA methyltransferases (DNMTs) play a vital role in DNA methylation in the genome. In mammals, DNMTs act with some elements to regulate the dynamic DNA methylation patterns of embryonic and adult cells. Conversely, the aberrant function of DNMTs is frequently the hallmark in judging cancer, including total hypomethylation and partial hypermethylation of tumor suppressor genes (TSGs), which improve the malignancy of tumors, aggravate the ailment for patients, and significantly exacerbate the difficulty of cancer therapy. Since DNA methylation is reversible, currently, DNMTs are viewed as an important epigenetic target for drug development. However, the impression of DNMTs on cancers is still controversial, and therapeutic methods targeting DNMTs remain under exploration. This review mainly summarizes the relationship between the main DNMTs and cancers as well as regulatory mechanisms and clinical applications of DNMTs in cancer and highlights several forthcoming strategies for targeting DNMTs.

17.
Front Genet ; 13: 927614, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36092911

RESUMO

Background: Head and neck squamous cell carcinomas (HNSCCs) are derived from the mucosal linings of the upper aerodigestive tract, salivary glands, thyroid, oropharynx, larynx, and hypopharynx. The present study aimed to identify the novel genes and pathways underlying HNSCC. Despite the advances in HNSCC research, diagnosis, and treatment, its incidence continues to rise, and the mortality of advanced HNSCC is expected to increase by 50%. Therefore, there is an urgent need for effective biomarkers to predict HNSCC patients' prognosis and provide guidance to the personalized treatment. Methods: Both HNSCC clinical and gene expression data were abstracted from The Cancer Genome Atlas (TCGA) database. Intersecting analysis was adopted between the gene expression matrix of HNSCC patients from TCGA database to extract TME-related genes. Differential gene expression analysis between HNSCC tissue samples and normal tissue samples was performed by R software. Then, HNSCC patients were categorized into clusters 1 and 2 via NMF. Next, TME-related prognosis genes (p < 0.05) were analyzed by univariate Cox regression analysis, LASSO Cox regression analysis, and multivariate Cox regression analysis. Finally, nine genes were selected to construct a prognostic risk model and a prognostic gene signature. We also established a nomogram using relevant clinical parameters and a risk score. The Kaplan-Meier curve, survival analysis, time-dependent receiver operating characteristic (ROC) analysis, decision curve analysis (DCA), and the concordance index (C-index) were carried out to assess the accuracy of the prognostic risk model and nomogram. Potential molecular mechanisms were revealed by gene set enrichment analysis (GSEA). Additionally, gene correlation analysis and immune cell correlation analysis were conducted for further enriching our results. Results: A novel HNSCC prognostic model was established based on the nine genes (GTSE1, LRRN4CL, CRYAB, SHOX2, ASNS, KRT23, ANGPT2, HOXA9, and CARD11). The value of area under the ROC curves (AUCs) (0.769, 0.841, and 0.816) in TCGA whole set showed that the model effectively predicted the 1-, 3-, and 5-year overall survival (OS). Results of the Cox regression assessment confirmed the nine-gene signature as a reliable independent prognostic factor in HNSCC patients. The prognostic nomogram developed using multivariate Cox regression analysis showed a superior C-index over other clinical signatures. Also, the calibration curve had a high level of concordance between estimated OS and the observed OS. This showed that its clinical net can precisely estimate the one-, three-, and five-year OS in HNSCC patients. The gene set enrichment analysis (GSEA) to some extent revealed the immune- and tumor-linked cascades. Conclusion: In conclusion, the TME-related nine-gene signature and nomogram can effectively improve the estimation of prognosis in patients with HNSCC.

18.
Brain Behav Immun ; 2022 Sep 17.
Artigo em Inglês | MEDLINE | ID: mdl-36126853

RESUMO

Neuroinflammation caused by the disorder of gut microbiota and its metabolites is associated with the pathogenesis of Parkinson's disease (PD). Thus, it is necessary to identify certain molecules derived from gut microbiota to verify whether they could become intervention targets for the treatment of PD. The branched-chain amino acids (BCAAs), as a common dietary supplement, could modulate brain function. Herein, we investigated the longitudinal shifts of microbial community in mice treated with rotenone for 0, 3 and 4 weeks by 16S rRNA gene sequencing to identify the microbial markers at different PD stages. Serum BCAAs were determined by gas chromatography-mass spectrometry. Then, rotenone-induced mice were given a high BCAA diet to evaluate the motor and non-motor functions, dopaminergic neuron loss, and inflammation levels. Using a PD mouse model, we discovered that during PD progression, the alterations of gut microbiota compositions led to the peripheral decrease of BCAAs. Based on the serum lipopolysaccharide binding protein concentrations and the levels of pro-inflammatory factors (including tumor necrosis factor-α, interleukin [IL]-1ß, and IL-6) in the colon and substantia nigra, we found that the high BCAA diet could attenuate the inflammatory levels in PD mice, and reverse motor and non-motor dysfunctions and dopaminergic neuron impairment. Together, our results emphasize the dynamic changes of gut microbiota and BCAA metabolism and propose a novel strategy for PD therapy: a high BCAA diet intervention could improve PD progression by regulating the levels of inflammation.

19.
Pestic Biochem Physiol ; 187: 105218, 2022 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-36127060

RESUMO

The Chinese wheat aphid Sitobion miscanthi (CWA) is an important harmful pest in wheat fields. Imidacloprid plays a critical role in controlling pests with sucking mouthparts. However, imidacloprid-resistant pests have been observed after insecticide overuse. Point mutations and low expression levels of the nicotinic acetylcholine receptor ß1 (nAchRß1) subunit are the main imidacloprid-resistant mechanisms. However, the regulatory mechanism underlying nAChRß1 subunit expression is poorly understood. In this study, a target of miR-263b was isolated from the 5'UTR of the nAchRß1 subunit in the CWA. Low expression levels were found in the imidacloprid-resistant strain CWA. Luciferase reporter assays showed that miR-263b could combine with the 5'UTR of the nAChRß1 subunit and suppress its expression by binding to a site in the CWA. Aphids treated with the miR-263b agomir exhibited a significantly reduced abundance of the nAchRß1 subunit and increased imidacloprid resistance. In contrast, aphids treated with the miR-263b antagomir exhibited significantly increased nAchRß1 subunit abundance and decreased imidacloprid resistance. These results provide a basis for an improved understanding of the posttranscriptional regulatory mechanism of the nAChRß1 subunit and further elucidate the function of miRNAs in regulating susceptibility to imidacloprid in the CWA. These results provide a better understanding of the mechanisms of posttranscriptional regulation of nAChRß1 and will be helpful for further studies on the role of miRNAs in the regulation of nAChRß1 subunit resistance in homopteran pests.

20.
Water Res ; 224: 119051, 2022 Sep 03.
Artigo em Inglês | MEDLINE | ID: mdl-36113234

RESUMO

Anoxic ammonium oxidation (anammox) is an energy-efficient nitrogen removal process for wastewater treatment. However, the unstable nitrite supply and residual nitrate in the anammox process have limited its wide application. Recent studies have proven coupling of sulfur-based denitrification with anammox (SDA) can achieve an effective nitrogen removal, owing to stable provision of substrate nitrite from the sulfur-based denitrification, thus making its process control more efficient in comparison with that of partial nitrification and anammox process. Meanwhile, the anammox-produced nitrate can be eliminated through sulfur-based denitrification, thereby enhancing SDA's overall nitrogen removal efficiency. Nonetheless, this process is governed by a complex microbial system that involves both complicated sulfur and nitrogen metabolisms as well as multiple interactions among sulfur-oxidising bacteria and anammox bacteria. A comprehensive understanding of the principles of the SDA process is the key to facilitating the development and application of this novel process. Hence, this review is conducted to systematically summarise various findings on the SDA process, including its associated biochemistry, biokinetic reactions, reactor performance, and application. The dominant functional bacteria and microbial interactions in the SDA process are further discussed. Finally, the advantages, challenges, and future research perspectives of SDA are outlined. Overall, this work gives an in-depth insight into the coupling mechanism of SDA and its potential application in biological nitrogen removal.

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