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1.
Cancer Manag Res ; 14: 67-88, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35023971

RESUMO

Purpose: The study aimed to identify an autophagy-related molecular subtype and characterize a novel defined autophagy-immune related genes score (AI-score) signature and prognosis model in bladder cancer (BLCA) patients using public databases. Methods: The transcriptome cohorts downloaded from TCGA and GEO database were carried out with genomic analysis and unsupervised methods to obtain autophagy-related molecular subtypes. The single-sample gene-set enrichment analysis (ssGSEA) was utilized to perform immune subtype clustering. We defined a novel autophagy subtype and evaluated the role in TME cell infiltration. Then, the principal-component analysis (PCA) was applied to construct an AI-score signature. Subsequently, two immunotherapeutic cohorts were used to evaluate the predictive value in immunotherapeutic benefits and immune response. Finally, univariate, Lasso and multivariate Cox regression algorithm were used to construct and evaluate an autophagy-immune-related genes prognosis model. Also, qRT-PCR and IHC was applied to validate the expression of the 6 genes in the model. Results: Three distinct autophagy clusters and immune-related clusters were identified, and a novel autophagy-related molecular subtypes were defined. Furthermore, the roles in TME cell infiltration and clinical traits for the autophagy subtypes were characterized. Meanwhile, we constructed an AI-score signature and demonstrated it could predict genetic mutation, clinicopathological traits, prognosis, and TME stromal activity. We found that it could accurately predict the clinicopathological characteristics and immune response of individual BLCA patients and provide guidance for selecting immunotherapy. Ultimately, we constructed and verified an autophagy-immune-related prognostic model of BLCA patients and established a prognostic nomogram with a good prediction accuracy. Conclusion: We constructed AI-score signatures and prognosis risk model to characterize their role in clinical features and TME immune cell infiltration. It revealed that the AI-score signature and prognosis model could be a valid predictive tool, which could accurately predict the prognosis of BLCA patients and contribute to choosing effective personalized immunotherapy strategies.

2.
J Org Chem ; 2022 Jan 11.
Artigo em Inglês | MEDLINE | ID: mdl-35014249

RESUMO

Herein, we report an efficient photoinduced radical tandem trifluoromethylation/cyclization reaction of N-cyanamide alkenes for the synthesis of functionalized quinazolinones. Importantly, the reaction is carried out under mild conditions without any additional photosensitizer, metal, or extra additives. A series of trifluoromethyl quinazolinones were prepared efficiently with good yields and excellent functional group tolerance. Preliminary mechanistic experiments were conducted to indicate that the transformation proceeds via a possible mechanism involving photoexcited EDA complex and chain propagation.

3.
Schizophr Res ; 240: 165-174, 2022 Jan 11.
Artigo em Inglês | MEDLINE | ID: mdl-35030446

RESUMO

Patients with schizophrenia show widespread impairments in clinical, cognitive and psychosocial functioning. Mismatch negativity (MMN) and gamma-band auditory steady-state response (ASSR) are two neurophysiological biomarkers widely used to inform diagnosis, guide treatments and track response to interventions in schizophrenia. However, evidence for the test-retest reliability of these indices across multiple sessions in schizophrenia patients remains scarce. In the present study, we included 34 schizophrenia patients (17 females) and obtained duration MMN (dMMN), frequency MMN (fMMN) and 40-Hz ASSR data across three sessions with intervals of 2 days. Event-related spectrum perturbation (ERSP) and inter-trial coherence (ITC) were calculated following Morlet wavelet time-frequency decomposition of ASSR data. The intra-class correlation coefficient (ICC) was used to quantify the reliability of MMN and ASSR measures among the three sessions. We found fair to good reliability for dMMN amplitudes but poor reliability for fMMN amplitudes. For the ASSR measures, ERSP showed good to excellent test-retest reliability while ITC had poor to fair test-retest reliability. In addition, the average of dMMN amplitudes was significantly correlated with that of ERSP across the three sessions. In summary, we established for the first time the short-term test-retest reliability of MMN and ASSR measures in schizophrenia patients. These findings demonstrate that dMMN amplitudes and ERSP of ASSR are reliable indices which may be used in longitudinal observational studies.

4.
Bioengineered ; 13(1): 995-1012, 2022 01.
Artigo em Inglês | MEDLINE | ID: mdl-34974814

RESUMO

The expression of prostate-specific membrane antigen (PSMA) is strikingly upregulated during oncogenesis and prostate cancer (PCa) progression, but the functions of this antigen in PCa remain unclear. Here, we constructed PSMA-knockdown LNCaP and 22rv1 cell lines and performed metabonomic and transcriptomic analyses to determine the effects of PSMA on PCa metabolism and transcription. The metabolism of arginine and proline was detected using specific kits. The mRNA and protein expression levels of the identified differentially expressed genes were quantified by RT-qPCR and Western blotting. The proliferation of each cell line was evaluated through CCK-8, EdU and colony formation assays. The migration and invasion abilities of each cell line were detected using wound healing and transwell assays, respectively. PSMA knockdown led to metabolic disorder and abnormal transcription in PCa and resulted in inhibition of the proliferation and metastasis of PCa cells in vitro and in vivo. The depletion of PSMA also promoted the biosynthesis of arginine and proline, inhibited the expression of AR and PSA, and induced the expression of c-Fos and FosB. PSMA plays an important role in the metabolism, proliferation and metastasis of human PCa and may be a promising therapeutic target.

5.
Front Bioeng Biotechnol ; 9: 774854, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34881237

RESUMO

The unicellular green alga Chlorella is an ideal protein source. However, the high production cost and low production capability of the current main photoautotrophic culture mode limit its application especially as an alternative protein source for food and feed, which might be overcome through high-cell-density cultivation in fermenters. In this study, a Chlorella sorokiniana strain CMBB276 with high protein content was selected from five Chlorella strains by comprehensive evaluation of their growth rates, protein contents, and yields. The optimal cultural temperature, pH, and mole ratio of carbon and nitrogen (C/N) for C. sorokiniana CMBB276 growth were found to be 30°C, 6.5, and 18, respectively. Ammonium chloride was proved to be the best nitrogen (N) source for C. sorokiniana CMBB276 growth, whereas growth inhibition caused by the accumulation of salts was observed under fed-batch cultivation when maintaining a constant C/N ratio of 18 by controlling pH with sodium hydroxide solution. By simultaneously reducing the concentration of ammonium chloride in the feeding medium and controlling pH with ammonium hydroxide, we finally achieved the ultrahigh-cell-density cultivation of C. sorokiniana CMBB276. The highest biomass concentration and protein yield reached 232 and 86.55 g l-1, respectively, showing the great potential of culturing C. sorokiniana CMBB276 in fermenters for economic and large-scale protein source production.

6.
BMC Med Genomics ; 14(Suppl 2): 32, 2021 Dec 02.
Artigo em Inglês | MEDLINE | ID: mdl-34856988

RESUMO

BACKGROUND: Multi-sample comparison is commonly used in cancer genomics studies. By using next-generation sequencing (NGS), a mutation's status in a specific sample can be measured by the number of reads supporting mutant or wildtype alleles. When no mutant reads are detected, it could represent either a true negative mutation status or a false negative due to an insufficient number of reads, so-called "coverage". To minimize the chance of false-negative, we should consider the mutation status as "unknown" instead of "negative" when the coverage is inadequately low. There is no established method for determining the coverage threshold between negative and unknown statuses. A common solution is to apply a universal minimum coverage (UMC). However, this method relies on an arbitrarily chosen threshold, and it does not take into account the mutations' relative abundances, which can vary dramatically by the type of mutations. The result could be misclassification between negative and unknown statuses. METHODS: We propose an adaptive mutation-specific negative (MSN) method to improve the discrimination between negative and unknown mutation statuses. For a specific mutation, a non-positive sample is compared with every known positive sample to test the null hypothesis that they may contain the same frequency of mutant reads. The non-positive sample can only be claimed as "negative" when this null hypothesis is rejected with all known positive samples; otherwise, the status would be "unknown". RESULTS: We first compared the performance of MSN and UMC methods in a simulated dataset containing varying tumor cell fractions. Only the MSN methods appropriately assigned negative statuses for samples with both high- and low-tumor cell fractions. When evaluated on a real dual-platform single-cell sequencing dataset, the MSN method not only provided more accurate assessments of negative statuses but also yielded three times more available data after excluding the "unknown" statuses, compared with the UMC method. CONCLUSIONS: We developed a new adaptive method for distinguishing unknown from negative statuses in multi-sample comparison NGS data. The method can provide more accurate negative statuses than the conventional UMC method and generate a remarkably higher amount of available data by reducing unnecessary "unknown" calls.

8.
Brain Behav ; : e2477, 2021 Dec 30.
Artigo em Inglês | MEDLINE | ID: mdl-34970857

RESUMO

INTRODCTION: Previous studies have argued that people tend to isolate themselves from negative information. This tendency is modulated by the individual's role in social interaction, that is, as an initiative actor (e.g., "I hit Tom") or a passive recipient (e.g., "Paul hits me"). Depressed patients tend to focus on negative aspects of themselves and cope with situations passively. It is still an open question how the actor/recipient role affects the behavioral and neural responses to self in depression. METHODS: The present study adopted functional magnetic resonance imaging (fMRI) technology to investigate behavioral and neural responses to self (as an actor/recipient) in depressed patients and the matched healthy controls when attributing negative events. RESULTS: Compared with healthy controls, depressed patients showed more self-attribution for negative events. Depressed patients showed increased brain activity in the dorsal medial prefrontal cortex (dmPFC) subsystem of the default mode network (DMN) when they played recipient role in self-related negative events. Activity of the dmPFC subsystem was negatively correlated with depressed patients' self-attribution for negative events in recipient condition. While decreased brain activity in the medial temporal lobe (MTL) subsystem was observed in depressed patients when they played the actor or recipient role in self-related negative events. Activity of the MTL subsystem was negatively correlated with depressed patients' reaction time when they played recipient role in selfrelated negative events. CONCLUSION: These results implicated that depressed patients manifested the negative self-view. Actor/recipient role affected their activation patterns in the DMN which were different from the healthy controls. The correlation between the abnormal brain activations of the DMN and the behavioral performances might manifest more easily when depressed patients played recipient role in negative events.

9.
Zhonghua Nan Ke Xue ; 27(4): 301-308, 2021 Apr.
Artigo em Chinês | MEDLINE | ID: mdl-34914211

RESUMO

Objective: To investigate the molecular mechanism of hsa_circ_0005221 regulating the progression of PCa through the miR-339-5p/STAT5a pathway. METHODS: Localizations of hsa_circ_0005221 and miR-339-5p in cells were detected by nuclear-cytoplasmic isolation. MiRNA-339-5p was selected as the target miRNA bound to hsa_circ_0005221 by RNA pull-down assay. The binding site of the luciferase reporter gene was predicted by software and the binding capability of miR-339-5p validated by luciferase assay. The expression of hsa_circ_0005221 in the prostatic epithelial and PCa cells was determined by qPCR. The hsa_circ_0005221-overexpressed plasmid and siRNA were transfected into the PCa cells for measurement of their proliferation, invasion and migration abilities and the levels of epithelial-mesenchymal transformation (EMT) and apoptosis. After knockdown of hsa_circ_0005221 and transfection of miR-339-5p mimics and miR-339-5p inhibitor, the proliferation, invasion and migration abilities of the DU145 and LNCaP cells were detected, and so were the levels of the EMT signature protein, STAT5a and cell apoptosis. RESULTS: The expression of hsa_circ_0005221 was significantly higher in the PCa than in the prostatic epithelial cells. Nuclear-cytoplasmic isolation experiments showed that hsa_circ_0005221 and miR-339-5p were mainly located in the cytoplasm. The proliferation, invasion and migration abilities and EMT were decreased and the apoptosis increased in the DU145 and LNCaP cells with knockdown of hsa_circ_0005221, which was just the reverse in those with overexpressed hsa_circ_0005221. Among the top 5 miRNAs predicted by software, miR-339-5p, miR-17 and miR-520h were shown by pull-down assay to be bound to hsa_circ_0005221, with most obvious changes in miR-339-5p when hsa_circ_0005221 knocked down or overexpressed. Luciferase reporter gene assay showed the binding of hsa_circ_0005221 to miR-339-5p. Knockdown of hsa_circ_0005221 and transfection of miR-339-5p mimics into the DU145 and LNCaP cells significantly reduced the proliferation, invasion and migration abilities of the cells and the N-cad level, increased their apoptosis and E-cad level, and up-regulated the expression of STAT5a, while overexpression of hsa_circ_0005221 and transfection of miR-339-5p mimics induced just the opposite effects. CONCLUSIONS: Hsa_circ_0005221 enhances the progression of prostate cancer through the miR-339-5p/STAT5a pathway.


Assuntos
MicroRNAs , Neoplasias da Próstata , RNA Circular/genética , Fator de Transcrição STAT5 , Humanos , Masculino , MicroRNAs/genética , Pelve , Próstata , Neoplasias da Próstata/genética , RNA Interferente Pequeno , Fator de Transcrição STAT5/genética , Proteínas Supressoras de Tumor
10.
Small ; : e2105415, 2021 Nov 17.
Artigo em Inglês | MEDLINE | ID: mdl-34787363

RESUMO

Carbon dot (CD) based long-lived afterglow emission materials have attracted attention in recent years, but demonstration of white-light room-temperature afterglow remains challenging, due to the difficulty of simultaneous generation of multiple long-lived excited states with distinct chromatic emission. In this work, a white-light room-temperature long-lived afterglow emission from a CD powder with a high efficiency of 5.8% and Commission International de l'Eclairage (CIE) coordinates of (0.396, 0.409) is realized. The afterglow of the CDs originates from a synergy between the phosphorescence of the carbon core and the delayed fluorescence associated with the surface CN moieties, which is accomplished by matching the singlet state of the surface groups of the CDs with the long-lived triplet state of the carbon core, resulting in an efficient energy transfer. It is demonstrated how the long-lived afterglow emission of CDs can be utilized for fabrication of white light emitting devices and in anticounterfeiting applications.

11.
Mol Cancer ; 20(1): 142, 2021 11 05.
Artigo em Inglês | MEDLINE | ID: mdl-34740354

RESUMO

Circular RNAs are a new class of non-coding RNAs that have been shown to play critical roles in the development and progression of renal cell carcinoma (RCC). However, little is known about the functional mechanisms and therapeutic role of ciRS-7 in RCC. A series of in vitro and in vivo experiments were performed to investigate the functional mechanism and therapeutic role of ciRS-7, such as real-time quantitative PCR, CCK-8, wound healing, transwell, colony formation, Edu, tumor xenograft and lung metastasis in NSG mice. RNA pull-down, dual luciferase reporter, fluorescence in situ hybridization (FISH) and rescue assays were used to determine the relationship between ciRS-7, miR-139-3p and TAGLN. In addition, we constructed PBAE/si-ciRS-7 nanocomplexes with PBAE material to evaluate the therapeutic effect of the nanocomplexes on tumor in vivo. ciRS-7 was highly expressed in RCC tumor tissues and cell lines, and high ciRS-7 expression correlated with tumor size, high Fuhrman grade and poor survival. Depletion of ciRS-7 significantly inhibited RCC cell proliferation, invasion, tumor growth and metastasis in vivo, while overexpression of ciRS-7 had the opposite effect. Mechanistically, ciRS-7 acts as a "ceRNA" for miR-139-3p to prevent TAGLN degradation and promoting RCC progression and metastasis via the PI3K/AKT signaling pathway. In addition, miR-139-3p mimics or inhibitor could reverse the altered malignant tumor behavior caused by ciRS-7 overexpression or silencing. Furthermore, the PBAE/siciRS-7 nanocomplexes could significantly inhibit RCC tumor progression and metastasis in vivo. ciRS-7 acts as a tumor promoter by regulating the miR-139-3p/TAGLN axis and activating the PI3K/AKT signaling pathway to promote RCC progression and metastasis. Drug development of PBAE/si-ciRS-7 nanocomplexes targeting ciRS-7 may represent a promising gene therapeutic strategy for RCC.

16.
Front Pharmacol ; 12: 692431, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34744705

RESUMO

Vascular calcification (VC) in macrovascular and peripheral blood vessels is one of the main factors leading to diabetes mellitus (DM) and death. Apart from the induction of vascular calcification, advanced glycation end products (AGEs) have also been reported to modulate autophagy and apoptosis in DM. Autophagy plays a role in maintaining the stabilization of the external and internal microenvironment. This process is vital for regulating arteriosclerosis. However, the internal mechanisms of this pathogenic process are still unclear. Besides, the relationship among autophagy, apoptosis, and calcification in HASMCs upon AGEs exposure has not been reported in detail. In this study, we established a calcification model of SMC through the intervention of AGEs. It was found that the calcification was upregulated in AGEs treated HASMCs when autophagy and apoptosis were activated. In the country, AGEs-activated calcification and apoptosis were suppressed in Atg7 knockout cells or pretreated with wortmannin (WM), an autophagy inhibitor. These results provide new insights to conduct further investigations on the potential clinical applications for autophagy inhibitors in the treatment of diabetes-related vascular calcification.

17.
J Org Chem ; 86(23): 17156-17163, 2021 Dec 03.
Artigo em Inglês | MEDLINE | ID: mdl-34794309

RESUMO

A visible-light-driven multistep tandem reaction between vinyl azides and alkyl bromides has been developed leading to the formation of tetralone skeletons under mild conditions, which can be easily scaled up to the gram scale. Various 1-tetralone derivatives are synthesized and transformed into desired products in good to high yields.

18.
Hum Exp Toxicol ; 40(12_suppl): S563-S572, 2021 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-34796763

RESUMO

BACKGROUND: Death-associated protein kinase (DAPK1) is one of the positive regulators of apoptosis, and it is widely involved in apoptosis induced by multiple pathways. We examined that the function of DAPK1 in Clinical treatment of arterial aneurysm and its underlying mechanisms. Arterial aneurysm is a common cerebrovascular disease with high disability and fatality rate. OBJECTIVES: Male C57BL/6 mice or DAPK1-/- mice were injected with 50 mg/kg pentobarbital sodium and then were injected with angiotensin II (AngII) infusion for vivo model. hASMCs (Human artery smooth muscle cell) were treated with murine recombinant IL-6 (20  ng ml-1; Cell Signaling) for vitro model. RESULTS: DAPK1 gene, mRNA expression, and protein expression were induced in mice of arterial aneurysm. DAPK1 mRNA expression was increased and Area Under Curve was 0.9075 in patients with arterial aneurysm. Knockout of DAPK1 decreased inflammation and vascular injury in mice model of arterial aneurysm. Beclin1/NLRP3 (NACHT, LRR, and PYD domains-containing protein 3) signal pathway is a critical downstream effector of DAPK1 by TAP production. The regulation of Beclin1 participated in the effects of DAPK1 on inflammation of arterial aneurysm by ATP-dependent NLRP3 inflammasome. The regulation of NLRP3 participated in the effects of DAPK1 on inflammation of arterial aneurysm. CONCLUSION: Collectively, our data indicated that DAPK1 may be a potential biomarker for arterial aneurysm in clinical treatment and activated inflammation levels in arterial aneurysm through NLRP3 inflammasome by Beclin1. DAPK1 might be a key pathogenic event underlying excess inflammation of arterial aneurysm.

19.
Front Oncol ; 11: 736640, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34760698

RESUMO

Purpose: This study aimed i) to identify the best cutoff points of neutrophil-lymphocyte ratio (NLR) and platelet-lymphocyte ratio (PLR) that predict sarcopenia and ii) to illustrate the association between sarcopenia risk and NLR or PLR in renal cell carcinoma (RCC) patients undergoing laparoscopic partial or radical nephrectomy. Methods: A total of 343 RCC patients who underwent laparoscopic partial or radical nephrectomy between 2014 and 2019 were enrolled in our study. Sarcopenia was assessed by lumbar skeletal muscle index (SMI). Receiver operating characteristic (ROC) curve was used to identify the best cutoff point of NLR or PLR to predict sarcopenia risk. Univariate and multivariate logistic regression and dose-response analysis curves of restricted cubic spline function were conducted to assess the relationship between sarcopenia and NLR or PLR. Results: The best cutoff points of NLR >2.88 or PLR >135.63 were confirmed by the ROC curve to predict sarcopenia risk. Dose-response curves showed that the risk of sarcopenia increased with raising NLR and PLR. Patients with NLR >2.88 or PLR >135.63 had a higher sarcopenia risk than those in the NLR ≤2.8 or PLR ≤135.63 group, respectively. By adjusting for all variables, we found that patients with NLR >2.88 and PLR >135.63 had 149% and 85% higher risk to develop sarcopenia, respectively, than those with NLR ≤2.8 (aOR = 2.49; 95% CI = 1.56-3.98; p < 0.001) or PLR ≤135.63 (aOR = 1.85; 95% CI = 1.16-2.95; p = 0.010). Conclusion: In RCC patients receiving laparoscopic partial or radical nephrectomy, NLR and PLR, which were biomarkers of systemic inflammation, were associated with sarcopenia risk.

20.
Front Chem ; 9: 767847, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34778216

RESUMO

Bacterial infection is a major threat to human health. However, many antibacterial agents currently used are severely limited due to drug-resistance, and the development of side effects. Herein, we have developed a non-antibiotic nanocomposite consisting of chitosan (ChS) coated silver nanoparticles (AgNPs) and graphene nanoribbon (GNR)-based nanowires for light-triggered eradication of bacteria. The presence of AgNP/ChS significantly enhanced the interactions of the GNR nanowires with Pseudomonas aeruginosa, a clinically common Gram-negative bacterium. Which enables the highly effective photothermal eradication of bacteria by GNR upon near-infrared light irradiation. The nanocomposite was shown to be applicable for the light-triggered eradication of bacterial biofilms and the inhibition of bacterial growth on medical patches used for abdominal-wall hernia surgery.

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