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1.
Neural Regen Res ; 17(4): 819-823, 2022 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-34472481

RESUMO

Leukoaraiosis (LA) results from ischemic injury in small cerebral vessels, which may be attributable to decreased vascular density, reduced cerebrovascular angiogenesis, decreased cerebral blood flow, or microcirculatory dysfunction in the brain. In this study, we enrolled 357 patients with mild intracerebral hemorrhage (ICH) from five hospitals in China and analyzed the relationships between LA and clinical symptom severity at admission, neurological function prognosis at 3 months, and 1-year stroke recurrence. Patients were divided into groups based on Fazekas scale scores: no LA (n = 83), mild LA (n = 64), moderate LA (n = 98) and severe LA (n = 112). More severe LA, larger hematoma volume, and higher blood glucose level at admission were associated with more severe neurological deficit. More severe LA, older age and larger hematoma volume were associated with worse neurological function prognosis at 3 months. In addition, moderate-to-severe LA, admission glucose and symptom-free cerebral infarction were associated with 1-year stroke recurrence. These findings suggest that LA severity may be a potential marker of individual ICH vulnerability, which can be characterized by poor tolerance to intracerebral attack or poor recovery ability after ICH. Evaluating LA severity in patients with mild ICH may help neurologists to optimize treatment protocols. This study was approved by the Ethics Committee of Ruijin Hospital Affiliated to Shanghai Jiao Tong University (approval No. 12) on March 10, 2011.

2.
Ther Apher Dial ; 2021 Dec 07.
Artigo em Inglês | MEDLINE | ID: mdl-34877787

RESUMO

INTRODUCTION: Multiple organ dysfunction syndrome (MODS) with secondary hemophagocytic lymphohistiocytosis (SHLH) causes significant mortality. We aimed to identify the predictor factors for death in pediatric patients with SHLH associated MODS receiving continuous renal replacement therapy (CRRT). METHODS: This multicentered nested case-control study was conducted from 2016 to 2020. The characteristics were compared between survivors and non-survivors. Logistic regression was applied to identify the risk factors for death. The cut-off values were assessed by receiver operating characteristics curves. RESULTS: 52 patients were enrolled in this study. Interleukin-6 level (P = 0.018) and the number of organ dysfunction (P = 0.047) were independent risk factors for death. The cut-off value of 13.12 pg/ml interleukin-6 and three organs dysfunction at CRRT initiation presented a high sensitivity and specificity. CONCLUSION: The number of organ dysfunction and interleukin-6 at CRRT initiation are independent risk factors for death in pediatric patients with SHLH-associated MODS. This article is protected by copyright. All rights reserved.

3.
Front Oncol ; 11: 772195, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34869008

RESUMO

The high mortality rate associated with hepatocellular carcinoma (HCC) is partly due to the high proportion of patients who present with advanced stage disease at diagnosis, for whom there are limited treatment options. For selected patients with initially unresectable HCC, locoregional and/or systemic treatments can result in tumor downstaging and consequently provide opportunities for surgical intervention and the potential for long-term survival. Therefore, the key aim of 'conversion therapy' is to reduce tumor burden so that patients become amenable to surgical resection. Various therapies have been investigated as candidates for downstaging patients with potentially resectable HCC including transarterial chemoembolization, transarterial radioembolization with yttrium-90 microspheres, radiotherapy, systemic therapies and combination or multimodality treatment approaches. However, downstaging conversion therapy remains controversial and there are several challenges such as defining the criteria used to identify the population of patients who are 'potentially resectable', the criteria used to define successful downstaging, and the optimum treatment approach to maximize the success of downstaging therapy. In this review article, we summarize clinical experience and evidence of downstaging conversion treatment in patients identified as having 'potentially resectable' HCC.

4.
Nanotechnology ; 2021 Dec 02.
Artigo em Inglês | MEDLINE | ID: mdl-34874315

RESUMO

Infrared optoelectronic devices are capable of operating in harsh environments with outstanding confidentiality and reliability. Nevertheless, suffering from the large band gap value, most semiconductor materials are difficult to detect infrared light signals. Here, Mg2Si/Si heterojunction photodetectors (PDs), which possess the advantages of low-cost, easy process, environmental friendliness, and compatibility with silicon CMOS technology, have been reported with a broadband spectral response as tested from 532 to 1550 nm under zero-bias. When the incident light wavelength is 808 nm, the Mg2Si/Si photodetector (PD) has a responsivity of 1.04 A/W and a specific detectivity of 1.51 × 1012 Jones. Furthermore, we find that the Ag nanoparticles (Ag_NPs) assembled on the Mg2Si layer can greatly improve the performance of the Mg2Si/Si PD. The responsivity and specific detectivity of Mg2Si/Si device with Ag_NPs under 808 nm illumination are 2.55 A/W and 2.60 × 1012 Jones, respectively. These excellent photodetection performances can be attributed to the high-quality of our grown Mg2Si material and the strong built-in electric field effect in the heterojunction, which can be further enhanced by the local surface plasmon effect and local electromagnetic field induced by Ag_NPs. Our study would provide significant guidance for the development of new self-powered infrared PDs based on silicon materials.

5.
J Neural Eng ; 2021 Dec 07.
Artigo em Inglês | MEDLINE | ID: mdl-34875634

RESUMO

OBJECTIVE: Parkinson's disease (PD) is one of the most common neurodegenerative diseases, and early diagnosis is crucial to delay disease progression. The diagnosis of early PD has always been a difficult clinical problem due to the lack of reliable biomarkers. Electroencephalogram (EEG) is the most common clinical detection method, and studies have attempted to discover the EEG spectrum characteristics of early PD, but the reported conclusions are not uniform due to the heterogeneity of early PD patients. There is an urgent need for a more advanced algorithm to extract spectrum characteristics from EEG to satisfy the personalized requirements. APPROACH: The structured power spectral density with spatial distribution was used as the input of convolutional neural network (CNN). A visualization technique called gradient-weighted class activation mapping (Grad-CAM) was used to extract the optimal frequency bands for identifying early PD. Based on the model visualization, we proposed a novel quantitative index of spectral characteristics, spatial-mapping relative power (SRP), to detect personalized abnormalities in the spatial spectral characteristics of EEG in early PD. MAIN RESULTS: We demonstrated the feasibility of applying CNN to identify the patients with early PD with an accuracy of 99.87% ± 0.03%. The models indicated the characteristic frequency bands (high-delta (3.5-4.5 Hz) and low-alpha (7.5-11 Hz) frequency bands) that are used to identify the early PD. The SRP of these two characteristic bands in early PD patients was significantly higher than that in the control group, and the abnormalities were consistent at the group and individual levels. SIGNIFICANCE: This study provides a novel personalized detection algorithm based on deep learning to reveal the optimal frequency bands for identifying early PD and obtain the spatial frequency characteristics of early PD. The findings of this study will provide an effective reference for the auxiliary diagnosis of early PD in clinical practice.

6.
Front Oncol ; 11: 724467, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34858812

RESUMO

Objective: The present study aimed to evaluate the role of integrating the pretreatment neutrophil-to-lymphocyte ratio (NLR) into the eighth edition of the AJCC staging system for nasopharynx cancer in an endemic region. Methods: Between May 2007 and December 2012, a total of 713 cases with NPC were retrospectively analyzed. The separation ability in terms of overall survival (OS), local failure-free survival (LFFS), distant metastasis-free survival (DMFS), and failure-free survival (FFS) was evaluated. The discriminatory ability was assessed using Harrell's concordance index (c-index). Recursive partitioning analysis (RPA) was conducted and incorporated with pretreatment NLR. Results: When integrated with NLR, the separate and discriminatory abilities for N classifications were improved in terms of OS and DMFS, but not for T categories. By using Recursive partitioning analysis, five subgroups were generated. Compared with the overall stage, the integration of NLR could not enhance the separate and discriminatory abilities. However, patients in the RPA 4 group gained significant benefits in terms of OS (HR 0.390 (95%CI 0.212-0.716), P = 0.002) and FFS (HR 0.548 (95%CI 0.314-0.958), P = 0.032) from the additional adjuvant chemotherapy after concurrent chemoradiotherapy. Conclusion: The integration of NLR into the 8th edition of the AJCC staging system could enhance the separation and discriminatory abilities for N classifications, but not for T categories. In addition, patients in the RPA 4 group could benefit from the addition of adjuvant chemotherapy to concurrent chemoradiotherapy.

7.
Cancer Med ; 2021 Dec 03.
Artigo em Inglês | MEDLINE | ID: mdl-34859600

RESUMO

BACKGROUND: The optimal cumulative cisplatin dose (CCD) during radiation therapy for locoregionally advanced nasopharyngeal carcinoma (LA-NPC) patients receiving induction chemotherapy (IC) plus CCRT remains controversial. This study aimed to explore the treatment efficiency of CCD for high-and low-risk patients with LA-NPC. METHODS: Data from 472 LA-NPC patients diagnosed from 2014 to 2018 and treated with IC plus CCRT were reviewed. After propensity score matching, the therapeutic effects of a CCD > 200 and CCD ≤ 200 mg/m2 were evaluated comparatively. Five factors selected by multivariate analysis were incorporated to develop a nomogram. Subgroup analysis was conducted to explore the role of different CCDs in nomogram-defined high- and low-risk groups. Additionally, acute toxicities were evaluated comparatively between the high- and low-CCD groups. RESULTS: After matching, there was no difference between different CCD groups for all patients in terms of 3-year overall survival (OS), distant metastasis-free survival (DMFS), locoregional recurrence-free survival (LRRFS), or progression-free survival (PFS). A nomogram was built by integrating pretreatment EBV DNA, clinical stage, and post-IC EBV DNA, post-IC primary gross tumor and lymph node volumes obtained a C-index of 0.674. The high-risk group determined by the nomogram had poorer 3-year PFS, OS, DMFS, and LRRFS than the low-risk group. A total of CCD > 200 mg/m2 increased the survival rates of 3-year PFS and DMFS (PFS: 72.5% vs. 54.4%, p = 0.012; DMFS: 81.9% vs. 61.5%, p = 0.014) in the high-risk group but not in the low-risk group. Moreover, the high CCD increased treatment-related acute toxicities. CONCLUSIONS: A high CCD was associated with better 3-year PFS and DMFS rates than a low dose for high-risk patients but could not produce a survival benefit for low-risk patients.

8.
Small ; : e2103345, 2021 Dec 04.
Artigo em Inglês | MEDLINE | ID: mdl-34862723

RESUMO

Aqueous zinc-ion batteries are a low-cost and safe energy storage system, but suffer from detrimental side reactions and Zn dendrites due to the strong interactions between Zn2+ and water molecules in the electrolytes, and random Zn2+ deposition on the anode surface. Here, an electrolyte involving a dual-functional additive of polyethylene glycol (PEG) to bypass these issues is reported. The electrolyte can not only tailor the solvation sheath of Zn2+ but also enable favorably oriented deposition of Zn2+ on the anode surface. The dendrite-free Zn anode in Zn//Zn cells is obtained with high Columbic efficiency (98.8%) and long cycling lifespan (1500 h), six times longer than that of electrolyte without PEG at 0.25 mA cm-2 . What is more, the excellent cycling stability of the prepared batteries (Zn//V2 O5 ·1.6 H2 O) suggests that the developed tailoring strategy may propel a promising pathway for stabilizing Zn metal anodes.

9.
Front Oncol ; 11: 778836, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34926289

RESUMO

Purpose: To evaluate the efficacy and safety of induction chemotherapy (IC) combined with concurrent chemoradiotherapy (CCRT) versus CCRT combined with adjuvant chemotherapy (AC) in patients with stage II-IVA nasopharyngeal carcinoma (NPC), we conducted a retrospective study and a meta-analysis combining the results of our studies. Patients and Methods: We used the propensity score matching (PSM) to balance variables. A total of 168 patients were chosen by one-to-two PSM, including 101 patients with IC + CCRT and 67 cases with CCRT + AC. We used the Kaplan-Meier curve to compare survival outcomes and also used Cox regression analysis to determine independent prognostic factors. For meta-analysis, we determined the related studies by searching the PubMed database. We used STATA v12 software to perform meta-analysis of the extracted data and calculate pooled hazard ratios, 95% confidence intervals of survival outcomes, and risk ratios for the toxicities. Results: In this retrospective study, there was no significant difference in 5-year overall survival (76.9% vs. 79.0%, P = 0.966), progression-free survival (71.3% vs. 68.5%, P = 0.332), distant metastasis-free survival (80.5% vs. 74.2%, P = 0.140), and locoregional relapse-free survival (91.5% vs. 91.8%, P = 0.894) among patients with NPC with IC + CCRT versus CCRT + AC after PSM. For meta-analysis, six articles (including our study) reporting 1,052 cases of IC + CCRT and 883 cases of CCRT + AC were included in the meta-analysis. There was no difference of OS (pooled HR = 0.90, 95% CI: 0.63-1.29, P = 0.561), PFS (pooled HR = 1.07, 95% CI: 0.87-1.33, P = 0.633), DMFS (pooled HR= 0.98, 95% CI: 0.76-1.25, P=0.861), and LRRFS (pooled HR = 1.06, 95% CI: 0.76-1.48, P = 0.724). Conclusion: The efficacy of IC + CCRT and CCRT + AC was comparable in patients with stage II-IVA NPC. In terms of compliance and acute adverse reactions, IC + CCRT may be a potential therapeutic strategy.

10.
J Inflamm Res ; 14: 6707-6718, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34916820

RESUMO

Purpose: Distant metastasis is the main pattern of treatment failure in nasopharyngeal carcinoma (NPC) in the era of intensity-modulated radiotherapy (IMRT). We aimed to establish and validate a prognostic nomogram to identify patients with a high risk of distant metastasis. Patients and Methods: A total of 503 patients with nonmetastatic NPC were included in this retrospective study. We established a prognostic nomogram for distant metastasis-free survival (DMFS) based on the Cox proportional hazards model. The predictive discriminative ability and accuracy of the nomogram were assessed with the concordance index (C-index), receiver operating characteristic (ROC) curve, and calibration curve. The nomogram's clinical utility was also evaluated using decision curve analysis (DCA) and Kaplan-Meier method. The predictive ability of the nomogram was validated in an independent cohort. Results: The multivariate analysis showed that circulating CD4+ T lymphocytes, lactate dehydrogenase (LDH), serum ferritin (SF), and N stage were independent prognostic factors for DMFS. Then, we constructed the nomogram based on these factors. The C-indexes of the nomogram for distant metastasis were 0.763 (95% CI: 0.685-0.841) and 0.760 (95% CI: 0.643-0.877) in the training cohort and validation cohort, respectively, which was higher than the 8th TNM staging system (0.672 and 0.677). The calibration curve showed that the prediction results of the nomogram were in high agreement with the actual observation. The ROC curve indicated that the nomogram had a better predictive ability than TNM staging. The DCA also demonstrated that the nomogram was clinically beneficial. In addition, the patients were classified into two different risk groups (high-risk, low-risk) by the nomogram. Conclusion: As a supplement to TNM staging, our nomogram could provide a more effective and accurate prognostic prediction of distant metastasis in NPC patients. It has the potential to guide the individualized treatment of patients to improve their survival.

11.
Small ; : e2105325, 2021 Dec 17.
Artigo em Inglês | MEDLINE | ID: mdl-34921496

RESUMO

Vanadium-based derivatives, featuring affordable cost and high theoretical capacity, have gathered widespread interest in the context of aqueous zinc-ion batteries (ZIBs). However, the further application of vanadium-based materials is hindered by the limited electrical conductivity and cycling lifespan. Herein, 1D chain-like structure vanadyl ethylene glycolate (VEG, (VO(CH2 O)2 )), growing on the Ti3 C2 Tx MXene nanosheets, is synthesized via a one-step oil-bath heating process as cathode materials for ZIBs. Benefiting from the hybrid structure with high conductivity and abundant reactive sites, the VEG@MXene cathode exhibits a remarkable specific capacity (360.3 mAh g-1 at 0.5 A g-1 ), and impressive capacity retention (up to 85.2% after 3000 cycles at 10 A g-1 ). Mechanism analysis reveals a gradual phase transition from the original VEG on MXene to the stable Zn3 V2 O7 (OH)2 ·2H2 O nanoflakes accompanied by continuous zinc ion intercalation/deintercalation, offering more pathways for zinc ion transport. This work suggests that engineering conductivity-enhanced vanadium-based materials is a rational approach for developing promising cathode materials of ZIBs.

12.
Cogn Neurodyn ; 15(6): 1157-1167, 2021 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-34790273

RESUMO

Cortical information has great importance to reflect the deep brain stimulation (DBS) effects for Parkinson's disease patients. Using cortical activities to feedback is an available closed-loop idea for DBS. Previous studies have demonstrated the pathological beta (12-35 Hz) cortical oscillations can be suppressed by appropriate DBS settings. Thus, here we propose to close the loop of DBS based on the beta oscillations in cortex. By modify the cortico-basal ganglia-thalamic neural loop model, more biologically realistic underlying the Parkinsonian phenomenon is approached. Stimulation results show the proposed closed-loop DBS strategy using cortical beta oscillation as feedback information has more profound roles in alleviating the pathological neural abnormality than the traditional open-loop DBS. Additionally, we compare the stimulation effects with subthalamic nucleus feedback strategy. It is shown that using cortical beta information as the feedback signals can further enlarge the control parameter space based on proportional-integral control structure with a lower energy expenditure. This work may pave the way to optimizing the DBS effects in a closed-loop arrangement.

13.
BMC Cancer ; 21(1): 1183, 2021 Nov 05.
Artigo em Inglês | MEDLINE | ID: mdl-34740324

RESUMO

BACKGROUND: Viral infections are prevalent in human cancers and they have great diagnostic and theranostic values in clinical practice. Recently, their potential of shaping the tumor immune microenvironment (TIME) has been related to the immunotherapy of human cancers. However, the landscape of viral expressions and immune status in human cancers remains incompletely understood. METHODS: We developed a next-generation sequencing (NGS)-based pipeline to detect viral sequences from the whole transcriptome and used machine learning algorithms to classify different TIME subtypes. RESULTS: We revealed a pan-cancer landscape of viral expressions in human cancers where 9 types of viruses were detected in 744 tumors of 25 cancer types. Viral infections showed different tissue tendencies and expression levels. Multi-omics analyses further revealed their distinct impacts on genomic, transcriptomic and immune responses. Epstein-Barr virus (EBV)-infected stomach adenocarcinoma (STAD) and Human Papillomavirus (HPV)-infected head and neck squamous cell carcinoma (HNSC) showed decreased genomic variations, significantly altered gene expressions, and effectively triggered anti-viral immune responses. We identified three TIME subtypes, in which the "Immune-Stimulation" subtype might be the promising candidate for immunotherapy. EBV-infected STAD and HPV-infected HNSC showed a higher frequency of the "Immune-Stimulation" subtype. Finally, we constructed the eVIIS pipeline to simultaneously evaluate viral infection and immune status in external datasets. CONCLUSIONS: Viral infections are prevalent in human cancers and have distinct influences on hosts. EBV and HPV infections combined with the TIME subtype could be promising biomarkers of immunotherapy in STAD and HNSC, respectively. The eVIIS pipeline could be a practical tool to facilitate clinical practice and relevant studies.

14.
Int J Gen Med ; 14: 8149-8160, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34803397

RESUMO

Background: Lower-grade glioma (LGG) is one of the prevalent malignancies threatening human health, with considerable intrinsic heterogeneities in their biological behavior. Previous studies have revealed that the immune component is a key factor influencing the formation and development of malignancies. In this study, we aim to use a novel approach to develop a prognostic signature of immune-related gene pairs (IRGPs) to determine the survival outcome of patients with LGG. Methods: Transcriptomic profiles and clinical data for LGG were obtained from The Cancer Genome Atlas (TCGA) and Chinese Glioma Genome Atlas (CGGA) databases, and used as training and validation data sets, respectively. IRGPs influencing the overall survival (OS) of patients with LGG in the training data set were screened by performing univariate Cox regression analysis. Next, a prognostic IRGPs signature was constructed using least absolute shrinkage and selection operator (LASSO) regression. Finally, we cross-validated the two databases to verify the stability of the prognostic signature. Results: A total of 33 IRGPs influencing prognosis of LGG in the training data set were included in the prognostic signature. Patients with high risk scores (RSs) in the training and validation data sets had a poorer OS than those with low RSs. Moreover, significant differences were observed in tumor-infiltrating immune cells (TICs) between high- and low-RS groups. Functional enrichment analyses results revealed that genes in the high-RS group were enriched in the immune-related activities and developmental processes. Conclusion: The prognostic signature containing 33 IRGPs has a significant correlation with OS and relative levels of immune cells associated with LGG. The results of the present study provide new insights into the prediction of survival outcome and therapeutic response of LGG.

15.
Elife ; 102021 11 16.
Artigo em Inglês | MEDLINE | ID: mdl-34783306

RESUMO

Heterogeneity of glucose-stimulated insulin secretion (GSIS) in pancreatic islets is physiologically important but poorly understood. Here, we utilize mouse islets to determine how microtubules (MTs) affect secretion toward the vascular extracellular matrix at single cell and subcellular levels. Our data indicate that MT stability in the ß-cell population is heterogenous, and that GSIS is suppressed in cells with highly stable MTs. Consistently, MT hyper-stabilization prevents, and MT depolymerization promotes the capacity of single ß-cell for GSIS. Analysis of spatiotemporal patterns of secretion events shows that MT depolymerization activates otherwise dormant ß-cells via initiation of secretion clusters (hot spots). MT depolymerization also enhances secretion from individual cells, introducing both additional clusters and scattered events. Interestingly, without MTs, the timing of clustered secretion is dysregulated, extending the first phase of GSIS and causing oversecretion. In contrast, glucose-induced Ca2+ influx was not affected by MT depolymerization yet required for secretion under these conditions, indicating that MT-dependent regulation of secretion hot spots acts in parallel with Ca2+ signaling. Our findings uncover a novel MT function in tuning insulin secretion hot spots, which leads to accurately measured and timed response to glucose stimuli and promotes functional ß-cell heterogeneity.

16.
Am J Nephrol ; 52(10-11): 788-797, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34749369

RESUMO

INTRODUCTION: Transplant glomerulopathy (TG) is a morphological lesion resulting from chronic glomerular endothelium injury, and it is strongly associated with poor graft survival. TG coexisting with focal segmental glomerulosclerosis (FSGS) can be found in renal allograft biopsies, but few related studies are available. METHODS: Consecutive kidney transplant recipients with biopsy-proven TG were studied retrospectively. Patients concomitant with FSGS were identified and compared with those without FSGS. The influence of FSGS on allograft outcomes was assessed using univariate and multivariate Cox regression models. RESULTS: Of the 66 patients with TG, 40 (60.6%) had concomitant FSGS. TG patients with FSGS had higher proteinuria (median, 2.6 vs. 0.8 g/24 h, p < 0.001) and serum creatinine levels (median, 2.5 vs. 2.1 mg/dL, p = 0.04), lower serum albumin levels, higher chronic glomerulopathy (cg) score, larger glomerular tuft area, lower number of podocytes, and higher incidences of podocyte hyperplasia, pseudotubule formation, and diffuse foot process effacement than those without FSGS (all p < 0.05). The kidney allograft loss rate of patients with FSGS was higher than that of patients without FSGS (65.7% vs. 37.5%, p = 0.03). The presence of FSGS was independently associated with allograft loss in TG (hazard ratio (HR) = 3.42, 95% confidence interval (CI): 1.30-8.98, p = 0.01). Other independent predictors were proteinuria (HR = 1.18, 95% CI: 1.02-1.37, p = 0.02), estimated glomerular filtration rate (HR = 0.94, 95% CI: 0.91-0.97, p < 0.001), and panel reactive antibody (HR = 3.99, 95% CI: 1.14-13.99, p = 0.03). Moreover, FSGS (odds ratio (OR) = 4.39, 95% CI: 1.29-14.92, p = 0.02) and cg (OR = 5.36, 95% CI: 1.56-18.40, p = 0.01) were independent risk factors for proteinuria. CONCLUSION: In this cohort of patients with TG, the presence of FSGS was strongly associated with more severe clinicopathological features and worse allograft survival.

17.
Mol Ther Nucleic Acids ; 26: 749-759, 2021 Dec 03.
Artigo em Inglês | MEDLINE | ID: mdl-34729245

RESUMO

MicroRNAs (miRNAs) are emerging as effective therapeutic agents. When testing whether miR-145-5p could alleviate kidney injury, we unexpectedly found that extracellular vesicles loaded with miR-145-5p induced proteinuria and podocyte foot process effacement in normal control mice. To explore the mechanism of miR-145-5p's toxicity to podocytes, we hypothesized that miR-145-5p could enter podocytes and inhibit genes essential for podocytes. We demonstrated that systemically administered miRNA can enter podocytes. Next, we predicted 611 podocyte essential genes based on single-cell RNA sequencing (RNA-seq) and found that 32 of them are predicted to be targeted by miR-145-5p. Functional annotation of the 32 podocyte essential genes revealed small GTPase-mediated signal transduction as the top pathway. We experimentally validated that miR-145-5p targeted Arhgap24 and Srgap1, the essential regulators of the Rho family of small GTPases, increased the activity of Rac1 and Cdc42, and reduced RhoA activity, accompanied by cellular injury, in podocytes. These results explain how miR-145-5p has deleterious effect on podocytes. Most importantly, our study provides a novel approach to investigate how a miRNA affects a given cell type, allowing not only identification of the molecular mechanism underlying an observed side effect of a miRNA drug but also prediction of miRNA drug toxicity on various cell types.

18.
Cancer Manag Res ; 13: 8109-8120, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34737639

RESUMO

Purpose: We set out to explore the prognostic value of circulating lymphocyte subsets in patients with nasopharyngeal carcinoma (NPC) before treatment and to investigate changes in lymphocyte subsets resulting from chemoradiotherapy. Patients and Methods: This retrospective study included 677 patients with non-metastatic NPC. The cutoff value of lymphocyte subsets was determined by the receiver operating characteristic curve (ROC), and the prognostic significance of lymphocyte subsets was evaluated by the Log rank test and Cox proportional hazards model. The endpoints were overall survival (OS), progression-free survival (PFS), locoregional relapse-free survival (LRFS) and distant metastasis-free survival (DMFS). Differences in lymphocyte subsets before and after chemoradiotherapy were analyzed by Wilcoxon signed rank test. Results: NPC patients with high levels of CD19+ B cells (>9.55%) had better 5-year OS (90.4% VS 76.8%, P < 0.001), 5-year PFS (85.3% VS 71.6%, P < 0.001) and 5-year DMFS (94% VS 86.8%, P = 0.002) than patients with low levels of CD19+ B cells. Patients with high levels of CD4+ T cells (> 37.05%) had better 5-year PFS (83% VS 74.2%, P = 0.015) and better 5-year DMFS (95.8% VS 86.7%, P < 0.001) than those with low levels of CD4+ T cells. Multivariate analyses indicated that CD19+ B cell was an independent prognostic factor for OS, PFS and DMFS in NPC. And CD4+ T cell was an independent prognostic factor for PFS and DMFS. Within 1 month after chemoradiotherapy, the percentages of CD4+ T cells, CD19+ B cells, and the CD4/CD8 ratio decreased significantly, while the percentages of CD8+ T cells increased significantly. Conclusion: NPC patients with low levels of CD19+ B cells or CD4+ T cells before treatment have a poor prognosis. In addition, chemoradiotherapy may reduce the body's immune function in NPC patients.

19.
Appl Opt ; 60(25): 7619-7627, 2021 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-34613229

RESUMO

Integrable nanophotodiode devices have attracted much research interest in recent years because of their potential applications in all-optical computing and optical communication systems. We propose a new optical diode design scheme. We use genetic algorithms (GAs) to design an optical diode, which has a device footprint of only 2.5×2.5µm2. These devices designed by GA have the ability to achieve high-efficiency unidirectional transmission. Simulations show the forward transmission efficiency can reach higher than 65% for a Gaussian beam between the wavelengths of 1400 and 1600 nm, and the peak transmission efficiency reaches 75%. The transmission contrast at the design wavelength between 1500 and 1600 nm is higher than 90%, which meets the requirements of high unidirectionality, wide operational bandwidth, and small scale. The devices have more advantages for optical diodes compared with structures designed by photonic crystals and gratings. The application of this scheme provides a new idea for the design and research of all-optical diodes in the field of optical communication.

20.
Materials (Basel) ; 14(19)2021 Sep 29.
Artigo em Inglês | MEDLINE | ID: mdl-34640076

RESUMO

Using butyl titanate and absolute ethanol as raw materials, TiO2 was prepared by a hydrothermal method with different hydrothermal times, and the influences of hydrothermal time on the structure and photocatalytic performance of TiO2 were investigated. The obtained samples were characterized by XRD, SEM, TEM, BET, PL and DRS, separately. The results show that TiO2 forms anatase when the hydrothermal time is 12 h, forms a mixed crystal composed of anatase and rutile when the hydrothermal time is 24 h, and forms rutile when the hydrothermal time is 36 h. With the extension of hydrothermal time, anatase gradually transforms into rutile and the surface area decreases. Although TiO2-24 h and TiO2-36 h show lower photoinduced charge recombination and higher light source utilization, TiO2-12 h exhibits the highest photocatalytic activity owing to its largest surface area (145.3 m2/g). The degradation degree of rhodamine B and tetracycline hydrochloride reach 99.6% and 90.0% after 45 min.

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