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Metallic Al has been deemed an ideal electrode material for aqueous batteries by virtue of its abundance and high theoretical capacity (8056 mAh cm-3). However, the development of aqueous Al metal batteries has been hindered by several side reactions, including water decomposition, Al corrosion, and passivation, which arise from the solvation reaction of Al and H2O in conventional aqueous electrolytes. In this work, we report that water activity in electrolyte can be suppressed by optimizing the Al3+ solvation structure through intercalation of polar pyridine-3-carboxylic acid in an aluminum trifluoromethanesulfonate aqueous environment. Furthermore, the pyridine-3-carboxylic acid molecules are inclined to alter the surface energy of Al, thus suppressing the random deposition of Al. As a result, the Al corrosion in the hybrid electrolyte is restrained, and the long-term electrochemical stability of the electrolyte is tremendously improved. These merits bring remarkable reversibility to aqueous Al batteries using Al-preintercalated MnO2 cathodes, delivering a retaining energy density of >250 Wh kg-1 at 0.2 A g-1 after 600 cycles.
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Aqueous zinc-ion batteries (AZIBs) suffer from sharp cycling deterioration due to serious interfacial side reactions and corrosion problems on the zinc anode. Herein, an efficacious approach to construct hydrophobic ZnMoO4 coatings on Zn (denoted as Zn@ZMO) is proposed to mitigate direct contact between the zinc anode and electrolyte and enhance its cycle life. The hydrophobic ZnMoO4 layer (contact angle = 128°) with a honeycomb-like structure is prepared by an in situ liquid phase deposition method. The as-prepared ZnMoO4 coating exhibits persistent corrosion protection for Zn through 30 days of immersion in a 2 M ZnSO4 electrolyte, indicating excellent stability of the ZnMoO4 layer and ensuring its available application in AZIBs. Unique microchannels in this kind of honeycomb-like structured coating favor Zn2+ ion diffusion and ease of ion transport, especially at high current cycling. Its robust surface exclusion can effectively counter other side reactions induced by water, simultaneously. As a result, the Zn@ZMO symmetrical cell shows a remarkable cycle lifespan exceeding 2700 h at 1 mA cm-2/1 mA h cm-2, surpassing that of the bare zinc cell by more than 100 folds. At a current density of 5 A g-1, the Zn@ZMO//V2O5 cell can still achieve a specific capacity of 167.0 mA h g-1 after 500 cycles with a capacity retention rate of 88%, which demonstrates its long-term cycling stability.
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BACKGROUND: Schwannomas are the most common intrathoracic neurogenic tumors. In the past, they were often treated by traditional open surgery. Video-assisted thoracic surgery (VATS) has also been used for some large tumors. Recently, minimally invasive posterior neurosurgical technique provides a new option for some of these tumors. METHOD: Here, we describe the specific steps involved in the O-arm guided minimally invasive removal of intrathoracic epidural schwannoma, as well as its advantages and limitations. CONCLUSION: O-arm guided minimally invasive resection of intrathoracic epidural schwannoma is safe and effective and causes little damage.
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Neurilemoma , Cirugía Asistida por Computador , Humanos , Imagenología Tridimensional , Tomografía Computarizada por Rayos X , Neurilemoma/diagnóstico por imagen , Neurilemoma/cirugía , Procedimientos NeuroquirúrgicosRESUMEN
There are various indoor fingerprint localization techniques utilizing the similarity of received signal strength (RSS) to discriminate the similarity of positions. However, due to the varied states of different wireless access points (APs), each AP's contribution to RSS similarity varies, which affects the accuracy of localization. In our study, we analyzed several critical causes that affect APs' contribution, including APs' health states and APs' positions. Inspired by these insights, for a large-scale indoor space with ubiquitous APs, a threshold was set for all sample RSS to eliminate the abnormal APs dynamically, a correction quantity for each RSS was provided by the distance between the AP and the sample position to emphasize closer APs, and a priority weight was designed by RSS differences (RSSD) to further optimize the capability of fingerprint distances (FDs, the Euclidean distance of RSS) to discriminate physical distance (PDs, the Euclidean distance of positions). Integrating the above policies for the classical WKNN algorithm, a new indoor fingerprint localization technique is redefined, referred to as FDs' discrimination capability improvement WKNN (FDDC-WKNN). Our simulation results showed that the correlation and consistency between FDs and PDs are well improved, with the strong correlation increasing from 0 to 76% and the high consistency increasing from 26% to 99%, which confirms that the proposed policies can greatly enhance the discrimination capabilities of RSS similarity. We also found that abnormal APs can cause significant impact on FDs discrimination capability. Further, by implementing the FDDC-WKNN algorithm in experiments, we obtained the optimal K value in both the simulation scene and real library scene, under which the mean errors have been reduced from 2.2732 m to 1.2290 m and from 4.0489 m to 2.4320 m, respectively. In addition, compared to not using the FDDC-WKNN, the cumulative distribution function (CDF) of the localization errors curve converged faster and the error fluctuation was smaller, which demonstrates the FDDC-WKNN having stronger robustness and more stable localization performance.
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BACKGROUND: Oncostatin M (OSM) may promote type 2 inflammation in chronic rhinosinusitis with nasal polyps (CRSwNP) by inducing thymic stromal lymphopoietin (TSLP). OBJECTIVE: We sought to study the impact of OSM on TSLP synthesis and release from nasal epithelial cells (NECs). METHODS: OSM receptors, IL-4 receptors (IL-4R), and TSLP were evaluated in mucosal tissue and primary NECs from patients with CRSwNP by quantitative PCR and immunofluorescence. Air-liquid interface-cultured NECs were stimulated with cytokines, including OSM, and quantitative PCR, ELISA, Western blot, and flow cytometry were used to assess the expression of OSM receptors, IL-4R, and TSLP. RESULTS: Increased levels of OSM receptor ß chain (OSMRß), IL-4Rα, and TSLP were observed in nasal polyp tissues and primary epithelial cells from nasal polyps of patients with CRSwNP compared with control tissues or cells from control subjects. The level of expression of OSMRß in tissue was correlated with levels of both IL-4Rα and TSLP. OSM stimulation of NECs increased the expression of OSMRß and IL-4Rα. Stimulation with IL-4 plus OSM augmented the production of TSLP; the response was suppressed by a signal transducer and activator of transcription 6 inhibitor. Stimulation of NECs with IL-4 plus OSM increased the expression of proprotein convertase subtilisin/kexin 3, an enzyme that truncates and activates TSLP. CONCLUSIONS: OSM increases the expression of IL-4Rα and synergizes with IL-4 to induce the synthesis and release of TSLP in NECs. Because the combination of IL-4 and OSM also augmented the expression of proprotein convertase subtilisin/kexin 3, these results suggest that OSM can induce both synthesis and posttranslational processing/activation of TSLP, promoting type 2 inflammation.
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Interleucina-4 , Pólipos Nasales , Oncostatina M , Rinitis , Sinusitis , Humanos , Enfermedad Crónica , Citocinas/metabolismo , Inflamación/metabolismo , Interleucina-4/metabolismo , Mucosa Nasal/metabolismo , Pólipos Nasales/metabolismo , Oncostatina M/metabolismo , Proproteína Convertasas/metabolismo , Rinitis/metabolismo , Sinusitis/metabolismo , Subtilisinas/metabolismo , Linfopoyetina del Estroma TímicoRESUMEN
BACKGROUND: Single nucleotide polymorphism (SNP) of candidate genes also affects the occurrence and prognosis of liver cancer. We mainly explored the effects of PIK3R3 and NOTCH2 polymorphisms on liver cancer risk among Chinese people. METHODS: Four SNPs (rs785468, rs785467, rs3795666, and rs17024525 in PIK3R3 and NOTCH2) from 709 liver cancer patients and 700 healthy controls were genotyped using the Agena MassARRAY system. The correlation between SNPs and liver cancer risk was evaluated using logistic regression analysis. The SNP-SNP interactions were conducted by the multifactor dimensionality reduction method. RESULTS: The results revealed that PIK3R3-rs785467 reduced the likelihood of liver cancer among Chinese Han people (p < 0.05). In addition, PIK3R3-rs785467 decreased the susceptibility to liver cancer in different populations (females, non-smokers, and age >55 years, p < 0.05). NOTCH2-rs3795666 reduced the susceptibility to liver cancer among males, drinkers, and patients aged >55 years (p < 0.05). CONCLUSIONS: Our results demonstrate that PIK3R3-rs785476 and NOTCH2-rs3795666 polymorphisms are responsible for decreasing the susceptibility of liver cancer development in the Chinese Han population.
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Predisposición Genética a la Enfermedad , Neoplasias Hepáticas , Fosfatidilinositol 3-Quinasas , Receptor Notch2 , Femenino , Humanos , Masculino , Estudios de Casos y Controles , China/epidemiología , Genotipo , Neoplasias Hepáticas/genética , Fosfatidilinositol 3-Quinasas/genética , Polimorfismo de Nucleótido Simple , Receptor Notch2/genética , Persona de Mediana Edad , Pueblos del Este de AsiaRESUMEN
INTRODUCTION: Chronic kidney disease-mineral and bone disorder (CKD-MBD) is frequently observed in maintenance hemodialysis (MHD) patients and is associated with fracture, muscle weakness, malnutrition, etc.; however, relationships of CKD-MBD markers and fatigue are not well established. METHODS: This was a cross-sectional study including 244 MHD patients (89 elders) from July to September 2021 in the First Affiliated Hospital of Shandong First Medical University. CKD-MBD markers and other clinical data were collected from medical records. Fatigue in the past week was measured by Standardized Outcomes in Nephrology-Hemodialysis (SONG-HD) fatigue measure; fatigue at the end of hemodialysis was measured by numeric rating scale (NRS). Spearman correlation, linear regression, and robust linear regression were. RESULTS: In all MHD patients, lg[25(OH)D] (nmol/L) was negatively correlated with SONG-HD score (ß = -1.503, 95% CI: -2.826 to 0.18, p = 0.026) and NRS score (ß = -1.532, p = 0.04) in multiple regression models adjusting for sex, age, and all CKD-MBD characters; but no correlations were found on univariate regression or in other multiple regression models. Interaction effects between age ≥65 years and lg(25[OH]D [nmol/L]) in terms of fatigue scores were significant based on multiple linear regressions (SONG-HD score ß = -3.613, p for interaction = 0.006; NRS score ß = -3.943, p for interaction = 0.008). Compared with non-elderly patients, elderly patients were with higher ACCI scores (7 [6, 8] vs. 4 [3, 5], p < 0.001), higher SONG-HD scores (3 [2, 6] vs. 2 [1, 3], p < 0.001), higher NRS score (4 [2, 7] vs. 3 [1, 5], p < 0.001), lower serum phosphate levels (1.65 [1.29, 2.10] vs. 1.87 [1.55, 2.26] mmol/L, p = 0.002), and lower serum iPTH levels (160.6 [90.46, 306.45] vs. 282.2 [139, 445.7] pg/mL, p < 0.001). There were no differences in serum calcium, alkaline serum, or 25(OH)D levels between the two groups. In elderly patients, lg[25(OH)D] was negatively correlated with SONG-HD score (ß = -3.323, p = 0.010) and NRS score (ß = -3.521, p = 0.006) on univariate linear regressions. Following adjustment for sex, age, and all CKD-MBD characters, lg[25(OH)D] was negatively correlated with SONG-HD scores (multiple linear regression ß = -4.012, p = 0.004; multiple robust regression ß = -4.012, p = 0.003) or NRS scores (multiple linear regression ß = -4.104, p = 0.002; multiple robust regression ß = -4.104, p = 0.001). There were no significant correlations between fatigue scores and other CKD-MBD markers (calcium, phosphate, lgiPTH, alkaline phosphatase) in elderly MHD patients, on either univariate linear regressions or multiple regressions. CONCLUSION: Serum 25(OH)D level is negatively associated with fatigue in elderly MHD patients.
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Trastorno Mineral y Óseo Asociado a la Enfermedad Renal Crónica , Humanos , Anciano , Persona de Mediana Edad , Calcio , Estudios Transversales , Diálisis Renal , Fatiga/etiología , Fosfatos , Hormona ParatiroideaRESUMEN
PURPOSE: To identify risk factors for major postoperative complications in meningioma patients and to construct and validate a nomogram that identify patients at high risk of these complications. METHODS: The medical records of meningioma patients who underwent surgical resection in our hospital from January 2018 to December 2020 were collected. The patients were divided into a training set (815 cases from the main campus in 2018 and 2019) and a validation set (300 cases from two other campuses in 2020). Major postoperative complications were defined as any new neurological deficits and complications classified as Clavien-Dindo Grading (CDG) II or higher. Univariate and multivariate analyses were conducted using the training set to identify independent risk factors. A nomogram was constructed based on these results. And then validated the nomogram through bootstrap re-sampling in both the training and validation sets. The concordance index (C-index) and the area under the curve (AUC) were used to assess the discriminative ability of the nomogram. The Hosmer-Lemeshow test was performed to evaluate the goodness-of-fit. The optimal cutoff point for the nomogram was calculated using Youden's index. RESULTS: In the training set, 135 cases (16.56%) experienced major postoperative complications. The independent risk factors identified were male sex, recurrent tumors, American Society of Anesthesiologists (ASA) class III-IV, preoperative Karnofsky Performance Scale (KPS) score < 80, preoperative serum albumin < 35 g/L, tumor in the skull base or central sulcus area, subtotal tumor resection (STR), allogeneic blood transfusion, and larger tumor size. A nomogram was constructed based on these risk factors. It demonstrated good predictive performance, with a C-index of 0.919 for the training set and 0.872 for the validation set. The area under the curve (AUC) > 0.7 indicated satisfactory discriminative ability. The Hosmer-Lemeshow test showed no significant deviation from the predicted probabilities. And the cutoff for nomogram total points was about 200 (specificity 0.881 and sensitivity 0.834). CONCLUSIONS: The constructed nomogram demonstrated robust predictive performance for major postoperative complications in meningioma patients. This model can be used by surgeons as a reference in clinical decision-making.
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Neoplasias Meníngeas , Meningioma , Humanos , Masculino , Femenino , Meningioma/cirugía , Nomogramas , Complicaciones Posoperatorias/epidemiología , Factores de Riesgo , Neoplasias Meníngeas/cirugía , Estudios RetrospectivosRESUMEN
OBJECTIVE: Adrenocorticotrophic hormone excessive secretion in pituitary-dependent Cushing disease (CD) patients may lead to anatomic variations of the nasal-sphenoidal corridor as a result of hormone-induced abnormal soft tissue change. However, there is still a lack of data on anatomic dimensions in CD patients. In this study, magnetic resonance images were analyzed to determine the anatomic variations of the nasal cavity and sphenoid sinus in CD patients. METHODS: A retrospective radiographic analysis was conducted on CD patients undergoing endonasal transsphenoidal surgery as primary treatment between January 2013 and December 2017. A total of 97 CD patients and 100 controls were included. The nasal and sphenoidal anatomic dimensions of CD patients were compared with the control group. RESULTS: Both sides of nasal cavity height, middle nasal meatus width, and inferior nasal meatus width in CD patients were narrower than that of controls. When compared with controls, the ratio of the middle turbinate to middle nasal meatus and the ratio of inferior turbinate to inferior nasal meatus was found to increase on both sides in CD patients. Intercarotid distance of CD patients was shorter than that of controls. The most prevalent pneumatization pattern of CD patients was postsellar, followed by sellar, presellar, and conchal. CONCLUSIONS: Cushing disease patients have nasal and sphenoidal anatomic variations affecting the endonasal transsphenoidal surgical corridor, especially the shorter intercarotid distance. The neurosurgeon should be aware of these anatomic variations, and adapt surgical techniques and optimal approaches to reach the sella safely.
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Hipersecreción de la Hormona Adrenocorticotrópica Pituitaria (HACT) , Silla Turca , Humanos , Silla Turca/diagnóstico por imagen , Silla Turca/cirugía , Estudios Retrospectivos , Hipersecreción de la Hormona Adrenocorticotrópica Pituitaria (HACT)/diagnóstico por imagen , Hipersecreción de la Hormona Adrenocorticotrópica Pituitaria (HACT)/cirugía , Cavidad Nasal/diagnóstico por imagen , Cavidad Nasal/cirugía , Cornetes Nasales , Seno Esfenoidal/diagnóstico por imagen , Seno Esfenoidal/cirugíaRESUMEN
BACKGROUND: Increased activation of the coagulation cascade and diminished fibrinolysis combine to promote fibrin deposition and polyp formation in chronic rhinosinusitis (CRS) with nasal polyps (CRSwNP). More information is needed concerning mechanisms of coagulation in CRSwNP. OBJECTIVE: We investigated the mechanisms as well as the initiation and regulation of coagulation cascade activation in CRS. METHODS: Samples were collected from 135 subjects with CRSwNP, 80 subjects with chronic CRS without nasal polyps (NP), and 65 control subjects. The levels of activated factor X (FXa), prothrombin fragment 1+2 (F1+2), thrombin-antithrombin complex, tissue factor (TF), and TF pathway inhibitor (TFPI) were monitored in CRS by real-time PCR, ELISA, immunohistochemistry, or immunofluorescence. Heteromeric complexes of TF with activated factor VII (FVII) and TF with activated FVII and FXa were assessed by coimmunoprecipitation and Western blotting. RESULTS: Increased levels of FXa, F1+2, and thrombin-antithrombin complex were detected in NP tissue compared to uncinate tissue from CRS and control subjects. Although free TF protein levels were not increased in NP, immunoprecipitation of TF in NP tissue revealed increased complexes of TF with FVII. Local expression of FVII was detected in sinonasal mucosa, and the ratio of TFPI to FXa was lower in NP tissue. CONCLUSION: The coagulation cascade is associated with NP compared to control and uncinate tissue from CRS patients, and TF and FVII are produced locally in sinonasal mucosa in patients. TF and FVII can activate the extrinsic coagulation pathway, suggesting that this pathway may activate fibrin deposition in CRSwNP. Reduced formation of the complex of FXa and TFPI in NP may reduce natural suppression of the extrinsic coagulation pathway in CRSwNP.
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Pólipos Nasales , Rinitis , Sinusitis , Coagulación Sanguínea , Enfermedad Crónica , Fibrina , Humanos , Pólipos Nasales/metabolismo , Rinitis/metabolismo , Sinusitis/metabolismo , TromboplastinaRESUMEN
Aqueous Zn-Iodine (I2 ) batteries are attractive for large-scale energy storage. However, drawbacks include, Zn dendrites, hydrogen evolution reaction (HER), corrosion and, cathode "shuttle" of polyiodines. Here we report a class of N-containing heterocyclic compounds as organic pH buffers to obviate these. We evidence that addition of pyridine /imidazole regulates electrolyte pH, and inhibits HER and anode corrosion. In addition, pyridine and imidazole preferentially absorb on Zn metal, regulating non-dendritic Zn plating /stripping, and achieving a high Coulombic efficiency of 99.6 % and long-term cycling stability of 3200â h at 2â mA cm-2 , 2â mAh cm-2 . It is also confirmed that pyridine inhibits polyiodines shuttling and boosts conversion kinetics for I- /I2 . As a result, the Zn-I2 full battery exhibits long cycle stability of >25 000â cycles and high specific capacity of 105.5â mAh g-1 at 10â A g-1 . We conclude organic pH buffer engineering is practical for dendrite-free and shuttle-free Zn-I2 batteries.
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Silicon is considered the most promising candidate for anode material in lithium-ion batteries due to the high theoretical capacity. Unfortunately, the vast volume change and low electric conductivity have limited the application of silicon anodes. In the silicon anode system, the binders are essential for mechanical and conductive integrity. However, there are few reviews to comprehensively introduce binders from the perspective of factors affecting performance and modification methods, which are crucial to the development of binders. In this review, several key factors that have great impact on binders' performance are summarized, including molecular weight, interfacial bonding, and molecular structure. Moreover, some commonly used modification methods for binders are also provided to control these influencing factors and obtain the binders with better performance. Finally, to overcome the existing problems and challenges about binders, several possible development directions of binders are suggested.
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Litio , Silicio , Suministros de Energía Eléctrica , Electrodos , IonesRESUMEN
OBJECTIVE: This study aimed to examine the effects of combining transcranial direct current stimulation (tDCS) and foot core exercise (FCE) on the sensorimotor function of the foot (i.e., toe flexor strength and passive ankle kinesthesia) and static balance. METHODS: In this double-blinded and randomized study, 30 participants were randomly assigned into two groups: tDCS combined with FCE and sham combined with FCE (i.e., control group). The participants received 2 mA stimulation for 20 min concurrently with FCE over 4 weeks (i.e., three sessions per week). After the first two groups completed the intervention, a reference group (FCE-only group) was included to further explore the placebo effects of sham by comparing it with the control group. Foot muscle strength, passive ankle kinesthesia, and static balance were assessed at baseline and after the intervention. RESULTS: Compared with the control group and baseline, tDCS combined with FCE could increase toe flexor strength (p < 0.001) and decrease the passive kinesthesia threshold of ankle eversion (p = 0.002). No significant differences in static balance were observed between tDCS + FCE and control groups. The linear regression models showed an association towards significance between the percent changes in metatarsophalangeal joint flexor strength and the anteroposterior average sway velocity of the center of gravity in one-leg standing with eyes closed following tDCS + FCE (r2 = 0.286; p = 0.057). The exploratory analysis also showed that compared with FCE alone, the sham stimulation did not induce any placebo effects during FCE. CONCLUSION: Participating in 4 weeks of intervention using tDCS in combination with FCE effectively enhances toe flexor strength and foot-ankle sensory function.
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Terapia por Ejercicio , Equilibrio Postural , Estimulación Transcraneal de Corriente Directa , Humanos , Extremidad Inferior , Equilibrio Postural/fisiologíaRESUMEN
LncRNA RHPN1-AS1 (RHPN1-AS1) has been confirmed to promote tumor progression in multiple cancers and is upregulated in prostate cancer (PCa), but whether it has an effect on PCa progression remains unclear. In this study, we found that PCa patients with high RHPN1-AS1 expression had a shorter survival time, and RHPN1-AS1 was significantly upregulated in PCa tissues and cells. Based on informatics analysis we predicted that miR-7-5p binds to 3'UTR of RHPN1-AS1 and epidermal growth factor receptor (EGFR) and verified it by luciferase reporter gene assay. Subsequently, we transfected PCa cells with RHPN1-AS1 overexpression vector (RHPN1-AS1), knockdown plasmids (sh-RHPN1-AS1) and/or miR-7-5p mimics or inhibitor and/or overexpression vector (EGFR) or small interfering RNA of EGFR (si-EGFR) or its control, and found that overexpression of RHPN1-AS1 inhibited miR-7-5p expression and promoted EGFR expression, silencing RHPN1-AS1 inhibited proliferation and invasion, and induced G2/M arrest, apoptosis and autophagy in PCa cells. 3MA (an inhibitor of autophagy)-mediated autophagy inhibition attenuated RHPN1-AS1 inhibition-induced apoptosis. Overexpression miR-7-5p or silencing EGFR promoted LC3-I to LC3-II conversion, enhanced autophagy activity, induced cleaved-caspase-3 expression and apoptosis in PCa cells. Furthermore, overexpression of RHPN1-AS1 promoted phosphorylation of phosphatidylinositol 3-kinase (PI3K), AKT and mTOR, inhibited LC3-I to LC3-II conversion and reduced apoptosis in PCa cells, while GSK2126458 (an inhibitor of PI3K) reversed the effect of RHPN1-AS1 on PCa cells. In summary, RHPN1-AS1 acted as a ceRNA of miR-7-5p to upregulate EGFR expression, silencing RHPN1-AS1 suppressed PCa tumor progression by inducing autophagy and apoptosis in PCa cells through the miR-7-5p/EGFR/PI3K/AKT/mTOR pathway.
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MicroARNs , Neoplasias de la Próstata , ARN Largo no Codificante , Masculino , Humanos , ARN Largo no Codificante/genética , ARN Largo no Codificante/metabolismo , Fosfatidilinositol 3-Quinasas/metabolismo , Proteínas Proto-Oncogénicas c-akt/metabolismo , Apoptosis/genética , Fosfatidilinositol 3-Quinasa/metabolismo , Fosfatidilinositol 3-Quinasa/farmacología , Proliferación Celular/genética , Línea Celular Tumoral , Puntos de Control de la Fase G2 del Ciclo Celular , MicroARNs/genética , MicroARNs/metabolismo , Serina-Treonina Quinasas TOR/genética , Serina-Treonina Quinasas TOR/metabolismo , Transducción de Señal/genética , Neoplasias de la Próstata/genética , Neoplasias de la Próstata/patología , Autofagia/genética , Receptores ErbB/genética , Receptores ErbB/metabolismoRESUMEN
BACKGROUND: A large-scale global outbreak of coronavirus disease-19 (COVID-19) out of Wuhan, from China, occurred in January 2020. To examine the clinical characteristics of COVID-19 in infected patients out of Wuhan, from China. METHODS: Thirteen patients were confirmed to be infected with novel coronavirus-2019 (2019-nCoV) between January 27 and February 8, 2020, in Baoji city, Shannxi, northwestern China. Epidemiological and clinical information, and computed to morphology imaging data from all COVID-19 patients were collected; cases were divided into two groups according to the severity of infection (mild or severe). RESULTS: Nine (9/13) COVID-19 patients exhibited mild disease severity, and defined as second-generation human-to-human transmission cases. Most patients (11/13) had a history of travel to or from Wuhan. There were no differences in sex and age between the mild and severe cases (all P > 0.05). A moderate degree of fever (11/13), cough (13/13), and fatigue (8/13) were common symptoms; however, there was no statistical difference between mild and severe cases in this regard (all P > 0.05). Oxyhemoglobin saturation and oxygenation index decreased, and C-reactive protein (CRP) and serum amyloid A (SAA) levels were elevated in all patients with COVID-19 infection, with statistically significant differences between those with severe disease and mild infection (all P < 0.05). Twelve of 13 COVID-19 patients exhibited changes in chest CT imaging features, and time course changes were different between mild and severe cases (all P < 0.05). CONCLUSION: Most cases of COVID-19 infection were second-generation human-to-human transmissions from Wuhan and were mild in severity. The clinical characteristics of COVID-19 varied. Oxyhemoglobin saturation, oxygenation index, CRP and SAA levels, and CT features were reliable parameters to evaluate the severity of COVID-19 infection. However, a few patients with mild COVID-19 disease lacked typical characteristics such as fever and changes in CT imaging features.
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COVID-19/complicaciones , SARS-CoV-2 , Adulto , Anciano , Proteína C-Reactiva/análisis , COVID-19/sangre , COVID-19/epidemiología , Estudios de Casos y Controles , China/epidemiología , Femenino , Humanos , Masculino , Persona de Mediana Edad , Proteína Amiloide A Sérica/análisis , Tomografía Computarizada por Rayos XRESUMEN
Objective: The aim of this study was to analyze the effects of saikosaponin-d (SSd) on autophagy activity and radiosensitivity of hepatoma cells, and to elucidate its related molecular mechanisms. Methods: The growth of SMMC-7721 and MHCC97L hepatoma cells were detected by clonal formation and survival fraction. Flow cytometry was used to detect the changes of apoptosis of hepatoma cells. The morphological changes of autophagy of hepatoma cells were observed by transmission electron microscopy and were further quantitatively detected by laser confocal microscopy. The expressions of related proteins were detected by Western blotting. Results: SSd can significantly increase the apoptosis of hepatoma cells induced by radiation and inhibit the proliferation of hepatoma cells. The addition of the autophagy inhibitor chloroquine (CQ) or an mTOR agonist (MHY1485), which could reduce the promoting effect of SSd on radiation-induced apoptosis and inhibitory effect on the proliferation of hepatoma cells. Transmission electron microscopy and confocal microscopy results also showed that the number of autophagosomes was significantly higher in the radiation and SSd co-treatment group than in the radiotherapy or SSd alone group; however, the effect of SSd on autophagy in hepatoma cells was decreased after adding MHY1485, siRNA-P53 or AMPK inhibitor (Compound C). Western blot analysis showed that after the addition of SSd, the phosphorylation of mTOR was significantly decreased by radiation, the expression of the autophagy-related proteins LC3-II and Beclin-1 was increased, p62 was decreased, and the expression of cleaved caspase-3 and cleaved PARP was enhanced; this effect of SSd was partially reversed after the addition of MHY1485, siRNA-P53 or Compound C. Conclusions: SSd increases radiation-induced apoptosis of hepatoma cells by promoting autophagy via inhibiting mTOR phosphorylation and providing a possible potential approach for radiosensitization therapy of liver cancer.
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Carcinoma Hepatocelular/terapia , Quimioradioterapia/métodos , Neoplasias Hepáticas/terapia , Ácido Oleanólico/análogos & derivados , Saponinas/farmacología , Apoptosis/efectos de los fármacos , Apoptosis/efectos de la radiación , Autofagia/efectos de los fármacos , Carcinoma Hepatocelular/patología , Línea Celular Tumoral , Humanos , Neoplasias Hepáticas/patología , Ácido Oleanólico/farmacología , Ácido Oleanólico/uso terapéutico , Fosforilación/efectos de los fármacos , Tolerancia a Radiación/efectos de los fármacos , Saponinas/uso terapéutico , Serina-Treonina Quinasas TOR/metabolismoRESUMEN
OBJECTIVES: Microglia activation, a key process in secondary injury following intracerebral hemorrhage (ICH), is divided to M1 and M2 phenotype. Protocatechuic acid (PCA) is a phenolic acid been proved neuroprotection in ICH without understanding of details. Thus, this study aimed to observe the influence of PCA on microglia activation and explore underlying mechanisms. MATERIALS AND METHODS: To assess PCA affected microglia activation in vivo, an experimental ICH mice model was established and then treated with PCA intraperitoneal injection. Immunofluorescence staining was performed in brain slices at day 3 post ICH. BV2 cells were stimulated with hemin for activation, then M1 and M2 biomarkers were analyzed using Western Blot and qPCR. At last, we detected the expression of mTOR and its downstream molecules to discuss possible mechanisms. RESULTS: At day 3 post ICH, less activated microglia gathering around hematoma after PCA treatment. Furtherly, in hemin treated BV2 cells, PCA downregulated M1 and promoted M2 biomarkers expression in both mRNA and protein level. PCA inhibited the phosphorylation of mTOR, S6K1 and 4E-BP1, while the inhibition was disappeared after supplemented with mTOR activator. CONCLUSIONS: PCA impacted microglia activation by suppressing the mTOR signaling pathway, thereby improving M1/M2 switch and attenuated neuroinflammation.
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Antiinflamatorios/farmacología , Hemorragia Cerebral/tratamiento farmacológico , Hidroxibenzoatos/farmacología , Microglía/efectos de los fármacos , Fármacos Neuroprotectores/farmacología , Proteínas Adaptadoras Transductoras de Señales/metabolismo , Animales , Proteínas de Ciclo Celular/metabolismo , Línea Celular , Hemorragia Cerebral/metabolismo , Hemorragia Cerebral/patología , Modelos Animales de Enfermedad , Masculino , Ratones Endogámicos C57BL , Microglía/metabolismo , Microglía/patología , Fenotipo , Fosforilación , Proteínas Quinasas S6 Ribosómicas 90-kDa/metabolismo , Transducción de Señal , Serina-Treonina Quinasas TOR/metabolismoRESUMEN
Acquired radioresistance compromises the efficacy of radiotherapy for carcinomas including esophageal cancer (EC), thus resulting in recurrence and poor survival. Recent research corroborated radiosensitive function of simvastatin in stem-like breast cancer cells. However, its role in EC radioresistance remains poorly elucidated. Here, we developed a radioresistant EC cell line Ec9706-R with higher resistance to irradiation relative to control Ec9706 cells. Intriguingly, Ec9706-R cells exhibited epithelial-mesenchymal transition (EMT) characteristics with high invasion and migration ability. Simvastatin sensitized radioresistance of Ec9706-R cells and suppressed cell proliferation, but aggravated radiation-induced apoptosis and caspase-3 activity. Furthermore, simvastatin reversed EMT and inhibited cell invasion and migration of Ec9706-R cells. Mechanism assay confirmed the activation of PI3K/AKT pathway after radiation, which was inhibited by simvastatin. After restoring this pathway by its activator, IGF-1, simvastatin-mediated radiosensitivity and EMT reversion were abrogated. Further assay substantiated the PTEN suppression after irradiation, which was elevated following simvastatin pre-treatment. Moreover, PTEN cessation attenuated the inhibitory effect of simvastatin on PI3K/AKT activation, and subsequently antagonized simvastatin-induced radiosensitivity and EMT reversion. Additionally, simvastatin aggravated radiation-mediated Ec9706-R tumor growth inhibition. Together, simvastatin inhibits the development of Ec9706-R cells by increasing radiosensitivity and reversing EMT via PTEN-PI3K/AKT pathway, implying a promising strategy against EC radioresistance.
Asunto(s)
Neoplasias Esofágicas/tratamiento farmacológico , Neoplasias Esofágicas/radioterapia , Tolerancia a Radiación/genética , Simvastatina/farmacología , Línea Celular Tumoral , Neoplasias Esofágicas/genética , Neoplasias Esofágicas/patología , Regulación Neoplásica de la Expresión Génica/efectos de los fármacos , Humanos , Proteína Oncogénica v-akt/genética , Fosfohidrolasa PTEN/genética , Fosfatidilinositol 3-Quinasas/genética , Tolerancia a Radiación/efectos de los fármacos , Transducción de Señal/efectos de los fármacosRESUMEN
BACKGROUND: Chronic rhinosinusitis with nasal polyps (CRSwNP) is associated with mast cell-mediated inflammation and heightened oxidant stress. Kynurenine (KYN), an endogenous tryptophan metabolite, can promote allergen-induced mast cell activation through the aryl hydrocarbon receptor (AhR). OBJECTIVES: We sought to determine the role of the KYN/AhR axis and oxidant stress in mast cell activation and the development of CRSwNP. METHODS: We measured the expression of indoleamine 2,3-dioxygenase 1, tryptophan 2,3-dioxygenase, KYN, and oxidized calmodulin-dependent protein kinase II (ox-CaMKII) in nasal polyps and controls. KYN-potentiated ovalbumin (OVA)-induced ROS generation, cell activation, and ox-CaMKII expression were investigated in wild-type and AhR-deficient (AhR-/-) mast cells. The role of ox-CaMKII in mast cell activation was further investigated. RESULTS: Nasal polyps in CRSwNP showed an increased expression of indoleamine 2,3-dioxygenase 1, tryptophan2,3-dioxygenase, and KYN compared with controls. AhR was predominantly expressed in mast cells in nasal polyps. Activated mast cells and local IgE levels were substantially increased in eosinophilic polyps compared with noneosinophilic polyps and controls. Furthermore, KYN potentiated OVA-induced ROS generation, intracellular Ca2+ levels, cell activation, and expression of ox-CaMKII in wild-type, but not in AhR-/- mast cells. Compared with noneosinophilic polyps and controls, eosinophilic polyps showed increased expression of ox-CaMKII in mast cells. Mast cells from ROS-resistant CaMKII MMVVδ mice or pretreated with CaMKII inhibitor showed protection against KYN-promoted OVA-induced mast cell activation. CONCLUSIONS: These studies support a potentially critical but previously unidentified function of the KYN/AhR axis in regulating IgE-mediated mast cell activation through ROS and ox-CaMKII in CRSwNP.
Asunto(s)
Factores de Transcripción con Motivo Hélice-Asa-Hélice Básico/inmunología , Pólipos Nasales/inmunología , Receptores de Hidrocarburo de Aril/inmunología , Receptores de Glutamato/inmunología , Rinitis/inmunología , Sinusitis/inmunología , Animales , Factores de Transcripción con Motivo Hélice-Asa-Hélice Básico/genética , Proteína Quinasa Tipo 2 Dependiente de Calcio Calmodulina/genética , Proteína Quinasa Tipo 2 Dependiente de Calcio Calmodulina/inmunología , Enfermedad Crónica , Eosinófilos/inmunología , Eosinófilos/patología , Humanos , Indolamina-Pirrol 2,3,-Dioxigenasa/genética , Indolamina-Pirrol 2,3,-Dioxigenasa/inmunología , Mastocitos/inmunología , Mastocitos/patología , Ratones , Ratones Noqueados , Pólipos Nasales/genética , Pólipos Nasales/patología , Receptores de Hidrocarburo de Aril/genética , Receptores de Glutamato/genética , Rinitis/genética , Rinitis/patología , Transducción de Señal/genética , Transducción de Señal/inmunología , Sinusitis/genética , Sinusitis/patologíaRESUMEN
OBJECTIVE: To investigate the effects of thanatos-associated protein 11 (THAP11) on the proliferation and apoptosis of esophageal cancer cell and the underlying mechanism.â© Methods: Expression of THAP11 in human esophageal epithelial cells (Het-1A) and esophageal cancer cells (Eca109, TE-1, Ec 9706) were detected by Western blotting. Esophageal cancer TE-1 cells were divided into 3 groups: a normal control (NC) group, a negative control (LV-NC) group and a THAP11 (LV-THAP11) group. Then the cell proliferation were detected by MTT assay, cell apoptosis were detected by flow cytometry, caspase-3 and caspase-9 levels were detected by caspases kits. Ubiquitination of p53 was determined in esophageal cancer TE-1 cells.â© Results: Expression of THAP11 was reduced in esophageal cancer cells compared with human esophageal epithelial cells (P<0.05). After transfection with LV-THAP11 in TE-1 cells, cell viability was reduced (P<0.05), while apoptosis rate and caspase-3 and caspase-9 levels were increased (P<0.05), indicating that THAP11 inhibited growth of esophageal cancer cells. In addition, the THAP11 increased the levels of p53 (P<0.05) and inhibited the ubiquitination of p53 regulated by MDM2. â© Conclusion: THAP11 may inhibit the proliferation of esophageal cancer cells by inhibiting ubiquitination of p53.