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Objective To evaluate the efficacy and safety of anlotinib monotherapy and combined therapy in patients with advanced pheochromocytoma/paraganglioma. Methods Nine patients with advanced pheochromocytoma/paraganglioma (PPGL) who were admitted to the Department of Urology, Sun Yat-sen University Cancer Center from January 2018 to June 2023 were collected. Patients were divided into four groups according to different treatments: anlotinib monotherapy group (3 patients), anlotinib combined with PD-1 monoclonal antibody immunotherapy group (3 patients), anlotinib combined with immunotherapy and chemotherapy group (2 patients), and anlotinib combined with chemotherapy group (1 patients). The effectiveness and safety of different treatment regiments of anlotinib were analyzed. Results Objective response rate (ORR) : (44%), Partial response(PR): (44%), Stable disease(SD): (44%), Progressive disease(PD): (11%), Disease control rate (DCR): (89%). The ORR of 2 patients with SDH gene mutation, SDHB and SDHD respectively, was 100%. Median overall survival time(OS) was 16.3 months (IQR: 11.3 ~ 21.8 months). Median progression-free survival (PFS) was 16.3 months (IQR: 9.8 ~ 20.8 months). There were 2 patients with adverse events grade ≥ 3/4, all of which were hypertension. Conclusions Anlotinib monotherapy and combined therapy have preliminary efficacy and manageable safety in the treatment of advanced pheochromocytoma/paraganglioma. [ABSTRACT FROM AUTHOR]

Edge intelligent computing has received extensive attention from all walks of life and is widely used in many application scenarios. Recently, edge intelligent computing technique applications for energy networks have become hot topics in both scientific research and industry. However, some unique problem complexities and challenges have emerged and require advanced approaches. This article comprehensively surveys edge intelligent computing techniques for model training methods, application deployment and optimization in the field of energy networks. We review the target identification, anomaly detection and airborne light detection and ranging point cloud techniques and discuss their research statuses. We further discuss a set of possible future opportunities and new perspectives on addressing the challenges. [ABSTRACT FROM AUTHOR]

At gatherings with some professionals, many Chinese philosophy scholars often express their sorrow at the decline in first–choice applications of philosophy, even in some famous univer

Background: NAD+, nicotinamide adenine dinucleotide, is mostly described to associate with the aging process. We aimed to investigate the association between human whole blood NAD+ contents and aging in a relative large-scale community-based population and further to address the gender impact on this association. Methods: We recruited 1,518 participants aged over 18 years old and free of cardiovascular and any type of cancer from the Jidong community from 2019 to 2020. Whole blood NAD+ level was measured by cycling assay and LC-mass spectroscopy assay. The chronological age and clinical data were collected using standard questionnaires. The participants were divided into five groups according to their chronological age. General liner regression model was performed to analyze the association between NAD+ contents and aging. In addition, we also conducted subgroup analysis by gender. Results: The mean age of included 1,518 participants was 43.0 years, and 52.6% of them were men. The average levels of whole blood NAD+ of total participants was 33.0 ± 5.5 μmol/L. The whole blood NAD+ contents in men were significantly higher than that in women (34.5 vs. 31.3 μmol/L). There was significant difference in the meat diet among NAD+ quartile groups (p = 0.01). We observed a decline trend of NAD+ contents with aging before 50 years in total participants with significant level in 40–49 years old group (β coefficients with 95% confidence interval (95% CI): −1.12 (−2.18, −0.06)), while this trend disappeared after the 50 years. In addition, this association was significantly altered by gender (p for interaction = 0.003). In men, as compared with ≤29 years group, adjusted β coefficient decreased with aging but was only significant in the ≥60 year group (β,−2.16; 95% CI, −4.16 to −0.15). In females, the level of whole blood NAD+ did not significantly differ among five age groups and without the trend as males. Conclusions: Association of whole blood NAD+ contents with aging significantly differed in males and females. The loss of blood NAD+ with aging only was observed in males, especially in the male middle-aged population. It is crucial to consider the gender difference in further NAD+ related studies in the future. [ABSTRACT FROM AUTHOR]

High quality video streaming for mobile devices implies high energy consumption due to the transmitted data and the variation of wireless signals. As an example, transmissions in mobile scenarios (e.g., inside a moving bus) consumes more energy for devices than when accessing from a static environment (e.g., at home). The QoE for the user does not substantially increase when watching high bitrate videos in a vibrating environment (i.e., a moving vehicle), as the context, in this case vehicle’s vibration, affects the perceived QoE. To address this problem, we propose to save energy by considering the context (environment) of video streaming. To model the impact of context, we exploit the embedded accelerometer in smartphones to record the vibration level during video streaming. Based on quality assessment experiments, we collect traces and model the impact of video bitrate and vibration level on QoE, and model the impact of video bitrate and signal strength on power consumption. Based on the QoE model and the power model, we formulate the context-aware and energy-aware video streaming problem as an optimization problem. We present an optimal algorithm which can maximize QoE and minimize energy. Since the optimal algorithm requires perfect knowledge of future tasks, we propose an online bitrate selection algorithm. To further improve the performance of the online algorithm, we propose a crowdsourcing based bitrate selection algorithm. Through real measurements and trace-driven simulations, we demonstrate that the proposed algorithms can significantly outperform existing approaches when considering both energy and QoE. [ABSTRACT FROM AUTHOR]

Long noncoding RNAs (lncRNAs) can participate in various biological behaviors, including regulating cell differentiation, proliferation, and apoptosis. The investigators have previously confirmed that highly conserved lncRNA NR_045363 controls cardiomyocyte (CM) proliferation and cardiac repair. The present study investigates the effects of NR_045363 on CM apoptosis. Seven‐day‐old mice were subjected to permanent left anterior descending coronary artery ligation (LAD), and the NR_045363 expression was analyzed by quantitative real‐time polymerase chain reaction (qRT‐PCR). The expression of NR_045363 in the MI group significantly exceeded the Sham group during the first week after the operation. The NR_045363 expression was knocked down in primary cultured CMs using an NR_045363‐targeting lncRNA Smart silencer, and the apoptosis of CMs was analyzed by terminal‐deoxynucleoitidyl transferase mediated nick end labeling and Annexin‐V/PI double staining. These present results indicate that the NR_045363 knockdown significantly promoted the apoptosis of CMs. In order to investigate the underlying mechanism, RNA‐sequencing (RNA‐seq) was performed, and ingenuity pathway analysis (IPA) was used to analyze the RNA‐seq results. The RNA‐seq data revealed that a total of 2,291 genes were upregulated or downregulated in NR_045363 knockdown CMs, and the IPA analysis indicated that tumor protein 53 (p53) was the upstream regulator. In vivo, the NR_045363 overexpression through the AAV9 system improved the heart function after MI in 7‐day‐old mice and inhibited the CM apoptosis. These data suggest that NR_045363 is involved in CM apoptosis and that NR_045363 overexpression exerts positive effects on cardiac repair by alleviating CM apoptosis through the inhibition of the p53 pathway. [ABSTRACT FROM AUTHOR]

The energy consumed by video streaming includes the energy consumed for data transmission and CPU processing, which are both affected by the CPU frequency. High CPU frequency can reduce the data transmission time but it consumes more CPU energy. Low CPU frequency reduces the CPU energy but increases the data transmission time and then increases the energy consumption. In this paper, we aim to reduce the total energy of mobile video streaming by adaptively adjusting the CPU frequency. Based on real measurement results, we model the effects of CPU frequency on TCP throughput and system power. Based on these models, we propose an Energy-aware CPU Frequency Scaling (EFS) algorithm which selects the CPU frequency that can achieve a balance between saving the data transmission energy and CPU energy. Since the downloading schedule of existing video streaming apps is not optimized in terms of energy, we also propose a method to determine when and how much data to download. Through trace-driven simulations and real measurement, we demonstrate that the EFS algorithm can reduce 30 percent of energy for the Youtube app, and the combination of our download method and EFS algorithm can save 50 percent of energy than the default Youtube app. [ABSTRACT FROM AUTHOR]

Background/Aims: Increasing evidence indicates that microRNAs (miRNAs) play important roles in Kawasaki disease (KD). Our previous study demonstrated that hsa-miR-27b-3p (miR-27b) was up-regulated in KD serum. However, the specific role of miR-27b in KD remains unclear. We aimed to investigate that miR-27b could be a biomarker and therapeutic target for KD treatment. As well, the specific mechanism of miR-27b effecting endothelial cell functions was studied. Methods: The expression of miR-27b and Smad7 was measured by qRT-PCR. Gain-of-function strategy was used to observe the effect of miR-27b on human umbilical vein endothelial cells (HUVECs) proliferation and migration. Bioinformatics analyses were applied to predict miR-27b targets and then we verified Smad7 by a luciferase reporter assay. Western blot was performed to detect the protein expression of Smad7, PCNA, MMP9, MMP12 and TGF-β-related genes. Results: We confirmed that miR-27b was shown to be dramatically up-regulated in KD serum and KD serum-treated HUVECs and that elevated expression of miR-27b suppressed the proliferation and migration of HUVECs. Furthermore, our results verified that miR-27b mediated cell functions by affecting the TGF-β via targeting Smad7 in HUVECs. Conclusion: These results suggested that up-regulated miR-27b had a protective role in HUVECs proliferation and migration via targeting Smad7 and affecting TGF-β pathway. Therefore, miR-27b represented a potential biomarker for KD and may serve as a promising therapeutic target for KD treatment. [ABSTRACT FROM AUTHOR]

Background: The purpose of this study was to evaluate the efficacy and safety of PD-1 blockade combined with cisplatin and paclitaxel (TP)-based chemotherapy as first-line treatment for advanced penile squamous cell carcinoma (PSCC)., Patients and Methods: A retrospective review was performed of 32 eligible patients with high-risk stage IV (cN3M0-1) PSCC who received first-line PD-1 blockade combined with TP-based chemotherapy at 5 medical centers (2019-2023). Clinical responses were assessed using RECIST version 1.1. Treatment-related adverse events (TrAEs) and postsurgical complications were graded according to CTCAE version 5.0. Progression-free survival (PFS) and overall survival (OS) were estimated using the Kaplan-Meier method. Multiplex immunofluorescence was used to explore potential biomarkers and to present the tumor microenvironment landscape before and after treatment., Results: After a median treatment duration of 4 cycles (range, 2-6), the overall objective response rate was 78.1% (25/32). Among 27 patients with locally advanced PSCC, 13 (48.1%) subsequently underwent consolidative surgery and 6 (22.2%) achieved a pathologic complete response (pCR). Additionally, 8 (25.0%) patients in the overall cohort underwent consolidated radiotherapy. Median follow-up was 21.1 months (95% CI, 14.1-42.7). Median PFS and OS were 15.0 months (95% CI, 11.4-not available [NA]) and 19.3 months (95% CI, 16.7-NA), respectively. All patients experienced TrAEs, with 50% (16/32) of them having grade ≥3 TrAEs. Higher intratumoral CD8+ T-cell infiltration was observed in pretreatment samples of responders compared with nonresponders (P=.03). CD4+ T-cells, natural killer cells, and macrophages, among others, exhibited significant changes after treatment (all P<.05), suggesting their potential involvement in the antitumor response to immunochemotherapy., Conclusions: PD-1 blockade plus TP-based chemotherapy was effective and well tolerated, with favorable survival outcomes for patients with stage IV PSCC. High pretreatment intratumoral CD8+ T-cell infiltration may help to identify potential responders.

Background: NAD + , nicotinamide adenine dinucleotide, is mostly described to associate with the aging process. We aimed to investigate the association between human whole blood NAD + contents and aging in a relative large-scale community-based population and further to address the gender impact on this association., Methods: We recruited 1,518 participants aged over 18 years old and free of cardiovascular and any type of cancer from the Jidong community from 2019 to 2020. Whole blood NAD + level was measured by cycling assay and LC-mass spectroscopy assay. The chronological age and clinical data were collected using standard questionnaires. The participants were divided into five groups according to their chronological age. General liner regression model was performed to analyze the association between NAD + contents and aging. In addition, we also conducted subgroup analysis by gender., Results: The mean age of included 1,518 participants was 43.0 years, and 52.6% of them were men. The average levels of whole blood NAD + of total participants was 33.0 ± 5.5 μmol/L. The whole blood NAD + contents in men were significantly higher than that in women (34.5 vs. 31.3 μmol/L). There was significant difference in the meat diet among NAD + quartile groups (p = 0.01). We observed a decline trend of NAD + contents with aging before 50 years in total participants with significant level in 40-49 years old group (β coefficients with 95% confidence interval (95% CI): -1.12 (-2.18, -0.06)), while this trend disappeared after the 50 years. In addition, this association was significantly altered by gender (p for interaction = 0.003). In men, as compared with ≤29 years group, adjusted β coefficient decreased with aging but was only significant in the ≥60 year group (β,-2.16; 95% CI, -4.16 to -0.15). In females, the level of whole blood NAD + did not significantly differ among five age groups and without the trend as males., Conclusions: Association of whole blood NAD + contents with aging significantly differed in males and females. The loss of blood NAD + with aging only was observed in males, especially in the male middle-aged population. It is crucial to consider the gender difference in further NAD + related studies in the future., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Yang, Deng, Yu, Luo, Chen, Zheng, Qiu, Xiao, Xie, Zhao, Guo, Hu, Zhang, Ju and Zhou.)

Chemical vapor deposition (CVD)-grown flakes of high-quality monolayers of WS 2 can be stabilized at elevated temperatures by encapsulation with several layer hexagonal boron nitride ( h- BN), but to different degrees in the presence of ambient air, flowing N 2 , and flowing forming gas (95% N 2 , 5% H 2 ). The best passivation of WS 2 at elevated temperature occurs for h -BN-covered samples with flowing N 2 (after heating to 873 K), as judged by optical microscopy and photoluminescence (PL) intensity after a heating/cooling cycle. Stability is worse for uncovered samples, but best with flowing forming gas. PL from trions, in addition to that from excitons, is seen for covered WS 2 only for forming gas, during cooling below ∼323 K; the trion has an estimated binding energy of ∼28 meV. It might occur because of doping level changes caused by charge defect generation by H 2 molecules diffusing between the h -BN and the SiO 2 /Si substrate. The decomposition of uncovered WS 2 flakes in air suggests a dissociation and chemisorption energy barrier of O 2 on the WS 2 surface of ∼1.6 eV. Fitting the high-temperature PL intensities in air gives a binding energy of a free exciton of ∼ 229 meV.

Transmembrane protein 30A ( Tmem30a ) is the β-subunit of P4-ATPases which function as flippase that transports aminophospholipids such as phosphatidylserine from the outer to the inner leaflets of the plasma membrane to maintain asymmetric distribution of phospholipids. It has been documented that deficiency of Tmem30a led to exposure of phosphatidylserine. However, the role of Tmem30a in vivo remains largely unknown. Here we found that Vav-Cre-driven conditional deletion of Tmem30a in hematopoietic cells led to embryonic lethality due to severe anemia by embryonic day 16.5. The numbers of erythroid colonies and erythroid cells were decreased in the Tmem30a deficient fetal liver. This was accompanied by increased apoptosis of erythroid cells. Confocal microscopy analysis revealed an increase of localization of erythropoietin receptor to areas of membrane raft microdomains in response to erythropoietin stimulation in Ter119 - erythroid progenitors, which was impaired in Tmem30a deficient cells. Moreover, erythropoietin receptor (EPOR)-mediated activation of the STAT5 pathway was significantly reduced in Tmem30a deficient fetal liver cells. Consistently, knockdown of TMEM30A in human CD34 + cells also impaired erythropoiesis. Our findings demonstrate that Tmem30a plays a critical role in erythropoiesis by regulating the EPOR signaling pathway through the formation of membrane rafts in erythroid cells., (Copyright© 2019 Ferrata Storti Foundation.)