bluuebunny/crossref_metadata_2025 huggingface dataset:
Mechanical characteristics analysis of horizontal lifting of subsea pipeline with different burial depths
Authors: Zhang Dapeng , Zhao Bowen , Zhu Keqiang
Published: September 2022

Different burial depths have different effects on the mechanical characteristics of the horizontal lifting of subsea pipelines. With the consideration of the soil resistance to subsea pipelines, combined with the specific sea condition parameters of a certain sea area, and based on the lumped mass method, the subsea pipeline is discretized into a lumped mass model, the dynamic analysis model of the three-point horizontal lifting of subsea pipelines with different burial depths is established. The stress and bending of the pipelines with different burial depths are analyzed. The calculation results with different burial depths are compared. The variation of mechanical characteristics of the process of lifting horizontal pipelines with different buried depths is obtained. The results show that the change of burial depth has a significant influence on the effective tension of the pipeline. With the increase of the burial depth, the maximum degree of stretching of the pipeline first decreases and then increases. Within a certain depth range, burying the pipeline in the seabed can reduce both the effective tension and the intensity of the fluctuation of the effective tension when the pipeline is lifted. The change of burial depths for the shear action is mainly reflected in the numerical values of the shear force. There is no significant impact on the degree and variation fluctuation of the shear force. The conclusions can provide a certain theoretical reference for the design of the process of horizontal pipeline lifting.
Multi-energy dispatching for uncertainty EV demand: A simulation approach
Authors: Ye Shengxuan , Dai Yuxuan , Zhang Fenglin , Qin Zhiqi , Jin Shuwen , Yan Qiyao , Xu Yangbing
Published: September 2022

Uncertainty and randomness in demand and supply bring significant challenges to the stable operation of the grid and the scheduling planning of multi-energy sources. To solve these challenges, we propose and analyze a multi-energy dispatching model which minimizes the total cost and enhances the efficiency of supplying power. Specifically, we design matching algorithms that simulate an appropriately scaled sequence of stochastic EV demand. We also analyze four different energy dispatching scenarios proving that the scheduling model and the multi-energy synergistic microgrid structure can bring higher efficiency and lower costs. Our main contribution is using a simulation approach to take EVs into account for demand-side uncertainty, which significantly improves the efficiency of grid dispatch.
Assessing the effect of energy poverty on the mental and physical health in China—Evidence from China family panel studies
Authors: Xu Wangzi , Xie Baiwei , Lou Bailu , Wang Weizheng , Wang Yuzi
Published: September 2022

Energy poverty is a crucial issue faced by countries all around the world, as the largest developing country in the world, China is also experiencing energy poverty problems. In order to explore the health effect of energy poverty in China, this paper first uses the principal component analysis (PCA) to construct a comprehensive index to measure energy poverty, and then adopts the ordinary least square method (OLS), fixed effect model (FE), instrumental variable two-stage least squares (IV-2SLS) regression to study the impact of energy poverty on the physical and mental health of Chinese people based on China Family Panel Studies 2018 (CFPS 2018). The study discovers that energy poverty significantly hampers the mental and physical health of Chinese people, an increase in energy poverty might cause 28.74%、18.69% decrease in mental and physical health respectively. Moreover, this paper further explores the influencing paths of energy poverty by intermediary effect and regulatory effect. It is revealed that in addition to directly affecting physical and mental health, energy poverty also have a negative impact on physical and mental health by affecting the accessibility of a series of resources, such as water and food, reducing the opportunities for physical exercise and increasing medical expenses. However, the impact is restricted by age and family income. Finally, under the national strategy of China, this paper further discusses how to give consideration to the joint implementation of heath and emission reduction strategies, then gives specific policy suggestions based on the results.
Review of corrosion monitoring and prognostics in offshore wind turbine structures: Current status and feasible approaches
Authors: Brijder Robert , Hagen Catalina H. M. , Cortés Ainhoa , Irizar Andoni , Thibbotuwa Upeksha Chathurani , Helsen Stijn , Vásquez Sandra , Ompusunggu Agusmian Partogi
Published: September 2022

As large wind farms are now often operating far from the shore, remote condition monitoring and condition prognostics become necessary to avoid excessive operation and maintenance costs while ensuring reliable operation. Corrosion, and in particular uniform corrosion, is a leading cause of failure for Offshore Wind Turbine (OWT) structures due to the harsh and highly corrosive environmental conditions in which they operate. This paper reviews the state-of-the-art in corrosion mechanism and models, corrosion monitoring and corrosion prognostics with a view on the applicability to OWT structures. Moreover, we discuss research challenges and open issues as well strategic directions for future research and development of cost-effective solutions for corrosion monitoring and prognostics for OWT structures. In particular, we point out the suitability of non-destructive autonomous corrosion monitoring systems based on ultrasound measurements, combined with hybrid prognosis methods based on Bayesian Filtering and corrosion empirical models.
Environmental protection and sustainable development of enterprises in China: The moderating role of media attention
Authors: Wu Lijuan , Qing Chenglin , Jin Shanyue
Published: September 2022

Faced with global environmental problems, such as global warming, enterprises have become important players in environmental protection. By fulfilling their environmental responsibilities, enterprises can create a good external image and gain support from the public and government, thereby increasing the influence of their enterprises. At the same time, the media plays the role of guiding public opinion and supervising the market economy in enterprise development and market economy. Therefore, this study investigates whether the environmental protection measures taken by enterprises have a positive effect on their sustainable development, and how media attention affects the relationship between environmental protection and sustainable development. This study uses the fixed effect regression method to empirically study the data of A share listed companies in China, from 2016 to 2019. The results of the study show that the enterprises’ fulfillment of environmental responsibilities or carbon trading can promote sustainable development. Furthermore, the higher the network or print media attention, the more environmentally responsible behavior and carbon emissions trading can promote sustainable development capabilities of enterprises. This study enriches the understanding of the important role played by environmental protection in driving enterprise sustainability and contributes to the literature by emphasizing the need for media attention about environmental responsibilities and carbon emissions trading.
Urban diagnostics and a systems approach to air quality management: Pathways towards sustainable economic development and a healthy nairobi, Kenya
Authors: Singh Ajit , Bakare Hakeem , Mazzeo Andrea , Avis William R. , Ng'ang'a David , Gatari Michael , Bartington Suzanne E. , Thomas G. Neil , Bryson John R. , Andres Lauren , Quinn Andrew , Burrow Michael , Ndegwa Elijah N. , Mwaniki George , Randa Tom , Pope Francis D.
Published: September 2022

Taking holistic actions to improve urban air quality is central to reducing the health risks associated with urbanisation, yet local evidence-based and institutional frameworks to achieve this are still challenging especially in many low-and middle-income countries (LMICs). This paper develops and applies an integrated systemic approach to explore the state of air quality management in Nairobi, Kenya; as an LMIC exemplar city. The urban diagnostics approach developed assesses current particulate matter air pollution in Nairobi; quantifies anthropogenic emissions for the years 2015 and 2020 and projects scenarios of impacts of actions and inactions to 2030. This was combined with a review of grey literature on air quality policies, urban development and interviews with key stakeholders. The analysis suggests that commendable progress has been made to improve air quality in Nairobi but continuing hazardous levels of air pollution still require concerted policy efforts. Data available for numerical simulations have low spatial resolution and are generated from global emission inventories that can miss or misrepresent local emission sources. The current air quality data gap that needs to be addressed are highlighted. Strong political support is required to ensure that current air quality improvement approaches are evidence based to achieve long-term sustainability goals.
Assessment of alterations in histone modification function and guidance for death risk prediction in cervical cancer patients
Authors: Zhao Tingting , Liu Bairong , Zhang Mengyuan , Li Shiguo , Zhao Can , Cheng Li
Published: September 2022

Background: Cervical cancer is the second most lethal malignancy among women, and histone modification plays a fundamental role in most biological processes, but the prognostic value of histone modification in cervical cancer has not been evaluated.

Methods: A total of 594 cervical cancer patients from TCGA-CESC, GSE44001, and GSE52903 cohorts were enrolled in the current study, along with the corresponding clinicopathological features. Patients with a follow-up time less than one month were removed. A total of 122 histone modification-associated signaling pathways were obtained from the MSigDB. The activation scores of these pathways were evaluated using the “GSVA” package, differentially expressed genes were identified by the “limma” package, and pathway enrichment was conducted using the “clusterProfiler 4.0” package. The subsequent least absolute shrinkage and selection operator (LASSO) regression analysis was performed using the “glmnet” package, and a prognostic nomogram was established using the “regplot” package. For the prediction of potential therapeutic drugs, we used the data from GDSC2016 and visualized them via “MOVICS”.

Results: Nine of 23 histone modification-associated prognostic genes were identified to construct the prognostic signature by LASSO analysis, named the histone modification-associated gene (HMAG) signature. Cervical patients with HMAG-H in TCGA-CESC cohort showed a 2.68-fold change of death risk, with the 95% CI from 1.533 to 4.671 (p < 0.001), as well as the increased death risk of HMAG-H in the GSE44001 cohort (HR: 2.83, 95% CI: 1.370–5.849, p = 0.005) and GSE44001 cohort (HR: 4.59, 95% CI: 1.658–12.697, p = 0.003). We observed the preferable AUC values of the HMAG signature in TCGA-CESC cohort (1-year: 0.719, 3-year: 0.741, and 5-year: 0.731) and GSE44001 cohort (1-year: 0.850, 3-year: 0.781, and 5-year: 0.755). The C-index of the nomogram showed a prognostic value as high as 0.890, while the C-index for age was only 0.562, and that for grade was only 0.542. Patients with high HMAG scores were more suitable for the treatment of CHIR-99021, embelin, FTI-277, JNK-9L, JQ12, midostaurin, PF-562271, pyrimethamine, and thapsigargin, and patients with low HMAG scores were more suitable for the treatment of BMS-536924, CP466722, crizotinib, PHA-665752, rapamycin, and TAE684.

Conclusion: We comprehensively evaluated the histone modification status in cervical cancer patients and revealed histone modification-associated prognostic genes to construct the HMAG signature, aiming to provide a new insight into prognosis prediction and precise clinical treatment.
Recent developments and future directions in meta-analysis of differential gene expression in livestock RNA-Seq
Authors: Keel Brittney N. , Lindholm-Perry Amanda K.
Published: September 2022

Decreases in the costs of high-throughput sequencing technologies have led to continually increasing numbers of livestock RNA-Seq studies in the last decade. Although the number of studies has increased dramatically, most livestock RNA-Seq experiments are limited by cost to a small number of biological replicates. Meta-analysis procedures can be used to integrate and jointly analyze data from multiple independent studies. Meta-analyses increase the sample size, which in turn increase both statistical power and robustness of the results. In this work, we discuss cutting edge approaches to combining results from multiple independent RNA-Seq studies to improve livestock transcriptomics research. We review currently published RNA-Seq meta-analyses in livestock, describe many of the key issues specific to RNA-Seq meta-analysis in livestock species, and discuss future perspectives.
Formation of silicon layer through aluminothermic reduction of quartz substrates
Authors: Islam Muhammad Monirul , Sawahata Junji , Akimoto Katsuhiro , Sakurai Takeaki
Published: September 2022

Silicon (Si) films were obtained through aluminothermic reduction of the quartz (SiO2) substrates, where the surface of the quartz in contact with the deposited aluminum (Al) layer has been converted to film Si during high-temperature annealing following reduction reaction. X-ray diffraction (XRD) patterns and Raman spectra show dominating peaks corresponding to elemental Si in the obtained films. Energy dispersive spectroscopy (EDS), as well as XRD of the obtained Si layer, suggests that reduction products consist of mainly elemental Si mixed with oxides of Al-related phases. Both the higher reaction temperature and high initial Al-content (larger thickness of Al film in Al/SiO2 structure), studied in this paper, were found in favor of obtaining higher contents of Si in the obtained films. Thus, crystallinity and quality of the obtained Si-layer improve with the increase of both reduction temperature as well as thickness of the Al layer, as confirmed by XRD and Raman spectra. The aluminothermic reduction mechanism has been discussed using XRD as well as a ternary phase diagram of the constituent elements, obtained from EDS data. Crystalline nature (nanocrystal to microcrystal to polycrystal) and the crystalline quality of the obtained Si layers were found to be affected by the thickness of the deposited Al layer on SiO2 substrates.
One of the active ingredients in Paeoniae Radix Alba functions as JAK1 inhibitor in rheumatoid arthritis
Authors: Xiao Lu , Lin Shudian , Zhan Feng
Published: September 2022

Objective: We aimed to explore and verify the mechanism underlying the action of the active ingredients of Paeoniae Radix Alba (PRA) in the treatment of rheumatoid arthritis (RA).

Methods: The protein targets of PRA’s six active ingredients and RA were identified. Then, the intersection of the two groups was studied. The drug–target network was constructed, visualized, and analyzed by Cytoscape software. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment were performed to analyze these genes. Furthermore, we validated our predictions of the potential targets through a docking study. Finally, the anti-inflammatory effect of Palbinone (PB), one of the active ingredients of PRA, was tested by conducting in vitro and in vivo studies.

Results: Six active ingredients of PRA were identified, and 103 overlapping genes were discovered. Functional enrichment analysis indicated that the genes are mostly enriched in IL-17 signaling pathway, Th17 cell differentiation, and the FoxO, ErbB, and TNF signaling pathways. 10 hub genes and two gene cluster modules were identified by Cytoscape. Molecular docking analysis proved that PB was able to bind to the ATP binding site of Janus kinase (JAK)1, thereby acting as a potential inhibitor of JAK1. In vitro and in vivo studies demonstrated that PB exerts its anti-inflammatory role via the inhibition of JAK1.

Conclusion: We constructed a multitarget pharmacological network of PRA in RA treatment. PB, one of the active compounds of PRA, was demonstrated to be a promising inhibitor of JAK1.
Efficacy and safety of tranexamic acid for patients with intertrochanteric fractures treated with intramedullary fixation: A systematic review and meta-analysis of current evidence in randomized controlled trials
Authors: Jiang Jiabao , Xing Fei , Zhe Man , Luo Rong , Xu Jiawei , Duan Xin , Xiang Zhou
Published: September 2022

Background: Tranexamic acid (TXA) has been widely applied to reduce perioperative bleeding. Recently, several studies focused on the administration of TXA in the treatment for with intertrochanteric fracture patients treated with intramedullary fixation. However, the efficacy and safety of TXA in these studies remain controversial. Therefore, we performed this systematic review and meta-analysis to investigate the efficacy and safety of TXA in intertrochanteric fracture patients treated with intramedullary fixation.

Methods: We systematically searched electronic databases, including Cochrane, PubMed, and EMBASE, up to 16 May 2022. The efficacy and safety of TXA was evaluated in four aspects, which were bleeding-related outcomes, non-bleeding-related outcomes, thromboembolic events, and other complications. The outcomes of these studies were extracted and analyzed by RevMan Manager 5.4.

Results: Finally, nine randomized controlled trials, involving nine hundred and seventy-two intertrochanteric fracture patients treated with TXA, were enrolled in this study. In the bleeding-related outcomes, TXA group was significantly lower than the control group in terms of total blood loss (MD = −219.42; 95% CI, −299.80 to −139.03; p < 0.001), intraoperative blood loss (MD = −36.81; 95% CI, −54.21 to −19.41; p < 0.001), hidden blood loss (MD = −189.23; 95% CI, −274.92 to −103.54; p < 0.001), and transfusion rate (RR = 0.64; 95% CI, 0.49 to 0.85; p = 0.002). Moreover, the postoperative hemoglobin on day 3 of the TXA group was significantly higher than that of the control group (MD = 5.75; 95% CI, 1.26 to 10.23; p = 0.01). In the non-bleeding-related outcomes, the length of hospital stays was significantly shorter in the TXA group (MD = −0.67; 95% CI, −1.12 to −0.23; p = 0.003). In terms of thromboembolic events, there was no significant differences between the TXA group and control group in deep vein thrombosis, pulmonary embolism, myocardial infarction, and ischemic stroke. As for complications and mortality, there was no significant differences between the TXA group and control group in respiratory infection, renal failure, and postoperative mortality within 1 year.

Conclusion: TXA is an effective and safe drug for perioperative bleeding control in intertrochanteric fracture patients treated with intramedullary fixation. However, the long-term efficacy of TXA still needs to be investigated by large-scale multicenter randomized controlled trials.

Level of evidence: II, Systematic review and Meta-analysis.

Systematic Review Registration:https://inplasy.com/, identifier [INPLASY202280027]
The novel antitumor compound clinopodiside A induces cytotoxicity via autophagy mediated by the signaling of BLK and RasGRP2 in T24 bladder cancer cells
Authors: Zhou Rong Sheng , Zhao Ji Zhong , Guo Li Ming , Guo Jia Li , Makawy Aida El , Li Zong Yun , Lee Shao Chin
Published: September 2022

In the study, we investigated the anti-cancer effect of clinopodiside A and the underlying mechanisms using T24 bladder cancer cells as an experimental model. We found that the compound inhibited the growth of the bladder cancer cells in vitro and in vivo in a in a concentration- and dose-dependent manner, respectively, which showed a combinational effect when used together with cisplatin. In the bladder cancer cells, clinopodiside A caused autophagy, which was mediated by the signaling of BLK and RasGRP2, independently. Inhibition of the autophagy by chemical inhibitor 3-methyladenine or by the inhibition of the signaling molecules attenuated the cytotoxicity of clinopodiside A. Further analyses showed that clinopodiside A acted in synergism with cisplatin which itself could trigger both autophagy and apoptosis, which occurred with concomitant enhancements in autophagy and the cisplatin-evoked apoptosis. In conclusion, our results suggest that clinopodiside A inhibits the growth of the bladder cancer cells via BLK- and RasGRP2-mediated autophagy. The synergistic effect between clinopodiside A and cisplatin is attributed to the increases in autophagy and autophagy-promoted apoptosis. Clinopodiside A is a promising investigational drug for the treatment of cancer, at least blabber, which can be used alone or in combination with clinical drug(s).
Causality Analysis and Risk Assessment of Haze Disaster in Beijing
Authors: Zhang Xiaobin , Yu Bo
Published: September 2022

Due to the lack of training data and effective haze disaster prediction model, the research on causality analysis and the risk prediction of haze disaster is mainly qualitative. In order to solve this problem, a nonlinear dynamic prediction model of Beijing haze disaster was built in this study. Based on the macroscopic evaluation of multiple influencing factors of haze disaster in Beijing, a causality model and flow diagrams of the Beijing crude oil consumption system, Beijing coal consumption system, Beijing urban greening system and sulfur dioxide emission system in Hebei and Tianjin were established. The risk prediction of Beijing haze disaster was simulated at different conditions of air pollutant discharge level for the Beijing–Tianjin–Hebei region. Compared with the governance strategies of vehicle emission reduction, petrochemical production emission reduction, coal combustion emission reduction, greening and reducing dust and collaborative governance policy, the Beijing–Tianjin–Hebei cross-regional collaborative governance policy was more effective in controlling the haze disaster of Beijing. In the prediction, from 2011 to 2017, the air quality of Beijing changed from light pollution to good. By 2017, the PM2.5 of Beijing reduced to 75 µg/m3. From 2017 to 2035, the control effect of urban haze disaster for Beijing further strengthened. By 2035, the PM2.5 of Beijing reduced to 35 μg/m3. Finally, the PM2.5 of Beijing continued to reduce from 2035 to 2050. The speed of reduction for PM2.5 in Beijing slowed down. Meanwhile, the achievements of haze control in Beijing were consolidated. By 2050, the risk of haze disaster for Beijing was basically solved. The nonlinear dynamic prediction model in this study provides better promise toward the future control and prediction of global haze disaster under the condition of limited data.
DRUNet: A Method for Infrared Point Target Detection
Authors: Wei Changan , Li Qiqi , Xu Ji , Yang Jingli , Jiang Shouda
Published: September 2022

Deep learning is widely used in vision tasks, but feature extraction of IR small targets is difficult due to the inconspicuous contours and lack of color information. This paper proposes a new convolutional neural network–based (CNN-based) method for IR small target detection called DRUNet. The algorithm is divided into two parts: the feature extraction network and the prediction head. For the small IR targets, which are difficult to accurately label, Gaussian soft labels are added to supervise the training process and make the network converge faster. We use a simplified object keypoint similarity to evaluate the network accuracy by the ratio of the distance to the radius of the inner tangent circle of the target box and a fair method for evaluating the model inference speed after GPU preheating. The experimental results show that our proposed algorithm performs better when compared with commonly used algorithms in the field of small target detection. The model size is 10.5 M, and the test speed reaches 133 FPS under the RTX3090 experimental platform.
Improved Variational Mode Decomposition and One-Dimensional CNN Network with Parametric Rectified Linear Unit (PReLU) Approach for Rolling Bearing Fault Diagnosis
Authors: Wang Xiaofeng , Liu Xiuyan , Wang Jinlong , Xiong Xiaoyun , Bi Suhuan , Deng Zhaopeng
Published: September 2022

As a critical component of rotating machinery, rolling bearings are essential for the safe and efficient operation of machinery. Sudden faults of rolling bearings can lead to unscheduled downtime and substantial economic costs. Therefore, diagnosing and identifying the equipment status is essential for ensuring the operation and decreasing the additional maintenance costs of the machines. However, extracting the features from the early bearing fault signals is challenging under background noise interference. With the purpose of solving the above problem, we propose an integrated rolling bearing fault diagnosis model based on the improved grey wolf optimized variational modal decomposition (IGVMD) and an improved 1DCNN with a parametric rectified linear unit (PReLU). Firstly, an improved grey wolf optimizer (IGWO) with the fitness function, the minimum envelope entropy, is designed for adaptively searching the optimal parameter values of the VMD model. The performance of the basic grey wolf optimizer (GWO) algorithm by introducing three improvement strategies, the non-linear convergence factor adjustment strategy, the grey wolf adaptive position update strategy, and the Levy flight strategy in the IGWO algorithm, is improved. Then, an improved 1DCNN model with the PReLU activation function is proposed, which extracts the bearing fault features, and a grid search to optimize the model parameters of the 1DCNN is introduced. Finally, the effectiveness of the proposed model is demonstrated well by employing two experimental datasets. The preliminary comparative results of the average identification accuracy in the proposed method in two datasets are 99.98% and 99.50%, respectively, suggesting that this proposed method has a relatively higher recognition accuracy and application values.
Research on Wind Turbine Blade Surface Damage Identification Based on Improved Convolution Neural Network
Authors: Zou Li , Cheng Haowen
Published: September 2022

Wind turbine blades are easily affected by the working environment and often show damage features such as cracks and surface shedding. An improved convolution neural network, ED Net, is proposed to identify their damage features. An EAC block based on the improved asymmetric convolution is introduced which strengthens the feature extraction during convolution. A DPCI_SC block, which is improved based on the attention module, is embedded to enhance the ability to obtain spatial location information of the damage. GELU is used as the activation function. The loss function is smoothed and labeled during training. Finally, three sets of experiments were conducted. Experiment 1 confirmed the efficacy of the ED Net for identifying damaged wind turbine blades. Experiment 2 confirmed the efficacy of the relevant improvements proposed in this work. Experiment 3 compares the recognition of wind turbine blade damage by commonly used lightweight networks and shows that the ED Net model proposed has a better performance with an accuracy range of 99.12% to 99.23% and a recall of 99.23%
Quantitative Measurement of Swallowing Performance Using Iowa Oral Performance Instrument: A Systematic Review and Meta-Analysis
Authors: Franciotti Raffaella , Di Maria Erica , D’Attilio Michele , Aprile Giuseppe , Cosentino Federica Giulia , Perrotti Vittoria
Published: September 2022

Swallowing is a complex but stereotyped motor activity aimed at serving two vital purposes: alimentary function and the protection of upper airways. Therefore, any impairment of the swallowing act can represent a significant clinical and personal problem that needs an accurate diagnosis by means of reliable and non-invasive techniques. Thus, a systematic review and meta-analysis was performed to investigate the reliability of the Iowa Oral Pressure Instrument (IOPI) in distinguishing healthy controls (HC) from patients affected by swallowing disorders or pathologies and conditions that imply dysphagia. A comprehensive search was conducted following the Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA) guidelines and using PubMed, Scopus, Web of Science, Cochrane, and Lilacs databases. Overall, 271 articles were identified and, after a three-step screening, 33 case-control and interventional studies reporting IOPI measurements were included. The methodological quality of the retrieved studies resulted in being at a low risk of bias. The meta-analysis on case-control studies showed that maximum tongue pressure (MIP) values were always higher in HC than in patients, with an overall effect of the MIP difference of 18.2 KPa (17.7–18.7 KPa CI). This result was also confirmed when the sample was split into adults and children, although the MIP difference between HC and patients was greater in children than in adults (21.0 vs. 15.4 KPa in the MIP mean difference overall effect, respectively). Tongue endurance (TE) showed conflicting results among studies, with an overall effect among studies near zero (0.7 s, 0.2–1.1 s CI) and a slight tendency toward higher TE values in HC than in patients. Among the intervention studies, MIP values were higher after treatment than before, with a better outcome after the experimental tongue training exercise than traditional treatments (the MIP mean difference overall effect was 10.8 and 2.3 KPa, respectively). In conclusion, MIP values can be considered as a reliable measure of swallowing function in adults and in children, with a more marked MIP difference between HC and patients for the children population. MIP measures in patients are also able to detect the best outcome on the tongue function after the training exercise compared to traditional training.
Itaconate Attenuates Neuroinflammation and Exerts Dopamine Neuroprotection in Parkinson’s Disease through Inhibiting NLRP3 Inflammasome
Authors: Sun Guoqing , Zhang Rui , Liu Chengxiao , Meng Wenjun , Pang Qi
Published: September 2022

Parkinson’s disease (PD) is a common age-associated neurodegenerative motor disorder, which is mainly caused by dopaminergic neuron loss in the substantia nigra. This study aimed to evaluate the function and the underlying molecular mechanism of itaconate in PD. PD models were established in vivo and in vitro using 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) and 1-methyl-4-phenylpyridinium (MPP+), respectively. Pole and rotarod tests were applied to evaluate the motor coordination of mice. The expression of tyrosine hydroxylase (TH) in MPTP-induced mice and the MPP+ revulsive PD cell model were detected using Western blotting and immunofluorescence. The inflammatory factors level was detected by quantitative real-time polymerase chain reaction. The content of superoxide dismutase (SOD), malondialdehyde (MDA), glutathione (GSH), and reactive oxygen species (ROS) in substantia nigra, striatum, and SH-SY5Y cells were analyzed. Moreover, the apoptosis of MPP+ revulsive SH-SY5Y cells was determined using terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick-end labeling (TUNEL) staining and flow cytometry. The expression of apoptosis- and Nod-like receptor family protein 3 (NLRP3) inflammasome-associated proteins was measured using Western blotting and immunofluorescence. Itaconate attenuated motor deficits of MPTP-induced PD mice. Itaconate inhibited dopamine neuronal damage, inflammatory response, oxidative stress, and neuronal apoptosis in MPTP-caused PD mice and the MPP+ revulsive PD cell model. Additionally, itaconate notably repressed the activation of NLRP3 inflammasome. This research demonstrated that itaconate could attenuate neuroinflammation and exert dopamine neuroprotection in PD through inhibiting NLRP3 inflammasome.
Viral Particle-Mediated SAMHD1 Depletion Sensitizes Refractory Glioblastoma to DNA-Damaging Therapeutics by Impairing Homologous Recombination
Authors: Daddacha Waaqo , Monroe Dominique , Carver Kristen , Usoro Edidiong R. , Alptekin Ahmet , Xu Hongyan , Osuka Satoru , Arbab Ali S. , Sakamuro Daitoku
Published: September 2022

The current standard-of-care treatment for glioblastoma includes DNA damaging agents, γ-irradiation (IR) and temozolomide (TMZ). These treatments fail frequently and there is limited alternative strategy. Therefore, identifying a new therapeutic target is urgently needed to develop a strategy that improves the efficacy of the existing treatments. Here, we report that tumor samples from GBM patients express a high level of SAMHD1, emphasizing SAMHD1’s importance. The depletion of SAMHD1 using virus-like particles containing Vpx, VLP(+Vpx), sensitized two independent GBM cell lines (LN-229 and U-87) to veliparib, a well-established PARP inhibitor, and slowed cell growth in a dose-dependent manner. In the mouse GBM xenograft model, Vpx-mediated SAMHD1 depletion reduced tumor growth and SAMHD1 knockout (KO) improved survival. In combination with IR or TMZ, SAMHD1 KO and exposure to 50% growth inhibitory dose (gID50) of VLP(+Vpx) displayed a synergistic effect, resulting in impaired HR, and improved LN-229 cells’ sensitivity to TMZ and IR. In conclusion, our finding demonstrates that SAMHD1 promotes GBM resistance to treatment, and it is a plausible therapeutic target to improve the efficacy of TMZ and IR in GBM. Furthermore, we show that Vpx could be a potential therapeutic tool that can be utilized to deplete SAMHD1 in GBM.
Ceramide Kinase (CERK) Emerges as a Common Therapeutic Target for Triple Positive and Triple Negative Breast Cancer Cells
Authors: Rajput Kajal , Ansari Mohammad Nafees , Jha Somesh K. , Pani Trishna , Medatwal Nihal , Chattopadhyay Somdeb , Bajaj Avinash , Dasgupta Ujjaini
Published: September 2022

Sphingolipids are key signaling biomolecules that play a distinct role in cell proliferation, migration, invasion, drug resistance, metastasis, and apoptosis. Triple-negative (ER−PR−HER2−) and triple-positive (ER+PR+HER2+) breast cancer (called TNBC and TPBC, respectively) subtypes reveal distinct phenotypic characteristics and responses to therapy. Here, we present the sphingolipid profiles of BT-474 and MDA-MB-231 breast cancer cell lines representing the TPBC and TNBC subtypes. We correlated the level of different classes of sphingolipids and the expression of their corresponding metabolizing enzymes with the cell proliferation and cell migration properties of BT-474 and MDA-MB-231 cells. Our results showed that each cell type exhibits a unique sphingolipid profile, and common enzymes such as ceramide kinase (CERK, responsible for the synthesis of ceramide-1-phosphates) are deregulated in these cell types. We showed that siRNA/small molecule-mediated inhibition of CERK can alleviate cell proliferation in BT-474 and MDA-MB-231 cells, and cell migration in MDA-MB-231 cells. We further demonstrated that nanoparticle-mediated delivery of CERK siRNA and hydrogel-mediated sustained delivery of CERK inhibitor to the tumor site can inhibit tumor progression in BT-474 and MDA-MB-231 tumor models. In summary, distinct sphingolipid profiles of TPBC and TNBC representing cell lines provide potential therapeutic targets such as CERK, and nanoparticle/hydrogel mediated pharmacological manipulations of such targets can be explored for future cancer therapeutics.
Crosstalk of Oxidative Phosphorylation-Related Subtypes, Establishment of a Prognostic Signature and Immune Infiltration Characteristics in Colorectal Adenocarcinoma
Authors: Wang Can , Cui Guoliang , Wang Dan , Wang Min , Chen Qi , Wang Yunshan , Lu Mengjie , Tang Xinyi , Yang Bolin
Published: September 2022

Oxidative phosphorylation (OXPHOS) is an emerging target in cancer therapy. However, the prognostic signature of OXPHOS in colorectal adenocarcinoma (COAD) remains non-existent. We comprehensively investigated the expression pattern of OXPHOS-related genes (ORGs) in COAD from public databases. Based on four ORGs, an OXPHOS-related prognostic signature was established in which COAD patients were assigned different risk scores and classified into two different risk groups. It was observed that the low-risk group had a better prognosis but lower immune activities including immune cells and immune-related function in the tumor microenvironment. Combining with relevant clinical features, a nomogram for clinical application was also established. Receiver operating characteristic (ROC) and calibration curves were constructed to demonstrate the predictive ability of this risk signature. Moreover, a higher risk score was significantly positively correlated with higher tumor mutation burden (TMB) and generally higher gene expression of immune checkpoint, N6-methyladenosine (m6A) RNA methylation regulators and mismatch repair (MMR) related proteins. The results also indicated that the high-risk group was more sensitive to immunotherapy and certain chemotherapy drugs. In conclusion, OXPHOS-related prognostic signature can be utilized to better understand the roles of ORGs and offer new perspectives for clinical prognosis and personalized treatment.
Neoadjuvant Efficacy of Three Targeted Therapy Strategies for HER2-Positive Breast Cancer Based on the Same Chemotherapy Regimen
Authors: Zhu Jiujun , Jiao Dechuang , Wang Chengzheng , Lu Zhenduo , Chen Xiuchun , Li Lianfang , Sun Xianfu , Qin Li , Guo Xuhui , Zhang Chongjian , Qiao Jianghua , Yan Min , Cui Shude , Liu Zhenzhen
Published: September 2022

(1) Background: The objective of our study was to provide evidence for choosing the optimal neoadjuvant therapy strategies for patients with human epidermal growth factor receptor 2 (HER2)-positive early breast cancer. Three neoadjuvant targeted therapy strategies (H + Py, trastuzumab plus pyrotinib; H, trastuzumab; HP, trastuzumab plus pertuzumab) based on the same chemotherapy regimen (TC, docetaxel and carboplatin) were included in the present study; (2) Methods: We retrospectively analyzed patients with HER2-positive breast cancer who were treated with neoadjuvant TCH + Py, TCH or TCHP, followed by surgery. The outcome was the pathological complete response (pCR) rate; (3) Results: In total, 545 patients were enrolled. The pCR rate was 55.6% (35/63) in the TCH + Py cohort, 32.7% (93/284) in the TCH cohort, and 56.6% (112/198) in the TCHP cohort. The multivariate analysis showed that patients who received TCH had less possibility to achieve pCR than those who received TCH + Py (odds ratio (OR) = 0.334, 95% confidence interval (CI): 0.181–0.619, p < 0.001), while patients who received TCHP had comparable possibility to those who received TCH + Py (OR = 1.043, 95%CI: 0.554–1.964, p = 0.896); (4) Conclusions: TCH + Py provides a better pCR rate compared with TCH, and a comparable pCR rate with TCHP among patients with HER2-positive breast cancer in the neoadjuvant setting. The present study supports a novel potential treatment option for these patients. Further studies need to be explored in the future.
Pure Solid Pattern of Non-Small Cell Lung Cancer and Clustered Circulating Tumor Cells
Authors: Sawabata Noriyoshi , Kawaguchi Takeshi , Watanabe Takashi , Yohikawa Daiki , Ouji-Sageshima Noriko , Ito Toshihiro
Published: September 2022

There are two solid patterns of non-small cell lung cancer (NSCLC) on computed tomography (CT): pure or mixed with ground-glass opacities (GGOs). They predict the degree of invasiveness, which may suggest the presence of clustered circulating tumor cells (CTCs), a predictor of poor prognosis. In this study, we assessed the implications of the solid patterns on CT and the preoperative clustered CTCs in surgically resected NSCLC. CTCs were detected using a size selection method. The correlation between the presence of preoperative clustered CTCs and the solid pattern and the prognostic implications were evaluated using co-variables from the clinical-pathological findings. Of the 142 cases, pure solid lesions (Group PS) and mixed GGOs (Group G) were observed in 92 (64.8%) and 50 (35.2%) patients, respectively. In Groups PS and G, clustered CTCs were detected in 29 (31.5%) and 1 (2.0%) patient (p < 0.01), respectively. The PS appearance was an independent predictor of preoperative clustered CTCs in the multivariable analysis, and preoperative clustered CTCs were an independent predictor of poor recurrence-free survival; the solid pattern was not an independent variable. Thus, the PS pattern of NSCLC on CT is an indicator of preoperative clustered CTCs, which is an independent poor prognosis predictor.
Biomimetic Red Blood Cell Membrane-Mediated Nanodrugs Loading Ursolic Acid for Targeting NSCLC Therapy
Authors: Wu Ting , Yan Dan , Hou Wenjun , Jiang Hui , Wu Min , Wang Yanling , Chen Gang , Tang Chunming , Wang Yijun , Xu Huae
Published: September 2022

As one of the most common cancers worldwide, non-small-cell lung cancer (NSCLC) treatment always fails owing to the tumor microenvironment and resistance. UA, a traditional Chinese medicine, was reported to have antitumor potential in tumor models in vitro and in vivo, but showed impressive results in its potential application for poor water solubility. In this study, a novel biomimetic drug-delivery system based on UA-loaded nanoparticles (UaNPs) with a red blood cell membrane (RBCM) coating was developed. The RBCM-coated UANPs (UMNPs) exhibited improved water solubility, high stability, good biosafety, and efficient tumor accumulation. Importantly, the excellent antitumor efficiency of the UMNPs was confirmed both in vitro and in vivo in cancer models. In addition, we further investigated the antitumor mechanism of UMNPs. The results of Western blotting showed that UMNPs exerted an anticancer effect by inducing the apoptosis and autophagy of NSCLC cells, which makes it superior to free UA. In addition, body weight monitoring, hematoxylin and eosin (HE) analysis, and immunohistochemical (IHC) analysis showed no significant difference between UMNPs and the control group, indicating the safety of UMNPs. Altogether, the preparation of biomimetic UMNPs provides a promising strategy to improve outcomes in NSCLC.
Body Composition as a Predictor of the Survival in Anal Cancer
Authors: Mohamed Ahmed Allam , Risse Kathrin , Stock Jennifer , Heinzel Alexander , Mottaghy Felix M. , Bruners Philipp , Eble Michael J.
Published: September 2022

Background and aim: Sarcopenia and body composition parameters such as visceral and subcutaneous adipose tissue and visceral-to-subcutaneous adipose tissue ratio have been shown to be relevant biomarkers for prognosis in patients with different types of cancer. However, these findings have not been well studied in anal cancer to date. Therefore, the aim of this study was to evaluate the prognostic value of different body composition parameters in patients undergoing radiation therapy for the treatment of anal cancer with curative intent. Material and Methods: After approval by the institutional ethical committee, we retrospectively identified 81 patients in our local registry, who received radical intensity-modulated radiotherapy for the management of anal squamous cell cancer (ASCC). Clinical information, including body mass index (BMI), survival, and toxicities outcome, were retrieved from the local hospital registry. Based on the pre-therapeutic computer tomography (CT), we measured the total psoas muscle area, visceral adipose tissue area (VAT), subcutaneous adipose tissue area (SAT), and visceral-to-subcutaneous adipose tissue area ratio (VSR). In addition to the classical prognostic factors as T-stage, N-stage, gender, and treatment duration, we analyzed the impact of body composition on the prognosis in univariate and multivariate analyses. Results: Sarcopenia was not associated with increased mortality in anal cancer patients, whereas increased BMI (≥27 kg/m2) and VSR (≥0.45) were significantly associated with worsened overall survival and cancer-specific survival in both univariate and multivariate analyses. VSR—not BMI—was statistically higher in males. Sarcopenia and VSR ≥ 0.45 were associated with advanced T-stages. None of the body composition parameters resulted in a significant increase in treatment-related toxicities. Conclusion: BMI and visceral adiposity are independent prognostic factors for the survival of patients with anal cancer. Measurements to treat adiposity at the time of diagnosis may be needed to improve the survival outcomes for the affected patients.
Tailorable Formation of Hierarchical Structure Silica (HMS) and Its Application in Hydrogen Production
Authors: Li Luming , Deng Jie , Guo Zhanglong , Chu Wei , Liu Yan
Published: September 2022

Relentless endeavors have been committed to seeking simple structure-directing agents for synthesizing hierarchical mesoporous silica (HMS) materials but remaining challenges. In this contribution, we offered an improved one-pot hydrothermal route to prepare HMS materials using a single non-ionic triblock copolymer (F127) structure-directing agent under a mild polycarboxylic (citric acid) mediated condition. Via studies of key synthetic parameters including acid concentration, crystallization temperature and aging time, it was found that citric acid medium presents an important bridging effect under the optimal concentration from 0.018 M (pH = 2.57) to 1.82 M (pH = 1.09), contributing to the self-assemblage of partially protonated non-ionic triblock copolymer and tetraethyl orthosilicate (TEOS) into a high-quality multistage structure of silica materials. The specific surface area (SSA) of HMS shows a volcanic trend and is closely associated with the concentration of citric acid while the highest SSA of 739.9 m2/g can be achieved at the citric concentration of 0.28 M. Moreover, the as-synthesized HMS-CTA supported Ni/CeO2 catalysts indicate an excellent production of hydrogen through dry reforming of methane (DRM) reaction over 172 h stability. The improved, facile synthesis strategy under polycarboxylic medium displays an expanded perspective for synthesizing other mesoporous materials in a wide range of applications such as catalytic material carriers and drug inhibitors.