bluuebunny/crossref_metadata_2025 huggingface dataset:
Rapamycin-induced autophagy in osteosarcoma cells is mediated via the biglycan/Wnt/β-catenin signaling axis
Authors: Giatagana Eirini-Maria , Berdiaki Aikaterini , Gaardløs Margrethe , Tsatsakis Aristidis M. , Samsonov Sergey A. , Nikitovic Dragana
Published: October 2022

Biglycan is a class I secreted small leucine-rich proteoglycan (SLRP), which regulates signaling pathways connected to bone pathologies. Autophagy is a vital catabolic process with a dual role in cancer progression. Here, we show that biglycan inhibits autophagy in two osteosarcoma cell lines ( P ≤ 0.001), while rapamycin-induced autophagy decreases biglycan expression in MG63 osteosarcoma cells and abrogates the biglycan-induced cell growth increase ( P ≤ 0.001). Rapamycin also inhibits β-catenin translocation to the nucleus, inhibiting the Wnt pathway ( P ≤ 0.001) and reducing biglycan’s colocalization with the Wnt coreceptor LRP6 ( P ≤ 0.05). Furthermore, biglycan exhibits protective effects against the chemotherapeutic drug doxorubicin in MG63 OS cells through an autophagy-dependent manner ( P ≤ 0.05). Cotreatment of these cells with rapamycin and doxorubicin enhances cells response to doxorubicin by decreasing biglycan ( P ≤ 0.001) and β-catenin ( P ≤ 0.05) expression. Biglycan deficiency leads to increased caspase-3 activation ( P ≤ 0.05), suggesting increased apoptosis of biglycan-deficient cells treated with doxorubicin. Computational models of LRP6 and biglycan complexes suggest that biglycan changes the receptor’s ability to interact with other signaling molecules by affecting the interdomain bending angles in the receptor structure. Biglycan binding to LRP6 activates the Wnt pathway and β-catenin nuclear translocation by disrupting β-catenin degradation complex ( P ≤ 0.01 and P ≤ 0.05). Interestingly, this mechanism is not followed in moderately differentiated, biglycan-nonexpressing U-2OS OS cells. To sum up, biglycan exhibits protective effects against the doxorubicin in MG63 OS cells by activating the Wnt signaling pathway and inhibiting autophagy.
Role of noncoding RNAs in pancreatic ductal adenocarcinoma associated cachexia
Authors: Uddin Md. Hafiz , Mohammad Ramzi M. , Philip Philip A. , Azmi Asfar S. , Muqbil Irfana
Published: October 2022

Cachexia is an acute syndrome that is very commonly observed in patients with cancer. Cachexia is the number one cause of death in patients with metastatic disease and is also the major factor for physical toxicity and financial burden. More importantly, the majority of patients with advanced-stage pancreatic ductal adenocarcinoma (PDAC) cancer undergo cachexia. Pancreatic cancer causes deaths of ∼50,000 Americans and about 400,000 people worldwide every year. The high mortality rates in metastatic PDAC are due to systemic pathologies and cachexia, which quickens death in these patients. About 90% of all patients with PDAC undergo wasting of muscle causing mobility loss and leading to a number of additional pathological conditions. PDAC-associated cancer cachexia emanates from complex signaling cues involving both mechanical and biological signals. Tumor invasion is associated with the loss of pancreatic function-induced digestive disorders and malabsorption, which causes subsequent weight loss and eventually promotes cachexia. Besides, systemic inflammation of patients with PDAC could release chemical cues (e.g., cytokine-mediated Atrogin-1/MAFbx expression) that participate in muscle wasting. Our understanding of genes, proteins, and cytokines involved in promoting cancer cachexia has evolved considerably. However, the role of epigenetic factors, particularly the role of noncoding RNAs (ncRNAs) in regulating PDAC-associated cachexia is less studied. In this review article, the most updated knowledge on the various ncRNAs including microRNAs (miRs), long noncoding RNA (lncRNAs), piwi interacting RNAs (PiwiRNAs), small nucleolar RNA (snoRNAs), and circular RNAs (circRNA) and their roles in cancer cachexia are described.
Hepatocyte- or macrophage-specific SREBP-1a deficiency in mice exacerbates methionine- and choline-deficient diet-induced nonalcoholic fatty liver disease
Authors: Araki Masaya , Nakagawa Yoshimi , Saito Hodaka , Yamada Yasunari , Han Song-Iee , Mizunoe Yuhei , Ohno Hiroshi , Miyamoto Takafumi , Sekiya Motohiro , Matsuzaka Takashi , Sone Hirohito , Shimano Hitoshi
Published: October 2022

Hepatocyte- and macrophage-specific SREBP-1a knockout mice were generated for the first time. This study reveals that SREBP-1a does not contribute to hepatic lipogenesis, but in either hepatocytes or macrophages distinctly controls the onset of pathological conditions in methionine- and choline-deficient diet-induced hepatitis.
Cross talk between the gut microbiome and host immune response in ulcerative colitis: nonpharmacological strategies to improve homeostasis
Authors: Bullard Brooke M. , VanderVeen Brandon N. , McDonald Sierra J. , Cardaci Thomas D. , Murphy E. Angela
Published: October 2022

Ulcerative colitis (UC) is a chronic disease that is characterized by diffuse inflammation of the colonic and rectal mucosa. The burden of UC is rising globally with significant disparities in levels and trends of disease in different countries. The pathogenesis of UC involves the presence of pathogenic factors including genetic, environmental, autoimmune, and immune-mediated components. Evidence suggests that disturbed interactions between the host immune system and gut microbiome contribute to the origin and development of UC. Current medications for UC include antibiotics, corticosteroids, and biological drugs, which can have deleterious off-target effects on the gut microbiome, contributing to increased susceptibility to severe infections and chronic immunosuppression. Alternative, nonpharmacological, and behavioral interventions have been proposed as safe and effective treatments to alleviate UC, while also holding the potential to improve overall life quality. This mini-review will discuss the interactions between the immune system and the gut microbiome in the case of UC. In addition, we suggest nonpharmacological and behavioral strategies aimed at restoring a proper microbial-immune relationship.
Differential temporal development of alveoli and the alveolar capillary network in the postnatal rat lung
Authors: Werner Julia , Schipke Julia , Brandenberger Christina , Schmiedl Andreas , Mühlfeld Christian
Published: October 2022

Quantitative data about the internal lung structure are needed to better understand normal and pathological lung development. Aberrant lung development causes deficits in alveolar and microvascular development; however, the normal temporal relationship between these processes is still not fully understood. We hypothesized that alveolar and capillary development show a differential time pattern. Lungs of rats aged 3, 7, 14, 21 days (d) or 3 mo ( n = 8–10 each) were fixed by vascular perfusion and processed for light microscopy. Using design-based stereology number, the surface area and volume of alveoli, septal capillaries, and alveolar septa were quantified. The total number and the total volume of alveoli increased progressively during postnatal development. Interestingly, the numerical density of capillary loops was significantly higher in 14- and 21-d-old rats than before or after this age, causing a duplication of the total number of capillary loops between 1 and 2 wk of age. The mean thickness of alveolar septa started to decline slightly at the age of 14d and more pronounced at later stages. Although the septal epithelial surface area increased in proportion to alveolar number during the first 3 wk, the capillary endothelial surface area grew only slightly compared with the number of capillaries. In conclusion, the number of elements composing the alveolar capillary network expands massively during the first two postnatal weeks and exceeds the formation of alveoli. The thinning of the alveolar septa during further development suggests a reduction of the capillary network during alveolarization.
Taurine‐Upregulated Gene 1 Attenuates Cerebral Angiogenesis following Ischemic Stroke in Rats
Authors: Li Fei , Yu Jun-Hua , Jiang Hong-Xiang , Zhang Hui-Kai , Cai Qiang , Liu Zai-Ming , Li Ming-Chang , Chen Qian-Xue
Published: October 2022

Objective. Angiogenesis is one of the therapeutic targets of cerebral infarction. Long noncoding RNAs (lncRNAs) can regulate the pathological process of angiogenesis following ischemic stroke. Taurine‐upregulated gene 1 (TUG1), an lncRNA, is correlated to ischemic stroke. We intended to determine the effect of TUG1 on angiogenesis following an ischemic stroke. Materials and Methods. Middle cerebral artery occlusion (MCAO) was adopted to build a focal ischemic model of the rat brain, and pcDNA‐TUG1 and miR‐26a mimics were injected into rats. Neurological function was estimated through modified neurological severity scores. The volume of focal brain infarction was calculated through 2,3,5‐triphenyltetrazolium chloride staining. The level of TUG1 and miR‐26a was measured by PCR. The expression of vascular endothelial growth factor (VEGF) and CD31 was checked using immunohistochemistry and western blot. The correlation between miR‐26a and TUG1 was verified through a luciferase reporter assay. Results. TUG1 increased noticeably while miR‐26a was markedly reduced in MCAO rats. Overexpression of miR‐26a improved neurological function recovery and enhanced cerebral angiogenesis in MCAO rats. TUG1 overexpression aggravated neurological deficits and suppressed cerebral angiogenesis in MCAO rats. Bioinformatics analysis revealed that miR‐26a was one of the predicted targets of TUG1. Furthermore, TUG1 combined with miR‐26a to regulate angiogenesis. TUG1 overexpression antagonized the role of miR‐26a in neurological recovery and angiogenesis in MCAO rats. Conclusions. TUG1/miR‐26a, which may act as a regulatory axis in angiogenesis following ischemic stroke, can be considered a potential target for cerebral infarction therapy.
Serum Lactate Dehydrogenase Is a Sensitive Predictor of Systemic Complications of Acute Pancreatitis
Authors: Huang Dong-Ni , Zhong Hao-Jie , Cai Ying-Li , Xie Wen-Rui , He Xing-Xiang
Published: October 2022

Background. Acute pancreatitis (AP) is a common and potentially life-threatening inflammatory disease that can cause various complications, including systemic inflammatory response syndrome (SIRS), pleural effusion, ascitic fluid, myocardial infarction, and acute kidney injury (AKI). However, there is still a lack of rapid and effective indicators to assess the disease. The aim of this study was to investigate the associations of high serum lactate dehydrogenase (LDH) levels with AP severity and systemic complications. Methods. AP patients treated from July 2014 to December 2020 were retrospectively enrolled. They were divided into elevated (

n
=
93

) and normal (

n
=
143

) LDH groups. Their demographic data, clinical data, hospital duration, and hospital expenses were analyzed. Linear and binary logistic regression analyses were used to determine whether elevated LDH is a risk factor for AP severity and complications after adjusting for confounders. Results. There were significant differences in AP severity scores (Ranson, MODS, BISAP, APACHE II, and CTSI), hospital duration, hospital expenses, and the incidences of complications (SIRS, pleural effusion, ascitic fluid, myocardial infarction, and AKI) between the elevated and normal LDH groups. After adjusting for confounders, elevated LDH was associated with AP severity scores and hospital duration and expenses (based on linear regression analyses) and was a risk factor for the occurrence of AP complications and interventions, that is, diuretic and vasoactive agent use (based on binary logistic regression analyses). Conclusions. Elevated LDH is associated with high AP severity scores and high incidences of complications (SIRS, pleural effusion, ascitic fluid, myocardial infarction, and AKI).
Trace Metals, Crude Protein, and TGA-FTIR Analysis of Evolved Gas Products in the Thermal Decomposition of Roasted Mopane Worms, Sweet Corn, and Peanuts
Authors: Masite Nonkululeko S. , Ncube Somandla , Madikizela Lawrence M. , Mtunzi Fanyana M. , Pakade Vusumzi E.
Published: October 2022

The thermal behavior of mopane worms (Imbrasia belina), roasted peanuts (Arachis hypogaea L.), and sweet corn (Zea mays L. saccharata) was investigated under inert conditions using the TGA-FTIR analytical technique heated from 64 to 844°C at a heating rate of 20°C/min. The degradation patterns of the food samples differed as sweet corn and peanuts exhibited four degradation stages 188, 248, 315, and 432°C and 145, 249, 322, and 435°C, respectively. Mopane worms displayed three (106, 398, and 403°C). The different decomposition patterns together with the types of evolved gases shown by FTIR analysis justified the varied biochemical and chemical composition of foods. The common evolved gas species between the food samples were H2O, CO2, P=O, CO, and CH4 but mopane worms showed two extra different bands of C-N and N-H. Higher volumes of evolved gases were recorded at temperatures between 276 and 450°C, which are higher than the usual cooking temperature of 150°C. This means that the food maintained its nutritional value at the cooking temperature. Mopane worms were found to contain twice and four times crude protein content than peanuts and corn, respectively. Only total arsenic metal was reported to be above threshold limits.
Assessment of Statin Treatment for Pulmonary Alveolar Proteinosis without Hypercholesterolemia: A 12‐Month Prospective, Longitudinal, and Observational Study
Authors: Shi Shenyun , Gui Xianhua , Ding Jingjing , Yang Shangwen , Xin Xiaoyan , Xu Kaifeng , Xiao Yonglong
Published: October 2022

Background. Pulmonary alveolar proteinosis (PAP) is a rare disorder which is characterized by the accumulation of excessive surfactant lipids and proteins in alveolar macrophages and alveoli. Oral statin therapy has been reported to be a novel therapy for PAP with hypercholesterolemia. We aimed to evaluate the safety and efficacy of oral statin therapy for PAP without hypercholesterolemia. Methods. In a prospective real‐world observational study, 47 PAP patients without hypercholesterolemia were screened. Oral statin was initiated as therapy for these PAP patients with 12 months of follow‐up. Results. Forty PAP patients completed the study. 26 (65%) of 40 PAP patients responded to statin therapy according to the study criteria. Partial pressure of arterial oxygen (PaO2) and percentage of diffusion capacity predicted (DLCO%) significantly increased while disease severity score (DSS) and radiographic abnormalities decreased after 12 months of statin therapy (all p < 0.05). The factors associated with response were higher levels of granulocyte‐macrophage colony‐stimulating factor (GM‐CSF) antibody and baseline total cholesterol/high‐density lipoprotein cholesterol (TC/HDL) (p = 0.015 and p = 0.035, respectively). The area under the receiver operating characteristic curve (AUROC) of dose of atorvastatin for predicting the response to statin therapy for PAP was 0.859 (95% CI: 0.738‐0.979, p < 0.001). The cutoff dose of atorvastatin was 67.5 mg daily with their corresponding specificity (64.3%) and sensitivity (96.2%). No severe side effects were observed during the study. Conclusions. In PAP patients without hypercholesterolemia, statin therapy resulted in improvements in arterial blood gas (ABG) measurement, pulmonary function, and radiographic assessment.
Smart Congestion Control in 5G/6G Networks Using Hybrid Deep Learning Techniques
Authors: Alnawayseh Saif E. A. , Al-Sit Waleed T. , Ghazal Taher M.
Published: October 2022

With the mobility and ease of connection, wireless sensor networks have played a significant role in communication over the last few years, making them a significant data carrier across networks. Additional security, lower latency, and dependable standards and communication capability are required for future‐generation systems such as millimeter‐wave LANs, broadband wireless access schemes, and 5G/6G networks, among other things. Effectual congestion control is regarded as of the essential aspects of 5G/6G technology. It permits operators to run many network illustrations on a single organization while maintaining higher service quality. A sophisticated decision‐making system for arriving network traffic is necessary to confirm load balancing, limit network slice letdown, and supply alternative slices in slice letdown or congestion. Because of the massive amount of data being generated, artificial intelligence (AI) and machine learning (ML) play a vital role in reconfiguring and improving a 5G/6G wireless network. In this research work, a hybrid deep learning method is being applied to forecast optimal congestion improvement in the wireless sensors of 5G/6G IoT networks. This proposed model is applied to a training dataset to govern the congestion in a 5G/6G network. The proposed approach provided promising results, with 0.933 accuracy, and 0.067 miss rate.
Parameter Acquisition Study of Mining-Induced Surface Subsidence Probability Integral Method Based on RF-AGA-ENN Model
Authors: Zhang Jinman , Xu Liangji , Li Jiewei , Yan Yueguan , Xu Ruirui
Published: October 2022

The mining of underground coal resources can trigger geological hazards such as subsidence basins, cave-in pits, and step cracks. In China, the probability integral method (PIM), the most popular method for predicting surface movement deformation caused by coal resource mining, has a prediction accuracy that is mainly influenced by both the measurement data (i.e., quantity and quality) from ground movement observatories and the parameter inversion method. To obtain more accurate PIM parameters in the absence of observational data, we propose a combined machine learning model (RF-AGA-ENN)—random forest (RF) extracts the best combination of features as the input layer of Elman neural network (ENN); ant colony algorithm (ACO) and genetic algorithm (GA) are combined (called AGA) for the weights and thresholds of ENN optimization. The results of the study show that (1) the RF-AGA-ENN model is used to obtain PIM values with MAXRE values between 1.94% and 9.18%, AVERY values between 0.98% and 3.98%, and RMSE values between 0.0050 and 0.9632. (2) Compared with the PIM parameters obtained from BP neural network, RF-ENN, RF-ACO-ENN, and RF-GA-ENN models, the PIM parameters obtained from the RF-AGA-ENN model have better stability and accuracy. (3) According to the PIM parameters obtained by the RF-AGA-ENN model, the predicted and measured values of surface settlement at the 11111 working face have a high degree of agreement. In summary, the RF-AGA-ENN model to obtain the PIM parameters has good application value.
Soliton Solutions of Generalized Third Order Time‐Fractional KdV Models Using Extended He‐Laplace Algorithm
Authors: Qayyum Mubashir , Ahmad Efaza , Afzal Sidra , Acharya Saraswati
Published: October 2022

In this research, the He‐Laplace algorithm is extended to generalized third order, time‐fractional, Korteweg‐de Vries (KdV) models. In this algorithm, the Laplace transform is hybrid with homotopy perturbation and extended to highly nonlinear fractional KdVs, including potential and Burgers KdV models. Time‐fractional derivatives are taken in Caputo sense throughout the manuscript. Convergence and error estimation are confirmed theoretically as well as numerically for the current model. Numerical convergence and error analysis is also performed by computing residual errors in the entire fractional domain. Graphical illustrations show the effect of fractional parameter on the solution as 2D and 3D plots. Analysis reveals that the He‐Laplace algorithm is an efficient approach for time‐fractional models and can be used for other families of equations.
Application Effect of Transparent Supervision Based on Informatization in Prevention and Control of Carbapenem-Resistant Klebsiella pneumoniae Nosocomial Infection
Authors: Wu Xiaoqin , Lu Quansheng , Feng Guo , Kan Hongxia , Shi Liran
Published: October 2022

Objective. To explore the effect of transparent supervision model on the prevention and control of carbapenem-resistant Klebsiella pneumoniae (CRKP) nosocomial infection and the value of the autoregressive integrated moving average (ARIMA) model in predicting the incidence of CRKP infection. Methods. A total of 46,873 inpatients from Jiawang District People’s Hospital of Xuzhou between January 2019 and December 2019 (prior to COVID-19 prevention and control) were selected as the preintervention group and 45,217 inpatients from January 2020 to December 2020 (after the COVID-19 prevention and control) as the postintervention group. We performed transparent supervision on CRKP patients detected by the real-time monitoring system for nosocomial infection. Incidence and detection rate of CRKP, utilization rate of special grade hydrocarbon enzyme alkene antibiotics, hand hygiene compliance rate, qualified rate of ATP tests on surface of environmental objects, and execution rate of CRKP core prevention and control were compared between the two groups. Results. Transparent supervision of CRKP-infected patients was conducted daily from January to December 2020, which resulted in the following: (a) the infection rate of CRKP decreased in a fluctuating manner, and the actual value of hydrocarbon alkene use rate was basically the same as the predicted value with an overall decreasing trend; (b) after the intervention, hand hygiene compliance rate increased from 53.30% to 70.24% (

P
<
0.001

) and the ATP qualified rate increased from 53.77% to 92.24% (

P
<
0.001

); (c) the fitted value of the ARIMA model was in good agreement with the actual value. The incidence of CRKP infection and the utilization rate of carbene antibiotics were also in good agreement with the predicted value. The average relative errors were 11% and 10.78%. Conclusions. During the COVID-19 outbreak in 2020, the ARIMA model effectively fit and predicted the CRKP infection rate, thereby providing scientific guidance for the prevention and control of CRKP infection. In addition, the transparent supervision intervention model improved the hand hygiene compliance and environmental hygiene qualification rates of medical staff, effectively reducing CRKP cross-infection in the hospital.
Life Prediction of the Gear Transmission System with Multicharacteristics
Authors: Li Junliang , Ren Bin , Xue Zhanpu , Yin Bowen , Zhang Hao
Published: October 2022

This study obtains and predicts multifault data in the key transmission and connection systems with gears. Model building is based on the multikernel extreme learning machine with the method of maximum correlation kurtosis deconvolution and variational mode decomposition. To this end, the realization form of the life prediction is first studied by enhancing the low-frequency signal. Then, the larger correlation coefficient is selected as the sensitive feature parameter aiming at mapping to a feature space by the randomly initialized hidden layer in the learning machine, and the weight value of output layer is obtained using the least square method. A case study on the fault diagnosis of gear transmission system is conducted in the end to illustrate the proposed approach.
Robustness-Based Transmission Strategy for Wireless-Powered Communication Networks
Authors: Liu Xiaoying , Wang Aodi , Xu Bin , Zheng Kechen , Yao Xinwei
Published: October 2022

In the wireless powered communication network (WPCN), the deployed nodes that harvest energy from the power station (PS) and then transmit data to the access point (AP) may waste wireless information transmission (WIT) opportunities due to the suffered faults. Confronting this dilemma, we propose a novel metric robustness, defined as the number of available nodes for WIT, and evaluate its impact on the throughput. To optimize the tradeoff between the throughput and robustness, we design an energy threshold approach, where the robustness decreases with the energy threshold and the throughput first increases and then decreases with it due to the tradeoff between the WIT rate and WIT opportunities. In the designed approach, we formulate the nodes with different energy states as Markov chain processes and prove the existence of steady-state probability distribution. Moreover, in the scenario with high robustness by the designed approach, we select the nodes with higher energy for WIT by the improved

k

-means++ algorithm, in order to increase the throughput. Finally, simulations validate the theoretical analysis of the throughput and robustness performances under the improved

k

-means++ algorithm and show that, compared with the comparison algorithms, the improved

k

-means++ algorithm achieves similar throughput and robustness performances with low computational complexity.
Multimodal Imaging and Macular Hyalocyte Count in a Patient with Acute Macular Neuroretinopathy
Authors: Schatz Michael J. , Otero-Marquez Oscar , Rosen Richard B. , Parikh Deep
Published: October 2022

Though rare, acute macular neuroretinopathy is a well-described clinical entity. We report for the first time a detailed analysis of macular hyalocyte count and morphology during the acute phase of acute macular neuroretinopathy. We present a case of a 19-year-old man with bilateral acute onset paracentral scotomas in the setting of an antecedent viral infection. Multimodal imaging demonstrated classic features of acute macular neuroretinopathy. Further analysis revealed increased macular hyalocyte count and an activated hyalocyte morphology during the acute phase of the disease course. Multimodal imaging not only allows for greater confidence in a diagnosis and prognosis but also helps to shed light on underlying pathophysiology. The new clinical capability of monitoring cellular behavior, such as hyalocyte count and morphology, in physiological and pathological conditions may prove useful as biomarkers of early disease activity or response to therapy.
Anatomical Resection Improved the Outcome of Intrahepatic Cholangiocarcinoma: A Propensity Score Matching Analysis of a Retrospective Cohort
Authors: Wang Chao , Ciren Pingcuo , Danzeng Awang , Li Yong , Zeng Cheng-Long , Zhang Zhi-Wei , Huang Zhi-Yong , Chen Yi-Fa , Zhang Wan-Guang , Zhang Bi-Xiang , Zhang Bin-Hao , Chen Xiao-Ping
Published: October 2022

Background. Intrahepatic cholangiocarcinoma (ICC) is the second most common liver malignancy after hepatocellular carcinoma (HCC), with a dismal prognosis and high heterogeneity. The oncological advantages of anatomical resection (AR) and nonanatomical resection (NAR) in HCC have been studied, but surgical strategies for ICC remain controversial with insufficient investigations. Materials and Methods. From Jan 2013 to Dec 2016, 3880 consecutive patients were retrospectively reviewed from a single center. Patients with ICC undergoing AR or NAR have been enrolled according to inclusion and exclusion criteria. Propensity score matching (PSM) analysis was performed between two groups with a 1 : 1 ratio. The primary endpoint was overall survival (OS), and the secondary endpoints included disease-free survival (DFS), intraoperative patterns, postoperative morbidity, mortality, complications and recurrence. A prognostic nomogram was developed by a multivariate Cox proportion hazard model. Results. After PSM, 99 paired cases were selected from 276 patients enrolled in this study. Patients in the AR group achieved better 1-, 3-, and 5-year OS (70%, 46%, and 34%, respectively) and DFS (61%, 21%, and 10%, respectively) than patients in the NAR group with statistical significance after PSM analysis. The postoperative complications and recurrence patterns were comparable between the two groups. Multivariate analysis identified NAR, tumor size >5 cm, multiple tumors, and poor differentiation as independent risk factors for OS (

p
<
0.05

). Selected patients can benefit most from AR, according to subgroup analysis. A prognostic nomogram based on six independent risk factors for OS and factors with clinical significance was constructed to predict OS in ICC patients. Conclusion. AR improved the long-term survival of ICC with comparable postoperative complications and similar recurrence patterns. AR is suggested in ICC patients with sufficient remnant liver volume. In addition to surgery strategy, malignant characteristics of tumors are risk factors for ICC prognosis.
Dynamin-Related Protein 1 Is Involved in Mitochondrial Damage, Defective Mitophagy, and NLRP3 Inflammasome Activation Induced by MSU Crystals
Authors: Jiang Hui , Chen Feng , Song DianZe , Zhou Xiaoqin , Ren Long , Zeng Mei
Published: October 2022

Excessive generation of reactive oxygen species (ROS) has great impacts on MSU crystal-induced inflammation. Drp1-dependent mitochondrial fission is closely associated with mitochondrial ROS levels. However, whether Drp1 signaling contributes to MSU crystal-induced inflammation remains unclear. Mice bone marrow-derived macrophages (BMDMs) were primed with LPS and then stimulated with MSU suspensions for 12 h. The protein levels associated with mitochondrial dynamics, oxidative stress, and mitophagy were detected by Western blot. BMDMs were loaded with MitoTracker Green probe to detect mitochondrial morphology. To measure mitochondrial reactive oxygen species (ROS) and total ROS levels, cells were loaded, respectively, with MitoSOX and DHE probes. The effects of Mito-TEMPO, an antioxidant that targets the mitochondria or DRP1 inhibitor (Mdivi-1) on MSU crystal-induced peritonitis and arthritis mouse models, were evaluated. Our study revealed that MSU crystal stimulation resulted in elevation of mitochondrial fragmentation of BMDMs. Treatment with Mito-TEMPO or Drp1 knockdown significantly ameliorated the mitochondrial damage induced by MSU crystals. BMDMs exposure to MSU crystals increased the expression of auto/mitophagy marker proteins and promoted the fusion of mitophagosomes with lysosomes, leading to accumulation of mitolysosomes. Drp1 knockdown alleviated defective mitophagy and activation of the NLRP3 inflammasome in MSU crystal-treated BMDMs. This study indicates that there is crosstalk between mitochondrial ROS and Drp1 signaling in MSU crystal-induced inflammation. Drp1 signaling is involved in MSU crystal-induced mitochondrial damage, impaired mitophagy and NLRP3 inflammasome activation.
Shear-Induced ITGB4 Promotes Endothelial Cell Inflammation and Atherosclerosis
Authors: Kong Xiangquan , Chen Siyu , Luo Shuai , Chen Aiqun , Wang Liguo , Tang Haoyue , Wang Feng , Wang Zhimei , Gao Xiaofei , Zuo Guangfeng , Zhou Wenying , Gu Yue , Ge Zhen , Zhang Junjie
Published: October 2022

The local heterogeneity in the distribution of atherosclerotic lesions is caused by local flow patterns. The integrin family plays crucial regulatory roles in diverse biological processes, but knowledge of integrin β4 (ITGB4) in shear stress-induced atherosclerosis is limited. This study clarified that low shear stress (LSS) regulates the generation of ITGB4 in endothelial cells with atheroprone phenotype to identify ITGB4’s role in atherosclerosis. We found that LSS led to an increase in ITGB4 protein expression both in vitro and in vivo. ITGB4 knockdown attenuated inflammation and ROS generation in human umbilical vein endothelial cells (HUVECs) and reduced atherosclerotic lesion areas in ApoE-/- mice fed with HFD, largely independent of effects on the lipid profile. Mechanistically, ITGB4 knockdown altered the phosphorylation levels of SRC, FAK, and NFκB in HUVECs under LSS conditions. In addition, the knockdown of NFκB inhibited the production of ITGB4 and SRC phosphorylation, and the knockdown of SRC downregulated ITGB4 protein expression and NFκB activation. These data demonstrate a critical role of ITGB4 in atherosclerosis via modulation of endothelial cell inflammation, and ITGB4/SRC/NFκB might form a positive feedback loop in the regulation of endothelial cell inflammation.
Regulatory Effects of Fyn on Trophoblast Cell Behaviors and Function
Authors: Liu Qian , Ding Jinli , Xie Qingzhen
Published: October 2022

Fyn has been proven to be involved in various cell behaviors and pathophysiological processes. However, the expression and roles of Fyn in trophoblasts remain unclear. Here, we aimed to evaluate the participation of Fyn in trophoblast behavior and function, and the related mechanisms were briefly explored. Fyn expression in the HTR‐8/SVneo, JEG‐3, and JAR cell lines was evaluated by immunofluorescence, quantitative real‐time PCR and western blotting. Fyn expression in human hydatidiform moles was also determined by immunohistochemistry and western blot. To explore the effects of Fyn, HTR‐8/SVneo and JEG‐3 cells were transfected with Fyn shRNA or overexpression plasmid or treated with the Fyn activity inhibitor SU6656 or ERK1/2 inhibitor U0126. The migration, proliferation, and apoptosis of trophoblast cells were assessed using transwell assays, flow cytometry, and cell counting kit‐8 assays, respectively. The production of primary inflammatory cytokines, HLA‐G and active matrix metallopeptidase (MMP) 2/9, and the phosphorylation of ERK1/2 and STAT3 were evaluated by ELISA, western blot, or gelatin zymography. The results showed that Fyn was expressed by trophoblast cells, mainly in the cytoplasm and membrane. Fyn expression and activity levels both increased in order from HTR‐8/SVneo and JAR to JEG‐3. The overexpression of Fyn promoted the proliferation and migration of trophoblast cells and inhibited their apoptosis, while the opposite effects were observed for Fyn knockdown and inhibition. Fyn regulated inflammatory cytokine production in trophoblast cells by promoting TGF‐β and IL‐4 secretion while inhibiting IFN‐γ and TNF‐α secretion. Moreover, HLA‐G expression in JEG‐3 was positively regulated by Fyn. Fyn also facilitated the expression of active MMP2/9 and the activation of ERK1/2 and STAT3. Besides, it was confirmed that Fyn regulated trophoblast cell activities through ERK1/2 signal pathway by using U0126. Our study first detected the expression of Fyn in trophoblast cells. Fyn played pivotal roles in trophoblast cell behaviors and function, ERK1/2 was one of its targets, and MMP2/9 and STAT3 may also be involved in the regulatory mechanism.
Impact of Various Wearability Conditions on the Performances of Meander-Line Z-Shaped Embroidered Antenna
Authors: Ali Adnan E. , Stojanović Goran M. , Jeoti Varun , Sekulić Dalibor , Sinha Ankita
Published: October 2022

The field of wearable computing technology describes the future of electronic systems being an integral part of our everyday clothing with various enhanced functionalities. The present work is aimed at making closer steps towards the real wearability of electronics using textiles. We designed a fully-textile meander line Z–shaped monopole antenna for radio-frequency (RF) harvesting and for short-range communication purposes in the body-area network for various wearable applications. The target antenna was designed in the Ansys HFSS software tool and fabricated on a single-layer cotton textile using silver conductive threads and an embroidery technique. The antenna was characterized using a vector network analyzer (VNA), and the selected design was found to be nearly invariant under different deployment conditions. Antenna performance was studied by measuring the return loss while the antenna was in close proximity to the human body, or under various bending scenarios and/or wet conditions with sweat. The simulated return loss was −20.36 dB at an operating frequency of 1.62 GHz, and the measured return loss for the fabricated antenna was −19.45 dB at 1.6275 GHz with a −10 dB bandwidth of 100 MHz (i.e., 1.58 GHz to 1.68 GHz), and a fractional bandwidth of 6.17%. The results of this study are very important for the design of future wearable antennas in the new concept of the Internet of bodies.
Evaluation of the Moral Distress Intensity and Its Relationship with the Quality of Work Life among Nurses Working in Oncology Wards in Shiraz, Southwest of Iran
Authors: Molazem Zahra , Bagheri Leila , Najafi Kalyani Majid
Published: October 2022

Background. Moral distress defined as an incident that prevents the appropriate functioning of individuals in spite of having the required knowledge. Nurses are commonly exposed to moral distress while doing their professional roles, which can influence the quality of their work life. The present study aimed to assess the relationship between the moral distress intensity and work life quality amongst nurses. Methods. In this descriptive‐correlational study, 180 nurses working in oncology wards were selected through census based on inclusion criteria (associate or higher degrees, having at least six months of clinical work experience, and not suffering from anxiety disorders). The data were collected using Corley’s questionnaire (2001) and Brooks’ investigation of work life quality of nurses (2001). Then, the data were entered into the SPSS 22 software and were analyzed using the Independent Sample t‐test, One‐way ANOVA, and Pearson’s correlation coefficient. Results. The nurses’ mean scores of moral distress and work life quality were 136.63 ± 27.39 and 133.83 ± 25.40, respectively. The results revealed a negative significant relationship between the nurses’ moral distress and work life quality (P < 0.001) (r = −0.53). There was also a significant difference between the nurses’ sex and work life quality (P < 0.05). Conclusion. Identifying the moral distress intensity and work life quality of nurses and proper planning from the authorities can improve job satisfaction in nurses and resulting to higher quality of care.
Residual Strength Estimation Method of Soft Coal Based on Equivalent Residual Strain Ratio
Authors: Liu Qingquan , Ling Hao , Lu Yanfei , Lin Jia , Liu Yuanyuan , Wang Jing , Huang Wenyi , Wang Liang
Published: October 2022

In underground mining engineering, the residual strength of surrounding rock has an important influence on the secondary stress distribution caused by excavation. Generally, the residual strength of coal can be measured by experiments, but for soft coal, due to its large postpeak deformation characteristics and the limitation of strain sensor range, it is difficult to measure residual strength. Therefore, it is of great practical significance to estimate the residual strength of soft coal with incomplete stress-strain curves. In this paper, a method for estimating residual strength of soft coal based on the ratio of equivalent residual strain to peak strain is proposed. Taking advantage of the characteristics that the strain-softening curve of soft coal decreases approximately linearly in the initial stage, keeping the drop modulus unchanged, the endpoint of the extension line can be determined based on the ratio of equivalent residual strain to peak strain, which is estimated residual strength. There are 342 groups of typical complete stress-strain curves analyzed to determine the value range of the ratio of equivalent residual strain to peak strain. It is concluded that for briquette composed of soft coal, the ratio of equivalent residual strain to peak strain is between 1 and 3.35 when the confining pressure is 0-6 MPa, and the maximum probability interval of the ratio value under different confining pressures is further calculated. When the confining pressure is higher than 6 MPa, the briquette composed of soft coal tends to ideal plastic state after peak. The feasibility of the residual strength estimation method is verified by comparing the numerical simulation results of triaxial compression of coal pillars with the experimental results.
Soy Isoflavones and Bone Health: Focus on the RANKL/RANK/OPG Pathway
Authors: Hooshiar Saeedeh Hosseini , Tobeiha Mohammad , Jafarnejad Sadegh
Published: October 2022

Bone remodels via resorption and formation, two phenomena that continuously occur in bone turnover. The RANKL/RANK/OPG pathway is one of the several mechanisms that affect bone turnover. The RANKL/OPG ratio has a substantial role in bone resorption. An imbalance between formation and resorption is related to an increased RANKL/OPG balance. OPG, a member of this system, can bind to RANKL and suppress RANK‐RANKL interaction, and subsequently, inhibit further osteoclastogenesis. The serum levels of RANKL and OPG in the bone microenvironment are vital for osteoclasts formation. The RANK/RANKL/OPG system plays a role in the pathogenesis of bone disorders. This system can be considered a new treatment target for bone disorders. Soy isoflavones affect the RANK/RANKL/OPG system through numerous mechanisms. Soy isoflavones decrease RANKL levels and increase OPG levels. Therefore, isoflavones improve bone metabolism and decrease bone resorption. Soy isoflavones decrease serum markers of bone resorption and improve bone metabolism. However, while the available data are promising, the results of several studies reported no change in RANKL and OPG levels with isoflavones supplementation. In this regard, current evidence is insufficient for conclusive approval of the efficacy of isoflavones on RANKL/RANK/OPG and further research, including animal and human studies, are needed to confirm the effect of soy isoflavones on the RANKL/RANK/OPG pathway. This study was a review of available evidence to determine the role of isoflavones in bone hemostasis and the RANK/RANKL/OPG pathway. The identification of the effects of isoflavones on the RANKL/RANK/OPG pathway directs future studies and leads to the development of effective treatment strategies for bone disorders.
Assessment of Protective Effects of Carvacrol on Haloperidol-Induced Oxidative Stress and Genotoxicity in Human Peripheral Blood Lymphocytes
Authors: Zamani Ehsan , Ahmadi Shad Alireza , Fatemi Hediye , Mahboubi Saba , Motavallian Azadeh , Evazalipour Mehdi
Published: October 2022

Haloperidol is a first-generation antipsychotic drug that has several indications in a wide range of mental conditions. The extensive prescription of haloperidol is correlated with some less-known adverse effects such as genotoxicity. Carvacrol is a monoterpenoid mainly found in oregano and thyme. It has the potential to scavenge free radicals in addition to increasing antioxidant defense enzyme activities and glutathione levels. In this study, we attempted to explore the possible potential of haloperidol in inducing genotoxicity in human peripheral lymphocytes as well as the protective role of carvacrol against this effect. The lymphocytes were divided into separate groups as follows: control group (cosolvent and NS); carvacrol group (5 μM); haloperidol group (25, 50, and 100 ng/ml); haloperidol (25, 50, and 100 ng/ml) + carvacrol (5 μM); positive control (0.8 μg/ml Cisplatin). After 24 hours of treatment, we conducted a cytokinesis-Block micronucleus test and an alkaline comet assay in order to determine genetic damage. Additionally, we measured glutathione and MDA levels as the biomarkers associated with oxidative stress. Significant increases in the levels of genotoxicity biomarkers (micronucleus frequency, DNA percentage in tail and tail moment) were observed in haloperidol-treated cells. The result of our oxidative stress tests also demonstrated that haloperidol had the potential to induce oxidative stress via reducing the levels of glutathione and increasing lipid peroxidation. Treatment with carvacrol significantly decreased the genotoxic events. It can be presumed that the induction of oxidative stress by haloperidol is the critical event associated with haloperidol-mediated genotoxicity. Therefore, using carvacrol as a natural antioxidant protected human lymphocytes against haloperidol genetic damage.
Spatial Transcriptomic Analysis of a Diverse Patient Cohort Reveals a Conserved Architecture in Triple-Negative Breast Cancer
Authors: Bassiouni Rania , Idowu Michael O. , Gibbs Lee D. , Robila Valentina , Grizzard Pamela J. , Webb Michelle G. , Song Jiarong , Noriega Ashley , Craig David W. , Carpten John D.
Published: October 2022

Triple-negative breast cancer (TNBC) is an aggressive disease that disproportionately affects African American (AA) women. Limited targeted therapeutic options exist for patients with TNBC. Here, we employ spatial transcriptomics to interrogate tissue from a racially diverse TNBC cohort to comprehensively annotate the transcriptional states of spatially resolved cellular populations. A total of 38,706 spatial features from a cohort of 28 sections from 14 patients were analyzed. Intratumoral analysis of spatial features from individual sections revealed heterogeneous transcriptional substructures. However, integrated analysis of all samples resulted in nine transcriptionally distinct clusters that mapped across all individual sections. Furthermore, novel use of join count analysis demonstrated nonrandom directional spatial dependencies of the transcriptionally defined shared clusters, supporting a conserved spatio-transcriptional architecture in TNBC. These findings were substantiated in an independent validation cohort comprising 17,861 spatial features representing 15 samples from 8 patients. Stratification of samples by race revealed race-associated differences in hypoxic tumor content and regions of immune-rich infiltrate. Overall, this study combined spatial and functional molecular analyses to define the tumor architecture of TNBC, with potential implications in understanding TNBC disparities.

Significance:

Spatial transcriptomics profiling of a diverse cohort of triple-negative breast cancers and innovative informatics approaches reveal a conserved cellular architecture across cancers and identify proportional differences in tumor cell composition by race.
Prostate Cancer Transcriptomic Regulation by the Interplay of Germline Risk Alleles, Somatic Mutations, and 3D Genomic Architecture
Authors: Yuan Jiapei , Houlahan Kathleen E. , Ramanand Susmita G. , Lee Sora , Baek GuemHee , Yang Yang , Chen Yong , Strand Douglas W. , Zhang Michael Q. , Boutros Paul C. , Mani Ram S.
Published: October 2022

Prostate cancer is one of the most heritable human cancers. Genome-wide association studies have identified at least 185 prostate cancer germline risk alleles, most noncoding. We used integrative three-dimensional (3D) spatial genomics to identify the chromatin interaction targets of 45 prostate cancer risk alleles, 31 of which were associated with the transcriptional regulation of target genes in 565 localized prostate tumors. To supplement these 31, we verified transcriptional targets for 56 additional risk alleles using linear proximity and linkage disequilibrium analysis in localized prostate tumors. Some individual risk alleles influenced multiple target genes; others specifically influenced only distal genes while leaving proximal ones unaffected. Several risk alleles exhibited widespread germline–somatic interactions in transcriptional regulation, having different effects in tumors with loss of PTEN or RB1 relative to those without. These data clarify functional prostate cancer risk alleles in large linkage blocks and outline a strategy to model multidimensional transcriptional regulation.

Significance:

Many prostate cancer germline risk alleles are enriched in the noncoding regions of the genome and are hypothesized to regulate transcription. We present a 3D genomics framework to unravel risk SNP function and describe the widespread germline–somatic interplay in transcription control.

This article is highlighted in the In This Issue feature, p. 2711