bluuebunny/crossref_metadata_2025_split huggingface dataset:
Short-term exposure to an obesogenic diet during adolescence elicits anxiety-related behavior and neuroinflammation: modulatory effects of exogenous neuregulin-1
Authors: Vega-Torres Julio David , Ontiveros-Angel Perla , Terrones Esmeralda , Stuffle Erwin C. , Solak Sara , Tyner Emma , Oropeza Marie , dela Peña Ike , Obenaus Andre , Ford Byron D. , Figueroa Johnny D. 
Published: February 2022

AbstractChildhood obesity leads to hippocampal atrophy and altered cognition. However, the molecular mechanisms underlying these impairments are poorly understood. The neurotrophic factor neuregulin-1 (NRG1) and its cognate ErbB4 receptor play critical roles in hippocampal maturation and function. This study aimed to determine whether exogenous NRG1 administration reduces hippocampal abnormalities and neuroinflammation in rats exposed to an obesogenic Western-like diet (WD). Lewis rats were randomly divided into four groups (12 rats/group): (1) control diet+vehicle(CDV); (2) CD + NRG1(CDN)(daily intraperitoneal injections: 5 μg/kg/day; between postnatal day, PND 21-PND 41); (3) WD + VEH(WDV); (4) WD + NRG1(WDN). Neurobehavioral assessments were performed at PND 43–49. Brains were harvested for MRI and molecular analyses at PND 49. We found that NRG1 administration reduced hippocampal volume (7%) and attenuated hippocampal-dependent cued fear conditioning in CD rats (56%). NRG1 administration reduced PSD-95 protein expression (30%) and selectively reduced hippocampal cytokine levels (IL-33, GM-CSF, CCL-2, IFN-γ) while significantly impacting microglia morphology (increased span ratio and reduced circularity). WD rats exhibited reduced right hippocampal volume (7%), altered microglia morphology (reduced density and increased lacunarity), and increased levels of cytokines implicated in neuroinflammation (IL-1α, TNF-α, IL-6). Notably, NRG1 synergized with the WD to increase hippocampal ErbB4 phosphorylation and the tumor necrosis alpha converting enzyme (TACE/ADAM17) protein levels. Although the results did not provide sufficient evidence to conclude that exogenous NRG1 administration is beneficial to alleviate obesity-related outcomes in adolescent rats, we identified a potential novel interaction between obesogenic diet exposure and TACE/ADAM17-NRG1-ErbB4 signaling during hippocampal maturation. Our results indicate that supraoptimal ErbB4 activities may contribute to the abnormal hippocampal structure and cognitive vulnerabilities observed in obese individuals.
Protracted abstinence in males with an opioid use disorder: partial recovery of nucleus accumbens function
Authors: Tolomeo Serenella , Baldacchino Alex , Volkow Nora D. , Steele J. Douglas 
Published: February 2022

AbstractOpioid use disorder (OUD) affects more than 27 million people globally accounting for more than 300,000 deaths annually. Protracted abstinence among individuals with OUD is rare due to a high relapse rate among those not receiving medications for OUD. Extensive preclinical studies form the basis of the allostasis theory, which proposes long-lasting functional brain abnormalities that persist after opioid withdrawal and contribute to relapse. Few studies have tested the allostasis theory in humans using neuroimaging. Here, we used fMRI and an instrumental learning task to test allostasis theory predictions (ATP) of functional abnormalities in both positive valence (PVS) and negative valence (NVS) accumbens systems in OUD patients with protracted abstinence (n = 15), comparing them with OUD patients receiving methadone treatment (MT) (n = 33), and with healthy controls (n = 23). As hypothesized, protracted abstinence OUD patients showed incomplete recovery of nucleus accumbens function, as evidenced by the blunted response to aversive events (NVS) during negative reinforcement, as observed in MT patients. In contrast, their accumbens response to rewarding events (PVS) during positive reinforcement was similar to that of controls and different from that in MT patients whose response was blunted. Protracted abstinence OUD patients also showed improvements in depression symptoms compared to MT patients. Residual depressive symptoms and pre-MT intravenous drug measures were associated with worse accumbens function in protracted abstinence. These results support the ATP of long-lasting dysfunction of NVS after withdrawal and show preliminary evidence of recovery of PVS function with protracted withdrawal. Therapeutic strategies that target NVS may facilitate recovery.
Grey matter covariation and the role of emotion reappraisal in mental wellbeing and resilience after early life stress exposure
Authors: Park Haeme R. P. , Quidé Yann , Schofield Peter R. , Williams Leanne M. , Gatt Justine M. 
Published: February 2022

AbstractResilience is a process of adaptive recovery crucial in maintaining mental wellbeing after stress exposure. A psychological factor known to buffer stress and promote positive wellbeing outcomes is the ability to regulate emotions. However, the neural networks underlying resilience, and the possible mediating role of emotion regulation, remain largely unknown. Here, we examined the association between resilience and grey matter covariation (GMC) in healthy adults with and without early life stress (ELS) exposure, and whether emotion regulation mediated this brain-resilience association. Source-based morphometry was used to identify spatial patterns of common GMC in 242 healthy participants. Wellbeing was measured using the COMPAS-W Wellbeing Scale. Linear mixed models were run to establish associations between GMC and wellbeing scores. Moderated mediation models were used to examine a conditional mediating effect of emotion regulation on the brain-wellbeing relationship, moderated by ELS exposure. Distinct ELS-related morphometric patterns were found in association with resilience. In participants without ELS exposure, decreased GMC in the temporo-parietal regions was associated with wellbeing. In participants with ELS exposure, we observed increased patterns of covariation in regions related to the salience and executive control networks, and decreased GMC in temporo-parietal areas, which were associated with resilience. Cognitive reappraisal mediated the brain-wellbeing relationship in ELS-exposed participants only. Patterns of stronger GMC in regions associated with emotional and cognitive functioning in ELS-exposed participants with high levels of wellbeing may indicate possible neural signatures of resilience. This may be further heightened by utilising an adaptive form of emotion regulation.
Identification of ultra-rare disruptive variants in voltage-gated calcium channel-encoding genes in Japanese samples of schizophrenia and autism spectrum disorder
Authors: Wang Chenyao , Horigane Shin-ichiro , Wakamori Minoru , Ueda Shuhei , Kawabata Takeshi , Fujii Hajime , Kushima Itaru , Kimura Hiroki , Ishizuka Kanako , Nakamura Yukako , Iwayama Yoshimi , Ikeda Masashi , Iwata Nakao , Okada Takashi , Aleksic Branko , Mori Daisuke , Yoshida Takashi , Bito Haruhiko , Yoshikawa Takeo , Takemoto-Kimura Sayaka , Ozaki Norio 
Published: February 2022

AbstractSeveral large-scale whole-exome sequencing studies in patients with schizophrenia (SCZ) and autism spectrum disorder (ASD) have identified rare variants with modest or strong effect size as genetic risk factors. Dysregulation of cellular calcium homeostasis might be involved in SCZ/ASD pathogenesis, and genes encoding L-type voltage-gated calcium channel (VGCC) subunits Cav1.1 (CACNA1S), Cav1.2 (CACNA1C), Cav1.3 (CACNA1D), and T-type VGCC subunit Cav3.3 (CACNA1I) recently were identified as risk loci for psychiatric disorders. We performed a screening study, using the Ion Torrent Personal Genome Machine (PGM), of exon regions of these four candidate genes (CACNA1C, CACNA1D, CACNA1S, CACNA1I) in 370 Japanese patients with SCZ and 192 with ASD. Variant filtering was applied to identify biologically relevant mutations that were not registered in the dbSNP database or that have a minor allele frequency of less than 1% in East-Asian samples from databases; and are potentially disruptive, including nonsense, frameshift, canonical splicing site single nucleotide variants (SNVs), and non-synonymous SNVs predicted as damaging by five different in silico analyses. Each of these filtered mutations were confirmed by Sanger sequencing. If parental samples were available, segregation analysis was employed for measuring the inheritance pattern. Using our filter, we discovered one nonsense SNV (p.C1451* in CACNA1D), one de novo SNV (p.A36V in CACNA1C), one rare short deletion (p.E1675del in CACNA1D), and 14 NSstrict SNVs (non-synonymous SNV predicted as damaging by all of five in silico analyses). Neither p.A36V in CACNA1C nor p.C1451* in CACNA1D were found in 1871 SCZ cases, 380 ASD cases, or 1916 healthy controls in the independent sample set, suggesting that these SNVs might be ultra-rare SNVs in the Japanese population. The neuronal splicing isoform of Cav1.2 with the p.A36V mutation, discovered in the present study, showed reduced Ca2+-dependent inhibition, resulting in excessive Ca2+ entry through the mutant channel. These results suggested that this de novo SNV in CACNA1C might predispose to SCZ by affecting Ca2+ homeostasis. Thus, our analysis successfully identified several ultra-rare and potentially disruptive gene variants, lending partial support to the hypothesis that VGCC-encoding genes may contribute to the risk of SCZ/ASD.
Circ-PKD2 promotes Atg13-mediated autophagy by inhibiting miR-646 to increase the sensitivity of cisplatin in oral squamous cell carcinomas
Authors: Gao Ling , Zhang Qian , Li Shaoming , Zheng Jingjing , Ren Wenhao , Zhi Keqian 
Published: February 2022

AbstractAutophagy is an evolutionally conserved catabolic process that degrades cells to maintain homeostasis. Cisplatin-activated autophagy promotes the expression of circ-PKD2, which plays a role as a tumor suppressor gene in the proliferation, migration, and invasion in oral squamous cell carcinoma (OSCC). However, the role of circ-PKD2 in regulating the sensitivity of OSCC patients to cisplatin remains to be elucidated. Overexpression of circ-PKD2 increased the formation of autophagosomes in OSCC cells and activation of proteins, such as LC3 II/I. Its activation effect on autophagy was, however, alleviated by 3-MA. Bioinformatics analyses and double luciferases reporter assays conducted in this study confirmed the existence of targeted relationships between circ-PKD2 and miR-646 and miR-646 and Atg13. Functional experiments further revealed that miR-646 reversed the autophagy and apoptosis effects of circ-PKD2 in OSCC cells treated with cisplatin. In addition, circ-PKD2 promoted the expression of ATG13 by adsorption of miR-646. Its interference with Atg13 alleviated the activation effects of circ-PKD2 on autophagy and apoptosis of miR-646. Notably, the in vivo animal experiments also confirmed that circ-PKD2 inhibited tumor proliferation and activated autophagy in OSCC cells. This study provides a theoretical basis for using circ-PKD2 as a target to regulate the sensitivity of OSCC patients to cisplatin, thus increasing its chemotherapeutic effects.
CircCYP24A1 hampered malignant phenotype of renal cancer carcinoma through modulating CMTM-4 expression via sponging miR-421
Authors: Wu Xiaorong , Zhou Jiale , Zhao Ling , Yang Zhaolin , Yang Chen , Chen Yonghui , Xue Wei 
Published: February 2022

AbstractRenal cell carcinoma (RCC) is a lethal urinary malignancy. Circular RNAs (circRNAs) contribute to the malignant phenotype and progression of several types of human cancers, including RCC. In this study, we identified relatively low hsa_circ_0060927 (circCYP24A1) expression in RCC tissue through high-throughput sequencing and RT–qPCR. Fluorescence in situ hybridization (FISH) was used to validate the expression and subcellular localization of circCYP24A1 in RCC tissues. CCK-8, Transwell, EdU, and wound-healing assays indicated that circCYP24A1 overexpression inhibited the proliferation, invasion, and migration of RCC cells. Dual-luciferase reporter, RNA immunoprecipitation (RIP), FISH, and RNA-pulldown assays verified that circCYP24A1 inhibited RCC progression by sponging miR-421, thus inducing CMTM-4 expression. Xenograft assays and metastasis models further indicated that circCYP24A1 significantly inhibited the metastasis and proliferation of RCC cells in vivo. Taken together, circCYP24A1 is a prognosis-related circRNA in RCC that functions through the circCYP24A1/miR-421/CMTM-4 axis to modulate RCC progression.
CDC7 kinase (DDK) inhibition disrupts DNA replication leading to mitotic catastrophe in Ewing sarcoma
Authors: Martin Jeffrey C. , Sims Jennie R. , Gupta Ajay , Hagoel Tamara J. , Gao Lingqiu , Lynch Miranda L. , Woloszynska Anna , Melendy Thomas , Kane Jeremy F. , Kuechle Joseph , Ohm Joyce E. 
Published: February 2022

AbstractEwing sarcoma is the second most common bone malignancy in children and adolescents. In recent years, a large body of evidence has emerged that suggests Ewing tumors harbor large amounts of replication stress (RS). CDC7, also known as DDK (DBF4-dependent kinase), is a serine/threonine kinase that is involved in a diverse array of cellular functions including the regulation of DNA replication initiation and activation of the RS response. Due to DDK’s diverse roles during replication, coupled with the fact that there is an increased level of RS within Ewing tumors, we hypothesized that Ewing sarcoma cells would be particularly vulnerable to DDK inhibition. Here, we report that DDK inhibition resulted a significant reduction in cell viability and the induction of apoptosis, specifically in Ewing sarcoma cells. Treatment with DDK inhibitors dramatically reduced the rate of replication, prolonged S-phase, and led to a pronounced increase in phospho-CDC2 (Y15), indicating delay of mitotic entry. The induction of cell death corresponded to mitotic exit and G1 entry, suggesting improper mitotic progression. In accordance with this, we find that DDK inhibition caused premature mitotic entry resulting in mitotic abnormalities such as anaphase bridges, lagging chromosomes, and cells with >2 poles in Ewing sarcoma cells. This abnormal progression through mitosis resulted in mitotic catastrophe as evidenced by the formation of micronuclei and induction of DNA damage. Together, these findings suggest that DDK activity is required for the faithful and timely completion of DNA replication in Ewing cells and that DDK inhibition may present a viable therapeutic strategy for the treatment of Ewing sarcoma.
MYSM1 induces apoptosis and sensitizes TNBC cells to cisplatin via RSK3–phospho-BAD pathway
Authors: Guan Xiaolin , Meng Xin , Zhu Keyu , Kai Jinyan , Liu Yixuan , Ma Qian , Tong Ying , Zheng Hui , Xie Suhong , Ma Xiaolu , Wang Yanchun , Lu Renquan , Guo Lin 
Published: February 2022

AbstractBreast cancer is one of the leading causes of mortality among women. Triple-negative breast cancer (TNBC) is responsible for a large percentage of all breast cancer deaths in women. This study demonstrated the function of Myb-like, SWIRM, and MPN domains 1 (MYSM1), an H2A deubiquitinase (DUB), in TNBC. MYSM1 expression was drastically decreased in breast cancer, especially in TNBC, suggesting a potential anticancer effect. Overexpressing and suppressing MYSM1 expression in TNBC cell lines led to significant biological changes in cell proliferation. Furthermore, MYSM1 overexpression increased cisplatin-induced apoptosis, which might be attributed to RSK3 inactivation and the subsequently decreased phosphorylation of Bcl-2 antagonist of cell death (BAD) (Ser 112). The findings suggest that MYSM1 is a potential target for regulating cell apoptosis and suppressing resistance to cisplatin in TNBC.
NVP-AUY922 alleviates radiation-induced lung injury via inhibition of autophagy-dependent ferroptosis
Authors: Li Li , Wu Dongming , Deng Shihua , Li Jin , Zhang Feng , Zou Ye , Zhang Ting , Xu Ying 
Published: February 2022

AbstractRadiation-induced lung injury (RILI) is a common complication of radiotherapy for which no effective interventions are available. NVP-AUY922, a resorcinylic isoxazole amide drug, exhibits anti-inflammatory, immunomodulatory, and therapeutic effects against various types of cancers. In this study, we explore the role and underlying mechanisms of NVP-AUY922 in the treatment of RILI. We established a model of BEAS-2B cell injury and a mouse model of RILI. Cell proliferation, death, gross weight, and survival rates of mice, and histological parameters were assessed. Additionally, inflammation-related indices and indicators related to ferroptosis were evaluated. Furthermore, immunofluorescence and co-immunoprecipitation were used to determine the interaction between GPX4, LAMP-2A, and HSC70. NVP-AUY922 significantly ameliorated radiation-induced lung tissue damage, inflammatory cell infiltration, proinflammatory cytokine release, and lung epithelial BEAS-2B cell damage. NVP-AUY922 markedly limited the activation of ferroptosis, which is involved in RILI. Mechanistically, NVP-AUY922 prevented chaperone-mediated autophagy of the GPX4 pathway in vitro and in vivo, and the autophagy inhibitor Baf-A1 significantly increased the level of GPX4 and alleviated lung inflammation. NVP-AUY922 can alleviate RILI by inhibiting chaperone-mediated lysosomal degradation of GPX4, demonstrating its potential as a novel protective agent against RILI.
Loss of Ripk3 attenuated neutrophil accumulation in a lipopolysaccharide-induced zebrafish inflammatory model
Authors: Wen Wanying , Chen Jiakui , Zhou Yuxin , Li Gaofei , Zhang Yiyue 
Published: February 2022

AbstractNeutrophils are important effector cells during inflammation, which play complex roles. Therefore, investigating the regulation of neutrophil accumulation during inflammation might provide targets for treating related diseases. In the present study, we generated aripk3-deficient zebrafish line to study the roles of Ripk3 in neutrophil-related inflammation. The homeostatic hematopoiesis and cytokine expression of theripk3-deficient larvae were unaltered. Theripk3-deficient larvae with caudal fin fold injury exhibited similar neutrophil enrichment with wild-type larvae, suggesting that Ripk3 is not essential for non-infectious inflammatory responses. When challenged with lipopolysaccharide (LPS), theripk3-deficient larvae showed significantly less neutrophil accumulation in the injection site and differential expression of several key cytokines. Ripk3 inhibitors could also attenuate neutrophil accumulation in wild-type larvae, indicating that Ripk3 could serve as a candidate target for inflammation treatment. In summary, our study indicated that Ripk3 has an essential role in LPS-induced inflammatory responses. It was suggested that theripk3-deficient zebrafish might be applied in developing infectious disease models, while Ripk3 also has potential as an inflammation-treatment target.
Microswimming by oxidation of dibenzylamine
Authors: Wittmann Martin , Heckel Sandra , Wurl Felix , Xiao Zuyao , Gemming Thomas , Strassner Thomas , Simmchen Juliane 
Published: February 2022

Photocatalytic BiVO4 microparticles with an inherent asymmetries can actively move by catalysing the oxidation of dibenzylamine.
SWOT analysis of e‐commerce development of rural tourism farmers' professional cooperatives in the era of big data
Authors: Li Kai 
Published: February 2022

AbstractIn the era of big data, strategy is an indicator that determines business growth and directly guides the sustainable development of business. This paper aims to study the construction of the SWOT (S stands for strength, W stands for weakness, O stands for opportunity, and T stands for threat.) structure analysis model of e‐commerce tourism development strategy based on the experience of big data. Through empirical analysis, it explores the factors that affect the development strategy of e‐commerce business, and proposes practical measures and development directions. Based on big data theory, this paper uses SWOT analysis to analyze the e‐commerce development strategy of China's rural tourism cooperatives in detail, and uses the analytic hierarchy process to analyze the green development direction of e‐commerce tourism enterprises. The experimental results of this paper show that the order of enterprise development strategy selection in the context of big data for tourism electronics is: SO strategy, ST strategy, WO strategy and WT strategy.
Low drift visual inertial odometry with UWB aided for indoor localization
Authors: Gao Bo , Lian Baowang , Wang Dongjia , Tang Chengkai 
Published: February 2022

AbstractVisual inertial odometry (VIO) would have an estimation drift problem in the process of long trajectory for indoor localization, especially in the absence of loop detection or in unknown complex scenes. To solve this problem, a low drift visual inertial odometry with ultra‐wideband (UWB) aided for indoor localization was proposed. Firstly, a single UWB anchor was dropped in an unknown position, and a cost function was formed by the position information output by VIO and the UWB ranging information to obtain the position of the anchor. Then, the single anchor position and the UWB ranging constraints were added to the tightly coupled visual inertial fusion algorithm framework, thereby improving the robustness of motion tracking and reducing the drift of the odometry. Finally, the effectiveness of the proposed method was verified in the actual indoor environment, and the experiment results demonstrated that, compared with state‐of‐the‐art localization methods, the positioning accuracy and robustness were improved significantly.
Gaussian estimation for non‐linear stochastic uncertain systems with time‐correlated additive noises and packet dropout compensations
Authors: Cheng Guo‐Rui , Ma Meng‐Chen , Tan Li‐Guo , Song Shen‐Min 
Published: February 2022

AbstractThis paper discusses the problem of state estimation for non‐linear stochastic uncertain systems with time‐correlated additive noise and packet dropout compensations. Both process noise and measurement noise are additive forms of noise that can be described as Gaussian first‐order Markov processes. The stochastic uncertainty of the system is described by synchronous correlated white multiplicative noise. When the measurement information from the current epoch is lost, a compensation strategy based on measurement information prediction is used. First, the state information, process noise, and measurement noise are augmented to enable the construction of a new vector to be estimated, and the filter, predictor, and smoother of the system are designed using a Gaussian iterative estimation algorithm based on innovation analysis. The multiplicative noise in the process equation is estimated in real time. Second, a numerical implementation of the proposed algorithm is derived based on the third‐degree spherical‐radial Cubature Kalman filter(CKF). Finally, the proposed algorithm is compared with an extended Kalman filter (EKF) based on Taylor series expansion. The effectiveness of the proposed algorithm is verified by comparing the simulation results.