bluuebunny/crossref_metadata_2025_split huggingface dataset:
2′-Hydroxycinnamaldehyde ameliorates imiquimod-induced psoriasiform inflammation by targeting PKM2-STAT3 signaling in mice
Authors: Hao Lihua , Mao Yuancheng , Park Jin , Kwon Byoung-Mog , Bae Eun Ju , Park Byung-Hyun 
Published: May 2021

Abstract2′-Hydroxycinnamaldehyde (HCA), the active component isolated from the stem bark of Cinnamomum cassia, exerts anticancer effects through multiple mechanisms. We recently determined that HCA inhibits signal transducer and activator of transcription 3 (STAT3) signaling in prostate cancer cells. Because STAT3 overactivation has been closely associated with the development of psoriasis, a chronic autoimmune skin disease, we examined whether HCA ameliorates skin lesions in an imiquimod-induced psoriasis-like mouse model. The results showed that intraperitoneal administration of HCA alleviated imiquimod-induced psoriasis-like dermatitis, epidermal thickening, dermal infiltration of inflammatory cells, and proinflammatory cytokine production. Mechanistically, HCA inhibited pyruvate kinase isozyme M2 and STAT3 signaling, leading to the suppression of T cell activation, Th17 cell differentiation, and keratinocyte hyperproliferation. These results suggest that HCA may be a new treatment for psoriasis and other STAT3-mediated skin disorders, such as infection, inflammation and carcinogenesis.
The loss of SHMT2 mediates 5-fluorouracil chemoresistance in colorectal cancer by upregulating autophagy
Authors: Chen Jian , Na Risi , Xiao Chao , Wang Xiao , Wang Yupeng , Yan Dongwang , Song Guohe , Liu Xueni , Chen Jiayi , Lu Huijun , Chen Chunyan , Tang Huamei , Zhuang Guohong , Fan Guangjian , Peng Zhihai 
Published: May 2021

Abstract5-Fluorouracil (5-FU)-based chemotherapy is the first-line treatment for colorectal cancer (CRC) but is hampered by chemoresistance. Despite its impact on patient survival, the mechanism underlying chemoresistance against 5-FU remains poorly understood. Here, we identified serine hydroxymethyltransferase-2 (SHMT2) as a critical regulator of 5-FU chemoresistance in CRC. SHMT2 inhibits autophagy by binding cytosolic p53 instead of metabolism. SHMT2 prevents cytosolic p53 degradation by inhibiting the binding of p53 and HDM2. Under 5-FU treatment, SHMT2 depletion promotes autophagy and inhibits apoptosis. Autophagy inhibitors decrease low SHMT2-induced 5-FU resistance in vitro and in vivo. Finally, the lethality of 5-FU treatment to CRC cells was enhanced by treatment with the autophagy inhibitor chloroquine in patient-derived and CRC cell xenograft models. Taken together, our findings indicate that autophagy induced by low SHMT2 levels mediates 5-FU resistance in CRC. These results reveal the SHMT2–p53 interaction as a novel therapeutic target and provide a potential opportunity to reduce chemoresistance.
Decentering as a core component in the psychological treatment and prevention of youth anxiety and depression: a narrative review and insight report
Authors: Bennett Marc P. , Knight Rachel , Patel Shivam , So Tierney , Dunning Darren , Barnhofer Thorsten , Smith Patrick , Kuyken Willem , Ford Tamsin , Dalgleish Tim 
Published: May 2021

AbstractDecentering is a ubiquitous therapeutic concept featuring in multiple schools of psychological intervention and science. It describes an ability to notice to day-to-day psychological stressors (negative thoughts, feelings, and memories) from an objective self-perspective and without perseverating on the themes they represent. Thus, decentering dampens the impact and distress associated with psychological stressors that can otherwise increase mental ill health in vulnerable individuals. Importantly, the strengthening of decentering-related abilities has been flagged as a core component of psychological interventions that treat and prevent anxiety and depression. We provide an in-depth review evidence of the salutary effects of decentering with a special focus on youth mental health. This is because adolescence is a critical window for the development of psychopathology but is often under-represented in this research line. A narrative synthesis is presented that integrates and summarizes findings on a range of decentering-related abilities. Section 1 reviews extant conceptualizations of decentering and data-driven approaches to characterize its characteristic. A novel definition is then offered to guide future empirical research. Section 2 overviews laboratory-based research into the development of decentering as well as its relationship with anxiety and depression. Section 3 examines the role decentering-related skills play in psychological interventions for anxiety and depression. Critically, we review evidence that treatment-related increases in decentering predict latter reductions in anxiety and depression severity. Each section highlights important areas for future research. The report concludes by addressing the vital questions of whether, how, why and when decentering alleviates youth anxiety and depression.
Tumor- and osteoclast-derived NRP2 in prostate cancer bone metastases
Authors: Polavaram Navatha Shree , Dutta Samikshan , Islam Ridwan , Bag Arup K. , Roy Sohini , Poitz David , Karnes Jeffrey , Hofbauer Lorenz C. , Kohli Manish , Costello Brian A. , Jimenez Raffael , Batra Surinder K. , Teply Benjamin A. , Muders Michael H. , Datta Kaustubh 
Published: May 2021

AbstractUnderstanding the role of neuropilin 2 (NRP2) in prostate cancer cells as well as in the bone microenvironment is pivotal in the development of an effective targeted therapy for the treatment of prostate cancer bone metastasis. We observed a significant upregulation of NRP2 in prostate cancer cells metastasized to bone. Here, we report that targeting NRP2 in cancer cells can enhance taxane-based chemotherapy with a better therapeutic outcome in bone metastasis, implicating NRP2 as a promising therapeutic target. Since, osteoclasts present in the tumor microenvironment express NRP2, we have investigated the potential effect of targeting NRP2 in osteoclasts. Our results revealed NRP2 negatively regulates osteoclast differentiation and function in the presence of prostate cancer cells that promotes mixed bone lesions. Our study further delineated the molecular mechanisms by which NRP2 regulates osteoclast function. Interestingly, depletion of NRP2 in osteoclasts in vivo showed a decrease in the overall prostate tumor burden in the bone. These results therefore indicate that targeting NRP2 in prostate cancer cells as well as in the osteoclastic compartment can be beneficial in the treatment of prostate cancer bone metastasis.
Cephalomannine inhibits hypoxia-induced cellular function via the suppression of APEX1/HIF-1α interaction in lung cancer
Authors: Ullah Asmat , Leong Sze Wei , Wang Jingjing , Wu Qing , Ghauri Mohsin Ahmad , Sarwar Ammar , Su Qi , Zhang Yanmin 
Published: May 2021

AbstractLung cancer (LC) is one of the leading causes of cancer-related death. As one of the key features of tumor microenvironment, hypoxia conditions are associated with poor prognosis in LC patients. Upregulation of hypoxic-induced factor-1α (HIF-1α) leads to the activation of various factors that contribute to the increased drug resistance, proliferation, and migration of tumor cells. Apurinic/apyrimidinic endonuclease-1 (APEX1) is a multi-functional protein that regulates several transcription factors, including HIF-1α, that contribute to tumor growth, oxidative stress responses, and DNA damage. In this study, we explored the mechanisms underlying cell responses to hypoxia and modulation of APEX1, which regulate HIF-1α and downstream pathways. We found that hypoxia-induced APEX1/HIF-1α pathways regulate several key cellular functions, including reactive oxygen species (ROS) production, carbonic anhydrase 9 (CA9)-mediated intracellular pH, migration, and angiogenesis. Cephalomannine (CPM), a natural compound, exerted inhibitory effects in hypoxic LC cells via the inhibition of APEX1/HIF-1α interaction in vitro and in vivo. CPM can significantly inhibit cell viability, ROS production, intracellular pH, and migration in hypoxic LC cells as well as angiogenesis of HUVECs under hypoxia through the inhibition of APEX1/HIF-1α interaction. Taken together, CPM could be considered as a promising compound for LC treatment.
The endoribonuclease N4BP1 prevents psoriasis by controlling both keratinocytes proliferation and neutrophil infiltration
Authors: Gou Chenliang , Ni Wenkai , Ma Panpan , Zhao Fengbo , Wang Zhou , Sun Rong , Wu Yingcheng , Wu Yuanyuan , Chen Miaomiao , Chen Hao , Zhang Jie , Shen Yu , Xiao Mingbing , Lu Cuihua , Mao Renfang , Fan Yihui 
Published: May 2021

AbstractPsoriasis is a common chronic skin disease, characterized by abnormal interplay between hyperproliferative epidermal keratinocytes and self-reactive immune cells with not fully addressed molecular mechanism. N4BP1 (NEDD4-binding protein 1) is considered as an immune regulator for a long time but its physiological role is not determined yet. Here, we found that the expression of N4BP1 in skin was highest among all 54 tested tissues, and its expression was further upregulated in psoriatic skin. N4BP1-deficient mice exhibited normal grossly, but developed severe and prolonged IMQ-induced psoriasis-like disease comparing to controls. N4BP1 mainly expressed in keratinocytes and located on nucleus. Up- but not downregulated genes in N4BP1-deficient skin were specifically enriched in keratinocyte proliferation and differentiation. The proliferation of N4BP1-deficient primary keratinocytes was faster compared to that of controls. The upregulated genes upon ablation of N4BP1 were highly enriched in targets of AP-1 transcription factor. Knocking out N4BP1 resulted in upregulation of JunB and FosB, and conversely, overexpression of N4BP1 greatly reduced their expression. Furthermore, N4BP1 binds with JunB and FosB encoding mRNAs and greatly reduces their stability. In addition, with a high expression in neutrophils, N4BP1 limits survival of neutrophils in blood and infiltration of neutrophils in psoriatic skin by targeting CXCL1, CCL20, and S100A8. These findings demonstrate that N4BP1 controls the proper function of keratinocytes and neutrophils by negatively regulating JunB, FosB, and CXCL1, respectively, and that is critical for psoriasis prevention.
Single cell RNA sequencing for breast cancer: present and future
Authors: Ren Lili , Li Junyi , Wang Chuhan , Lou Zheqi , Gao Shuangshu , Zhao Lingyu , Wang Shuoshuo , Chaulagain Anita , Zhang Minghui , Li Xiaobo , Tang Jing 
Published: May 2021

AbstractBreast cancer is one of the most common malignant tumors in women. It is a heterogeneous disease related to genetic and environmental factors. Presently, the treatment of breast cancer still faces challenges due to recurrence and metastasis. The emergence of single-cell RNA sequencing (scRNA-seq) technology has brought new strategies to deeply understand the biological behaviors of breast cancer. By analyzing cell phenotypes and transcriptome differences at the single-cell level, scRNA-seq reveals the heterogeneity, dynamic growth and differentiation process of cells. This review summarizes the application of scRNA-seq technology in breast cancer research, such as in studies on cell heterogeneity, cancer cell metastasis, drug resistance, and prognosis. scRNA-seq technology is of great significance to deeply analyze the mechanism of breast cancer occurrence and development, identify new therapeutic targets and develop new therapeutic approaches for breast cancer.
3D particle averaging and detection of macromolecular symmetry in localization microscopy
Authors: Heydarian Hamidreza , Joosten Maarten , Przybylski Adrian , Schueder Florian , Jungmann Ralf , Werkhoven Ben van , Keller-Findeisen Jan , Ries Jonas , Stallinga Sjoerd , Bates Mark , Rieger Bernd 
Published: May 2021

AbstractSingle molecule localization microscopy offers in principle resolution down to the molecular level, but in practice this is limited primarily by incomplete fluorescent labeling of the structure. This missing information can be completed by merging information from many structurally identical particles. In this work, we present an approach for 3D single particle analysis in localization microscopy which hugely increases signal-to-noise ratio and resolution and enables determining the symmetry groups of macromolecular complexes. Our method does not require a structural template, and handles anisotropic localization uncertainties. We demonstrate 3D reconstructions of DNA-origami tetrahedrons, Nup96 and Nup107 subcomplexes of the nuclear pore complex acquired using multiple single molecule localization microscopy techniques, with their structural symmetry deducted from the data.
The effect of levodopa on bilateral coordination and gait asymmetry in Parkinson’s disease using inertial sensor
Authors: Son Minji , Han Seung Hwan , Lyoo Chul Hyoung , Lim Joo Ae , Jeon Jeanhong , Hong Kee-Bum , Park Hoon 
Published: May 2021

AbstractThis study aimed to evaluate the effect of levodopa on the phase coordination index (PCI) and gait asymmetry (GA) of patients with Parkinson’s disease (PD) and to investigate correlations between the severity of motor symptoms and gait parameters measured using an inertial sensor. Twenty-six patients with mild-to-moderate-stage PD who were taking levodopa participated in this study. The Unified Parkinson’s Disease Rating Scale part III (UPDRS III) was used to assess the severity of motor impairment. The Postural Instability and Gait Difficulty (PIGD) subscore was calculated from UPDRS III. Patients were assessed while walking a 20-m corridor in both “OFF” and “ON” levodopa medication states, and gait analysis was performed using inertial sensors. We investigated the changes in gait parameters after taking levodopa and the correlations between UPDRS III, PIGD, and gait parameters. There was a significant improvement in PCI after taking levodopa. No significant effect of levodopa on GA was found. In “OFF” state, PCI and GA were not correlated with UPDRS III and PIGD. However, in “ON” state, PCI was the only gait parameter correlating with UPDRS III, and it was also highly correlated with PIGD compared to other gait parameters. Significant improvement in bilateral-phase coordination was identified in patients with PD after taking levodopa, without significant change in gait symmetricity. Considering the high correlation with UDPRS III and PIGD in “ON” states, PCI may be a useful and quantitative parameter to measure the severity of motor symptoms in PD patients who are on medication.
Association of asthma with low serum vitamin D and its related musculoskeletal and psychological symptoms in adults: a case-control study
Authors: Alkhatatbeh Mohammad J. , Almomani Haneen S. , Abdul-Razzak Khalid K. , Samrah Shaher 
Published: May 2021

AbstractThere are complex potential inter-relationships between the chronic inflammation of asthma and poor control, vitamin D deficiency, musculoskeletal pain and anxiety and depression. The aim was to investigate associations between vitamin D and these possible co-morbidities. This case-controlled study involved 75 adults with asthma and 75 controls. Serum 25-hydroxyvitamin D (25(OH)D) was measured, levels of anxiety, depression, musculoskeletal pain, and asthma control were assessed. Participants with asthma had lower 25(OH)D and higher anxiety scores and higher measures of musculoskeletal pain compared to controls. Binary logistic regression showed that asthma was associated with decreased 25(OH)D (Odds ratio (OR) = 0.86), general weakness (OR = 13.29), complaint of musculoskeletal pain (OR = 13.73), and increased intensity of musculoskeletal pain (OR = 0.61) and number of painful sites (OR = 2.58). Asthma was not associated with anxiety or depression. Further studies are required to investigate if vitamin D supplementation can improve asthma symptoms and musculoskeletal pain.
Single-shot detection of 8 unique monochrome fringe patterns representing 4 distinct directions via multispectral fringe projection profilometry
Authors: Omidi Parsa , Najiminaini Mohamadreza , Diop Mamadou , Carson Jeffrey J. L. 
Published: May 2021

AbstractSpatial resolution in three-dimensional fringe projection profilometry is determined in large part by the number and spacing of fringes projected onto an object. Due to the intensity-based nature of fringe projection profilometry, fringe patterns must be generated in succession, which is time-consuming. As a result, the surface features of highly dynamic objects are difficult to measure. Here, we introduce multispectral fringe projection profilometry, a novel method that utilizes multispectral illumination to project a multispectral fringe pattern onto an object combined with a multispectral camera to detect the deformation of the fringe patterns due to the object. The multispectral camera enables the detection of 8 unique monochrome fringe patterns representing 4 distinct directions in a single snapshot. Furthermore, for each direction, the camera detects two π-phase shifted fringe patterns. Each pair of fringe patterns can be differenced to generate a differential fringe pattern that corrects for illumination offsets and mitigates the effects of glare from highly reflective surfaces. The new multispectral method solves many practical problems related to conventional fringe projection profilometry and doubles the effective spatial resolution. The method is suitable for high-quality fast 3D profilometry at video frame rates.
Predictive SNPs for β0-thalassemia/HbE disease severity
Authors: Munkongdee Thongperm , Tongsima Sissades , Ngamphiw Chumpol , Wangkumhang Pongsakorn , Peerapittayamongkol Chayanon , Hashim Hafizah Binti , Fucharoen Suthat , Svasti Saovaros 
Published: May 2021

Abstractβ-Thalassemia/HbE disease has a wide spectrum of clinical phenotypes ranging from asymptomatic to dependent on regular blood transfusions. Ability to predict disease severity is helpful for clinical management and treatment decision making. A thalassemia severity score has been developed from Mediterranean β-thalassemia patients. However, different ethnic groups may have different allele frequency and linkage disequilibrium structures. Here, Thai β0-thalassemia/HbE disease genome-wild association studies (GWAS) data of 487 patients were analyzed by SNP interaction prioritization algorithm, interacting Loci (iLoci), to find predictive SNPs for disease severity. Three SNPs from two SNP interaction pairs associated with disease severity were identifies. The three-SNP disease severity risk score composed of rs766432 in BCL11A, rs9399137 in HBS1L-MYB and rs72872548 in HBE1 showed more than 85% specificity and 75% accuracy. The three-SNP predictive score was then validated in two independent cohorts of Thai and Malaysian β0-thalassemia/HbE patients with comparable specificity and accuracy. The SNP risk score could be used for prediction of clinical severity for Southeast Asia β0-thalassemia/HbE population.
A numerical study on capillary-evaporation behavior of porous wick in electronic cigarettes
Authors: Gao Yihan , Li Dian , Ru Jiexiong , Yang Muyun , Lu Lehua , Lu Li , Wu Jinlu , Huang Zhonghui , Xie Yan , Gao Naiping 
Published: May 2021

AbstractA mathematical model based on heat and mass transfer processes in the porous wick of electronic cigarettes was established to describe the atomization of e-liquids according to max liquid temperature, vaporization rate and thermal efficiency in a single puff. Dominant capillary-evaporation effects were defined in the model to account for the effects of electrical power, e-liquid composition and porosity of the wick material on atomization and energy transmission processes. Liquid temperature, vaporization rate, and thermal efficiency were predicted using the mathematical model in 64 groups, varying with electrical power, e-liquid composition and wick porosity. Experimental studies were carried out using a scaled-model test bench to validate the model’s prediction. A higher PG/VG ratio in the e-liquid promoted energy transfer for vaporization, and the e-liquid temperature was comparatively reduced at a relatively high power, which was helpful to avoid atomizer overheating. Compared with the other factors, wick porosity affected the thermal efficiency more significantly. The vaporization rate increased with a higher wick porosity in a certain range. The modelling results suggested that a greater wick porosity and a higher PG ratio in e-liquids helped to improve the overall thermal efficiency.
EGR1 as a potential marker of prognosis in extranodal NK/T-cell lymphoma
Authors: Lee Ji Yun , Kim Joo Hyun , Bang Heejin , Cho Junhun , Ko Young Hyeh , Kim Seok Jin , Kim Won Seog 
Published: May 2021

AbstractExtranodal natural killer T-cell lymphoma (ENKTL) is an aggressive malignancy with a dismal prognosis. In the present study, gene expression profiling was performed to provide more information on ENKTL molecular signature and offer a rationale for further investigation of prognostic markers in ENKTL. NanoString nCounter Analysis encompassing 133 target genes was used to compare gene expression levels of 43 ENKTL tumor samples. The majority of the patients were under 60 years of age (79.1%); 32 (74.4%) patients had nasal type ENKTL and 23 patients (53.5%) had intermediate/high risk ENKTL based on the prognostic index for natural killer cell lymphoma (PINK). The median follow-up was 15.9 months and the median overall survival (OS) was 16.1 months (95% CI 13.0–69.8). EGR1 upregulation was consistently identified in the localized stage with a low risk of prognostic index based on the PINK. Among the six significantly relevant genes for EGR1 expression, high expression levels of genes, including CD59, GAS1, CXCR7, and RAMP3, were associated with a good survival prognosis. The in vitro test showed EGR1 modulated the transcriptional activity of the target genes including CD59, GAS1, CXCR7, and RAMP3. Downregulation of EGR1 and its target genes significantly inhibited apoptosis and decreased chemosensitivity and attenuated radiation-induced apoptosis. The findings showed EGR1 may be a candidate for prognostic markers in ENKTL. Considerable additional characterization may be necessary to fully understand EGR1.