bluuebunny/crossref_metadata_2025 huggingface dataset:
Strategi Bank NTB Syariah Dalam Meningkatkan Kepuasan Nasabah Melalui Layanan Digital Di Masa Pandemi Covid-19
Authors: Sundari Listia , Haryanti Peni
Published: June 2022

Pada tahun 2020 lalu muncul adanya penyakit menular di indonesia yang dinamakan virus corona. Virus ini juga berdampak buruk pada perekonomian indonesia termasuk lembaga keuangan seperti perbankan. Namun dikala pandemi ini terjadi Bank NTB Syariah membuktikan bahwa ia mampu bertahan yang ditunjukkan dengan peningkatan aset pada desember 2020 lalu bahkan melampaui target yang telah ditentukan, hal ini tentu karena masyarakat masih percaya dan nyaman dengan pelayanan yang ditawarkan oleh Bank NTB Syariah. Penelitian ini bertujuan untuk mengetahui bentuk-bentuk layanan digital Bank NTB Syariah di masa pandemi covid-19 dan mengetahui upaya Bank NTB Syariah dalam meningkatkan kepuasan nasabah melalui layanan digital di masa pandemi covid-19. Metode penelitian yang digunakan adalah pendekatan kualitatif dengan metode analisis deskriptif. Hasil penelitian ini menunjukkan bahwa (I) bentuk-bentuk layanan digital Bank NTB Syariah di masa pandemi covid-19 adalah mobile Banking, sms banking dan ATM. Pembayaran pajak bumi dan bangunan melalui fitur go bills diplatform gopay. (II) nasabah merasa puas dengan adanya layanan digital Bank NTB Syariah karena transaksi cepat, aman dengan fitur yang lengkap.
Kata kunci: Bank Syariah, Digital, Kepuasan, Pelayanan
Differentiation of Bone Mesenchymal Stem Cells Into Vascular Endothelial Cell-Like Cells Using Functionalized Single-Walled Carbon Nanotubes
Authors: Luo Feng , Li Ruyi , Zheng Huaping , Xu Yichen , Yang Linxin , Qu Changxing , Hong Guang , Wan Qianbing
Published: June 2022

Carbon nanotubes (CNTs) are a promising bioactive scaffold for bone regeneration because of their superior mechanical and biological properties. Vascularization is crucial in bone tissue engineering, and insufficient vascularization is a long-standing problem in tissue-engineered scaffolds. However, the effect of CNTs on vascularization is still minimal. In the current study, pristine single-walled carbon nanotubes (SWNTs) were purified to prepare different ratios of SWNTs/EDC composites, and their surface morphology and physicochemical properties of SWNTs/EDC were studied. Furthermore, the effect of SWNTs/EDC on vascularization was investigated by inducing the differentiation of bone mesenchymal stem cells (BMSCs) into vascular endothelial cell-like cells (VEC-like cells). Results showed that SWNTs/EDC composite was successfully prepared, and EDC was embedded in the SWNTs matrix and uniformly distributed throughout the composites. The AFM, FTIR spectra, and Raman results confirmed the formation of SWNTs/EDC composites. Besides, the surface topography of the SWNTs/EDC composites presents a rough surface, which may positively affect cell function. In vitro cell culture revealed that SWNTs and SWNTs/EDC composites exhibited excellent biocompatibility and bioactivity. The SWNTs/EDC composite at mass/volume ratios 1:10 had the best enhancement of proliferation and differentiation of BMSCs. Moreover, after culture with SWNTs/EDC composite, approximately 78.3% ± 4.2% of cultured cells are double-positive for FITC-UEA-1 and DiI-Ac-LDL double staining. Additionally, the RNA expression of representative endothelial cell markers VEGF, VEGF-R2, CD31, and vWF in the SWNTs/EDC composite group was significantly higher than those in the control and SWNTs group. With the limitation of our study, the results suggested that SWNTs/EDC composite can promote BMSCs differentiation into VEC-like cells and positively affect angiogenesis and bone regeneration.
Comprehensive Bioinformatics Analysis to Reveal Key RNA Targets and Hub Competitive Endogenous RNA Network of Keratoconus
Authors: Ouyang Shuai , Ma Jingyu , Sun Qihang , Li Jinyan , Chen Yijia , Luo Lixia
Published: June 2022

Keratoconus (KC) is the most common corneal ectatic disease, with its pathological mechanisms unclear. We mainly performed bioinformatics approaches to reveal core RNA targets and hub competitive endogenous RNA (ceRNA) network and explored the potential regulatory mechanisms of ceRNA in KC. The high-throughput sequencing datasets GSE77938 and GSE151631 were downloaded from the Gene Expression Omnibus (GEO) database. The differential expression of mRNAs and lncRNAs was identified using the DESeq2 package. Functional enrichment analyses and protein–protein interaction (PPI) were executed. Then, the hub genes were filtered and molecular docking analysis was performed. Moreover, we predicted miRNAs through a website database and validated them using quantitative PCR (qPCR). Eventually, the lncRNA–miRNA–mRNA regulatory network was constructed by Cytoscape. We revealed that 428 intersected differentially expressed mRNA (DEGs) and 68 intersected differentially expressed lncRNA (DELs) were shared between the two datasets. Functional enrichment results innovatively showed that the ubiquitin-dependent protein catabolic process was upregulated in KC. The pathway enrichment showed that DEGs were mainly involved in NF-kB signaling and neurodegenerative diseases. In addition, we uncovered the top 20 hub genes in which FBXW11, FBXO9, RCHY1, and CD36 were validated by qPCR. Particularly, a small-molecule drug triptolide was predicted by molecular docking to be a candidate drug for treating KC. Moreover, we innovatively predicted and validated four core miRNAs (miR-4257, miR-4494, miR-4263, and miR-4298) and constructed a ceRNA network that contained 165 mRNA, eight lncRNAs, and four core miRNAs. Finally, we proposed a potential regulatory mechanism for KC. Overall, we uncovered a hub ceRNA network that might underlie a critical posttranslational regulatory mechanism in KC, in which miR-4257, miR-4494, miR-4263, and miR-4298 could be valuable biomarkers and provided core RNAs therapeutic targets for KC.
Human Neutrophils Present Mild Activation by Zika Virus But Reduce the Infection of Susceptible Cells
Authors: Aggio Juliana Bernardi , Porto Bárbara Nery , Duarte dos Santos Claudia Nunes , Mosimann Ana Luiza Pamplona , Wowk Pryscilla Fanini
Published: June 2022

The emergence of the Zika virus (ZIKV) has highlighted the need for a deeper understanding of virus-host interactions in order to pave the way for the development of antiviral therapies. The present work aimed to address the response of neutrophils during ZIKV infection. Neutrophils are important effector cells in innate immunity implicated in the host’s response to neurotropic arboviruses. Our results indicate that human neutrophils were not permissive to Asian or African ZIKV strain replication. In fact, after stimulation with ZIKV, neutrophils were mild primed against the virus as evaluated through CD11b and CD62L modulation, secretion of inflammatory cytokines and granule content, production of reactive oxygen species, and neutrophil extracellular traps formation. Overall, neutrophils did not affect ZIKV infectivity. Moreover, in vitro ZIKV infection of primary innate immune cells did not trigger neutrophil migration. However, neutrophils co-cultured with ZIKV susceptible cell lineages resulted in lower cell infection frequencies, possibly due to cell-to-cell contact. In vivo, neutrophil depletion in immunocompetent mice did not affect ZIKV spreading to the draining lymph nodes. The data suggest that human neutrophils do not play an antiviral role against ZIKV per se, but these cells might participate in an infected environment shaping the ZIKV infection in other target cells.
Adoptive NK Cell Transfer as a Treatment in Colorectal Cancer Patients: Analyses of Tumour Cell Determinants Correlating With Efficacy In Vitro and In Vivo
Authors: Lanuza Pilar M. , Alonso M. Henar , Hidalgo Sandra , Uranga-Murillo Iratxe , García-Mulero Sandra , Arnau Raquel , Santos Cristina , Sanjuan Xavier , Santiago Llipsy , Comas Laura , Redrado Sergio , Pazo-Cid Roberto , Agustin-Ferrández M. Jose , Jaime-Sánchez Paula , Pesini Cecilia , Gálvez Eva M. , Ramírez-Labrada Ariel , Arias Maykel , Sanz-Pamplona Rebeca , Pardo Julián
Published: June 2022

Background

Colorectal cancer (CRC) is a heterogeneous disease with variable mutational profile and tumour microenvironment composition that influence tumour progression and response to treatment. While chemoresistant and poorly immunogenic CRC remains a challenge, the development of new strategies guided by biomarkers could help stratify and treat patients. Allogeneic NK cell transfer emerges as an alternative against chemoresistant and poorly immunogenic CRC.

Methods

NK cell-related immunological markers were analysed by transcriptomics and immunohistochemistry in human CRC samples and correlated with tumour progression and overall survival. The anti-tumour ability of expanded allogeneic NK cells using a protocol combining cytokines and feeder cells was analysed in vitro and in vivo and correlated with CRC mutational status and the expression of ligands for immune checkpoint (IC) receptors regulating NK cell activity.

Results

HLA-I downmodulation and NK cell infiltration correlated with better overall survival in patients with a low-stage (II) microsatellite instability-high (MSI-H) CRC, suggesting a role of HLA-I as a prognosis biomarker and a potential benefit of NK cell immunotherapy. Activated allogeneic NK cells were able to eliminate CRC cultures without PD-1 and TIM-3 restriction but were affected by HLA-I expression. In vivo experiments confirmed the efficacy of the therapy against both HLA+ and HLA− CRC cell lines. Concomitant administration of pembrolizumab failed to improve tumour control.

Conclusions

Our results reveal an immunological profile of CRC tumours in which immunogenicity (MSI-H) and immune evasion mechanisms (HLA downmodulation) favour NK cell immunosurveillance at early disease stages. Accordingly, we have shown that allogeneic NK cell therapy can target tumours expressing mutations conferring poor prognosis regardless of the expression of T cell-related inhibitory IC ligands. Overall, this study provides a rationale for a new potential basis for CRC stratification and NK cell-based therapy.
Targeting Cytokine Signals to Enhance γδT Cell-Based Cancer Immunotherapy
Authors: Song Yuan , Liu Yonghao , Teo Huey Yee , Liu Haiyan
Published: June 2022

γδT cells represent a small percentage of T cells in circulation but are found in large numbers in certain organs. They are considered to be innate immune cells that can exert cytotoxic functions on target cells without MHC restriction. Moreover, γδT cells contribute to adaptive immune responseviaregulating other immune cells. Under the influence of cytokines, γδT cells can be polarized to different subsets in the tumor microenvironment. In this review, we aimed to summarize the current understanding of antigen recognition by γδT cells, and the immune regulation mediated by γδT cells in the tumor microenvironment. More importantly, we depicted the polarization and plasticity of γδT cells in the presence of different cytokines and their combinations, which provided the basis for γδT cell-based cancer immunotherapy targeting cytokine signals.
Impact of Torulaspora delbrueckii During Fermentation on Aromatic Profile of Vidal Blanc Icewine
Authors: Li Jing , Hong Mengnan , Qi Baiyu
Published: June 2022

Non-Saccharomyces yeasts usually have a positive effect on improving the diversity of wine aroma and increasing the differentiation of wine products. Among these non-Saccharomyces yeast species, Torulaspora delbrueckii is often studied and used in winemaking in recent years, but its application in icewine has not been reported yet. In this study, indigenous T. delbrueckii strains (TD1 and TD2) and Saccharomyces cerevisiae strains (commercial yeast SC1 and indigenous icewine yeast SC2) were sequentially inoculated for icewine fermentations; meanwhile, pure S. cerevisiae (SC1 and SC2) fermentations were used as the control; TD1, TD2, and SC2 strains used were screened from spontaneous fermentations of Vidal blanc icewine. The aim was to investigate the effect of T. delbrueckii on the aroma complexity of icewine, which is of great significance to the application of T. delbrueckii in icewine production. The results showed that T. delbrueckii was completely replaced by S. cerevisiae at the middle and later fermentative stages in mixed culture fermentations. Compared with the icewine fermented with pure S. cerevisiae, mixed culture fermented icewines contained lower acetic acid and ethanol, and higher glycerol. The inoculation of T. delbrueckii greatly impacted the levels of several important volatile compounds, and more 2-phenylethyl alcohol, isoamyl acetate, linalool, D-limonene, p-cymene and cineole were produced, and the fruity, flowery, and sweet characteristic was intensified. Moreover, the relevance of strain-specificity within T. delbrueckii to aroma compound differences was shown. To our knowledge, this study is the first to investigate the application of T. delbrueckii in Vidal blanc icewine fermentation, and volatile aroma compounds in the icewine fermented by T. delbrueckii and S. cerevisiae.
Limbic Responses Following Shock Wave Exposure in Male and Female Mice
Authors: McNamara Eileen H. , Tucker Laura B. , Liu Jiong , Fu Amanda H. , Kim Yeonho , Vu Patricia A. , McCabe Joseph T.
Published: June 2022

Blast traumatic brain injury (bTBI) presents a serious threat to military personnel and often results in psychiatric conditions related to limbic system dysfunction. In this study, the functional outcomes for anxiety- and depressive-like behaviors and neuronal activation were evaluated in male and female mice after exposure to an Advanced Blast Simulator (ABS) shock wave. Mice were placed in a ventrally exposed orientation inside of the ABS test section and received primary and tertiary shock wave insults of approximately 15 psi peak pressure. Evans blue staining indicated cases of blood-brain barrier breach in the superficial cerebral cortex four, but not 24 h after blast, but the severity was variable. Behavioral testing with the elevated plus maze (EPM) or elevated zero maze (EZM), sucrose preference test (SPT), and tail suspension test (TST) or forced swim test (FST) were conducted 8 days–3.5 weeks after shock wave exposure. There was a sex difference, but no injury effect, for distance travelled in the EZM where female mice travelled significantly farther than males. The SPT and FST did not indicate group differences; however, injured mice were less immobile than sham mice during the TST; possibly indicating more agitated behavior. In a separate cohort of animals, the expression of the immediate early gene, c-Fos, was detected 4 h after undergoing bTBI or sham procedures. No differences in c-Fos expression were found in the cerebral cortex, but female mice in general displayed enhanced c-Fos activation in the paraventricular nucleus of the thalamus (PVT) compared to male mice. In the amygdala, more c-Fos-positive cells were observed in injured animals compared to sham mice. The observed sex differences in the PVT and c-Fos activation in the amygdala may correlate with the reported hyperactivity of females post-injury. This study demonstrates, albeit with mild effects, behavioral and neuronal activation correlates in female rodents after blast injury that could be relevant to the incidence of increased post-traumatic stress disorder in women.
The Alteration Profiles of m6A-Tagged circRNAs in the Peri-Infarct Cortex After Cerebral Ischemia in Mice
Authors: Li Yudi , Li Hanzhao , Luo Yang , Li Xiaoqiang , Chen Zhefeng , Zhang Wanzhou , Li Fangming , Ling Li
Published: June 2022

The N6-methyladenosine (m6A) modification acts as a dynamic regulatory factor in diseases by regulating the metabolism and function of the transcriptome, especially mRNAs. However, little is known regarding the functional effects of m6A modifications on circRNAs. In this research, we established a distal middle cerebral artery occlusion (MCAO) model in adult C57BL/6J mice. The mice were divided into three groups: sham surgery, 3 days after MCAO (3d), and 7 days after MCAO (7d). Reverse transcription quantitative polymerase chain reaction (RT-qPCR) demonstrated that the mRNA expression levels of m6A-related methyltransferases (METTL3, METTL14), demethylases (FTO, ALKBH5), and reading proteins (YTHDF1, YTHDF3) altered compared to the sham group. Furthermore, the translation level of ALKBH5 and YTHDF3 was significantly decreased in the 3d group while increased in 7d group. Methylated RNA immunoprecipitation (MeRIP) and circRNA microarray indicated 85 hypermethylated and 1621 hypomethylated circRNAs in the 3d group. In the 7d group, the methylation level increased in 57 and decreased in 66 circRNAs. Subsequently, our results were verified by MeRIP-qPCR. Bioinformatics analysis was performed to analyze the functions of differentially m6A-modified circRNAs. We found some m6A modified-circRNAs associated with cerebral infarction, providing a new direction for the molecular mechanism of stroke.
Extracellular Adenosine Triphosphate Binding to P2Y1 Receptors Prevents Glutamate-Induced Excitotoxicity: Involvement of Erk1/2 Signaling Pathway to Suppress Autophagy
Authors: Xiong Yiping , Zhou Duanyang , Zheng Kai , Bi Wenchuan , Dong Yun
Published: June 2022

Glutamate-induced neuroexcitotoxicity could be related to the pathophysiology of some neurodegenerative diseases including Parkinson’s disease and Alzheimer’s disease. Extracellular ATP exerts a wide variety of functions, such as attenuating Aβ-mediated toxicity, inhibitingN-Methyl-D-Aspartate (NMDA) receptor subunit combinations, and aggravating ischemic brain injury. However, the effect of extracellular ATP on glutamate-induced neuroexcitotoxicity remains largely unknown. Herein, we showed that extracellular ATP prevented the glutamate-induced excitotoxicityviabinding to its P2Y1 receptors. We found that excessive glutamate triggered cellular reactive oxygen species (ROS) overproduction and mitochondrial membrane potential damage, which were significantly attenuated by extracellular ATP. Besides, glutamate activated autophagy, as illustrated by the increased protein level of autophagic marker LC3II and decreased level of p62, and glutamate-induced neuroexcitotoxicity could be completely abolished by autophagy inhibitor chloroquine. In addition, we revealed that extracellular ATP activated Erk1/2 signaling to suppress autophagy and to exert its neuroprotective effects, which was further reduced by autophagy agonist rapamycin and the selective Erk1/2 inhibitor PD0325901. Taken together, our findings suggest that extracellular ATP binding to P2Y1 receptors protected against glutamate-induced excitotoxicityviaErk1/2-mediated autophagy inhibition, implying the potential of ATP for the treatment of neurodegenerative disorders.
Short-Term High-Fat Diet Fuels Colitis Progression in Mice Associated With Changes in Blood Metabolome and Intestinal Gene Expression
Authors: Wu Zhen-Hua , Yang Jing , Chen Lei , Du Chuang , Zhang Qi , Zhao Shan-Shan , Wang Xiao-Yu , Yang Jing , Liu Yang , Cai Demin , Du Jian , Liu Hui-Xin
Published: June 2022

Clinical cases and animal experiments show that high-fat (HF) diet is involved in inflammatory bowel disease (IBD), but the specific mechanism is not fully clear. A close association between long-term HF-induced obesity and IBD has been well-documented. However, there has been limited evaluation of the impact of short-term HF feeding on the risk of intestinal inflammation, particularly on the risk of disrupted metabolic homeostasis. In this study, we analyzed the metabolic profile and tested the vulnerability of 2,4,6-trinitrobenzenesulfonic acid (TNBS)-induced colitis after short-term HF feeding in mice. The results showed that compared with the control diet (CD), the fatty acid (FA), amino acid (AA), and bile acid (BA) metabolisms of mice in the HF group were significantly changed. HF-fed mice showed an increase in the content of saturated and unsaturated FAs and a decrease in the content of tryptophan (Trp). Furthermore, the disturbed spatial distribution of taurocholic acid (TCA) in the ileum and colon was identified in the HF group using matrix-assisted laser desorption/ionization-mass spectrometry imaging (MALDI-MSI). After HF priming, mice on TNBS induction were subjected to more severe colonic ulceration and histological damage compared with their CD counterparts. In addition, TNBS enema induced higher gene expressions of mucosal pro-inflammatory cytokines under HF priming conditions. Overall, our results show that HF may promote colitis by disturbing lipid, AA, and BA metabolic homeostasis and inflammatory gene expressions.
Emerging Role of MicroRNAs in the Therapeutic Response in Cervical Cancer: A Systematic Review
Authors: Ravegnini Gloria , Gorini Francesca , Dondi Giulia , Tesei Marco , De Crescenzo Eugenia , Morganti Alessio G. , Hrelia Patrizia , De Iaco Pierandrea , Angelini Sabrina , Perrone Anna Myriam
Published: June 2022

Cervical cancer is a common female cancer, with nearly 600,000 cases and more than 300,000 deaths worldwide every year. From a clinical point of view, surgery plays a key role in early cancer management, whereas advanced stages are treated with chemotherapy and/or radiation as adjuvant therapies. Nevertheless, predicting the degree of cancer response to chemotherapy or radiation therapy at diagnosis in order to personalize the clinical approach represents the biggest challenge in locally advanced cancers. The feasibility of such predictive models has been repeatedly assessed using histopathological factors, imaging and nuclear methods, tissue and fluid scans, however with poor results. In this context, the identification of novel potential biomarkers remains an unmet clinical need, and microRNAs (miRNAs) represent an interesting opportunity. With this in mind, the aim of this systematic review was to map the current literature on tumor and circulating miRNAs identified as significantly associated with the therapeutic response in cervical cancer; finally, a perspective point of view sheds light on the challenges ahead in this tumor.

Systematic Review Registration

PROSPERO (CRD42021277980).
Efficacy of Osimertinib in EGFR-Mutated Advanced Non-small-Cell Lung Cancer With Different T790M Status Following Resistance to Prior EGFR-TKIs: A Systematic Review and Meta-analysis
Authors: Yi Xiao-Fang , Song Jun , Gao Ruo-Lin , Sun Li , Wu Zhi-Xuan , Zhang Shu-Ling , Huang Le-Tian , Ma Jie-Tao , Han Cheng-Bo
Published: June 2022

Purpose

Epidermal growth factor receptor (EGFR) T790M-negative/unknown advanced non-small cell lung cancer (NSCLC) patients lack subsequent approved targeted therapies. This meta-analysis aimed to assess the efficacy of osimertinib in advanced NSCLC patients with different T790M status after resistance to prior first- or second-generation EGFR-tyrosine kinase inhibitors (EGFR-TKIs) and to predict the subgroups that may benefit beside T790M-positive disease.

Methods

PubMed, Embase, Web of Science, and Cochrane Library databases were searched for relevant trials. Meeting abstracts were also reviewed to identify appropriate studies. Studies evaluating the efficacy and/or survival outcomes of osimertinib in patients with different T790M status (positive, negative, or unknown) after resistance to prior first- or second-generation EGFR-TKIs were enrolled, and data were pooled to assess hazard ratios (HRs) or relative risk ratios (RRs) in terms of overall survival (OS), progression-free survival (PFS), and objective response rate (ORR).

Results

A total of 1,313 EGFR-mutated NSCLC patients from 10 retrospective and one prospective studies treated with osimertinib after resistance to first- or second-generation EGFR-TKIs were included. In overall groups, T790M-positive patients showed an improved OS (HR=0.574, p=0.015), PFS (HR = 0.476, p = 0.017), and ORR (RR = 2.025, p = 0.000) compared with T790M-negative patients. In the brain metastases subgroup, no significant difference in OS was observed between T790M-positive and T790M-negative patients (HR = 0.75, p = 0.449) or between T790M-positive and T790M-unknown patients (HR = 0.90, p = 0.673). In the plasma genotyping subgroup, PFS was similar between T790M-positive and T790M-negative patients (HR = 1.033, p = 0.959).

Conclusion

Patients with progressive brain metastases on first- or second-generation EGFR-TKIs can benefit from subsequent osimertinib therapy regardless of T790M status. Patients with plasma T790M-negative status and lack of tissue genotyping should be allowed to receive osimertinib treatment.
Targeting MDK Abrogates IFN-γ-Elicited Metastasis inCancers of Various Origins
Authors: Zheng Luyu , Liu Qun , Li Ruijun , Chen Shibin , Tan Jingyu , Li Lina , Dong Xichen , Huang Changzhi , Wen Tao , Liu Jian
Published: June 2022

IFN-γ is a pleiotropic cytokine with immunomodulatory and tumoricidal functions. It has been used as an anti-tumor agent in adjuvant therapies for various cancers. Paradoxically, recent advances have also demonstrated pro-tumorigenic effects of IFN-γ, especially in promoting cancer metastasis, with the mechanism remains unclear. This will undoubtedly hinder the application of IFN-γ in cancer treatment. Here, we verified that IFN-γ treatment led to activation of the epithelial-to-mesenchymal transition (EMT) programme and metastasis in cell lines of various cancers, including the kidney cancer cell line Caki-1, the lung cancer cell line A549, the cervical carcinoma cell line CaSki, the breast cancer cell line BT549 and the colon cancer cell line HCT116. We further disclosed that midkine (MDK), an emerging oncoprotein and EMT inducer, is a common responsive target of IFN-γ in these cell lines. Mechanistically, IFN-γ upregulated MDK via STAT1, a principle downstream effector in the IFN-γ signalling. MDK is elevated in the majority of cancer types in the TCGA database, and its overexpression drove EMT activation and cancer metastasis in all examined cell lines. Targeting MDK using a specific MDK inhibitor (iMDK) broadly reversed IFN-γ-activated EMT, and subsequently abrogated IFN-γ-triggered metastasis. Collectively, our data uncover a MDK-dependent EMT inducing mechanism underlying IFN-γ-driven metastasis across cancers which could be attenuated by pharmacological inhibition of MDK. Based on these findings, we propose that MDK may be used as a potential therapeutic target to eliminate IFN-γ-elicited pro-metastatic adverse effect, and that combined MDK utilization may expand the application of IFN-γ in cancer and improve the clinical benefits from IFN-γ-based therapies.
Multidisciplinary Team Meeting Proposal and Final Therapeutic Choice in Early Breast Cancer: Is There an Agreement?
Authors: Bortot Lucia , Targato Giada , Noto Claudia , Giavarra Marco , Palmero Lorenza , Zara Diego , Bertoli Elisa , Dri Arianna , Andreetta Claudia , Pascoletti Gaetano , Poletto Elena , Russo Stefania , Seriau Luca , Mansutti Mauro , Cedolini Carla , Basile Debora , Fasola Gianpiero , Bonotto Marta , Minisini Alessandro Marco
Published: June 2022

Background

A multidisciplinary team meeting (MDM) approach in breast cancer (BC) management is a standard of care. One of the roles of MDMs is to identify the best diagnostic and therapeutic strategies for patients (pts) with new diagnosis of early BC. The purpose of this study was to define whether there was an agreement between the planned program (i.e., MDMs-based decision) and that actually applied. In addition, the study explored factors associated with discordance.

Methods

We conducted a retrospective study of a consecutive series of 291 patients with new diagnosis of early BC, discussed at MDMs at the University Hospital of Udine (Italy), from January 2017 to June 2018. The association between clinico-biological factors and discordance between what was decided during the MDMs and what was consequently applied by the oncologist was explored through uni- and multivariate logistic regression analyses.

Results

The median age was 62 years (range 27–88 years). Among invasive early BC patients, the most frequent phenotype was luminal A (38%), followed by luminal B (33%), HER2-positive (12%), and triple-negative (5%). In situ carcinoma (DCIS) represented 12% of cases. The median time from MDM discussion to first oncologic examination was 2 weeks. The rate of discordance between MDM-based decision and final choice, during a face-to-face consultation with the oncologist, was 15.8% (46/291). The most frequent reason for changing the MDM-based program was clinical decision (87%). Follow-up was preferred to the chemotherapy (CT) proposed within the MDMs in 15% of cases, and to the endocrine therapy (ET) in 39% of cases (among these, 44.5% had a diagnosis of DCIS). Therapeutic change from sequential CT-ET to ET alone was chosen in 16/46 pts (35%): among these patients, seven had a luminal B disease and six had an HER2-positive disease. On univariate analysis, factors associated with discordance were values of Ki-67 14%–30% (OR 3.91; 95% CI 1.19–12.9), age >70 years (OR 2.44, 95% CI 1.28–4.63), housewife/retired status (OR 2.35, 95% CI 1.14–4.85), polypharmacy (OR 1.95; 95% CI 1.02–3.72), postmenopausal status (OR 4.15; 95% CI 1.58–10.9), and high Charlson Comorbidity Index (OR 1.31; 95% CI 1.09–1.57). The association with marital status, educational level, alcohol and smoke habits, presence of a caregiver, parity, grading, histotype and phenotype, and stage was not statistically significant. On multivariate analysis, only Ki-67 value maintained its statistical significance.

Conclusion

The results of our study could be useful for enhancing the role of MDMs in the clinical decision-making process in early BC.
The Orexin-A/OX1R System Induces Cell Death in Pancreatic Cancer Cells Resistant to Gemcitabine and Nab-Paclitaxel Treatment
Authors: Voisin Thierry , Nicole Pascal , Gratio Valérie , Chassac Anaïs , Mansour Dounia , Rebours Vinciane , Couvelard Anne , Couvineau Alain
Published: June 2022

Pancreatic ductal adenocarcinoma (PDAC) represents the fourth cause of cancer-associated death in the West. This type of cancer has a very poor prognosis notably due to the development of chemoresistance when treatments including gemcitabine and Abraxane (Nab-paclitaxel) were prescribed. The identification of new treatment circumventing this chemoresistance represents a key challenge. Previous studies demonstrated that the activation of orexin receptor type 1 (OX1R), which was ectopically expressed in PDAC, by its natural ligand named orexin-A (OxA), led to anti-tumoral effect resulting in the activation of mitochondrial pro-apoptotic mechanism. Here, we demonstrated that OxA inhibited the pancreatic cancer cell (AsPC-1) growth and inhibited the tumor volume in preclinical models as effectively as gemcitabine and Nab-paclitaxel. Moreover, the combination therapy including OxA plus gemcitabine or OxA plus Nab-paclitaxel was additive on the inhibition of cancer cell growth and tumor development. More importantly, the treatment by OxA of chemoresistant tumors to gemcitabine or Nab-paclitaxel obtained by successive xenografts in mice revealed that OxA was able to induce a strong inhibition of tumor development, whereas no OxA resistance was identified in tumors. The OX1R/OxA system might be an innovative and powerful alternative treatment of chemoresistant PDAC.
Anopheles stephensi Feeding, Flight Behavior, and Infection With Malaria Parasites are Altered by Ingestion of Serotonin
Authors: Briggs Anna M. , Hambly Malayna G. , Simão-Gurge Raquel M. , Garrison Sarah M. , Khaku Zainab , Van Susteren Grace , Lewis Edwin E. , Riffell Jeffrey A. , Luckhart Shirley
Published: June 2022

Approximately 3.4 billion people are at risk of malaria, a disease caused by infection with Plasmodium spp. parasites, which are transmitted by Anopheles mosquitoes. Individuals with severe falciparum malaria often exhibit changes in circulating blood levels of biogenic amines, including reduced serotonin or 5-hydroxytryptamine (5-HT), and these changes are associated with disease pathology. In insects, 5-HT functions as an important neurotransmitter for many behaviors and biological functions. In Anopheles stephensi, we show that 5-HT is localized to innervation in the head, thorax, and midgut, suggesting a gut-to-brain signaling axis that could support the effects of ingested 5-HT on mosquito biology and behavioral responses. Given the changes in blood levels of 5-HT associated with severe malaria and the key roles that 5-HT plays in insect neurophysiology, we investigated the impact of ingesting blood with healthy levels of 5-HT (1.5 µM) or malaria-associated levels of 5-HT (0.15 µM) on various aspects of A. stephensi biology. In these studies, we provisioned 5-HT and monitored fecundity, lifespan, flight behavior, and blood feeding of A. stephensi. We also assessed the impact of 5-HT ingestion on infection of A. stephensi with the mouse malaria parasite Plasmodium yoelii yoelii 17XNL and the human malaria parasite Plasmodium falciparum. Our data show that ingestion of 5-HT associated with severe malaria increased mosquito flight velocity and investigation of visual objects in response to host odor (CO2). 5-HT ingestion in blood at levels associated with severe malaria also increased the tendency to take a second blood meal 4 days later in uninfected A. stephensi. In mosquitoes infected with P. y. yoelii 17XNL, feeding tendency was decreased when midgut oocysts were present but increased when sporozoites were present. In addition to these effects, treatment of A. stephensi with 5-HT associated with severe malaria increased infection success with P. y. yoelii 17XNL compared to control, while treatment with healthy levels of 5-HT decreased infection success with P. falciparum. These changes in mosquito behavior and infection success could be used as a basis to manipulate 5-HT signaling in vector mosquitoes for improved control of malaria parasite transmission.
Interference of Arabidopsis N-Acetylglucosamine-1-P Uridylyltransferase Expression Impairs Protein N-Glycosylation and Induces ABA-Mediated Salt Sensitivity During Seed Germination and Early Seedling Development
Authors: Chen Ya-Huei , Shen Hwei-Ling , Chou Shu-Jen , Sato Yasushi , Cheng Wan-Hsing
Published: June 2022

N-acetylglucosamine (GlcNAc) is the fundamental amino sugar moiety that is essential for protein glycosylation. UDP-GlcNAc, an active form of GlcNAc, is synthesized through the hexosamine biosynthetic pathway (HBP). Arabidopsis N-acetylglucosamine-1-P uridylyltransferases (GlcNAc1pUTs), encoded by GlcNA.UTs, catalyze the last step in the HBP pathway, but their biochemical and molecular functions are less clear. In this study, the GlcNA.UT1 expression was knocked down by the double-stranded RNA interference (dsRNAi) in the glcna.ut2 null mutant background. The RNAi transgenic plants, which are referred to as iU1, displayed the reduced UDP-GlcNAc biosynthesis, altered protein N-glycosylation and induced an unfolded protein response under salt-stressed conditions. Moreover, the iU1 transgenic plants displayed sterility and salt hypersensitivity, including delay of both seed germination and early seedling establishment, which is associated with the induction of ABA biosynthesis and signaling. These salt hypersensitive phenotypes can be rescued by exogenous fluridone, an inhibitor of ABA biosynthesis, and by introducing an ABA-deficient mutant allele nced3 into iU1 transgenic plants. Transcriptomic analyses further supported the upregulated genes that were involved in ABA biosynthesis and signaling networks, and response to salt stress in iU1 plants. Collectively, these data indicated that GlcNAc1pUTs are essential for UDP-GlcNAc biosynthesis, protein N-glycosylation, fertility, and the response of plants to salt stress through ABA signaling pathways during seed germination and early seedling development.
Breeding of Penta Null Soybean [Glycine max (L.) Merr.] for Five Antinutritional and Allergenic Components of Lipoxygenase, KTI, Lectin, 7S α′ Subunit, and Stachyose
Authors: Choi Sang Woo , Ly Sarath , Lee Jeong Hwan , Oh Hyeon Su , Kim Se Yeong , Kim Na Hyeon , Chung Jong II
Published: June 2022

Soybean [Glycine max (L.) Merr.] is an excellent source of protein, oil, carbohydrates and many other bioactive ingredients for humans. However, several antinutritional and allergenic components such as lipoxygenase, KTI, lectin, 7S α′ subunit, and stachyose exist in the raw mature seed. Genetic removal of these components would be the best method to improve soybean food quality. The objectives of this research were to breed a new soybean line with penta null recessive alleles (lox1/lox1/lox2/lox2/lox3/lox3-ti/ti-le/le-cgy1/cgy1-rs2/rs2) for these five components and to evaluate agronomic traits for a breeding line with penta null alleles. Seven germplasms were used to breed the penta null strain. Analysis of lipoxygenase, KTI, lectin, 7S α′ subunit, and stachyose components in mature seeds was conducted by SDS-PAGE, western blot, and HPLC. One breeding line with penta null recessive alleles was developed. The breeding line has purple flowers, tawny pubescence, a determinate growth habit, and light yellow pods at maturity. The seed of the breeding line has a yellow hilum and yellow seed coat color. The stem height of the breeding line was 53.0 cm. The stachyose content of the breeding line was 2.9 g/kg. The 100-seed weight of the breeding line was 31.1 g and yield (t/ha) was 2.80. This is the first soybean strain with the penta null (lox1lox2lox3/lox1lox2lox3-ti/ti-le/le-cgy1/cgy1-rs2/rs2) genotype (free of lipoxygenase, KTI, lectin, and 7S α′ subunit proteins, and with low stachyose content).
The Influence of Erotic Stimulation on Brand Preference of Male and Female Consumers: From the Perspective of Human Reproductive Motives
Authors: Wei Xia , Huang Xin , Xie Yufeng , Tu Rungting
Published: June 2022

Based on the theory of human reproductive motives, this study discusses how erotic stimulation can help activate male and female consumers’ reproductive motives (i.e., mate-attraction and mate-retention motives), influencing product purchase intention and brand personality perception. Specifically, the results of four experiments reveal that when a man receives erotic stimulation from women, his mate-attraction motive is activated. Consequently, he perceives that the brand personality of his possessions is more rugged, and his preference for products with a rugged brand personality is stronger. Unlike male consumers, when a heterosexual woman in an intimate romantic relationship receives erotic stimulation from other women, her mate-retention motive is activated. As a result, she perceives that the brand personality of her partner’s possessions is sincerer and prefers to purchase products with a sincere brand personality for her partner. This effect will not occur when a product is owned by her male colleague than her partner.
Relooking at the Roles of Translanguaging in English as a Foreign Language Classes for Multilingual Learners: Practices and Implications
Authors: Wang Ping
Published: June 2022

The use of translanguaging pedagogy rather than favoring English-only teaching put those who hold monolingual ideology in foreign language pedagogy. A study of English as a foreign language (EFL) for multilingual students showed that embracing translanguaging appeared compelling that it emerged in Neidi Xinjiang Classes (NXC) in China. After reviewing the concepts of translanguaging, this writing presents the translanguaging theory and translanguaging pedagogy. Guided by translanguaging lenses and stances, a longitudinal case study was carried out to look into the EFL pedagogy in NXC. The focal data was heavily drawn from reflective interviews and classroom observations. The data analyses were particularly paid on the triangulation of data with the interviews and classroom observational data. The findings indicate the students made full use of the affordances to do translanguaging practices while a few EFL teachers with the monolingual ideology still violated English-only constraints against the background of the multilingual turn. Therefore, the conclusion builds on dynamic multilingual stances to identify the significance of enabling the presence of translanguaging pedagogy.
The Effect of Alternative vs. Focal Identity Accessibility on the Intent to Purchase Products: An Exploratory Study Based on Chinese Culture
Authors: Chen Fei , Yan Cheng Cheng , Wang Lin , Lou Xiao Jing
Published: June 2022

Much of early western research has focused on identity. A primed identity can inhibit the priming of other alternative identities, and also negatively affect the intention to purchase products related to those alternative identities. In western culture, individuals operate within a cultural framework that makes them more likely to prioritize their own goals and less likely to rely on environmental factors when evaluating others. Individuals are more likely to choose products that fit their primed identity. In this study, we suggest that in collectivist Chinese culture, individuals may give priority to group-level goals and attach more importance to situational factors when evaluating others. Therefore, a primed identity may not necessarily inhibit the priming of alternative identities. In this research, we examine the association between a focal identity and alternative identities, with particular emphasis on the accessibility, discrepancies, and effects on purchase intention of alternative identities. We also examine the intent to purchase products related to the alternative identity vs. the focal identity, developing a model with which to explore this construct. We test four hypotheses through experiments using an online questionnaire and analyzing the resulting data using statistical product service solutions (SPSS) 22.0 and the PROCESS macro modeling tool. The results are as follows: First, the association between a focal identity and alternative identity has a positive impact on the accessibility of the alternative identity. The clearer the alternative identity is, the greater the impact of the association between the focal identity and alternative identity on the latter’s accessibility. Second, the accessibility of the alternative identity has a positive impact on the intent to purchase alternative identity vs. focal identity-related products. The greater the discrepancy between the focal identity and the alternative identity, the greater the impact on the intent to purchase alternative identity vs. focal identity-related products. The results of this study confirmed the interaction between identity association and the clarity of the alternative identity, as well as the influence of the accessibility of the alternative identity on the intent to purchase alternative identity vs. focal identity-related products. We contribute to the development of a theory on intention to purchase identity-related products.
Newly Qualified Teachers’ Well-Being During the COVID-19 Pandemic: Testing a Social Support Intervention Through Design-Based Research
Authors: Froehlich Dominik E. , Morinaj Julia , Guias Dorothea , Hobusch Ulrich
Published: June 2022

Around the world, newly qualified teachers are leaving the profession after only a short time working at school. This not only has a negative effect on the capacities of the respective education systems, but also for the teachers themselves, as it often due to factors such as stress and burnout that leads to this decision. The COVID-19 pandemic has exacerbated this situation by adding to the teachers’ workload, uncertainty, and stress. Previous research has investigated strategies that may help teachers improve their well-being and, among other factors, found social support to be an important condition. In this mixed methods design-based research study, we developed a design to enhance social support among newly qualified teachers in their first months working at school. Our quantitative and qualitative results show that the design has positive effects on many aspects of teachers’ well-being in the intervention group both longitudinally (before and after the intervention) and when compared to a comparison group. The findings are being discussed considering the recent changes in the working conditions of teachers as imposed by the COVID-19 pandemic.
Clinical Predictive Models for Delayed Cerebral Infarction After Ruptured Intracranial Aneurysm Clipping for Patients: A Retrospective Study
Authors: Su Jun , Huang Hao , Xin Yuan-jun , Liang Yi-dan , Wu Xin-tong , Yang Xiao-lin , Liu Xiao-zhu , He Zhaohui
Published: June 2022

Objective

A nomogram was developed in this work to predict the probability of delayed cerebral infarction (DCI) after ruptured intracranial aneurysms (RIA) clipping.

Methods

Clinical data of patients with intracranial aneurysm were obtained from the neurosurgery department of the First Affiliated Hospital of Chongqing Medical University from January 2016 to December 2020. A total of 419 patients receiving surgery of ruptured intracranial aneurysm clipping were included and a total of 37 patients with DCI were set as the observation group. The control group consisted of 382 patients without DCI. Risk factors of DCI were screened by univariate and multivariate logistic regression analysis and included in the nomogram.

Results

Univariate analysis showed that female (P = 0.009), small aneurysm (P = 0.031), intraoperative aneurysm rupture (P = 0.007) and cerebral vasospasm (P < 0.001) were risk factors for postoperative DCI while smoking history (P = 0.044) were protective factors for postoperative DCI. Multivariate Logistic regression analysis showed that small aneurysm (P = 0.002, OR = 3.332, 95%–7.104), intraoperative aneurysm rupture (P = 0.004, OR = 0.122, 95%-CI, 0.029–0.504)and cerebral vasospasm (P < 0.001, OR = 0.153, 95%-CI, 0.070–0.333) were independent risk factors of postoperative DCI. The calibration curve of the probability of occurrence showed that the nomogram was in good correspondence with the observed results with a C-index of 0.766 (95% CI, 0.684–0.848). Meanwhile, the Decision curve analysis (DCA) showed that the established predictive model had a good clinical net benefit.

Conclusion

The well-established nomogram is expected to be an effective tool to predict the occurrence of DCI after intracranial ruptured aneurysm and can be used to assist clinicians to develop more effective treatment strategies and improve the prognosis of patients.
Molecular Mechanisms behind Safranal’s Toxicity to HepG2 Cells from Dual Omics
Authors: Nelson David Roy , Hrout Ala’a Al , Alzahmi Amnah Salem , Chaiboonchoe Amphun , Amin Amr , Salehi-Ashtiani Kourosh
Published: June 2022

The spice saffron (Crocus sativus) has anticancer activity in several human tissues, but the molecular mechanisms underlying its potential therapeutic effects are poorly understood. We investigated the impact of safranal, a small molecule secondary metabolite from saffron, on the HCC cell line HepG2 using untargeted metabolomics (HPLC–MS) and transcriptomics (RNAseq). Increases in glutathione disulfide and other biomarkers for oxidative damage contrasted with lower levels of the antioxidants biliverdin IX (139-fold decrease, p = 5.3 × 105), the ubiquinol precursor 3-4-dihydroxy-5-all-trans-decaprenylbenzoate (3-fold decrease, p = 1.9 × 10−5), and resolvin E1 (−3282-fold decrease, p = 45), which indicates sensitization to reactive oxygen species. We observed a significant increase in intracellular hypoxanthine (538-fold increase, p = 7.7 × 10−6) that may be primarily responsible for oxidative damage in HCC after safranal treatment. The accumulation of free fatty acids and other biomarkers, such as S-methyl-5′-thioadenosine, are consistent with safranal-induced mitochondrial de-uncoupling and explains the sharp increase in hypoxanthine we observed. Overall, the dual omics datasets describe routes to widespread protein destabilization and DNA damage from safranal-induced oxidative stress in HCC cells.