bluuebunny/crossref_metadata_2025 huggingface dataset:
Through the Eyes of Another: Using a Narrative Lens to Navigate Complex Social-Ecological Systems and to Embrace Multiple Ways of Knowing
Authors: Vigliano Relva Julieta , Jung Julia
Published: July 2021

Many social-ecological issues are characterised by a multiplicity of stakeholder voices with often fundamentally divergent values, beliefs or worldviews. Those differences in perspective can be also viewed as different narratives on individual, community and cultural scales that both express and reinforce people’s identity, value system and manifested behaviours. Navigating between those narratives requires approaches that facilitate the co-existence of multiple ways of knowing. The currently dominant knowledge production system of Western scientific knowledge often fails to meet those challenges due to its positivist and reductionist tendencies. However, embracing a co-existence of knowledges isn’t just necessary from a pragmatic perspective to adequately engage in those situations, but also represents an ethical imperative that includes acknowledging the colonial and oppressive history of Western scientific knowledge toward other knowledges, especially regarding Indigenous knowledge production systems. We propose adopting a narrative lens as a metaphor for embracing multiple ways of knowing and being as narratives play a key role for human cognition, communication and in shaping and expressing fundamental values at different levels. Using an example of contested narratives from a fisheries management conflict, we illustrate how narratives can help to develop a richer understanding of social-ecological conflicts. We also reflect on some narrative discourses commonly used in marine science that stem from the binary nature-culture divide prominent in Western scientific knowledge and discuss their implication for hindering sustainable ocean governance. Furthermore, we demonstrate how storytelling methods can be used to surface and share those narratives and to unravel the underlying values and fundamental beliefs and to re-shape them. The narrative lens we propose is suitable under multiple simultaneous disciplinary homes including Indigenous methodologies and systems thinking. They share the key features of having a holistic and relational approach that recognises the co-existence of multiple ways of knowing and being and use self-reflection as key for critical engagement with the situation and to surface and acknowledge one’s own internal narratives. This represents no exhaustive review of narrative inquiry, but a reflective journey illustrating how engaging with narratives can facilitate knowledge co-existence including different ways of relating to human and non-human beings.
How Does Pikeperch Sander lucioperca Respond to Dietary Insect Meal Hermetia illucens? Investigation on Gut Microbiota, Histomorphology, and Antioxidant Biomarkers
Authors: Tran Hung Quang , Prokešová Markéta , Zare Mahyar , Gebauer Tatyana , Elia Antonia Concetta , Colombino Elena , Ferrocino Ilario , Caimi Christian , Gai Francesco , Gasco Laura , Stejskal Vlastimil
Published: July 2021

Effects of feeding dietary defatted black soldier fly (Hermetia illucens) larvae meal (HI) on intestine microbiota, and on histomorphology, oxidative enzyme activities in liver and intestine of pikeperch (Sander lucioperca) were investigated. Four isoproteic (45% crude protein) and isolipidic (18% ether extract) diets were formulated to include 0% (CO), 9% (HI9), 18% (HI18) and 36% (HI36) of HI as replacement for fishmeal at 0, 25, 50, and 100%, respectively, and were fed to triplicate groups of juvenile pikeperch (initial body weight, 68.7 ± 7.1 g) for 84 days. No adverse effects were detected on the intestine of pikeperch fed diet groups, in terms of histomorphology (P > 0.05), while fish fed free or low levels of HI (≤ 9% in diet) showed significant liver degeneration (P < 0.05). Dietary HI significantly affected the oxidative enzyme activities of catalase and glutathione peroxidase in the liver, and glutathione S-transferase in the intestine (P < 0.05), while activity of superoxide dismutase in both liver and intestine was HI-dose independent (P > 0.05). Feeding HI-containing diets positively modulated the richness and diversity of intestinal microbiota, especially for HI18 group (P < 0.05). Inclusion HI up to 18% (50% fishmeal replacement) in pikeperch diets increased abundance of Clostridium, Oceanobacillus, Bacteroides, and Faecalibacterium genera, whereas the predominant bacterium, Cetobacterium was found in control and HI36 groups. This study reveals the potential of HI as an immune and health booster for juvenile pikeperch.
PTEN Hamartoma Tumor Syndrome: Skin Manifestations and Insights Into Their Molecular Pathogenesis
Authors: Innella Giovanni , Bonora Elena , Neri Iria , Virdi Annalucia , Guglielmo Alba , Pradella Laura Maria , Ceccarelli Claudio , Amato Laura Benedetta , Lanzoni Anna , Miccoli Sara , Gasparre Giuseppe , Zuntini Roberta , Turchetti Daniela
Published: July 2021

Germline PTEN pathogenic variants cause a spectrum of disorders collectively labeled PTEN Hamartoma Tumor Syndrome (PHTS) and featured by hamartomas, developmental anomalies and increased cancer risk. Studies on experimental models provided evidence that PTEN is a “haploinsufficient” tumor-suppressor gene, however, mechanisms involved in the pathogenesis of clinical manifestations in PHTS patients remain elusive. Beyond analyzing clinical and molecular features of a series of 20 Italian PHTS patients, we performed molecular investigations to explore the mechanisms involved in the pathogenesis of PTEN-associated manifestations, with special focus on mucocutaneous manifestations. Typical mucocutaneous features were present in all patients assessed, confirming that these are the most important clue to the diagnosis. The most frequent were papules located in the trunk or extremities (73.7%), oral mucosa papules (68.4%), acral/palmoplantar keratosis and facial papules (both 57.9%), according with literature data. Molecular analyses on one trichilemmoma suggested that the wild-type PTEN allele was retained and expressed, reinforcing the evidence that PTEN does not require a second somatic hit to initiate pathogenic processes. Unexpectedly, one patient also displayed a cutaneous phenotype consistent with atypical mole/melanoma syndrome; no variants were detected in known melanoma genes, but Whole Exome Sequencing showed the rare truncating variant c.495G>A in the CDH13 gene that might have cooperated with PTEN-haploinsufficiency to generate such phenotype. Our findings confirm the reproducibility of known PHTS manifestations in real-world practice, highlighting the role of mucocutaneous manifestations in facilitating prompt diagnosis of the syndrome, and provide some insights into the pathogenic process induced by PTEN alterations, which may contribute to its understanding.
Characteristics of Peripheral Lymphocyte Subsets in Patients With Acute-On-Chronic Liver Failure Associated With Hepatitis B
Authors: Li Juan , Hu Chun-Hua , Chen Yi , Zhou Mi-Mi , Gao Zhi-Jie , Fu Meng-Jun , Wang Jing , Li Jian-Zhou , Chen Tian-Yan , Zhao Ying-Ren , He Ying-Li
Published: July 2021

Background and Aims: Acute-on-chronic liver failure (ACLF) is a rare, but dramatic clinical syndrome. There is substantial evidence suggesting that immunity-mediated inflammation plays an important role in HBV-ACLF. Our aim was to characterize the proportion and cell counts of peripheral blood lymphocyte subsets in acute-on-chronic liver failure patients caused by HBV infection.

Methods: One hundred and seventeen patients were enrolled in this study, including those with HBV-related ACLF (HBV-ACLF; n = 70), and HBV related non-ACLF patients (HBV non-ACLF; n = 47). Demographics, clinical and laboratory data at hospital admission were retrospectively analyzed. The percentage and cell count of peripheral lymphocyte subsets were evaluated by flow cytometry. Comparison analysis was performed by t-test or non-parametric Mann–Whitney U-test. Actuarial probabilities of death were calculated by the Kaplan-Meier method.

Results: Both circulating lymphocyte count and lymphocyte percentage were significantly reduced in patients with HBV-ACLF (P < 0.001). The CD8+ T cell, CD4+ T cell, and CD16+CD56+ NK cell counts were significantly decreased in HBV-ACLF. Consistently, flow cytometric analysis showed that CD8+ T cell counts were significantly decreased in non-survivors, while no significant differences were found in CD4+ T cell, CD19+ B cell, or CD56+CD16+ NK cell counts. Furthermore, the group with the lower CD8+ T cell count displayed a significantly higher mortality rate compared with the group with the higher CD8+ T cell count.

Conclusions: The abnormal prevalence of lymphocyte subsets may be important in the pathogenesis of HBV-ACLF. The decrease in CD8+ T cell counts may be related to poor survival in HBV-ACLF patients.
Regulation of Tumor Necrosis Factor-α by Peptide Lv in Bone Marrow Macrophages and Synovium
Authors: Mukai Manabu , Uchida Kentaro , Okubo Tadashi , Takano Shotaro , Matsumoto Toshihide , Satoh Masashi , Inoue Gen , Takaso Masashi
Published: July 2021

Background:Bone marrow-derived monocytes/macrophages are recruited into synovial tissue, where they contribute to synovial inflammation in osteoarthritis through inflammatory cytokine production. Recent studies have suggested that V-Set and transmembrane domain-containing 4 (VSTM4) and its fragment, peptide Lv, exhibit immunosuppressive activity on T cells and vascular endothelial growth factor (VEGF)-like activity, respectively. Given that evidence suggests that VEGF may play a role in macrophage function, we investigated peptide Lv-mediated regulation of inflammatory cytokines in bone marrow macrophages (BMMs) and synovial inflammation.

Method:To investigate the effects of peptide Lv, BMMs were stimulated with vehicle, LPS, or LPS + peptide Lv, andTnfa, Il1b, Il6, andIfngexpression were evaluated using quantitative PCR (qPCR). TNF-α and IFN-γ production was measured using ELISA. To examine the effect of peptide Lv deficiency on macrophages and synovitis,peptide Lv-deficient mice were generated using genome editing. LPS-inducedTnfaandIfngexpression and TNF-α and IFN-γ production were evaluated in BMM isolated from wild-type andpeptide Lv-deficient mice. Additionally,TnfaandIfngexpression levels were compared between wild-type andpeptide Lv-deficient mice before and after knee injury.

Results:Peptide Lv suppressed the LPS-mediated elevation in TNF-α and IFN-γ. LPS stimulation significantly increased TNF-α and IFN-γ production in BMM derived frompeptide Lv-deficient mice compared to wild-type mice. Synovial TNF-α expression in the injured knee was elevated inpeptide Lv-deficient compared to wild-type mice.

Conclusion:Peptide Lv suppressed TNF-α in macrophages and plays a role in synovial inflammation. Thus, peptide Lv may be a useful therapeutic target for synovitis.
Tuberculosis Burden and Determinants of Treatment Outcomes According to Age in Brazil: A Nationwide Study of 896,314 Cases Reported Between 2010 and 2019
Authors: Barreto-Duarte Beatriz , Araújo-Pereira Mariana , Nogueira Betânia M. F. , Sobral Luciana , Rodrigues Moreno M. S. , Queiroz Artur T. L. , Rocha Michael S. , Nascimento Vanessa , Souza Alexandra B. , Cordeiro-Santos Marcelo , Kritski Afrânio L. , Sterling Timothy R. , Arriaga María B. , Andrade Bruno B.
Published: July 2021

Approximately 1.4 million people die annually worldwide from tuberculosis. Large epidemiologic studies can identify determinants of unfavorable clinical outcomes according to age, which can guide public health policy implementation and clinical management to improve outcomes. We obtained data from the national tuberculosis case registry; data were reported to the Brazilian National Program (SINAN) between 2010 and 2019. Clinical and epidemiologic variables were compared between age groups (child: <10 years, young: 10–24years, adult: 25–64years, and elderly: ≥65years). Univariate comparisons were performed together with second-generation p-values. We applied a backward stepwise multivariable logistic regression model to identify characteristics in each age group associated with unfavorable TB treatment outcomes. There were 896,314 tuberculosis cases reported during the period. Tuberculosis incidence was highest among adult males, but the young males presented the highest growth rate during the period. Directly observed therapy (DOT) was associated with protection against unfavorable outcomes in all age groups. The use of alcohol, illicit drugs, and smoking, as well as occurrence of comorbidities, were significantly different between age groups. Lack of DOT, previous tuberculosis, race, location of tuberculosis disease, and HIV infection were independent risk factors for unfavorable outcome depending on the age group. The clinical and epidemiological risk factors for unfavorable tuberculosis treatment outcomes varied according to age in Brazil. DOT was associated with improved outcomes in all age groups. Incidence according to age and sex identified adults and young males as the groups that need prevention efforts. This supports implementation of DOT in all populations to improve tuberculosis outcomes.
Antimicrobial Resistance Profiling and Phylogenetic Analysis of Neisseria gonorrhoeae Clinical Isolates From Kenya in a Resource-Limited Setting
Authors: Juma Meshack , Sankaradoss Arun , Ndombi Redcliff , Mwaura Patrick , Damodar Tina , Nazir Junaid , Pandit Awadhesh , Khurana Rupsy , Masika Moses , Chirchir Ruth , Gachie John , Krishna Sudhir , Sowdhamini Ramanathan , Anzala Omu , Meenakshi Iyer S.
Published: July 2021

Background

Africa has one of the highest incidences of gonorrhea. Neisseria gonorrhoeae is gaining resistance to most of the available antibiotics, compromising treatment across the world. Whole-genome sequencing (WGS) is an efficient way of predicting AMR determinants and their spread in the population. Recent advances in next-generation sequencing technologies like Oxford Nanopore Technology (ONT) have helped in the generation of longer reads of DNA in a shorter duration with lower cost. Increasing accuracy of base-calling algorithms, high throughput, error-correction strategies, and ease of using the mobile sequencer MinION in remote areas lead to its adoption for routine microbial genome sequencing. To investigate whether MinION-only sequencing is sufficient for WGS and downstream analysis in resource-limited settings, we sequenced the genomes of 14 suspected N. gonorrhoeae isolates from Nairobi, Kenya.

Methods

Using WGS, the isolates were confirmed to be cases of N. gonorrhoeae (n = 9), and there were three co-occurrences of N. gonorrhoeae with Moraxella osloensis and N. meningitidis (n = 2). N. meningitidis has been implicated in sexually transmitted infections in recent years. The near-complete N. gonorrhoeae genomes (n = 10) were analyzed further for mutations/factors causing AMR using an in-house database of mutations curated from the literature.

Results

We observe that ciprofloxacin resistance is associated with multiple mutations in both gyrA and parC. Mutations conferring tetracycline (rpsJ) and sulfonamide (folP) resistance and plasmids encoding beta-lactamase were seen in all the strains, and tet(M)-containing plasmids were identified in nine strains. Phylogenetic analysis clustered the 10 isolates into clades containing previously sequenced genomes from Kenya and countries across the world. Based on homology modeling of AMR targets, we see that the mutations in GyrA and ParC disrupt the hydrogen bonding with quinolone drugs and mutations in FolP may affect interaction with the antibiotic.

Conclusion

Here, we demonstrate the utility of mobile DNA sequencing technology in producing a consensus genome for sequence typing and detection of genetic determinants of AMR. The workflow followed in the study, including AMR mutation dataset creation and the genome identification, assembly, and analysis, can be used for any clinical isolate. Further studies are required to determine the utility of real-time sequencing in outbreak investigations, diagnosis, and management of infections, especially in resource-limited settings.
Drug-Coated Balloons for the Treatment of Symptomatic Intracranial High-Grade Stenosis: A Review of the Current Rationale
Authors: Gruber Philipp , Singh Samarth , Andereggen Lukas , Berberat Jatta , Remonda Luca
Published: July 2021

Symptomatic intracranial atherosclerotic disease (sICAD) remains a challenging disorder in the neurovascular field. Despite best medical treatment, the recurrence rate for stroke remains high in patients with intracranial high-grade stenosis (>70–99%). Furthermore, two large randomized trials (SAMMPRIS and VISSIT) failed to prove the efficacy of percutaneous transluminal angioplasty and stenting in patients with sICAD. Drug-coated balloon percutaneous transluminal angioplasty (DCB-PTA) represents an alternative treatment modality with therapeutic benefits for interventional cardiology. However, there are very few articles in the existing literature that relate to the use of DCB-PTA in sICAD patients. Here, we aimed to review the rationale underlying the use of DCB-PTA in sICAD patients and summarize recent developments in the neurovascular field.
Red and White Meat Intake in Relation to Mental Disorders in Iranian Adults
Authors: Kazemi Shiva , Keshteli Ammar Hassanzadeh , Saneei Parvane , Afshar Hamid , Esmaillzadeh Ahmad , Adibi Peyman
Published: July 2021

Background: The association between meat consumption and mental disorders is less investigated in Iranian population. We examined the association between meat consumption and prevalence of symptoms of depression, anxiety, and psychological distress in Iranian adults.

Methods: This cross-sectional study included 3,362 participants aged 18–55 years old. A dish-based 106-item semiquantitative food frequency questionnaire (FFQ) was used to assess usual dietary intake of study population. Hospital Anxiety and Depression Scale (HADS) and General Health Questionnaire (GHQ), all validated in Iranian population, were applied to collect data on symptoms of anxiety, depression, and psychological distress, respectively.

Results: The prevalence of symptoms of depression, anxiety, and psychological distress in the study population was 28.6, 13.6, and 22.6%, respectively. After considering potential confounders, individuals in the top quartile of red meat intake had 43% increased risk of depression symptoms [odds ratio (OR) = 1.43; 95% CI: 1.09–1.89] compared to those in the first quartile. No significant relation was observed between red meat intake and anxiety or psychological distress symptoms. White meat consumption was not associated with mental disorders. Stratified analysis by sex showed that male participants in the highest quartile of red meat intake had 92% greater risk of depression symptoms (95% CI: 1.17–3.15) than those individuals in the lowest category. Red and white meat intake was not associated with mental disorders in women. In overweight or obese individuals, despite lack of any association between red meat intake and mental disorders, high intake of white meat was associated with a lower odds of psychological distress symptoms (OR = 0.64; 95% CI: 0.42–0.99) and a lower risk of depression symptoms (OR = 0.68; 95% CI: 0.45–1.00). In normal-weight participants, those in the highest quartile of red meat intake had greater odds for depression symptoms than those in the lowest quartile (OR = 1.66; 95% CI: 1.14–2.42).

Conclusions: We found that red meat consumption was associated with increased risk of depression symptoms, especially in men, and normal-weight participants. In overweight or obese participants, white meat intake was inversely associated with psychological distress symptoms.
Evaluation of Oncogene NUP37 as a Potential Novel Biomarker in Breast Cancer
Authors: Li Kangdi , Liu Ting
Published: July 2021

Purpose

There is an urgent need to identify oncogenes that may be beneficial to diagnose and develop target therapy for breast cancer.

Methods

Based on the GEO database, DECenter was used to screen the differentially overexpressed genes in breast cancer samples. Search Tool for the Retrieval of Interacting Genes and Cytoscape were performed to construct the PPI network to predict the hub gene. Functional and pathway enrichment were performed based on GO analysis. GEO2R, Oncomine, human tissue microarray staining, and western blot were applied to confirm the expression of NUP37. The association between NUP37 expression and prognosis in patients with breast cancer were assessed using the Kaplan–Meier plotter online tool and OncoLnc. siRNAs were used to knock down NUP37 and evaluate proliferation, migration, and stemness in breast cancer cells.

Results

We found that 138 genes were differentially upregulated in breast cancer samples, mainly comprising components of the nucleus and involved in the cell cycle process. NUP37 was identified as a hub gene that is upregulated in breast cancer patients related to a significantly worse survival rate. Furthermore, we confirmed that the downregulation of NUP37 in breast cancer cells results in the inhibition of cell growth, migration, and stemness.

Conclusions

High expression of NUP37 in breast cancer patients is associated with a poorer prognosis and promotion of cell growth, migration, and stemness. The multiple bioinformatics and experimental analysis help provide a comprehensive understanding of the roles of NUP37 as a potential marker for diagnosis and prognosis and as a novel therapeutic target in breast cancer.
Mucin-1 Protein Is a Prognostic Marker for Pancreatic Ductal Adenocarcinoma: Results From the CONKO-001 Study
Authors: Striefler Jana Käthe , Riess Hanno , Lohneis Philipp , Bischoff Sven , Kurreck Annika , Modest Dominik Paul , Bahra Marcus , Oettle Helmut , Sinn Marianne , Bläker Henrik , Denkert Carsten , Stintzing Sebastian , Sinn Bruno Valentin , Pelzer Uwe
Published: July 2021

Background

The Mucin-family protein, MUC1, impacts on carcinogenesis and tumor invasion. We evaluated the impact of MUC1 expression on outcome in a cohort of 158 patients with resected pancreatic ductal adenocarcinomas (PDAC) in the CONKO-001 study (adjuvant gemcitabine [gem] vs. observation [obs]).

Methods

The percentage of MUC1-positive tumor cells by immunohistochemistry (IHC) and the staining intensity were evaluated by two observers blinded to outcome. The numeric values of both parameters were multiplied, resulting in an immunoreactivity score (IRS) ranging from 0 to 12. The level of MUC1 expression was defined as follows: IRS 0–4 (low) vs IRS >4 (high). Outcomes in terms of disease-free (DFS) and overall survival (OS) were evaluated by Kaplan–Meier method, log-rank tests and Cox regressions.

Results

In total, tumors of 158 study patients were eligible for immunohistochemistry of MUC1. High cytoplasmic MUC1 expression was associated with impaired DFS and OS in the overall study population (hazard ratio (HR) for DFS: 0.49, 95% CI 0.31 to 0.78, p = .003; HR for OS: 0.46, 95% CI 0.29 to 0.73, p = .001). In the study arms, prognostic effects of MUC1 were also evident in the observation group (HR for DFS: 0.55; 95% CI 0.29 to 1.04, p = .062; HR for OS: 0.34, 95% CI 0.17 to 0.67, p = .001) and trending in the gem group (HR for DFS: 0.48, 95% CI 0.24 to 0.95, p = .041; HR for OS: 0.56, 95% CI 0.28 to1.11, p = .093).

Conclusion

Our data suggest that MUC1 expression is a powerful prognostic marker in patients with PDAC after curatively intended resection.
Carbon Nanotubes: A Summary of Beneficial and Dangerous Aspects of an Increasingly Popular Group of Nanomaterials
Authors: Zhang Chengke , Wu Licun , de Perrot Marc , Zhao Xiaogang
Published: July 2021

Carbon nanotubes (CNTs) are nanomaterials with broad applications that are produced on a large scale. Animal experiments have shown that exposure to CNTs, especially one type of multi-walled carbon nanotube, MWCNT-7, can lead to malignant transformation. CNTs have characteristics similar to asbestos (size, shape, and biopersistence) and use the same molecular mechanisms and signaling pathways as those involved in asbestos tumorigenesis. Here, a comprehensive review of the characteristics of carbon nanotubes is provided, as well as insights that may assist in the design and production of safer nanomaterials to limit the hazards of currently used CNTs.
The Clinical Application of Neoantigens in Esophageal Cancer
Authors: Gu Yi-Min , Zhuo Yue , Chen Long-Qi , Yuan Yong
Published: July 2021

Esophageal cancer (EC) is a common malignant tumor with poor prognosis, and current treatments for patients with advanced EC remain unsatisfactory. Recently, immunotherapy has been recognized as a new and promising approach for various tumors. EC cells present a high tumor mutation burden and harbor abundant tumor antigens, including tumor-associated antigens and tumor-specific antigens. The latter, also referred to as neoantigens, are immunogenic mutated peptides presented by major histocompatibility complex class I molecules. While current genomics and bioinformatics technologies have greatly facilitated the identification of tumor neoantigens, identifying individual neoantigens systematically for successful therapies remains a challenging problem. Owing to the initiation of strong, specific tumor-killing cytotoxic T cell responses, neoantigens are emerging as promising targets to develop personalized treatment and have triggered the development of cancer vaccines, adoptive T cell therapies, and combination therapies. This review aims to give a current understanding of the clinical application of neoantigens in EC and provide direction for future investigation.
The Circular RNA circXPO1 Promotes Tumor Growth via Sponging MicroRNA-23a in Prostate Carcinoma
Authors: Chen Haoyan , Zhang Ping , Yu Bo , Liu Jinlong
Published: July 2021

It has been shown that circular RNA XPO1 (circXPO1) is involved in cancer (e.g., lung adenocarcinoma and osteosarcoma) progression by sponging microRNAs. Nevertheless, the role of circXPO1 and its interaction with microRNAs in prostate cancer remains unknown. In this study, the results of quantitative real-time PCR showed that circXPO1 levels were dramatically increased in human prostate cancer tissue and cell lines compared with those in normal tissue and cell line. Furthermore, cell proliferation, colony formation, and cell invasion assays showed that circXPO1 promoted the malignant behavior of pancreatic cellsin vitro. Mechanistically, bioinformatics prediction, a dual-luciferase reporter assay, and pull-down assay suggested that circXPO1 physically targets miR-23a and negatively regulates its expression in pancreatic cancer cells. miR-23a mimics and inhibitors effectively reversed the effects of circXPO1 on the malignant behavior of prostate cancer cellsin vitro. Consistent results were observed in the xenograft tumor model. In conclusion, circXPO1 promotes prostate cancer progressionviatargeting miR-23a, thus suggesting the circXPO1/miR-23a axis can be used as a potential therapeutic target for prostate cancer treatment.
Prostate Cancer Progression: as a Matter of Fats
Authors: Scaglia Natalia , Frontini-López Yesica Romina , Zadra Giorgia
Published: July 2021

Advanced prostate cancer (PCa) represents the fifth cause of cancer death worldwide. Although survival has improved with second-generation androgen signaling and Parp inhibitors, the benefits are not long-lasting, and new therapeutic approaches are sorely needed. Lipids and their metabolism have recently reached the spotlight with accumulating evidence for their role as promoters of PCa development, progression, and metastasis. As a result, interest in targeting enzymes/transporters involved in lipid metabolism is rapidly growing. Moreover, the use of lipogenic signatures to predict prognosis and resistance to therapy has been recently explored with promising results. Despite the well-known association between obesity with PCa lethality, the underlying mechanistic role of diet/obesity-derived metabolites has only lately been unveiled. Furthermore, the role of lipids as energy source, building blocks, and signaling molecules in cancer cells has now been revisited and expanded in the context of the tumor microenvironment (TME), which is heavily influenced by the external environment and nutrient availability. Here, we describe how lipids, their enzymes, transporters, and modulators can promote PCa development and progression, and we emphasize the role of lipids in shaping TME. In a therapeutic perspective, we describe the ongoing efforts in targeting lipogenic hubs. Finally, we highlight studies supporting dietary modulation in the adjuvant setting with the purpose of achieving greater efficacy of the standard of care and of synthetic lethality. PCa progression is “a matter of fats”, and the more we understand about the role of lipids as key players in this process, the better we can develop approaches to counteract their tumor promoter activity while preserving their beneficial properties.
Action Mode of Gut Motility, Fluid and Electrolyte Transport in Chronic Constipation
Authors: Zhao Qi , Chen Yan-Yan , Xu Ding-Qiao , Yue Shi-Jun , Fu Rui-Jia , Yang Jie , Xing Li-Ming , Tang Yu-Ping
Published: July 2021

Chronic constipation is a common gastrointestinal disorder, with a worldwide incidence of 14–30%. It negatively affects quality of life and is associated with a considerable economic burden. As a disease with multiple etiologies and risk factors, it is important to understand the pathophysiology of chronic constipation. The purpose of this review is to discuss latest findings on the roles of gut motility, fluid, and electrolyte transport that contribute to chronic constipation, and the main drugs available for treating patients. We conducted searches on PubMed and Google Scholar up to 9 February 2021. MeSH keywords “constipation”, “gastrointestinal motility”, “peristalsis”, “electrolytes”, “fluid”, “aquaporins”, and “medicine” were included. The reference lists of searched articles were reviewed to identify further eligible articles. Studies focusing on opioid-induced constipation, evaluation, and clinic management of constipation were excluded. The occurrence of constipation is inherently connected to disorders of gut motility as well as fluid and electrolyte transport, which involve the nervous system, endocrine signaling, the gastrointestinal microbiota, ion channels, and aquaporins. The mechanisms of action and application of the main drugs are summarized; a better understanding of ion channels and aquaporins may be helpful for new drug development. This review aims to provide a scientific basis that can guide future research on the etiology and treatment of constipation.
Follistatin Attenuates Myocardial Fibrosis in Diabetic Cardiomyopathy via the TGF-β–Smad3 Pathway
Authors: Wang Yinhui , Yu Kun , Zhao Chengcheng , Zhou Ling , Cheng Jia , Wang Dao Wen , Zhao Chunxia
Published: July 2021

Follistatin (FST) is an endogenous protein that irreversibly inhibits TGF-β superfamily members and plays an anti-fibrotic role in other diseases. However, the role of FST in diabetic cardiomyopathy remains unclear. In this study, we investigated the effects of FST on diabetic cardiomyopathy. The expression of FST was downregulated in the hearts of db/db mice. Remarkably, overexpressing FST efficiently protected against cardiac dysfunction. In addition, overexpression of FST promoted cardiac hypertrophy with an unchanged expression of atrial natriuretic peptide (ANP) and the ratio of myosin heavy chain-β/myosin heavy chain-α (MYH7/MYH6). Furthermore, FST reduced cardiac fibrosis and the production of reactive oxygen species (ROS), and enhanced matrix metallopeptidase 9 (MMP9) activities in db/db mouse hearts. We also observed that overexpressing FST decreased the level of transforming growth factor beta (TGF-β) superfamily members and the phosphorylation of Smad3; consistently, in vitro experiments also verified the above results. Our findings revealed the cardioprotective role of FST in attenuating diabetic cardiomyopathy through its anti-fibrotic effects through the TGF-β–Smad3 pathway and provided a promising therapeutic strategy for diabetic cardiomyopathy.
Inhibition of β-Catenin/CREB Binding Protein Signaling Attenuates House Dust Mite-Induced Goblet Cell Metaplasia in Mice
Authors: Kuchibhotla Virinchi N. S. , Starkey Malcolm R. , Reid Andrew T. , Heijink Irene H. , Nawijn Martijn C. , Hansbro Philip M. , Knight Darryl A.
Published: July 2021

Excessive mucus production is a major feature of allergic asthma. Disruption of epithelial junctions by allergens such as house dust mite (HDM) results in the activation of β-catenin signaling, which has been reported to stimulate goblet cell differentiation. β-catenin interacts with various co-activators including CREB binding protein (CBP) and p300, thereby regulating the expression of genes involved in cell proliferation and differentiation, respectively. We specifically investigated the role of the β-catenin/CBP signaling pathway in goblet cell metaplasia in a HDM-induced allergic airway disease model in mice using ICG-001, a small molecule inhibitor that blocks the binding of CBP to β-catenin. Female 6- 8-week-old BALB/c mice were sensitized to HDM/saline on days 0, 1, and 2, followed by intranasal challenge with HDM/saline with or without subcutaneous ICG-001/vehicle treatment from days 14 to 17, and samples harvested 24 h after the last challenge/treatment. Differential inflammatory cells in bronchoalveolar lavage (BAL) fluid were enumerated. Alcian blue (AB)/Periodic acid–Schiff (PAS) staining was used to identify goblet cells/mucus production, and airway hyperresponsiveness (AHR) was assessed using invasive plethysmography. Exposure to HDM induced airway inflammation, goblet cell metaplasia and increased AHR, with increased airway resistance in response to the non-specific spasmogen methacholine. Inhibition of the β-catenin/CBP pathway using treatment with ICG-001 significantly attenuated the HDM-induced goblet cell metaplasia and infiltration of macrophages, but had no effect on eosinophils, neutrophils, lymphocytes or AHR. Increased β-catenin/CBP signaling may promote HDM-induced goblet cell metaplasia in mice.
Blockage of C-X-C Motif Chemokine Receptor 2 (CXCR2) Suppressed Uric Acid (UA)-Induced Cardiac Remodeling
Authors: Xu Mingxi , Zheng Xu , Wang Dongxia , Fu Xiaodan , Xing Yida , Liu Yu , Wang Hongjiang , Kong Xiaodan
Published: July 2021

Hyperuricemia-induced cardiac remodeling is at least in part via pressure-dependent mechanisms, yet the pressure-independent mechanisms are not well understood. C-X-C motif chemokine ligand 1 (CXCL1) was upregulated in renal tubules from mice subjected to uric acid (UA)-induced nephropathy. Given that CXCL1 is a master chemokine responsible for the recruitment of macrophage by binding with its receptor C-X-C motif chemokine receptor 2 (CXCR2), we thus hypothesized that UA-induced cardiac injury is via promoting the recruitment of CXCR2 + macrophages into the heart, which enhances cardiac inflammation. Within a mouse model of UA injection (500 mg/kg, twice/day, 14 days), we measured the level of cardiac CXCL1. We also tested the efficacy of the CXCR2 antagonist on UA-induced cardiac inflammation and remodeling. We found a high plasma level of UA-induced upregulation of CXCL1 in heart tissues. CXCR2 antagonist relieved UA-induced cardiac hypertrophy and suppressed cardiac inflammation and fibrosis. The silencing of CXCR2 in human monocytes abolished the migration of UA-induced monocyte. Thus, the interventions against CXCL1/CXCR2 may be effective for the prevention and treatment of UA-induced cardiac hypertrophy and inflammatory responses.
Plastid Phylogenomic Data Offers Novel Insights Into the Taxonomic Status of the Trichosanthes kirilowii Complex (Cucurbitaceae) in South Korea
Authors: Park Inkyu , Song Jun-Ho , Yang Sungyu , Chae Sungwook , Moon Byeong Cheol
Published: July 2021

Trichosanthes is a genus in Cucurbitaceae comprising 90–100 species. Trichosanthes species are valuable as herbaceous medicinal ingredients. The fruits, seeds, and roots of species such as T. kirilowii and T. rosthornii are used in Korean traditional herbal medicines. T. rosthornii is only found in China, whereas in South Korea two varieties, T. kirilowii var. kirilowii and T. kirilowii var. japonica, are distributed. T. kirilowii var. kirilowii and T. kirilowii var. japonica have different fruit and leaf shapes but are recognized as belonging to the same species. Furthermore, although its members have herbal medicine applications, genomic information of the genus is still limited. The broad goals of this study were (i) to evaluate the taxonomy of Trichosanthes using plastid phylogenomic data and (ii) provide molecular markers specific for T. kirilowii var. kirilowii and T. kirilowii var. japonica, as these have differences in their pharmacological effectiveness and thus should not be confused and adulterated. Comparison of five Trichosanthes plastid genomes revealed locally divergent regions, mainly within intergenic spacer regions (trnT-UGU–trnL-UAA: marker name Tri, rrn4.5–rrn5: TRr, trnE-UUC–trnT-GGU: TRtt). Using these three markers as DNA-barcodes for important herbal medicine species in Trichosanthes, the identity of Trichosanthes material in commercial medicinal products in South Korea could be successfully determined. Phylogenetic analysis of the five Trichosanthes species revealed that the species are clustered within tribe Sicyoeae. T. kirilowii var. kirilowii and T. rosthornii formed a clade with T. kirilowii var. japonica as their sister group. As T. kirilowii in its current circumscription is paraphyletic and as the two varieties can be readily distinguished morphologically (e.g., in leaf shape), T. kirilowii var. japonica should be treated (again) as an independent species, T. japonica.
Metabolome-Based Genome-Wide Association Study Provides Genetic Insights Into the Natural Variation of Foxtail Millet
Authors: Wei Wei , Li Shuangdong , Wang Yixiang , Wang Bin , Fan Guangyu , Zeng Qisen , Zhao Fang , Xu Congping , Zhang Xiaolei , Tang Tang , Feng Xiaolei , Shi Jian , Shi Gaolei , Zhang Weiqin , Song Guoliang , Li Huan , Wang Feng , Zhang Yali , Li Xinru , Wang Dequan , Zhang Wenying , Pei Jingjing , Wang Xiaoming , Zhao Zhihai
Published: July 2021

The plant metabolome is considered as a bridge between the genome and the phenome and is essential for the interaction between plant growth and the plant environment. Here, we used the liquid chromatography-tandem mass spectrometry method to perform a widely targeted metabolomics analysis of 150 millet germplasm and simultaneous identification and quantification of 330 annotated metabolites. Comparing the metabolic content of different millets revealed significant natural variation of both primary and secondary metabolites, including flavonoids, phenolamides, hydroxycinnamoyl derivatives, nucleotides, and lipids, in the millets from India and the north and south of China; among them, some of the flavonoids are the most prominent. A total of 2.2 TB sequence data were obtained by sequencing 150 accessions of foxtail millet using the Illumina platform. Further digging into the genetic basis of metabolites by mGWAS analysis found that cyanidin 3-O-glucoside and quercetin O-acetylhexside are concentratedly located at 43.55 Mb on chromosome 5 and 26.9 Mb on chromosome 7, and two Lc were mined as candidate genes, respectively. However, the signals of luteolin 7-O-glucoside and kaempferol 3-O-glucoside were also detected at 14.36 Mb on chromosome 3, and five glycosyltransferase genes on this loci were deemed to regulate their content. Our work is the first research to use mGWAS in millet, and it paves the way for future dissection of complex physiological traits in millet.
An R2R3-MYB Transcription Factor RmMYB108 Responds to Chilling Stress of Rosa multiflora and Conferred Cold Tolerance of Arabidopsis
Authors: Dong Jie , Cao Lei , Zhang Xiaoying , Zhang Wuhua , Yang Tao , Zhang Jinzhu , Che Daidi
Published: July 2021

A sudden cooling in the early spring or late autumn negatively impacts the plant growth and development. Although a number of studies have characterized the role of the transcription factors (TFs) of plant R2R3-myeloblastosis (R2R3-MYB) in response to biotic and abiotic stress, plant growth, and primary and specific metabolisms, much less is known about their role in Rosa multiflora under chilling stress. In the present study, RmMYB108, which encodes a nuclear-localized R2R3-MYB TF with a self-activation activity, was identified based on the earlier published RNA-seq data of R. multiflora plants exposed to short-term low-temperature stress and also on the results of prediction of the gene function referring Arabidopsis. The RmMYB108 gene was induced by stress due to chilling, salt, and drought and was expressed in higher levels in the roots than in the leaves. The heterologous expression of RmMYB108 in Arabidopsis thaliana significantly enhanced the tolerance of transgenic plants to freezing, water deficit, and high salinity, enabling higher survival and growth rates, earlier flowering and silique formation, and better seed quantity and quality compared with the wild-type (WT) plants. When exposed to a continuous low-temperature stress at 4°C, transgenic Arabidopsis lines–overexpressing RmMYB108 showed higher activities of superoxide dismutase and peroxidase, lower relative conductivity, and lower malondialdehyde content than the WT. Moreover, the initial fluorescence (Fo) and maximum photosynthetic efficiency of photosystem II (Fv/Fm) changed more dramatically in the WT than in transgenic plants. Furthermore, the expression levels of cold-related genes involved in the ICE1 (Inducer of CBF expression 1)-CBFs (C-repeat binding factors)-CORs (Cold regulated genes) cascade were higher in the overexpression lines than in the WT. These results suggest that RmMYB108 was positively involved in the tolerance responses when R. multiflora was exposed to challenges against cold, freeze, salt, or drought and improved the cold tolerance of transgenic Arabidopsis by reducing plant damage and promoting plant growth.
Item-Weighted Likelihood Method for Measuring Growth in Longitudinal Study With Tests Composed of Both Dichotomous and Polytomous Items
Authors: Xue Xuemei , Lu Jing , Zhang Jiwei
Published: July 2021

In this paper, a new item-weighted scheme is proposed to assess examinees’ growth in longitudinal analysis. A multidimensional Rasch model for measuring learning and change (MRMLC) and its polytomous extension is used to fit the longitudinal item response data. In fact, the new item-weighted likelihood estimation method is not only suitable for complex longitudinal IRT models, but also it can be used to estimate the unidimensional IRT models. For example, the combination of the two-parameter logistic (2PL) model and the partial credit model (PCM, Masters, 1982) with a varying number of categories. Two simulation studies are carried out to further illustrate the advantages of the item-weighted likelihood estimation method compared to the traditional Maximum a Posteriori (MAP) estimation method, Maximum likelihood estimation method (MLE), Warm’s (1989) weighted likelihood estimation (WLE) method, and type-weighted maximum likelihood estimation (TWLE) method. Simulation results indicate that the improved item-weighted likelihood estimation method better recover examinees’ true ability level for both complex longitudinal IRT models and unidimensional IRT models compared to the existing likelihood estimation (MLE, WLE and TWLE) methods and MAP estimation method, with smaller bias, root-mean-square errors, and root-mean-square difference especially at the low-and high-ability levels.
Humor in Workplace Leadership: A Systematic Search Scoping Review
Authors: Rosenberg Caroline , Walker Arlene , Leiter Michael , Graffam Joe
Published: July 2021

Humor studies are increasingly prevalent in workplace and leadership domains, it has shown significant development in the last 40 years. The multifaceted nature of humor means varied definitions and diverse measurement approaches have been approved. As a result, research methodologies and findings are not easily clarified, and have not been synthesized. The aim of this scoping review was to review the existing body of literature relevant to humor in workplace leadership to identify key research areas, methodologies used, guiding theoretical frameworks, and gaps that are persisting over the last 40 years. Using qualitative review methods, four key themes in the research emerged relating to: (1) humor styles and outcomes; (2) humor as communication and discursive resource; (3) variables in the humor and leadership relationship; and (4) cultural context. This review demonstrates significant research progress on the topic of humor in workplace leadership. Research progress and gaps are discussed based on five key questions. Future research directions are outlined and discussed.
Food Consumption Behavior of Pakistani Students Living in China: The Role of Food Safety and Health Consciousness in the Wake of Coronavirus Disease 2019 Pandemic
Authors: Khayyam Muhammad , Chuanmin Shuai , Qasim Haroon , Ihtisham Muhammad , Anjum Raheel , Jiaxin Li , Tikhomirova Anna , Khan Nawab
Published: July 2021

The emergence of coronavirus disease 2019 (COVID-19) has considerably changed global food production, processing, and consumption at different levels. Sojourners are among those who have experienced a higher level of food insecurity during the crisis of the COVID-19 outbreak. The current research aimed to investigate the immediate consumption behavioral intentions of the Pakistani international students in the People's Republic of China (PRC) during the wake of COVID-19 pandemic. This study applied the Theory of Planned Behavior (TPB) and background factors of food safety and health consciousness that influence the consumption behavioral intention of Pakistani students toward unfamiliar local food in China. A relational model was analyzed where food safety and health consciousness were hypothesized to serve as background variables associated with TPB components. Moreover, the indirect effects of food safety and health consciousness on behavioral intentions were assessed. The data were collected through convenience samples from 462 Pakistani international students and were analyzed through partial least square structural equation modeling (PLS-SEM). The results confirmed that food safety and health consciousness were positively associated with attitude (ATT), subjective norm (SN), and perceived behavioral control (PBC). However, food safety and health consciousness were indirectly associated with the behavioral intention only through ATT and SN. The results highlighted the role of food safety and health consciousness as important antecedents of classical TPB components that affect intentions and behaviors to avoid unfamiliar local food in a migrated context. The present study provides enlightenment to those who aim to investigate the consumption behavioral intentions of sojourners in the wake of the pandemic situation based on food safety and health consciousness. The findings of the current study are also applicable to general consumption patterns in the food sector.