bluuebunny/crossref_metadata_2025 huggingface dataset:
Copy Number Variations Analysis Identifies QPRT as a Candidate Gene Associated With Susceptibility for Solitary Functioning Kidney
Authors: Zhou Xiao Y. , Zheng Hao Y. , Han Li , Wang Yan , Zhang Li , Shu Xiao M. , Zhang Mu L. , Liu Guan N. , Ding Lian S.
Published: May 2021

Background

The lack of understanding of molecular pathologies of the solitary functioning kidney makes improving and strengthening the continuity of care between pediatric and adult nephrological patients difficult. Copy number variations (CNVs) account for a molecular cause of solitary functioning kidney, but characterization of the pathogenic genes remains challenging.

Methods

In our prospective cohort study, 99 fetuses clinically diagnosed with a solitary functioning kidney were enrolled and evaluated using chromosomal microarray analysis (CMA). The genetic drivers for the pathogenic CNVs were analyzed. We characterized QPRT localization in fetal kidneys using immunohistochemistry and its expression in adult kidneys using quantitative RT-PCR. Further, QPRT was knocked down using siRNA in human embryonic kidney (HEK293T) cells, and the cell cycle and proliferation were tested.

Results

Besides one Triple X syndrome and one Down syndrome, we identified a total of 45 CNVs out of 34 subjects. Among the 14 pathogenic CNVs, CNV 16p11.2 reached the highest number of records with the phenotype of kidney anomalies in the Decipher database. Among the 26 genes within the 16p11.2 region, as a key enzyme for nicotinamide adenine dinucleotide (NAD+) biosynthesis, QPRT was distinctly localized in renal tubules but was barely observed in renal interstitial and glomeruli in fetal kidneys. The loss of QPRT prevented cells’ efficient transition into S phase, affected cell-cycle progression, and abrogated proliferation of human embryonic kidney cells.

Conclusion

Our data suggest that QPRT is a candidate gene associated with susceptibility for solitary functioning kidney. The CNVs discovered in our study exhibit great potential for future applications in genetic counseling and pregnancy management.
Erythrocyte Adhesion of Merozoite Surface Antigen 2c1 Expressed During Extracellular Stages of Babesia orientalis
Authors: Nie Zheng , Ao Yangsiqi , Wang Sen , Shu Xiang , Li Muxiao , Zhan Xueyan , Yu Long , An Xiaomeng , Sun Yali , Guo Jiaying , Zhao Yangnan , He Lan , Zhao Junlong
Published: May 2021

Babesia orientalis, a major infectious agent of water buffalo hemolytic babesiosis, is transmitted by Rhipicephalus haemaphysaloides. However, no effective vaccine is available. Essential antigens that are involved in parasite invasion of host red blood cells (RBCs) are potential vaccine candidates. Therefore, the identification and the conduction of functional studies of essential antigens are highly desirable. Here, we evaluated the function of B. orientalis merozoite surface antigen 2c1 (BoMSA-2c1), which belongs to the variable merozoite surface antigen (VMSA) family in B. orientalis. We developed a polyclonal antiserum against the purified recombinant (r)BoMSA-2c1 protein. Immunofluorescence staining results showed that BoMSA-2c1 was expressed only on extracellular merozoites, whereas the antigen was undetectable in intracellular parasites. RBC binding assays suggested that BoMSA-2c1 specifically bound to buffalo erythrocytes. Cytoadherence assays using a eukaryotic expression system in vitro further verified the binding and inhibitory ability of BoMSA-2c1. We found that BoMSA-2c1 with a GPI domain was expressed on the surface of HEK293T cells that bound to water buffalo RBCs, and that the anti-rBoMSA2c1 antibody inhibited this binding. These results indicated that BoMSA-2c1 was involved in mediating initial binding to host erythrocytes of B. orientalis. Identification of the occurrence of binding early in the invasion process may facilitate understanding of the growth characteristics, and may help in formulating strategies for the prevention and control of this parasite.
Immunometabolism at the Nexus of Cancer Therapeutic Efficacy and Resistance
Authors: Traba Javier , Sack Michael N. , Waldmann Thomas A. , Anton Olga M.
Published: May 2021

Constitutive activity of the immune surveillance system detects and kills cancerous cells, although many cancers have developed strategies to avoid detection and to resist their destruction. Cancer immunotherapy entails the manipulation of components of the endogenous immune system as targeted approaches to control and destroy cancer cells. Since one of the major limitations for the antitumor activity of immune cells is the immunosuppressive tumor microenvironment (TME), boosting the immune system to overcome the inhibition provided by the TME is a critical component of oncotherapeutics. In this article, we discuss the main effects of the TME on the metabolism and function of immune cells, and review emerging strategies to potentiate immune cell metabolism to promote antitumor effects either as monotherapeutics or in combination with conventional chemotherapy to optimize cancer management.
OmpA, a Common Virulence Factor, Is Under RNA Thermometer Control in Yersinia pseudotuberculosis
Authors: Scheller Daniel , Twittenhoff Christian , Becker Franziska , Holler Marcel , Narberhaus Franz
Published: May 2021

The outer membrane protein OmpA is a virulence factor in many mammalian pathogens. In previous global RNA structure probing studies, we found evidence for a temperature-modulated RNA structure in the 5'-untranslated region (5'-UTR) of the Yersinia pseudotuberculosis ompA transcript suggesting that opening of the structure at host-body temperature might relieve translational repression. Here, we support this hypothesis by quantitative reverse transcription PCR, translational reporter gene fusions, enzymatic RNA structure probing, and toeprinting assays. While ompA transcript levels decreased at 37°C compared to 25°C, translation of the transcript increased with increasing temperature. Biochemical experiments show that this is due to melting of the RNA structure, which permits ribosome binding to the 5'-UTR. A point mutation that locks the RNA structure in a closed conformation prevents translation by impairing ribosome access. Our findings add another common virulence factor to the growing list of pathogen-associated genes that are under RNA thermometer control.
Transfer RNA-Derived Fragments, the Underappreciated Regulatory Small RNAs in Microbial Pathogenesis
Authors: Li Zhongyou , Stanton Bruce A.
Published: May 2021

In eukaryotic organisms, transfer RNA (tRNA)-derived fragments have diverse biological functions. Considering the conserved sequences of tRNAs, it is not surprising that endogenous tRNA fragments in bacteria also play important regulatory roles. Recent studies have shown that microbes secrete extracellular vesicles (EVs) containing tRNA fragments and that the EVs deliver tRNA fragments to eukaryotic hosts where they regulate gene expression. Here, we review the literature describing microbial tRNA fragment biogenesis and how the fragments secreted in microbial EVs suppress the host immune response, thereby facilitating chronic infection. Also, we discuss knowledge gaps and research challenges for understanding the pathogenic roles of microbial tRNA fragments in regulating the host response to infection.
Ranking-Based Convolutional Neural Network Models for Peptide-MHC Class I Binding Prediction
Authors: Chen Ziqi , Min Martin Renqiang , Ning Xia
Published: May 2021

T-cell receptors can recognize foreign peptides bound to major histocompatibility complex (MHC) class-I proteins, and thus trigger the adaptive immune response. Therefore, identifying peptides that can bind to MHC class-I molecules plays a vital role in the design of peptide vaccines. Many computational methods, for example, the state-of-the-art allele-specific method MHCflurry, have been developed to predict the binding affinities between peptides and MHC molecules. In this manuscript, we develop two allele-specific Convolutional Neural Network-based methods named ConvM and SpConvM to tackle the binding prediction problem. Specifically, we formulate the problem as to optimize the rankings of peptide-MHC bindings via ranking-based learning objectives. Such optimization is more robust and tolerant to the measurement inaccuracy of binding affinities, and therefore enables more accurate prioritization of binding peptides. In addition, we develop a new position encoding method in ConvM and SpConvM to better identify the most important amino acids for the binding events. We conduct a comprehensive set of experiments using the latest Immune Epitope Database (IEDB) datasets. Our experimental results demonstrate that our models significantly outperform the state-of-the-art methods including MHCflurry with an average percentage improvement of 6.70% on AUC and 17.10% on ROC5 across 128 alleles.
Perspective: Humanized Pig Models of Bladder Cancer
Authors: Segatto Natália Vieira , Bender Camila Bonemann , Seixas Fabiana Kommling , Schachtschneider Kyle , Schook Lawrence , Robertson Noah , Qazi Aisha , Carlino Maximillian , Jordan Luke , Bolt Courtni , Collares Tiago
Published: May 2021

Bladder cancer (BC) is the 10th most common neoplasia worldwide and holds expensive treatment costs due to its high recurrence rates, resistance to therapy and the need for lifelong surveillance. Thus, it is necessary to improve the current therapy options and identify more effective treatments for BC. Biological models capable of recapitulating the characteristics of human BC pathology are essential in evaluating the effectiveness of new therapies. Currently, the most commonly used BC models are experimentally induced murine models and spontaneous canine models, which are either insufficient due to their small size and inability to translate results to clinical basis (murine models) or rarely spontaneously observed BC (canine models). Pigs represent a potentially useful animal for the development of personalized tumors due to their size, anatomy, physiology, metabolism, immunity, and genetics similar to humans and the ability to experimentally induce tumors. Pigs have emerged as suitable biomedical models for several human diseases. In this sense, the present perspective focuses on the genetic basis for BC; presents current BC animal models available along with their limitations; and proposes the pig as an adequate animal to develop humanized large animal models of BC. Genetic alterations commonly found in human BC can be explored to create genetically defined porcine models, including the BC driver mutations observed in the FGFR3, PIK3CA, PTEN, RB1, HRAS, and TP53 genes. The development of such robust models for BC has great value in the study of pathology and the screening of new therapeutic and diagnostic approaches to the disease.
CXCL1 Regulated by miR-302e Is Involved in Cell Viability and Motility of Colorectal Cancer via Inhibiting JAK-STAT Signaling Pathway
Authors: Chen Biyin , Song Li , Nie Xiuzhen , Lin Fangfeng , Yu Zongyang , Kong Wencui , Qi Xiaoyan , Wang Wenwu
Published: May 2021

Purpose

This study made a systemic description for the CXCL1-dependent regulatory mechanism in colorectal cancer (CRC).

Methods

Bioinformatics methods were applied to obtain target mRNA CXCL1 and corresponding upstream miRNA. qRT-PCR and Western blot were performed to measure the levels of CXCL1 and miR-302e in CRC tissue and cells. Experiments including CCK-8, wound healing assay, Transwell invasion assay, and flow cytometry were conducted to assess cell biological behaviors. Dual-luciferase reporter assay was carried out for verification of the targeting relationship between CXCL1 and miR-302e. The inhibitor AG490 of JAK-STAT signaling pathway was used to identify the functional mechanism of CXCL1/JAK-STAT underlying progression of CRC, and tumor xenograft experiments were performed for further validation.

Results

CXCL1 was highly expressed in CRC tissue and cells, while miR-302e was poorly expressed. Silencing CXCL1 or overexpressing miR-302e could lead to inhibition of cell proliferation, migration, invasion but promotion of cell apoptosis of CRC. Besides, CXCL1 was identified as a direct target of miR-302e, and CXCL1 could reverse the effect of miR-302e on cell proliferation, migration, invasion, and apoptosis. Furthermore, CXCL1 functioned on CRC cell biological behaviors via activation of JAK-STAT signaling pathway.

Conclusion

CXCL1 could be regulated by miR-302e to inactivate JAK-STAT signaling pathway, in turn affecting cell proliferation, migration, invasion, and apoptosis of CRC. Our result provides a potential therapeutic target for CRC treatment.
Downregulation of lncRNA XR_429159.1 Linked to Brain Metastasis in Patients With Limited-Stage Small-Cell Lung Cancer
Authors: Li Ji , Jing Wang , Jia Wenxiao , Zhai Xiaoyang , Zhu Hui , Yu Jinming
Published: May 2021

Purpose: The purpose of this study was to identify aberrant long non-coding RNAs (lncRNAs) and explore the predictive value of lncRNA expression patterns on the risk of brain metastases (BMs) in patients with limited-stage small-cell lung cancer (SCLC).

Patients and Methods: We executed an array of lncRNA and mRNA chip assays to examine the expression in peripheral blood mononuclear cells obtained from SCLC patients with BMs and compared the expression patterns against those from patients without BMs to identify lncRNAs associated with BMs. Validation was performed against clinical data to further confirm the relationship between lncRNAs and BM. Kaplan–Meier analysis was applied to estimate the cumulative incidence of BMs, and differences between the groups were analyzed using the log-rank test.

Results: The expression of 67 lncRNAs (27 upregulated and 40 downregulated) and 47 mRNAs (20 upregulated and 27 downregulated) was significantly different between the BM and non-BM groups (fold change ≥ 2.0, p-value ≤ 0.05), based on the lncRNA and mRNA chip assays. Four lncRNAs were verified by quantitative real-time polymerase chain reaction (qRT-PCR) to confirm the accuracy of the microarray data, and the results of 11 patient pairs (11 patients with BM and 11 patients without BM) revealed that low LncRNA XR_429159.1 expression was a high-risk factor for BM. Further clinical data showed that the incidence of BM among 25 patients with low-level LncRNA XR_429159.1 expression was 31% at 1 year, compared with 14.3% among the 18 patients with high-level LncRNA XR_429159.1 expression (p = 0.035).

Conclusion: Our present study identified the low-level expression of lncRNA XR_429159.1 as a high-risk factor among BM in patients with limited-stage SCLC. LncRNA XR_429159.1 is a critical molecule that regulates SCLC metastasis, involved in the neuroepithelial transforming gene 1 (NET1) pathway, and serum levels of this lncRNA are significantly associated with the risk of BM.
Differentiating TP53 Mutation Status in Pancreatic Ductal Adenocarcinoma Using Multiparametric MRI-Derived Radiomics
Authors: Gao Jing , Chen Xiahan , Li Xudong , Miao Fei , Fang Weihuan , Li Biao , Qian Xiaohua , Lin Xiaozhu
Published: May 2021

Objectives

This study assessed the preoperative prediction of TP53 status based on multiparametric magnetic resonance imaging (mpMRI) radiomics extracted from two-dimensional (2D) and 3D images.

Methods

57 patients with pancreatic cancer who underwent preoperative MRI were included. The diagnosis and TP53 gene test were based on resections. Of the 57 patients included 37 mutated TP53 genes and the remaining 20 had wild-type TP53 genes. Two radiologists performed manual tumour segmentation on seven different MRI image acquisition sequences per patient, including multi-phase [pre-contrast, late arterial phase (ap), portal venous phase, and delayed phase] dynamic contrast enhanced (DCE) T1-weighted imaging, T2-weighted imaging (T2WI), Diffusion-weighted imaging (DWI), and apparent diffusion coefficient (ADC). PyRadiomics-package was used to generate 558 two-dimensional (2D) and 994 three-dimensional (3D) image features. Models were constructed by support vector machine (SVM) for differentiating TP53 status and DX score method were used for feature selection. The evaluation of the model performance included area under the curve (AUC), accuracy, calibration curves, and decision curve analysis.

Results

The 3D ADC-ap-DWI-T2WI model with 11 selected features yielded the best performance for differentiating TP53 status, with accuracy = 0.91 and AUC = 0.96. The model showed the good calibration. The decision curve analysis indicated that the radiomics model had clinical utility.

Conclusions

A non-invasive and quantitative mpMRI-based radiomics model can accurately predict TP53 mutation status in pancreatic cancer patients and contribute to the precision treatment.
Dapagliflozin Alleviates Hepatic Steatosis by Restoring Autophagy via the AMPK-mTOR Pathway
Authors: Li Liuran , Li Qinghua , Huang Wenbin , Han Yibing , Tan Huiting , An Min , Xiang Qianru , Zhou Rui , Yang Li , Cheng Yanzhen
Published: May 2021

As a newly approved oral hypoglycaemic agent, the sodium-glucose cotransporter 2 (SGLT2) inhibitor dapagliflozin, which is derived from the natural product phlorizin can effectively reduce blood glucose. Recent clinical studies have found that dapagliflozin alleviates non-alcoholic fatty liver disease (NAFLD), but the specific mechanism remains to be explored. This study aimed to investigate the underlying mechanism of dapagliflozin in alleviating hepatocyte steatosis in vitro and in vivo. We fed the spontaneous type 2 diabetes mellitus rats with high-fat diets and cultured human normal liver LO2 cells and human hepatocellular carcinoma HepG2 cells with palmitic acid (PA) to induce hepatocellular steatosis. Dapagliflozin attenuated hepatic lipid accumulation both in vitro and in vivo. In Zucker diabetic fatty (ZDF) rats, dapagliflozin reduced hepatic lipid accumulation via promoting phosphorylation of acetyl-CoA carboxylase 1 (ACC1), and upregulating lipid β-oxidation enzyme acyl-CoA oxidase 1 (ACOX1). Furthermore, dapagliflozin increased the expression of the autophagy-related markers LC3B and Beclin1, in parallel with a drop in p62 level. Similar effects were observed in PA-stimulated LO2 cells and HepG2 cells. Dapagliflozin treatment could also significantly activated AMPK and reduced the phosphorylation of mTOR in ZDF rats and PA-stimulated LO2 cells and HepG2 cells. We demonstrated that dapagliflozin ameliorates hepatic steatosis by decreasing lipogenic enzyme, while inducing fatty acid oxidation enzyme and autophagy, which could be associated with AMPK activation. Moreover, our results indicate that dapagliflozin induces autophagy via the AMPK-mTOR pathway. These findings reveal a novel clinical application and functional mechanism of dapagliflozin in the treatment of NAFLD.
Long-Acting Metformin Vs. Metformin Immediate Release in Patients With Type 2 Diabetes: A Systematic Review
Authors: Tan Jixue , Wang Yang , Liu Song , Shi Qingyang , Zhou Xu , Zhou Yiling , Yang Xiaoling , Chen Pingshan , Li Sheyu
Published: May 2021

Background: Metformin, a commonly used antidiabetic medication, is available in both an immediate-release (IR) formulation and a long-acting formulation (metformin extended-release; XR).

Objective: We performed a systematic review to compare the effectiveness, safety, and patient compliance and satisfaction between the metformin IR and XR formulations.

Method: We searched for randomized control trials (RCTs) and observational studies comparing the effectiveness, safety, or patient compliance and satisfaction of metformin XR with metformin IR using the MEDLINE, Embase, and Cochrane Central Register of Controlled Trials databases. Following report screening, data collection, and risk of bias assessment, we separately pooled data from RCTs and observational studies using the Grading of Recommendation Assessment, Development, and Evaluation approach to rate the quality of evidence.

Result: We included five RCTs, comprising a total of 1,662 patients, and one observational study, comprising 10,909 patients. In the meta-analyses, no differences were identified in outcomes of effectiveness and safety between the two forms of metformin (including change in HbA1c: mean difference (MD), 0.04%, 95% confidence interval [CI], −0.05–0.13%, fasting blood glucose: MD, −0.03 mmol/L, 95% CI, −0.22–0.15 mmol/L, postprandial blood glucose: MD, 0.50 mmol/L, 95% CI, −0.71–1.72 mmol/L, adverse events of abdominal pain: relative risk (RR), 1.15, 95% CI, 0.57–2.33, all-cause death (RR, 3.02, 95% CI 0.12–73.85), any adverse events (RR, 1.14, 95% CI 0.97–1.34), any adverse events leading to treatment discontinuation: RR, 1.51, 95% CI, 0.82–2.8, any gastrointestinal adverse events: RR, 1.09, 95% CI, 0.93–1.29, diarrhea: RR, 0.82, 95% CI, 0.53–1.27, flatulence: RR, 0.43, 95% CI, 0.15–1.23, nausea: RR, 0.97, 95% CI, 0.64–1.47, severe adverse events: RR, 0.64, 95% CI, 0.28–1.42, and vomiting: RR, 1.46, 95% CI, 0.6–3.56). Data from both the RCTs and the observational study indicate mildly superior patient compliance with metformin XR use compared with metformin IR use; this result was attributable to the preference for once-daily administration with metformin XR.

Conclusion: Our systematic review indicates that metformin XR and IR formulations have similar effectiveness and safety, but that metformin XR is associated with improved compliance to treatment.
Visual Perception and the Emergence of Minimal Representation
Authors: Arnellos Argyris , Moreno Alvaro
Published: May 2021

There is a long-lasting quest of demarcating a minimally representational behavior. Based on neurophysiologically-informed behavioral studies, we argue in detail that one of the simplest cases of organismic behavior based on low-resolution spatial vision–the visually-guided obstacle avoidance in the cubozoan medusaTripedalia cystophora–implies already a minimal form of representation. We further argue that the characteristics and properties of this form of constancy-employing structural representation distinguish it substantially from putative representational states associated with mere sensory indicators, and we reply to some possible objections from the liberal representationalists camp by defending and qualitatively demarcating the minimal nature of our case. Finally, we briefly discuss the implications of our thesis within a naturalistic framework.
The Impact of COVID-19 on Diverse Older Adults and Health Equity in the United States
Authors: Guerrero Lourdes R. , Wallace Steven P.
Published: May 2021

Older adults are most at risk of negative COVID-19 outcomes and consequences. This study applies the World Health Organization's Health Inequity Causal Model to identify different factors that may be driving the higher observed hospitalizations and deaths among older adults of color compared to non-Latinx Whites in the United States. We used multiple data sets, including the US Census American Community Survey and PULSE COVID data, along with published reports, to understand the social context of older adults, including income distributions by race and ethnicity, household composition and potential COVID-19 exposure to older adults by working family members. Our findings point to multiple social determinants of health, beyond individual health risks, which may explain why older adults of color are the most at risk of negative COVID-19 outcomes and consequences. Current health policies do not adequately address disproportionate impact; some even worsen it. This manuscript provides new data and analysis to support the call for equity-focused solutions to this pandemic and health in general in the future, focusing on meeting the needs of our most vulnerable communities.
Engendering Governance After Armed Conflict: Observations From Kosovo
Authors: Holzner Brigitte M.
Published: May 2021

This article addresses gender-responsive governance reforms in post-conflict Kosovo from two perspectives: (1) the perspective of human rights as fundamental for state-building, and (2) the resolutions of the UN Security Council regarding Women, Peace, and Security (WPS), notably the initial UNSCR 1325. Special focus is laid on women's agency in governance matters—at the level of the state and at the level of civil society. A gender approach to three dimensions of governance—political-administrative governance, security governance, and socioeconomic governance—shows successes and problems in this post-conflict society. Special attention is given to the strategies of the women's movement in reaching gender-responsive governance. Some initiatives for new masculinities address the necessity of norm change in gender governance. The analysis of the literature and documents, supplemented by interviews, reveals the transformative potential of gender governance that solidly roots in women's rights and combines a multi-actor approach at grassroots, and at national and international levels with strong alliances and very concrete actions.
Anti-bribery and Corruption Policies in International Sports Governing Bodies
Authors: Philippou Christina , Hines Tony
Published: May 2021

International Sports Governing Bodies (“ISGBs”) are diverse in their aims but share a need to maintain a reputation of accountability in the eyes of their stakeholders. While some literature analyses the general governance concerns faced by these organizations, there is limited focus on anti-bribery and corruption (“ABC”) within this sphere. This paper's research aim is an exploratory evaluation of the ABC best practice policies that exist within ISGBs, asking how they can be assessed and what best practice policies currently exist within this framework. This paper undertakes a critical review of the diverse ABC governance policies in the largest ISGBs through content analysis on governance documents publically available on the sample ISGB websites. This review was undertaken twice on the same ISGBs, in 2017 and 2020, and the changes reviewed. The research highlights best practice policies for recommendation to all ISGBs, and illuminates the absence of adequate policies with regards to the risk of bribery in ISGBs. The findings show there was no area within the framework that ISGBs performed well at as a collective, and there was no single ISGB whose anti-bribery policies were strong in all areas. However, the comparison between 2017 and 2020 shows an improvement in ABC policies in some ISGBs over the timeframe analyzed. The implications are a need for sharing best practice in this area of governance, and providing global guidance on ABC policies for ISGBs to ensure integrity in the sector.
Development and Validation a Nomogram for Predicting Overall Survival in Patients With Intrahepatic Cholangiocarcinoma
Authors: Yuan Chen , Hu Zhigang , Wang Kai , Zou Shubing
Published: May 2021

Background: This study aims to establish an effective nomogram to predict the overall survival of patients with intrahepatic cholangiocarcinoma (ICC).

Patients and Methods: Data used to build the nomogram comes from the Surveillance, Epidemiology, and End Results (SEER) database. Patients diagnosed with ICC between 2005 and 2016 were retrospectively collected. Prediction accuracy and discrimination ability of the nomogram was evaluated by concordance index (C-index) and calibration curve. The area under receiver operating characteristic (ROC) curve (AUC) and decision curve analysis (DCA) were used to compare the precision of the 1-, 3-, and 5-year survival of the nomogram with 8th American Joint Commission on Cancer (AJCC) tumor–node–metastasis (TNM) staging system. Finally, it was verified in a prospective study of patients diagnosed with ICC in the Second Affiliated Hospital of Nanchang University from 2013 to 2020 by bootstrap resampling.

Result: The study contains two parts of data; we establish a nomogram using external data, and we conducted internal verification and external verification. The nomogram that we have established has good calibration, with a concordance index (C-index) of 0.75 (95% CI, 0.74–0.76) for overall survival (OS) prediction. The AUC value of the nomogram predicting 1-, 3-, and 5-year OS rates were 0.821, 0.828, and 0.836, which were higher than those of the 8th AJCC TNM staging systems. The calibration curve for the probability of survival between prediction by nomogram and actual observation shows good agreement. The nomogram showed better accuracy than the 8th edition AJCC TNM staging.

Conclusion: The nomogram established can provide a more accurate prognosis for patients with intrahepatic cholangiocarcinoma.
Cultivating for the Industry: Cropping Experiences with Hypericum perforatum L. in a Mediterranean Environment
Authors: Lazzara Silvia , Carrubba Alessandra , Napoli Edoardo
Published: May 2021

Hypericum perforatum is an intensively studied medicinal plant, and much experimental activity has been addressed to evaluate its bio-agronomical and phytochemical features as far. In most cases, plant material used for experimental purposes is obtained from wild populations or, alternatively, from individuals grown in vases and/or pots. When Hypericum is addressed to industrial purposes, the most convenient option for achieving satisfactory amounts of plant biomass is field cultivation. Pot cultivation and open field condition, however, are likely to induce different responses on plant’s metabolism, and the obtained yield and composition are not necessarily the same. To compare these management techniques, a 4-year cultivation trial (2013–2016) was performed, using three Hypericum biotypes obtained from different areas in Italy: PFR-TN, from Trento province, Trentino; PFR-SI, from Siena, Tuscany; PFR-AG, from Agrigento province, Sicily. Both managements gave scarce biomass and flower yields at the first year, whereas higher yields were measured at the second year (in open field), and at the third year (in pots). Plant ageing induced significant differences in phytochemical composition, and the total amount of phenolic substances was much higher in 2015 than in 2014. A different performance of genotypes was observed; the local genotype was generally more suitable for field cultivation, whereas the two non-native biotypes performed better in pots. Phytochemical profile of in-pots plants was not always reflecting the actual situation of open field. Consequently, when cultivation is intended for industrial purposes, accurate quality checks of the harvested material are advised.
3D Point Cloud on Semantic Information for Wheat Reconstruction
Authors: Yang Yuhang , Zhang Jinqian , Wu Kangjie , Zhang Xixin , Sun Jun , Peng Shuaibo , Li Jun , Wang Mantao
Published: May 2021

Phenotypic analysis has always played an important role in breeding research. At present, wheat phenotypic analysis research mostly relies on high-precision instruments, which make the cost higher. Thanks to the development of 3D reconstruction technology, the reconstructed wheat 3D model can also be used for phenotypic analysis. In this paper, a method is proposed to reconstruct wheat 3D model based on semantic information. The method can generate the corresponding 3D point cloud model of wheat according to the semantic description. First, an object detection algorithm is used to detect the characteristics of some wheat phenotypes during the growth process. Second, the growth environment information and some phenotypic features of wheat are combined into semantic information. Third, text-to-image algorithm is used to generate the 2D image of wheat. Finally, the wheat in the 2D image is transformed into an abstract 3D point cloud and obtained a higher precision point cloud model using a deep learning algorithm. Extensive experiments indicate that the method reconstructs 3D models and has a heuristic effect on phenotypic analysis and breeding research by deep learning.
Factors That Determine Innovation in Agrifood Firms
Authors: Castillo-Valero Juan Sebastián , García-Cortijo María Carmen
Published: May 2021

In this study, we aim to find the determinants of innovation in the agrifood industry in an inland region in southeast Spain, which depends upon and specializes in this sector. The determinants we propose are firm and environmental factors. From the empirical analyses based on Box–Cox models, we deduce that a firm’s internal factors or characteristics are those that have the greatest influence on its propensity to innovate. Among them, firm size has the greatest effect. Innovation culture has the potential for exerting a multiplying effect via mechanisms such as knowledge spillovers or learning by doing.
Diversity of Cowpea [Vigna unguiculata (L.) Walp] Landraces in Mozambique: New Opportunities for Crop Improvement and Future Breeding Programs
Authors: Gomes Ana Maria Figueira , Draper David , Nhantumbo Nascimento , Massinga Rafael , Ramalho José C. , Marques Isabel , Ribeiro-Barros Ana I.
Published: May 2021

Cowpea (Vigna unguiculata) is a neglected crop native to Africa, with an outstanding potential to contribute to the major challenges in food and nutrition security, as well as in agricultural sustainability. Two major issues regarding cowpea research have been highlighted in recent years—the establishment of core collections and the characterization of landraces—as crucial to the implementation of environmentally resilient and nutrition-sensitive production systems. In this work, we have collected, mapped, and characterized the morphological attributes of 61 cowpea genotypes, from 10 landraces spanning across six agro-ecological zones and three provinces in Mozambique. Our results reveal that local landraces retain a high level of morphological diversity without a specific geographical pattern, suggesting the existence of gene flow. Nevertheless, accessions from one landrace, i.e., Maringué, seem to be the most promising in terms of yield and nutrition-related parameters, and could therefore be integrated into the ongoing conservation and breeding efforts in the region towards the production of elite varieties of cowpea.
Canine Placenta Histological Findings and Microvascular Density: The Histological Basis of a Negative Neonatal Outcome?
Authors: Sarli Giuseppe , Castagnetti Carolina , Bianco Carlo , Ballotta Giulia , Tura Giorgia , Caporaletti Martina , Cunto Marco , Avallone Giancarlo , Benazzi Cinzia , Ostanello Fabio , Zambelli Daniele
Published: May 2021

Placenta is essential for the development of the fetus, and its impaired function can lead to a negative outcome (i.e., neonatal mortality). In dogs, investigations on placenta histology and neonatal outcome in healthy bitches are lacking, and a contribution is provided in this study to emphasize the use of placenta histology in practice. Fifty-one placentas from 11 litters were collected during cesarean section, classified according to the litter size (large (L) or small (S)) and the outcome, this latter as healthy (Group 1) or dead within 7 days (Group 2). The placenta/puppy weight ratio (PPR) was calculated, and specimens were formalin-fixed and paraffin-wax embedded, and on the resulting histological slides, capillary density (CD) was quantified. Among necrosis, calcification, and intravascular leucocytes, only the presence of multifocal-confluent necrosis (significantly more frequent in Group 2) was associated with a higher risk of death within 7 days (odds ratio = 30.7). Mixed logistic regression ruled out the effect on death both of a bitch and cesarean type (programmed vs. emergency). PPR and CD values were associated with litter size; large litters had lower PPR (p < 0.01) and higher CD (p < 0.05) than small litters. The relationship between PPR and CD was negative and significant (p < 0.01). Necrosis was a frequent finding in canine placentas, but only when multifocal-confluent was it associated with a poor outcome. The litter size influenced PPR (lower in L) and CD (higher in L), and this is likely due to the plasticity of placenta adaptation.
The “Sandwich” System: A Potential Solution for Protecting Overwintering Cornu aspersum Snails Reared in Semi-Intensive Heliciculture Farms in Colder Climates
Authors: Manea Dan , Ienciu Anișoara Aurelia , Ștef Ramona , Peț Ioan , Șmuleac Laura , Grozea Ioana , Cărăbeț Alin , Drăghici George Andrei , Nica Dragoș Vasiles
Published: May 2021

(1) Background: Hibernation in pens covered with LFC was associated with high mortality of C. aspersum snails in Romanian snail farms. This three-year study aimed to develop a simple, but effective system for protecting breeders in colder climates. (2) Methods: The first phase investigated the (pre)hibernal burrowing behavior and the overwintering habitat choice. Protective structures based on straw, LFC, and/or HDPE were tested at pilot level (no snails). The most suitable system was applied under farm conditions. (3) Results: Wood and ridge-tile micro shelters were significantly preferred to corrugated iron micro shelters. Burrowing specimens acted as shallow-burrowers, and this behaviorwas significantly more common for looser soils. All pilot systems displayed significantly higher thermal protection efficiency compared to the sole use of LFC. The balance between straw moistening and thermal protection favored using structure soil/LFC/straw/10-cm air cushion/HDPE. Its use yielded significantly higher survival compared to the sole use of LFC. Most hibernating snails clustered together in large groups, attached on the lower surface of micro shelters. Predator occurrence appeared to marginally affect overwintering survival. (4) Conclusions: The “sandwich” system could be an effective solution for overwintering mature C. aspersum snails in colder climates.
Estimation of Genetic Parameters and Correlation between Yearling Ultrasound Measurements and Carcass Traits in Hanwoo Cattle
Authors: Naserkheil Masoumeh , Lee Deuk-Hwan , Kong Hong-Sik , Seong Jiyeon , Mehrban Hossein
Published: May 2021

Genetic parameters have a significant role in designing a breeding program and are required to evaluate economically important traits. The objective of this study was to estimate heritability and genetic correlation between yearling ultrasound measurements, such as backfat thickness (UBFT), eye muscle area (UEMA), intramuscular fat content (UIMF), and carcass traits, such as backfat thickness (BFT), carcass weight (CW), eye muscle area (EMA), marbling score (MS) at approximately 24 months of age, as well as yearling weight (YW) in Hanwoo bulls (15,796) and steers (5682). The (co) variance components were estimated using a multi-trait animal model. Moderate to high heritability estimates were obtained and were 0.42, 0.50, 0.56, and 0.59 for CW, EMA, BFT, and MS, respectively. Heritability estimates for yearling measurements of YW, UEMA, UBFT, and UIMF were 0.31, 0.32, 0.30, and 0.19, respectively. Favorable and strong genetic correlations were observed between UIMF and MS (0.78), UBFT and BFT (0.63), and UEMA and EMA (0.65). Moreover, the estimated genetic correlation between YW and CW was high (0.84) and relatively moderate between YW and EMA (0.43). These results suggest that genetic improvement can be achieved for carcass traits when using yearling ultrasound measurements as selection criteria in ongoing Hanwoo breeding programs.
Expression Analysis of Circular RNAs in Young and Sexually Mature Boar Testes
Authors: Zhang Fei , Zhang Xiaodong , Ning Wei , Zhang Xiangdong , Ru Zhenyuan , Wang Shiqi , Sheng Mei , Zhang Junrui , Zhang Xueying , Luo Haiqin , Wang Xin , Cao Zubing , Zhang Yunhai
Published: May 2021

Testicular development is critical for male animals’ reproduction and is tightly regulated by epigenetic factors. Circular RNAs (circRNAs) were recently identified in the testes of humans and bulls. However, the expression profile of circRNAs and their potential biological functions in boar testicular development remain unclear. We identified 34,521 and 31,803 circRNAs in piglet (30 d) and adult (210 d) boar testes by high-throughput sequencing, respectively. Bioinformatics analysis revealed that these circRNAs are widely distributed on autosomes and sex chromosomes. Some of the host genes can generate multiple circRNAs. A total of 2326 differentially expressed circRNAs (DECs) derived from 1526 host genes was found in testicular development, of which 1003 circRNAs were up-regulated in adult boar testes and 1323 circRNAs were down-regulated. Furthermore, gene ontology analysis of host genes of DECs revealed that these circRNAs are mainly involved in regulating spermatogenesis, cilia motility, and hormone biosynthesis. The Kyoto Encyclopedia of Genes and Genomes pathway enrichment analysis revealed that the DECs are markedly enriched to stem cell pluripotency regulation, tight junctions, adhesion junctions, and cAMP signaling pathway. These results indicate that circRNAs are abundantly expressed in boar testes and exhibit dynamic changes during testicular development.
Antimicrobial Activity of Sorghum Phenolic Extract on Bovine Foodborne and Mastitis-Causing Pathogens
Authors: Schnur Sydney E. , Amachawadi Raghavendra G. , Baca Giovanna , Sexton-Bowser Sarah , Rhodes Davina H. , Smolensky Dmitriy , Herald Thomas J. , Perumal Ramasamy , Thomson Daniel U. , Nagaraja Tiruvoor G.
Published: May 2021

Antimicrobial resistance in bacterial pathogens associated with bovine mastitis and human foodborne illnesses from contaminated food and water have an impact on animal and human health. Phenolic compounds have antimicrobial properties and some specialty sorghum grains are high in phenolic compounds, and the grain extract may have the potential as a natural antimicrobial alternative. The study’s objective was to determine antimicrobial effects of sorghum phenolic extract on bacterial pathogens that cause bovine mastitis and human foodborne illnesses. Bacterial pathogens tested included Escherichia coli, Salmonella Typhimurium, Campylobacter jejuni, Campylobacter coli, Pseudomonas aeruginosa, Klebsiella pneumoniae, Klebsiella oxytoca, Staphylococcus aureus, and Enterococcus faecalis. Antibacterial activities of sorghum phenolic extracts were determined by agar-well diffusion assay. Sorghum phenolic extract was added to the wells in concentrations of 0, 100, 200, 500, 1000, or 4000 µg/mL. The control wells did not receive phenolic extract. Plates were incubated for 18–24 h, and the diameter of each zone of inhibition was measured. The results indicated that sorghum phenolic extract had inhibitory effects on Staphylococcus aureus, Enterococcus faecalis, Campylobacter jejuni, and Campylobacter coli.
Recent Molecular Mechanisms and Beneficial Effects of Phytochemicals and Plant-Based Whole Foods in Reducing LDL-C and Preventing Cardiovascular Disease
Authors: Islam Salman Ul , Ahmed Muhammad Bilal , Ahsan Haseeb , Lee Young-Sup
Published: May 2021

Abnormal lipid metabolism leads to the development of hyperlipidemia, a common cause of multiple chronic disorders, including cardiovascular disease (CVD), obesity, diabetes, and cerebrovascular disease. Low-density lipoprotein cholesterol (LDL-C) currently remains the primary target for treatment of hyperlipidemia. Despite the advancement of treatment and prevention of hyperlipidemia, medications used to manage hyperlipidemia are limited to allopathic drugs, which present certain limitations and adverse effects. Increasing evidence indicates that utilization of phytochemicals and plant-based whole foods is an alternative and promising strategy to prevent hyperlipidemia and CVD. The current review focuses on phytochemicals and their pharmacological mode of actions for the regulation of LDL-C and prevention of CVD. The important molecular mechanisms illustrated in detail in this review include elevation of reverse cholesterol transport, inhibition of intestinal cholesterol absorption, acceleration of cholesterol excretion in the liver, and reduction of cholesterol synthesis. Moreover, the beneficial effects of plant-based whole foods, such as fresh fruits, vegetables, dried nuts, flax seeds, whole grains, peas, beans, vegan diets, and dietary fibers in LDL-C reduction and cardiovascular health are summarized. This review concludes that phytochemicals and plant-based whole foods can reduce LDL-C levels and lower the risk for CVD.
Identification of a Stable, Non-Canonically Regulated Nrf2 Form in Lung Cancer Cells
Authors: Mikac Sara , Rychłowski Michał , Dziadosz Alicja , Szabelska-Beresewicz Alicja , Fahraeus Robin , Hupp Theodore , Sznarkowska Alicja
Published: May 2021

Nrf2 (nuclear factor erythroid 2 (NF-E2)-related factor 2) transcription factor is recognized for its pro-survival and cell protective role upon exposure to oxidative, chemical, or metabolic stresses. Nrf2 controls a number of cellular processes such as proliferation, differentiation, apoptosis, autophagy, lipid synthesis, and metabolism and glucose metabolism and is a target of activation in chronic diseases like diabetes, neurodegenerative, and inflammatory diseases. The dark side of Nrf2 is revealed when its regulation is imbalanced (e.g., via oncogene activation or mutations) and under such conditions constitutively active Nrf2 promotes cancerogenesis, metastasis, and radio- and chemoresistance. When there is no stress, Nrf2 is instantly degraded via Keap1-Cullin 3 (Cul3) pathway but despite this, cells exhibit a basal activation of Nrf2 target genes. It is yet not clear how Nrf2 maintains the expression of its targets under homeostatic conditions. Here, we found a stable 105 kDa Nrf2 form that is resistant to Keap1-Cul3-mediated degradation and translocates to the nucleus of lung cancer cells. RNA-Seq analysis indicate that it might originate from the exon 2 or exon 3-truncated transcripts. This stable 105 kDa Nrf2 form might help explain the constitutive activity of Nrf2 under normal cellular conditions.
Quercetin and Isorhamnetin Attenuate Benzo[a]pyrene-Induced Toxicity by Modulating Detoxification Enzymes through the AhR and NRF2 Signaling Pathways
Authors: Kim Min , Jee Seung-Cheol , Kim Kyeong-Seok , Kim Hyung-Sik , Yu Kyoung-Nae , Sung Jung-Suk
Published: May 2021

Benzo[a]pyrene, classified as a Group 1 carcinogen, is metabolized to B[a]P-7,8-dihydrodiol-9,10-epoxide (BPDE), causing DNA mutations and eventually cancer. Quercetin is a dietary flavonoid abundant in fruits and vegetables. After quercetin intake, quercetin’s metabolites isorhamnetin and miquelianin are more highly concentrated than quercetin in the human plasma. In this study, we investigated the molecular mechanisms associated with the cytoprotective effect of quercetin and its metabolites against benzo[a]pyrene from a detoxification perspective. Quercetin and its metabolite isorhamnetin reduced benzo[a]pyrene-induced cytotoxicity, whereas the metabolite miquelianin did not mitigate benzo[a]pyrene-induced cytotoxicity. Moreover, quercetin and isorhamnetin reduced intracellular levels of BPDE-DNA adducts. The formation and elimination of BPDE is mediated by the xenobiotic detoxification process. Quercetin and isorhamnetin increased the gene and protein expression levels of phase I, II, and III enzymes involved in xenobiotic detoxification. Furthermore, quercetin and isorhamnetin induced the translocation of aryl hydrocarbon receptor (AhR) and nuclear factor erythroid 2-related factor 2 (NRF2), which regulate the expression level of phase enzymes. Our results suggest that quercetin and isorhamnetin promote the metabolism, detoxification, and elimination of B[a]P, thereby increasing anti-genotoxic effects and protecting against B[a]P-induced cytotoxicity.