bluuebunny/crossref_metadata_2025 huggingface dataset:
Rare combination of causes of ischemic stroke in young patient (clinical observation)
Authors: Kokukhin A. V. , Lebedev I. A. , Dubrovina O. A. , Tyapkin A. V. , Verbakh T. E.
Published: June 2022

In the presented clinical observation in early age patients with thrombophilia, bacterial endocarditis, mechanical compression of the iliac vessels of large uterine ﬁbroids, the detection of recurrence of ischemic stroke. The article discusses the diagnostic requirements for the veriﬁcation of these pathologies.
Optimization of Biomimetic, Leukocyte-Mimicking Nanovesicles for Drug Delivery Against Colorectal Cancer Using a Design of Experiment Approach
Authors: Rampado Riccardo , Biccari Andrea , D’Angelo Edoardo , Collino Federica , Cricrì Giulia , Caliceti Paolo , Giordano Federica , Taraballi Francesca , Pucciarelli Salvatore , Agostini Marco
Published: June 2022

The development of biomimetic nanoparticles (NPs) has revolutionized the concept of nanomedicine by offering a completely new set of biocompatible materials to formulate innovative drug delivery systems capable of imitating the behavior of cells. Specifically, the use of leukocyte-derived membrane proteins to functionalize nanovesicles (leukosomes) can enable their long circulation and target the inflamed endothelium present in many inflammatory pathologies and tumors, making them a promising and versatile drug delivery system. However, these studies did not elucidate the critical experimental parameters involved in leukosomes formulation. In the present study, we approached the preparation of leukosomes using a design of experiment (DoE) method to better understand the influence of experimental parameters on leukosomes features such as size, size distribution, and protein loading. We also validated this formulation technologically and tested its behavior in in vitro colorectal cancer (CRC) models, including CRC patient-derived tumor organoids (PDOs). We demonstrated leukosomes biocompatibility, endothelium adhesion capability, and tumor target in three-dimensional (3D) settings using CRC cell lines. Overall, our study offers a novel conceptual framework for biomimetic NPs using a DoE strategy and consolidates the high therapeutic potential of leukosomes as a viable drug delivery system for anti-inflammatory and antineoplastic applications.
VEGF-Loaded Heparinised Gelatine-Hydroxyapatite-Tricalcium Phosphate Scaffold Accelerates Bone Regeneration via Enhancing Osteogenesis-Angiogenesis Coupling
Authors: Chen Xu , Gao Chun-Yan , Chu Xiao-Yang , Zheng Chun-Yan , Luan Ying-Yi , He Xin , Yang Kai , Zhang Dong-Liang
Published: June 2022

Background: Bone tissue defect, one of the common orthopaedicdiseases, is traumatizing and affects patient’s lifestyle. Although autologous and xenograft bone transplantations are performed in bone tissue engineering, clinical development of bone transplantation is limited because ofvarious factors, such as varying degrees of immune rejection, lack of bone sources, and secondary damage to bone harvesting.

Methods: We synthesised a heparinised gelatine-hydroxyapatite-tricalcium phosphate (HG-HA-TCP) scaffold loaded with sustained-release vascular endothelial growth factor (VEGF) analysed their structure, mechanical properties, and biocompatibility. Additionally, the effects of HG-HA-TCP (VEGF) scaffolds on osteogenic differentiation and vascularisation of stem cells from human exfoliated deciduous teeth (SHED) in vitro and bone regeneration in vivo were investigated.

Results: HG-HA-TCP scaffold possessed good pore structure, mechanical properties, and biocompatibility. HG-HA-TCP scaffold loaded with VEGF could effectively promote SHED proliferation, migration, and adhesion. Moreover, HG-HA-TCP (VEGF) scaffold increased the expression of osteogenesis- and angiogenesis-related genes and promoted osteogenic differentiation and vascularisation in cells. In vivo results demonstrated that VEGF-loaded HG-HA-TCP scaffold improved new bone regeneration and enhanced bone mineral density, revealed byhistological, micro-CT and histochemical straining analyses. Osteogenic and angiogenic abilities of the three biological scaffolds wereranked as follows: HG-HA-TCP (VEGF) > G-HA-TCP (VEGF) > G-HA-TCP.

Conclusion: HG-HA-TCP (VEGF) scaffold with good biocompatibility could create an encouraging osteogenic microenvironment that could accelerate vessel formation and osteogenesis, providing an effective scaffold for bone tissue engineering and developing new clinical treatment strategies for bone tissue defects.
A Framework for User Centric LCA Tool Development for Early Planning Stages of Buildings
Authors: Hollberg Alexander , Tjäder Maria , Ingelhag Gerda , Wallbaum Holger
Published: June 2022

As the high greenhouse gas (GHG) emissions caused by the construction and real estate sector receive more attention, more and more countries include an environmental assessment of buildings based on Life Cycle Assessment (LCA) in their building regulations. Sweden introduced mandatory climate declarations in January 2022, for example. To support stakeholders in conducting the climate declarations and using the results to reduce GHG emissions, user-friendly tools for early planning stages are needed. The aim of this study is to develop and test a framework for user centric development of such tools. The framework builds on three steps; 1) interviewing stakeholders to define tool requirements, 2) developing a prototype tool according to the requirements, and 3) evaluating it based on user feedback. We developed and tested the framework in the Swedish context to provide a blueprint applicable to other countries and contexts. The primary target users are architects with computational design experience but also engineers and real estate developers working in early phases. The results show that the users’ expectations can be met when the requirements are integrated from the very beginning. In the current version, the developed building LCA tool only targets the embodied GHG emissions from the production and construction phase of the building, but it could be extended to include further life cycle phases in the future.
Trunk Neural Crest Migratory Position and Asymmetric Division Predict Terminal Differentiation
Authors: Alhashem Zain , Camargo-Sosa Karen , Kelsh Robert N. , Linker Claudia
Published: June 2022

The generation of complex structures during embryogenesis requires the controlled migration and differentiation of cells from distant origins. How these processes are coordinated and impact each other to form functional structures is not fully understood. Neural crest cells migrate extensively giving rise to many cell types. In the trunk, neural crest cells migrate collectively forming chains comprised of cells with distinct migratory identities: one leader cell at the front of the group directs migration, while followers track the leader forming the body of the chain. Herein we analysed the relationship between trunk neural crest migratory identity and terminal differentiation. We found that trunk neural crest migration and fate allocation is coherent. Leader cells that initiate movement give rise to the most distal derivativities. Interestingly, the asymmetric division of leaders separates migratory identity and fate. The distal daughter cell retains the leader identity and clonally forms the Sympathetic Ganglia. The proximal sibling migrates as a follower and gives rise to Schwann cells. The sympathetic neuron transcription factor phox2bb is strongly expressed by leaders from early stages of migration, suggesting that specification and migration occur concomitantly and in coordination. Followers divide symmetrically and their fate correlates with their position in the chain.
Research of Synergistic Substances on Tobacco Beetle [Lasioderma serricorne (Fabricius) (Coleoptera: Anobiidae)] Adults Attractants
Authors: Ren Yanling , Wang Tao , Jiang Yingjie , Chen Pengchao , Tang Jian , Wang Juan , Jin Daochao , Guo Jianjun
Published: June 2022

In this study, four kinds of chemical substances (2,3,5,6-tetramethylpyrazine, β-ionone, citronellal, and paeonol), three kinds of plant essential oils (tea tree essential oil, lavender essential oil, and myrrh essential oil), and their combinations were selected to explore their synergistic effects on tobacco beetle [Lasioderma serricorne (Fabricius) (Coleoptera: Anobiidae)] adults by the behavioral test and laboratory simulation test. Behavioral test results showed that some of the combinations revealed a synergistic effect on tobacco beetle adults, especially the sexual attractant +2,3,5,6-tetramethylpyrazine + β-ionone + citronellal + paeonol (SABCD, one portion of sexual attractant, and 1 mg/L synergistic substances) combination and the food attractant +2,3,5,6-tetramethylpyrazine + paeonol (FAD, 1 ml of food attractant and 1 mg/L synergistic substances) combination showed the best behavioral effect on tobacco beetle adults with average dwell times of 120.97 and 126.74 s, respectively, compared to those of other combinations. Meanwhile, SABCD had the highest selection rate [89.47%, about 1.5 times that of the sexual attractant (S)] on tobacco beetle adults compared with those of other combinations. In addition, laboratory simulation test results showed that the SABCD combination had the highest average selection rate (37.31%, about 2 times that of S) on tobacco beetle adults at 1 mg/L. However, our results showed that there was no significant difference in the indoor simulation results of food attractant synergistic substances. Our results will provide guidance for the development of new pesticides for tobacco beetle adults.
Construction of a Tumor Immune Microenvironment-Related Prognostic Model in BRAF-Mutated Papillary Thyroid Cancer
Authors: Xia Yuxiao , Jiang Xue , Huang Yuan , Liu Qian , Huang Yin , Zhang Bo , Mei Zhanjun , Xu Dongkun , Shi Yuhong , Tu Wenling
Published: June 2022

BRAF mutation is a representative oncogenic mutation, with a frequency of 60% in papillary thyroid carcinoma (PTC), but the reasons for the poor prognosis and more aggressive course of BRAF-mutated PTC are controversial. Tumor immune microenvironment (TIME) is an essential factor permitting the development and progression of malignancy, but whether TIME participates in the prognosis of BRAF-mutated PTC has not yet been reported. The primary goal of the present study was to provide a comprehensive TIME-related prognostic model to increase the predictive accuracy of progression-free survival (PFS) in patients with BRAF-mutated PTC. In this study, we analyzed the mRNA-seq data and corresponding clinical data of PTC patients obtained from the TCGA database. By calculating the TIME scores (immune score, stromal score and ESTIMATE score), the BRAF mutation group (n=237) was dichotomized into the high- and low-score groups. By functional analysis of differentially expressed genes (DEGs) in different high/low score groups, we identified 2 key TIME-related genes, HTR3A and NIPAL4, which affected PFS in BRAF-mutated PTC. A risk scoring system was developed by multivariate Cox analysis based on the abovementioned 2 TIME-related genes. Then, the BRAF-mutated cohort was divided into the high- and low-risk groups using the median risk score as a cutoff. A high risk score correlated positively with a higher HTR3A/NIPAL4 expression level but negatively with PFS in BRAF-mutated PTC. Ultimately, a nomogram was constructed by combining risk score with clinical parameter (Tumor stage), and the areas under the ROC curve (AUCs) of the nomogram for predicting 1-, 3- and 5-year PFS were then calculated and found to be 0.694, 0.707 and 0.738, respectively, indicating the improved accuracy and clinical utility of the nomogram versus the risk score model in the BRAF-mutated PTC cohort. Moreover, we determined the associations between prognostic genes or risk score and immune cell infiltration by two-way ANOVA. In the high-risk score, high HTR3A expression, and high NIPAL4 expression groups, higher infiltration of immune cells was found. Collectively, these findings confirm that the nomogram is effective in predicting the outcome of BRAF-mutated PTC and will add a spatial dimension to the developing risk stratification system.
Construction of Operation Portraits Based on a Cloud Model for Power Distribution Networks
Authors: Liang Jifeng , Li Tiecheng , Fan Hui , Hu Xuekai , Wang Lei , Jiang Shan
Published: June 2022

With the high proportion of new energy access in power distribution networks, the operation of distribution networks becomes more uncertain and complex. The mechanism on how to extract features that embody the full perspective of the distribution network from the diverse and varying conditions is of great significance to master the operating property of distribution networks under the high proportion of new energy. This study investigates the portrait construction of power distributions. A data-driven method of portrait construction for a distribution network based on a cloud model is proposed. First, the indexes describing the operation of the medium voltage distribution network (MVDN) and low-voltage station area (LVSA) are established. By means of statistics, fuzzy label templates are provided for the indexes. Then, based on the daily monitoring power grid data, the operation index is calculated to form the collected samples, and the reverse cloud generator is used as the data-driven method to process the samples, and the fuzzy model of cloud parameter representation is obtained. Finally, the fuzzy distance between the obtained fuzzy model and the label template is calculated, and the scores of operation indexes are obtained, thus forming a portrait method of distribution network operation behavior. Taking the IEEE 33 distribution network and real distribution network as examples and taking the LVSA as an example, it is verified that this method can effectively construct the distribution network operation portrait.
Circular RNAs as Prognostic Biomarkers in Renal Cell Carcinoma: A Systematic Review and Meta-Analysis
Authors: Liao Dan , Lin Qiu , Xiao Huan , Zhang Fenglian , Han Qin
Published: June 2022

Background: Recently, several studies have shown that circRNAs play critical roles in renal cell carcinoma (RCC) oncogenesis and development. However, whether the level of circRNA expression in RCC is correlated with prognosis remains unclear. Hence, we conducted a meta-analysis to explore the association between circRNA expression levels and the prognosis of RCC patients.

Methods: We systematically searched Ovid, Embase, PubMed, and Web of Science from January 1950 to June 2021 for the literature published in English. According to the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) guidelines, we conducted a meta-analysis of 21 selected studies to confirm the association between the circRNA expression level and prognosis of RCC.

Results: This meta-analysis included 20 articles and 1,559 RCC patients. The results showed that the high expression of oncogenic circRNAs (OS: HR = 2.04, 95% CI: 1.63–2.56, p = 0.20; PFS: HR = 2.82, 95% CI: 0.82–9.72, p = 0.03) and low expression of tumor-suppressor circRNAs (OS: HR: 1.92, 95% CI: 1.61–2.30, p < 0.05; PFS: HR: 2.40, 95% CI: 1.76–3.28, p = 0.36) were closely related to poor survival outcomes.

Conclusion: The meta-analysis verifies that circRNAs can be potential prognostic biomarkers of RCC.
First-Principles Calculations of the Exchange Interaction of the CrGeTe3/NiO Interface
Authors: Liu Xuehua , Li Zhaoyuan , Zhang Whenli , Yao Pei , Zhu Haoran , Liu Xin , Zuo Xu
Published: June 2022

Two-dimensional (2D) magnetic materials have recently attracted a great attention due to their potential applications in information processing and storage. It was observed in an experiment that the CrGeTe3/NiO heterostructure shows a higher Curie temperature and a stronger perpendicular anisotropy. This suggests that antiferromagnet NiO can be coupled with ferromagnetic CrGeTe3 by the proximity effect, which enhances ferromagnetism. However, the mechanism behind the coupling is unknown. In this work, we built a CrGeTe3/NiO heterostructure model and investigated the electronic structure and magnetic properties of the CrGeTe3/NiO interface by first-principles calculations. It is shown that the intralayer exchange interaction between the Cr atoms is ferromagnetic, and the interlayer exchange interaction between the Ni atoms and Cr atoms at the interface is antiferromagnetic. The interlayer interaction is equivalent to a magnetic field as strong as B=100.3 T applied by the NiO substrate to the CrGeTe3 layer, which results in the higher Curie temperature of CrGeTe3 observed in the experiment.
A Preliminary Review of Modified Polymethyl Methacrylate and Calcium-Based Bone Cement for Improving Properties in Osteoporotic Vertebral Compression Fractures
Authors: Gong Yining , Zhang Bo , Yan Liang
Published: June 2022

The incidence of osteoporotic vertebral compression fractures (OVCFs) increases gradually with age, resulting in different degrees of pain for patients, even possible neurological damage and deformity, which can seriously affect their quality of life. Vertebral augmentation plays an important role in the surgical treatment of OVCFs. As the most widely used bone cement material, polymethyl methacrylate (PMMA) offers inherent advantages, such as injectability, ease of handling, and cost-effectiveness. However, with its application in the clinic, some disadvantages have been found, including cytotoxicity, high polymerization temperature, high elastic modulus, and high compressive strength. To improve the mechanical properties and the biological performance of conventional PMMA bone cement, several studies have modified it by adding bioceramics, bioglass, polymer materials, nanomaterials, and other materials, which have exhibited some advantages. In addition, other alternative materials, such as calcium phosphate, calcium sulfate, and calcium silicate cements—including their modifications—have also been explored. In this review, we examined the existing research on the side-effects of conventional PMMA bone cement, modified PMMA bone cement, and other alternative materials designed to improve properties in OVCFs. An overview of various modified bone cements can help further scientific research and clinical applications.
A Novel Rabies Vaccine Based on a Recombinant Bovine Herpes Virus Type 1 Expressing Rabies Virus Glycoprotein
Authors: Zhao Caiquan , Gao Jie , Wang Yongzhi , Ji Lina , Qin Hui , Hu Wei , Yang Yang
Published: June 2022

Rabies is a highly prevalent zoonotic disease and a public health threat worldwide. Currently licensed rabies vaccines are effective but less is known which would protect cattle. This study describes the construction of a novel recombinant bovine herpes virus type I (BHV-1) expressing rabies virus glycoprotein (RABV G) instead of its gE glycoprotein (gE) by CRISPR-Cas9 and homologous recombination technology (BHV-1-ΔgE-G). Insertion of the RABV G gene is stable after 20 rounds ofin vitropassaging and the recombinant virus replicates to high titers in MDBK cells. The RABV G expresses in the recombinant virus-infected cells and on the virion surface of BHV-1-ΔgE-G. One single immunization with BHV-1-ΔgE-G-activated dendritic cells (DCs) and B cells furthermore induced a protective immune response in mice against severe lethal challenge infection. A protective level of RABV-specific virus-neutralizing antibody (VNA) was detected in intramuscular immunized mice and cattle without any clinical symptoms. This research demonstrated that the BHV-1 vector-based RABV vaccine is a potential candidate for cattle.
Epidermal Immunity and Function: Origin in Neonatal Skin
Authors: Visscher Marty O. , Carr Andrew N. , Narendran Vivek
Published: June 2022

The fascinating story of epidermal immunity begins in utero where the epidermal barrier derives from the ectoderm and evolves through carefully orchestrated biological processes, including periderm formation, keratinocyte differentiation, proliferation, cornification, and maturation, to generate a functional epidermis. Vernix caseosa derives from epidermal cells that mix with sebaceous lipids and coat the fetus during late gestation, likely to provide conditions for cornification. At birth, infants dramatically transition from aqueous conditions to a dry gaseous environment. The epidermal barrier begins to change within hours, exhibiting decreased hydration and low stratum corneum (SC) cohesion. The SC varied by gestational age (GA), transformed over the next 2–3 months, and differed considerably versus stable adult skin, as indicated by analysis of specific protein biomarkers. Regardless of gestational age, the increased infant SC proteins at 2–3 months after birth were involved in late differentiation, cornification, and filaggrin processing compared to adult skin. Additionally, the natural moisturizing factor (NMF), the product of filaggrin processing, was higher for infants than adults. This suggests that neonatal skin provides innate immunity and protection from environmental effects and promotes rapid, continued barrier development after birth. Functional genomic analysis showed abundant differences across biological processes for infant skin compared to adult skin. Gene expression for extracellular matrix, development, and fatty acid metabolism was higher for infant skin, while adult skin had increased expression of genes for the maintenance of epidermal homeostasis, antigen processing/presentation of immune function, and others. These findings provide descriptive information about infant epidermal immunity and its ability to support the newborn’s survival and growth, despite an environment laden with microbes, high oxygen tension, and irritants.
Regional Downregulation of Dopamine Receptor D1 in Bilateral Dorsal Lateral Geniculate Nucleus of Monocular Form-Deprived Amblyopia Models
Authors: Lin Dongyue , Wang Zhonghao , Chen Wei , Shen Tao , Qiu Xuan , Wei Kun , Li Jiahui , Yang Dongsheng , Wang Ping , Li Xuri , Yan Jianhua , Tang Zhongshu
Published: June 2022

Amblyopia is a common eye disease characterized by impaired best-corrected visual acuity. It starts in early childhood and leads to permanent vision reduction if left untreated. Even though many young patients with amblyopia are well treated in clinical practice, the underlying mechanism remains to be elucidated, which limits not only our understanding of this disease but also the therapeutic approach. To investigate the molecular mechanism of amblyopia, primate and rodent models of monocular-deprived amblyopia were created for mRNA screening and confirmation. We obtained 818 differentially expressed genes from the dorsal lateral geniculate nucleus (dLGN) of a primate model of amblyopia. After Gene Ontology and kyoto encyclopedia of genes and genomes (KEGG) enrichment analyses, the main enriched pathways were related to neural development. Interestingly, a particular neurotransmitter pathway, the dopaminergic pathway, was identified. The downregulation of dopamine receptor D1 (DRD1) was confirmed in both monkey and mouse samples. Furthermore, the immunofluorescence staining indicated that DRD1 expression was downregulated in both ventrolateral region of the contralateral dLGN and the dorsomedial region of the ipsilateral dLGN in the mouse model. The regions with downregulated expression of DRD1 were the downstream targets of the visual projection from the amblyopic eye. This study suggested that the downregulation of DRD1 in the LGN may be a cause for amblyopia. This may also be a reason for the failure of some clinical cases of levodopa combined with carbidopa applied to amblyopes.
A Novel Score Combining Magnetic Resonance Spectroscopy Parameters and Systemic Immune-Inflammation Index Improves Prognosis Prediction in Non-Small Cell Lung Cancer Patients With Brain Metastases After Stereotactic Radiotherapy
Authors: Guo Dong , Liu Jiafeng , Li Yanping , Chen Qingqing , Zhao Yunzheng , Guo Xinwei , Zhu Shuchai , Ji Shengjun
Published: June 2022

Objective

The aim of this study was to evaluate the prognostic significance of the combination of the magnetic resonance spectroscopy (MRS) parameters and systemic immune-inflammation index (SII) in patients with brain metastases (BMs) from non-small cell lung cancer (NSCLC) treated with stereotactic radiotherapy.

Methods

A total of 118 NSCLC patients with BM who were treated with stereotactic radiotherapy were retrospectively enrolled in this study. All patients underwent MRS and blood samples test for SII analysis before the initiation of stereotactic radiotherapy. The correlation between the parameters of MRS and SII level was assessed using Spearman’s correlation coefficient. The cutoff values for the parameters of MRS, SII, and clinical laboratory variables were defined by the receiver operating characteristic (ROC) curve analysis to quantify these predictive values. The prognostic factors of overall survival (OS) and progression-free survival (PFS) curves were assessed using the Kaplan–Meier and Cox proportional hazards models.

Results

The median follow-up time was 25 months (range, 12–49 months). The optimal cutoff point for the choline/creatine (Cho/Cr) ratio and SII were 1.50 and 480, respectively. The Cho/Cr ratio was negatively correlated with SII (rs = 0.164, p = 0.075), but there was a trend. The C-SII score was established by combining the Cho/Cr ratio and SII. Patients with both an elevated Cho/Cr ratio (>1.50) and an elevated SII (>480) were given a C-SII score of 2, and patients with one or neither were given a C-SII score of 1 or 0, respectively. The Kaplan–Meier analysis showed that a C-SII score of 2 was significantly linked with poor OS and PFS (p < 0.001 and p < 0.001, respectively). In the Cox proportional hazards model, the C-SII score independently predicted OS [hazard ratio (HR), 1.749; 95% CI, 1.176–2.601; p = 0.006] and PFS (HR, 2.472; 95% CI, 1.624–3.763; p < 0.001).

Conclusion

The C-SII score was more accurate for predicting the clinical outcomes of NSCLC patients with BM who underwent stereotactic radiotherapy. The C-SII score, which was superior to either score alone, could be used to identify BM in NSCLC patients with poor outcomes.
Perineural Invasion Is a Significant Indicator of High Malignant Degree and Poor Prognosis in Esophageal Cancer: A Systematic Review and Meta-Analysis
Authors: Bai Liuyang , Yan Liangying , Guo Yaping , He Luyun , Sun Zhiyan , Cao Wenbo , Lu Jing , Mo Saijun
Published: June 2022

Background

Perineural invasion (PNI) is a malignant metastatic mode of tumors and has been reported in many tumors including esophageal cancer (EC). However, the role of PNI in EC has been reported differently. This systematic review and meta-analysis aims to focus on the role of PNI in EC.

Methods

Eight databases of CNKI, VIP, Wanfang, Scopus, Wiley, ISI, PubMed, and EBSCO are used for literature search. The association of PNI with gender, pathological stages of T and N (pT and pN), lymphovascular invasion (LVI), lymph node metastasis, 5-year overall survival (OS), and 5-year disease-free survival (DFS) was examined in the meta-analysis by Revman5.0 Software. The pooled OR/HR and 95% CI were used to assess the risk and prognostic value.

Results

Sixty-nine published studies were screened for analysis of PNI in EC. The incidence of PNI in esophageal squamous carcinoma (ESCC) and esophageal adenocarcinoma (EAC) was different, but not statistically significant (p > 0.05). The PNI-positive patients had a significantly higher risk of pT stage (OR = 3.85, 95% CI = 2.45–6.05, p < 0.00001), pN stage (OR = 1.86, 95% CI = 1.52–2.28, p < 0.00001), LVI (OR = 2.44, 95% CI = 1.55–3.85, p = 0.0001), and lymph node metastasis (OR = 2.87, 95% CI = 1.56–5.29, p = 0.0007). Furthermore, the cumulative analysis revealed a significant correlation between PNI and poor OS (HR = 1.37, 95% CI = 1.24–1.51, p < 0.0001), as well as poor DFS (HR = 1.55, 95% CI = 1.38–1.74, p < 0.0001).

Conclusion

PNI occurrence is significantly related to tumor stage, LVI, lymph node metastasis, OS, and DFS. These results indicate that PNI can serve as an indicator of high malignant degree and poor prognosis in EC.
Cyclin-Dependent Kinase Inhibitors Function as Potential Immune Regulators via Inducing Pyroptosis in Triple Negative Breast Cancer
Authors: Xu Tao , Wang Zhen , Liu Jiahao , Wang Ge , Zhou Dongchen , Du Yaying , Li Xingrui , Xia Yu , Gao Qinglei
Published: June 2022

Background

Immunotherapy is the most promising treatment in triple-negative breast cancer (TNBC), and its efficiency is largely dependent on the intra-tumoral immune cells infiltrations. Thus, novel ways to assist immunotherapy by increasing immune cell infiltrations were highly desirable.

Methods

To find key immune-related genes and discover novel immune-evoking molecules, gene expression profiles of TNBC were downloaded from Gene Expression Omnibus (GEO). Single-sample gene set enrichment analysis (ssGSEA) and Weighted Gene Co-expression Network Analysis (WGCNA) were conducted to identified hub genes. The CMap database was used subsequently to predicate potential drugs that can modulate the overall hub gene expression network. In vitro experiments were conducted to assess the anti-tumor activity and the pyroptosis phenotypes induced by GW-8510.

Results

Gene expression profiles of 198 TNBC patients were downloaded from GEO dataset GSE76124, and ssGSEA was used to divide them into Immune Cell Proficiency (ICP) group and Immune Cell Deficiency (ICD) group. Hub differential expressed gene modules between two groups were identified by WGCNA and then annotated by Gene Ontology (GO) annotation and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis. A cyclin-dependent kinase (CDK) 2 inhibitor, GW-8510 was then identified by the CMap database and further investigated. Treatment with GW-8510 resulted in potent inhibition of TNBC cell lines. More importantly, in vitro and in vivo studies confirmed that GW-8510 and other CDK inhibitors (Dinaciclib, and Palbociclib) can induce pyroptosis by activating caspase-3 and GSDME, which might be the mechanism for their immune regulation potentials.

Conclusion

GW-8510, as well as other CDK inhibitors, might serve as potential immune regulators and pyroptosis promotors in TNBC.
Bioenergetic Phenotyping of DEN-Induced Hepatocellular Carcinoma Reveals a Link Between Adenylate Kinase Isoform Expression and Reduced Complex I-Supported Respiration
Authors: McLaughlin Kelsey L. , Nelson Margaret A.M. , Coalson Hannah S. , Hagen James T. , Montgomery McLane M. , Wooten Ashley R. , Zeczycki Tonya N. , Vohra Nasreen A. , Fisher-Wellman Kelsey H.
Published: June 2022

Hepatocellular carcinoma (HCC) is the most common form of liver cancer worldwide. Increasing evidence suggests that mitochondria play a central role in malignant metabolic reprogramming in HCC, which may promote disease progression. To comprehensively evaluate the mitochondrial phenotype present in HCC, we applied a recently developed diagnostic workflow that combines high-resolution respirometry, fluorometry, and mitochondrial-targeted nLC-MS/MS proteomics to cell culture (AML12 and Hepa 1-6 cells) and diethylnitrosamine (DEN)-induced mouse models of HCC. Across both model systems, CI-linked respiration was significantly decreased in HCC compared to nontumor, though this did not alter ATP production rates. Interestingly, CI-linked respiration was found to be restored in DEN-induced tumor mitochondria through acute in vitro treatment with P1, P5-di(adenosine-5′) pentaphosphate (Ap5A), a broad inhibitor of adenylate kinases. Mass spectrometry-based proteomics revealed that DEN-induced tumor mitochondria had increased expression of adenylate kinase isoform 4 (AK4), which may account for this response to Ap5A. Tumor mitochondria also displayed a reduced ability to retain calcium and generate membrane potential across a physiological span of ATP demand states compared to DEN-treated nontumor or saline-treated liver mitochondria. We validated these findings in flash-frozen human primary HCC samples, which similarly displayed a decrease in mitochondrial respiratory capacity that disproportionately affected CI. Our findings support the utility of mitochondrial phenotyping in identifying novel regulatory mechanisms governing cancer bioenergetics.
Molecular Mechanism of β-Sitosterol and its Derivatives in Tumor Progression
Authors: Bao Xingxun , Zhang Yanan , Zhang Hairong , Xia Lei
Published: June 2022

β-Sitosterol (SIT), a white powdery organic substance with a molecular formula of C29H50O, is one of the most abundant naturally occurring phytosterols in plants. With a chemical composition similar to that of cholesterol, SIT is applied in various fields such as medicine, agriculture, and chemical industries, owing to its unique biological and physicochemical properties. Modern pharmacological studies have elucidated good anti-tumor therapeutic effect activity of SIT, which mainly manifests as pro-apoptotic, anti-proliferative, anti-metastatic, anti-invasive, and chemosensitizing on tumor cells. In addition, SIT exerts an anti-tumor effect on multiple malignant tumors such as breast, gastric, lung, kidney, pancreatic, prostate, and other cancers. Further, SIT derivatives with structural modifications are promising anti-tumor drugs with significant anti-tumor effects. This review article focuses on recent studies relevant to the anti-tumor effects of SIT and summarizes its anti-tumor mechanism to provide a reference for the clinical treatment of malignant tumors and the development of novel anti-tumor drugs.
Substrates and Loaded Iron Ions Relative Position Influence the Catalytic Characteristics of the Metalloenzymes Angelica archangelica Flavone Synthase I and Camellia sinensis Flavonol Synthase
Authors: Wang Zhen , Liu An , Liu Juan , Huang Xu , Xiao Feiyao , Tian Miaomiao , Ding Shenghua , Qin Si , Shan Yang
Published: June 2022

Metalloenzymes are a class of enzymes that catalyze through the metal ions they load. Angelica archangelica flavone synthase I (AnFNS I) and Camellia sinensis flavonol synthase (CaFLS), both of which belong to metalloenzymes, have highly similar structures and metal catalytic cores. However, these two enzymes catalyze the same substrate to produce significantly different products. To identify the cause for the differences in the catalytic characteristics of AnFNS I and CaFLS, their protein models were constructed using homology modeling. Structural alignment and molecular docking was also used to elucidate the molecular basis of the differences observed. To analyze and verify the cause for the differences in the catalytic characteristics of AnFNS I and CaFLS, partial fragments of AnFNS I were used to replace the corresponding fragments on CaFLS, and the catalytic characteristics of the mutants were determined by bioconversion assay in E. coli and in vitro catalytic test. The results suggest that the difference in catalytic characteristics between AnFNS I and CaFLS is caused by the depth of the active pockets and the relative position of the substrate. Mutant 10 which present similar dock result with AnFNS I increased the proportion of diosmetin (a flavone) from 2.54 to 16.68% and decreased the proportion of 4′-O-methyl taxifolin (a flavanol) from 47.28 to 2.88%. It was also indicated that the atoms in the substrate molecule that determine the catalytic outcome may be H-2 and H-3, rather than C-2 and C-3. Moreover, it is speculated that the change in the catalytic characteristics at the changes relative spatial position of H-2/H-3 of hesperetin and the loaded carbonyl iron, caused by charged residues at the entrance of the active pocket, is the key factor for the biosynthesis of flavone from flavanone.
Systematic Bibliometric and Visualized Analysis of Research Hotspots and Trends on the Application of Artificial Intelligence in Ophthalmic Disease Diagnosis
Authors: Zhao Junqiang , Lu Yi , Zhu Shaojun , Li Keran , Jiang Qin , Yang Weihua
Published: June 2022

Background: Artificial intelligence (AI) has been used in the research of ophthalmic disease diagnosis, and it may have an impact on medical and ophthalmic practice in the future. This study explores the general application and research frontier of artificial intelligence in ophthalmic disease detection.

Methods: Citation data were downloaded from the Web of Science Core Collection database to evaluate the extent of the application of Artificial intelligence in ophthalmic disease diagnosis in publications from 1 January 2012, to 31 December 2021. This information was analyzed using CiteSpace.5.8. R3 and Vosviewer.

Results: A total of 1,498 publications from 95 areas were examined, of which the United States was determined to be the most influential country in this research field. The largest cluster labeled “Brownian motion” was used prior to the application of AI for ophthalmic diagnosis from 2007 to 2017, and was an active topic during this period. The burst keywords in the period from 2020 to 2021 were system, disease, and model.

Conclusion: The focus of artificial intelligence research in ophthalmic disease diagnosis has transitioned from the development of AI algorithms and the analysis of abnormal eye physiological structure to the investigation of more mature ophthalmic disease diagnosis systems. However, there is a need for further studies in ophthalmology and computer engineering.
A Poultry Subclinical Necrotic Enteritis Disease Model Based on Natural Clostridium perfringens Uptake
Authors: He Wanwei , Goes Emanuele C. , Wakaruk Jeremy , Barreda Daniel R. , Korver Douglas R.
Published: June 2022

Necrotic enteritis (NE) in poultry is an opportunistic infection caused by Clostridium perfringens. Well-known as a multifactorial disease, NE development is under the influence of a wide range of environmental risk factors that promote the proliferation of pathogenic C. perfringens at the expense of nonpathogenic strains. Current in vivo NE challenge models typically incorporate pre-exposure to disease risk factors, in combination with exogenous C. perfringens inoculation. Our goal was to enhance current models using a natural uptake of C. perfringens from the barn environment to produce a subclinical infection. We incorporated access to litter, coccidial exposure (either 10× or 15× of the manufacturer-recommended Coccivac B52 Eimeria vaccine challenge; provided unspecified doses of E. acervulina, E. mivati, E. tenella, and two strains of E. maxima), feed composition, and feed withdrawal stress, and achieved the commonly observed NE infection peak at 3 weeks post-hatch. NE severity was evaluated based on gut lesion pathology, clinical signs, and mortality rate. Under cage-reared conditions, 15× coccidial vaccine-challenged birds showed overall NE lesion prevalence that was 8-fold higher than 10× coccidial vaccine-challenged birds. NE-associated mortality was observed only in a floor-reared flock after a 15× coccidial vaccine challenge.
An Anthocyanin-Related Glutathione S-Transferase, MrGST1, Plays an Essential Role in Fruit Coloration in Chinese Bayberry (Morella rubra)
Authors: Xue Lei , Huang Xiaorong , Zhang Zehuang , Lin Qihua , Zhong Qiuzhen , Zhao Yun , Gao Zhongshan , Xu Changjie
Published: June 2022

Chinese bayberry (Morella rubra) is a fruit tree economically important in China and accumulates abundant amounts of anthocyanins in fruit as it ripens. Owing to the fact that all anthocyanin containing fruit tissues in Chinese bayberry are edible and anthocyanins can provide various health benefits in human body, the mechanisms underpinning anthocyanin accumulation in this fruit are worthy of investigation. It has been known that in plants anthocyanins are synthesized in the cytoplasmic surface of the endoplasmic reticulum and subsequently transported into the vacuole for storage, and glutathione S-transferases (GSTs) have been verified to be involved in this process. But the characterization and functionalization of the GST counterpart in Chinese bayberry is not available. The GST anthocyanin transporter MrGST1 was discovered to be related with anthocyanin accumulation in fruit from distinct developmental stages of “Biqi,” a staple cultivar that accumulates over 1 mg/g anthocyanins in ripe fruit. The expression of MrGST1 was well associated with anthocyanin accumulation either in fruit collected at six developmental stages or in ripe fruit from 12 cultivars. MrGST1 was found to be responsible for the transport of anthocyanins but not proanthocyanidins when the Arabidopsis tt19 mutant was functionally complemented. Transient ectopic expression of MrGST1 in combination with MrMYB1.1 and MrbHLH1 dramatically boosted pigmentation in Nicotiana tabacum leaves in contrast to MrMYB1.1 and MrbHLH1. The promoter of MrGST1 comprised eight MYB binding sites (MBSs) according to cis-element analysis. Data from yeast one-hybrid assay and dual-luciferase tests demonstrated that MrMYB1.1 exerted considerable transactivation effect on the MrGST1 promoter by recognizing the MBS4, the fourth MBS from the ATG start site. Our results together provided molecular evidence for the contribution of MrGST1 in regulating anthocyanin accumulation in Chinese bayberry fruit.
The Pm5e Gene Has No Negative Effect on Wheat Agronomic Performance: Evidence From Newly Established Near-Isogenic Lines
Authors: Qiu Dan , Huang Jiang , Guo Guanghao , Hu Jinghuang , Li Yahui , Zhang Hongjun , Liu Hongwei , Yang Li , Zhou Yang , Yang Benzhou , Zhang Yudan , Liu Zhiyong , Li Hongjie
Published: June 2022

Wheat genotypes resistant to powdery mildew (Blumeria graminis f. sp. tritici, Bgt) provide a sustainable means for disease control. We developed a pair of near-isogenic lines H962R and H962S with contrasting reactions to powdery mildew from a residue heterozygous line. H962R was resistant to 127 out of the 136 Bgt isolates collected from the major wheat-producing regions of China and showed a similar virulence/avirulence pattern as Fuzhuang 30, Xiaobaidong, and Hongquanmang carrying resistance allele of Pm5e, but H962S was resistant to none of them. A dominant gene was responsible for the powdery mildew resistance of H962R as revealed by the genetic analysis using segregating populations derived from a cross between H962R and H962S. Molecular marker analysis detected a resistance locus, designated PmH962, on a genetic interval of the chromosome arm 7BL where Pm5e resides. This locus was co-segregated with the functional marker of Pm5e. The PCR-based sequence alignment of Pm5e demonstrated that H962R had an identical sequence as Fuzhuang 30 (haplotype HapGA), and H962S possessed the same sequence as the powdery mildew susceptible cultivar Kenong 199. The genomic compositions of lines H962R and H962S were highly comparable as evidenced by only a small percentage of SNP variations detected by the 16K Genotyping by Target Sequencing (GBTS) SNP array and the 90K Illumina iSelect Wheat SNP array. The two lines performed similarly in the yield-related and plant growth traits investigated, except for greater kernel weight in H962R than in H962S. This indicates that Pm5e has no deleterious effect and can be served as an excellent disease resistance gene in wheat breeding.
Initial Motivations for Choosing Teaching as a Career
Authors: Alvariñas-Villaverde Myriam , Domínguez-Alonso José , Pumares-Lavandeira Lucía , Portela-Pino Iago
Published: June 2022

The objective of the study is to verify the reliability and validity of the Factors Influencing Teaching Choice, as well as to determine the teaching of Early childhood and Primary education students’ motivations and perceptions for the choice of this degree. The sample consisted of 262 student teachers aged between 18 and 27 (83.2% female and 16.8% male). According to degree, 54.2% of the participants were enrolled in Early Childhood Education and 45.8% in Primary Education. The instrument used in the study was the Factors Influencing Teaching Choice, FIT-Choice Scale, adapted to Spanish by Gratacós and López-Jurado. Results evidenced the high reliability and validity of the scale that is similar to the original model, presenting 12 motivational factors and 6 perceptions. The main reasons that lead to choose teaching profession, despite gender differences, are: having influence in the educational children’s process, the intrinsic value of the qualification, the fact that this profession contributes socially, or working with children. Also, students consider that teaching is a demanding profession and they are satisfied with the degree choice. The most important factors influencing the choice of education degree are intrinsic motivations and perceptions as the vocation, in contrast to external reasons such as economic incentives or social recognition.
The Impact of Online Reviews on Consumers’ Purchasing Decisions: Evidence From an Eye-Tracking Study
Authors: Chen Tao , Samaranayake Premaratne , Cen XiongYing , Qi Meng , Lan Yi-Chen
Published: June 2022

This study investigated the impact of online product reviews on consumers purchasing decisions by using eye-tracking. The research methodology involved (i) development of a conceptual framework of online product review and purchasing intention through the moderation role of gender and visual attention in comments, and (ii) empirical investigation into the region of interest (ROI) analysis of consumers fixation during the purchase decision process and behavioral analysis. The results showed that consumers’ attention to negative comments was significantly greater than that to positive comments, especially for female consumers. Furthermore, the study identified a significant correlation between the visual browsing behavior of consumers and their purchase intention. It also found that consumers were not able to identify false comments. The current study provides a deep understanding of the underlying mechanism of how online reviews influence shopping behavior, reveals the effect of gender on this effect for the first time and explains it from the perspective of attentional bias, which is essential for the theory of online consumer behavior. Specifically, the different effects of consumers’ attention to negative comments seem to be moderated through gender with female consumers’ attention to negative comments being significantly greater than to positive ones. These findings suggest that practitioners need to pay particular attention to negative comments and resolve them promptly through the customization of product/service information, taking into consideration consumer characteristics, including gender.