bluuebunny/crossref_metadata_2025 huggingface dataset:
EVALUATION BY RUBRIC OF SOLIDARITY IN ACQUISITION SKILLS COLLEGE
Authors: Morales Rodríguez Francisco Manuel
Published: September 2021

The European Higher Education Area involves major changes in the teaching-learning process for the acquisition of transversal skills, such as social and citizens. It establishes a need for active methods, learning and so to develop in students the ability to make decisions and learn independently, reflective and critical promoting these skills. Considering the importance of a program, training in values and ethics of solidarity that joins the university curriculum (educational innovation program, PIE10-127), we performed a comparative study on ethical issues in college students before and after of their application the program and an evaluation of effectiveness of different active methodologies to promote solidarity skills acquisition, and its impact on performance. Participants in this study were 4103 university students, aged 18 and 57, of the Faculty of Psychology and Educational Sciences of the University of Málaga (2010-2012). The results show an increase in the acquisition of skills solidarity, following the implementation of the program and that the methodologies employed active, positive impact on academic performance. The relevant conclusion obtained, points to the need to reinforce and develop these values solidarity actions in college.
Key words: academic performance, active methods, values, solidarity.
LACK OF INTEREST IN SCHOOL SCIENCE AMONG NON-SCIENCE STUDENTS AT THE SENIOR HIGH SCHOOL LEVEL
Authors: Adu-Gyamfi Kenneth
Published: September 2021

This study investigated the factors that contribute to the non-science students’ lack of interest in school science through the use of a 27-item questionnaire. This assisted in comparing the male and female non-science students’ lack of interest in school science. There were 259 male and female students from three senior high schools in three District Assemblies of the Ashanti Region of Ghana who participated in the study. Quantitative data were collected from the 259 students through a cross-sectional survey. The research questions were answered with mean, standard deviation, percentage, boxplot, and independent-samples t-test. The results of the study have shown that the factors that contribute to students’ lack of interest in school science include as higher demands of students’ time in learning science, less practical nature of science teaching and learning, failure of science students with larger aggregate from high school to gain admission into tertiary institutions, too broad nature of science content, lack of sponsorship for science students, school science as difficult subject compared to others, and teaching of science is a transmission of knowledge from science teachers or textbooks to students. The results of the study have further shown that there was a statistical significant difference between the mean scores of male and female non-science students’ lack of interest in school science. Science teachers are therefore encouraged to adopt strategies that could encourage students to develop and show interest in science related subjects and courses.
Key words: factors; lack of interest; male and female; non-science students; school science.
THE EUROPEAN PORTFOLIO OF LANGUAGES: ITS IMPACT AND DEVELOPMENT IN ALBANIA
Authors: Tamo Daniela , Rira Shpresa , Xhillari Rudina
Published: September 2021

Generally speaking, teaching and learning could be better carried out through discussions and debates with others, and the results obtained in this way then turn into means of encouraging, helping, stimulating and informing thus making it possible for us to achieve an individual reflection.
There might be people who try to link the word Portfolio with the world of Arts and Projects. This is true to some extend but there exist other components such as the Language Section and Language Biography, which in fact are closely connected with the world of learning and teaching and are part of the guidelines approved by the Council of Europe (Portofoli Evropian i Gjuhëve: Një Udhëzues për Mësuesit dhe Trajnuesit e Mësuesve, Ministria e Arsimit dhe Shkencës, Këshilli i Europës, 2005.)
As a result of the use of Portfolio of Languages the teaching aims became clearer, students started to see their progress with ease. It served as a motivation for all, quick and slow learners, it helped increase self-awareness, it developed critical thinking, etc. It improved teachers’ motivation, their reflecting ability and encouraged them to undertake initiatives during the teaching process.
Key words: activity, approach, assessment, curriculum, evaluation, function, integration, motivation pilot, portfolio, project, reflection.
Algoritmo de detección de líneas aplicado a la mejora de los procesos de calibración del microscopio LEXT OLYMPUS.
Authors: Bergues Guillermo Juan , Schürrer Clemar , Caselles Juan , Brambilla Nancy
Published: September 2021

En este trabajo se presenta un método para procesar imágenes para optimizar la calibración de microscopios ópticos Lext Olympus con plantillas. El algoritmo propuesto ya funciona en las escalas de los autocolimadores Nikon, que son similares a las presentes en las plantillas de calibración de estos microscopios. El algoritmo fue adaptado para medir estas plantillas y así optimizar la calibración.
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Variaciones en método de síntesis de UiO-66-NH2 para esterificación catalítica del ácido levulínico
Authors: Bravo Fuchineco Daiana Antonella , Heredia Angélica Constanza , Rodríguez Castellón Enrique , Crivello Mónica Elsie
Published: September 2021

La creciente tendencia al reemplazo parcial de los combustibles derivados del petróleo por aquellos provenientes de la revalorización de biomasa ha tomado gran importancia en el último tiempo. Es por ello que el presente trabajo propone la obtención de ésteres levulínicos mediante una reacción catalítica de esterificación del ácido levulínico, molécula plataforma, con diferentes alcoholes. Para ello se han sintetizado nanocatalizadores  MOFs, que fueron utilizados como catalizadores (UiO-66-NH2), constituidos por circonio como fuente metálica y ácido aminotereftálico como agente ligante orgánico. Se presenta una alternativa de síntesis mediante agitación por vía ultrasónica a temperatura de 60 ºC y una variación en el tiempo de mufla. La finalidad fue lograr una síntesis en condiciones más favorables y mejorar las propiedades estructurales de los catalizadores. Las mismas fueron analizadas por difracción de rayos X, espectroscopía infrarroja,  microscopía electrónica de barrido, espectroscopia de emisión atómica de plasma de microondas,  isotermas de adsorción de N2 y espectrometría de fotoelectrones inducidos por rayos X. El progreso de la reacción catalítica fue seguido por cromatografía gaseosa y espectroscopía de masa. Se optimizaron parámetros como temperatura, masa de catalizador y relación molar de reactivos, buscando mejorar el rendimiento catalítico. Para todos los esteres levulínicos, el MOF que presentó la mayor actividad y selectividad al producto deseado fue el obtenido con un tiempo de síntesis de 6hs, con un rendimiento de 77,54 % a levulinato de metilo, de 34,58 % a levulinato de etilo y de 31,41 % a levulinato de butilo.
OSMANLI DEVLETİ’NDE CİNSEL SALDIRI SUÇLARI: 1869 VAKÂYİ-İ ZABTİYE GAZETESİ ÖRNEĞİ
Authors: KIZILAY Muhammed Emin
Published: September 2021

Tanzimat sonrası dönemde Osmanlı Devleti’nde birçok alanda yenileşme ve değişim hareketleri yaşanmıştır. Bu değişim ve yenileşmenin yargı alanındaki yansıması ise yeni mahkemelerin kurulması ve klasik fıkhın bazı konuları ile ilgili davalara bakma yetkisinin bu mahkemelere verilmesidir. Ne var ki bu mahkemelere ait kayıtlara ulaşmak çok kolay olmamakta, ulaşılan kayıtlarda ise konu bazlı tasnif yapılmadığından teorik anlamda istenilen çalışmalar yapılamamaktadır. Tanzimat Dönemi’nin getirdiği yeniliklerden biri olan basının yaygınlaşması sonucu yayımlanmaya başlayan bir gazete olan Vakâyi-i Zabtiyye, bu sorunu aşmada önemli bir katkı sunmaktadır. Dava kayıtlarının kamuya duyurulması maksadıyla çıkarılmaya başlanan gazete, dönemin dava kayıtlarına kolayca ulaşımı sağlamaktadır. Gazetede, İstanbul mahkemelerinde görülen ceza davalarına ait kayıtlar özet olarak yayımlanmıştır. Kayıtlar, bugün dahi toplumun muzdarip olduğu cinsel saldırı suçlarına, gazetenin yayımlandığı dönemde de sıkça rastlandığını göstermektedir. Çalışmada Türk pozitif hukukuyla karşılaştırmalı olarak kanunlaştırma sonrası Osmanlı pozitif hukukunda cinsel saldırı kapsamına giren suçlar, dava kayıtları ve bu kayıtların atıfta bulunduğu kanun metinleri üzerinden incelenecektir. Böylece bugünkü hukuk dilinin gazetenin yayımlandığı dönemlerde oluşmaya başladığı, Tanzimat sonrası dönemde yargı sisteminde hızlı ve kısmen istenilen düzeyde bir değişikliğin yaşandığı görülecektir.
Legal regulation of medical secrecy as an object of offenses of medical organizations and their employees
Authors:   Postgraduate Institute for Public Health Workers under Health Ministry of Khabarovsk Krai, Savkova V.M. , Savkov D.S. ,   Far Eastern State Medical University under Health Ministry of Russia
Published: September 2021

The article presents an analysis of the legal regulation of medical secrecy as an object of offenses by medical organizations and their employees. The requirements of the legislation of the Russian Federation, as well as materials of law enforcement practice related to the preservation of medical secrets are considered
Rehabilitation methods for pneumonia. Recommendations for patients for self-rehabilitation after illness caused by COVID-19 (part II)
Authors:   Postgraduate Institute for Public Health Workers under Health Ministry of Khabarovsk Krai, Nevrycheva E.V. , Kuzmicheva N.E. ,   Postgraduate Institute for Public Health Workers under Health Ministry of Khabarovsk Krai
Published: September 2021

The article contains a description of basic rehabilitation exercise and related guidance for adults who have been hospitalized for severe COVID-19 illness.
Bone Mesenchymal Stem Cells Promote Extracellular Matrix Remodeling of Degenerated Nucleus Pulposus Cells via the miR-101-3p/EIF4G2 Axis
Authors: Wang Zeng , Ding Xiaolin , Cao Feifei , Zhang Xishan , Wu Jingguo
Published: September 2021

The etiology of lumbocrural pain is tightly concerned with intervertebral disk degeneration (IDD). Bone mesenchymal stem cell (BMSC)-based therapy bears potentials for IDD treatment. The properties of microRNA (miRNA)-modified BMSCs may be altered. This study investigated the role and mechanism of BMSCs promoting extracellular matrix (ECM) remodeling of degenerated nucleus pulposus cells (NPCs) via the miR-101-3p/EIF4G2 axis. NPCs were collected from patients with IDD and lumbar vertebral fracture (LVF). The expressions of miR-101-3p and ECM-related proteins, Collagen-I (Col-I) and Collagen-II (Col-II), were detected using the reverse transcription-quantitative polymerase chain reaction. The expressions of Col-I and Col-II, major non-collagenous component Aggrecan, and major catabolic factor Matrix metalloproteinase-13 (MMP-13) were detected using Western blotting. BMSCs were cocultured with degenerated NPCs from patients with IDD. Viability and apoptosis of NPCs were measured using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay and flow cytometry. After the degenerated NPCs were transfected with the miR-101-3p inhibitor, the expressions of ECM-related proteins, cell viability, and apoptosis were detected. The targeting relationship between miR-101-3p and EIF4G2 was verified. Functional rescue experiments verified the effects of miR-101-3p and EIF4G2 on ECM remodeling of NPCs. Compared with the NPCs of patients with LVF, the degenerated NPCs of patients with IDD showed downregulated miR-101-3p, Col-II, and Aggrecan expressions and upregulated MMP-13 and Col-I expressions. BMSCs increased the expressions of miR-101-3p, Aggrecan, and Col-II, and decreased the expressions of MMP-13 and Col-I in degenerated NPCs. BMSCs enhanced NPC viability and repressed apoptosis. Downregulation of miR-101-3p suppressed the promoting effect of BMSCs on ECM remodeling. miR-101-3p targeted EIF4G2. Downregulation of EIF4G2 reversed the inhibiting effect of the miR-101-3p inhibitor on ECM remodeling. In conclusion, BMSCs increased the miR-101-3p expression in degenerated NPCs to target EIF4G2, thus promoting the ECM remodeling of NPCs.
Boost Tendon/Ligament Repair With Biomimetic and Smart Cellular Constructs
Authors: Zhao Jianping , Wang Xiang , Han Jinyu , Yu Yin , Chen Fei , Yao Jun
Published: September 2021

Tendon and ligament are soft connective tissues that play essential roles in transmitting forces from muscle to bone or bone to bone. Despite significant progress made in the field of ligament and tendon regeneration over the past decades, many strategies struggle to recapitulate basic structure-function criteria of native ligament/tendon. The goal here is to provide a fundamental understanding of the structure and composition of ligament/tendon and highlight few key challenges in functional regeneration of these connective tissues. The remainder of the review will examine several biomaterials strategies including biomimetic scaffold with non-linear mechanical behavior, hydrogel patch with anisotropic adhesion and gene-activated scaffold for interactive healing of tendon/ligament. Finally, emerging technologies and research avenues are suggested that have the potential to enhance treatment outcomes of tendon/ligament injuries.
Exosomes Derived From Human Adipose-Derived Stem Cells Inhibit Lipogenesis Involving Hedgehog Signaling Pathway
Authors: Ji Ziwan , Cai Zhongming , Gu Shuming , He Yucang , Zhang Zikai , Li Tian , Wei Qing , Wang Jingping , Ke Chen , Li Liqun
Published: September 2021

Since obesity impairs wound closure and adipose-derived exosomes (ADEs) regulate wound healing in clinical applications, we hypothesized that ADEs may inhibit adipogenesis of adipose-derived stem cells (ADSCs) to reduce the adverse effects of obesity on wound healing. Hedgehog (Hh) signaling has been previously shown to inhibit adipogenesis in ADSCs. The present study aimed to determine the role of ADEs in the adipogenesis of ADSCs and the Hh signaling pathway. ADSCs collected from human adipose tissues were co-cultured with ADEs and treated with an adipogenic inducer. qRT-PCR showed that ADEs could inhibit adipogenic differentiation of ADSCs and activate Hh signaling. The differences in the mRNA expression profiles of genes related to Hh signaling between the groups that were exposed to either high fat or low fat indicated that increased Hh signaling activation is necessary but not sufficient to inhibit adipogenic differentiation in the ADSC differentiation process. The Hh signaling pathway can be activated effectively by ADEs, especially during high-fat exposure after treatment with ADEs. Oil Red O staining of adipocytes suggested that ADEs inhibited not only adipogenic differentiation, but also lipogenesis in ADSCs. Overall, targeted activation of Hh signaling by ADEs reduced lipid accumulation in ADSCs and may be explored for clinical applications.
Novel Characterization of Myeloid-Derived Suppressor Cells in Tumor Microenvironment
Authors: Li Yanan , He Hongdan , Jihu Ribu , Zhou Junfu , Zeng Rui , Yan Hengxiu
Published: September 2021

Myeloid-derived suppressor cells (MDSCs) are a heterogeneous group of cells generated in various pathologic conditions, which have been known to be key components of the tumor microenvironment (TME) involving in tumor immune tolerance. So MDSCs have been extensively researched recently. As its name suggests, immunosuppression is the widely accepted function of MDSCs. Aside from suppressing antitumor immune responses, MDSCs in the TME also stimulate tumor angiogenesis and metastasis, thereby promoting tumor growth and development. Therefore, altering the recruitment, expansion, activation, and immunosuppression of MDSCs could partially restore antitumor immunity. So, this view focused on the favorable TME conditions that promote the immunosuppressive effects of MDSCs and contribute to targeted therapies with increased precision for MDSCs.
Comprehensive Analysis of a Nine-Gene Signature Related to Tumor Microenvironment in Lung Adenocarcinoma
Authors: Zhong Haihui , Wang Jie , Zhu Yaru , Shen Yefeng
Published: September 2021

Lung adenocarcinoma (LUAD) is the most common malignancy, leading to more than 1 million related deaths each year. Due to low long-term survival rates, the exploration of molecular mechanisms underlying LUAD progression and novel prognostic predictors is urgently needed to improve LUAD treatment. In our study, cancer-specific differentially expressed genes (DEGs) were identified using the robust rank aggregation (RRA) method between tumor and normal tissues from six Gene Expression Omnibus databases (GSE43458, GSE62949, GSE68465, GSE115002, GSE116959, and GSE118370), followed by a selection of prognostic modules using weighted gene co-expression network analysis. Univariate Cox regression, least absolute shrinkage and selection operator (LASSO), and multivariate Cox regression analyses were applied to identify nine hub genes (CBFA2T3, CR2, SEL1L3, TM6SF1, TSPAN32, ITGA6, MAPK11, RASA3, and TLR6) that constructed a prognostic risk model. The RNA expressions of nine hub genes were validated in tumor and normal tissues by RNA-sequencing and single-cell RNA-sequencing, while immunohistochemistry staining from the Human Protein Atlas database showed consistent results in the protein levels. The risk model revealed that high-risk patients were associated with poor prognoses, including advanced stages and low survival rates. Furthermore, a multivariate Cox regression analysis suggested that the prognostic risk model could be an independent prognostic factor for LUAD patients. A nomogram that incorporated the signature and clinical features was additionally built for prognostic prediction. Moreover, the levels of hub genes were related to immune cell infiltration in LUAD microenvironments. A CMap analysis identified 13 small molecule drugs as potential agents based on the risk model for LUAD treatment. Thus, we identified a prognostic risk model including CBFA2T3, CR2, SEL1L3, TM6SF1, TSPAN32, ITGA6, MAPK11, RASA3, and TLR6 as novel biomarkers and validated their prognostic and predicted values for LUAD.
Synovial Fluid of Patient With Rheumatoid Arthritis Enhanced Osmotic Sensitivity Through the Cytotoxic Edema Module in Synoviocytes
Authors: Ji Min Jeong , Ryu Hee Jung , Hong Jeong Hee
Published: September 2021

Rheumatoid arthritis (RA) is an autoimmune disease that causes inflammation of the synovial membrane ultimately leading to permanent damage in the affected joints. For this study, synovial fluids from 16 patients diagnosed with either RA or osteoarthritis (OA) were used to examine volume regulation and cooperative water channels, both of which are involved in the cytotoxic edema identified in RA-fibroblast-like synoviocytes (FLS). The osmolarity and inflammatory cytokine interleukin (IL)-6 of synovial fluids from RA patients were mildly enhanced compared to that from OA patients. RA-FLS demonstrated the enhanced property of regulatory volume increase in response to IL-6 and synovial fluids from RA patients. Although there was no difference in the protein expression of the volume-associated protein sodium–potassium–chloride cotransporter1 (NKCC1), its activity was increased by treatment with IL-6. Membrane localization of NKCC1 was also increased by IL-6 treatment. Additionally, both the protein and membrane expressions of aquaporin-1 were increased in RA-FLS by IL-6 stimulation. The IL-6-mediated enhanced osmotic sensitivity of RA-FLS likely involves NKCC1 and aquaporin-1, which mainly constitute the volume-associated ion transporter and water channel elements. These results suggest that RA-FLS provide enhanced electrolytes and concomitant water movement through NKCC1 and aquaporin-1, thereby inducing cellular swelling ultimately resulting in cytotoxic edema. Attenuation of cytotoxic edema and verification of its related mechanism will provide novel therapeutic approaches to RA treatment within the scope of cytotoxic edema.
Advances in Understanding Leishmania Pathobiology: What Does RNA-Seq Tell Us?
Authors: Salloum Tamara , Tokajian Sima , Hirt Robert P.
Published: September 2021

Leishmaniasis is a vector-borne disease caused by a protozoa parasite from over 20 Leishmania species. The clinical manifestations and the outcome of the disease vary greatly. Global RNA sequencing (RNA-Seq) analyses emerged as a powerful technique to profile the changes in the transcriptome that occur in the Leishmania parasites and their infected host cells as the parasites progresses through their life cycle. Following the bite of a sandfly vector, Leishmania are transmitted to a mammalian host where neutrophils and macrophages are key cells mediating the interactions with the parasites and result in either the elimination the infection or contributing to its proliferation. This review focuses on RNA-Seq based transcriptomics analyses and summarizes the main findings derived from this technology. In doing so, we will highlight caveats in our understanding of the parasite’s pathobiology and suggest novel directions for research, including integrating more recent data highlighting the role of the bacterial members of the sandfly gut microbiota and the mammalian host skin microbiota in their potential role in influencing the quantitative and qualitative aspects of leishmaniasis pathology.
A Novel Classifier Based on Urinary Proteomics for Distinguishing Between Benign and Malignant Ovarian Tumors
Authors: Ni Maowei , Zhou Jie , Zhu Zhihui , Yuan Jingtao , Gong Wangang , Zhu Jianqing , Zheng Zhiguo , Zhao Huajun
Published: September 2021

Background

Preoperative differentiation of benign and malignant tumor types is critical for providing individualized treatment interventions to improve prognosis of patients with ovarian cancer. High-throughput proteomics analysis of urine samples was performed to identify reliable and non-invasive biomarkers that could effectively discriminate between the two ovarian tumor types.

Methods

In total, 132 urine samples from 73 malignant and 59 benign cases of ovarian carcinoma were divided into C1 (training and test datasets) and C2 (validation dataset) cohorts. Mass spectrometry (MS) data of all samples were acquired in data-independent acquisition (DIA) mode with an Orbitrap mass spectrometer and analyzed using DIA-NN software. The generated classifier was trained with Random Forest algorithm from the training dataset and validated in the test and validation datasets. Serum CA125 and HE4 levels were additionally determined in all patients. Finally, classification accuracy of the classifier, serum CA125 and serum HE4 in all samples were evaluated and plotted via receiver operating characteristic (ROC) analysis.

Results

In total, 2,199 proteins were quantified and 69 identified with differential expression in benign and malignant groups of the C1 cohort. A classifier incorporating five proteins (WFDC2, PTMA, PVRL4, FIBA, and PVRL2) was trained and validated in this study. Evaluation of the performance of the classifier revealed AUC values of 0.970 and 0.952 in the test and validation datasets, respectively. In all 132 patients, AUCs of 0.966, 0.947, and 0.979 were achieved with the classifier, serum CA125, and serum HE4, respectively. Among eight patients with early stage malignancy, 7, 6, and 4 were accurately diagnosed based on classifier, serum CA125, and serum HE4, respectively.

Conclusion

The novel classifier incorporating a urinary protein panel presents a promising non-invasive diagnostic biomarker for classifying benign and malignant ovarian tumors.
HIV Tat-Mediated Induction of Monocyte Transmigration Across the Blood–Brain Barrier: Role of Chemokine Receptor CXCR3
Authors: Niu Fang , Liao Ke , Hu Guoku , Moidunny Shamsudheen , Roy Sabita , Buch Shilpa
Published: September 2021

HIV trans-activator of transcription (Tat), one of the cytotoxic proteins secreted from HIV-infected cells, is also known to facilitate chemokine-mediated transmigration of monocytes into the brain leading, in turn, to neuroinflammation and thereby contributing to the development of HIV-associated neurocognitive disorders (HAND). The mechanism(s) underlying HIV Tat-mediated enhancement of monocyte transmigration, however, remain largely unknown. CXC chemokine receptor 3 (CXCR3) that is expressed by the peripheral monocytes is known to play a role in the monocyte influx and accumulation. In the present study, we demonstrate for the first time that exposure of human monocytes to HIV Tat protein resulted in upregulated expression of CXCR3 leading, in turn, to increased monocyte transmigration across the blood–brain barrier (BBB) both in thein vitroandin vivomodel systems. This process involved activation of toll-like receptor 4 (TLR4), with downstream phosphorylation and activation of TANK-binding kinase 1 (TBK1), and subsequent phosphorylation and nuclear translocation of interferon regulatory factor 3 (IRF3), ultimately leading to enhanced expression of CXCR3 in human monocytes. These findings imply a novel molecular mechanism underlying HIV Tat-mediated increase of monocyte transmigration across the BBB, while also implicating a novel role of CXCR3-dependent monocyte transmigration in HIV Tat-mediated neuroinflammation.
Molecular Classification of Knee Osteoarthritis
Authors: Lv Zhongyang , Yang Yannick Xiaofan , Li Jiawei , Fei Yuxiang , Guo Hu , Sun Ziying , Lu Jun , Xu Xingquan , Jiang Qing , Ikegawa Shiro , Shi Dongquan
Published: September 2021

Knee osteoarthritis (KOA) is the most common form of joint degeneration with increasing prevalence and incidence in recent decades. KOA is a molecular disorder characterized by the interplay of numerous molecules, a considerable number of which can be detected in body fluids, including synovial fluid, urine, and blood. However, the current diagnosis and treatment of KOA mainly rely on clinical and imaging manifestations, neglecting its molecular pathophysiology. The mismatch between participants’ molecular characteristics and drug therapeutic mechanisms might explain the failure of some disease-modifying drugs in clinical trials. Hence, according to the temporal alteration of representative molecules, we propose a novel molecular classification of KOA divided into pre-KOA, early KOA, progressive KOA, and end-stage KOA. Then, progressive KOA is furtherly divided into four subtypes as cartilage degradation-driven, bone remodeling-driven, inflammation-driven, and pain-driven subtype, based on the major pathophysiology in patient clusters. Multiple clinical findings of representatively investigated molecules in recent years will be reviewed and categorized. This molecular classification allows for the prediction of high-risk KOA individuals, the diagnosis of early KOA patients, the assessment of therapeutic efficacy, and in particular, the selection of homogenous patients who may benefit most from the appropriate therapeutic agents.
Ferroptosis Driver SOCS1 and Suppressor FTH1 Independently Correlate With M1 and M2 Macrophage Infiltration in Head and Neck Squamous Cell Carcinoma
Authors: Hu Zhang-Wei , Wen Yi-Hui , Ma Ren-Qiang , Chen Lin , Zeng Xue-Lan , Wen Wei-Ping , Sun Wei
Published: September 2021

Objective

To investigate the role of ferroptosis, an iron-dependent form of non-apoptotic cell death, in the head and neck squamous cell carcinoma (HNSCC) immune microenvironment.

Materials and Methods

A list of ferroptosis-related genes was obtained from the FerrDb database. Gene expression data were acquired from the cancer genome atlas (TCGA) and analyzed using the R language. Protein–protein interaction analysis was conducted using STRING and GeneMANIA. The correlations between gene expression levels and a patient’s survival were analyzed using GEPIA, the Kaplan–Meier estimate, and a multivariate Cox proportional hazards model. The expression results were verified using Oncomine and Human Protein Atlas data. We used the TIMER, GEPIA2, GEPIA2021, and TIMER2 databases to investigate the relationships between gene expression and infiltrating immune cells.

Results

Analysis of differentially expressed genes (DEGs) identified nine each ferroptosis drivers and ferroptosis suppressors, among which four genes correlated with survival as follows: two drivers (SOCS1, CDKN2A) associated with better survival and two suppressors (FTH1, CAV1) associated with poorer survival. Multivariate Cox survival analysis identified SOCS1 and FTH1 as independent prognostic factors for HNSCC, and their higher expression levels were verified using Oncomine and HPA data. The results acquired using TIMER, GEPIA2, GEPIA2021, and TIMER2 data revealed that the driver SOCS1 and the suppressor FTH1 independently correlated with M1 and M2 macrophage infiltration.

Conclusions

The ferroptosis driver SOCS1 and suppressor FTH1 are independent prognostic factors and that correlate with M1 and M2 macrophage infiltration in HNSCC. Targeting ferroptosis-immunomodulation may serve as a strategy to enhance the activity of immunotherapy.
Update on the Role of the Endothelial Glycocalyx in Angiogenesis and Vascular Inflammation
Authors: Hu Zhengping , Cano Issahy , D’Amore Patricia A.
Published: September 2021

The endothelial glycocalyx is a negatively charged, carbohydrate-rich structure that arises from the luminal surface of the vascular endothelium and is comprised of proteoglycans, glycoproteins, and glycolipids. The glycocalyx, which sits at the interface between the endothelium and the blood, is involved in a wide array of physiological and pathophysiological processes, including as a mechanotransducer and as a regulator of inflammation. Most recently, components of the glycocalyx have been shown to play a key role in controlling angiogenesis. In this review, we briefly summarize the structure and function of the endothelial glycocalyx. We focus on its role and functions in vascular inflammation and angiogenesis and discuss the important unanswered questions in this field.
Targeting Ferroptosis to Treat Cardiovascular Diseases: A New Continent to Be Explored
Authors: Huang Fangze , Yang Ronghua , Xiao Zezhou , Xie Yu , Lin Xuefeng , Zhu Peng , Zhou Pengyu , Lu Jun , Zheng Shaoyi
Published: September 2021

Cardiovascular diseases, including cardiomyopathy, myocardial infarction, myocardial ischemia/reperfusion injury, heart failure, vascular injury, stroke, and arrhythmia, are correlated with cardiac and vascular cell death. Ferroptosis is a novel form of non-apoptotic regulated cell death which is characterized by an iron-driven accumulation of lethal lipid hydroperoxides. The initiation and execution of ferroptosis are under the control of several mechanisms, including iron metabolism, glutamine metabolism, and lipid peroxidation. Recently, emerging evidence has demonstrated that ferroptosis can play an essential role in the development of various cardiovascular diseases. Recent researches have shown the ferroptosis inhibitors, iron chelators, genetic manipulations, and antioxidants can alleviate myocardial injury by blocking ferroptosis pathway. In this review, we systematically described the mechanisms of ferroptosis and discussed the role of ferroptosis as a novel therapeutic strategy in the treatment of cardiovascular diseases.
Carbon Material Based Electrochemical Immunosensor for Gastric Cancer Markers Detection
Authors: Zhang Zhuliang , Peng Minsi , Li Defeng , Yao Jun , Li Yingxue , Wu Benhua , Wang Lisheng , Xu Zhenglei
Published: September 2021

Gastric cancer is one of the most common malignant tumors, and early diagnosis will be of great significance to improve the survival quality and overall treatment outcome evaluation of patients. Nanoelectrochemical immunosensor is an emerging biosensor combining nanotechnology, electrochemical analysis method and immunological technology, which has simple operation, fast analysis speed, high sensitivity, and good selectivity. This mini-review summarized immunoassay techniques, nanotechnology and electrochemical sensing for the early detection of gastric cancer. In particular, we focus on the tension of carbon nanomaterials in this field, including the functionalized preparation of materials, signal enhancement and the construction of novel sensing interfaces. Currently, various tumor markers are being developed, but the more recognized gastric cancer tumor markers are carcinoembryonic antigen (CEA), carbohydrate antigen (CA), CD44V9, miRNAs, and programmed death ligand 1. Among them, the electrochemical immunosensor allows the detection of CEA, CA, and miRNAs. The mini-review focused on the development of using carbon based materials, especially carbon nanotubes and graphene for immunosensor fabrication and gastric cancer markers detection.
Insight Into the Potential Value of Gut Microbial Signatures for Prediction of Gestational Anemia
Authors: Wei Hongcheng , Deng Siting , Qin Yufeng , Yang Xu , Chen Ting , Wang Xu , Xia Yankai
Published: September 2021

The gut microbiota alternations are associated with gestational anemia (GA); however, limited predictive value for the subsequent incidence of anemia in normal gestational women has been obtained. We sought to rigorously characterise gut dysbiosis in subjects with GA and explored the potential predictive value of novel microbial signatures for the risk of developing GA. A prospective cohort of subjects with GA (n = 156) and healthy control (n = 402), all of whom were free of GA in the second trimester, by 16S rRNA gene sequencing was conducted. Microbial signatures altered dramatically in GA compared with healthy control in the second trimester. Megamonas, Veillonella, and Haemophilus were confirmed to show differential abundances in GA after adjusting for covariates. On the contrary, Lachnospiraceae and Blautia were enriched in control. Microbial co-abundance group (CAG) network was constructed. Prospectively, CAG network relatively accurately predicted upcoming GA in normal pregnant women with an AUC of 0.7738 (95%CI: 0.7171, 0.8306) and the performance was further validated in Validation set (0.8223, 95%CI: 0.7573, 0.8874). Overall, our study demonstrated that alterations in the gut microbial community were associated with anemia in pregnancy and microbial signatures could accurately predict the subsequent incidence of anemia in normal pregnant women. Our findings provided new insights into understanding the role of gut microbiota in GA, identifying high-risk individuals, and modulating gut microbiota as a therapeutic target, thus improving quality of life and well-being of women and children.
Internal Ocean Dynamics Control the Long-Term Evolution of Weddell Sea Polynya Activity
Authors: Rheinlænder Jonathan W. , Smedsrud Lars H. , Nisanciouglu Kerim H.
Published: September 2021

Open-ocean polynyas effectively couple the ocean and atmosphere through large ice-free areas within the sea-ice cover, release vast quantities of oceanic heat, and impact deep ocean ventilation. Changes in polynya activity, particularly in the Weddell Sea, may be key to longer time-scale climate fluctuations, feedbacks and abrupt change. While changes in the occurrence of Weddell Sea polynyas are generally attributed to changes in the atmospheric surface forcing, the role of internal ocean dynamics for polynya variability is not well-resolved. In this study we employ a global coupled ocean-sea ice model with a repeating annual atmospheric cycle to explore changes in Weddell Sea water mass properties, stratification and ocean circulation driven by open-ocean polynyas. During the 1300-year long simulation, two large polynyas occur in the central Weddell Sea. Our results suggest that Weddell polynyas may be triggered without inter-annual changes in the atmospheric forcing. This highlights the role of ocean processes in preconditioning and triggering open-ocean polynyas on multi-centennial time-scales. The simulated polynyas form due to internal ocean-sea ice dynamics associated with a slow build-up and subsequent release of subsurface heat. A strong stratification and weak vertical mixing is necessary for building the subsurface heat reservoir. Once the water column turns unstable, enhanced vertical mixing of warm and saline waters into the surface layer causes efficient sea ice melt and the polynya appears. Subsequent, vigorous deep convection is maintained through upwelling of warm deep water leading to enhanced bottom water formation. We find a cessation of simulated deep convection and polynya activity due to long-term cooling and freshening of the subsurface heat reservoir. As subsurface waters in the Southern Ocean are now becoming warmer and saltier, we speculate that larger and more persistent Weddell polynyas could become more frequent in the future.
The Role of Transthoracic Echocardiography in the Evaluation of Patients With Ischemic Stroke
Authors: Teodoro Robson Sarmento , Sampaio Silva Gisele , Modolo Gabriel Pinheiro , Trivellato Stella De Angelis , Souza Juli Thomaz de , Luvizutto Gustavo José , Nunes Hélio Rubens de Carvalho , Martin Luis Cuadrado , Bazan Rodrigo , Zanati Bazan Silméia Garcia
Published: September 2021

Background: Ischemic stroke can be classified into five etiological types, according to the Trial of Org 10172 in Acute Stroke Treatment (TOAST) classification, and its adequate investigation and characterization can aid in its clinical management and in preventing new events. Transthoracic echocardiography (TTE) plays a key role in investigating its etiology; approximately one-third of the patients remain without an adequate definition of the etiology or are classified as the undetermined TOAST type.

Objectives: To evaluate if the percentage of patients with indeterminate etiology according to the TOAST classification decreased after transthoracic echocardiography, to determine whether or not the prognosis after ischemic stroke is worse among patients classified as the undetermined TOAST type, and to verify the predictive capacity of echocardiography on the prognosis after ischemic stroke.

Methods: In this retrospective cohort study, clinical, neurological, and echocardiographic examinations were conducted when the patient was hospitalized for stroke. In-hospital mortality and functional capacity were evaluated at hospital discharge and 90 days thereafter. Multiple linear regression and multiple logistic regression models were adjusted for confounding factors. The level of significance was 5%.

Results: A total of 1,100 patients (men = 606; 55.09%), with a mean age of 68.1 ± 13.3 years, were included in this study. Using TTE, 977 patients (88.82%) were evaluated and 448 patients (40.7%) were classified as the undetermined TOAST type. The patients who underwent TTE were 3.1 times less likely to classified as the undetermined TOAST type (OR = 0.32; p < 0.001). Echocardiography during hospitalization was a protective factor against poor prognosis, and reduced the odds of in-hospital death by 11.1 times (OR: 0.090; p < 0.001). However, the presence of the undetermined TOAST classification elevated the chance of mortality during hospitalization by 2.0 times (OR: 2.00; p = 0.013).

Conclusions: Echocardiography during hospitalization for ischemic stroke reduces the chances of an undetermined TOAST classification and the risk of in-hospital mortality. However, being classified as the undetermined TOAST type increases the chance of mortality during hospitalization, suggesting that evaluating patients using echocardiography during hospitalization for acute ischemic stroke is important.
Homeostasis Disrupted and Restored—A Fresh Look at the Mechanism and Treatment of Obesity During COVID-19
Authors: Dickey Jacqueline , Davtyan Camelia , Davtyan David , Taegtmeyer Heinrich
Published: September 2021

The prevalence of obesity in the United States approaches half of the adult population. The COVID-19 pandemic endangers the health of obese individuals. In addition, the metabolic syndrome poses a challenge to the health of obese adults. Bariatric surgery and diet restore metabolic homeostasis in obese individuals; however, it is still unclear which strategy is most effective. For example, intermittent fasting improves insulin sensitivity and diet alone decreases visceral adipose tissue at a disproportionately high rate compared to weight loss. Bariatric surgery causes rapid remission of type 2 diabetes and increases incretins for long-term remission of insulin resistance before meaningful weight loss has occurred. Malabsorptive surgeries have provided insight into the mechanism of altering metabolic parameters, but strong evidence to determine the duration of their effects is yet to be established. When determining the best method of weight loss, metabolic parameters, target weight loss, and risk-benefit analysis must be considered carefully. In this review, we address the pros and cons for the optimal way to restore metabolic homeostasis.
Developmental Angiogenesis Requires the Mitochondrial Phenylalanyl-tRNA Synthetase
Authors: Li Bowen , Chen Kun , Liu Fangfang , Zhang Juan , Chen Xihui , Chen Tangdong , Chen Qi , Yao Yan , Hu Weihong , Wang Li , Wu Yuanming
Published: September 2021

Background: Mitochondrial aminoacyl-tRNA synthetases (mtARSs) catalyze the binding of specific amino acids to their cognate tRNAs and play an essential role in the synthesis of proteins encoded by mitochondrial DNA. Defects in mtARSs have been linked to human diseases, but their tissue-specific pathophysiology remains elusive. Here we examined the role of mitochondrial phenylalanyl-tRNA synthetase (FARS2) in developmental angiogenesis and its potential contribution to the pathogenesis of cardiovascular disease.

Methods: Morpholinos were injected into fertilized zebrafish ova to establish an in vivo fars2 knock-down model. A visualization of the vasculature was achieved by using Tg (fli1: EGFP)y1 transgenic zebrafish. In addition, small interference RNAs (siRNAs) were transferred into human umbilical vein endothelial cells (HUVECs) to establish an in vitro FARS2 knock-down model. Cell motility, proliferation, and tubulogenesis were determined using scratch-wound CCK8, transwell-based migration, and tube formation assays. In addition, mitochondria- and non-mitochondria-related respiration were evaluated using a Seahorse XF24 analyzer and flow cytometry assays. Analyses of the expression levels of transcripts and proteins were performed using qRT-PCR and western blotting, respectively.

Results: The knock-down of fars2 hampered the embryonic development in zebrafish and delayed the formation of the vasculature in Tg (fli1: EGFP)y1 transgenic zebrafish. In addition, the siRNA-mediated knock-down of FARS2 impaired angiogenesis in HUVECs as indicated by decreased cell motility and tube formation capacity. The knock-down of FARS2 also produced variable decreases in mitochondrial- and non-mitochondrial respiration in HUVECs and disrupted the regulatory pathways of angiogenesis in both HUVECs and zebrafish.

Conclusion: Our current work offers novel insights into angiogenesis defects and cardiovascular diseases induced by FARS2 deficiency.
On the Validity of the Relationship 1/T = 1/TB+1/TS+1/TD in NMR Techniques With Regards to Permeability Estimation of Natural Porous Media
Authors: Díaz-Curiel Jesús , Biosca Bárbara , Arévalo-Lomas Lucía , Miguel María Jesús , Loayza-Muro Raúl
Published: September 2021

One of the most relevant feature of geophysical techniques based on nuclear magnetic resonance is their ability to estimate the permeability of natural porous media, since other geophysical techniques, as the use of the formation factor and neutron well-logs, allow to quantify the volume of water in the media. Permeability is conventionally obtained from decay time of the total resonance signal. However, the fluid in the pores of a medium normally has different mobility degree that can be differentiated by the NMR results. Therefore, a detailed estimation of permeability requires decomposing the total resonance signal as a function of the decay times corresponding to the three mechanisms that contribute to the signal: the intergranular free fluid, the surface layer, and the diffusion relaxation mechanism. The relationship currently used to make this decomposition states that the exponential decay rate attributed to the total resonance signal is the sum of the three existing decay rates. We demonstrate that this relationship is not generally applicable in porous media, showing the contradiction with the much more widely accepted relationships as well as computation examples from three typical decay rates in a single pore and from sandstone with bulk and surface relaxation mechanisms. Consequently, we conclude that the assertion whereby the permeability of any porous medium does not depend on the decay time of the free fluid is an overstatement, since it only applies to very small pore sizes.
Sedimentary Dynamics of the Central South Yellow Sea Revealing the Relation Between East Asian Summer and Winter Monsoon Over the Past 6000 years
Authors: Lyu Wenzhe , Fu Tengfei , Hu Zhangxi , Tang Ying Zhong , Chen Guangquan , Xu Xingyong , Chen Yanping , Chen Shenliang
Published: September 2021

The mud areas of East Asian marginal seas record considerable information about regional environmental evolution. However, debate continues regarding the relative importance of the major factors in regional sedimentary dynamics, i.e., the East Asian summer monsoon, East Asian winter monsoon, and oceanic circulation. In this study, we investigated the characteristics of grain size from a gravity core obtained in the South Yellow Sea to reveal changes in sedimentary dynamics since 6,000 years BP, and to elucidate the relationship between the East Asian summer monsoon and the East Asian winter monsoon. We found that the mean grain size was in the range of 6.9–7.8 Φ, the sediment was poorly sorted within a small range (1.2, 1.5), and the M values from 4.7 to 6.7 μm and most of the C values from 24 to 65 μm suggested pelagic suspension transport. Results indicated that the intensity of both the East Asian summer monsoon and the East Asian winter monsoon showed a fluctuating trend of decrease after approximately 6,000 years BP, and that the relationship between them was generally anticorrelated. Based on these results, we suggest that positive correlation between the East Asian summer monsoon and the East Asian winter monsoon usually results in the fall or establishment of ancient dynasties in the Central Plains of China and that negative correlation between them is controlled by strong solar radiation. Weakening of solar radiation diminishes its control of the intensity of (and thus the correlation between) the East Asian summer monsoon and the East Asian winter monsoon, at which time the North Atlantic Oscillation plays a modulating role.