bluuebunny/crossref_metadata_2025 huggingface dataset:
Elas podem se machucar: As Lutas no combate ao preconceito de gênero na Educação Física Escolar
Authors: Mariano Eder Rodrigo , Silva Francisco Eduardo Lopes da , Souza Sérgio , Rizzo Deyvid Tenner de Souza , Rosa Vitor Alberto Valadas , Monteiro Luís Fernandes
Published: March 2021

Na atualidade, as mulheres ainda são estigmatizadas no âmbito esportivo, principalmente no que se refere a prática das Artes Marciais e Esportes de Combate (AM&EC). No contexto escolar, estudos científicos que tratam da interface entre Lutas e questões de gênero são escassos. Esta investigação buscou apontar a acepção dos alunos sobre a participação feminina nas aulas de Lutas na Educação Física. Os estudantes do 3º ano do ensino médio responderam à um questionário semiestruturado, antes e após, serem submetidos a seis encontros que envolviam aulas teóricas e aulas práticas subsequentemente, totalizando 140 minutos, cada encontro. O estudo ocorreu no Centro Educacional Dom Ungarelli, em Pinheiro-MA, numa sala de aula adaptada com Tatame e abrangeu 13 modalidades de Lutas. Os pais autorizaram-nos a participar, assinando o Termo de Consentimento Livre e Esclarecido, sendo excluídos aqueles que não frequentaram 75% das aulas ou não responderam. Os resultados mostram que, preliminarmente, 150 estudantes que participaram do estudo, 120 consideraram negativa a participação das meninas, pelo risco de se machucarem; apenas 19 julgaram-nas capazes e 11 com direitos iguais aos meninos. Posteriormente, todos aprovaram-nas nas aulas de Lutas, 35 confirmaram a capacidade delas e 60 estudantes passaram a reconhecer como uma prática em que as meninas também tem direito de participar; e destacamos que 55 estudantes perceberam que as Lutas rompem o preconceito de gênero. Portanto, concluímos que o conteúdo Lutas pode ser uma importante ferramenta educacional no combate aos estereótipos e preconceitos.
Anatophysiology of Vouacapoua americana Aubl. in the juvenile phase: A species included in the IUCN red list of threatened species
Authors: Trevisan Solange Henchen , Herrera Raírys Cravo , Vieira Thiago Bernardi , Drosdosky Maike Vieira , Cunha Roberto Lisboa , Reis Alisson Rodrigo Souza , Oliveira Lenaldo Muniz de
Published: March 2021

The Amazon is undergoing environmental changes that can cause morphological and physiological changes in plants. The general objective of this study was to evaluate the anatomical and eco-physiological features of Vouacapoua americana during development in the Brazilian Amazon. It was observed that the stomata only occur in the abaxial face. Secretory structures are present throughout the leaf blade. In the central vein and petiole region it was observed that the xylem occupies the vein’s central part, presenting an arc shape. The eco-physiological evaluations revealed that the dry period presented higher values of leaf temperature and steam pressure deficit, and lower values of leaf humidity, stomatal conductance, and transpiration. Anatomical and physiological differences occur at each stage of development.
Ações e impactos na redução de óbitos fetais: Percepção de integrantes do comitê de mortalidade
Authors: Manorov Maraisa , Paiz Alessandra , Souza Jeane Barros de , Macedo Laura Christina
Published: March 2021

Objetivo: desvelar as ações desenvolvidas nos serviços de saúde e seus impactos na redução de óbitos fetais, na percepção de integrantes de um Comitê de Mortalidade do Sul do Brasil. Método: estudo descritivo, de abordagem qualitativa, envolvendo sete profissionais de saúde, membros do Comitê de Mortalidade de um município do Paraná. Realizou-se entrevistas semi-estruturadas, que foram transcritas e analisadas de acordo com a análise de conteúdo. Resultados: Identificaram-se como principais causas para prevenção de óbitos fetais as infecções vaginais e/ou urinárias e entre as dificuldades enfrentadas surgiram a falta de qualificação e rotatividade de profissionais, bem como a falta de adesão ao pré-natal. Para tanto, estabeleceram-se diversas estratégias: elaboração de protocolos, capacitação de profissionais, aquisição de testes, medicamento e monitoramento de prontuários da maternidade. Conclusão: a identificação das fragilidades e posterior implementação de ações contribuiu para redução dos óbitos fetais no município, sendo que o maior impacto envolveu a qualificação dos profissionais para a assistência ao pré-natal.
Cutting efficiency of ProDesign R, Reciproc Blue and WaveOne Gold reciprocating instruments
Authors: Campos Ana Elisa Aguiar , Soares Adriana de Jesus , Limoeiro Ana Grasiela da Silva , Cintra Fernanda Tessaro , Frozoni Marcos , Campos Gabriel Rocha
Published: March 2021

This study aimed to evaluate, in vitro, the cutting efficiency and time spent for instrumentation of three different heat-treated reciprocating systems in simulated straight canals. Forty-five acrylic blocks with a straight simulated root canal with 21 millimeters in length were initially weighed (P1). After weighing the blocks were divided into three groups (n = 15) and each group prepared with the following systems:  ProDesign R 25.06 (Bassi/Easy, Belo Horizonte, Brazil), Reciproc Blue25.08 (VDW, Munich, Germany) and Wave one Gold (Dentsply Sirona, Ballaigues, Switzerland). The time spent for the total preparation of each block was recorded. After instrumentation, they were subjected to final weighing (P2). The difference between P1 and P2 determined the amount of material removed (cutting efficiency) by each mechanized system. The statistical analysis was performed by the ANOVA test of each of the variables, for multiple comparisons of means the turkey test was used. As for preparation time, it can be seen that ProDesign R showed a longer preparation time (P <0.5) compared to Reciproc Blue and Wave one Gold. Regarding cutting efficiency, there was no statistical difference between the groups (P> 0.5). In straight simulated canals, the type of reciprocating instrument influences the time for instrumentation; however, it shows similar cutting efficiency.
Pengaruh Gaya Kepemimpinan dan Komunikasi Organisasi Terhadap Kepuasaan Kerja Pada BP3IP Jakarta
Authors: Maharani Atria , Dewi Ratna Kurnia
Published: March 2021

Tujuan penelitian ini adalah untuk mengetahui seberapa besar pengaruh gaya kepemimpinan dan komunikasi organiasasi pada BP3IP Jakarta terhadap kepuasaan kinerja pegawainya. Metode pengumpulan data yang digunakan oleh peneliti adalah melalui data primer dan sekunder yang diperoleh melalui wawancara dan pengamatan (observasi) dilingkungan kantor BP3IP Jakarta. Dari hasil permbahasan diperoleh bahwa : 1) gaya kepemimpinan mempunyai dampak positif dan signifikan dengan kepuasan kerja instansi, 2) pelaksanaan komunikasi organisasi masih memerlukan perhatian yang lebih lanjut dari instansi, walaupun secara umum pelaksanaan komunikasi organisasi sudah berjalan dengan baik. Akan tetapi dengan melihat situasi, perlu perluasan kelas komunikasi organisasi, karena hal ini dapat memberikan kenyamanan dan kebebasan dalam mengembangkan kreatifitas pegawai, dan perubahan evaluasi karena adanya penilaian komunikasi organisasi yang professional.
Physiotherapy in Urinary Dysfunction Post-Surgery for Endometriosis: Case Report
Authors: Mainardi Simas Natália , Borges Filho Domingos Mantelli , Mantelli Borges Erica M. C. , de Abreu Pereira Carla Maria , dos Santos Alves Vera Lúcia
Published: March 2021

Endometriosis is characterised by the presence of endometrial tissue outside the uterine cavity that responds to oestrogen and stimulates local inflammatory processes, adhesions, pelvic pain, and infertility. The treatment of endometriosis includes the use of medications and videolaparoscopy for excision of adhesions or lesions. Some complications are associated with the videolaparoscopy, such as vascular, intestinal, urinary, neurological, and more rarely, vulvar oedema, which makes the rehabilitation difficult in the immediate postoperative period. In relation to the urinary dysfunction and to the vulvar oedema, physiotherapy has resources with demonstrated efficacy in the treatment of such complications after videolaparoscopy; they can rehabilitate the patient and improve their quality of life in a short time. In this study, the authors report the case of a patient treated by the Physical Therapy Service of the Santa Casa de Misericórdia Hospital of São Paulo, São Paulo, Brazil, with urinary retention and vulvar oedema after videolaparoscopy for endometriosis, which showed improvement in vulvar oedema with the application of physiotherapy.
Analysis of the Effectiveness of Toro Rosso Team as a Supporting Team of Red Bull Concern in Formula 1
Authors: Egorov Nikita , Averin Alexander
Published: March 2021

Background. The main goal of this research was to study the activities of Formula 1 team Toro Rosso in order to understand the peculiarities of its functioning and its role in realization of the performance program of Red Bull concern in this auto racing championship. This study provided an in-depth look at one of the most unusual examples of partnership in professional sports – Red Bull and Toro Rosso alliance.

Methods. The main research method was the collection and interpretation of statistical data concerning various characteristics of the performance of Toro Rosso team and its pilots in Formula 1, primarily sports performance. Also, additional facts were collected, which made it possible to give a more detailed description of the role of the Toro Rosso team in realizing the goals of Red Bull concern in Formula 1.

Results. During the study various characteristics were identified that reflect the peculiarities of managing Toro Rosso team. Among them we want to admit the next ones: A) Toro Rosso confirms the status of the team that prepares pilots for the performance in the main team Red Bull; B) TR, with some features, matches the status of “junior” team; C)–among the personnel decisions, connected with the Toro Rosso team in Formula 1, there were both successful and ineffective ones; D) the team brings sufficient benefits to both the main team of Red Bull and the entire Austrian concern.

Conclusions. Toro Rosso team proves the effectiveness of its existence and its value for Red Bull concern, and in order to increase the efficiency of its activity the leaders of Austrian company should continue to realize the strengths of the team, taking into account the interests of the RB main team, and, at the same time, improve the principles of personnel policy, carefully think out the positioning of team and correct the character of work of Red Bull Junior Team program.

Keywords: sports partnership, management, motorsport, team-satellite.
Revisiting the Qur’anic aḥbār in Historical Context
Authors: Dascalu Raphael
Published: March 2021

The precise identity of the Qur'anic aḥbār, some kind of Jewish communal leaders, has long been debated. This study presents a fresh examination of this term in its Qur'anic context, alongside its cognates in pre-Qur'anic Jewish texts, and engages seriously with both traditional and academic scholarship of the Qur'an.
THE INFLUENCE OF THE STUDENT FACILITATOR AND EXPLAINING ON STUDENT LEARNING OUTCOMES IN ELEMENTARY SCHOOLS
Authors: Astutiningsih Yuli , Supratno Haris , Siswanto M. Bambang Edi
Published: March 2021

The research objective was to describe the effect of using the Student Facilitator and Explaining model of learning on thematic learning at SDN Balongbesuk, Diwek, Jombang. The experimental method used in this study, and the research design used the Noneequivalent Control Group. Grade IV students were used as subjects in this study. Data were collected by observation, interviews, and tests. The t-test formula is used to analyze the data results. It is shown by the results of the research on learning mechanisms to be more effective by using the Student Facilitator And Explaining learning model, because it participates and engages students directly in the learning mechanism. Make students competent to express ideas or ideas to their friends. The use of the Student Facilitator And Explaining model can increase students' insight while learning, direct student involvement in the learning mechanism, because it can increase student learning outcomes.
THE EFFECT OF THE PICTURE AND PICTURE MODEL ON THE LEARNING OUTCOMES OF GRADE II ELEMENTARY SCHOOL STUDENT
Authors: Marodha Khoirum , Supratno Haris , Siswanto M. Bambang Edi
Published: March 2021

Learning activities achieved affect the level of understanding of students who impact on learning outcomes, especially in writing skills. The purpose of this study was to find out about the results before and after the use of picture and picture models and the influence of the use of picture and picture models on student learning outcomes in narrative story writing skills in class II SDN Ceweng. Data collection techniques used through observation, tests and documentation. The type of approach used is experimental pre-experimental designs with one-group pretest-posttest design. Data analysis techniques include: (1) normality test and (2) Hypothesis test or T-test. The results of this study can be seen from the results of the calculation in the paired samples test table. If the value of tcount> ttable, then Ho is rejected and H1 is accepted. Based on the above analysis, the result of tcount = 21.777 and df = 35 while ttable = 2.04. Shows that the results of testing the hypothesis Ho are accepted and H1 is rejected. With significance 2 tailed 0,000 <0.05. Meaning strong and there is a significant influence on student learning outcomes.
Simultaneous Ablation of the Catalytic AMPK α-Subunit SNF1 and Mitochondrial Matrix Protease CLPP Results in Pronounced Lifespan Extension
Authors: Heinz Daniela , Krotova Evgeniia , Hamann Andrea , Osiewacz Heinz D.
Published: March 2021

Organismic aging is known to be controlled by genetic and environmental traits. Pathways involved in the control of cellular metabolism play a crucial role. Previously, we identified a role of PaCLPP, a mitochondrial matrix protease, in the control of the mitochondrial energy metabolism, aging, and lifespan of the fungal aging modelPodospora anserina. Most surprisingly, we made the counterintuitive observation that the ablation of this component of the mitochondrial quality control network leads to lifespan extension. In the current study, we investigated the role of energy metabolism ofP. anserina. An age-dependent metabolome analysis of the wild type and aPaClpPdeletion strain verified differences and changes of various metabolites in cultures of thePaClpPmutant and the wild type. Based on these data, we generated and analyzed aPaSnf1deletion mutant and a ΔPaSnf1/ΔPaClpPdouble mutant. In both mutants PaSNF1, the catalytic α-subunit of AMP-activated protein kinase (AMPK) is ablated. PaSNF1 was found to be required for the development of fruiting bodies and ascospores and the progeny of sexual reproduction of this ascomycete and impact mitochondrial dynamics and autophagy. Most interestingly, while the singlePaSnf1deletion mutant is characterized by a slight lifespan increase, simultaneous deletion ofPaSnf1andPaClpPleads to a pronounced lifespan extension. This synergistic effect is strongly reinforced in the presence of the mating-type “minus”-linked allele of thermp1gene. Compared to the wild type, culture temperature of 35°C instead of the standard laboratory temperature of 27°C leads to a short-lived phenotype of the ΔPaSnf1/ΔPaClpPdouble mutant. Overall, our study provides novel evidence for complex interactions of different molecular pathways involved in mitochondrial quality control, gene expression, and energy metabolism in the control of organismic aging.
Cleavage and Polyadenylation Specific Factor 1 Promotes Tumor Progression via Alternative Polyadenylation and Splicing in Hepatocellular Carcinoma
Authors: Chen Shi-lu , Zhu Zhong-xu , Yang Xia , Liu Li-li , He Yang-fan , Yang Ming-ming , Guan Xin-yuan , Wang Xin , Yun Jing-ping
Published: March 2021

Alternative polyadenylation (APA) is an important post-transcriptional regulatory mechanism required for cleavage and polyadenylation (CPA) of the 3′ untranslated region (3′ UTR) of mRNAs. Several aberrant APA events have been reported in hepatocellular carcinoma (HCC). However, the regulatory mechanisms underlying APA remain unclear. In this study, we found that the expression of cleavage and polyadenylation specific factor 1 (CPSF1), a major component of the CPA complex, was significantly increased in HCC tissues and correlated with unfavorable survival outcomes. Knockdown of CPSF1 inhibited HCC cell proliferation and migration, whereas overexpression of CPSF1 caused the opposite effect. Based on integrative analysis of Iso-Seq and RNA-seq data from HepG2.2.15 cells, we identified a series of transcripts with differential 3′ UTR lengths following the knockdown of CPSF1. These transcripts were related to the biological functions of gene transcription, cytoskeleton maintenance, and endomembrane system transportation. Moreover, knockdown of CPSF1 induced an increase in alternative splicing (AS) events in addition to APA. Taken together, this study provides new insights into our understanding of the post-transcriptional regulatory mechanisms in HCC and implies that CPSF1 may be a potential prognostic biomarker and therapeutic target for HCC.
Meditation Effective in Reducing Teacher Burnout and Improving Resilience: A Randomized Controlled Study
Authors: Valosek Laurent , Wendt Staci , Link Jan , Abrams Allan , Hipps Jerry , Grant James , Nidich Randi , Loiselle Marie , Nidich Sanford
Published: March 2021

Teacher burnout affects job performance and mental and physical health. This study evaluated the effects of a meditation-based wellness program on burnout, resilience, psychological distress, and fatigue. Seventy-eight participants, randomly assigned to the Transcendental Meditation program (n = 39) or to a wait-list control group (n = 39), were administered the Maslach Burnout Inventory, Resilience Scale, Perceived Stress Scale, and the National Institutes of Health Patient-Reported Outcomes Measurement Information System fatigue and depression scales at baseline and at four-month posttest. Intention-to-treat with all 78 participants was used for all analyses. Significant reduction on emotional exhaustion, the main scale of the Maslach Burnout Inventory, was found for the meditation group compared to controls (p = 0.019). Significant improvements were also found on resilience (p = 0.014), perceived stress (p < 0.001), fatigue (p = 0.001), and depression (p = 0.091). Eighty-seven percent were compliant with their meditation home practice. Findings indicate that meditation is effective in improving burnout and associated resilience, psychological distress, and fatigue factors. Teachers may benefit from in-school wellness programs.
Adaptive Thermogenesis Driving Catch-Up Fat Is Associated With Increased Muscle Type 3 and Decreased Hepatic Type 1 Iodothyronine Deiodinase Activities: A Functional and Proteomic Study
Authors: Di Munno Celia , Busiello Rosa Anna , Calonne Julie , Salzano Anna Maria , Miles-Chan Jennifer , Scaloni Andrea , Ceccarelli Michele , de Lange Pieter , Lombardi Assunta , Senese Rosalba , Cioffi Federica , Visser Theo J. , Peeters Robin P. , Dulloo Abdul G. , Silvestri Elena
Published: March 2021

Refeeding after caloric restriction induces weight regain and a disproportionate recovering of fat mass rather than lean mass (catch-up fat) that, in humans, associates with higher risks to develop chronic dysmetabolism. Studies in a well-established rat model of semistarvation-refeeding have reported that catch-up fat associates with hyperinsulinemia, glucose redistribution from skeletal muscle to white adipose tissue and suppressed adaptive thermogenesis sustaining a high efficiency for fat deposition. The skeletal muscle of catch-up fat animals exhibits reduced insulin-stimulated glucose utilization, mitochondrial dysfunction, delayed in vivo contraction-relaxation kinetics, increased proportion of slow fibers and altered local thyroid hormone metabolism, with suggestions of a role for iodothyronine deiodinases. To obtain novel insights into the skeletal muscle response during catch-up fat in this rat model, the functional proteomes of tibialis anterior and soleus muscles, harvested after 2 weeks of caloric restriction and 1 week of refeeding, were studied. Furthermore, to assess the implication of thyroid hormone metabolism in catch-up fat, circulatory thyroid hormones as well as liver type 1 (D1) and liver and skeletal muscle type 3 (D3) iodothyronine deiodinase activities were evaluated. The proteomic profiling of both skeletal muscles indicated catch-up fat-induced alterations, reflecting metabolic and contractile adjustments in soleus muscle and changes in glucose utilization and oxidative stress in tibialis anterior muscle. In response to caloric restriction, D3 activity increased in both liver and skeletal muscle, and persisted only in skeletal muscle upon refeeding. In parallel, liver D1 activity decreased during caloric restriction, and persisted during catch-up fat at a time-point when circulating levels of T4, T3 and rT3 were all restored to those of controls. Thus, during catch-up fat, a local hypothyroidism may occur in liver and skeletal muscle despite systemic euthyroidism. The resulting reduced tissue thyroid hormone bioavailability, likely D1- and D3-dependent in liver and skeletal muscle, respectively, may be part of the adaptive thermogenesis sustaining catch-up fat. These results open new perspectives in understanding the metabolic processes associated with the high efficiency of body fat recovery after caloric restriction, revealing new implications for iodothyronine deiodinases as putative biological brakes contributing in suppressed thermogenesis driving catch-up fat during weight regain.
Microbiome in Death and Beyond: Current Vistas and Future Trends
Authors: Roy Dipayan , Tomo Sojit , Purohit Purvi , Setia Puneet
Published: March 2021

Forensic medicine has, for a long time, been relying on biochemical, anthropologic, and histopathologic evidences in solving various investigations. However, depending on the method used, lengthy sample processing time, scanty sample, and less sensitivity and accuracy pervade these procedures. Accordingly, newer arenas such as the thanatomicrobiome have come forward to aid in its quandaries; furthermore, the parallel advances in genomic and proteomic techniques have complemented and are still emerging to be used in forensic experiments and investigations. Postmortem interval (PMI) is one of the most important aspects of medico-legal investigations. The current trend in PMI estimation is toward genomic analyses of autopsy samples. Similarly, determination of cause of death, although a domain of medical sciences, is being targeted as the next level of forensic casework. With the current trend in laboratory sciences moving to the discovery of newer disease-specific markers for diagnostic and prognostic purposes, the same is being explored for the determination of the cause of death by using techniques such as Real-Time PCR, DNA micro-array, to Next-Gen Sequencing. Establishing an individual’s biological profile has been done using medicolegal methods and anthropology as well as bar-bodies/Davidson bodies (gender determination); and in cases where the determination of age/gender is a challenge using morphological characteristics; the recent advances in the field of genomics and proteomics have played a significant role, e.g., use of mitochondrial DNA in age estimation and in maternity disputes. The major hurdle forensic medical research faces is the fact that most of the studies are conducted in animal models, which are often difficult to mimic in human and real-time scenarios. Additionally, the high accuracy required in criminal investigations to be used in a court of law as evidence has prevented these results to come out of the labs and be used to the optimum. The current review aims at giving a comprehensive and critical account of the various molecular biology techniques including “thanatogenomics,” currently being utilized in the veritable fields of forensic medicine.
ITPR1 Mutation Contributes to Hemifacial Microsomia Spectrum
Authors: Liu Zhixu , Sun Hao , Dai Jiewen , Xue Xiaochen , Sun Jian , Wang Xudong
Published: March 2021

Hemifacial microsomia (HM) is a craniofacial congenital defect involving the first and second branchial arch, mainly characterized by ocular, ear, maxilla-zygoma complex, mandible, and facial nerve malformation. HM follows autosomal dominant inheritance. Whole-exome sequencing of a family revealed a missense mutation in a highly conserved domain ofITPR1. ITPR1 is a calcium ion channel. By studyingITPR1’s expression pattern, we found that ITPR1 participated in craniofacial development, especially the organs that corresponded to the phenotype of HM. In zebrafish,itpr1b, which is homologous to humanITPR1, is closely related to craniofacial bone formation. The knocking down ofitpr1bin zebrafish could lead to a remarkable decrease in craniofacial skeleton formation. qRT-PCR suggested that knockdown ofitpr1bcould increase the expression ofplcb4while decreasing the mRNA level of Dlx5/6. Our findings highlighted ITPR1’s role in craniofacial formation for the first time and suggested thatITPR1mutation contributes to human HM.
Medical Image Protection Algorithm Based on Deoxyribonucleic Acid Chain of Dynamic Length
Authors: Xue Xianglian , Jin Haiyan , Zhou Dongsheng , Zhou Changjun
Published: March 2021

Current image encryption algorithms have various deficiencies in effectively protecting medical images with large storage capacity and high pixel correlation. This article proposed a new image protection algorithm based on the deoxyribonucleic acid chain of dynamic length, which achieved image encryption by DNA dynamic coding, generation of DNA dynamic chain, and dynamic operation of row chain and column chain. First, the original image is encoded dynamically according to the binary bit from a pixel, and the DNA sequence matrix is scrambled. Second, DNA sequence matrices are dynamically segmented into DNA chains of different lengths. After that, row and column deletion operation and transposition operation of DNA dynamic chain are carried out, respectively, which made DNA chain matrix double shuffle. Finally, the encrypted image is got after recombining DNA chains of different lengths. The proposed algorithm was tested on a list of medical images. Results showed that the proposed algorithm showed excellent security performance, and it is immune to noise attack, occlusion attack, and all common cryptographic attacks.
NOD1 Agonist Protects Against Lipopolysaccharide and D-Galactosamine-Induced Fatal Hepatitis Through the Upregulation of A20 Expression in Hepatocytes
Authors: Jia Fang , Deng Fuxue , Xu Pan , Li Shiying , Wang Xuefu , Hu Peng , Ren Hong , Tong Shiwen , Yin Wenwei
Published: March 2021

Increasing evidence suggests that NODs are involved in liver diseases; however, the underlying mechanisms remain obscure. In the present study, we analyzed the effect of NOD1 agonist pretreatment on acute liver failure induced by lipopolysaccharide (LPS) in D-galactosamine (D-GalN)-sensitized mice. We found that pretreatment with the NOD1 agonist markedly reduced LPS/D-GalN-induced mortality, elevation of serum ALT levels, and hepatocyte apoptosis. The protective effect of NOD1 agonist was independent of tumor necrosis factor (TNF)-α inhibition. NOD1 agonist pretreatment also attenuated TNF-α/D-GalN-induced apoptotic liver damage. The anti-apoptotic protein A20 expression was more pronounced in NOD1 agonist pretreated mice than in controls, and knockdown of A20 abrogated the protective effect of NOD1 agonist on LPS/D-GalN-induced liver injury and hepatocyte apoptosis. Further experiments showed that NOD1 agonist-induced A20 upregulation required the presence of kupffer cells and TNF-α. Taken together, our data strongly indicate that NOD1 is involved in the regulation of liver injury and could be a potential therapeutic target for liver diseases.
Activation of Bone Marrow Adaptive Immunity in Type 2 Diabetes: Rescue by Co-stimulation Modulator Abatacept
Authors: Santopaolo Marianna , Sullivan Niall , Thomas Anita Coral , Alvino Valeria Vincenza , Nicholson Lindsay B. , Gu Yue , Spinetti Gaia , Kallikourdis Marinos , Blom Ashley , Madeddu Paolo
Published: March 2021

Background: Chronic low-grade inflammation and alterations in innate and adaptive immunity were reported in Type 2 diabetes (T2D). Here, we investigated the abundance and activation of T cells in the bone marrow (BM) of patients with T2D. We then verified the human data in a murine model and tested if the activation of T cells can be rescued by treating mice with abatacept, an immunomodulatory drug employed for the treatment of rheumatoid arthritis. Clinical evidence indicated abatacept can slow the decline in beta-cell function.

Methods: A cohort of 24 patients (12 with T2D) undergoing hip replacement surgery was enrolled in the study. Flow cytometry and cytokine analyses were performed on BM leftovers from surgery. We next compared the immune profile of db/db and control wt/db mice. In an additional study, db/db mice were randomized to receive abatacept or vehicle for 4 weeks, with endpoints being immune cell profile, indices of insulin sensitivity, and heart performance.

Results: Patients with T2D showed increased frequencies of BM CD4+ (2.8-fold, p = 0.001) and CD8+ T cells (1.8-fold, p = 0.01), with the upregulation of the activation marker CD69 and the homing receptor CCR7 in CD4+ (1.64-fold, p = 0.003 and 2.27-fold, p = 0.01, respectively) and CD8+ fractions (1.79-fold, p = 0.05 and 1.69-fold, p = 0.02, respectively). These differences were confirmed in a multivariable regression model. CCL19 (CCR7 receptor ligand) and CXCL10/11 (CXCR3 receptor ligands), implicated in T-cell migration and activation, were the most differentially modulated chemokines. Studies in mice confirmed the activation of adaptive immunity in T2D. Abatacept reduced the activation of T cells and the levels of proinflammatory cytokines and improved cardiac function but not insulin sensitivity.

Conclusions: Results provide proof-of-concept evidence for the activation of BM adaptive immunity in T2D. In mice, treatment with abatacept dampens the activation of adaptive immunity and protects from cardiac damage.
Neutrophils: Many Ways to Die
Authors: Pérez-Figueroa Erandi , Álvarez-Carrasco Pablo , Ortega Enrique , Maldonado-Bernal Carmen
Published: March 2021

Neutrophils or polymorphonuclear leukocytes (PMN) are key participants in the innate immune response for their ability to execute different effector functions. These cells express a vast array of membrane receptors that allow them to recognize and eliminate infectious agents effectively and respond appropriately to microenvironmental stimuli that regulate neutrophil functions, such as activation, migration, generation of reactive oxygen species, formation of neutrophil extracellular traps, and mediator secretion, among others. Currently, it has been realized that activated neutrophils can accomplish their effector functions and simultaneously activate mechanisms of cell death in response to different intracellular or extracellular factors. Although several studies have revealed similarities between the mechanisms of cell death of neutrophils and other cell types, neutrophils have distinctive properties, such as a high production of reactive oxygen species (ROS) and nitrogen species (RNS), that are important for their effector function in infections and pathologies such as cancer, autoimmune diseases, and immunodeficiencies, influencing their cell death mechanisms. The present work offers a synthesis of the conditions and molecules implicated in the regulation and activation of the processes of neutrophil death: apoptosis, autophagy, pyroptosis, necroptosis, NETosis, and necrosis. This information allows to understand the duality encountered by PMNs upon activation. The effector functions are carried out to eliminate invading pathogens, but in several instances, these functions involve activation of signaling cascades that culminate in the death of the neutrophil. This process guarantees the correct elimination of pathogenic agents, damaged or senescent cells, and the timely resolution of the inflammation that is essential for the maintenance of homeostasis in the organism. In addition, they alert the organism when the immunological system is being deregulated, promoting the activation of other cells of the immune system, such as B and T lymphocytes, which produce cytokines that potentiate the microbicide functions.
Molecular Diversity and Distribution of Arbuscular Mycorrhizal Fungi at Different Elevations in Mt. Taibai of Qinling Mountain
Authors: Zhang Mengge , Shi Zhaoyong , Yang Mei , Lu Shichuan , Cao Libing , Wang Xugang
Published: March 2021

Arbuscular mycorrhizal fungi (AMFs) play a vital role in ecosystems, especially in ecosystem variability, diversity, and function. Understanding the AMF diversity, distribution, and their driver at different altitudinal gradients is a benefit for understanding the ecological function of AMF in mountain ecosystems. In this study, we explored the AMF molecular diversity and their distribution from 660 to 3,500 m a.s.l. in Mount Taibai of Qinling Mountains based on high-throughput sequencing technology. A total of 702 operational taxonomic units (OTUs) in 103 species of AMF are isolated from soil samples, which belong to 18 identified and 1 unidentified genus in 10 families. The fungi in the genus ofGlomusis the most dominant, with the occurrence frequency of 100% and the relative abundance of 42.268% and 33.048% on the species and OTU level, respectively. The AMF colonization in root could be simulated by a cubic function with the change of altitudes with the peak and trough at a.s.l. 1,170 and 2,850 m, respectively. Further, AMF diversity indices including Sob, Shannon diversity, and Pielou evenness also showed the same cubic function change trends with increasing altitude at OTU and species levels. However, the average values of diversity indices at OTU level are always higher than these at the species level. Based on the OTU level, the highest and lowest values of Shannon and Pielou indices are observed at the altitudes of 1,400 and 2,800 m, respectively. The pattern of AMF community distribution in Mt. Taibai is driven by altitude with the characteristics of more abundance in the medium- to low-altitude than high-altitude areas. In general, abundant AMF molecular diversity and species exit in different elevations of Mt. Taibai, which indicate gradient changes with elevations.
Machine Learning Models on ADC Features to Assess Brain Changes of Children With Pierre Robin Sequence
Authors: Wang Ying , Yang Feng , Zhu Meijiao , Yang Ming
Published: March 2021

In order to evaluate brain changes in young children with Pierre Robin sequence (PRs) using machine learning based on apparent diffusion coefficient (ADC) features, we retrospectively enrolled a total of 60 cases (42 in the training dataset and 18 in the testing dataset) which included 30 PRs and 30 controls from the Children's Hospital Affiliated to the Nanjing Medical University from January 2017–December 2019. There were 21 and nine PRs cases in each dataset, with the remainder belonging to the control group in the same age range. A total of 105 ADC features were extracted from magnetic resonance imaging (MRI) data. Features were pruned using least absolute shrinkage and selection operator (LASSO) regression and seven ADC features were developed as the optimal signatures for training machine learning models. Support vector machine (SVM) achieved an area under the receiver operating characteristic curve (AUC) of 0.99 for the training set and 0.85 for the testing set. The AUC of the multivariable logistic regression (MLR) and the AdaBoost for the training and validation dataset were 0.98/0.84 and 0.94/0.69, respectively. Based on the ADC features, the two groups of cases (i.e., the PRs group and the control group) could be well-distinguished by the machine learning models, indicating that there is a significant difference in brain development between children with PRs and normal controls.
Geographical Discrimination of Croatian Wines by Stable Isotope Ratios and Multielemental Composition Analysis
Authors: Leder Renata , Petric Ivana Vladimira , Jusup Josipa , Banović Mara
Published: March 2021

The δ18O and δ13C (analyzed by isotope ratio mass spectrometry, IRMS) and concentration of 22 selected elements (analyzed by inductively coupled plasma—optical emission spectrometry, ICP-OES) in 190 Croatian microvinified and commercial wine samples from continental and coastal winegrowing areas and from three viticultural zones (B, CI, and CII) were measured to investigate whether multivariate statistical methods could provide the fingerprint for geographical origin determination. The highest power for discrimination of wines produced in Croatian winegrowing areas was achieved by general discriminant analysis (GDA) showing correct classification of 97.9% of all investigated samples, 100.0% of microvinified samples and 84.8% of commercial samples in the cross-validation matrix. The most significant markers for discrimination of coastal and continental areas found by GDA were δ18O and Co, followed by K, Rb, Sn, Li, and δ13C in descending order. GDA showed higher levels of correctly classified samples from three viticultural zones in Croatia if only microvinified samples were employed in the analysis (94.9%) than for all samples together (86.3%) or for commercial samples (66.1%) in the cross-validation matrix. The discrimination of viticultural zones B, CI, and CII in Croatia was achieved by δ18O, Co, Rb, Li, K, and Sn. The results obtained showed that the relationships between the isotopic ratios and concentrations of different considered elements combined with appropriate statistical model represent a powerful tool in discrimination of wines produced in different Croatian winegrowing areas.
Development of an Iberian Chorizo Salted With a Combination of Mineral Salts (Seawater Substitute) and Better Nutritional Profile
Authors: Tejada Luis , Buendía-Moreno Laura , Álvarez Elisa , Palma Agustín , Salazar Eva , Muñoz Beatriz , Abellán Adela
Published: March 2021

The present study evaluated the effect of salt reduction using a seawater substitutes, at the nutritional and mineral composition, its physicochemical, biochemical, microbiological, and sensory characteristics of Iberian chorizo, compared with one elaborated with low salt content (KCl) and another with a normal salt content (CTRL). To this end, three batches of chorizo were prepared [Treatment 1: CTRL, 100% NaCl; Treatment 2: KCl, 31% KCl, and Treatment 3: SC (Winbi®), <3% NaCl]. In KCl and SC chorizo lots, values of moisture, salt, and water activity (aw) were significantly lower (P < 0.05) than in the CTRL chorizo. The chorizo with lower salt content presented higher proteolytic activity; with the nutritional declaration “reduced Na content “with Na values 25% lower than the CTRL. In addition, using this combination caused significant effects (P < 0.05) on the mineral composition of chorizo SC, allowing the inclusion of more nutritional and health claims in its labeling under legislation. The partial substitution of NaCl for KCl (31%), caused an increase in the gumminess, chewiness, and hardness of the chorizo. The SC chorizo lost the reddish hue typical of this sausage, although it was the best sensory valued by a panel of consumers. No differences were observed in the microbiological quality of the different batches of chorizo, always fulfilling the legally established microbiological criteria.
Pan-Cancer Analysis of NOS3 Identifies Its Expression and Clinical Relevance in Gastric Cancer
Authors: Zou Dan , Li Zhi , Lv Fei , Yang Yi , Yang Chunjiao , Song Jincheng , Chen Yang , Jin Zi , Zhou Jinpeng , Jiang Yang , Ma Yanju , Jing Zhitao , Tang Yu , Zhang Ye
Published: March 2021

Background:NOS3 (endothelial NOS, eNOS) is a member of the nitric oxide synthase (NOS) enzyme family, mainly participating in nitric oxide (NO) generation. NOS3 has been reported to inhibit apoptosis and promote angiogenesis, proliferation, and invasiveness. However, the expression pattern of NOS3 and its diagnostic and prognostic potential has not been investigated in a pan-cancer perspective.

Methods: Data from the Genotype-Tissue Expression (GTEx), the Cancer Genome Atlas (TCGA), the Cancer Cell Line Encyclopedia (CCLE), and the Cancer Therapeutics Response Portal (CTRP) were employed and NOS3 expression was comprehensively analyzed in normal tissues, cancer tissues, and cell lines. Immunohistochemical staining of tissue sections were used to validate the prognostic role of NOS3 in gastric cancer patients. GSVA and GSEA analyses were performed to investigate signaling pathways related to NOS3 expression.

Results: In normal tissues, NOS3 was expressed highest in the spleen and lowest in the blood. NOS3 expression was increased in stomach adenocarcinoma (STAD) and significantly associated with poor prognosis of patients. Immunohistochemical staining validated that NOS3 was an independent prognostic factor of gastric cancer. Several canonical cancer-related pathways were found to be correlated with NOS3 expression in STAD. The expression of NOS3 was related to the response to QS-11 and brivinib in STAD.

Conclusions:NOS3 was an independent prognostic factor for patients with STAD. Increased expression of NOS3 influenced occurrence and development of STAD through several canonical cancer-related pathways. Drug response analysis reported drugs to suppress NOS3. NOS3 might be a novel target for gastric cancer treatment.
Liraglutide Alleviates Hepatic Steatosis and Liver Injury in T2MD Rats via a GLP-1R Dependent AMPK Pathway
Authors: Zhou Rui , Lin Chuman , Cheng Yanzhen , Zhuo Xiaoyun , Li Qinghua , Xu Wen , Zhao Liang , Yang Li
Published: March 2021

Non-alcoholic fatty liver disease (NAFLD), ranging from non-alcoholic fatty liver to non-alcoholic steatohepatitis, can be prevalent in patients with type 2 diabetes mellitus (T2DM). However, no antidiabetic drug has been approved for the treatment of NAFLD in T2DM patients. Multiple daily injections of basal-bolus insulin are often the final therapeutic option for T2DM. We found that insulin treatment aggravated hepatic steatosis and oxidative stress in Zucker diabetic fatty (ZDF) rats. In addition to glycaemic control, we demonstrated the stimulatory role of liraglutide in relieving hepatic steatosis and liver injury in ZDF rats. Interestingly, liraglutide could also alleviate insulin-aggravated hepatic fatty accumulation. The glucagon-like peptide-1 (GLP-1) agonists liraglutide and Ex-4 activated the expression of peroxisome proliferator-activated receptor alpha (PPARα) via a GLP-1 receptor-dependent 5′ AMP-activated protein kinase pathway. As a nuclear transcription factor, PPARα could mediate the effect of GLP-1 in alleviating hepatic steatosis by differentially regulating the expression of its target genes, including acetyl CoA carboxylase and carnitine palmitoyl transferase la both in vitro and in vivo. Moreover, GLP-1 could relieve liver injury by decreasing oxidative stress stimulated by hepatic steatosis. Insulin might aggravate hepatic steatosis and liver injury by inhibiting GLP-1R expression. The findings indicate the feasibility of liraglutide treatment combined with basal insulin in attenuating hepatic steatosis and liver injury in ZDF rats. This knowledge, and the evidence for the underlying mechanism, provide a theoretical basis for the combination treatment recommended by the latest clinical practice guidelines for T2DM.
Angiotensin (1-7) Attenuates Sepsis-Induced Acute Kidney Injury by Regulating the NF-κB Pathway
Authors: Zhu Ying , Xu Daliang , Deng Fang , Yan Yonglin , Li Jian , Zhang Chenyu , Chu Jing
Published: March 2021

This study explores the protective mechanism of angiotensin (1-7) [Ang-(1-7)] on kidneys by examining its effects on renal histomorphology, inflammatory response, oxidative stress, and NF-κB signaling in mice suffering from sepsis-induced acute kidney injury. A sepsis-induced acute kidney injury mouse model was established by intracervically injecting lipopolysaccharides (LPS group), followed by the administration of Ang-(1-7) [LPS + Ang-(1-7) group]. The serum levels of urea nitrogen, creatinine and cystatin. c were measured with an automatic biochemical analyzer, and changes in proinflammatory cytokines and angiotensin II (Ang II) in the serum and kidneys were quantified by enzyme-linked immunosorbent assays. Changes in oxidative stress indices in the renal cortex were detected by colorimetry. The localization of Ang II in kidneys was examined by immunohistochemistry. Western blotting was used to examine phosphorylated NF-κB-p65 and IκBα levels in kidneys. Compared with the control group, the serum levels of urea nitrogen, creatinine and cystatin. c were increased, whereas the levels of Ang II, TNFα, IL-1β, IL-6, and malondialdehyde (mda) were increased significantly. The levels of Ang II and phosphorylated NF-κB-p65 were elevated in kidneys, whereas the levels of superoxide dismutase (sod), Total antioxidative capacity (TAOC), and inhibitor of NF-κB (IκBα) were reduced in the LPS group (p < 0.05). Pathological damage was also observed in kidneys of LPS-group mice. In Pearson correlation analysis, there was a positive correlation between Ang II and phosphorylated NF-κB-p65 levels, and a negative correlation between Ang II and IκBα levels (p < 0.05). After the application of Ang-(1-7), the levels of urea nitrogen, creatinine, cystatin. c, Ang II, TNFα, IL-1β, IL-6, and mda, as well as the expression of Ang II and phosphorylated NF-κB-p65 in kidneys of LPS + Ang-(1-7)-group mice, were lower than those in kidneys of LPS-group mice, but the levels of sod, TAOC, and IκBα were higher than those of LPS-group mice (p < 0.05). Pathological changes were less severe in mice of the LPS + Ang-(1-7) group. Overall, Ang-(1-7) can decrease the Ang II level, inhibit NF-κB signaling, reduce the inflammatory response, decrease oxidative stress, and mitigate sepsis-associated acute kidney injury.
Altered Expression of Chemosensory and Odorant Binding Proteins in Response to Fungal Infection in the Red Imported Fire Ant, Solenopsis invicta
Authors: Wei Zhang , Ortiz-Urquiza Almudena , Keyhani Nemat O.
Published: March 2021

Social insects have evolved acute mechanisms for sensing and mitigating the spread of microbial pathogens within their communities that include complex behaviors such as grooming and sanitation. Chemical sensing involves detection and transport of olfactory and other chemicals that are mediated by at least two distinct classes of small molecular weight soluble proteins known as chemosensory- and odorant binding proteins (CSPs and OBPs, respectively) that exist as protein families in all insects. However, to date, a systematic examination of the expression of these genes involved in olfactory and other pathways to microbial infection has yet to be reported. The red imported fire ant, Solenopsis invicta, is one of the most successful invasive organisms on our planet. Here, we examined the temporal gene expression profiles of a suite of S. invicta CSPs (SiCSPs1-22) and OBPs (SiOBPs1-16) in response to infection by the broad host range fungal insect pathogen, Beauveria bassiana. Our data show that within 24 h post-infection, i.e., before the fungus has penetrated the host cuticle, the expression of SiCSPs and SiOBPs is altered (mainly increased compared to uninfected controls), followed by suppression of SiCSP and select SiOBP expression 48 h post-infection and mixed responses at 72 h post-infection. A smaller group of SiBOPs, however, appeared to respond to fungal infection, with expression of SiOBP15 consistently higher during fungal infection over the time course examined. These data indicate dynamic gene expression responses of CSPs and OBPs to fungal infection that provide clues to mechanisms that might mediate detection of microbial pathogens, triggering grooming, and nest sanitation.