bluuebunny/crossref_metadata_2025 huggingface dataset:
Estudo e influência dos óleos essenciais de cravo, canela e laranja na preparação de filmes de poli (ácido lático): desenvolvimento de embalagens ativas
Authors: Lima Jéssica Camilla da Costa , Pereira Juliana de Castro Nunes , Andrade Michelle Félix de , Góis Gelsoneide da Silva , Simões Ivana Taciana de Almeida , Silva Maria Alcilene Alexandre Dantas da , Almeida Yêda Medeiros Bastos de , Vinhas Glória Maria
Published: April 2021

O poli (ácido lático) – PLA é um polímero biocompatível e biodegradável com algumas propriedades semelhantes aos polímeros convencionais, destacando-se em diversas aplicações, dentre elas, a indústria de embalagens. A substituição dos aditivos convencionais por componentes naturais como os óleos essenciais, vem tornando-se uma alternativa promissora para a produção das chamadas embalagens ativas, que promovem a segurança alimentar a partir da ação antimicrobiana. Sendo assim, o objetivo deste trabalho foi produzir filmes de PLA por casting aditivados com óleos essenciais (OE) de cravo, laranja e canela, para sua possível aplicação como embalagem ativa. Os óleos foram caracterizados por Cromatografia Gasosa acoplada com Espectrômetro de Massa (GC-MS), Espectroscopia no infravermelho com transformada de Fourier (FTIR) e por disco-difusão em ágar. Os filmes foram caracterizados por Microscopia óptica (MO), Calorimetria Exploratória Diferencial (DSC), FTIR, Análise Termogravimétrica (TG) e Análise antimicrobiana do filme. Com os resultados obtidos foi possível observar que o filme de PLA com os óleos essenciais apresentaram melhora no desempenho quanto a sua propriedade térmica e atividade antimicrobiana. Dentre os três filmes aditivados, o filme PLA/OE Cravo destacou-se por haver uma intensa ação bactericida sem degradação do filme, o que o torna um promissor aditivo adicionado ao PLA para aplicações em indústrias de embalagens.
Dental education and proportion of inhabitants by Dentist in Angola
Authors: Moimaz Suzely Adas Saliba , Songa Marcial António Simão , Saliba Nemre Adas , Saliba Tânia Adas
Published: April 2021

The objective was to verify the proportion of dentists in relation to the Angolan population, to undergraduate and graduate courses in dentistry, and to analyze the pedagogical projects of the existing courses. This is a descriptive, exploratory and documentary study that analyzed data on the population and the number of dentists in Angola, obtained through information from the National Statistics Institute and the Order of Doctors of Angola. An application for cell phones called “Qualificar”, made available by the Angolan government, was used to collect information about the existing courses. The websites of the Ministry of Higher Education, Science, Technology and Innovation; National Institute for Evaluation, Accreditation and Recognition of Higher Education Studies in Angola; and the National Press were consulted to collect data related to higher education in Angola. Information on pedagogical projects was obtained directly from Higher Education Institutions (HEIs). Angola has 701 dentists registered for a population of 30,175,553 inhabitants, that is, a proportion of 1/43,460. Among the eighty existing HEIs, only ten were authorized by the government to offer undergraduate courses in dentistry: six were located in the country's capital and four were distributed in other provinces, with workload varying from 4,688 to 5,536 hours. It was concluded that of the seven academic regions in the country, 4 do not have courses in dentistry; the number of dentists is not compatible with the population of Angola; no HEI offered postgraduate courses in dentistry and there is no standardization of pedagogical projects among the existing undergraduate courses.
Epidemiologia da Doença de Alzheimer em Sergipe no período de 2008 a 2018: morbidade hospitalar e mortalidade
Authors: Correia João Paulo Siqueira , Campos André Luiz Baião , Correia Samara Siqueira , Nascimento Crysvânia Santos
Published: April 2021

A Doença de Alzheimer é a doença neurodegenerativa mais comum e principal causa de demência em todo o mundo, sendo um dos grandes desafios da saúde no século XXI. Nos últimos anos, a demência representou a quinta principal causa de morte no mundo, com cerca de 2,4 milhões de óbitos. Este trabalho teve como objetivo analisar os dados epidemiológicos da morbidade hospitalar e a mortalidade ocasionadas pela Doença de Alzheimer no Estado de Sergipe, entre os anos de 2008 e 2018. Trata-se de um estudo epidemiológico descritivo, retrospectivo e transversal realizado com dados do DATASUS. No período analisado, foram registradas apenas 21 internações, sendo treze do sexo feminino, doze atendimentos foram feitos em pacientes com 80 anos ou mais. Dados como raça/cor foram ignorados em 18 pacientes atendidos. Com relação a mortalidade, foram registrados 979 óbitos. A maioria dos moradores, 547, eram residentes de Aracaju. O sexo feminino foi o mais acometido com 645 casos e a faixa etária mais acometida foi a de pacientes com 80 anos ou mais, com 697 casos. Através do estudo foi possível avaliar a falta alimentação do sistema, principalmente no Sistema de Informações Hospitalares, uma vez que há poucos casos para serem analisados e algumas informações não são adequadamente registradas. É preciso ressaltar também a importância e contribuição de bases de dados como o DATASUS, pois a disponibilidade de informações públicas é essencial para execução de medidas de ação em saúde, realizadas de acordo com as características epidemiológicas das enfermidades estudadas.
Aleitamento materno durante a pandemia da COVID-19: Revisão integrativa
Authors: Rezende Caique Alves , Barbosa Thays Cristina Pereira , Bernardes Isabelle Aparecida de Sousa , Santos Isabela Teodoro dos , Lima Mariana Rodrigues Moraes , Camilo Amanda Aparecida Vieira , Bernardo Glória Janaína Rodrigues , Oliveira Maíla Martins
Published: April 2021

O objetivo deste estudo é compreender como a pandemia do COVID-19 influenciou no aleitamento materno das gestantes nesse período. Refere-se a um estudo de revisão integrativa, realizada em de janeiro de 2021. Assim, o delineamento desse estudo surgiu a partir da seguinte questão de pesquisa: o que se sabe até o momento da literatura científica sobre o aleitamento materno durante a pandemia da COVID-19? Após percorrer as etapas metodológicas foi possível identificar 08 artigos e todas as publicações são datadas no ano 2020 e focadas sobre o aleitamento materno em tempos de pandemia. De acordo com o que foi abordado no presente artigo, o objetivo foi devidamente contemplado demostrando através dos estudos utilizados como base dessa revisão acerca do aleitamento mediante ao cenário da pandemia da COVID-19. Visto isso, torna-se viável continuar os estudos sobre o tema e realizar futuras publicações com novas atualizações do assunto. Pelo fato de ser uma doença na qual ainda há muito que descobrir é essenciais novas produções desse cenário.
Opinionsgeneratorn: Tips och råd om influencing
Authors: Larsson Martin , Raninger Sabine
Published: April 2021

Om oss
Vi som skapat denna blogg heter Sabine och Martin. Vi är två språk- och litteraturstudenter som skrivit en del vad man bör tänka på om man är intresserad av sociala medier och influencers, främst med ungdomar i åtanke. Detta är superviktigt anser vi då väldigt många idag spenderar mycket tid på sociala medier, inte minst ungdomar, varav många lägger ett stort värde i hur de och deras inlägg bemöts av andra på nätet. På denna blogg vill vi belysa att detta är fallet, samt att det finns saker man bör tänka på om man vill ha en närvaro på nätet som influencer
Mera svamp!
Authors: Malmros Erik
Published: April 2021

Mera Svamp! är ett icke-vinstdrivande projekt vars huvudsyfte är att öka medvetenheten kring svensk svamp genom informativa och underhållande texter.

Tanken bakom varje text är att de ska fungera som diskussionsunderlag i den bredare diskussionen om hållbarhet; samtidigt som fler ska lockas till att lära sig mer om svensk svamp!

Initiativtagare bakom projektet Mera Svamp! heter Erik, som för närvarande är student i Linköping och som brinner för hållbarhetsfrågor.
The Impact of Locomotor Speed on the Human Metatarsophalangeal Joint Kinematics
Authors: Wang Kunyang , Raychoudhury Sivangi , Hu Dan , Ren Lei , Liu Jing , Xiu Haohua , Liang Wei , Li Bingqian , Wei Guowu , Qian Zhihui
Published: April 2021

This paper aims to further our previous study to investigate the effect of speed on the human metatarsophalangeal (MP) joint kinematics during running on level ground. The 3D motion of the foot segments was captured by a twelve-camera motion analysis system, and the ground reaction forces and moments were recorded by using a six-force plate array. The relative movement between the tarsometatarsi (hindfoot) and phalanges (forefoot) segments were recorded to obtain the 3D orientation and position of the functional axis (FA) of the MP joint. The results show that the FA locates about an average of 19% foot length (FL) anterior to the anatomical axis (AA) across all running speeds, and is also 4.8% FL inferior to the AA during normal and fast run. Similar to walking, the functional axis is more oblique than the anatomical axis with a more anterior–inferior orientation across all the running speeds. This suggests that representing MP joint with the AA may mislead the calculation of joint moment/power and muscle moment arms in both running and walking gait. Compared with previous study, we found that walking and running speeds have statistically significant effects on the position of the FA. The functional axis moves frontward to a more anterior position when the speed increases during walking and running. It transfers upward in the superior direction with increasing speed of walking, but moves more toward the inferior position when the velocity increased further to running. Also, the orientation of FA in sagittal plane became more oblique toward the vertical direction as the speed increased. This may help in moderating the muscular effort, increase the muscle EMA and improve the locomotor performance. These results would contribute to understanding the in vivo biomechanical function of the MP joint and also the foot propulsion during human locomotion.
Synergistic and Antagonistic Effects of Biogenic Silver Nanoparticles in Combination With Antibiotics Against Some Pathogenic Microbes
Authors: Aabed Kawther , Mohammed Afrah E.
Published: April 2021

The latest advances in green nanoparticle synthesis have preserved natural and non-renewable resources and decreased environmental pollution. The current study was designed to evaluate silver nanoparticles (AgNPs) fabricated using aqueous extracts of two medicinal plants,Anastatica hierochunticaL. (Kaff Maryam) andArtemisia absinthium. The phytochemicals were detected by Fourier-transform infrared spectroscopy (FTIR) and Chromatography/Mass Spectrometry (GC-MS). The effects of the AgNPs onPseudomonas aeruginosa, Escherichia coli,Staphylococcus aureus, andCandida albicansas well as the cytotoxicity against MDA-MB-231 cells were examined. The synergistic and antagonistic effects of the biogenic AgNPs in combination with standard antibiotics against several microbes were also investigated. The ability of the plant extracts to transfer silver ions to AgNPs was measured via dynamic light scattering, zeta potential measurement, and transmission electron microscopy. The most sensitive microbes to AgNP treatment were examined via scanning electron microscopy to assess morphological changes. Biogenic AgNPs showed significant antibacterial effects against most of the tested microbes and significant cytotoxicity was noted. Polysaccharides, proteins and Phenolic compounds are likely involved in AgNP biosynthesis since hydroxyl groups and amides were detected via FTIR as well as GC-MS. This study confirmed that plant-based AgNP fabrication with AgNO3as the Ag (I) delivering salt can be an economical and practical approach for large-scale production of particles with antimicrobial and cytotoxic potential. The synergistic effects of biogenic AgNPs in combination with some antibiotics support their potential as a safe therapeutic for bacterial infections because they are capped with organic biomolecules.
Engineering Cardiovascular Tissue Chips for Disease Modeling and Drug Screening Applications
Authors: Chan Alex H. P. , Huang Ngan F.
Published: April 2021

In recent years, the cost of drug discovery and development have been progressively increasing, but the number of drugs approved for treatment of cardiovascular diseases (CVDs) has been limited. Current in vitro models for drug development do not sufficiently ensure safety and efficacy, owing to their lack of physiological relevance. On the other hand, preclinical animal models are extremely costly and present problems of inaccuracy due to species differences. To address these limitations, tissue chips offer the opportunity to emulate physiological and pathological tissue processes in a biomimetic in vitro platform. Tissue chips enable in vitro modeling of CVDs to give mechanistic insights, and they can also be a powerful approach for drug screening applications. Here, we review recent advances in CVD modeling using tissue chips and their applications in drug screening.
Isoalantolactone Increases the Sensitivity of Prostate Cancer Cells to Cisplatin Treatment by Inducing Oxidative Stress
Authors: Huang Hang , Li Ping , Ye Xueting , Zhang Fangyi , Lin Qi , Wu Keming , Chen Wei
Published: April 2021

Prostate cancer is the most common malignancy among men worldwide. Platinum (II)-based chemotherapy has been used to treat a number of malignancies including prostate cancer. However, the potential of cisplatin for treating prostate cancer is restricted owing to its limited efficacy and toxic side effects. Combination therapies have been proposed to increase the efficacy and reduce the toxic side effects. In the present study, we investigated how isoalantolactone (IATL), a sesquiterpene lactone extracted from the medicinal plant Inula helenium L., acts synergistically with cisplatin on human prostate cancer cells. We show that IATL significantly increased cisplatin-induced growth suppression and apoptosis in human prostate cancer cells. Mechanistically, the combined treatment resulted in an excessive accumulation of intracellular reactive oxygen species (ROS), which leads to the activation of endoplasmic reticulum (ER) stress and the JNK signaling pathway in human prostate cancer cells. Pretreatment of cells with the ROS scavenger N-acetylcysteine (NAC) significantly abrogated the combined treatment-induced ROS accumulation and cell apoptosis. In addition, the activation of ER stress and the JNK signaling pathway prompted by IATL and cisplatin was also reversed by NAC pretreatment. In vivo, we found that IATL combined with cisplatin showed the strongest antitumor effects compared with single agents. These results support the notion that IATL and cisplatin combinational treatment may be more effective for treating prostate cancer than cisplatin alone.
Theileria’s Strategies and Effector Mechanisms for Host Cell Transformation: From Invasion to Immortalization
Authors: Woods Kerry , Perry Carmen , Brühlmann Francis , Olias Philipp
Published: April 2021

One of the first events that follows invasion of leukocytes byTheileriasporozoites is the destruction of the surrounding host cell membrane and the rapid association of the intracellular parasite with host microtubules. This is essential for the parasite to establish its niche within the cytoplasm of the invaded leukocyte and setsTheileriaspp. apart from other members of the apicomplexan phylum such asToxoplasma gondiiandPlasmodiumspp., which reside within the confines of a host-derived parasitophorous vacuole. After establishing infection, transformingTheileriaspecies (T. annulata,T. parva) significantly rewire the signaling pathways of their bovine host cell, causing continual proliferation and resistance to ligand-induced apoptosis, and conferring invasive properties on the parasitized cell. Having transformed its target cell,Theileriahijacks the mitotic machinery to ensure its persistence in the cytoplasm of the dividing cell. Some of the parasite and bovine proteins involved in parasite-microtubule interactions have been fairly well characterized, and the schizont expresses at least two proteins on its membrane that contain conserved microtubule binding motifs.Theileria-encoded proteins have been shown to be translocated to the host cell cytoplasm and nucleus where they have the potential to directly modify signaling pathways and host gene expression. However, little is known about their mode of action, and even less about how these proteins are secreted by the parasite and trafficked to their target location. In this review we explore the strategies employed byTheileriato transform leukocytes, from sporozoite invasion until immortalization of the host cell has been established. We discuss the recent description of nuclear pore-like complexes that accumulate on membranes close to the schizont surface. Finally, we consider putative mechanisms of protein and nutrient exchange that might occur between the parasite and the host. We focus in particular on differences and similarities with recent discoveries inT. gondiiandPlasmodiumspecies.
Reck-Notch1 Signaling Mediates miR-221/222 Regulation of Lung Cancer Stem Cells in NSCLC
Authors: Guo Yuefan , Wang Guangxue , Wang Zhongrui , Ding Xin , Qian Lu , Li Ya , Ren Zhen , Liu Pengfei , Ma Wenjing , Li Danni , Li Yuan , Zhao Qian , Lü Jinhui , Li Qinchuan , Wang Qinhong , Yu Zuoren
Published: April 2021

Cancer stem cells (CSCs) contribute to the cancer initiation, metastasis and drug resistance in non-small cell lung cancer (NSCLC). Herein, we identified a miR-221/222 cluster as a novel regulator of CSCs in NSCLC. Targeted overexpression or knockdown of miR-221/222 in NSCLC cells revealed the essential roles of miR-221/222 in regulation of lung cancer cell proliferation, mammosphere formation, subpopulation of CD133+ CSCs and the expression of stemness genes including OCT4, NANOG and h-TERT. The in vivo animal study showed that overexpression of miR-221/222 significantly enhanced the capacity of lung cancer cells to develop tumor and grow faster, indicating the importance of miR-221/222 in tumorigenesis and tumor growth. Mechanistically, Reck was found to be a key direct target gene of miR-221/222 in NSCLC. Overexpression of miR-221/222 significantly suppressed Reck expression, activated Notch1 signaling and increased the level of NICD. As an activated form of Notch1, NICD leads to enhanced stemness in NSCLC cells. In addition, knockdown of Reck by siRNA not only mimicked miR-221/222 effects, but also demonstrated involvement of Reck in the miR-221/222-induced activation of Notch1 signaling, verifying the essential roles of the miR-221/222-Reck-Notch1 axis in regulating stemness of NSCLC cells. These findings uncover a novel mechanism by which lung CSCs are significantly manipulated by miR-221/222, and provide a potential therapeutic target for the treatment of NSCLC.
Recent Developments in Ring-Opening Copolymerization of Epoxides With CO2 and Cyclic Anhydrides for Biomedical Applications
Authors: Liang Xue , Tan Fei , Zhu Yunqing
Published: April 2021

The biomedical applications of polyesters and polycarbonates are of interest due to their potential biocompatibility and biodegradability. Confined by the narrow scope of monomers and the lack of controlled polymerization routes, the biomedical-related applications of polyesters and polycarbonates remain challenging. To address this challenge, ring-opening copolymerization (ROCOP) has been exploited to prepare new alternating polyesters and polycarbonates, which would be hard to synthesize using other controlled polymerization methods. This review highlights recent advances in catalyst development, including the emerging dinuclear organometallic complexes and metal-free Lewis pair systems. The post-polymerization modification methods involved in tailoring the biomedical functions of resultant polyesters and polycarbonates are summarized. Pioneering attempts for the biomedical applications of ROCOP polyesters and polycarbonates are presented, and the future opportunities and challenges are also highlighted.
From Conception to Development: Investigating PROTACs Features for Improved Cell Permeability and Successful Protein Degradation
Authors: Cecchini Carlotta , Pannilunghi Sara , Tardy Sébastien , Scapozza Leonardo
Published: April 2021

Proteolysis Targeting Chimeras (PROTACs) are heterobifunctional degraders that specifically eliminate targeted proteins by hijacking the ubiquitin-proteasome system (UPS). This modality has emerged as an orthogonal approach to the use of small-molecule inhibitors for knocking down classic targets and disease-related proteins classified, until now, as “undruggable.” In early 2019, the first targeted protein degraders reached the clinic, drawing attention to PROTACs as one of the most appealing technology in the drug discovery landscape. Despite these promising results, PROTACs are often affected by poor cellular permeability due to their high molecular weight (MW) and large exposed polar surface area (PSA). Herein, we report a comprehensive record of PROTAC design, pharmacology and thermodynamic challenges and solutions, as well as some of the available strategies to enhance cellular uptake, including suggestions of promising biological tools for the in vitro evaluation of PROTACs permeability toward successful protein degradation.
Comparison of Clinical Outcomes Between Second-and First-Generation Drug-Eluting Stents in Patients With Chronic Total Occlusion Lesion: A Meta-Analysis
Authors: Qiao Xuan , Zhang Wen-Jiao , Guo Wen-Fen , Li Yan , Liang Xi-Ying , Wang Zhi-Lu
Published: April 2021

Background and Objectives: The second-generation drug-eluting stents have been used to treat chronic total occlusion lesion. However, there is limited evidence of the clinical outcomes that whether the second-generation drug-eluting stents is superior to first-generation ones in patients with chronic total occlusion lesion undergoing percutaneous coronary intervention. The study aimed to compare the differences in clinical outcomes between the two generations drug-eluting stents in patients with those by a meta-analysis.

Methods: PubMed, Embase, the Cochrane library and Web of science databases were systemically searched before March, 2021. Randomized controlled trials and observational studies were included to compare the second-generation drug-eluting stents with the first-generation ones in patients with chronic total occlusion lesion undergoing percutaneous coronary intervention. The clinical outcomes were major adverse cardiac events (MACE), target vessel revascularization, myocardial infarction, all-cause death. Fixed effects models were used to calculate the odds ratio (OR) and 95% confidence interval (CI) of each clinical outcome. Sensitivity analysis was performed to detect potential sources of heterogeneity. Subgroup analyses were used to assess the differential effects.

Results: The meta-analysis included eight studies involving 4,583 patients with chronic total occlusion lesion undergoing percutaneous coronary intervention. Pooled analysis showed that the incidence of MACE (OR = 0.68, 95%CI 0.54–0.85, P = 0.0008), target vessel revascularization (OR = 0.70, 95%CI 0.54–0.91, P = 0.007), and myocardial infarction (OR = 0.58, 95%CI 0.37–0.93, P = 0.02) were lower in the second-generation drug-eluting stents compared with the first-generation ones. However, there was not difference in all-cause deaths between two drug-eluting stents (OR = 0.67, 95%CI 0.45–1.01, P = 0.05).

Conclusions: The second-generation drug-eluting stents are associated with lower MACE, target vessel revascularization, and myocardial infarction compared with the first-generation ones in patients with chronic total occlusion lesion undergoing percutaneous coronary intervention. The results of this study can provide a reference for the selection of stents in patients with chronic total occlusion lesion. Further randomized controlled trials are needed to verify that the second-generation drug-eluting stents is superior to the first-generation ones in patients with chronic total occlusion (Registered by PROSPERO, CRD42020158406).
Arterial Doppler Waveforms Are Independently Associated With Maximal Walking Distance in Suspected Peripheral Artery Disease Patients
Authors: Miossec Annaïg , Tollenaere Quentin , Lanéelle Damien , Guilcher Antoine , Métairie Antoine , Le Pabic Estelle , Carel Awenig , Le Faucheur Alexis , Mahé Guillaume
Published: April 2021

Objective: Arterial Doppler waveform recordings are commonly used to assess lower extremity arterial disease (LEAD) severity. However, little is known about the relationship between arterial Doppler waveform profiles and patients' walking capacity. The purpose of this study was to assess whether arterial Doppler waveforms are independently associated with maximal walking distance (MWD) in patients experiencing exertional limb symptoms.

Materials and Methods: This cross-sectional study included suspected LEAD patients experiencing exertional limb symptoms. In both lower extremities, arterial Doppler waveforms and ankle-brachial index (ABI) values were obtained from the pedis and tibial posterior arteries. Each arterial flow measurement was ranked using the Saint-Bonnet classification system. Treadmill stress testing (3.2 km/h, 10% slope) coupled with exercise oximetry (Exercise-TcPO2) were used to determine MWD. Delta from rest oxygen pressure (DROP) was calculated. Following treadmill stress testing, post-exercise ABI values were recorded. Univariate and multivariate analyses were used to determine the clinical variables associated with MWD.

Results: 186 patients experiencing exertional limb symptoms (62 ± 12 years and 26.8 ± 4.5 kg/m2) were included between May 2016 and June 2019. Median [25th; 75th] treadmill MWD was 235 [125;500]m. Better arterial Doppler waveforms were associated with better walking distance (p = 0.0012). Whereas, median MWD was 524 [185;525]m in the group that yielded the best Doppler waveforms, it was 182 [125,305]m in the group with the poorest Doppler waveforms (p = 0.0012). MWD was significantly better (p = 0.006) in the patients with the best ABIs. However, arterial Doppler waveforms alone were significantly associated with MWD (p = 0.0009) in the multivariate model. When exercise variables (post-exercise ABI or DROP) were incorporated into the multivariate model, these were the only variables to be associated with MWD.

Conclusion: Of the various clinical parameters at rest, Doppler flow waveform profiles were associated with MWD in suspected LEAD patients. A stronger link was however found between exercise variables and MWD.
AMPA-Type Glutamate Receptors Associated With Vascular Smooth Muscle Cell Subpopulations in Atherosclerosis and Vascular Injury
Authors: Gallina Alessandro L. , Rykaczewska Urszula , Wirka Robert C. , Caravaca April S. , Shavva Vladimir S. , Youness Mohamad , Karadimou Glykeria , Lengquist Mariette , Razuvaev Anton , Paulsson-Berne Gabrielle , Quertermous Thomas , Gisterå Anton , Malin Stephen G. , Tarnawski Laura , Matic Ljubica , Olofsson Peder S.
Published: April 2021

Objectives and Aims: Vascular smooth muscle cells (VSMCs) are key constituents of both normal arteries and atherosclerotic plaques. They have an ability to adapt to changes in the local environment by undergoing phenotypic modulation. An improved understanding of the mechanisms that regulate VSMC phenotypic changes may provide insights that suggest new therapeutic targets in treatment of cardiovascular disease (CVD). The amino-acid glutamate has been associated with CVD risk and VSMCs metabolism in experimental models, and glutamate receptors regulate VSMC biology and promote pulmonary vascular remodeling. However, glutamate-signaling in human atherosclerosis has not been explored.

Methods and Results: We identified glutamate receptors and glutamate metabolism-related enzymes in VSMCs from human atherosclerotic lesions, as determined by single cell RNA sequencing and microarray analysis. Expression of the receptor subunits glutamate receptor, ionotropic, α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic (AMPA)-type subunit 1 (GRIA1) and 2 (GRIA2) was restricted to cells of mesenchymal origin, primarily VSMCs, as confirmed by immunostaining. In a rat model of arterial injury and repair, changes of GRIA1 and GRIA2 mRNA level were most pronounced at time points associated with VSMC proliferation, migration, and phenotypic modulation. In vitro, human carotid artery SMCs expressed GRIA1, and selective AMPA-type receptor blocking inhibited expression of typical contractile markers and promoted pathways associated with VSMC phenotypic modulation. In our biobank of human carotid endarterectomies, low expression of AMPA-type receptor subunits was associated with higher content of inflammatory cells and a higher frequency of adverse clinical events such as stroke.

Conclusion: AMPA-type glutamate receptors are expressed in VSMCs and are associated with phenotypic modulation. Patients suffering from adverse clinical events showed significantly lower mRNA level of GRIA1 and GRIA2 in their atherosclerotic lesions compared to asymptomatic patients. These results warrant further mapping of neurotransmitter signaling in the pathogenesis of human atherosclerosis.
Disentangling Sedimentary Pathways for the Pleniglacial Lower Danube Loess Based on Geochemical Signatures
Authors: Pötter Stephan , Veres Daniel , Baykal Yunus , Nett Janina J. , Schulte Philipp , Hambach Ulrich , Lehmkuhl Frank
Published: April 2021

The source of aeolian sediments such as loess has been investigated since decades. Reliable knowledge on potential dust sources is crucial to understand past climatic and environmental conditions accompanying the dispersal of early modern humans (EMH) into Europe. Provenance studies are usually performed on small sample sets and most established methods are expensive and time-consuming. Here, we present the results of high-resolution geochemical analyses performed on five loess-palaeosol sequences from the Lower Danube Basin (LDB), a region, despite its importance as a trajectory for EMH, largely underrepresented in loess provenance studies. We compare our results with geochemical data of loess-palaeosol sequences from Austria, Hungary, Serbia, and Ukraine. Based on published literature, we thus evaluate five plausible sedimentary pathways for the LDB loess: 1) the Danube alluvium (DA) pathway, which constrains the transport and re-deposition of detrital material by the Danube and its tributaries; 2) the Carpathian Bending (CB) pathway, where sediment is mainly transported from the Cretaceous to Neogene flysch of the Eastern Carpathian Bending; 3) the Eastern Carpathian (EC) pathway, in which sediment is eroded from the flysch of the Outer Eastern Carpathians, transported by rivers, and deflated by northwesterly to westerly winds; 4) the glaciofluvial (GF) pathway, where dust is deflated from glacial outwash plains in nowadays Ukraine, and 5) the Black Sea (BS) pathway, where dust originates from the exposed shelf of the Black Sea. Based on geochemical data, we consider the DA pathway to be the major sediment trajectory for loess in the LDB. Especially the sequences located close to the Danube and the Dobrogea show similarities to sites in Central and Northeast Hungary as well as Northern Serbia. For the northeastern part of the LDB, we demonstrate that dust input is mainly sourced from primary material from the Eastern Carpathians. Mineralogical estimations and geochemical data render the CB pathway as an additional substantial source of detrital material for the loess of this area. We consider the influence of the GF pathway in the LDB as negligible, whereas some minor influences of the BS pathway cannot be ruled out based on geochemical data.
Centering Loss and Grief: Positioning Schools as Sites of Collective Healing in the Era of COVID-19
Authors: Castrellón Liliana E. , Fernández Érica , Reyna Rivarola Alonso R. , López Gerardo R.
Published: April 2021

When the COVID-19 pandemic hit the United States, everyday life was fundamentally transformed. Schools and small businesses were forced to shut down. Individuals were encouraged to wear masks in public settings, “shelter-in-place” orders were implemented across several cities and states, and social distancing became a routine practice. Some lost their jobs and livelihood, while others lost the day-to-day physical connection with colleagues and friends, as their “work-life” had shifted to home. To be certain, the variety of losses that people individually and collectively experienced during the COVID-19 pandemic is quite vast—ranging from small, seemingly inconsequential losses (like the freedom to get a haircut) to more considerable and painful losses (like the loss of life). It is important to note that these losses overlapped with other crises that were fomenting across the nation at the same time—for example, the rise of the white supremacist movement, Black Lives Matter, anti-Asian racism, and draconian immigration enforcement, amongst others. These other pandemics also produced losses, such as the loss of civil rights, crackdowns on civic participation, and fundamental violations of basic human rights and civil liberties. In this paper, we discuss the “losses” we are currently experiencing as a nation and the need for school leaders to pay attention to the range of losses people are experiencing in their daily lives. We draw particular attention to those losses compounded by intersecting historical oppressions that disproportionately impact historically marginalized students, families, and communities. We also (re)imagine the transformation of schools to sites of collective healing that work to humanize the collective experience by anchoring actions in resistance, love, collective well-being, hope, and solidarity with and alongside teachers, students, families, and communities.
Tmod3 Phosphorylation Mediates AMPK-Dependent GLUT4 Plasma Membrane Insertion in Myoblasts
Authors: Shrestha Man Mohan , Lim Chun-Yan , Bi Xuezhi , Robinson Robert C. , Han Weiping
Published: April 2021

Insulin and muscle contractions mediate glucose transporter 4 (GLUT4) translocation and insertion into the plasma membrane (PM) for glucose uptake in skeletal muscles. Muscle contraction results in AMPK activation, which promotes GLUT4 translocation and PM insertion. However, little is known regarding AMPK effectors that directly regulate GLUT4 translocation. We aim to identify novel AMPK effectors in the regulation of GLUT4 translocation. We performed biochemical, molecular biology and fluorescent microscopy imaging experiments using gain- and loss-of-function mutants of tropomodulin 3 (Tmod3). Here we report Tmod3, an actin filament capping protein, as a novel AMPK substrate and an essential mediator of AMPK-dependent GLUT4 translocation and glucose uptake in myoblasts. Furthermore, Tmod3 plays a key role in AMPK-induced F-actin remodeling and GLUT4 insertion into the PM. Our study defines Tmod3 as a key AMPK effector in the regulation of GLUT4 insertion into the PM and glucose uptake in muscle cells, and offers new mechanistic insights into the regulation of glucose homeostasis.
Unraveling the Complex Interplay Between Transcription Factors and Signaling Molecules in Thyroid Differentiation and Function, From Embryos to Adults
Authors: López-Márquez Arístides , Carrasco-López Carlos , Fernández-Méndez Celia , Santisteban Pilar
Published: April 2021

Thyroid differentiation of progenitor cells occurs during embryonic development and in the adult thyroid gland, and the molecular bases of these complex and finely regulated processes are becoming ever more clear. In thisReview, we describe the most recent advances in the study of transcription factors, signaling molecules and regulatory pathways controlling thyroid differentiation and development in the mammalian embryo. We also discuss the maintenance of the adult differentiated phenotype to ensure the biosynthesis of thyroid hormones. We will focus on endoderm-derived thyroid epithelial cells, which are responsible for the formation of the thyroid follicle, the functional unit of the thyroid gland. The use of animal models and pluripotent stem cells has greatly aided in providing clues to the complicated puzzle of thyroid development and function in adults. The so-called thyroid transcription factors – Nkx2-1, Foxe1, Pax8 and Hhex – were the first pieces of the puzzle identified in mice. Other transcription factors, either acting upstream of or directly with the thyroid transcription factors, were subsequently identified to, almost, complete the puzzle. Among them, the transcription factors Glis3, Sox9 and the cofactor of the Hippo pathway Taz, have emerged as important players in thyroid differentiation and development. The involvement of signaling molecules increases the complexity of the puzzle. In this context, the importance of Bmps, Fgfs and Shh signaling at the onset of development, and of TSH, IGF1 and TGFβ both at the end of terminal differentiation in embryos and in the adult thyroid, are well recognized. All of these aspects are covered herein. Thus, readers will be able to visualize the puzzle of thyroid differentiation with most – if not all – of the pieces in place.
Body Adiposity, But Not Elements of Objectively Measured Sedentary Behavior or Physical Activity, Is Associated With Circulating Liver Enzymes in Adults With Overweight and Obesity
Authors: Laine Saara , Sjöros Tanja , Vähä-Ypyä Henri , Garthwaite Taru , Löyttyniemi Eliisa , Sievänen Harri , Vasankari Tommi , Knuuti Juhani , Heinonen Ilkka H. A.
Published: April 2021

Objective

We studied the associations between accelerometer-measured sedentary behavior (SB) and habitual physical activity (PA) as well as markers of body adiposity and other cardiometabolic risk factors with liver enzymes alanine aminotransferase (ALT), aspartate aminotransferase (AST) and γ-glutamyltransferase (GGT).

Methods

A total of 144 middle-aged adults (mean age 57 (SD 6.5) years) with overweight or obesity (mean body mass index [BMI] 31.8 [SD 3.9] kg/m2) participated. Different components of SB (sitting, lying) and PA (standing, breaks in SB, daily steps, light PA, moderate-to-vigorous PA and total PA) were measured with validated hip-worn accelerometers for four consecutive weeks (mean 25 days, [SD 4]). Fasting venous blood samples were analysed using standard assays. The associations were examined with Pearson’s partial correlation coefficient test and linear mixed model.

Results

Among 102 women and 42 men accelerometer measured SB or the elements of PA were not associated with circulating liver enzymes. When adjusted for age and sex, liver enzymes correlated positively with BMI and waist circumference (WC) (ALT r=0.34, p<0.0001, r=0.41, < 0.0001, AST r=0.17, p=0.049, r=0.26, p=0.002, GGT r=0.29, p=0.0005, r=0.32, p < 0.0001, respectively). SB proportion associated positively with BMI (r=0.21, p=0.008) and WC (r=0.27, p=0.001). Components of PA associated negatively with BMI (MVPA r=-0.23, p=0.005, daily steps r=-0.30, p<0.0001 and breaks in sedentary time r=-0.32, p<0.0001), as well as with WC (breaks in SB r=-0.35, p<0.0001, MVPA r=-0.26, p=0.002, daily steps r=-0.31, p<0.0001, standing time r=-0.27, p=0.001). Liver enzymes associated positively with common cardiometabolic markers such as resting heart rate (ALT; β=0.17, p=0.03, AST; β=0.25, p=0.002, GGT; β=0.23, p=0.004) and systolic/diastolic blood pressure (ALT β=0.20, p=0.01, β=0.22, p=0.005, AST (only diastolic) β=0.23, p=0.006, GGT β=0.19, p=0.02, = 0.23, p=0.004, respectively), fasting insulin (ALT β=0.41, p<0.0001, AST β=0.36, p=0.0003, GGT β=0.20, p=0.04) and insulin resistance index (ALT β=0.42, p<0.0001, AST β=0.36, p=0.0003, GGT β=0.21, p=0.03), even after adjustment with BMI.

Conclusions

Liver enzymes correlate with body adiposity and appear to cluster with other common cardiometabolic risk factors, even independently of body adiposity. SB and PA appear not to be essential in modulating the levels of circulating liver enzymes.
Review on Coordinated Planning of Source-Network-Load-Storage for Integrated Energy Systems
Authors: Fan Hong , Yu Zichun , Xia Shiwei , Li Xuan
Published: April 2021

The integration of electricity, gas, and heat (cold) in the integrated energy system (IES) breaks the limitation of every single energy source, which is the development trend of future energy systems. To realize the coordinated planning of “source-network-load-storage,” the IES has to be conducive to improving energy efficiency, bringing economic and environmental benefit, and achieving sustainable development of energy. In this paper, the techniques and methods involved in IES planning are summarized. First, the structure and characteristics of the IES are briefly introduced. Second, the key findings of the IES planning are summarized from four perspectives: source, network, load, and storage. Then, the modeling methods of the IES collaborative planning are summarized, and the optimization methods for solving complex planning problems are analyzed. Compared with previous reviews, this paper focuses on the modeling of multi-energy coupling of each part of source-network-load-storage and modeling of the overall collaborative planning. Finally, the future research direction of IES planning is forecast.
Think Before You Act: Improving the Conservation Outcomes of CITES Listing Decisions
Authors: Cooney Rosie , Challender Daniel W. S. , Broad Steven , Roe Dilys , Natusch Daniel J. D.
Published: April 2021

The CITES treaty is the major international instrument designed to safeguard wild plants and animals from overexploitation by international trade. CITES is now approaching 50 years old, and we contend that it is showing its age. In stark contrast to most environmental policy arenas, CITES does not require, encourage, or even allow for, consideration of the impacts of its key decisions—those around listing species in the CITES Appendices. Decisions to list species in CITES are based on a simplistic set of biological and trade criteria that do not relate to the impact of the decision, and have little systematic evidentiary support. We explain the conservation failures that flow from this weakness and propose three key changes to the CITES listing process: (1) development of a formal mechanism for consideration by Parties of the likely consequences of species listing decisions; (2) broadening of the range of criteria used to make listing decisions; and (3) amplification of the input of local communities living alongside wildlife in the listing process. Embracing these changes will help to ensure CITES decisions more effectively respond to the needs of wildlife in today’s highly complex and dynamic conservation context.
Ecological Correlates of 20-Year Population Trends of Wintering Waterbirds in Deep Bay, South China
Authors: Sung Yik-Hei , Pang Chun-chiu , Li Tom Chung-hoi , Wong Paulina Pui Yun , Yu Yat-tung
Published: April 2021

Along the East Asian-Australasian flyway (EAAF), waterbirds are threatened by a wide range of human activities. Studies have shown that wintering populations of many species have declined in Australia and Japan; however, long term data along China’s coast are limited. In this study, we analyzed data collected from monthly bird surveys to quantify population trends of wintering waterbirds from 1998 to 2017 in the Deep Bay area, South China. Of the 42 species studied, 12 declined, while nine increased significantly. Phylogenetic comparative analysis revealed that population trends were negatively correlated to reliance on the Yellow Sea and body size. Further, waterbird species breeding in Southern Siberia declined more than those breeding in East Asia. These findings, coupled with a relatively high number of increasing species, support the continual preservation of wetlands in the Deep Bay area. This study provides another case study showing that data collected from wintering sites provide insights on the threats along migratory pathway and inform conservation actions. As such, we encourage population surveys in the EAAF to continue, particularly along the coast of China.
Metagenomic Geolocation Prediction Using an Adaptive Ensemble Classifier
Authors: Anyaso-Samuel Samuel , Sachdeva Archie , Guha Subharup , Datta Somnath
Published: April 2021

Microbiome samples harvested from urban environments can be informative in predicting the geographic location of unknown samples. The idea that different cities may have geographically disparate microbial signatures can be utilized to predict the geographical location based on city-specific microbiome samples. We implemented this idea first; by utilizing standard bioinformatics procedures to pre-process the raw metagenomics samples provided by the CAMDA organizers. We trained several component classifiers and a robust ensemble classifier with data generated from taxonomy-dependent and taxonomy-free approaches. Also, we implemented class weighting and an optimal oversampling technique to overcome the class imbalance in the primary data. In each instance, we observed that the component classifiers performed differently, whereas the ensemble classifier consistently yielded optimal performance. Finally, we predicted the source cities of mystery samples provided by the organizers. Our results highlight the unreliability of restricting the classification of metagenomic samples to source origins to a single classification algorithm. By combining several component classifiers via the ensemble approach, we obtained classification results that were as good as the best-performing component classifier.
Strategies for Using Muramyl Peptides - Modulators of Innate Immunity of Bacterial Origin - in Medicine
Authors: Guryanova Svetlana V. , Khaitov Rahim M.
Published: April 2021

The spread of infectious diseases is rampant. The emergence of new infections, the irrational use of antibiotics in medicine and their widespread use in agriculture contribute to the emergence of microorganisms that are resistant to antimicrobial drugs. By 2050, mortality from antibiotic-resistant strains of bacteria is projected to increase up to 10 million people per year, which will exceed mortality from cancer. Mutations in bacteria and viruses are occurring faster than new drugs and vaccines are being introduced to the market. In search of effective protection against infections, new strategies and approaches are being developed, one of which is the use of innate immunity activators in combination with etiotropic chemotherapy drugs. Muramyl peptides, which are part of peptidoglycan of cell walls of all known bacteria, regularly formed in the body during the breakdown of microflora and considered to be natural regulators of immunity. Their interaction with intracellular receptors launches a sequence of processes that ultimately leads to the increased expression of genes of MHC molecules, pro-inflammatory mediators, cytokines and their soluble and membrane-associated receptors. As a result, all subpopulations of immunocompetent cells are activated: macrophages and dendritic cells, neutrophils, T-, B- lymphocytes and natural killer cells for an adequate response to foreign or transformed antigens, manifested both in the regulation of the inflammatory response and in providing immunological tolerance. Muramyl peptides take part in the process of hematopoiesis, stimulating production of colony-stimulating factors, which is the basis for their use in the treatment of oncological diseases. In this review we highlight clinical trials of drugs based on muramyl peptides, as well as clinical efficacy of drugs mifamurtide, lycopid, liasten and polimuramil. Such a multifactorial effect of muramyl peptides and a well-known mechanism of activity make them promising drugs in the treatment and preventing of infectious, allergic and oncological diseases, and in the composition of vaccines.