bluuebunny/crossref_metadata_2025_split huggingface dataset:
Alamandine/MrgD axis prevents TGF-β1-mediated fibroblast activation via regulation of aerobic glycolysis and mitophagy
Authors: Wang Wei , Zhang Yue , Huang Wenhui , Yuan Yafei , Hong Qiaohui , Xie Zhanzhan , Li Lijuan , Chen Yixin , Li Xu , Meng Ying 
Published: January 2023

Abstract
Background
Idiopathic pulmonary fibrosis is a chronic progressive, lethal disease in which ectopic lung fibroblast (LF) activation plays a vital part. We have previously shown that alamandine (ALA) exerts anti-fibrosis effects via the MAS-related G-protein coupled receptor D (MrgD). Here, we further investigate how it moderates transforming growth factor β1 (TGF-β1)-induced LF activation by regulating glucose metabolism and mitochondria autophagy (mitophagy).

Methods
In vitro, we examined glycolysis-related protein hexokinase 2 (HK2), 6-phosphofructo-2-kinase/fructose-2,6-biphosphatase 3 (PFKFB3), and lactic acid in cells treated with TGF-β1. The oxygen consumption rate and the extracellular acidification rate were detected using Seahorse assays. Then, mitophagy was evaluated using transmission electron microscopy, mt-Keima, and the co-localization of Parkin and COX IV with LC3 and LAMP1, respectively. The autophagic degradation of HK2 and PFKFB3 was detected by 3MA and bafilomycin A1 and assessed by their co-localization with LC3 and LAMP1, respectively. The effects of ALA on LF activation markers collagen I and α-SMA were detected. The effects of ALA on glucose metabolism, mitophagy, and the activation of LF were also investigated in vivo.

Results
We found that the ALA/MrgD axis improved TGF-β1-mediated LF activation by repressing glycolysis by downregulating HK2 and PFKFB3 expression. Lactic acid sustained positive feedback between glycolysis and LF activation by maintaining the expression of HK2 and PFKFB3. We also showed that glycolysis enhancement resulted from blocking the autophagic degradation of HK2 and PFKFB3 while upregulated mRNA levels by TGF-β1, while all of those improved by ALA adding. Importantly, we determined that moderation of Parkin/LC3-mediated mitophagy by TGF-β1 also promotes glycolysis but is reversed by ALA. Furthermore, we proved that ALA counteracts the effects of bleomycin on HK2, PFKFB3, LC3, Parkin, and LF activation in vivo.

Conclusion
In this study, we show that the ALA/MrgD axis prevents TGF-β1-mediated fibroblast activation via regulation of aerobic glycolysis and mitophagy.
Blocking interleukin-23 ameliorates neuromuscular and thymic defects in myasthenia gravis
Authors: Villegas José A. , Van Wassenhove Jérôme , Merrheim Judith , Matta Karen , Hamadache Samy , Flaugère Clémence , Pothin Pauline , Truffault Frédérique , Hascoët Sébastien , Santelmo Nicola , Alifano Marco , Berrih-Aknin Sonia , le Panse Rozen , Dragin Nadine 
Published: January 2023

AbstractAcetylcholine receptor (AChR) myasthenia gravis (MG) is a chronic autoimmune disease characterized by muscle weakness. The AChR+ autoantibodies are produced by B-cells located in thymic ectopic germinal centers (eGC). No therapeutic approach is curative. The inflammatory IL-23/Th17 pathway is activated in the thymus as well as in the blood and the muscle, contributing to the MG pathogenic events. We aimed to study a potential new therapeutic approach that targets IL-23p19 (IL-23) in the two complementary preclinical MG models: the classical experimental MG mouse model (EAMG) based on active immunization and the humanized mouse model featuring human MG thymuses engrafted in NSG mice (NSG-MG). In both preclinical models, the anti-IL-23 treatment ameliorated MG clinical symptoms. In the EAMG, the treatment reduced IL-17 related inflammation, anti-AChR IgG2b antibody production, activated transduction pathway involved in muscle regeneration and ameliorated the signal transduction at the neuromuscular junction. In the NSG-MG model, the treatment reduced pathogenic Th17 cell population and expression of genes involved in eGC stabilization and B-cell development in human MG thymus biopsies. Altogether, these data suggest that a therapy targeting IL-23p19 may promote significant clinical ameliorations in AChR+ MG disease due to concomitant beneficial effects on the thymus and skeletal muscle defects.
HIV infection of non-classical cells in the brain
Authors: Wahl Angela , Al-Harthi Lena 
Published: January 2023

AbstractHIV-associated neurological disorders (HAND) affect up to 50% of people living with HIV (PLWH), even in the era of combination antiretroviral therapy (cART). HIV-DNA can be detected in the cerebral spinal fluid (CSF) of approximately half of aviremic ART-suppressed PLWH and its presence is associated with poorer neurocognitive performance. HIV DNA + and HIV RNA + cells have also been observed in postmortem brain tissue of individuals with sustained cART suppression. In this review, we provide an overview of how HIV invades the brain and HIV infection of resident brain glial cells (astrocytes and microglia). We also discuss the role of resident glial cells in persistent neuroinflammation and HAND in PLWH and their potential contribution to the HIV reservoir. HIV eradication strategies that target persistently infected glia cells will likely be needed to achieve HIV cure.
Radiation-induced senescence: therapeutic opportunities
Authors: Kim Jae Ho , Brown Stephen L. , Gordon Marcia N. 
Published: January 2023

AbstractThe limitation of cancer radiotherapy does not derive from an inability to ablate tumor, but rather to do so without excessively damaging critical tissues and organs and adversely affecting patient’s quality of life. Although cellular senescence is a normal consequence of aging, there is increasing evidence showing that the radiation-induced senescence in both tumor and adjacent normal tissues contributes to tumor recurrence, metastasis, and resistance to therapy, while chronic senescent cells in the normal tissue and organ are a source of many late damaging effects. In this review, we discuss how to identify cellular senescence using various bio-markers and the role of the so-called senescence-associated secretory phenotype characteristics on the pathogenesis of the radiation-induced late effects. We also discuss therapeutic options to eliminate cellular senescence using either senolytics and/or senostatics. Finally, a discussion of cellular reprogramming is presented, another promising avenue to improve the therapeutic gain of radiotherapy.
The relationship between quality of life and health promotion behavior in patients with type B aortic dissection: a cross-sectional study
Authors: Tu Jianxin , Wang Fei , Yin Furong , Zhang Linxue , Zhao Benli , Zhou Jiamei 
Published: January 2023

Abstract
Background
To understand the current situation of health promotion behavior and quality of life among aortic dissection survivors and the correlation between them.

Methods
Sociodemographic characteristics were collected. T-test and variance analysis were applied for univariate analysis. Quality of life was measured using the SF-36 Questionnaire, and health-promoting behaviors were measured using the aortic dissection health promotion behavior questionnaire. The association between type B aortic dissection survivors’ health promotion behavior and health status questionnaire (SF-36) scores was determined through Pearson’s correlation coefficients. This association was analyzed through multivariable regression analysis.

Results
A total of 131 type B aortic dissection survivors were evaluated through the self-developed aortic dissection patient health promotion behavior scale and health status questionnaire (SF-36). Results showed that the health promotion behavior of Stanford B aortic dissection survivors (85.05 ± 11.28) correlated with their Mental Component Summary (MCS) (55.23 ± 30.72; r = 0.359, P < 0.01). The model showed 39.00% variance shared between behavior motivation and MCS (R2 = 0.390, F = 13.189, P < 0.01).

Conclusion
Type B aortic dissection survivors in Zunyi, China had a lower quality of life. Medical staff can formulate intervention measures from behavioral motivation to improve the quality of life of aortic dissection survivors.
Aldosterone inhibits Dot1l expression in guinea pig cochlea
Authors: Zhong Shixun , Zhang Biyun , Qin Li , Wang Qianying , Luo Xiaoli 
Published: January 2023

Abstract
Background
Aldosterone relieves transcriptional repression of epithelial sodium channel (ENaC) by inhibiting Dot1a and Af9 expression and their interaction with ENaC promoter in various tissues. Expressions of ENaC and Af9 in inner ear have been identified. However, it is not known how Dot1l is regulated by aldosterone in inner ear.

Methods
Twenty-eight adult guinea pigs were randomly divided into the control group and treatment group. Aldosterone 1 mg/kg/d was injected intraperitoneally in the treatment group and saline in the control group for 7 days. Animals were killed 1 month later following auditory brainstem response examination. Histomorphology of cochlea was detected with hematoxylin–eosin staining, and Dot1l expression was examined with immunohistochemistry and Western blot.

Results
There was no significant difference in ABR thresholds before and after injection of aldosterone or saline in either group. Endolymphatic hydrops was found in 75% of animals in the treatment group. Dot1l was found in both groups in the stria vascularis, Reissner’s membrane, spiral limbus, organ of Corti and spiral ligament. Dot1l expression in the treatment group was decreased by aldosterone.

Conclusions
Dot1l in guinea pig cochlea is inhibited by aldosterone with induction of endolymphatic hydrops. Dot1l may be closely related to endolymph regulation by aldosterone and to pathogenesis of Meniere’s disease.
Reversible flowering of CuO nanoclusters via conversion reaction for dual-ion Li metal batteries
Authors: Li Siying , Lee Jung-Hun , Hwang Soo Min , Kim Young-Jun 
Published: January 2023

AbstractDual-ion Li metal batteries based on non-flammable SO2-in-salt inorganic electrolytes ( Li–SO2 batteries) offer high safety and energy density. The use of cupric oxide (CuO) as a self-activating cathode material achieves a high specific capacity with cost-effective manufacturing in Li–SO2 batteries, but its cycle retention performance deteriorates owing to the significant morphological changes of the cathode active materials. Herein, we report the catalytic effect of carbonaceous materials used in the cathode material of Li–SO2 batteries, which act as templates to help recrystallize the active materials in the activation and conversion reactions. We found that the combination of oxidative-cyclized polyacrylonitrile (PAN) with N-doped carbonaceous materials and multi-yolk-shell CuO (MYS-CuO) nanoclusters as cathode active materials can significantly increase the specific capacity to 315.9 mAh g− 1 (93.8% of the theoretical value) at 0.2 C, which corresponds to an energy density of 1295 Wh kgCuO−1, with a capacity retention of 84.46% at the 200th cycle, and the cathode exhibited an atypical blossom-like morphological change.
Stable overexpression and targeted gene deletion of the causative agent of ash dieback Hymenoscyphus fraxineus
Authors: Lutz Tobias , Hadeler Birgit , Jaeckel Mareike , Schulz Barbara , Heinze Cornelia 
Published: January 2023

Abstract
Background
Due to the infection with the invasive ascomycete Hymenoscyphus fraxineus, which has been replacing the closely related and non-pathogenic native Hymenoscyphus albidus, the European ashes, Fraxinus excelsior (also known as the common ash), Fraxinus angustifolia (also known as narrow-leaved ash) and Fraxinus ornus (also known as the manna ash) are at risk. Hymenoscyphus fraxineus is the causative agent of ash dieback of the European ashes, but is non-pathogenic to the native Asian ash Fraxinus mandshurica (also known as the Manchurian ash). Even though the invasion of H. fraxineus is a great threat for ashes in Europe, the fungal biology is still poorly understood. By the use of live cell imaging and targeted gene knock-out, the fungal life cycle and host–pathogen interaction can be studied in more detail.

Results
Here, we developed a protocol for the preparation of protoplasts from mycelium of H. fraxineus, for their regeneration and for stable transformation with reporter genes and targeted gene knock-out by homologous recombination. We obtained mutants with various levels of reporter gene expression which did not correlate with the number of integrations. In an in vitro infection assay, we demonstrated the suitability of reporter gene overexpression for fungal detection in plant tissue after inoculation. As a proof of principle for targeted gene knock-out, the hygromycin resistance cassette of a reporter gene-expressing mutant was replaced with a geneticin resistance cassette.

Conclusions
The invasive fungal pathogen H. fraxineus is threatening the European ashes. To develop strategies for pest management, a better understanding of the fungal life cycle and its host interaction is crucial. Here, we provide a protocol for stable transformation of H. fraxineus to obtain fluorescence reporter strains and targeted gene knock-out mutants. This protocol will help future investigations on the biology of this pathogen.
Digital technologies, technological improvement rates, and innovations “Made in Switzerland”
Authors: Niggli Matthias , Rutzer Christian 
Published: January 2023

AbstractTechnologies evolve at different paces and their rate of improvement varies considerably. We demonstrate that the fastest technological progress currently occurs in the digital domain and empirically investigate the relationship between technologies’ improvement rates and breakthrough innovations as measured by forward citations of patents. Our empirical estimates suggest that patents from the digital sphere, as well as those related to fast-improving technologies, are associated with a higher probability to produce breakthrough innovations. We then investigate Swiss core industries’ specialization patterns toward these potential high-impact technologies and compare the state of cutting-edge innovation in Switzerland to other countries. Our findings imply that the Swiss innovation system is among the laggards regarding innovations in today’s fastest improving digital technologies.
Taste adaptations associated with host specialization in the specialistDrosophila sechellia
Authors: Reisenman Carolina E. , Wong Joshua , Vedagarbha Namrata , Livelo Catherine , Scott Kristin 
Published: January 2023

ABSTRACTChemosensory-driven host plant specialization is a major force mediating insect ecological adaptation and speciation. Drosophila sechellia, a species endemic to the Seychelles islands, feeds and oviposits on Morinda citrifolia almost exclusively. This fruit is harmless to D. sechellia but toxic to other Drosophilidae, including the closely related generalists D. simulans and D. melanogaster, because of its high content of fatty acids. While several olfactory adaptations mediating D. sechellia’s preference for its host have been uncovered, the role of taste has been much less examined. We found that D. sechellia has reduced taste and feeding aversion to bitter compounds and host fatty acids that are aversive to D. melanogaster and D. simulans. The loss of aversion to canavanine, coumarin and fatty acids arose in the D. sechellia lineage, as its sister species D. simulans showed responses akin to those of D. melanogaster. Drosophila sechellia has increased taste and feeding responses towards M. citrifolia. These results are in line with D. sechellia’s loss of genes that encode bitter gustatory receptors (GRs) in D. melanogaster. We found that two GR genes which are lost in D. sechellia, GR39a.a and GR28b.a, influence the reduction of aversive responses to some bitter compounds. Also, D. sechellia has increased appetite for a prominent host fatty acid compound that is toxic to its relatives. Our results support the hypothesis that changes in the taste system, specifically a reduction of sensitivity to bitter compounds that deter generalist ancestors, contribute to the specialization of D. sechellia for its host.
Impact of Modularity Design on Mobile App Launch Success
Authors: Chung Moonwon , Sharma Luv , Malhotra Manoj K. 
Published: January 2023

Problem definition: Initial product design decisions are critically important for mobile apps, which show a relatively short time from launch to peak usage, thus providing a narrow window for success and no time for course correction based on market reaction. Mobile apps are designed using a highly modular architecture based on software development kits (SDKs), with SDK choices being sequentially determined along three dimensions—multiplicity (total number of SDKs), compatibility (SDK co-occurrence frequency), and novelty (SDK degree of newness to the developer). We evaluate the consequence of these decisions on initial market success in the context of mobile gaming app design. Academic/practical relevance: The resulting conceptual framework aids developers in determining the modularity of digital product development. Methodology: We formulate an instrumental variables least absolute shrinkage and selection operator regression model to estimate relationships of interest using a proprietary data set extracted from the application programming interface server of a leading mobile apps intelligence firm. Results: We find a negative impact of SDK multiplicity on initial success. High SDK compatibility can mitigate this negative effect, whereas high SDK novelty can exacerbate the negative effect of multiplicity. Post hoc analysis shows that business-to-consumer (B2C) communication features can also mitigate this negative impact. Managerial implications: Prior product modularity research has predominantly focused on physical products or relied on single-dimensional modularity measures. Our study conceptualizes modularity as multidimensional and investigates how these multidimensional SDK-based modularity choices impact the performance of a key category of digital products—mobile apps. We demonstrate that increasing multiplicity, essential in certain markets, negatively affects initial success. However, firms can enhance SDK compatibility, reduce SDK novelty, and use B2C communication channels to mitigate this negative impact. Supplemental Material: The online appendix is available at https://doi.org/10.1287/msom.2022.1181 .
Statistical Inference for Aggregation of Malmquist Productivity Indices
Authors: Pham Manh , Simar Léopold , Zelenyuk Valentin 
Published: January 2023

A Comprehensive Set of Asymptotic Properties for a Meaningful Aggregation of Malmquist Indices The Malmquist productivity index (MPI) has become one of the most widely used tools for analyzing dynamic performance of decision-making units. Whereas accounting for economic weights of individual units in aggregations of indices is emphasized in the literature, statistical theory for constructing confidence intervals and performing hypothesis tests based on weighted aggregation of the MPI are still unavailable. In “Statistical Inference for Aggregation of Malmquist Productivity Indices,” Pham, Simar, and Zelenyuk use a novel approach (based on the uniform delta method) to develop new asymptotic theory (including new central limit theorems) for aggregate MPIs as the basis for the statistical inference and test. They also verify the finite-sample performance of their approach via extensive Monte Carlo experiments and provide an illustration using real-world data.
Acessibilidade digital do canal de governança pública 'Central 156' de Curitiba, Brasil
Authors: Liu Eunice , Fonseca Keiko Veronica Ono , Kozievitch Nadia , Cascione Lukas Wesley 
Published: January 2023

A 'Central 156' é um serviço da Prefeitura de Curitiba (Paraná, Brasil), em aplicativo e site, onde os cidadãos podem solicitar serviços municipais, informações, bem como registrar demandas e queixas de problemas de ordem pública. Este trabalho analisa a acessibilidade desta plataforma, com o objetivo de definir uma metodologia de avaliação, a fim de diagnosticar pontos de melhoria para os seus canais. Nesta pesquisa, guias e manuais de acessibilidade, nacionais e internacionais, que definem diretrizes de design universal, internet acessível, ergonomia e princípios de acessibilidade foram utilizados. O resultado é um relatório com sugestões de melhorias para implementação, de modo que mais cidadãos possam participar ativamente dos processos de tomada de decisão do município. O banco de dados pode subsidiar gestores públicos em tomada de decisões e contribuir para a construção de uma cidade mais inteligente e sustentável. A metodologia pode também ser aplicada para outras plataformas de governança digital.
A Diplomacia do Etanol na América Latina e Caribe: O que queria o Brasil? | Ethanol Diplomacy in Latin America and the Caribbean: What Did Brazil Want? (2003-2010)
Authors: Feitosa Lucas Marques , Mazzarella Maria Gabriela Mendonça , Do Nascimento Luiz Fernando Oliveira 
Published: January 2023

Este trabalho discute a diplomacia do etanol realizada pelo Brasil durante o governo Lula, com especial atenção aos atos internacionais assinados nesse período. Esta pesquisa se estrutura em torno de um eixo principal: entender quais eram as preferências do Brasil ao promover a diplomacia do etanol em meio aos países da América Latina e do Caribe. A metodologia utilizada envolveu a construção de um banco de dados original, bem como a aplicação de técnicas de estatística descritiva e análise de conteúdo. Os achados indicam que o Brasil utilizou a diplomacia do etanol através da assinatura de atos internacionais para construir coalizões dentro da região com o intuito de estabelecer um mercado internacional de etanol. Contudo, pudemos verificar que os atos internacionais assinados não resultaram de fato nos efeitos esperados pelo Brasil para a região.Palavras-chave: Acordos Internacionais. Etanol. Brasil.ABSTRACTThis paper discusses the ethanol diplomacy carried out by Brazil during the Lula administration, with special attention to the international agreements signed during this period. This research is structured around a main axis: understanding what Brazil's preferences were when promoting ethanol diplomacy among Latin American and Caribbean countries. The methodology used involved the construction of an original database, as well as the application of descriptive statistics and content analysis techniques. The findings indicate that Brazil used ethanol diplomacy through the signing of international acts to build coalitions within the region in order to establish an international ethanol market. However, we were able to verify that the signed international agreements did not actually result in the effects expected by Brazil for the region.Keywords: International Agreements. Ethanol. Brazil. Recebido em: 14 jun. 2022 | Aceito em: 20 dez. 2022.