bluuebunny/crossref_metadata_2025 huggingface dataset:
Theoretical Study on Relaxed Surrounding Rock Pressure on Shallow Bias Neighborhood Tunnels under Seismic Load
Authors: Liu Xinrong , Xiong Fei , Liu Dongshuang , Zhou Xiaohan , Li Dongliang , Wang Linfeng , Han Yafeng , He Chunmei
Published: August 2021

To study the distribution of relaxed surrounding rock pressure on the shallow bias neighborhood tunnels under the combined action of horizontal and vertical earthquake force, finite element software was used for failure mode analysis. Moreover, with the pseudo-static method, the calculation formula for the relaxed pressure on the shallow bias neighborhood tunnels was derived and used to analyze the variation of the rupture angle of these tunnels under the action of the seismic force. The study shows that: shallow bias neighborhood tunnels basically follow a “W” failure pattern under the combined action of horizontal and vertical seismic force, and the failure scope of the surrounding rock is controlled by four rupture angles. Rupture angles β2 and β3 between the deep and shallow tunnels of the shallow bias neighborhood tunnels are not affected by the surface slope. For tunnels with the same grade of the surrounding rock, the greater the seismic intensity, the smaller the value of β2, and the greater the value of β3. While at the same seismic intensity, the higher the grade of the surrounding rock, the smaller the β2 and β3. Ruptures angles β1 and β4 are influenced by the surface slope, seismic intensity and surrounding rock grades. A steeper surface slope leads to a smaller β1 and a greater β4; β1 increase and β4 decrease with increasing seismic intensity; while, β1 and β4 both show a decreasing trend with an increasing rock grade.
A STUDY OF VOLUNTEERS’ SCIENCE SERVICE SATISFACTION IN RELATION TO THEIR SELF-DIRECTED LEARNING AND MOTIVATION
Authors: Chien Hui-Min
Published: August 2021

In Taiwan, the Science Volunteer Locomotive (SVL) Program has been in operation for the past ten years. During these years of its implementation, the SVL Program has continued to participate in and co-ordinate various national scientific activities. This study examined the relationships between volunteers’ prime motivations, self-directed learning and satisfaction among Taiwanese science volunteers. To explore volunteers’ perspectives on their involvement in science service, in this research, we developed three questionnaires to investigate the relationships among volunteers’ motivation, self-directed learning and satisfaction with their science service. The study sample included 289 volunteers, taken from a project for science volunteers run by the Ministry of Science and Technology in Taiwan. The results indicate that the prime motivations and self-directed learning of science volunteers are focused on doing something meaningful for others and for society in general. It was found that the science volunteers’ motivation, self-directed learning and satisfaction all had significant positive correlations. The findings suggest that science training programs may provide some motivational support to enhance satisfaction, so that science volunteers will be more inclined to participate in collaborative scientific projects.
Keywords: prime motivation, service satisfaction, science volunteers, self-directed learning.
RCIU severo: A propósito de un caso y revisión de la literatura
Authors: Ayala Yauri Maryllini , Guerrero Torres Jhon Carlo , Ventura Laveriano Walter R. , Sugajara Rosario Ricardo R. , Ibañez Rodríguez Cecilia , Castillo Urquiaga Walter
Published: August 2021

La restricción del crecimiento intrauterino se define como aquel feto que no alcanza su potencial de crecimiento. Las presentaciones temprana (<32 semanas) y tardía (> 32 semanas) tienen características diferenciales pero no excluyentes; en relación al grado de compromiso obstructivo placentario que repercute en la severidad de las manifestaciones hemodinámicas. Para su diagnóstico, seguimiento y manejo, contamos con la evaluación Doppler multivaso, la cual provee información sobre el deterioro y el riesgo de mortalidad intra útero para establecer el momento oportuno del nacimiento.

Presentamos el reporte de un caso de restricción de crecimiento intrauterino de presentación temprana con alteración doppler severa evaluado por nuestro servicio y revisamos la patogenia, clínica y el enfoque diagnóstico y manejo de esta condición
Caracterización epidemiológica, anticoncepción y bienestar psicológico en mujeres a dos años post aborto terapéutico
Authors: Guevara Ríos Enrique , Carranza-Asmat Cesar , Meza-Santibañez Luis , Ayala-Peralta Félix , Arango-Ochante Pedro , Espinola-Sánchez Marcos , Guevara Beltrán Nora Patricia , Mejía-Muñoz Ana María , Rondón Rondón Marta
Published: August 2021

Objetivo: Describir las características epidemiológicas, anticoncepción y bienestar psicológico en una serie de mujeres a dos años de post aborto terapéutico. Materiales y métodos: Estudio observacional, descriptivo de una serie de casos. Participaron las mujeres cuyo procedimiento de aborto terapéutico fue realizado en el Instituto Nacional Materno Perinatal del Perú el año 2018 y que al momento de la entrevista hayan transcurrido dos años, previo consentimiento informado. Se recogieron datos sociodemográficos, perfil obstétrico, método de planificación familiar antes del aborto terapéutico y actual. Se aplicó la Escala BIEPS para medir el bienestar psicológico de las participantes a dos años post aborto terapéutico. Se efectuó análisis descriptivo y se salvaguardó la identidad de las participantes. Resultados: Se estudiaron 12 mujeres a dos años de presentar aborto terapéutico. Al momento del aborto terapéutico tenían una edad entre 21 y 38 años, la edad gestacional se encontraba entre 14 y 22 semanas, de los 12 casos cinco mujeres no usaban métodos de anticoncepción. Todos los casos presentaban patología fetal, siendo más frecuente Hidrops fetal e higroma quístico. Todas las mujeres tenían alteración en su salud mental. El procedimiento de aborto más frecuente empleado fue el uso de misoprostol y legrado uterino, en 11 casos. Posterior al aborto terapéutico 7 de 12 no usaron algún método, 5 mujeres presentaron un grado de bienestar psicológico elevado y 7 un nivel alto. En los dominios evaluados de bienestar psicológico los puntajes más altos fueron en propósito en la vida (11 casos de 12), seguido de auto aceptación (10 casos de 12) y crecimiento personal (3 casos de 12). Mientras que, los dominios con una puntuación media fueron relaciones positivas, autonomía y dominio del entorno. Conclusiones: Estos hallazgos sugieren que las mujeres con una gestación con un feto con malformaciones congénitas incompatibles con la vida presentaban una alteración en su salud mental. En estas condiciones, las mujeres presentaron una interrumpen terapéutica de su embarazo; y posteriormente a dos años presentaron un bienestar psicológico adecuado.
Pengetahuan dan Sumber Informasi Berhubungan dengan Tindakan Pemeriksaan Payudara Sendiri pada Siswi SMA
Authors: Ningsi Agustina , Mukarramah Sitti , Cahyanti Arika
Published: August 2021

Breast Self-Examination (BSE) is the development of a woman's concern for the condition of her own breasts. Breast cancer is a malignant tumor that grows in the breast tissue. The incidence of breast cancer reaches 42.1 per 100,000 population with an average death rate of 17 per 100,000 population. BSE on a regular basis is an important step for early detection of breast cancer. This study aims to determine the relationship between knowledge and sources of information about breast self-examination with early detection of breast cancer in female students of SMA Muhammadiyah 5 Tallo, Makassar City, using an analytic survey method and a Cross Sectional Design. The subjects of this study were young women in SMA Muhammadiyah 5 Tallo Makassar City with a population of 53 respondents who were taken by total sampling. Statistical analysis used in this study is Chi-Square statistic, with a confidence level of ɑ=0.05. Based on the results of the study, it is known that the knowledge significance value is P = 0.001 (p < 0.05) with a coefficient value (Phi = 0.465), the source of information is p = 0.000 (p < 0.05) with a coefficient value (Phi = 0.635). So it can be concluded that there is a relationship between knowledge and sources of information about breast self-examination at SMA Muhammadiyah 5 Tallo Makassar City. It is recommended for education providers and health workers to increase counseling about breast self-examination.
Influences of atmospheric circulation patterns on interannual variability of winter precipitation over the northern part of the Korean Peninsula
Authors: Jong SI , Om KC , Pak YI
Published: August 2021

Explaining the relationship between atmospheric circulation patterns and precipitation over a given area is one of the key problems in predicting climate variables for monthly and seasonal leadtime. We investigated the influence of atmospheric circulation indices on winter precipitation over the northern part of the Korean Peninsula (WP-NPKP) during the period 1949-�2020. Data from 37 weather stations were used to calculate the correlation coefficients between WP-NPKP and the Siberian High (SH) and the Aleutian Low (AL), which are thought to dominate the winter weather systems over the study area. We chose those atmospheric circulation indices which are closely connected with the interannual variability of WP-NPKP and explained their possible mechanisms. To identify circulation patterns which most strongly correlated with WP-NPKP, one-point simultaneous correlation maps were created using Pearson correlation analysis, and their monotonic trends were tested with the Mann-Kendall method. We found that interannual variability of WP-NPKP had a closer connection with the difference in area-averaged climate variable anomalies over any 2 areas than with the anomalies themselves. Increased AL index minus decreased SH index had some correlation with winter rainfall; higher sea level pressure over the ocean, rather than that over land, was favorable for the transport of moisture toward the study area. Also, the indices which describe differences in air temperature anomalies at lower and middle latitudes had a relatively high correlation with WP-NPKP, and the difference indices of area-averaged zonal and meridional wind anomalies indicated a considerable linkage with winter precipitation over the study area. Their possible mechanisms, which we discuss in comparison to other studies of winter climate over East Asia, are very useful in selecting the predictors for monthly and seasonal prediction of climate variables over the study area.
Engineering Functional Vasculature in Decellularized Lungs Depends on Comprehensive Endothelial Cell Tropism
Authors: Akinnola Ifeolu , Rossi Daniel R. , Meyer Carolyn , Lindsey Ashley , Haase Douglas R. , Fogas Samuel , Ehrhardt Michael J. , Blue Rachel E. , Price Andrew. P. , Johnson Max , Alvarez Diego F. , Taylor Doris A. , Panoskaltsis-Mortari Angela
Published: August 2021

Tissue engineering using decellularized whole lungs as matrix scaffolds began as a promise for creating autologous transplantable lungs for patients with end-stage lung disease and can also be used to study strategies for lung regeneration. Vascularization remains a critical component for all solid organ bioengineering, yet there has been limited success in generating functional re-endothelialization of most pulmonary vascular segments. We evaluated recellularization of the blood vessel conduits of acellular mouse scaffolds with highly proliferating, rat pulmonary microvascular endothelial progenitor cells (RMEPCs), pulmonary arterial endothelial cells (PAECs) or microvascular endothelial cells (MVECs). After 8 days of pulsatile perfusion, histological analysis showed that PAECs and MVECs possessed selective tropism for larger vessels or microvasculature, respectively. In contrast, RMEPCs lacked site preference and repopulated all vascular segments. RMEPC-derived endothelium exhibited thrombomodulin activity, expression of junctional genes, ability to synthesize endothelial signaling molecules, and formation of a restrictive barrier. The RMEPC phenotype described here could be useful for identifying endothelial progenitors suitable for efficient vascular organ and tissue engineering, regeneration and repair.
The Effects of Maternal Smoking on Pregnancy and Offspring: Possible Role for EGF?
Authors: Janbazacyabar Hamed , van Daal Marthe , Leusink-Muis Thea , van Ark Ingrid , Garssen Johan , Folkerts Gert , van Bergenhenegouwen Jeroen , Braber Saskia
Published: August 2021

Cigarette smoke exposure during pregnancy and lactation is associated with adverse pregnancy outcomes. Here, we investigated the effects of maternal smoke exposure on pregnancy and offspring immunity and explored whether, epidermal growth factor (EGF), an important growth-promoting factor in human colostrum and milk, might be a possible missing link in maternal smoke exposure and changes in infants’ immune responses. Pregnant BALB/c mice were exposed to either cigarette smoke or air during gestation and lactation, and effects on pulmonary inflammation in dams and immune responses in offspring were examined. Maternal smoke exposure increased airway hyperresponsiveness and accumulation of inflammatory cells in the lungs of pregnant dams compared to non-pregnant dams. The E-cadherin protein expression was reduced in mammary glands of cigarette smoke-exposed pregnant dams. EGF levels were higher in mammary glands and serum of smoke-exposed pregnant dams compared to air-exposed pregnant dams. Offspring from cigarette smoke-exposed dams exhibited elevated levels of IL-17A, MCP-1, IL-22, and IL-13 in anti-CD3 stimulated spleen cell culture supernatants. EGF levels were also increased in serum of offspring from smoke-exposed dams. A positive correlation was observed between serum EGF levels and neutrophil numbers in bronchoalveolar lavage fluid of the dams. Interestingly, IL-17A, MCP-1, IL-22, IL13, and IFN-γ levels in anti-CD3 stimulated spleen cell culture supernatants of male pups also showed a positive correlation with EGF serum levels. In summary, our results reveal that maternal smoke exposure predisposes dams to exacerbated airway inflammation and offspring to exacerbated immune responses and both phenomena are associated with elevated EGF concentrations.
Microbial Warfare on Three Fronts: Mixed Biofilm of Aspergillus fumigatus and Staphylococcus aureus on Primary Cultures of Human Limbo-Corneal Fibroblasts
Authors: Ramírez-Granillo Adrián , Bautista-Hernández Luis Antonio , Bautista-De Lucío Víctor Manuel , Magaña-Guerrero Fátima Sofía , Domínguez-López Alfredo , Córdova-Alcántara Itzel Margarita , Pérez Néstor O. , Martínez-Rivera María de los Angeles , Rodríguez-Tovar Aída Verónica
Published: August 2021

Background

Coinfections with fungi and bacteria in ocular pathologies are increasing at an alarming rate. Two of the main etiologic agents of infections on the corneal surface, such as Aspergillus fumigatus and Staphylococcus aureus, can form a biofilm. However, mixed fungal–bacterial biofilms are rarely reported in ocular infections. The implementation of cell cultures as a study model related to biofilm microbial keratitis will allow understanding the pathogenesis in the cornea. The cornea maintains a pathogen-free ocular surface in which human limbo-corneal fibroblast cells are part of its cell regeneration process. There are no reports of biofilm formation assays on limbo-corneal fibroblasts, as well as their behavior with a polymicrobial infection.

Objective

To determine the capacity of biofilm formation during this fungal–bacterial interaction on primary limbo-corneal fibroblast monolayers.

Results

The biofilm on the limbo-corneal fibroblast culture was analyzed by assessing biomass production and determining metabolic activity. Furthermore, the mixed biofilm effect on this cell culture was observed with several microscopy techniques. The single and mixed biofilm was higher on the limbo-corneal fibroblast monolayer than on abiotic surfaces. The A. fumigatus biofilm on the human limbo-corneal fibroblast culture showed a considerable decrease compared to the S. aureus biofilm on the limbo-corneal fibroblast monolayer. Moreover, the mixed biofilm had a lower density than that of the single biofilm. Antibiosis between A. fumigatus and S. aureus persisted during the challenge to limbo-corneal fibroblasts, but it seems that the fungus was more effectively inhibited.

Conclusion

This is the first report of mixed fungal–bacterial biofilm production and morphological characterization on the limbo-corneal fibroblast monolayer. Three antibiosis behaviors were observed between fungi, bacteria, and limbo-corneal fibroblasts. The mycophagy effect over A. fumigatus by S. aureus was exacerbated on the limbo-corneal fibroblast monolayer. During fungal–bacterial interactions, it appears that limbo-corneal fibroblasts showed some phagocytic activity, demonstrating tripartite relationships during coinfection.
Systematic Comparison of the Performances of De Novo Genome Assemblers for Oxford Nanopore Technology Reads From Piroplasm
Authors: Wang Jinming , Chen Kai , Ren Qiaoyun , Zhang Ying , Liu Junlong , Wang Guangying , Liu Aihong , Li Youquan , Liu Guangyuan , Luo Jianxun , Miao Wei , Xiong Jie , Yin Hong , Guan Guiquan
Published: August 2021

Background

Emerging long reads sequencing technology has greatly changed the landscape of whole-genome sequencing, enabling scientists to contribute to decoding the genetic information of non-model species. The sequences generated by PacBio or Oxford Nanopore Technology (ONT) be assembled de novo before further analyses. Some genome de novo assemblers have been developed to assemble long reads generated by ONT. The performance of these assemblers has not been completely investigated. However, genome assembly is still a challenging task.

Methods and Results

We systematically evaluated the performance of nine de novo assemblers for ONT on different coverage depth datasets. Several metrics were measured to determine the performance of these tools, including N50 length, sequence coverage, runtime, easy operation, accuracy of genome and genomic completeness in varying depths of coverage. Based on the results of our assessments, the performances of these tools are summarized as follows: 1) Coverage depth has a significant effect on genome quality; 2) The level of contiguity of the assembled genome varies dramatically among different de novo tools; 3) The correctness of an assembled genome is closely related to the completeness of the genome. More than 30× nanopore data can be assembled into a relatively complete genome, the quality of which is highly dependent on the polishing using next generation sequencing data.

Conclusion

Considering the results of our investigation, the advantage and disadvantage of each tool are summarized and guidelines of selecting assembly tools are provided under specific conditions.
Respecting Human Autonomy in Critical Care Clinical Decision Support
Authors: Hendriks Monique , Willemsen Martijn C. , Sartor Francesco , Hoonhout Jettie
Published: August 2021

Clinical Decision Support (CDS) aims at helping physicians optimize their decisions. However, as each patient is unique in their characteristics and preferences, it is difficult to define the optimal outcome. Human physicians should retain autonomy over their decisions, to ensure that tradeoffs are made in a way that fits the unique patient. We tend to consider autonomy in the sense of not influencing decision-making. However, as CDS aims to improve decision-making, its very aim is to influence decision-making. We advocate for an alternative notion of autonomy as enabling the physician to make decisions in accordance with their professional goals and values and the goals and values of the patient. This perspective retains the role of autonomy as a gatekeeper for safeguarding other human values, while letting go of the idea that CDS should not influence the physician in any way. Rather than trying to refrain from incorporating human values into CDS, we should instead aim for a value-aware CDS that actively supports the physician in considering tradeoffs in human values. We suggest a conversational AI approach to enable the CDS to become value-aware and the use of story structures to help the user integrate facts and data-driven learnings provided by the CDS with their own value judgements in a natural way.
Within-Species Trait Variation Can Lead to Size Limitations in Seed Dispersal of Small-Fruited Plants
Authors: Rehling Finn , Jaroszewicz Bogdan , Braasch Leonie Victoria , Albrecht Jörg , Jordano Pedro , Schlautmann Jan , Farwig Nina , Schabo Dana G.
Published: August 2021

The inability of small-gaped animals to consume very large fruits may limit seed dispersal of the respective plants. This has often been shown for large-fruited plant species that remain poorly dispersed when large-gaped animal species are lost due to anthropogenic pressure. Little is known about whether gape-size limitations similarly influence seed dispersal of small-fruited plant species that can show a large variation in fruit size within species. In this study, fruit sizes of 15 plant species were compared with the gape sizes of their 41 animal dispersers in the temperate, old-growth Białowieża Forest, Poland. The effect of gape-size limitations on fruit consumption was assessed at the plant species level, and for a subset of nine plant species, also at the individual level, and subindividual level (i.e., fruits of the same plant individual). In addition, for the species subset, fruit-seed trait relationships were investigated to determine whether a restricted access of small-gaped animals to large fruits results in the dispersal of fewer or smaller seeds per fruit. Fruit sizes widely varied among plant species (74.2%), considerably at the subindividual level (17.1%), and to the smallest extent among plant individuals (8.7%). Key disperser species should be able to consume fruits of all plant species and all individuals (except those of the largest-fruited plant species), even if they are able to consume only 28-55% of available fruits. Fruit and seed traits were positively correlated in eight out of nine plant species, indicating that gape size limitations will result in 49% fewer (in one) or 16–21% smaller seeds (in three plant species) dispersed per fruit by small-gaped than by large-gaped main dispersers, respectively. Our results show that a large subindividual variation in fruit size is characteristic for small-fruited plant species, and increases their connectedness with frugivores at the level of plants species and individuals. Simultaneously, however, the large variation in fruit size leads to gape-size limitations that may induce selective pressures on fruit size if large-gaped dispersers become extinct. This study emphasizes the mechanisms by which gape-size limitation at the species, individual and subindividual level shape plant-frugivore interactions and the co-evolution of small-fruited plants.
CNV-MEANN: A Neural Network and Mind Evolutionary Algorithm-Based Detection of Copy Number Variations From Next-Generation Sequencing Data
Authors: Huang Tihao , Li Junqing , Jia Baoxian , Sang Hongyan
Published: August 2021

Copy number variation (CNV), is defined as repetitions or deletions of genomic segments of 1 Kb to 5 Mb, and is a major trigger for human disease. The high-throughput and low-cost characteristics of next-generation sequencing technology provide the possibility of the detection of CNVs in the whole genome, and also greatly improve the clinical practicability of next-generation sequencing (NGS) testing. However, current methods for the detection of CNVs are easily affected by sequencing and mapping errors, and uneven distribution of reads. In this paper, we propose an improved approach, CNV-MEANN, for the detection of CNVs, involving changing the structure of the neural network used in the MFCNV method. This method has three differences relative to the MFCNV method: (1) it utilizes a new feature, mapping quality, to replace two features in MFCNV, (2) it considers the influence of the loss categories of CNV on disease prediction, and refines the output structure, and (3) it uses a mind evolutionary algorithm to optimize the backpropagation (neural network) neural network model, and calculates individual scores for each genome bin to predict CNVs. Using both simulated and real datasets, we tested the performance of CNV-MEANN and compared its performance with those of seven widely used CNV detection methods. Experimental results demonstrated that the CNV-MEANN approach outperformed other methods with respect to sensitivity, precision, and F1-score. The proposed method was able to detect many CNVs that other approaches could not, and it reduced the boundary bias. CNV-MEANN is expected to be an effective method for the analysis of changes in CNVs in the genome.
Analysis of the Clinical Efficacy of Laparoscopy and Hysteroscopy in the Treatment of Tubal-Factor Infertility
Authors: Nian Lei , Yang De-Hong , Zhang Jie , Zhao Han , Zhu Cai-Fen , Dong Ming-Feng , Ai Ying
Published: August 2021

Objective: This study aims to investigate the clinical efficacy of laparoscopy and hysteroscopy in the treatment of tubal-factor infertility (TFI) to provide a basis for predicting postoperative pregnancy rates.

Methods: The clinical data of 336 patients who underwent laparoscopy and hysteroscopy for TFI between February 2018 and December 2018 in the Department of Reproductive Gynecology at the First People's Hospital of Yunnan were retrospectively analyzed. After implementing the inclusion and exclusion criteria, 278 patients were included in the study. The patients were grouped according to pelvic adhesions, hydrosalpinx, twisted fallopian tubes, and fimbriae structure. The impact of the extent of fallopian tube diseases on postoperative pregnancy outcomes was analyzed.

Results: Of the 278 patients, 129 got pregnant (pregnancy rate = 46.4%). Pelvic adhesions, hydrosalpinx, twisted/folded fallopian tubes, and damage to the fimbriae of the fallopian tubes were found to affect the natural pregnancy rate after surgery, and it decreased significantly with the aggravation of the disease (P < 0.001). Of the 129 patients who had natural pregnancies, 29 had ectopic pregnancies (ectopic pregnancy rate = 22.48%). Twisted/folded fallopian tubes and damage to the fimbriae structure significantly increased the incidence of postoperative ectopic pregnancy (P < 0.001).

Conclusion: Laparoscopy and hysteroscopy are effective treatments for TFI. Pelvic adhesions, twisted/folded fallopian tubes, hydrosalpinx, and damage to the fimbriae of the fallopian tubes can affect postoperative pregnancy outcomes and lead to failure of a natural pregnancy after the operation. The incidence of ectopic pregnancy increases with the degree of fallopian tube twisting/folding and the degree of damage to the fimbriae of the fallopian tubes.
Effects of NaCl Concentrations on Growth Patterns, Phenotypes Associated With Virulence, and Energy Metabolism in Escherichia coli BW25113
Authors: Li Fen , Xiong Xue-Song , Yang Ying-Ying , Wang Jun-Jiao , Wang Meng-Meng , Tang Jia-Wei , Liu Qing-Hua , Wang Liang , Gu Bing
Published: August 2021

According to the sit-and-wait hypothesis, long-term environmental survival is positively correlated with increased bacterial pathogenicity because high durability reduces the dependence of transmission on host mobility. Many indirectly transmitted bacterial pathogens, such as Mycobacterium tuberculosis and Burkhoderia pseudomallei, have high durability in the external environment and are highly virulent. It is possible that abiotic stresses may activate certain pathways or the expressions of certain genes, which might contribute to bacterial durability and virulence, synergistically. Therefore, exploring how bacterial phenotypes change in response to environmental stresses is important for understanding their potentials in host infections. In this study, we investigated the effects of different concentrations of salt (sodium chloride, NaCl), on survival ability, phenotypes associated with virulence, and energy metabolism of the lab strain Escherichia coli BW25113. In particular, we investigated how NaCl concentrations influenced growth patterns, biofilm formation, oxidative stress resistance, and motile ability. In terms of energy metabolism that is central to bacterial survival, glucose consumption, glycogen accumulation, and trehalose content were measured in order to understand their roles in dealing with the fluctuation of osmolarity. According to the results, trehalose is preferred than glycogen at high NaCl concentration. In order to dissect the molecular mechanisms of NaCl effects on trehalose metabolism, we further checked how the impairment of trehalose synthesis pathway (otsBA operon) via single-gene mutants influenced E. coli durability and virulence under salt stress. After that, we compared the transcriptomes of E. coli cultured at different NaCl concentrations, through which differentially expressed genes (DEGs) and differential pathways with statistical significance were identified, which provided molecular insights into E. coli responses to NaCl concentrations. In sum, this study explored the in vitro effects of NaCl concentrations on E. coli from a variety of aspects and aimed to facilitate our understanding of bacterial physiological changes under salt stress, which might help clarify the linkages between bacterial durability and virulence outside hosts under environmental stresses.
Genome-Resolved Metagenomics of the Chicken Gut Microbiome
Authors: Segura-Wang Maia , Grabner Nikolaus , Koestelbauer Andreas , Klose Viviana , Ghanbari Mahdi
Published: August 2021

Increasing evidence shows that the chicken gastrointestinal microbiota has a major effect on the modulation of metabolic functions and is correlated with economic parameters, such as feed efficiency and health. Some of these effects derive from the capacity of the chicken to digest carbohydrates and produce energy-rich metabolites such as short-chain fatty acids (SCFA) and from host-microbe interactions. In this study, we utilized information from metagenomic assembled genomes (MAGs) from chicken gastrointestinal tract (GIT) samples, with detailed annotation of carbohydrate-active enzymes (CAZymes) and genes involved in SCFA production, to better understand metabolic potential at different ages. Metagenomic sequencing of 751 chicken GIT samples was performed to reconstruct 155 MAGs, representing species which belong to six phyla, primarily Firmicutes followed by Proteobacteria. MAG diversity significantly (p < 0.001) increased with age, with early domination of Lachnospiraceae, followed by other families including Oscillospiraceae. Age-dependent shifts were observed in the abundance of genes involved in CAZyme and SCFA production, exemplified by a significant increase in glycosyltransferases (GTs) and propionic acid production pathways (p < 0.05), and a lower abundance of glycoside hydrolases (GHs) (p < 0.01). Co-occurrence analysis revealed a large cluster highly interconnected by enzymes from GT2_2 and GH3 families, underscoring their importance in the community. Furthermore, several species were identified as interaction hubs, elucidating associations of key microbes and enzymes that more likely drive temporal changes in the chicken gut microbiota, and providing further insights into the structure of the complex microbial community. This study extends prior efforts on the characterization of the chicken GIT microbiome at the taxonomic and functional levels and lays an important foundation toward better understanding the broiler chicken gut microbiome helping in the identification of modulation opportunities to increase animal health and performance.
Inhibition of Fatty Acid Synthesis Aggravates Brain Injury, Reduces Blood-Brain Barrier Integrity and Impairs Neurological Recovery in a Murine Stroke Model
Authors: Janssen Lisa , Ai Xiaoyu , Zheng Xuan , Wei Wei , Caglayan Ahmet B. , Kilic Ertugrul , Wang Ya-chao , Hermann Dirk M. , Venkataramani Vivek , Bähr Mathias , Doeppner Thorsten R.
Published: August 2021

Inhibition of fatty acid synthesis (FAS) stimulates tumor cell death and reduces angiogenesis. When SH-SY5Y cells or primary neurons are exposed to hypoxia only, inhibition of FAS yields significantly enhanced cell injury. The pathophysiology of stroke, however, is not only restricted to hypoxia but also includes reoxygenation injury. Hence, an oxygen-glucose-deprivation (OGD) model with subsequent reoxygenation in both SH-SY5Y cells and primary neurons as well as a murine stroke model were used herein in order to study the role of FAS inhibition and its underlying mechanisms. SH-SY5Y cells and cortical neurons exposed to 10 h of OGD and 24 h of reoxygenation displayed prominent cell death when treated with the Acetyl-CoA carboxylase inhibitor TOFA or the fatty acid synthase inhibitor cerulenin. Such FAS inhibition reduced the reduction potential of these cells, as indicated by increased NADH2+/NAD+ ratios under both in vitro and in vivo stroke conditions. As observed in the OGD model, FAS inhibition also resulted in increased cell death in the stroke model. Stroke mice treated with cerulenin did not only display increased brain injury but also showed reduced neurological recovery during the observation period of 4 weeks. Interestingly, cerulenin treatment enhanced endothelial cell leakage, reduced transcellular electrical resistance (TER) of the endothelium and contributed to poststroke blood-brain barrier (BBB) breakdown. The latter was a consequence of the activated NF-κB pathway, stimulating MMP-9 and ABCB1 transporter activity on the luminal side of the endothelium. In conclusion, FAS inhibition aggravated poststroke brain injury as consequence of BBB breakdown and NF-κB-dependent inflammation.
[18F]PBR146 and [18F]DPA-714 in vivo Imaging of Neuroinflammation in Chronic Hepatic Encephalopathy Rats
Authors: Kong Xiang , Luo Song , Wang Yun Fei , Yang Gui Fen , Lu Guang Ming , Zhang Long Jiang
Published: August 2021

Neuroinflammation is an important pathogenesis of hepatic encephalopathy (HE). The upregulation of translocator protein (TSPO) during neuroinflammation provides an imaging molecular target to evaluate the severity of neuroinflammation in chronic HE rats. [18F]DPA-714 and [18F]PBR146 targeting TSPO are often used for neuroinflammation imaging. This study performed bile duct ligation (BDL) in rats to simulate chronic HE model, tested the behavioral experiments, and conducted [18F]PBR146 and [18F]DPA-714 micro-PET/CT scans followed analyzing the average %ID/g values of the whole brain, brain regions and main organs of subjects. After sacrifice the rats, the blood plasma samples were taken for blood biochemical indexes and plasma inflammatory factor levels examination, the liver and brain specimens were obtained for pathological analysis. The BDL rats showed chronic liver failure with defects in cognition, motor coordination ability and mental state. [18F]PBR146 and [18F]DPA-714 micro-PET/CT imaging results were similar in whole brain of BDL group and Sham group. Besides, some regional brain areas in BDL rats were found abnormal uptakes mainly located in basal ganglia area, auditory cortex, motor cortex, cingulate gyrus, somatosensory cortex, hippocampus, thalamus, midbrain, and medulla oblongata, and these regions also correlated with behavioral alterations. In conclusion, both [18F]PBR146 and [18F]DPA-714 had the similar imaging effects in hepatic encephalopathy models could quantitatively evaluate neuroinflammation load and distribution. The difference brain regions with higher uptake values of radiotracers in BDL rats were correlated with behavioral alterations.
Acupuncture With deqi Modulates the Hemodynamic Response and Functional Connectivity of the Prefrontal-Motor Cortical Network
Authors: Si Xiaopeng , Xiang Shaoxin , Zhang Ludan , Li Sicheng , Zhang Kuo , Ming Dong
Published: August 2021

As a world intangible cultural heritage, acupuncture is considered an essential modality of complementary and alternative therapy to Western medicine. Despite acupuncture’s long history and public acceptance, how the cortical network is modulated by acupuncture remains largely unclear. Moreover, as the basic acupuncture unit for regulating the central nervous system, how the cortical network is modulated during acupuncture at the Hegu acupoint is mostly unclear. Here, multi-channel functional near-infrared spectroscopy (fNIRS) data were recorded from twenty healthy subjects for acupuncture manipulation, pre- and post-manipulation tactile controls, and pre- and post-acupuncture rest controls. Results showed that: (1) acupuncture manipulation caused significantly increased acupuncture behavioral deqi performance compared with tactile controls. (2) The bilateral prefrontal cortex (PFC) and motor cortex were significantly inhibited during acupuncture manipulation than controls, which was evidenced by the decreased power of oxygenated hemoglobin (HbO) concentration. (3) The bilateral PFC’s hemodynamic responses showed a positive correlation trend with acupuncture behavioral performance. (4) The network connections with bilateral PFC as nodes showed significantly increased functional connectivity during acupuncture manipulation compared with controls. (5) Meanwhile, the network’s efficiency was improved by acupuncture manipulation, evidenced by the increased global efficiency and decreased shortest path length. Taken together, these results reveal that a cooperative PFC-Motor functional network could be modulated by acupuncture manipulation at the Hegu acupoint. This study provides neuroimaging evidence that explains acupuncture’s neuromodulation effects on the cortical network.
The Spatiotemporal Evolution of MRI-Derived Oxygen Extraction Fraction and Perfusion in Ischemic Stroke
Authors: Wu Di , Zhou Yiran , Cho Junghun , Shen Nanxi , Li Shihui , Qin Yuanyuan , Zhang Guiling , Yan Su , Xie Yan , Zhang Shun , Zhu Wenzhen , Wang Yi
Published: August 2021

Purpose

This study aimed to assess the spatiotemporal evolution of oxygen extraction fraction (OEF) in ischemic stroke with a newly developed cluster analysis of time evolution (CAT) for a combined quantitative susceptibility mapping and quantitative blood oxygen level-dependent model (QSM + qBOLD, QQ).

Method

One hundred and fifteen patients in different ischemic stroke phases were retrospectively collected for measurement of OEF of the infarcted area defined on diffusion-weighted imaging (DWI). Clinical severity was assessed using the National Institutes of Health Stroke Scale (NIHSS). Of the 115 patients, 11 underwent two longitudinal MRI scans, namely, three-dimensional (3D) multi-echo gradient recalled echo (mGRE) and 3D pseudo-continuous arterial spin labeling (pCASL), to evaluate the reversal region (RR) of the initial diffusion lesion (IDL) that did not overlap with the final infarct (FI). The temporal evolution of OEF and the cerebral blood flow (CBF) in the IDL, the RR, and the FI were assessed.

Results

Compared to the contralateral mirror area, the OEF of the infarcted region was decreased regardless of stroke phases (p < 0.05) and showed a declining tendency from the acute to the chronic phase (p = 0.022). Five of the 11 patients with longitudinal scans showed reversal of the IDL. Relative oxygen extraction fraction (rOEF, compared to the contralateral mirror area) of the RR increased from the first to the second MRI (p = 0.044). CBF was about 1.5-fold higher in the IDL than in the contralateral mirror area in the first MRI. Two patients showed penumbra according to the enlarged FI volume. The rOEF of the penumbra fluctuated around 1.0 at earlier scan times and then decreased, while the CBF decreased continuously.

Conclusion

The spatiotemporal evolution of OEF and perfusion in ischemic lesions is heterogeneous, and the CAT-based QQ method is feasible to capture cerebral oxygen metabolic information.
Long-Term Effects of Maternal Low-Protein Diet and Post-weaning High-Fat Feeding on Glucose Metabolism and Hypothalamic POMC Promoter Methylation in Offspring Mice
Authors: Zheng Jia , Zhang Ling , Liu Jiayi , Li Yanli , Zhang Junqing
Published: August 2021

Substantial evidence indicated that maternal malnutrition could increase the susceptibility to obesity, insulin resistance, and type 2 diabetes in adulthood. It is increasingly apparent that the brain, especially the hypothalamus, plays a critical role in glucose homeostasis. However, little information is known about the mechanisms linking maternal protein restriction combined with post-weaning high-fat (HF) feeding with altered expression of brain neurotransmitters, and investigations into the epigenetic modifications of hypothalamus in offspring have not been fully elucidated. Our objective was to explore the effects of maternal protein restriction combined with post-weaning HF feeding on glucose metabolism and hypothalamic POMC methylation in male offspring mice. C57/BL6 mice were fed on either low-protein (LP) or normal chow (NC) diet throughout gestation and lactation. Then, the male offspring were randomly weaned to either NC or high-fat (HF) diet until 32 weeks of age. Gene expressions and DNA methylation of hypothalamic proopiomelanocortin (POMC) and melanocortin receptor 4 (MC4R) were determined in male offspring. The results showed that birth weights and body weights at weaning were both significantly lower in male offspring mice of the dams fed with a LP diet. Maternal protein restriction combined with post-weaning high-fat feeding, predisposes higher body weight, persistent glucose intolerance (from weaning to 32 weeks of age), hyperinsulinemia, and hyperleptinemia in male offspring mice. POMC and MC4R expressions were significantly increased in offspring mice fed with maternal LP and postnatal high-fat diet (P < 0.05). Furthermore, maternal protein restriction combined with post-weaning high-fat feeding induced hypomethylation of POMC promoter in the hypothalamus (P < 0.05) and POMC-specific methylation (%) was negatively correlated with the glucose response to a glucose load in male offspring mice (r = −0.42, P = 0.039). In conclusion, maternal LP diet combined with post-weaning high-fat feeding predisposed the male offspring to impaired glucose metabolism and hypothalamic POMC hypomethylation. These findings can advance our thinking about hypothalamic POMC gene methylation between maternal LP diet combined with post-weaning high-fat feeding and metabolic health in offspring.
The Extract of Sonneratia apetala Leaves and Branches Ameliorates Hyperuricemia in Mice by Regulating Renal Uric Acid Transporters and Suppressing the Activation of the JAK/STAT Signaling Pathway
Authors: Wu Yu-Lin , Chen Jin-Fen , Jiang Lin-Yun , Wu Xiao-Li , Liu Yu-Hong , Gao Chang-Jun , Wu Yan , Yi Xiao-Qing , Su Zi-Ren , Cai Jian , Chen Jian-Nan
Published: August 2021

Sonneratia apetala Buch-Ham., an exotic mangrove species with antidiabetic, antibacterial, and antioxidant capacities, mainly distributes in the southeast coastal areas in China. The present work investigated the protective effects of Sonneratia apetala leaves and branches extraction (SAL) on hyperuricemia (HUA) in mice. Potassium oxonate (PO) and hypoxanthine (HX) were used to establish the HUA model by challenge for consecutive 7 days. Results revealed that SAL inhibited the increases in kidney weight and index compared to the vehicle group. Meanwhile, SAL significantly decreased the levels of uric acid (UA), creatinine (CRE), and blood urea nitrogen (BUN) in serum. Additionally, SAL inhibited the activity of xanthine oxidase (XOD) in the liver. SAL ameliorated PO- and HX-induced histopathological changes. Moreover, it regulated oxidative stress markers including malondialdehyde (MDA), catalase (CAT), superoxide dismutase (SOD) activity, and glutathione (GSH) content. Also, SAL inhibited the increases in renal levels of interleukin-6 (IL-6), interleukin-18 (IL-18), interleukin-1β (IL-1β), tumor necrosis factor (TNF-α), monocyte chemotactic protein 1 (MCP-1), and transforming growth factor-β (TGF-β). SAL remarkably reduced suppressor of cytokine signaling 3 (SOCS3), Janus kinase 2 (JAK2), and subsequent phosphorylation of signal transducer and activator of transcription 3 (STAT3) expression. In addition, SAL inhibited the activation of nuclear factor kappa-B (NF-κB) in the kidney. Furthermore, SAL protected against HUA by regulating renal UA transporters of organic anion transporter (OAT1), urate reabsorption transporter 1 (URAT1), and glucose transporter 9 (GLUT9). These findings suggested that SAL ameliorated HUA by inhibiting the production of uric acid and enhancing renal urate excretion, which are related to oxidative stress and inflammation, and the possible molecular mechanisms include its ability to inhibit the JAK/STAT signaling pathway. Thus, SAL might be developed into a promising agent for HUA treatments.
Dihydroartemisinin Alleviates Imiquimod-Induced Psoriasis-like Skin Lesion in Mice Involving Modulation of IL-23/Th17 Axis
Authors: Liu Jiang-Min , Jin Quan-Xin , Fujimoto Manabu , Li Fang-Fang , Jin Lin-Bo , Yu Ran , Yan Guang-Hai , Zhu Lian-Hua , Meng Fan-Ping , Zhang Qing-Gao , Jin Gui-Hua
Published: August 2021

Background: Psoriasis is a T help 17 (Th17) cell-mediated chronic inflammatory skin disease. Recent studies have shown that dihydroartemisinin (DHA) can significantly reduce experimental autoimmune encephalomyelitis and rheumatoid arthritis by regulating Th17 cells.

Objective: To verify whether DHA can improve the symptoms of psoriasis and to further explore the possible mechanism.

Methods: The efficiency of DHA was preliminary detected on human keratinocytes (HaCaT) cells in psoriatic condition. Then, imiquimod-induced psoriasis-like model in BALB/c mice was established to evaluate the effects of DHA in vivo.

Results: Under the stimulation of tumor necrosis factor-α (TNF-α) and interferon-γ (IFN-γ), DHA inhibited the proliferation of HaCaT cells and significantly affected the mRNA expression levels of IFN-γ, interleukin (IL), IL-17A and IL-23. DHA treatment reduced the severity of psoriasis-like skin and resulted in less infiltration of immune cells in skin lesions. DHA restored the expression of IFN-γ, IL-17A, and IL-23 in skins, as well as a decrease of cytokines and chemokines in skin supernatant. DHA also altered the cellular composition in the spleen, which is the makeup of the T cells, dendritic cells (DCs), and macrophages. DHA recovered Th17-related profile with decreased frequency of IL-17+CD4+T cells from splenocyte of mice. Furthermore, DHA also inhibited the concentration of IL-17 from Th17 cells and the expression of Th17 cell-related transcription factors retinoid-related orphan receptor-gamma t (ROR-γt) in vitro. In addition, phosphorylation of signal transducer and activator of transcription-3 (STAT3) was significantly reduced in DHA treatment mice, suggesting that the IL-23/Th17 axis plays a pivotal role.

Conclusion: DHA inhibits the progression of psoriasis by regulating IL-23/Th17 axis and is expected to be an effective drug for the treatment of psoriasis.
Lymph Nodes-On-Chip: Promising Immune Platforms for Pharmacological and Toxicological Applications
Authors: Shanti Aya , Hallfors Nicholas , Petroianu Georg A , Planelles Lourdes , Stefanini Cesare
Published: August 2021

Organs-on-chip are gaining increasing attention as promising platforms for drug screening and testing applications. However, lymph nodes-on-chip options remain limited although the lymph node is one of the main determinants of the immunotoxicity of newly developed pharmacological drugs. In this review, we describe existing biomimetic lymph nodes-on-chip, their design, and their physiological relevance to pharmacology and shed the light on future directions associated with lymph node-on-chip design and implementation in drug discovery and development.