bluuebunny/crossref_metadata_2025 huggingface dataset:
Fertilization of Ascidians: Gamete Interaction, Self/Nonself Recognition and Sperm Penetration of Egg Coat
Authors: Saito Takako , Sawada Hitoshi
Published: January 2022

Fertilization is one of the most important events in living organisms to generate a new life with a mixed genetic background. To achieve successful fertilization, sperm and eggs must undergo complex processes in a sequential order. Fertilization of marine invertebrate Ciona intestinalis type A (Ciona robusta) has been studied for more than a hundred years. Ascidian sperm are attracted by chemoattractants from eggs and bind to the vitelline coat. Subsequently, sperm penetrate through the vitelline coat proteolytically and finally fuse with the egg plasma membrane. Here, we summarize the fertilization mechanisms of ascidians, particularly from sperm-egg interactions to sperm penetration of the egg coat. Since ascidians are hermaphrodites, inbreeding depression is a serious problem. To avoid self-fertilization, ascidians possess a self-incompatibility system. In this review, we also describe the molecular mechanisms of the self-incompatibility system in C. intestinalis type A governed by three allelic gene pairs of s-Themis and v-Themis.
Synthesis of Copper Telluride Thin Films by Electrodeposition and Their Electrical and Thermoelectric Properties
Authors: Park Jungjoon , Seo Jinmyeong , Lim Jae-Hong , Yoo Bongyoung
Published: January 2022

Intermetallic copper telluride thin films, which are important in a number of electronics fields, were electrodeposited using a potentiostatic method in low-pH aqueous electrolyte baths with various ion-source concentrations, and the electrical properties of the formed films were investigated after exfoliation from the substrate. The films were electrochemically analyzed by cyclic voltammetry, while surface and cross-sectional morphologies, compositional ratios, and electrical properties were analyzed by scanning electron microscopy, X-ray diffractometry, X-ray photoelectron spectroscopy, ultraviolet photoelectron spectroscopy, and Hall-effect experiments. The copper telluride thin films, which were synthesized at various potentials in each bath, exhibit different composition ratios and structures; consequently, they show a variety of electrical and thermoelectric properties, including different electrical conductivities, carrier concentrations, mobilities, and Seebeck coefficients. Among them, the thin film with a 1:1 Cu:Te ratio delivered the highest power factor due to carrier filtering at the interface between the two phases.
Flower Bulb Waste Material is a Natural Niche for the Sexual Cycle in Aspergillus fumigatus
Authors: Zhang Jianhua , Verweij Paul E. , Rijs Antonius J. M. M. , Debets Alfons J. M. , Snelders Eveline
Published: January 2022

With population genetic evidence of recombination ongoing in the natural Aspergillus fumigatus population and a sexual cycle demonstrated in the laboratory the question remained what the natural niche for A. fumigatus sex is. Composting plant-waste material is a known substrate of A. fumigatus to thrive and withstand temperatures even up to 70°C. Previous studies have shown indirect evidence for sexual reproduction in these heaps but never directly demonstrated the sexual structures due to technical limitations. Here, we show that flower bulb waste material from stockpiles undergoing composting can provide the conditions for sexual reproduction. Direct detection of ascospore structures was shown in agricultural flower bulb waste material by using a grid-based detection assay. Furthermore, we demonstrate that ascospores can germinate after exposure to 70°C for up to several days in contrast to asexual conidia that are unable to survive a two-hour heat shock. This indicates a sufficient time frame for ascospores to survive and escape composting stockpiles. Finally, sexual crosses with cleistothecium and viable ascospore formation could successfully be performed on flower bulb waste material. Recombination of A. fumigatus can now be explained by active sexual reproduction in nature as we show in this study that flower bulb waste material provides an environmental niche for sex.
Investigating Rainfall Patterns in the Hubei Province, China and Northern Italy During the Covid-19 Lockdowns
Authors: Sharif Ridwana Binte , Houser Paul , Aquila Valentina , Maggioni Viviana
Published: January 2022

In the spring of 2020, many countries enacted strict lockdowns to contain the spread of the 2019 coronavirus disease (COVID-19), resulting in a sharp observed decrease in regional atmospheric pollutant concentrations, such as NOx and aerosols in early 2020. Atmospheric composition can influence cloud properties and might have a significant effect on the initiation of precipitation. This study investigated changes in precipitation patterns during COVID-19 lockdowns and compared them to patterns observed during the previous 19 years (2001 through 2019) across two regions of interest, the Hubei province in China and Northern Italy using a satellite-based precipitation dataset. Results indicated that overall rainfall averages were higher in the spring of 2020 with respect to their corresponding climatological means, with higher standard deviations especially in the more urbanized regions like Wuhan, China and Milan, Italy. Precipitation rates observed during the Spring of 2020 tend to fall outside of the climatological 25–75th percentile bounds. Similarly, the number of rainy pixels was in several cases in Spring 2020 higher than the climatological 75th percentile and sometimes even higher than the 95th one. These anomalies may be due to natural variations and may not be caused directly by the reduction in atmospheric pollutant concentrations. Nevertheless, our analysis proved that precipitation patterns during the lockdowns were on the extreme tails of the precipitation climatological distributions for both regions of interest. Lastly, decorrelation lags and distances in Northern Italy remained similar to their corresponding climatological values, whereas in the Hubei province some differences were observed, with the Spring 2020 spatial correlation variogram almost overlapping the climatological 5th percentile and with a decorrelation distance shorter than the climatological value.
Real-World Data of Anticoagulant Treatment in Non-valvular Atrial Fibrillation
Authors: Calderon Jose Miguel , Martinez Fernando , Diaz Javier , Fernandez Antonio , Sauri Inmaculada , Uso Ruth , Trillo Jose Luis , Vela Sara , Bea Carlos , Redon Josep , Forner Maria Jose
Published: January 2022

Aims

To assess the impact of anticoagulant treatment on risk for stroke and all-cause mortality of patients with atrial fibrillation using real-world data (RWD).

Methods

Patients with prevalent or incident atrial fibrillation were selected throughout a study period of 5 years. Stroke, transitory ischemic attack, hemorrhagic stroke, and all-cause mortality were identified in the claims of the electronic health records (EHRs). Subjects were classified according to the anticoagulant treatment in four groups: untreated, vitamin K antagonists (VKAs), New Oral Anticoagulants (NOACs), and antiplatelet (AP). Risk of events and protection with anticoagulant therapy were calculated by Cox proportional hazard models adjusted by potential confounders.

Results

From a total population of 3,799,884 patients older than 18,123,227 patients with incident or prevalent atrial fibrillation (AF) were identified (mean age 75.2 ± 11.5 years old; 51.9% women). In a follow-up average of 3.2 years, 17,113 patients suffered from an ischemic stroke and transitory ischemic attack (TIA), 780 hemorrhagic stroke, and 42,558 all-cause death (incidence of 46, 8, 2, and 120 per 1,000 patients/year, respectively). Among CHA2DS2, VASc Score equal or >2, 11.7% of patients did not receive any anticoagulant therapy, and a large proportion of patients, 47%, shifted from one treatment to another. Although all kinds of anticoagulant treatments were significantly protective against the events and mortality, NOAC treatment offered significantly better protection compared to the other groups.

Conclusion

In the real world, the use of anticoagulant treatments is far from guidelines recommendations and is characterized by variability in their use. NOACs offered better protection compared with VKAs.
Cardiovascular Phenotypes Profiling for L-Transposition of the Great Arteries and Prognosis Analysis
Authors: He Qiyu , Shen Huayan , Shao Xinyang , Chen Wen , Wu Yafeng , Liu Rui , Li Shoujun , Zhou Zhou
Published: January 2022

Objectives

Congenitally corrected transposition of the great arteries (ccTGA) is a rare and complex congenital heart disease with the characteristics of double discordance. Enormous co-existed anomalies are the culprit of prognosis evaluation and clinical decision. We aim at delineating a novel ccTGA clustering modality under human phenotype ontology (HPO) instruction and elucidating the relationship between phenotypes and prognosis in patients with ccTGA.

Methods

A retrospective review of 270 patients diagnosed with ccTGA in Fuwai hospital from 2009 to 2020 and cross-sectional follow-up were performed. HPO-instructed clustering method was administered in ccTGA risk stratification. Kaplan-Meier survival, Landmark analysis, and cox regression analysis were used to investigate the difference of outcomes among clusters.

Results

The median follow-up time was 4.29 (2.07–7.37) years. A total of three distinct phenotypic clusters were obtained after HPO-instructed clustering with 21 in cluster 1, 136 in cluster 2, and 113 in cluster 3. Landmark analysis revealed significantly worse mid-term outcomes in all-cause mortality (p = 0.021) and composite endpoints (p = 0.004) of cluster 3 in comparison with cluster 1 and cluster 2. Multivariate analysis indicated that pulmonary arterial hypertension (PAH), atrioventricular septal defect (AVSD), and arrhythmia were risk factors for composite endpoints. Moreover, the surgical treatment was significantly different among the three groups (p < 0.001) and surgical strategies had different effects on the prognosis of the different phenotypic clusters.

Conclusions

Human phenotype ontology-instructed clustering can be a potentially powerful tool for phenotypic risk stratification in patients with complex congenital heart diseases, which may improve prognosis prediction and clinical decision.
The Effect of China's Pilot Low-Carbon City Initiative on Enterprise Labor Structure
Authors: Sun Xiaoyang , Zheng Yuhua , Zhang Chenyu , Li Xuelian , Wang Baosheng
Published: January 2022

Based on the background of China's pilot low-carbon city initiative in 2010, 2012, and 2017, this article captures the exogenous change of enterprise labor structure based on A-share listed companies from 2007 to 2019 in Shenzhen and Shanghai Stock exchanges. With the integration of macro data on the city level and micro data on the enterprise level, adopting the time-varying difference-in-differences (DID) model, we found that 1) China's pilot low-carbon city initiative can significantly promote the upgrading of enterprise labor structure; 2) China's pilot low-carbon city initiative can significantly increase R&D investment of listed companies, suggesting that R&D investment is a channel for the impact of China's pilot low-carbon city initiative on enterprise labor structure in the pilot cities; 3) the heterogeneity analysis shows that the labor structure of the state-owned listed companies has been optimized significantly, while the labor structure of the non–state-owned listed companies is not significant. Meanwhile, the labor structure of the listed companies under high-quality government control has been optimized significantly, while the labor structure of the listed companies under low-quality government control is not significant. Overall, our study shows that the pilot low-carbon city initiative has played a governance role in China and optimized enterprise labor structure.
Regional Characteristics of Precipitation in the Nanpan River Basin, China
Authors: Qin Xinlong , Wang Long , Li Xuehui , Yu Hang , Wang Kui , Fan Defang
Published: January 2022

Nanpan River is the source of the Pearl River in China, and thus, the exploitation of water resources in the Nanpan River Basin directly affects development in its middle and lower reaches. In the present study, the availability of water resources in the Nanpan River Basin and their differences were investigated. Sixteen statistical variables including the 25th and 75th percentiles, the coefficient of variation of the seasonal and annual precipitation and the annual precipitation concentration index were examined using monthly precipitation data collected in 33 stations in the Nanpan River Basin from 1956 to 2016. This paper studies the relationship between the Spearman’s rank correlation coefficient and the distance between stations, and uses principal component analysis (PCA) and cluster analysis to identify the homogeneous precipitation regions in the Nanpan River Basin. The results reveal the following: 1) The Spearman’s rank correlation coefficients for the monthly, seasonal and annual precipitation of the stations exhibit negative correlations with the interstation distance; the stronger the spatial correlation between both parameters, the shorter the time scale. 2) The factors controlling the spatial patterns of precipitation in the basin are its interannual and intra-annual variations. 3) Precipitation for the Nanpan River Basin produce two homogenous regions, which are associated with the influences of the South Asian monsoon, the North Atlantic Oscillation and the South Branch Trough. The first region is mainly to the east of longitude 104°E, while the second is principally to the west.
Characteristics of Secondary PM2.5 Under Different Photochemical Reactivity Backgrounds in the Pearl River Delta Region
Authors: Yu Xinyang , Zhang Yin , Liu Ningwei , Yang Suying
Published: January 2022

With the increasing control of air pollution, the levels of atmospheric particulates in the Pearl River Delta (PRD) region are gradually decreasing. However, ozone pollution has become more and more serious, and the problem of secondary aerosol pollution caused by photochemical reactions cannot be ignored. Based on the observation data of environmental and meteorological stations in the nine cities of the PRD during 2019, we investigated the variations of secondary PM2.5 (PM2.5-sec) in the PRD under different photochemical reactivity backgrounds. It was shown that the photochemical reactivities appeared more significant in the central and western areas than those in the eastern areas of the PRD and appeared more significant in inland areas than those in coastal areas. The days of moderate and high photochemical reactivities mainly appeared from August to November. PM2.5-sec concentrations were the highest in autumn, during which the regional discrepancies appeared most significantly with the highest levels in the southern areas. With the enhancement of the photochemical reactivity background, the PM2.5-sec level at each station increased significantly, which appeared significantly higher in coastal areas than in inland areas. Both PM2.5-sec and ozone concentrations showed single-peak variations, which appeared higher in the daytime than at night with the peak occurring at about 15:00. For each pollutant, the average maximum concentration appeared higher for polluted stations than for clean ones, indicating that the atmospheric oxidation background was conducive to the formation of PM2.5-sec.
Correspondence Between Genomic- and Genealogical/Coalescent-Based Inference of Homozygosity by Descent in Large French-Canadian Genealogies
Authors: Burkett Kelly M. , Rakesh Mohan , Morris Patricia , Vézina Hélène , Laprise Catherine , Freeman Ellen E. , Roy-Gagnon Marie-Hélène
Published: January 2022

Research on the genetics of complex traits overwhelmingly focuses on the additive effects of genes. Yet, animal studies have shown that non-additive effects, in particular homozygosity effects, can shape complex traits. Recent investigations in human studies found some significant homozygosity effects. However, most human populations display restricted ranges of homozygosity by descent (HBD), making the identification of homozygosity effects challenging. Founder populations give rise to higher HBD levels. When deep genealogical data are available in a founder population, it is possible to gain information on the time to the most recent common ancestor (MRCA) from whom a chromosomal segment has been transmitted to both parents of an individual and in turn to that individual. This information on the time to MRCA can be combined with the time to MRCA inferred from coalescent models of gene genealogies. HBD can also be estimated from genomic data. The extent to which the genomic HBD measures correspond to the genealogical/coalescent measures has not been documented in founder populations with extensive genealogical data. In this study, we used simulations to relate genomic and genealogical/coalescent HBD measures. We based our simulations on genealogical data from two ongoing studies from the French-Canadian founder population displaying different levels of inbreeding. We simulated single-nucleotide polymorphisms (SNPs) in a 1-Mb genomic segment from a coalescent model in conjunction with the observed genealogical data. We compared genealogical/coalescent HBD to two genomic methods of HBD estimation based on hidden Markov models (HMMs). We found that genomic estimates of HBD correlated well with genealogical/coalescent HBD measures in both study genealogies. We described generation time to coalescence in terms of genomic HBD estimates and found a large variability in generation time captured by genomic HBD when considering each SNP. However, SNPs in longer segments were more likely to capture recent time to coalescence, as expected. Our study suggests that estimating the coalescent gene genealogy from the genomic data to use in conjunction with observed genealogical data could provide valuable information on HBD.
Chromosome-Scale Genome of Masked Palm Civet (Paguma larvata) Shows Genomic Signatures of Its Biological Characteristics and Evolution
Authors: Lan Tianming , Fang Dongming , Li Haimeng , Sahu Sunil Kumar , Wang Qing , Yuan Hao , Zhu Yixin , Yang Zipeng , Zhang Le , Yang Shangchen , Lu Haorong , Han Lei , Zhang Shaofang , Yu Jieyao , Mahmmod Yasser S. , Xu Yanchun , Hua Yan , He Fengping , Yuan Ziguo , Liu Huan
Published: January 2022

The masked palm civet (Paguma larvata) is a small carnivore with distinct biological characteristics, that likes an omnivorous diet and also serves as a vector of pathogens. Although this species is not an endangered animal, its population is reportedly declining. Since the severe acute respiratory syndrome (SARS) epidemic in 2003, the public has been particularly concerned about this species. Here, we present the first genome of the P. larvata, comprising 22 chromosomes assembled using single-tube long fragment read (stLFR) and Hi-C technologies. The genome length is 2.41 Gb with a scaffold N50 of 105.6 Mb. We identified the 107.13 Mb X chromosome and one 1.34 Mb Y-linked scaffold and validated them by resequencing 45 P. larvata individuals. We predicted 18,340 protein-coding genes, among which 18,333 genes were functionally annotated. Interestingly, several biological pathways related to immune defenses were found to be significantly expanded. Also, more than 40% of the enriched pathways on the positively selected genes (PSGs) were identified to be closely related to immunity and survival. These enriched gene families were inferred to be essential for the P. larvata for defense against the pathogens. However, we did not find a direct genomic basis for its adaptation to omnivorous diet despite multiple attempts of comparative genomic analysis. In addition, we evaluated the susceptibility of the P. larvata to the SARS-CoV-2 by screening the RNA expression of the ACE2 and TMPRSS2/TMPRSS4 genes in 16 organs. Finally, we explored the genome-wide heterozygosity and compared it with other animals to evaluate the population status of this species. Taken together, this chromosome-scale genome of the P. larvata provides a necessary resource and insights for understanding the genetic basis of its biological characteristics, evolution, and disease transmission control.
Four MicroRNAs, miR-13b-3p, miR-278-5p, miR-10483-5p, and miR-10485-5p, Mediate Insecticide Tolerance in Spodoptera frugiperda
Authors: Yang Yuanxue , Zhang Yun , Wang Aiyu , Duan Ailing , Xue Chao , Wang Kaiyun , Zhao Ming , Zhang Jianhua
Published: January 2022

Spodoptera frugiperda is the world’s major agricultural pest and has the distinctive features of high fecundity, strong migratory capacity, and high resistance to most insecticides. At present, the control of S. frugiperda in China relies mainly on the spraying of chemical insecticides. MicroRNAs (miRNAs) are a class of small, single-stranded, non-coding RNAs and play crucial regulatory roles in various physiological processes, including the insecticide resistance in insects. However, little is known about the regulatory roles of miRNAs on the resistance of S. frugiperda to insecticides. In the present research, the miRNAs that were differentially expressed after cyantraniliprole, spinetoram, and emamectin benzoate treatment were analyzed by RNA-Seq. A total of 504 miRNAs were systematically identified from S. frugiperda, and 24, 22, and 31 miRNAs were differentially expressed after treatments of cyantraniliprole, spinetoram, and emamectin benzoate. GO and KEGG enrichment analyses were used to predict the function of differentially expressed target genes of miRNAs. Importantly, ten miRNAs were significantly differentially expressed among the treatments of three insecticides. miR-278-5p, miR-13b-3p, miR-10485-5p, and miR-10483-5p were significantly downregulated among the treatments of three insecticides by RT-qPCR. Furthermore, the overexpression of miR-278-5p, miR-13b-3p, miR-10485-5p, and miR-10483-5p significantly increased the mortality of S. frugiperda to cyantraniliprole and emamectin benzoate. The mortality was significantly increased with spinetoram treatment after the overexpression of miR-13b-3p, miR-10485-5p, and miR-10483-5p. These results suggest that miRNAs, which are differentially expressed in response to insecticides, may play a key regulatory role in the insecticide tolerance in S. frugiperda.
RNA-Cholesterol Nanoparticles Function as Potent Immune Activators via TLR7 and TLR8
Authors: Obermann Hannah-Lena , Lederbogen Ines I. , Steele Jenny , Dorna Jens , Sander Leif Erik , Engelhardt Konrad , Bakowsky Udo , Kaufmann Andreas , Bauer Stefan
Published: January 2022

The innate immune system senses viral and bacterial ribonucleic acid (RNA) via pattern recognition receptors (PRR) leading to subsequent activation of the immune system. One group of RNA sensors is formed by endosomal/lysosomal Toll-like receptors (TLR) such as TLR7 and TLR8. During viral or bacterial infection, immunostimulatory RNA is part of the pathogen reaching the endosomal/lysosomal compartment after cellular uptake. Synthetic single-stranded or double-stranded oligoribonucleotides (ORN) can mimic RNA from pathogens and are widely used as activating ligands for TLR7 and TLR8. However, one limitation in the use of synthetic ORN driven immune stimulation is the need for transfection reagents for RNA delivery into cells. Here we demonstrate that the conjugation of cholesterol to a double-stranded version of immunostimulatory RNA40 strongly enhanced RNA uptake into monocytes and plasmacytoid dendritic cells when compared to naked RNA. Cholesterol-conjugated RNA (RNA-chol) formed nanoparticles that were superior to RNA-liposomes complexes in regard to induction of type I interferon from human and murine plasmacytoid dendritic cells as well as proinflammatory cytokine production (e.g. TNF-α, IL12p70 or IL-6) in human monocytes. Furthermore, the RNA40-chol induced cytokines in human monocyte cultures supported TH1 and TFH cell differentiation underscoring a strong adjuvant function of RNA-chol nanoparticles for adaptive immune responses. In summary, cholesterol-conjugated immunostimulatory RNA forms nanoparticles and functions as a potent immune adjuvant in human and murine immune cells. It further simplifies the use of immunostimulatory RNA by avoiding the need for liposomal transfection reagents.
An Artifact in Intracellular Cytokine Staining for Studying T Cell Responses and Its Alleviation
Authors: Gong Zheng , Li Qing , Shi Jiayuan , Ren Guangwen
Published: January 2022

Intracellular cytokine staining (ICS) is a widely employed ex vivo method for quantitative determination of the activation status of immune cells, most often applied to T cells. ICS test samples are commonly prepared from animal or human tissues as unpurified cell mixtures, and cell-specific cytokine signals are subsequently discriminated by gating strategies using flow cytometry. Here, we show that when ICS samples contain Ly6G+ neutrophils, neutrophils are ex vivo activated by an ICS reagent – phorbol myristate acetate (PMA) – which leads to hydrogen peroxide (H2O2) release and death of cytokine-expressing T cells. This artifact is likely to result in overinterpretation of the degree of T cell suppression, misleading immunological research related to cancer, infection, and inflammation. We accordingly devised easily implementable improvements to the ICS method and propose alternative methods for assessing or confirming cellular cytokine expression.
A Multi-Region and Multi-Period Harvest Schedule of the Trawl Fleet
Authors: Alizadeh Ashrafi Tannaz , Ersdal Anne Mai , Nordli Anders Samuelsen
Published: January 2022

Under the individual vessel quota regulations, the expected economic return of a multi species fishery is influenced by an array of a multi-component choice such as targeted species, landings per haul, harvesting time and its location. The components of effort allocation decisions are further complicated by changes in the market conditions and the constant movements of fish between spawning and feeding habitats. Migratory behavior influences the dispersal of species, relative availability of fish and its composition, and the bycatch likelihood across different locations over the course of a fishing year. The objective of this article is to investigate the optimal allocation of fishing effort in the Norwegian bottom-trawl fleet within economically important species; cod, saithe, and haddock across three heavily trawled areas—including southern and northern parts of the west coast of Norway, and the high sea areas of the Arctic—to achieve maximum expected economic return, with respect to the individual vessel quota constraints and bycatch considerations. The results from a mixed integer non-linear optimization problem evidence that the spawning migration of Northeast Arctic cod along the northwest coast, effort allocation behavior of coastal fleet, together with institutional regulations necessitate the substitution of fishing effort across different fishing locations within the fishing season to maximize expected return. The results of our study further reveal that the Arctic region to target cod is the biggest contributor to annual fishing revenue. By contrast, conducting saithe fishery in the southwest of the Norwegian coast has the lowest economic contribution. The results from Monte Carlo simulation demonstrate that the proposed model is effective and applicable for effort allocation decision analysis.
Two-Dimensional Hexagonal Boron Nitride Nanosheets as Lateral Heat Spreader With High Thermal Conductivity
Authors: Kong Xiangdong , Li Linhong , Li Maohua , Xia Juncheng , Wang Yandong , Wei Xianzhe , Xiong Shaoyang , Gong Ping , Pan Zhongbin , Wu Xinfeng , Cai Tao , Nishimura Kazuhito , Lin Cheng-Te , Jiang Nan , Yu Jinhong
Published: January 2022

A highly thermally conductive heat spreader for applications in electronic devices is becoming increasingly demanding, and therefore the removal of excess heat requires an efficient heat dissipating device. Boron nitride nanosheets (BNNSs) were prepared as thermally conductive fillers using hexagonal boron nitride (h-BN) powder as raw material by a water exfoliation method. A composite film was prepared by vacuum filtration using cellulose nanofibers (CNFs) as the substrate with an in-plane thermal conductivity (TC) of 82.4 W m−1 K−1, thermal conductivity enhancement increasing by 9,486% compared to pure cellulose film. Thus, CNF/BNNS composite films are promising as effective thermal interface materials (TIMs) in electronic devices and electronic component applications.
Velvet Antler Peptides Reduce Scarring via Inhibiting the TGF-β Signaling Pathway During Wound Healing
Authors: Zhang Guokun , Wang Dongxu , Ren Jing , Sun Hongmei , Li Jiping , Wang Shengnan , Shi Liyan , Wang Zhen , Yao Mengjie , Zhao Haiping , Li Chunyi
Published: January 2022

Aim

Scar formation generally occurs in cutaneous wound healing in mammals, mainly caused by myofibroblast aggregations, and currently with few effective treatment options. However, the pedicle wound (about 10 cm in diameter) of the deer can initiate regenerative healing, which has been found to be achieved via paracrine factors from the internal tissues of antlers.

Methods

Enzymatically digested velvet antler peptides (EVAP) were prepared along with other types of antler extracts as the controls. The effects of EVAP on healing of full-thickness skin wounds were evaluated using rats in vivo, and on myofibroblast transdifferentiation tested using transforming growth factor-β1 (TGF-β1)-induced human dermal fibroblasts in vitro.

Results

EVAP significantly accelerated the wound healing rate, reduced scar formation, and improved the healing quality, including promoted angiogenesis, increased number of skin appendages (hair follicles and sebaceous glands) and improved the distribution pattern of collagen fibers (basket-wave like) in the healed tissue. Moreover, EVAP significantly down-regulated the expression levels of genes pro- scar formation (Col1a2 and TGF-β1), and up-regulated the expression levels of genes anti-scar formation (Col3a1 and TGF-β3), and suppressed the excessive transdifferentiation of myofibroblasts and the formation of collagen I in vivo and in vitro. Furthermore, we found these effects were highly likely achieved by inhibiting the TGF-β signaling pathway, evidenced by decreased expression levels of the related genes, including TGF-β1, Smad2, p-Smad2, α-SMA, and collagen I.

Conclusions

EVAP may be a promising candidate to be developed as a clinic drug for regenerative wound healing.
In-Person and Remote Workshops for People With Neurocognitive Disorders: Recommendations From a Delphi Panel
Authors: Manera Valeria , Agüera-Ortiz Luis , Askenazy Florence , Dubois Bruno , Corveleyn Xavier , Cross Liam , Febvre-Richards Emma , Fabre Roxane , Fernandez Nathalie , Foulon Pierre , Gros Auriane , Gueyraud Cedric , Lebourhis Mikael , Malléa Patrick , Martinez Léa , Pancrazi Marie-Pierre , Payne Magali , Robert Vincent , Tamagno Laurent , Thümmler Susanne , Robert Philippe
Published: January 2022

Workshops using arts and board games are forms of non-pharmacological intervention widely employed in seniors with neurocognitive disorders. However, clear guidelines on how to conduct these workshops are missing. The objective of the Art and Game project (AGAP) was to draft recommendations on the structure and content of workshops for elderly people with neurocognitive disorders and healthy seniors, with a particular focus on remote/hybrid workshops, in which at least a part of the participants is connected remotely. Recommendations were gathered using a Delphi methodology. The expert panel (N = 18) included experts in the health, art and/or board games domains. They answered questions via two rounds of web-surveys, and then discussed the results in a plenary meeting. Some of the questions were also shared with the general public (N = 101). Both the experts and the general public suggested that organizing workshops in a hybrid format (some face-to-face sessions, some virtual session) is feasible and interesting for people with neurocognitive disorders. We reported guidelines on the overall structure of workshops, practical tips on how to organize remote workshops, and a SWOT analysis of the use of remote/hybrid workshops. The guidelines may be employed by clinicians to decide, based on their needs and constraints, what interventions and what kind of workshop format to employ, as well as by researcher to standardize procedures to assess the effectiveness of non-pharmacological treatments for people with neurocognitive disorders.
Salidroside Ameliorates Alzheimer's Disease by Targeting NLRP3 Inflammasome-Mediated Pyroptosis
Authors: Cai Yawen , Chai Yuhui , Fu Yu , Wang Yingdi , Zhang Yiming , Zhang Xue , Zhu Lingpeng , Miao Mingxing , Yan Tianhua
Published: January 2022

Amyloid β-protein (Aβ) is reported to activate NLRP3 inflammasomes and drive pyroptosis, which is subsequently involved in the pathogenesis of neurodegenerative diseases, such as Alzheimer's disease (AD). To date, the pathogenesis of AD is unfortunately insufficiently elucidated. Therefore, this study was conducted to explore whether Salidroside (Sal) treatment could benefit AD by improving pyroptosis. Firstly, two animal models of AD, induced, respectively, by Aβ1-42 and D-galactose (D-gal)/AlCl3, have been created to assist our appreciation of AD pathophysiology. We then confirmed that pyroptosis is related to the pathogenesis of AD, and Sal can slow the progression of AD by inhibiting pyroptosis. Subsequently, we established the D-gal and Nigericin-induced PC12 cells injury model in vitro to verify Sal blocks pyroptosis mainly by targeting the NLRP3 inflammasome. For in vivo studies, we observed that Aβ accumulation, Tau hyperphosphorylation, neurons of hippocampal damage, and cognitive dysfunction in AD mice, caused by bilateral injection of Aβ1-42 into the hippocampus and treatments with D-gal combine AlCl3. Besides, accumulated Aβ promotes NLRP3 inflammasome activation, which leads to the activation and release of a pro-inflammatory cytokine, interleukin-1 beta (IL-1β). Notably, both Aβ accumulation and hyperphosphorylation of Tau decreased and inhibited pyroptosis by downregulating the expression of IL-1β and IL-18, which can be attributed to the treatment of Sal. We further found that Sal can reverse the increased protein expression of TLR4, MyD88, NF-κB, P-NF-κB, NLRP3, ASC, cleaved Caspase-1, cleaved GSDMD, IL-1β, and IL-18 in vitro. The underlying mechanism may be through inhibiting TLR4/NF-κB/NLRP3/Caspase-1 signaling pathway. Our study highlights the importance of NLRP3 inflammasome-mediated pyroptosis in AD, and how the administration of pharmacological doses of Sal can inhibit NLRP3 inflammasome-mediated pyroptosis and ameliorate AD. Thus, we conclude that NLRP3 inflammasome-mediated pyroptosis plays a significant role in AD and Sal could be a therapeutic drug for AD.
Type II Opsins in the Eye, the Pineal Complex and the Skin of Xenopus laevis: Using Changes in Skin Pigmentation as a Readout of Visual and Circadian Activity
Authors: Bertolesi Gabriel E. , Debnath Nilakshi , Malik Hannan R. , Man Lawrence L. H. , McFarlane Sarah
Published: January 2022

The eye, the pineal complex and the skin are important photosensitive organs. The African clawed frog, Xenopus laevis, senses light from the environment and adjusts skin color accordingly. For example, light reflected from the surface induces camouflage through background adaptation while light from above produces circadian variation in skin pigmentation. During embryogenesis, background adaptation, and circadian skin variation are segregated responses regulated by the secretion of α-melanocyte-stimulating hormone (α-MSH) and melatonin through the photosensitivity of the eye and pineal complex, respectively. Changes in the color of skin pigmentation have been used as a readout of biochemical and physiological processes since the initial purification of pineal melatonin from pigs, and more recently have been employed to better understand the neuroendocrine circuit that regulates background adaptation. The identification of 37 type II opsin genes in the genome of the allotetraploid X. laevis, combined with analysis of their expression in the eye, pineal complex and skin, is contributing to the elucidation of the role of opsins in the different photosensitive organs, but also brings new questions and challenges. In this review, we analyze new findings regarding the anatomical localization and functions of type II opsins in sensing light. The contribution of X. laevis in revealing the neuroendocrine circuits that regulate background adaptation and circadian light variation through changes in skin pigmentation is discussed. Finally, the presence of opsins in X. laevis skin melanophores is presented and compared with the secretory melanocytes of birds and mammals.
Biosensing, Characterization of Biosensors, and Improved Drug Delivery Approaches Using Atomic Force Microscopy: A Review
Authors: Sarkar Anwesha
Published: January 2022

Since its invention, atomic force microscopy (AFM) has come forth as a powerful member of the “scanning probe microscopy” (SPM) family and an unparallel platform for high-resolution imaging and characterization for inorganic and organic samples, especially biomolecules, biosensors, proteins, DNA, and live cells. AFM characterizes any sample by measuring interaction force between the AFM cantilever tip (the probe) and the sample surface, and it is advantageous over other SPM and electron micron microscopy techniques as it can visualize and characterize samples in liquid, ambient air, and vacuum. Therefore, it permits visualization of three-dimensional surface profiles of biological specimens in the near-physiological environment without sacrificing their native structures and functions and without using laborious sample preparation protocols such as freeze-drying, staining, metal coating, staining, or labeling. Biosensors are devices comprising a biological or biologically extracted material (assimilated in a physicochemical transducer) that are utilized to yield electronic signal proportional to the specific analyte concentration. These devices utilize particular biochemical reactions moderated by isolated tissues, enzymes, organelles, and immune system for detecting chemical compounds via thermal, optical, or electrical signals. Other than performing high-resolution imaging and nanomechanical characterization (e.g., determining Young’s modulus, adhesion, and deformation) of biosensors, AFM cantilever (with a ligand functionalized tip) can be transformed into a biosensor (microcantilever-based biosensors) to probe interactions with a particular receptors of choice on live cells at a single-molecule level (using AFM-based single-molecule force spectroscopy techniques) and determine interaction forces and binding kinetics of ligand receptor interactions. Targeted drug delivery systems or vehicles composed of nanoparticles are crucial in novel therapeutics. These systems leverage the idea of targeted delivery of the drug to the desired locations to reduce side effects. AFM is becoming an extremely useful tool in figuring out the topographical and nanomechanical properties of these nanoparticles and other drug delivery carriers. AFM also helps determine binding probabilities and interaction forces of these drug delivery carriers with the targeted receptors and choose the better agent for drug delivery vehicle by introducing competitive binding. In this review, we summarize contributions made by us and other researchers so far that showcase AFM as biosensors, to characterize other sensors, to improve drug delivery approaches, and to discuss future possibilities.
The Elephant in the Room: A Systematic Review of Stimulus Control in Neuro-Measurement Studies on Figurative Language Processing
Authors: Koller Sina , Müller Nadine , Kauschke Christina
Published: January 2022

The processing of metaphors and idioms has been the subject of neuroscientific research for several decades. However, results are often contradictory, which can be traced back to inconsistent terminology and stimulus control. In this systematic review of research methods, we analyse linguistic aspects of 116 research papers which used EEG, fMRI, PET, MEG, or NIRS to investigate the neural processing of the two figurative subtypes metaphor and idiom. We critically examine the theoretical foundations as well as stimulus control by performing a systematic literature synthesis according to the PRISMA guidelines. We explicitly do not analyse the findings of the studies but instead focus on four primary aspects: definitions of figurative language and its subtypes, linguistic theory behind the studies, control for factors influencing figurative language processing, and the relationship between theoretical and operational definitions. We found both a lack and a broad variety in existing definitions and operationalisation, especially in regard to familiarity and conventionality. We identify severe obstacles in the comparability and validation potential of the results of the papers in our review corpus. We propose the development of a consensus in fundamental terminology and more transparency in the reporting of stimulus design in the research on figurative language processing.
A Flexible Pulse Generator Based on a Field Programmable Gate Array Architecture for Functional Electrical Stimulation
Authors: Mercado-Gutierrez Jorge A. , Dominguez Ricardo , Hernandez-Popo Ignacio , Quinzaños-Fresnedo Jimena , Vera-Hernandez Arturo , Leija-Salas Lorenzo , Gutierrez-Martinez Josefina
Published: January 2022

Non-invasive Functional Electrical Stimulation (FES) is a technique applied for motor rehabilitation of patients with central nervous system injury. This technique requires programmable multichannel systems to configure the stimulation parameters (amplitude, frequency, and pulse width). Most FES systems are based on microcontrollers with fixed architecture; this limits the control of the parameters and the scaling to multiple channels. Although field programmable gate arrays (FPGA) have been used in FES systems as alternative to microcontrollers, most of them focus on signal acquisition, processing, or communication functions, or are for invasive stimulation. A few FES systems report using FPGAs for parameter configuration and pulse generation in non-invasive FES. However, generally they limit the value of the frequency or amplitude parameters to enable multichannel operation. This restricts free selection of parameters and implementation of modulation patterns, previously reported to delay FES-induced muscle fatigue. To overcome those limitations, this paper presents a proof-of-concept (technology readiness level three-TRL 3) regarding the technical feasibility and potential use of an FPGA-based pulse generator for non-invasive FES applications (PG-nFES). The main aims were: (1) the development of a flexible pulse generator for FES applications and (2) to perform a proof-of-concept of the system, comprising: electrical characterization of the stimulation parameters, and verification of its potential for upper limb FES applications. Biphasic stimulation pulses with high linearity (r2 > 0.9998) and repeatability (>0.81) were achieved by combining the PG-nFES with a current-controlled output stage. Average percentage error in the characterizations was under 3% for amplitude (1–48 mA) and pulse width (20–400 μs), and 0% for frequency (10–150 Hz). A six-channel version of the PG-nFES was implemented to demonstrate the scalability feature. The independence of parameters was tested with three patterns of co-modulation of two parameters. Moreover, two complete FES channels were implemented and the claimed features of the PG-nFES were verified by performing upper limb functional movements involving the hand and the arm. Finally, the system enabled implementation of a stimulation pattern with co-modulation of frequency and pulse width, applied successfully for efficient elbow during repetitions of a functional movement.
Decontaminate Traces From Fluorescence Calcium Imaging Videos Using Targeted Non-negative Matrix Factorization
Authors: Bao Yijun , Redington Emily , Agarwal Agnim , Gong Yiyang
Published: January 2022

Fluorescence microscopy and genetically encoded calcium indicators help understand brain function by recording large-scale in vivo videos in assorted animal models. Extracting the fluorescent transients that represent active periods of individual neurons is a key step when analyzing imaging videos. Non-specific calcium sources and background adjacent to segmented neurons contaminate the neurons’ temporal traces with false transients. We developed and characterized a novel method, temporal unmixing of calcium traces (TUnCaT), to quickly and accurately unmix the calcium signals of neighboring neurons and background. Our algorithm used background subtraction to remove the false transients caused by background fluctuations, and then applied targeted non-negative matrix factorization to remove the false transients caused by neighboring calcium sources. TUnCaT was more accurate than existing algorithms when processing multiple experimental and simulated datasets. TUnCaT’s speed was faster than or comparable to existing algorithms.
Dual-Task nTMS Mapping to Visualize the Cortico-Subcortical Language Network and Capture Postoperative Outcome—A Patient Series in Neurosurgery
Authors: Ohlerth Ann-Katrin , Bastiaanse Roelien , Nickels Lyndsey , Neu Beate , Zhang Wei , Ille Sebastian , Sollmann Nico , Krieg Sandro M.
Published: January 2022

Background

Perioperative assessment of language function in brain tumor patients commonly relies on administration of object naming during stimulation mapping. Ample research, however, points to the benefit of adding verb tasks to the testing paradigm in order to delineate and preserve postoperative language function more comprehensively. This research uses a case series approach to explore the feasibility and added value of a dual-task protocol that includes both a noun task (object naming) and a verb task (action naming) in perioperative delineation of language functions.

Materials and Methods

Seven neurosurgical cases underwent perioperative language assessment with both object and action naming. This entailed preoperative baseline testing, preoperative stimulation mapping with navigated Transcranial Magnetic Stimulation (nTMS) with subsequent white matter visualization, intraoperative mapping with Direct Electrical Stimulation (DES) in 4 cases, and postoperative imaging and examination of language change.

Results

We observed a divergent pattern of language organization and decline between cases who showed lesions close to the delineated language network and hence underwent DES mapping, and those that did not. The latter displayed no new impairment postoperatively consistent with an unharmed network for the neural circuits of both object and action naming. For the cases who underwent DES, on the other hand, a higher sensitivity was found for action naming over object naming. Firstly, action naming preferentially predicted the overall language state compared to aphasia batteries. Secondly, it more accurately predicted intraoperative positive language areas as revealed by DES. Thirdly, double dissociations between postoperatively unimpaired object naming and impaired action naming and vice versa indicate segregated skills and neural representation for noun versus verb processing, especially in the ventral stream. Overlaying postoperative imaging with object and action naming networks revealed that dual-task nTMS mapping can explain the drop in performance in those cases where the network appeared in proximity to the resection cavity.

Conclusion

Using a dual-task protocol for visualization of cortical and subcortical language areas through nTMS mapping proved to be able to capture network-to-deficit relations in our case series. Ultimately, adding action naming to clinical nTMS and DES mapping may help prevent postoperative deficits of this seemingly segregated skill.