bluuebunny/crossref_metadata_2025 huggingface dataset:
Barocaloric Properties of Thermoplastic Elastomers
Authors: Weerasekera Naveen , Ajjarapu Kameswara Pavan Kumar , Sudan Kavish , Sumanasekera Gamini , Kate Kunal , Bhatia Bikram
Published: June 2022

Solid-state refrigeration represents a promising alternative to vapor compression refrigeration systems which are inefficient, unreliable, and have a high global warming potential. However, several solid-state cooling technologies—including those relying on a temperature change induced by an applied electric field (electrocaloric effect), magnetic field (magnetocaloric effect), and uniaxial stress (elastocaloric effect)—have been investigated, but their efficiency and scalability remain a concern. Materials with a large barocaloric response—temperature/entropy change induced by hydrostatic pressure—hold a significant promise for solid-state cooling but remain comparatively less explored. These materials need to be inexpensive, compressible, and show a large barocaloric response around the temperature of interest. Soft materials have the potential to meet these requirements and enable the development of low-cost high-efficiency solid-state heat pumps. Here, we investigate the barocaloric performance of commercially available block copolymer thermoplastic elastomers. We characterized the mechanical, thermal, and barocaloric properties of these materials and evaluated their potential for solid-state refrigeration. We utilized rheometric measurements to evaluate the isothermal compressibility and normalized refrigerant capacity of the thermoplastic elastomers. In addition, we directly measured the pressure-induced temperature change of the test materials and compared them with their normalized refrigeration capacity. The measured isothermal compressibility was in the 0.1–0.4 GPa−1 range, while the normalized refrigeration capacity varied between 13.2 and 41.9 kJ K−1 GPa−1 for a 100 MPa applied pressure and 65°C temperature span. The corresponding pressure-induced temperature change for an applied pressure of 434.1 MPa varied between 2.2 and 28°C. These results demonstrated the superior barocaloric properties of thermoplastic elastomers and their promise for next generation barocaloric solid-state refrigeration devices.
Perspectives of Development of Low Emission Zones in Poland: A Short Review
Authors: Kowalska-Pyzalska Anna
Published: June 2022

Introduction of low emission zones (LEZs) in many cities is supposed to mitigate negative externalities from urban transportation, such as noise and GHG emissions. LEZ is present in most of Western European countries, but in Eastern and Central Europe they are rare, even though in this part of Europe the air quality norms in the cities are very often exceeded. The experience from many countries proves that introduction of LEZ should be preceded with the examination of social acceptance to forecast and overcome the potential barriers of adoption to new rules and regulations. It is especially important in country such as Poland, where LEZs are going to be introduced in the near future. Hence, this article aims to review the factors responsible for social acceptance of LEZ and to discuss the prospects of establishing LEZ in Poland in the light of the experiences of other countries, urban and transport challenges in Polish cities, and legislative, economic, and social aspects. The results of the study are presented by means of SWOT analysis, showing that well thought-out solutions and the gradual introduction of restrictions in car traffic can have a positive impact on the level of social acceptance and behavioral change. Measuring social preferences and opinions before the establishment of LEZ could help investigate the relation between the level of restrictions and behavioral adoption of the residents and car users. It is also recommended to take a lesson from the zones already existing in other cities and to follow the solutions that have occurred to meet the expectations of the society while leading to lower GHG emissions and higher standard of living.
Wind Turbine Gearbox Failure Detection Through Cumulative Sum of Multivariate Time Series Data
Authors: Latiffianti Effi , Sheng Shawn , Ding Yu
Published: June 2022

The wind energy industry is continuously improving their operational and maintenance practice for reducing the levelized costs of energy. Anticipating failures in wind turbines enables early warnings and timely intervention, so that the costly corrective maintenance can be prevented to the largest extent possible. It also avoids production loss owing to prolonged unavailability. One critical element allowing early warning is the ability to accumulate small-magnitude symptoms resulting from the gradual degradation of wind turbine systems. Inspired by the cumulative sum control chart method, this study reports the development of a wind turbine failure detection method with such early warning capability. Specifically, the following key questions are addressed: what fault signals to accumulate, how long to accumulate, what offset to use, and how to set the alarm-triggering control limit. We apply the proposed approach to 2 years’ worth of Supervisory Control and Data Acquisition data recorded from five wind turbines. We focus our analysis on gearbox failure detection, in which the proposed approach demonstrates its ability to anticipate failure events with a good lead time.
The Possible Incoming Runoff Under Extreme Rainfall Event in the Fenhe River Basin
Authors: Jian Shengqi , Yin Changyan , Wang Yafei , Yu Xin , Li Yong
Published: June 2022

Prediction of runoff is of great significance for the sustainable utilization of water resources and flood control and disaster reduction in the basin. In this study, a method for predicting the runoff caused by extreme sub-rainfall events was constructed based on the identification of extreme rainfall events, Mann–Kendall Test, R/S analysis, and regression analysis. The method was applied to the Jingle sub-basin, and the results showed that the extreme precipitation in this basin will maintain a slight rising trend in the future, assuming that the climate and underlying conditions remain the same as they were in the current scenario. There is a more stable correlational relationship between rainfall characteristic factors and runoff in extreme rainfall events. The extreme precipitation of 1–5 consecutive days under the 100a return period designed by the hydrological frequency method is 38.74, 60.01, 66.00, 71.44, and 73.69 mm, respectively, and the possible runoff predicted by the four empirical formulas is 1295−2495, 2108−4935, 2408−5801, and 3051−7062 × 104 m3, respectively. The rainfall designed by the hydrological frequency combination method is 203.64 mm, and the possible runoff predicted by the four empirical formulas is 2.8−5.3 × 108 m3. This study can provide a new reference for predicting the possible incoming runoff under extreme sub-rainfall events.
Highly Efficient PANI-WH Novel Composite for Remediation of Ni(II), Pb(II), and Cu(II) From Wastewater
Authors: Arsalan Muhammad , Siddique Imran , Awais Azka , Baoji Miao , Khan Ilyas , Badran Mohamed , Mousa Abd Allah A.
Published: June 2022

The present study comprises the synthesis of a novel composite polyaniline-wheat husk (PANI-WH) and the adsorption of heavy metals (Cu, Pb, and Ni) by using this composite. Characterizations such as SEM of the composite were used to check the chemical composition, state (XPS), crystallographic nature (XRD), and functional groups (FT-IR) of the novel composite before and after the adsorption of heavy metals. The results indicate that the adsorption performance of the PANI-WH novel composite (on heavy metals) is good with excellent binding capacity of 155 mg g−1 for Ni, 95 mg g−1 for Cu, and 110 mg g−1 for Pb. The PANI-WH novel composite shows maximum adsorption at optimum conditions. The remediation capacity of heavy metals was observed up to 99% by using the PANI-WH composite. The present study also involves kinetic, thermodynamic, and isotherm studies, showing that the adsorption of heavy metals is increased by using the PANI-WH composite. The composite material used in this work comes from industrial/agricultural by-products which provide a twofold benefit of not only providing a means of treating water but also an effective method of utilization of these by-products, which otherwise form an additional waste stream. The PANI-WH shows good stability and reusability. In future, the PANI-WH composite can be used for the detection of other heavy metals.
Deforestation as a Cause of Increased Surface Runoff in the Catchment: Remote Sensing and SWAT Approach—A Case Study of Southern Serbia
Authors: Potić Ivan , Mihajlović Ljiljana M. , Šimunić Vanja , Ćurčić Nina B. , Milinčić Miroljub
Published: June 2022

In the past two decades, the South part of Serbia has been affected by exploitive and illegal logging. As this trend is not decreasing to this day, there is a need to determine the area where this logging occurred precisely. The consequences of these actions are tremendous, causing the forest owners’ financial loss (regardless of whether it is private or state property) and a negative impact on the environment. Significant environmental and forest management problems deriving from these actions are erosion increase and more frequent torrential floods occurrence in the catchment. Since it is difficult to update the national forest inventories in remote areas, remote sensing techniques using different satellite imagery types can provide up-to-date data. The initial analysis that employed Normalized Difference Vegetation Index (created using Landsat 7 and Landsat 8 imagery) indicates massive deforestation in the research area between 1999 and 2021. Headwaters of the Štavska river catchment is selected as the research area to determine the amount of erosion in two periods—before and after deforestation occurred. Change in land cover (LC) is presented with two LC maps created applying supervised classification to Landsat 7 imagery from 1999 as a pre-deforestation LC state and Landsat 8 imagery acquired in 2021 as the current LC state. The erosion in the catchment for both periods is determined using the Soil and Water Assessment Tool (SWAT). The analysis results show the erosion change incurred as a deforestation effect in the river catchment. With the data obtained by remote sensing and SWAT analysis, it is possible to track changes in the area and acquire essential data, making the right and fast decisions to protect the natural resources economy and make sustainable development possible in this impoverished region.
Chloroplast Genomic Resources and Genetic Divergence of Endangered Species Bretschneidera sinensis (Bretschneideraceae)
Authors: Shang Ce , Li Enze , Yu Zhucheng , Lian Mengjia , Chen Zhuo , Liu Kangjia , Xu Linli , Tong Zhe , Wang Meifang , Dong Wenpan
Published: June 2022

Bretschneidera sinensis is an endangered woody species found in East and South China. Comprehensive intraspecies chloroplast genome studies have demonstrated novel genetic resources to assess the genetic variation and diversity of this species. Using genome skimming method, we assembled the whole chloroplast genome of 12 genotypes of B. sinensis from different geographical locations, covering most wild populations. The B. sinensis chloroplast genome size ranged from 158,959 to 159,045 base pairs (bp) and displayed a typical circular quadripartite structure. Comparative analyses of 12 B. sinensis chloroplast genome revealed 33 polymorphic simple sequence repeats (SSRs), 105 polymorphic single nucleotide polymorphisms (SNPs), and 55 indels. Phylogenetic analysis showed that the 12 genotypes were grouped into 2 branches, which is consistent with the geographical distribution (Eastern clade and Western clade). Divergence time estimates showed that the two clades were divergent from 0.6 Ma in the late Pleistocene. Ex situ conservation is essential for this species. In this study, we identified SNPs, indels, and microsatellites of B. sinensis by comparative analyses of chloroplast genomes and determined genetic variation between populations using these genomic markers. Chloroplast genomic resources are also important for further domestication, population genetic, and phylogenetic analysis, possibly in combination with molecular markers of mitochondrial and/or nuclear genomes.
Effects of Fertilization and Dry-Season Irrigation on Litterfall Dynamics and Decomposition Processes in Subtropical Eucalyptus Plantations
Authors: Kong Jiejun , Lin Yubiao , Huang Feng , Liu Wenquan , He Qian , Su Yan , Li Jiyue , Wang Guangyu , Qiu Quan
Published: June 2022

Nutrient management in Eucalyptus plantations is critical for wood production and sustainable development. The biogeochemical mechanisms in Eucalyptus plantations are not fully understood due to changes in the spatiotemporal pattern of precipitation and plantation management. The nutrients released from litterfall are important sources of soil nutrition. We measured the seasonal production of various litterfall types and the proportions of their released nutrients in Eucalyptus urophylla × E. grandis plantations under compound fertilization, dry-season irrigation, and a combined compound fertilization and dry-season irrigation treatment. Our results showed that fertilization increased aboveground biomass and annual litterfall production (except leaf), and that the peak of litterfall production occurred in the rainy season. We found that the decomposition rates of leaf were significantly higher than that of twig, which were mainly controlled by stoichiometric characteristics, followed by soil enzyme activity (β-glucosidase, urease, and polyphenol oxidase). Fertilization decreased the carbon: nitrogen ratio and carbon: phosphorus ratio in litter, and increased soil enzyme activities, which accelerates litter decomposition and nutrient release. Dry-season irrigation increased litter decomposition and only affected the proportion of released potassium by changing the carbon: potassium ratio. Fertilization and dry-season irrigation accelerated the nutrient cycle to enhance compensatory growth. These results help to comprehend the effects of forest management on litterfall dynamics and decomposition processes in Eucalyptus plantations with seasonal drought.
In the Pursuit of Synchrony: Northward Shifts in Western Spruce Budworm Outbreaks in a Warming Environment
Authors: Tai Amberly R. , Carroll Allan L.
Published: June 2022

Outbreaks of western spruce budworm (Choristoneura freemani Freeman) in Douglas-fir [Pseudotsuga menziesii (Mirb.) Franco] forests of western Canada have shifted northward in recent decades. Using forest health survey data collected during the previous century (1909 to 2011) to assess the pattern of range shifts, we found that outbreaks have rapidly shifted to higher latitudes and elevations while gradually retracting from the southern and western portions of its range. Given that the survival of western spruce budworm is affected by access to developing buds, we tested the prediction that this shift was associated with climate change-induced alterations in synchrony between budworm larval emergence and Douglas-fir bud development. We simulated the dates of larval emergence and host budburst annually from 1901 to 2011 using existing phenology models and long-term weather data. Over the last century, the timing of larval emergence in relation to budburst has converged toward optimal synchrony at higher latitudes and elevations, while diverging at lower latitudes and elevations. Shifting synchrony arises from differential responses to temperature by the insect and its host tree; both are reliant upon degree day accumulation, but Douglas-fir bud development is putatively dependent upon an additional photoperiodic threshold. Thus, the potential for warming to cause directional shifts in phenological matching between early season folivores and their host trees may be contingent upon the degree to which each depends on different components of their environments for their development.
The Mitochondrial tRNAPhe 625G>A Mutation in Three Han Chinese Families With Cholecystolithiasis
Authors: Hou Lingling , Hu Cuifang , Ji Lili , Wang Qiongdan , Liang Min
Published: June 2022

In this study, we assessed three Chinese families with inherited cholecystolithiasis and conducted the clinical, genetic, and molecular characterization of these subjects. Eight of eighteen matrilineal relatives had a clinical phenotype in these three families. Sequence analysis of complete mitochondrial genomes in these probands identified the homoplasmic tRNAPhe 625 G > A mutation and distinct sets of mtDNA polymorphisms belonging to haplogroups H2, F4b, and M10a. The 625G > A mutation disturbed the classic G-C base-pairings at a highly conserved position 49 in the T-stem of mitochondrial tRNAs. Molecular dynamics simulation showed that the structure of tRNAphe with 625 G > A mutation was noticeably remodeled while compared with the isoform of the wild type. The occurrence of tRNAPhe 625 G > A mutation in these various genetically unrelated subjects strongly indicates that this mutation is involved in the pathogenesis of cholecystolithiasis. This is the first evidence that tRNA mutations are associated with cholecystolithiasis, and it provided more insights into the genetic mechanism of cholecystolithiasis.
Integration of Protein-Protein Interaction Networks and Gene Expression Profiles Helps Detect Pancreatic Adenocarcinoma Candidate Genes
Authors: Su Lili , Liu Guang , Guo Ying , Zhang Xuanping , Zhu Xiaoyan , Wang Jiayin
Published: June 2022

More and more cancer-associated genes (CAGs) are being identified with the development of biological mechanism research. Integrative analysis of protein-protein interaction (PPI) networks and co-expression patterns of these genes can help identify new disease-associated genes and clarify their importance in specific diseases. This study proposed a PPI network and co-expression integration analysis model (PRNet) to integrate PPI networks and gene co-expression patterns to identify potential risk causative genes for pancreatic adenocarcinoma (PAAD). We scored the importance of the candidate genes by constructing a high-confidence co-expression-based edge-weighted PPI network, extracting protein regulatory sub-networks by random walk algorithm, constructing disease-specific networks based on known CAGs, and scoring the genes of the sub-networks with the PageRank algorithm. The results showed that our screened top-ranked genes were more critical in tumours relative to the known CAGs list and significantly differentiated the overall survival of PAAD patients. These results suggest that the PRNet method of ranking cancer-associated genes can identify new disease-associated genes and is more informative than the original CAGs list, which can help investigators to screen potential biomarkers for validation and molecular mechanism exploration.
Developing a National Newborn Genomes Program: An Approach Driven by Ethics, Engagement and Co-design
Authors: Pichini Amanda , Ahmed Arzoo , Patch Christine , Bick David , Leblond Mathilde , Kasperaviciute Dalia , Deen Dasha , Wilde Simon , Garcia Noriega Sofia , Matoko Christella , Tuff-Lacey Alice , Wigley Chris , Scott Richard H.
Published: June 2022

The transformative potential of whole genome sequencing (WGS) as a diagnostic tool in healthcare has been demonstrated by initiatives including the 100,000 Genomes Project and is now offered to certain patients in the National Health Service (NHS) in England. Building on these foundations, the utility of WGS in the newborn period can now be explored. Genomics England is working in partnership with NHS England and NHS Improvement and other healthcare, patient and public interest groups to design a research program embedded in the NHS to explore the potential challenges and implications of offering WGS in all newborns. The program will aim to: 1) evaluate the feasibility, utility and impact on the NHS of screening for childhood-onset rare actionable genetic conditions; 2) understand how, with consent, genomic and healthcare data could be used to enable research to develop new diagnostics and treatments; and 3) explore the implications of storing an individual’s genome for use over their lifetime. Recognizing the important practical, scientific and ethical questions that we must explore in dialogue with the public and experts, we are taking a collaborative, evidence-based and ethically deliberate approach to designing the program. An iterative co-design process including a nationwide public dialogue has identified emergent themes and ethical considerations which are the focus of the program’s design. These themes will be further developed through continued engagement with healthcare professionals, researchers, ethics experts, patient groups and the public, with an ongoing commitment to embedding ongoing ethics research and co-design into the delivery of the program.
Identification of Feature Genes of a Novel Neural Network Model for Bladder Cancer
Authors: Zhang Yongqing , Hua Shan , Jiang Qiheng , Xie Zhiwen , Wu Lei , Wang Xinjie , Shi Fei , Dong Shengli , Jiang Juntao
Published: June 2022

Background: The combination of deep learning methods and oncogenomics can provide an effective diagnostic method for malignant tumors; thus, we attempted to construct a reliable artificial neural network model as a novel diagnostic tool for Bladder cancer (BLCA).

Methods: Three expression profiling datasets (GSE61615, GSE65635, and GSE100926) were downloaded from the Gene Expression Omnibus (GEO) database. GSE61615 and GSE65635 were taken as the train group, while GSE100926 was set as the test group. Differentially expressed genes (DEGs) were filtered out based on the logFC and FDR values. We also performed Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses to explore the biological functions of the DEGs. Consequently, we utilized a random forest algorithm to identify feature genes and further constructed a neural network model. The test group was given the same procedures to validate the reliability of the model. We also explored immune cells’ infiltration degree and correlation coefficients through the CiberSort algorithm and corrplot R package. The qRT–PCR assay was implemented to examine the expression level of the feature genes in vitro.

Results: A total of 265 DEGs were filtered out and significantly enriched in muscle system processes, collagen-containing and focal adhesion signaling pathways. Based on the random forest algorithm, we selected 14 feature genes to construct the neural network model. The area under the curve (AUC) of the training group was 0.950 (95% CI: 0.850–1.000), and the AUC of the test group was 0.667 (95% CI: 0.333–1.000). Besides, we observed significant differences in the content of immune infiltrating cells and the expression levels of the feature genes.

Conclusion: After repeated verification, our neural network model had clinical feasibility to identify bladder cancer patients and provided a potential target to improve the management of BLCA.
Immunoproteasome Inhibition Reduces the T Helper 2 Response in Mouse Models of Allergic Airway Inflammation
Authors: Oliveri Franziska , Basler Michael , Rao Tata Nageswara , Fehling Hans Joerg , Groettrup Marcus
Published: June 2022

Background

Allergic asthma is a chronic disease and medical treatment often fails to fully control the disease in the long term, leading to a great need for new therapeutic approaches. Immunoproteasome inhibition impairs T helper cell function and is effective in many (auto-) inflammatory settings but its effect on allergic airway inflammation is unknown.

Methods

Immunoproteasome expression was analyzed in in vitro polarized T helper cell subsets. To study Th2 cells in vivo acute allergic airway inflammation was induced in GATIR (GATA-3-vYFP reporter) mice using ovalbumin and house dust mite extract. Mice were treated with the immunoproteasome inhibitor ONX 0914 or vehicle during the challenge phase and the induction of airway inflammation was analyzed.

Results

In vitro polarized T helper cell subsets (Th1, Th2, Th17, and Treg) express high levels of immunoproteasome subunits. GATIR mice proved to be a useful tool for identification of Th2 cells. Immunoproteasome inhibition reduced the Th2 response in both airway inflammation models. Furthermore, T cell activation and antigen-specific cytokine secretion was impaired and a reduced infiltration of eosinophils and professional antigen-presenting cells into the lung and the bronchoalveolar space was observed in the ovalbumin model.

Conclusion

These results show the importance of the immunoproteasome in Th2 cells and airway inflammation. Our data provides first insight into the potential of using immunoproteasome inhibition to target the aberrant Th2 response, e.g. in allergic airway inflammation.
Differences in SARS-CoV-2-Specific Antibody Responses After the First, Second, and Third Doses of BNT162b2 in Naïve and Previously Infected Individuals: A 1-Year Observational Study in Healthcare Professionals
Authors: Ogrič Manca , Žigon Polona , Podovšovnik Eva , Lakota Katja , Sodin-Semrl Snezna , Rotar Žiga , Čučnik Saša
Published: June 2022

Background

Safe and effective vaccines against COVID-19 are critical for preventing the spread of SARS-CoV-2, but little is known about the humoral immune response more than 9 months after vaccination. We aimed to assess the humoral immune response after the first, second, and third (booster) doses of BNT162b2 vaccine in SARS-CoV-2 naïve and previously infected healthcare professionals (HCP) and the humoral immune response after infection in vaccinated HCP.

Methods

We measured anti-spike (anti-S) and anti-nucleocapsid antibodies at different time points up to 12 months in the sera of 300 HCP who had received two or three doses of BNT162b2 vaccine. Mixed-model analyses were used to assess anti-S antibody dynamics and to determine their predictors (age, sex, BMI, and previous infection).

Results

Naïve individuals had statistically lower anti-S antibody concentrations after the first dose (median 253 BAU/ml) than previously infected individuals (median 3648 BAU/ml). After the second dose, anti-S antibody concentrations increased in naïve individuals (median 3216 BAU/ml), whereas the second dose did not significantly increase concentrations in previously infected individuals (median 4503 BAU/ml). The third dose resulted in an additional increase in concentrations (median 4844 BAU/ml in naïve and median 5845 BAU/ml in previously infected individuals). Anti-S antibody concentrations steadily decreased after the second dose and after the third dose in naïve and previously infected individuals. In addition, we found that age had an effect on the humoral immune response. Younger individuals had higher anti-S antibody concentrations after the first and second doses. After infection with the new variant Omicron, a further increase in anti-S antibody concentrations to a median value of 4794 BAU/ml was observed in three times vaccinated HCP whose anti-S antibody concentrations were relatively high before infection (median 2141 BAU/ml). Our study also showed that individuals with systemic adverse events achieved higher anti-S antibody concentrations.

Conclusion

In this study, significant differences in humoral immune responses to BNT162b2 vaccine were observed between naïve and previously infected individuals, with age playing an important role, suggesting that a modified vaccination schedule should be practiced in previously infected individuals. In addition, we showed that the high anti-S antibodies were not protective against new variants of SARS-CoV-2.
Dsg1 and Dsg3 Composition of Desmosomes Across Human Epidermis and Alterations in Pemphigus Vulgaris Patient Skin
Authors: Schmitt Thomas , Pircher Julia , Steinert Letyfee , Meier Katharina , Ghoreschi Kamran , Vielmuth Franziska , Kugelmann Daniela , Waschke Jens
Published: June 2022

Desmosomes are important epidermal adhesion units and signalling hubs, which play an important role in pemphigus pathogenesis. Different expression patterns of the pemphigus autoantigens desmoglein (Dsg)1 and Dsg3 across different epidermal layers have been demonstrated. However, little is known about changes in desmosome composition in different epidermal layers or in patient skin. The aim of this study was thus to characterize desmosome composition in healthy and pemphigus skin using super-resolution microscopy. An increasing Dsg1/Dsg3 ratio from lower basal (BL) to uppermost granular layer (GL) was observed. Within BL desmosomes, Dsg1 and Dsg3 were more homogeneously distributed whereas superficial desmosomes mostly comprised one of the two molecules or domains containing either one but not both. Extradesmosomal, desmoplakin (Dp)-independent, co-localization of Dsg3 with plakoglobin (Pg) was found mostly in BL and extradesmosomal Dsg1 co-localization with Pg in all layers. In contrast, in the spinous layer (SL) most Dsg1 and Dsg3 staining was confined to desmosomes, as revealed by the co-localization with Dp. In pemphigus patient skin, Dsg1 and Dsg3 immunostaining was altered especially along blister edges. The number of desmosomes in patient skin was reduced significantly in basal and spinous layer keratinocytes with only few split desmosomes found. In addition, Dsg1-Pg co-localization at the apical BL and Dsg3-Pg co-localization in SL were significantly reduced in patients, suggesting that that extradesmosomal Dsg molecules were affected. These results support the hypothesis that pemphigus is a desmosome assembly disease and may help to explain histopathologic differences between pemphigus phenotypes.
Bacillus subtilis Expressing the Infectious Pancreatic Necrosis Virus VP2 Protein Retains Its Immunostimulatory Properties and Induces a Specific Antibody Response
Authors: Docando Félix , Nuñez-Ortiz Noelia , Gonçalves Gabriela , Serra Cláudia R. , Gomez-Casado Eduardo , Martín Diana , Abós Beatriz , Oliva-Teles Aires , Tafalla Carolina , Díaz-Rosales Patricia
Published: June 2022

Bacillus subtilis has been documented in the past years as an effective probiotic for different aquacultured species, with recognized beneficial effects on water quality, fish growth and immune status. Furthermore, its potential as a vaccine adjuvant has also been explored in different species. In the current work, we have used B. subtilis spores as delivery vehicles for the presentation of the VP2 protein from infectious pancreatic necrosis virus (IPNV). For this, the VP2 gene was amplified and translationally fused to the crust protein CotY. The successful expression of VP2 on the spores was confirmed by Western blot. We then compared the immunostimulatory potential of this VP2-expressing strain (CRS208) to that of the original B. subtilis strain (168) on rainbow trout (Oncorhynchus mykiss) leukocytes obtained from spleen, head kidney and the peritoneal cavity. Our results demonstrated that both strains significantly increased the percentage of IgM+ B cells and the number of IgM-secreting cells in all leukocyte cultures. Both strains also induced the transcription of a wide range of immune genes in these cultures, with small differences between them. Importantly, specific anti-IPNV antibodies were detected in fish intraperitoneally or orally vaccinated with the CRS208 strain. Altogether, our results demonstrate B. subtilis spores expressing foreign viral proteins retain their immunomodulatory potential while inducing a significant antibody response, thus constituting a promising vaccination strategy.
A Novel Tree Shrew Model of Chronic Experimental Autoimmune Uveitis and Its Disruptive Application
Authors: Hu Kaijiao , Lv Longbao , Huang Hui , Yin Guangnian , Gao Jie , Liu Jianping , Yang Yaying , Zeng Wenxin , Chen Yan , Zhang Ni , Zhang Feiyan , Ma Yuhua , Chen Feilan
Published: June 2022

Background

Previous studies have established several animal models for experimental autoimmune uveitis (EAU) in rodents without the fovea centralis in the human retina. This study aimed to develop and explore the application of a novel EAU model in tree shrews with a cone-dominated retina resembling the human fovea.

Methods

Tree shrews were clinically and pathologically evaluated for the development and characteristics of EAU immunized with six inter-photoreceptor retinoid-binding proteins (IRBPs). IRBP-specific T-cell proliferation and serum cytokine of tree shrews were evaluated to determine the immune responses. Differentially expressed genes (DEGs) were identified in the eyes of tree shrews with EAU by RNA-sequencing. The disruptive effects of the DEG RGS4 inhibitor CCG 203769 and dihydroartemisinin on the EAU were investigated to evaluate the potential application of tree shrew EAU.

Results

IRBP1197–1211and R14 successfully induced chronic EAU with subretinal deposits and retinal damage in the tree shrews. The immunological characteristics presented the predominant infiltration of microglia/macrophages, dendritic cells, and CD4-T-cells into the uvea and retina and pathogenic T helper (Th) 1 and Th17 responses. The subretinal deposits positively expressed amyloid β-protein (Aβ), CD8, and P2Y purinoceptor 12 (P2RY12). The crucial DEGs in R14-induced EAU, such asP2RY2andadenylate cyclase 4 (ADCY4), were enriched for several pathways, including inflammatory mediator regulation of transient receptor potential (TRP) channels. The upregulatedRGS4in IRBP-induced EAU was associated with mitogen-activated protein kinase (MAPK) activity. RGS4 inhibition and dihydroartemisinin could significantly alleviate the retinal pathological injuries of IRBP1197-1211-induced EAU by decreasing the expression of CD4 T-cells.

Conclusion

Our study provides a novel chronic EAU in tree shrews elicited by bovine R14 and tree shrew IRBP1197-1211characterized by retinal degeneration, retinal damage with subretinal Aβ deposits and microglia/macrophage infiltration, and T-cell response, probably by altering important pathways and genes related to bacterial invasion, inflammatory pain, microglial phagocytosis, and lipid and glucose metabolism. The findings advance the knowledge of the pathogenesis and therapeutics of the fovea-involved visual disturbance in human uveitis.
Retrospective Comparison of Efficacy and Safety of Rabbit Anti-Thymocyte Globulin and Porcine Anti-Lymphocyte Globulin in Patients With Acquired Aplastic Anemia Undergoing Hematopoietic Stem Cell Transplantation From Matched Sibling Donors
Authors: Zhang Yuanfeng , Chen Xin , Li Lin , Li Yun , Lin Li , Cao Yang , Wang Na , Yang Donglin , Pang Aiming , Zhang Rongli , Ma Qiaoling , Zhai Weihua , He Yi , Wei Jialin , Jiang Erlie , Han MingZhe , Zhang Yicheng , Feng Sizhou
Published: June 2022

We compared the efficacy and safety of porcine anti-lymphocyte globulin (pALG) (n=140) and rabbit anti-thymocyte globulin (rATG) (n=86) in patients with acquired aplastic anemia (AA) receiving hematopoietic stem cell transplantation (HSCT) from matched sibling donors (MSD) in two transplantation centers in China ranging from 2005 to 2020. The groups had similar baseline characteristics except for a higher number of infused mononuclear cells (P<0.001) and a higher proportion of peripheral blood stem cells as graft sources (P=0.003) in the pALG group. The rates of neutrophil engraftment at day 28 (P=1), platelet engraftment at day 28 (P=0.228), bloodstream infection before engraftment (P=0.867), invasive fungal diseases (P=0.362), cytomegalovirus viremia (P=0.667), and graft rejection (P=0.147) were similar in the two groups. A higher cumulative incidence of grades II-IV acute graft versus host disease (aGvHD) at 100 days occurred in the pALG group (19% vs. 8%, P=0.035) while no significant differences in grades III-IV aGvHD (P=0.572), mild to severe chronic GvHD (cGvHD) (P=0.181), and moderate to severe cGvHD (P=0.586) were observed. The actuarial 5-year overall survival (OS), failure-free survival (FFS), and GvHD-free, FFS rates of the pALG group were 87% (95% confidence interval [CI], 82-93), 85% (95% CI, 80-92), and 78% (95% CI, 72-92) versus 91% (95% CI, 86-99) (P=0.33), 88% (95% CI, 82-97) (P=0.428), and 79% (95% CI, 72-90) (P=0.824) in the rATG group, respectively. A busulfan-containing conditioning regimen was the only adverse risk factor for OS and FFS in multivariate analysis. In conclusion, pALG is an alternative to rATG in patients with severe AA receiving MSD-HSCT. A prospective, large-sample study is needed to explore this therapy further.
Egg-Derived Anti-SARS-CoV-2 Immunoglobulin Y (IgY) With Broad Variant Activity as Intranasal Prophylaxis Against COVID-19
Authors: Frumkin Lyn R. , Lucas Michaela , Scribner Curtis L. , Ortega-Heinly Nastassja , Rogers Jayden , Yin Gang , Hallam Trevor J. , Yam Alice , Bedard Kristin , Begley Rebecca , Cohen Courtney A. , Badger Catherine V. , Abbasi Shawn A. , Dye John M. , McMillan Brian , Wallach Michael , Bricker Traci L. , Joshi Astha , Boon Adrianus C. M. , Pokhrel Suman , Kraemer Benjamin R. , Lee Lucia , Kargotich Stephen , Agochiya Mahima , John Tom St. , Mochly-Rosen Daria
Published: June 2022

COVID-19 emergency use authorizations and approvals for vaccines were achieved in record time. However, there remains a need to develop additional safe, effective, easy-to-produce, and inexpensive prevention to reduce the risk of acquiring SARS-CoV-2 infection. This need is due to difficulties in vaccine manufacturing and distribution, vaccine hesitancy, and, critically, the increased prevalence of SARS-CoV-2 variants with greater contagiousness or reduced sensitivity to immunity. Antibodies from eggs of hens (immunoglobulin Y; IgY) that were administered the receptor-binding domain (RBD) of the SARS-CoV-2 spike protein were developed for use as nasal drops to capture the virus on the nasal mucosa. Although initially raised against the 2019 novel coronavirus index strain (2019-nCoV), these anti-SARS-CoV-2 RBD IgY surprisingly had indistinguishable enzyme-linked immunosorbent assay binding against variants of concern that have emerged, including Alpha (B.1.1.7), Beta (B.1.351), Delta (B.1.617.2), and Omicron (B.1.1.529). This is different from sera of immunized or convalescent patients. Culture neutralization titers against available Alpha, Beta, and Delta were also indistinguishable from the index SARS-CoV-2 strain. Efforts to develop these IgY for clinical use demonstrated that the intranasal anti-SARS-CoV-2 RBD IgY preparation showed no binding (cross-reactivity) to a variety of human tissues and had an excellent safety profile in rats following 28-day intranasal delivery of the formulated IgY. A double-blind, randomized, placebo-controlled phase 1 study evaluating single-ascending and multiple doses of anti-SARS-CoV-2 RBD IgY administered intranasally for 14 days in 48 healthy adults also demonstrated an excellent safety and tolerability profile, and no evidence of systemic absorption. As these antiviral IgY have broad selectivity against many variants of concern, are fast to produce, and are a low-cost product, their use as prophylaxis to reduce SARS-CoV-2 viral transmission warrants further evaluation.

Clinical Trial Registration

https://www.clinicaltrials.gov/ct2/show/NCT04567810, identifier NCT04567810.
Case Report: Mucous Membrane Pemphigoid With IgG and IgA Anti-Laminin γ1 Antibodies and IgA Anti-Laminin α5 Antibodies
Authors: Kuang Wenjing , Qian Hua , Zhang Qiyue , Li Wei , Hashimoto Takashi , Zeng Xin , Li Xiaoguang
Published: June 2022

Mucous membrane pemphigoid (MMP) and anti-laminin (LM) γ1 pemphigoid, two subtypes of subepidermal autoimmune bullous diseases characterized by autoantibodies against epidermal basement membrane zone proteins, mainly show mucosal and skin lesions, respectively. The known autoantigens of MMP includes BP180, BP230, LM332, integrin α6β4 and type VII collagen, and anti-LMγ1 pemphigoid targets LMγ1. In this study, we present an unique MMP case with oral mucosal lesions, which showed positive IgA signals on basement membrane zone in indirect immunofluorescence using normal human skin and on dermal side in indirect immunofluorescence using salt-split skin, positive IgA autoantibodies against LMγ1 by immunoblotting of epidermal extracts, positive IgA autoantibodies against LMα5 by immunoblotting of LM521 recombinant protein (rLM521) and positive IgG autoantibodies against LMγ1 by immunoblotting of rLM111 and rLM521 at first visit (Day 0). After therapy, further serological analyses of serum samples collected at Day 30 and Day 50 indicated that IgA autoantibodies against LMγ1 were likely to be pathogenic. These results suggest that LMγ1 is another autoantigen of MMP, and our patient might be the first reported case of anti-LMγ1 MMP.
Characterization of Zymosan-Modulated Neutrophils With Neuroregenerative Properties
Authors: Jerome Andrew D. , Atkinson Jeffrey R. , McVey Moffatt Arnetta L. , Sepeda Jesse A. , Segal Benjamin M. , Sas Andrew R.
Published: June 2022

Recent studies using advanced techniques such as single cell RNA sequencing (scRNAseq), high parameter flow cytometry, and proteomics reveal that neutrophils are more heterogeneous than previously appreciated. Unique subsets have been identified in the context of bacterial and parasitic infections, cancer, and tissue injury and repair. The characteristics of infiltrating neutrophils differ depending on the nature of the inflammation-inciting stimulus, the stage of the inflammatory response, as well as the tissue microenvironment in which they accumulate. We previously described a new subpopulation of immature Ly6Glow neutrophils that accumulate in the peritoneal cavity 3 days following intraperitoneal (i.p.) administration of the fungal cell wall extract, zymosan. These neutrophils express markers of alternative activation and possess neuroprotective/regenerative properties. In addition to inducing neurite outgrowth of explanted neurons, they enhance neuronal survival and axon regeneration in vivo following traumatic injury to the optic nerve or spinal cord. In contrast, the majority of neutrophils that accumulate in the peritoneal fluid 4 hours following i.p. zymosan injection (4h NΦ) have features of conventional, mature Ly6Ghi neutrophils and lack neuroprotective or neuroregenerative properties. In the current study, we expand upon on our previously published observations by performing a granular, in-depth analysis of these i.p. zymosan-modulated neutrophil populations using scRNAseq and high parameter flow cytometry. We also analyze cell lysates of each neutrophil population by liquid chromatography/mass spectrometry. Circulating blood neutrophils, harvested from naive mice, are analyzed in parallel as a control. When samples were pooled from all three groups, scRNAseq revealed 11 distinct neutrophil clusters. Pathway analyses demonstrated that 3d NΦ upregulate genes involved in tissue development and wound healing, while 4h NΦ upregulate genes involved in cytokine production and perpetuation of the immune response. Proteomics analysis revealed that 3d NΦ and 4h NΦ also express distinct protein signatures. Adding to our earlier findings, 3d NΦ expressed a number of neuroprotective/neuroregenerative candidate proteins that may contribute to their biological functions. Collectively, the data generated by the current study add to the growing literature on neutrophil heterogeneity and functional sub-specialization and might provide new insights in elucidating the mechanisms of action of pro-regenerative, neuroprotective neutrophil subsets.
Clinical Variables, Deep Learning and Radiomics Features Help Predict the Prognosis of Adult Anti-N-methyl-D-aspartate Receptor Encephalitis Early: A Two-Center Study in Southwest China
Authors: Xiang Yayun , Dong Xiaoxuan , Zeng Chun , Liu Junhang , Liu Hanjing , Hu Xiaofei , Feng Jinzhou , Du Silin , Wang Jingjie , Han Yongliang , Luo Qi , Chen Shanxiong , Li Yongmei
Published: June 2022

Objective

To develop a fusion model combining clinical variables, deep learning (DL), and radiomics features to predict the functional outcomes early in patients with adult anti-N-methyl-D-aspartate receptor (NMDAR) encephalitis in Southwest China.

Methods

From January 2012, a two-center study of anti-NMDAR encephalitis was initiated to collect clinical and MRI data from acute patients in Southwest China. Two experienced neurologists independently assessed the patients’ prognosis at 24 moths based on the modified Rankin Scale (mRS) (good outcome defined as mRS 0–2; bad outcome defined as mRS 3-6). Risk factors influencing the prognosis of patients with acute anti-NMDAR encephalitis were investigated using clinical data. Five DL and radiomics models trained with four single or combined four MRI sequences (T1-weighted imaging, T2-weighted imaging, fluid-attenuated inversion recovery imaging and diffusion weighted imaging) and a clinical model were developed to predict the prognosis of anti-NMDAR encephalitis. A fusion model combing a clinical model and two machine learning-based models was built. The performances of the fusion model, clinical model, DL-based models and radiomics-based models were compared using the area under the receiver operating characteristic curve (AUC) and accuracy and then assessed by paired t-tests (P < 0.05 was considered significant).

Results

The fusion model achieved the significantly greatest predictive performance in the internal test dataset with an AUC of 0.963 [95% CI: (0.874-0.999)], and also significantly exhibited an equally good performance in the external validation dataset, with an AUC of 0.927 [95% CI: (0.688-0.975)]. The radiomics_combined model (AUC: 0.889; accuracy: 0.857) provided significantly superior predictive performance than the DL_combined (AUC: 0.845; accuracy: 0.857) and clinical models (AUC: 0.840; accuracy: 0.905), whereas the clinical model showed significantly higher accuracy. Compared with all single-sequence models, the DL_combined model and the radiomics_combined model had significantly greater AUCs and accuracies.

Conclusions

The fusion model combining clinical variables and machine learning-based models may have early predictive value for poor outcomes associated with anti-NMDAR encephalitis.
Uterine Natural Killer Cells: A Rising Star in Human Pregnancy Regulation
Authors: Xie Min , Li Yan , Meng Yi-Zi , Xu Peng , Yang Yong-Guang , Dong Shuai , He Jin , Hu Zheng
Published: June 2022

Uterine natural killer (uNK) cells are an immune subset located in the uterus. uNK cells have distinct tissue-specific characteristics compared to their counterparts in peripheral blood and lymphoid organs. Based on their location and the pregnancy status of the host, uNK cells are classified as endometrial NK (eNK) cells or decidua NK (dNK) cells. uNK cells are important in protecting the host from pathogen invasion and contribute to a series of physiological processes that affect successful pregnancy, including uterine spiral artery remodeling, fetal development, and immunity tolerance. Abnormal alterations in uNK cell numbers and/or impaired function may cause pregnancy complications, such as recurrent miscarriage, preeclampsia, or even infertility. In this review, we introduce recent advances in human uNK cell research under normal physiological or pathological conditions, and summarize their unique influences on the process of pregnancy complications or uterine diseases. Finally, we propose the potential clinical use of uNK cells as a novel cellular immunotherapeutic approach for reproductive disorders.