bluuebunny/crossref_metadata_2025 huggingface dataset:
Post-Translational Modification of Lamins: Mechanisms and Functions
Authors: Zheng Mingyue , Jin Guoxiang , Zhou Zhongjun
Published: May 2022

Lamins are the ancient type V intermediate filament proteins contributing to diverse biological functions, such as the maintenance of nuclear morphology, stabilization of chromatin architecture, regulation of cell cycle progression, regulation of spatial-temporal gene expressions, and transduction of mechano-signaling. Deregulation of lamins is associated with abnormal nuclear morphology and chromatin disorganization, leading to a variety of diseases such as laminopathy and premature aging, and might also play a role in cancer. Accumulating evidence indicates that lamins are functionally regulated by post-translational modifications (PTMs) including farnesylation, phosphorylation, acetylation, SUMOylation, methylation, ubiquitination, and O-GlcNAcylation that affect protein stabilization and the association with chromatin or associated proteins. The mechanisms by which these PTMs are modified and the relevant functionality become increasingly appreciated as understanding of these changes provides new insights into the molecular mechanisms underlying the laminopathies concerned and novel strategies for the management. In this review, we discussed a range of lamin PTMs and their roles in both physiological and pathological processes, as well as potential therapeutic strategies by targeting lamin PTMs.
Five-Year Results of Aortic Remodeling for Acute, Subacute, and Chronic Type B Aortic Dissection Following Endovascular Repair
Authors: Yang Guangmin , Ge Hongwei , Wu Guangyan , Zhang Yepeng , Zhang Leiyang , Zhang Ming , Li Xiaoqiang , Zhou Min
Published: May 2022

Background

This study was performed to compare aortic remodeling and clinical outcomes in patients with acute, subacute, and chronic type B aortic dissection (TBAD) after thoracic endovascular aortic repair (TEVAR).

Methods

We retrospectively examined 323 consecutive patients with acute (n = 129), subacute (n = 161), and chronic (n = 33) TBAD who underwent TEVAR from June 2013 to December 2016 in in multicenter institution. Patient demographics, clinical data, and imaging characteristics were recorded and compared among the three groups.

Results

The three groups had comparable baseline characteristics. Perioperative mortality rates were similar among the acute (2.3%), subacute (0.0%), and chronic (0.0%) groups (P = 0.34). Perioperative morbidity rates, including the rates of visceral and lower limb malperfusion and cerebral infraction, were also similar. The rate of perioperative endoleak was significantly higher in the chronic group (18.1%) than in the acute (3.9%) and subacute (3.7%) groups (P = 0.02). The mean follow-up duration was 78 ± 22 months (range, 36–101 months). The mortality rates were comparable among the three groups. The rates of reintervention and lower limb malperfusion were higher in the chronic group than in the acute and subacute groups. FL diameter reduction were more robust in the acute and subacute groups than in the chronic group.

Conclusion

Patients with acute, subacute, and chronic TBAD had different outcomes in this study. Patients with acute and subacute TBAD had fewer complications than those with chronic TBAD. Aortic remodeling after TEVAR was more favorable in patients with acute and subacute TBAD than in patients with chronic TBAD. TEVAR promotes more positive remodeling at the stent graft level than at the distal level of the aorta.
Assessment and Management of Older Patients With Transthyretin Amyloidosis Cardiomyopathy: Geriatric Cardiology, Frailty Assessment and Beyond
Authors: Irabor Biobelemoye , McMillan Jacqueline M. , Fine Nowell M.
Published: May 2022

Transthyretin amyloidosis cardiomyopathy (ATTR-CM) is commonly diagnosed in older adults, in particular the wild-type (ATTRwt), which is regarded as an age-related disease. With an aging population and improved diagnostic techniques, the prevalence and incidence of ATTR-CM will continue to increase. With increased availability of mortality reducing ATTR-CM therapies, patients are living longer. The predominant clinical manifestation of ATTR-CM is heart failure, while other cardiovascular manifestations include arrhythmia and aortic stenosis. Given their older age at diagnosis, patients often present with multiple age-related comorbidities, some of which can be exacerbated by ATTR, including neurologic, musculoskeletal, and gastrointestinal problems. Considerations related to older patient care, such as frailty, cognitive decline, polypharmacy, falls/mobility, functional capacity, caregiver support, living environment, quality of life and establishing goals of care are particularly important for many patients with ATTR-CM. Furthermore, the high cost ATTR treatments has increased interest in establishing improved predictors of response to therapy, with assessment of frailty emerging as a potentially important determinant. Multidisciplinary care inclusive of collaboration with geriatric and elder care medicine specialists, and others such as neurology, orthopedic surgery, electrophysiology and transcatheter aortic valve replacement clinics, is now an important component of ATTR-CM management. This review will examine current aspects of the management of older ATTR-CM patients, including shared care with multiple medical specialists, the emerging importance of frailty assessment and other considerations for using ATTR therapies.
Estimation of Heart Rate Variability Parameters by Machine Learning Approaches Applied to Facial Infrared Thermal Imaging
Authors: Di Credico Andrea , Perpetuini David , Izzicupo Pascal , Gaggi Giulia , Cardone Daniela , Filippini Chiara , Merla Arcangelo , Ghinassi Barbara , Di Baldassarre Angela
Published: May 2022

Heart rate variability (HRV) is a reliable tool for the evaluation of several physiological factors modulating the heart rate (HR). Importantly, variations of HRV parameters may be indicative of cardiac diseases and altered psychophysiological conditions. Recently, several studies focused on procedures for contactless HR measurements from facial videos. However, the performances of these methods decrease when illumination is poor. Infrared thermography (IRT) could be useful to overcome this limitation. In fact, IRT can measure the infrared radiations emitted by the skin, working properly even in no visible light illumination conditions. This study investigated the capability of facial IRT to estimate HRV parameters through a face tracking algorithm and a cross-validated machine learning approach, employing photoplethysmography (PPG) as the gold standard for the HR evaluation. The results demonstrated a good capability of facial IRT in estimating HRV parameters. Particularly, strong correlations between the estimated and measured HR (r = 0.7), RR intervals (r = 0.67), TINN (r = 0.71), and pNN50 (%) (r = 0.70) were found, whereas moderate correlations for RMSSD (r = 0.58), SDNN (r = 0.44), and LF/HF (r = 0.48) were discovered. The proposed procedure allows for a contactless estimation of the HRV that could be beneficial for evaluating both cardiac and general health status in subjects or conditions where contact probe sensors cannot be used.
Blue Energy Spearheading the Energy Transition: The Case of Crete
Authors: Stančin Hrvoje , Pfeifer Antun , Perakis Christoforos , Stefanatos Nikolaos , Damasiotis Marko , Magaudda Stefano , Di Pietrantonio Federica , Mikulčić Hrvoje
Published: May 2022

Decarbonization of remote or isolated island communities represents a significant challenge nowadays. Nevertheless, the environmental, economic, and social benefits seek more attention. Lately, blue energy sources, particularly offshore wind power, are gaining momentum to take the lead in the energy transition process, simultaneously offering numerous benefits for local communities and potential investors. In this research, offshore wind power is considered the main driver of the energy transition for the case of the island of Crete. The energy systems’ development scenarios are developed using an energy planning model EnergyPLAN, starting from a reference model developed for the year 2017. Since the island was recently isolated without connections to the mainland grid, integrating renewable energy sources was a challenging task that led to poor energy potential exploitation. The decarbonization of the power generation sector by offshore and onshore wind and photovoltaics can only partially reduce the import dependence on fossil fuels. At the same time, more significant efforts are expected in the transport and industry sectors. With the operational interconnections, 300 MW of offshore wind capacities can be deployed, averaging annual electricity production of 1.17 TWh, satisfying around 70% of total electricity demand.
Spatiotemporal Analysis and Modeling of Sea Ice Growth Rate in Nella Fjord, Antarctica: Based on Observations During the 36th Chinese National Antarctic Research Expedition in 2020
Authors: Sun Xiaoyu , He Yawen , Lv Tingting , Li Chunhua , Gao Yi , Zhao Fu , Xue Zhenshan
Published: May 2022

Obtaining field sea ice data is crucial for the validation and improvement of satellite data and numerical models. During the 36th Chinese National Antarctic Research Expedition, seven field observations covering the whole area were conducted in Nella Fjord, and large amounts of in situ sea ice and snow thickness data were acquired. Then, the influences of snow cover, topography, and air temperature on the sea ice growth rate were examined. Based on the relationship between the sea ice growth rate and air temperature, an empirical model of sea ice thickness was developed. The results show that sea ice started to freeze in early March, and the peak growth rate was reached in mid-June, with a mean growth rate of 0.62 cm/d. Between mid-June and mid-October, the mean growth rate was 0.36–0.4 cm/d; between mid-October and mid-November, the mean growth rate decreased to 0.15 cm/d. After mid-November, ice growth stopped, and the ice thickness decreased. The growth rate and thickness of sea ice near the shore were generally greater than those closer to the center of the fjord, with differences of 0.25 cm/d in mean growth rate and 7.16 cm in mean thickness. Because of the large exchanges of heat between the atmosphere and the ocean, the sea ice thickness increased rapidly during the early stage of freeze-up. When the air temperature was between -12 and −15°C, the ice growth rate was between 0.36 and 0.4 cm/d. However, when the ice thickness reached 0.5 m, the sea ice growth rate became less sensitive to air temperature. In addition, we found that the proposed model has high simulation accuracy for the growth rate of sea ice. Based on the model, we estimated that the growth rates become zero at an air temperature of approximately −4°C. Our study highlights the inverse relationship between the sea ice growth rate and the snow thickness and the fact that the sea ice thickness is mainly affected by air temperature.
Potential of Biochar to Reduce Greenhouse Gas Emissions and Increase Nitrogen Use Efficiency in Boreal Arable Soils in the Long-Term
Authors: Kalu Subin , Kulmala Liisa , Zrim Jure , Peltokangas Kenneth , Tammeorg Priit , Rasa Kimmo , Kitzler Barbara , Pihlatie Mari , Karhu Kristiina
Published: May 2022

Biochars have potential to provide agricultural and environmental benefits such as increasing soil carbon sequestration, crop yield, and soil fertility while reducing greenhouse gas (GHG) emissions and nitrogen leaching. However, whether these effects will sustain for the long-term is still unknown. Moreover, these effects were observed mostly in highly weathered (sub-) tropical soils with low pH and soil organic carbon (SOC). The soils in northern colder boreal regions have typically higher SOC and undergo continuous freeze-thaw cycles. Therefore, effects of biochars in these regions may be different from those observed in other climates. However, only a few biochar studies have been conducted in boreal regions. We aimed to assess the long-term effects of biochars on GHG emissions, yield-normalized non-CO2 GHG emissions (GHGI), and N dynamics in boreal soils. For this, we collected data from four existing Finnish biochar field experiments during 2018 growing season. The experiments were Jokioinen (Stagnosol), Qvidja (Cambisol), Viikki-1 (Stagnosol), and Viikki-2 (Umbrisol), where biochars were applied, 2, 2, 8, and 7 years before, respectively. The GHG emissions, crop yield, soil mineral N, and microbial biomass were measured from all fields, whereas, additional measurements of plant N contents and N leaching were conducted in Qvidja. Biochars increased CO2 efflux in Qvidja and Viikki-2, whereas, there were no statistically significant effects of biochars on the fluxes of N2O or CH4, but in Qvidja, biochars tended to reduce N2O fluxes at the peak emission points. The tendency of biochars to reduce N2O emissions seemed higher in soils with higher silt content and lower initial soil carbon. We demonstrated the long-term effects of biochar on increased crop yield by 65% and reduced GHGI by 43% in Viikki-2. In Qvidja, the significant increment of plant biomass, plant N uptake, nitrogen use efficiency, and crop yield, and reduction of NO3−–N leaching by the spruce biochar is attributed to its ability to retain NO3−–N, which could be linked to its significantly higher specific surface area. The ability of the spruce biochar to retain soil NO3−–N and hence to reduce N losses, has implications for sustainable management of N fertilization.
Sleep and Late-Onset Alzheimer’s Disease: Shared Genetic Risk Factors, Drug Targets, Molecular Mechanisms, and Causal Effects
Authors: Chen Dongze , Wang Xinpei , Huang Tao , Jia Jinzhu
Published: May 2022

Late-onset Alzheimer’s disease (AD) is associated with sleep-related phenotypes (SRPs). The fact that whether they share a common genetic etiology remains largely unknown. We explored the shared genetics and causality between AD and SRPs by using high-definition likelihood (HDL), cross-phenotype association study (CPASSOC), transcriptome-wide association study (TWAS), and bidirectional Mendelian randomization (MR) in summary-level data for AD (N = 455,258) and summary-level data for seven SRPs (sample size ranges from 359,916 to 1,331,010). AD shared a strong genetic basis with insomnia (rg = 0.20; p = 9.70 × 10–5), snoring (rg = 0.13; p = 2.45 × 10–3), and sleep duration (rg = −0.11; p = 1.18 × 10–3). The CPASSOC identifies 31 independent loci shared between AD and SRPs, including four novel shared loci. Functional analysis and the TWAS showed shared genes were enriched in liver, brain, breast, and heart tissues and highlighted the regulatory roles of immunological disorders, very-low-density lipoprotein particle clearance, triglyceride-rich lipoprotein particle clearance, chylomicron remnant clearance, and positive regulation of T-cell–mediated cytotoxicity pathways. Protein–protein interaction analysis identified three potential drug target genes (APOE, MARK4, and HLA-DRA) that interacted with known FDA-approved drug target genes. The CPASSOC and TWAS demonstrated three regions 11p11.2, 6p22.3, and 16p11.2 may account for the shared basis between AD and sleep duration or snoring. MR showed insomnia had a causal effect on AD (ORIVW = 1.02, PIVW = 6.7 × 10–6), and multivariate MR suggested a potential role of sleep duration and major depression in this association. Our findings provide strong evidence of shared genetics and causation between AD and sleep abnormalities and advance our understanding of the genetic overlap between them. Identifying shared drug targets and molecular pathways can be beneficial for treating AD and sleep disorders more efficiently.
Comprehensive Biochemical, Physiological, and Transcriptomic Analyses Provide Insights Into Floral Bud Dormancy in Rhododendron delavayi Franch
Authors: Zhang Lu , Song Jie , Peng Lvchun , Xie Weijia , Li Shifeng , Wang Jihua
Published: May 2022

Due to a scarcity of relevant data, the ornamental woody flowerRhododendron delavayiFranch. is examined in the current study for its low temperature-induced floral bud dormancy (late October–end December) aspect. This study used transcriptome data profiling and co-expression network analyses to identify the interplay between endogenous hormones and bud dormancy phases such as pre-dormancy, para-dormancy, endo-dormancy, eco-dormancy, and dormancy release. The biochemical and physiological assays revealed the significance of the abundance of phytohormones (abscisic acid, auxin, zeatin, and gibberellins), carbohydrate metabolism, oxidative species, and proteins (soluble proteins, proline, and malondialdehyde) in the regulatory mechanism of floral bud dormancy. The transcriptome sequencing generated 65,531 transcripts, out of which 504, 514, 307, and 240 expressed transcripts were mapped uniquely to pre-, para-, endo-, and eco-phases of dormancy, showing their roles in the stimulation of dormancy. The transcripts related toLEA29,PGM,SAURfamily,RPL9e,ATRX,FLOWERING LOCUS T,SERK1,ABFs,ASR2, andGID1were identified as potential structural genes involved in floral bud dormancy. The transcription factors, includingZinc fingers,CAD,MADS-boxfamily,MYB, andMYC2,revealed their potential regulatory roles concerning floral bud dormancy.The gene co-expression analysis highlighted essential hub genes involved in cold stress adaptations encoding proteins,viz,SERPIN,HMA,PMEI,LEA_2,TRX,PSBT, andAMAT. We exposed the connection among low temperature-induced dormancy in floral buds, differentially expressed genes, and hub genesviastrict screening steps to escalate the confidence in selected genes as being truly putative in the pathways regulating bud dormancy mechanism. The identified candidate genes may prove worthy of further in-depth studies on molecular mechanisms involved in floral bud dormancy ofRhododendronspecies.
Analysis of Whole-Transcriptome RNA-Seq Data Reveals the Involvement of Alternative Splicing in the Drought Response of Glycyrrhiza uralensis
Authors: Li Guozhi , Xu Dengxian , Huang Gang , Bi Quan , Yang Mao , Shen Haitao , Liu Hailiang
Published: May 2022

Alternative splicing (AS) is a post-transcriptional regulatory mechanism that increases protein diversity. There is growing evidence that AS plays an important role in regulating plant stress responses. However, the mechanism by which AS coordinates with transcriptional regulation to regulate the drought response in Glycyrrhiza uralensis remains unclear. In this study, we performed a genome-wide analysis of AS events in G. uralensis at different time points under drought stress using a high-throughput RNA sequencing approach. We detected 2,479 and 2,764 AS events in the aerial parts (AP) and underground parts (UP), respectively, of drought-stressed G. uralensis. Of these, last exon AS and exon skipping were the main types of AS. Overall, 2,653 genes undergoing significant AS regulation were identified from the AP and UP of G. uralensis exposed to drought for 2, 6, 12, and 24 h. Gene Ontology analyses indicated that AS plays an important role in the regulation of nitrogen and protein metabolism in the drought response of G. uralensis. Notably, the spliceosomal pathway and basal transcription factor pathway were significantly enriched with differentially spliced genes under drought stress. Genes related to splicing regulators in the AP and UP of G. uralensis responded to drought stress and underwent AS under drought conditions. In summary, our data suggest that drought-responsive AS directly and indirectly regulates the drought response of G. uralensis. Further in-depth studies on the functions and mechanisms of AS during abiotic stresses will provide new strategies for improving plant stress resistance.
Discovering miRNAs Associated With Multiple Sclerosis Based on Network Representation Learning and Deep Learning Methods
Authors: Sun Xiaoping , Ren Xingshuai , Zhang Jie , Nie Yunzhi , Hu Shan , Yang Xiao , Jiang Shoufeng
Published: May 2022

Identifying biomarkers of Multiple Sclerosis is important for the diagnosis and treatment of Multiple Sclerosis. The existing study has shown that miRNA is one of the most important biomarkers for diseases. However, few existing methods are designed for predicting Multiple Sclerosis-related miRNAs. To fill this gap, we proposed a novel computation framework for predicting Multiple Sclerosis-associated miRNAs. The proposed framework uses a network representation model to learn the feature representation of miRNA and uses a deep learning-based model to predict the miRNAs associated with Multiple Sclerosis. The evaluation result shows that the proposed model can predict the miRNAs associated with Multiple Sclerosis precisely. In addition, the proposed model can outperform several existing methods in a large margin.
Single-Cell RNA-seq Analysis Reveals Cellular Functional Heterogeneity in Dermis Between Fibrotic and Regenerative Wound Healing Fates
Authors: Chen Cao-Jie , Kajita Hiroki , Takaya Kento , Aramaki-Hattori Noriko , Sakai Shigeki , Asou Toru , Kishi Kazuo
Published: May 2022

Background

Fibrotic scars are common in both human and mouse skin wounds. However, wound-induced hair neogenesis in the murine wounding models often results in regenerative repair response. Herein, we aimed to uncover cellular functional heterogeneity in dermis between fibrotic and regenerative wound healing fates.

Methods

The expression matrix of single-cell RNA sequencing (scRNA-seq) data of fibrotic and regenerative wound dermal cells was filtered, normalized, and scaled; underwent principal components analysis; and further analyzed by Uniform Manifold Approximation and Projection (UMAP) for dimension reduction with the Seurat package. Cell types were annotated, and cell–cell communications were analyzed. The core cell population myofibroblast was identified and the biological functions of ligand and receptor genes between myofibroblast and macrophage were evaluated. Specific genes between fibrotic and regenerative myofibroblast and macrophage were identified. Temporal dynamics of myofibroblast and macrophage were reconstructed with the Monocle tool.

Results

Across dermal cells, there were six cell types, namely, EN1-negative myofibroblasts, EN1-positive myofibroblasts, hematopoietic cells, macrophages, pericytes, and endothelial cells. Ligand and receptor genes between myofibroblasts and macrophages mainly modulated cell proliferation and migration, tube development, and the TGF-β pathway. Specific genes that were differentially expressed in fibrotic compared to regenerative myofibroblasts or macrophages were separately identified. Specific genes between fibrotic and regenerative myofibroblasts were involved in the mRNA metabolic process and organelle organization. Specific genes between fibrotic and regenerative macrophages participated in regulating immunity and phagocytosis. We then observed the underlying evolution of myofibroblasts or macrophages.

Conclusion

Collectively, our findings reveal that myofibroblasts and macrophages may alter the skin wound healing fate through modulating critical signaling pathways.
Tofacitinib Downregulates TNF and Poly(I:C)-Dependent MHC-II Expression in the Colonic Epithelium
Authors: Gopalakrishnan Shreya , Hansen Marianne Doré , Skovdahl Helene Kolstad , Roseth Ingrid Aass , van Beelen Granlund Atle , Østvik Ann Elisabet , Bakke Ingunn , Sandvik Arne Kristian , Bruland Torunn
Published: May 2022

Major Histocompatibility Complex (MHC)-I and -II genes are upregulated in intestinal epithelial cells (IECs) during active inflammatory bowel diseases (IBD), but little is known about how IBD-relevant pro-inflammatory signals and IBD drugs can regulate their expression. We have previously shown that the synthetic analog of double-stranded RNA (dsRNA) Polyinosinic:polycytidylic acid (Poly(I:C)), induces interferon stimulated genes (ISGs) in colon organoids (colonoids). These ISGs may be involved in the induction of antigen presentation. In the present study, we applied colonoids derived from non-IBD controls and ulcerative colitis patients to identify induction and effects of IBD-drugs on antigen presentation in IECs in the context of Tumor Necrosis Factor (TNF)-driven inflammation. By RNA sequencing, we show that a combination of TNF and Poly(I:C) strongly induced antigen-presentation gene signatures in colonoids, including expression of MHC-II genes. MHC-I and -II protein expression was confirmed by immunoblotting and immunofluorescence. TNF+Poly(I:C)-dependent upregulation of MHC-II expression was associated with increased expression of Janus KinasesJAK1/2as well as increased activation of transcription factor Signal transducer and activator of transcription 1 (STAT1). Accordingly, pre-treatment of colonoids with IBD-approved pan-Janus Kinase (JAK) inhibitor Tofacitinib led to the downregulation of TNF+Poly(I:C)-dependent MHC-II expression associated with the abrogation of STAT1 activation. Pre-treatment with corticosteroid Budesonide, commonly used in IBD, did not alter MHC-II expression. Collectively, our results identify a regulatory role for IBD-relevant pro-inflammatory signals on MHC-II expression that is influenced by Tofacitinib.
Long-Lived Immunity in SARS-CoV-2-Recovered Children and Its Neutralizing Capacity Against Omicron
Authors: Sieber Justyna , Mayer Margareta , Schmidthaler Klara , Kopanja Sonja , Camp Jeremy V. , Popovitsch Amelie , Dwivedi Varsha , Hoz Jakub , Schoof Anja , Weseslindtner Lukas , Szépfalusi Zsolt , Stiasny Karin , Aberle Judith H.
Published: May 2022

SARS-CoV-2 infection is effectively controlled by humoral and cellular immune responses. However, the durability of immunity in children as well as the ability to neutralize variants of concern are unclear. Here, we assessed T cell and antibody responses in a longitudinal cohort of children after asymptomatic or mild COVID-19 over a 12-month period. Antigen-specific CD4 T cells remained stable over time, while CD8 T cells declined. SARS-CoV-2 infection induced long-lived neutralizing antibodies against ancestral SARS-CoV-2 (D614G isolate), but with poor cross-neutralization of omicron. Importantly, recall responses to vaccination in children with pre-existing immunity yielded neutralizing antibody activities against D614G and omicron BA.1 and BA.2 variants that were 3.9-fold, 9.9-fold and 14-fold higher than primary vaccine responses in seronegative children. Together, our findings demonstrate that SARS-CoV-2 infection in children induces robust memory T cells and antibodies that persist for more than 12 months, but lack neutralizing activity against omicron. Vaccination of pre-immune children, however, substantially improves the omicron-neutralizing capacity.
Shift of Neutrophils From Blood to Bone Marrow Upon Extensive Experimental Trauma Surgery
Authors: Teuben Michel P. J. , Heeres Marjolein , Blokhuis Taco , Spijkerman Roy , Knot Eric , Vrisekoop Nienke , Pfeifer Roman , Pape Hans-Christoph , Koenderman Leo , Leenen Luke P. H.
Published: May 2022

Introduction

Extensive trauma surgery evokes an immediate cellular immune response including altered circulatory neutrophil numbers. The concurrent bone marrow (BM) response however is currently unclear. We hypothesize that these BM changes include (1) a relative reduction of the bone marrow neutrophil fraction and (2) increasing heterogeneity of the bone marrow neutrophil pool due to (3) the appearance of aged/returning neutrophils from circulation into the BM-compartment.

Materials and Methods

Eight pigs were included in a standardized extensive trauma surgery model. Blood and bone marrow samples were collected at baseline and after 3 hours of ongoing trauma surgery. Leukocyte and subtype counts and cell surface receptor expression levels were studied by flow cytometry.

Results

All animals survived the interventions. A significant drop in circulating neutrophil counts from 9.3 to 3.2x106cells/ml (P=0.001) occurred after intervention, whereas circulatory neutrophil cell surface expression of CD11b increased. The concurrent bone marrow response included an increase of the BM neutrophil fraction from 63 ± 3 to 71 ± 3 percent (P<0.05). Simultaneously, the BM neutrophil pool became increasingly mature with a relative increase of a CXCR4high-neutrophil subtype that was virtually absent at baseline.

Conclusion

The current study shows a shift in composition of the BM neutrophil pool during extensive trauma surgery that was associated with a relatively circulatory neutropenia. More specifically, under these conditions BM neutrophils were more mature than under homeostatic conditions and a CXCR4high-neutrophil subset became overrepresented possibly reflecting remigration of aged neutrophils to the BM. These findings may contribute to the development of novel interventions aimed to modify the trauma-induced immune response in the BM.
Liver Ischemia and Reperfusion Induce Periportal Expression of Necroptosis Executor pMLKL Which Is Associated With Early Allograft Dysfunction After Transplantation
Authors: Shi Shaojun , Bonaccorsi-Riani Eliano , Schurink Ivo , van den Bosch Thierry , Doukas Michael , Lila Karishma A. , Roest Henk P. , Xhema Daela , Gianello Pierre , de Jonge Jeroen , Verstegen Monique M. A. , van der Laan Luc J. W.
Published: May 2022

Background

Early allograft dysfunction (EAD) following liver transplantation (LT) remains a major threat to the survival of liver grafts and recipients. In animal models, it is shown that hepatic ischemia-reperfusion injury (IRI) triggers phosphorylation of Mixed Lineage Kinase domain-like protein (pMLKL) inducing necroptotic cell death. However, the clinical implication of pMLKL-mediated cell death in human hepatic IRI remains largely unexplored. In this study, we aimed to investigate the expression of pMLKL in human liver grafts and its association with EAD after LT.

Methods

The expression of pMLKL was determined by immunohistochemistry in liver biopsies obtained from both human and rat LT. Human liver biopsies were obtained at the end of preservation (T0) and ~1 hour after reperfusion (T1). The positivity of pMLKL was quantified electronically and compared in rat and human livers and post-LT outcomes. Multiplex immunofluorescence staining was performed to characterize the pMLKL-expressing cells.

Results

In the rat LT model, significant pMLKL expression was observed in livers after IRI as compared to livers of sham-operation animals. Similarly, the pMLKL score was highest after IRI in human liver grafts (in T1 biopsies). Both in rats and humans, the pMLKL expression is mostly observed in the portal triads. In grafts who developed EAD after LT (n=24), the pMLKL score at T1 was significantly higher as compared to non-EAD grafts (n=40). ROC curve revealed a high predictive value of pMLKL score at T1 (AUC 0.70) and the ratio of pMLKL score at T1 and T0 (pMLKL-index, AUC 0.82) for EAD. Liver grafts with a high pMLKL index (>1.64) had significantly higher levels of serum ALT, AST, and LDH 24 hours after LT compared to grafts with a low pMLKL index. Multivariate logistical regression analysis identified the pMLKL-index (Odds ratio=1.3, 95% CI 1.1-1.7) as a predictor of EAD development. Immunohistochemistry on serial sections and multiplex staining identified the periportal pMLKL-positive cells as portal fibroblasts, fibrocytes, and a minority of cholangiocytes.

Conclusion

Periportal pMLKL expression increased significantly after IRI in both rat and human LT. The histological score of pMLKL is predictive of post-transplant EAD and is associated with early liver injury after LT. Periportal non-parenchymal cells (i.e. fibroblasts) appear most susceptible to pMLKL-mediated cell death during hepatic IRI.
Clinical and Molecular Characteristics of 60 Patients With Human Immunodeficiency Virus-Negative Castleman Disease
Authors: Qian Siyu , Ding Mengjie , Hou Huting , Wang Zeyuan , Zhang Jieming , Zhang Yue , Dong Meng , Zhu Linan , Wang Guannan , Li Wencai , Zhang Xudong
Published: May 2022

Castleman disease (CD) is a rare lymphoproliferative disorder. The mechanistic target of rapamycin (mTOR) pathway is a key regulator of various cellular functions, which may be related with the potential mechanisms of CD occurrence. We retrospectively collected the clinical information of 60 CD patients diagnosed in the First Affiliated Hospital of Zhengzhou University. And FFPE biopsy specimens were collected from 31 patients (12 unicentric CD patients and 19 multicentric CD patients) to detect the mTOR pathway protein expression. We are the first to demonstrate that thrombocytopenia and hypoalbuminemia are independent poor prognostic factors for CD. Moreover, mTOR activation was higher in CD compared to reactive lymphoid hyperplasia (used as a control group). This study offers some elucidation for the management and treatment of CD patients.
Nucleoprotein of a Rice Rhabdovirus Serves as the Effector to Attenuate Hemolymph Melanization and Facilitate Viral Persistent Propagation in its Leafhopper Vector
Authors: Zhang Ruonan , Zhang Xiao-Feng , Chi Yunhua , Xu Yuanyuan , Chen Hongyan , Guo Zhongxin , Wei Taiyun
Published: May 2022

Melanization in the hemolymph of arthropods is a conserved defense strategy against infection by invading pathogens. Numerous plant viruses are persistently transmitted by insect vectors, and must overcome hemolymph melanization. Here, we determine that the plant rhabdovirus rice stripe mosaic virus (RSMV) has evolved to evade the antiviral melanization response in the hemolymph in leafhopepr vectors. After virions enter vector hemolymph cells, viral nucleoprotein N is initially synthesized and directly interacts with prophenoloxidase (PPO), a core component of the melanization pathway and this process strongly activates the expression of PPO. Furthermore, such interaction could effectively inhibit the proteolytic cleavage of the zymogen PPO to active phenoloxidase (PO), finally suppressing hemolymph melanization. The knockdown of PPO expression or treatment with the PO inhibitor also suppresses hemolymph melanization and causes viral excessive accumulation, finally causing a high insect mortality rate. Consistent with this function, microinjection of N into leafhopper vectors attenuates melanization and promotes viral infection. These findings demonstrate that RSMV N serves as the effector to attenuate hemolymph melanization and facilitate viral persistent propagation in its insect vector. Our findings provide the insights in the understanding of ongoing arms race of insect immunity defense and viral counter-defense.
Blue Whale Body Condition Assessed Over a 14-Year Period in the NE Pacific: Annual Variation and Connection to Measures of Ocean Productivity
Authors: Wachtendonk Rachel , Calambokidis John , Flynn Kiirsten
Published: May 2022

Large marine mammals can serve as an indicator of the overall state of the environment due to their apex position in marine food webs and their functions as sentinels of change. Reductions in prey, driven by changes in environmental conditions can manifest in reduced fat stores that are visible on whales. We developed a non-invasive technique using photographs of blue whales taken on the US west coast from 2005-2018 (n=3,660) and scored body condition based on visible undulations from the vertebral processes and body shape. We analyzed patterns in the body condition of whales across years and their relation to oceanographic conditions. Females with calves had significantly poorer body conditions and calves had significantly better body conditions compared to other adult whales (Chi-Square, x2 = 170.36, df=6, p<2.2e-16). Year was a significant factor in body condition (Chi-Square, x2 = 417.73, df=39, p<0.001). The highest proportion of whales in poor body condition was observed for 2015 (one of the only two years along with 2017 where >50% had poor body condition) coincides with the marine heat wave that affected the NE Pacific 2014-2016. A cumulative mixed model examining the relationship between body condition and environmental variables revealed that negative Pacific Decadal Oscillation and longer upwelling seasons correlated with better blue whale body condition, likely to be due to higher primary productivity and prey availability. This study indicates that with an adequate scoring method, photographs collected during boat based surveys can be used to effectively evaluate whale health in response to a changing ocean.
Melting Rate Determination of Mold Powders: Continuous Casting Process Versus Laboratory Conditions
Authors: Kölbl Nathalie
Published: May 2022

In the continuous casting of steel, the melting behavior of mold powders influences the slag pool thickness and slab quality. Various methods have been implemented in laboratories to investigate this property, and in particular, melting rates are of interest. This study aimed to assess the existing methods with respect to their ability to determine melting rates under service-related conditions and to develop criteria for this purpose. These methods are divided into two groups, one of which can provide the necessary heat-transfer coefficient owing to the application of a preheated furnace or steel bath. The second condition is a sufficiently low mold powder layer thickness to allow for the desired mean heating rate. For the case study, the required heating rate is determined, and the maximum limit for this layer thickness is calculated from the conditions for Fourier and Biot numbers of varying test setups. Suitable test arrangements are also identified.
Integration and Encapsulation of Light-Emitting Diode and CMOS-MEMS Chips for Fluorescence Quenching Gas Sensor
Authors: Lee Ya-Chu , Liou Cheng-Shiun , Chien Tung-Lin , Tsou Chingfu , Fang Weileun
Published: May 2022

Environmental sensing units such as gas sensors, humidity sensors, pressure sensors, PM 2.5 sensors, or temperature sensors are widely used in our daily lives. In this study, CMOS-MEMS technology is exploited to fabricate and monolithically integrate the photo-sensors, temperature sensor, and mechanical structures for an optical gas sensing chip. An LED is bonded (heterogeneous integration) on the CMOS-MEMS chip as an excitation light source, and fluorescence quenching technology is employed for the presented optical gas sensor. Finally, the light emitted from the LED is reflected and redirected onto the CMOS-MEMS chip by using an encapsulated optical reflector to increase the sensitivity and reduce the power consumption for the presented sensor. In applications, the sensing materials are, respectively, mixed with C30H24Cl2N6Ru·6H2O and C16H7Na3O10S3 for O2 and CO2 detection. Moreover, the Si-based (by micromachining) and polymer-based (by 3D printing) optical reflectors are used to encapsulate the sensing chip to demonstrate the presented concept. Measurements show that the LED driving currents for gas sensors with reflectors are significantly reduced. Measurements also indicate that the sensitivities of gas sensors for sensing chips without optical reflectors are, respectively, 0.023 μA/% (O2/N2) and 0.12 μA/% (CO2/N2); for sensing chips with hemispherical shell optical reflectors are, respectively, 0.12 μA/% (O2/N2) and 0.19 μA/% (CO2/N2); and for sensing chips with flat plate optical reflectors are, respectively, 0.24 μA/% (O2/N2) and 0.32 μA/% (CO2/N2). The sensitivity of the temperature sensor is 0.07%/°C.
Protection Against Post-resuscitation Acute Kidney Injury by N-Acetylcysteine via Activation of the Nrf2/HO-1 Pathway
Authors: Wang Shiwei , Liu Guoxiang , Jia Tianyuan , Wang Changsheng , Lu Xiaoye , Tian Lei , Yang Qian , Zhu Changqing
Published: May 2022

Background and Objective

Acute kidney injury (AKI), the common complication after cardiopulmonary resuscitation (CPR), seriously affects the prognosis of cardiac arrest (CA) patients. However, there are limited studies on post-resuscitation AKI. In addition, it has been demonstrated that N-acetylcysteine (N-AC) as an ROS scavenger, has multiorgan-protective effects on systemic and regional ischaemia-reperfusion injuries. However, no studies have reported its protective effects against post-resuscitation AKI and potential mechanisms. This study aimed to clarify the protective effects of N-AC on post-resuscitation AKI and investigate whether its potential mechanism was mediated by activating Nrf-2/HO-1 pathway in the kidney.

Methods

We established cardiac arrest models in rats. All animals were divided into four groups: the sham, control, N-AC, and ZnPP groups. Animals in each group except for the ZnPP group were assigned into two subgroups based on the survival time: 6 and 48 h. The rats in the control, N-AC, and ZnPP groups underwent induction of ventricular fibrillation (VF), 8 min untreated VF and cardiopulmonary resuscitation. Renal function indicators, were detected using commercial kits. Renal pathologic changes were assessed by haematoxylin–eosin (HE) staining. Oxidative stress and inflammatory responses were measured using the corresponding indicators. Apoptosis was evaluated using terminal uridine nick-end labeling (TUNEL) staining, and expression of proteins associated with apoptosis and the Nrf-2/HO-1 pathway was measured by western blotting.

Results

N-AC inhibited post-resuscitation AKI. We observed that N-AC reduced the levels of biomarkers of renal function derangement; improved renal pathological changes; and suppressed apoptosis, oxidative stress, and inflammatory response. Additionally, the production of ROS in the kidneys markedly decreased by N-AC. More importantly, compared with the control group, N-AC further upregulated the expression of nuclear Nrf2 and endogenous HO-1 in N-AC group. However, N-AC-determined protective effects on post-resuscitation AKI were markedly reversed after pretreatment of the HO-1 inhibitor zinc protoporphyrin (ZnPP).

Conclusions

N-AC alleviated renal dysfunction and prolonged survival in animal models of CA. N-AC partially exerts beneficial renal protection via activation of the Nrf-2/HO-1 pathway. Altogether, all these findings indicated that N-AC as a common clinical agent, may have the potentially clinical utility to improve patients the outcomes in cardiac arrest.
Time-Controlled Adaptive Ventilation Does Not Induce Hemodynamic Impairment in a Swine ARDS Model
Authors: Lescroart Mickael , Pequignot Benjamin , Bitker Laurent , Pina Héloïse , Tran N'Guyen , Hébert Jean-Louis , Richard Jean-Christophe , Lévy Bruno , Koszutski Matthieu
Published: May 2022

Background

The current standard of care during severe acute respiratory distress syndrome (ARDS) is based on low tidal volume (VT) ventilation, at 6 mL/kg of predicted body weight. The time-controlled adaptive ventilation (TCAV) is an alternative strategy, based on specific settings of the airway pressure release ventilation (APRV) mode. Briefly, TCAV reduces lung injury, including: (1) an improvement in alveolar recruitment and homogeneity; (2) reduction in alveolar and alveolar duct micro-strain and stress-risers. TCAV can result in higher intra-thoracic pressures and thus impair hemodynamics resulting from heart-lung interactions. The objective of our study was to compare hemodynamics between TCAV and conventional protective ventilation in a porcine ARDS model.

Methods

In 10 pigs (63–73 kg), lung injury was induced by repeated bronchial saline lavages followed by 2 h of injurious ventilation. The animals were then randomized into two groups: (1) Conventional protective ventilation with a VT of 6 mL/kg and PEEP adjusted to a plateau pressure set between 28 and 30 cmH2O; (2) TCAV group with P-high set between 27 and 29 cmH2O, P-low at 0 cmH2O, T-low adjusted to terminate at 75% of the expiratory flow peak, and T-high at 3–4 s, with I:E > 6:1.

Results

Both lung elastance and PaO2:FiO2 were consistent with severe ARDS after 2 h of injurious mechanical ventilation. There was no significant difference in systemic arterial blood pressure, pulmonary blood pressure or cardiac output between Conventional protective ventilation and TCAV. Levels of total PEEP were significantly higher in the TCAV group (p < 0.05). Driving pressure and lung elastance were significantly lower in the TCAV group (p < 0.05).

Conclusion

No hemodynamic adverse events were observed in the TCAV group compared as to the standard protective ventilation group in this swine ARDS model, and TCAV appeared to be beneficial to the respiratory system.
Immune-Mediated Thrombotic Thrombocytopenic Purpura Following mRNA-Based COVID-19 Vaccine BNT162b2: Case Report and Mini-Review of the Literature
Authors: Buetler Vanessa Alexandra , Agbariah Nada , Schild Deborah Pia , Liechti Fabian D. , Wieland Anna , Andina Nicola , Hammann Felix , Kremer Hovinga Johanna A.
Published: May 2022

Introduction

An increasing number of case reports have associated vaccinations against coronavirus disease 2019 (COVID-19) with immune-mediated thrombotic thrombocytopenic purpura (iTTP), a very rare but potentially life-threatening thrombotic microangiopathy, which leads to ischemic organ dysfunction. Thrombus formation in iTTP is related to a severe deficiency of the specific von Willebrand-factor-cleaving protease ADAMTS13 due to ADAMTS13 autoantibodies.

Methods

We present a case of iTTP following exposure to the mRNA-based COVID-19 vaccine BNT162b2 (Comirnaty®, Pfizer-BioNTech). In addition, we review previously reported cases in the literature and assess current evidence.

Results

Apart from our case, twenty cases of iTTP occurring after COVID-19 vaccination had been published until the end of November 2021. There were 11 male and 10 female cases; their median age at diagnosis was 50 years (range 14–84 years). Five patients (24%) had a preexisting history of iTTP. Recombinant adenoviral vector-based vaccines were involved in 19%, mRNA-based vaccines in 81%. The median onset of symptoms after vaccination was 12 days (range 5–37), with 20 cases presenting within 30 days. Treatment included therapeutic plasma exchange in all patients. Additional rituximab, caplacizumab, or both these treatments were given in 43% (9/21), 14% (3/21), and 24% (5/21) of cases, respectively. One patient died, despite a prolonged clinical course in one patient, all surviving patients were in clinical remission at the end of the observational period.

Conclusion

Clinical features of iTTP following COVID-19 vaccination were in line with those of pre-pandemic iTTP. When timely initiated, an excellent response to standard treatment was seen in all cases. ADAMTS13 activity should be determined pre-vaccination in patients with a history of a previous iTTP episode. None of the reported cases met the WHO criteria for assessing an adverse event following immunization (AEFI) as a consistent causal association to immunization. Further surveillance of safety data and additional case-based assessment are needed.
Potential Use of Microbial Community Genomes in Various Dimensions of Agriculture Productivity and Its Management: A Review
Authors: Iquebal Mir Asif , Jagannadham Jaisri , Jaiswal Sarika , Prabha Ratna , Rai Anil , Kumar Dinesh
Published: May 2022

Agricultural productivity is highly influenced by its associated microbial community. With advancements in omics technology, metagenomics is known to play a vital role in microbial world studies by unlocking the uncultured microbial populations present in the environment. Metagenomics is a diagnostic tool to target unique signature loci of plant and animal pathogens as well as beneficial microorganisms from samples. Here, we reviewed various aspects of metagenomics from experimental methods to techniques used for sequencing, as well as diversified computational resources, including databases and software tools. Exhaustive focus and study are conducted on the application of metagenomics in agriculture, deciphering various areas, including pathogen and plant disease identification, disease resistance breeding, plant pest control, weed management, abiotic stress management, post-harvest management, discoveries in agriculture, source of novel molecules/compounds, biosurfactants and natural product, identification of biosynthetic molecules, use in genetically modified crops, and antibiotic-resistant genes. Metagenomics-wide association studies study in agriculture on crop productivity rates, intercropping analysis, and agronomic field is analyzed. This article is the first of its comprehensive study and prospects from an agriculture perspective, focusing on a wider range of applications of metagenomics and its association studies.