bluuebunny/crossref_metadata_2025 huggingface dataset:
Thrombospondin-4 Is a Soluble Dermal Inflammatory Signal That Selectively Promotes Fibroblast Migration and Keratinocyte Proliferation for Skin Regeneration and Wound Healing
Authors: Klaas Mariliis , Mäemets-Allas Kristina , Heinmäe Elizabeth , Lagus Heli , Cárdenas-León Claudia Griselda , Arak Terje , Eller Mart , Kingo Külli , Kankuri Esko , Jaks Viljar
Published: September 2021

Thrombospondin-4 (THBS4) is a non-structural extracellular matrix molecule associated with tissue regeneration and a variety of pathological processes characterized by increased cell proliferation and migration. However, the mechanisms of how THBS4 regulates cell behavior as well as the pathways contributing to its effects have remained largely unexplored. In the present study we investigated the role of THBS4 in skin regeneration both in vitro and in vivo. We found that THBS4 expression was upregulated in the dermal compartment of healing skin wounds in humans as well as in mice. Application of recombinant THBS4 protein promoted cutaneous wound healing in mice and selectively stimulated migration of primary fibroblasts as well as proliferation of keratinocytes in vitro. By using a combined proteotranscriptomic pathway analysis approach we discovered that β-catenin acted as a hub for THBS4-dependent cell signaling and likely plays a key role in promoting its downstream effects. Our results suggest that THBS4 is an important contributor to wound healing and its incorporation into novel wound healing therapies may be a promising strategy for treatment of cutaneous wounds.
Diacetyl and Other Ketones in e-Cigarette Aerosols: Some Important Sources and Contributing Factors
Authors: McAdam Kevin , Waters Gareth , Moldoveanu Serban , Margham Jennifer , Cunningham Anthony , Vas Carl , Porter Andrew , Digard Helena
Published: September 2021

Background: Concerns over the presence of the diketones 2,4 butanedione (DA) and 2,3 pentanedione (AP) in e-cigarettes arise from their potential to cause respiratory diseases. Their presence in e-liquids is a primary source, but they may potentially be generated by glycerol (VG) and propylene glycol (PG) when heated to produce aerosols. Factors leading to the presence of AP, DA and acetoin (AC) in e-cigarette aerosols were investigated. We quantified direct transfer from e-liquids, examined thermal degradation of major e-liquid constituents VG, PG and 1,3 propanediol (1,3 PD) and the potential for AC, AP and DA production from sugars and flavor additives when heated in e-cigarettes.

Method: Transfers of AC, AP and DA from e-liquids to e-cigarette aerosols were quantified by comparing aerosol concentrations to e-liquid concentrations. Thermal generation from VG, PG or 1,3 PD e-liquids was investigated by measuring AC, AP and DA emissions as a function of temperature in an e-cigarette. Thermal generation of AC, AP and DA from sugars was examined by aerosolising e-liquids containing sucrose, fructose or glucose in an e-cigarette. Pyrolytic formation of AP and DA from a range of common flavors was assessed using flash pyrolysis techniques.

Results: AC transfer efficiency was >90%, while AP and DA were transferred less efficiently (65%) indicating losses during aerosolisation. Quantifiable levels of DA were generated from VG and PG, and to a lesser extent 1,3 PD at coil temperatures >300°C. Above 350°C AP was generated from VG and 1,3 PD but not PG. AC was not generated from major constituents, although low levels were generated by thermal reduction of DA. Aerosols from e-liquids containing sucrose contained quantifiable (>6 ng/puff) levels of DA at all sucrose concentrations tested, with DA emissions increasing with increasing device power and concentration. 1% glucose, fructose or sucrose e-liquids gave comparable DA emissions. Furanose ring compounds also generate DA and AP when heated to 250°C.

Conclusions: In addition to less than quantitative direct transfer from the e-liquid, DA and AP can be present in the e-cigarette aerosol due to thermal decomposition reactions of glycols, sugars and furanonse ring flavors under e-cigarette operating conditions.
Intriguing Heteroleptic ZnII bis(dipyrrinato) Emitters in the Far-Red Region With Large Pseudo-Stokes Shift for Bioimaging
Authors: Tabone Roberta , Feser Dominik , Lemma Enrico D. , Schepers Ute , Bizzarri Claudia
Published: September 2021

Novel heteroleptic ZnII bis(dipyrrinato) complexes were prepared as intriguing emitters. With our tailor-made design, we achieved far-red emissive complexes with a photoluminescence quantum yield up to 45% in dimethylsulfoxide and 70% in toluene. This means that heteroleptic ZnII bis(dipyrrinato) complexes retain very intense emission also in polar solvents, in contrast to their homoleptic counterparts, which we prepared for comparing the photophysical properties. It is evident from the absorption and excitation spectra that heteroleptic complexes present the characteristic features of both ligands: the plain dipyrrin (Lp) and the π-extended dipyrrin (Lπ). On the contrary, the emission comes exclusively from the π-extended dipyrrin Lπ, suggesting an interligand nonradiative transition that causes a large pseudo-Stokes shift (up to 4,600 cm−1). The large pseudo-Stokes shifts and the emissive spectral region of these novel heteroleptic ZnII bis(dipyrrinato) complexes are of great interest for bioimaging applications. Thus, their high biocompatibiliy with four different cell lines make them appealing as new fluorophores for cell imaging.
Complete Chloroplast Genome Variants Reveal Discrete Long-Distance Dispersal Routes of Rhizophora in the Western Indian Ocean
Authors: Triest Ludwig , Sierens Tim , Van der Stocken Tom
Published: September 2021

Historical processes of long-distance migration and ocean-wide expansion feature the global biogeographic pattern ofRhizophoraspecies. Throughout the Indian Ocean,Rhizophora stylosaandRhizophora mucronataseem to be a young phylogenetic group with an expansion ofR. mucronatatoward the Western Indian Ocean (WIO) driven by the South Equatorial Current (SEC). Nuclear microsatellites revealed genetic patterns and breaks; however, the estimation of propagule dispersal routes requires maternally inherited cytoplasmic markers. Here, we examine the phylogeography of 21R. mucronataprovenances across a >4,200 km coastal stretch in the WIO usingR. stylosaas an outgroup. Full-length chloroplast genome (164,474 bp) and nuclear ribosomal RNA cistron (8,033 bp) sequences were assembled. The boundaries, junction point, sequence orientation, and stretch between LSC/IRb/SSC/IRa/LSC showed no differences withR. stylosachloroplast genome. A total of 58 mutations inR. mucronataencompassing transitions/transversions, insertions-deletions, and mononucleotide repeats revealed three major haplogroups. Haplonetwork, Bayesian maximum likelihood (ML), and approximate Bayesian computation (ABC) analyses supported discrete historical migration events. An ancient haplogroup A in the Seychelles and eastern Madagascar was as different from other haplogroups as fromR. stylosa. A star-like haplonetwork referred as the recent range expansion of haplogroup B from northern Madagascar toward the African mainland coastline, including a single variant spanning >1,800 km across the Mozambique Channel area (MCA). Populations in the south of Delagoa Bight contained haplogroup C and was originated from a unique bottleneck dispersal event. Divergence estimates of pre- and post-Last Glacial Maximum (LGM) illustrated the recent emergence ofRhizophoramangroves in the WIO compared to other oceans. Connectivity patterns could be aligned with the directionality of major ocean currents. Madagascar and the Seychelles each harbored haplogroups A and B, albeit among spatially separated populations, explained from a different migration era. Likewise, the Aldabra Atoll harbored spatially distinct haplotypes. Nuclear ribosomal cistron (8,033 bp) variants corresponded to haplogroups and confirmed admixtures in the Seychelles and Aldabra. These findings shed new light on the origins and dispersal routes ofR. mucronatalineages that have shaped their contemporary populations in large regions of the WIO, which may be the important information for defining marine conservation units both at ocean scale and at the level of small islands.
Left Atrial Spontaneous Echo Contrast and Ischemic Stroke in Patients Undergoing Percutaneous Left Atrial Appendage Closure
Authors: Wang Binhao , Wang Zhao , Fu Guohua , He Bin , Wang Hangxuan , Zhuo Weidong , Zhang Shengmin , Chu Huimin
Published: September 2021

Objectives: Spontaneous echo contrast (SEC) in the left atrium (LA) is frequently observed in atrial fibrillation (AF) patients and may lead to thromboembolic events. We aimed to investigate both periprocedural and long-term stroke risks associated with LA SEC in AF patients undergoing percutaneous left atrial appendage closure (LAAC).

Methods: A total of 408 consecutive AF patients treated with LAAC between March 2015 and February 2019 were divided into two groups based on preprocedural transesophageal echocardiography: the study group (moderate/severe LA SEC; n = 41) and the control group (none, mild, or mild to moderate LA SEC; n = 367). To attenuate the observed imbalance in baseline covariates, a propensity score matching technique was used.

Results: No periprocedural stroke/transient ischemic attack (TIA) was documented. The incidence of device-related thrombus was higher in the study group than in the control group (8.8 vs. 1.3%; P = 0.025). The mean follow-up period was 3.2 ± 1.1 years, during which 8 patients (2.2%) in the control group and 4 (9.8%) in the study group experienced stroke/TIA (P = 0.024). Moderate/severe LA SEC was identified as an independent predictor of stroke/TIA in both the original population (HR = 5.71, 95% CI 1.47–22.19, P = 0.012) and the matched population (HR = 9.79, 95% CI 1.44–66.86, P = 0.020).

Conclusions: LA SEC did not show a relationship with periprocedural stroke events in patients undergoing percutaneous LAAC. However, moderate/severe LA SEC increased the incidence of device-related thrombus and the risk of late stroke/TIA.
Design of Control Strategy and Effect Evaluation for Primary Frequency Regulation of Wind Storage System
Authors: Li Cuiping , Zhang Zheshen , Li Junhui , Ma Yunbao , Zou Jiajun
Published: September 2021

Because of wind sources’ volatility and intermittent news, wind power has made a more and more heavy burden on the power system. This paper analyzes in detail the traditional control method, parallel control strategy and serial control strategy of the wind storage system, and combines the advantages of the two to propose an optimal control strategy. A comprehensive performance evaluation method for the primary frequency regulation of the ESS participating in the power grid is proposed based on the power system operation requirements. In the example, the frequency modulation performance of the optimal control strategy is verified by the evaluation method described in this paper in the Chinese frequency adjustment market.
Prioritizing Street Tree Planting Locations to Increase Benefits for All Citizens: Experience From Joliette, Canada
Authors: Sousa-Silva Rita , Cameron Elyssa , Paquette Alain
Published: September 2021

As the climate continues to warm and the world becomes more urbanized, our reliance on trees and the benefits they provide is rapidly increasing. Many cities worldwide are planting trees to offset rising temperatures, trap pollutants, and enhance environmental and human health and well-being. To maximize the benefits of planting trees and avoid further increasing social inequities, a city needs to prioritize where to establish trees by first identifying those areas of greatest need. This work aims to demonstrate a spatially explicit approach for cities to determine these priority locations to achieve the greatest returns on specific benefits. Criteria for prioritization were developed in tandem with the City of Joliette, Canada, and based on nine indicators: surface temperature, tree density, vegetation cover, resilience, tree size and age, presence of species at risk, land use type, socioeconomic deprivation, and potential for active transportation. The City’s preferences were taken into account when assigning different weights to each indicator. The resulting tree planting priority maps can be used to target street tree plantings to locations where trees are needed most. This approach can be readily applied to other cities as these criteria can be adjusted to accommodate specific tree canopy goals and planning constraints. As cities are looking to expand tree canopy, we hope this work will assist in sustaining and growing their urban forest, enabling it to be more resilient and to keep providing multiple and sustained benefits where they are needed the most.
Teasing Apart Impacts of Human Activity and Regional Drought on Madagascar’s Large Vertebrate Fauna: Insights From New Excavations at Tsimanampesotse and Antsirafaly
Authors: Godfrey Laurie R. , Crowley Brooke E. , Muldoon Kathleen M. , Burns Stephen J. , Scroxton Nick , Klukkert Zachary S. , Ranivoharimanana Lovasoa , Alumbaugh Jamie , Borths Matthew , Dart Ryan , Faina Peterson , Goodman Steven M. , Gutierrez Isaac J. , Hansford James P. , Hekkala Evon R. , Kinsley Christopher W. , Lehman Phillip , Lewis Margaret E. , McGee David , Pérez Ventura R. , Rahantaharivao Noromamy J. , Rakotoarijaona Mamy , Rasolonjatovo Harimanjaka A. M. , Samonds Karen E. , Turvey Samuel T. , Vasey Natalie , Widmann Patrick
Published: September 2021

Madagascar experienced a major faunal turnover near the end of the first millenium CE that particularly affected terrestrial, large-bodied vertebrate species. Teasing apart the relative impacts of people and climate on this event requires a focus on regional records with good chronological control. These records may document coeval changes in rainfall, faunal composition, and human activities. Here we present new paleontological and paleoclimatological data from southwestern Madagascar, the driest part of the island today. We collected over 1500 subfossil bones from deposits at a coastal site called Antsirafaly and from both flooded and dry cave deposits at Tsimanampesotse National Park. We built a chronology of Late Holocene changes in faunal assemblages based on 65 radiocarbon-dated specimens and subfossil associations. We collected stalagmites primarily within Tsimanampesotse but also at two additional locations in southern Madagascar. These provided information regarding hydroclimate variability over the past 120,000 years. Prior research has supported a primary role for drought (rather than humans) in triggering faunal turnover at Tsimanampesotse. This is based on evidence of: (1) a large freshwater ecosystem west of what is now the hypersaline Lake Tsimanampesotse, which supported freshwater mollusks and waterfowl (including animals that could not survive on resources offered by the hypersaline lake today); (2) abundant now-extinct terrestrial vertebrates; (3) regional decline or disappearance of certain tree species; and (4) scant local human presence. Our new data allow us to document the hydroclimate of the subarid southwest during the Holocene, as well as shifts in faunal composition (including local extirpations, large-vertebrate population collapse, and the appearance of introduced species). These records affirm that climate alone cannot have produced the observed vertebrate turnover in the southwest. Human activity, including the introduction of cattle, as well as associated changes in habitat exploitation, also played an important role.
A Tiered Genetic Screening Strategy for the Molecular Diagnosis of Intellectual Disability in Chinese Patients
Authors: Dai Limeng , Zhang Danyan , Wu Zhifeng , Guan Xingying , Ma Mingfu , Li Lianbing , Zhang Yuping , Bai Yun , Guo Hong
Published: September 2021

Objective: Intellectual disability (ID) is one of the most common developmental disabilities. To identify the genetic etiology of IDs in Chongqing, we conducted a multistage study in Chinese Han patients.

Methods: We collected the clinical and etiological data of 1665 ID patients, including 1,604 from the disabled children evaluation center and 61 from the pediatric rehabilitation unit. Routine genetic screening results were obtained, including karyotype and candidate gene analysis. Then 105 idiopathic cases with syndromic and severe ID/developmental delay (DD) were selected and tested by chromosomal microarray (CMA) and whole exome sequencing (WES) sequentially. The pathogenicity of the CNVs and SNVs were evaluated according to ACMG guidelines.

Results: Molecular diagnosis was made by routine genetic screening in 216 patients, including 196 chromosomal syndromes. Among the 105 idiopathic patients, 49 patients with pathogenic/likely pathogenic CNVs and 21 patients with VUS were identified by CMA. Twenty-six pathogenic CNVs underlying well-known syndromic cases, such as Williams-Beuren syndrome, were confirmed by multiplex ligation-dependent probe amplification (MLPA). Nine novel mutations were identified by WES in thirty-fix CNV-negative ID cases.

Conclusions: The study illustrated the genetic aberrations distribution of a large ID cohort in Chongqing. Compared with conventional or single methods, a tiered high-throughput diagnostic strategy was developed to greatly improve the diagnostic yields and extend the variation spectrum for idiopathic syndromic ID cases.
Promising Epigenetic Biomarkers Associated With Cancer-Associated-Fibroblasts for Progression of Kidney Renal Clear Cell Carcinoma
Authors: You Yongke , Ren Yeping , Liu Jikui , Qu Jianhua
Published: September 2021

Kidney renal clear cell carcinoma (KIRC) is the most common malignant kidney tumor as its characterization of highly metastatic potential. Patients with KIRC are associated with poor clinical outcomes with limited treatment options. Up to date, the underlying molecular mechanisms of KIRC pathogenesis and progression are still poorly understood. Instead, particular features of Cancer-Associated Fibroblasts (CAFs) are highly associated with adverse outcomes of patients with KIRC, while the precise regulatory mechanisms at the epigenetic level of KIRC in governing CAFs remain poorly defined. Therefore, explore the correlations between epigenetic regulation and CAFs infiltration may help us better understand the molecular mechanisms behind KIRC progression, which may improve clinical outcomes and patients quality of life. In the present study, we identified a set of clinically relevant CAFs-related methylation-driven genes, NAT8, TINAG, and SLC17A1 in KIRC. Our comprehensive in silico analysis revealed that the expression levels of NAT8, TINAG, and SLC17A1 are highly associated with outcomes of patients with KIRC. Meanwhile, their methylation levels are highly correlates with the severity of KIRC. We suggest that the biomarkers might contribute to CAFs infiltration in KIRC. Taken together, our study provides a set of promising biomarkers which could predict the progression and prognosis of KIRC. Our findings could have potential prognosis and therapeutic significance in the progression of KIRC.
Case Report: A Deletion Variant in the DCAF17 Gene Underlying Woodhouse-Sakati Syndrome in a Chinese Consanguineous Family
Authors: Chen Guangmin , Zhou Ling , Chen Qimou , Wang Juan , Jiang Peng , Shen Rufei , Long Min , Zhou Houdi
Published: September 2021

Woodhouse-Sakati syndrome (WSS, MIM 241080) is a rare neuroendocrine disease characterized by hair loss, hypogonadism, diabetes, hearing loss, and extrapyramidal syndrome, and is usually caused by mutations in the DCAF17 gene as an inherited disease. DCAF17 plays an important role in mammalian gonadal development and infertility. So far, there have been no WSS reports in China. The patient introduced in this case is from a consanguineous family. The main symptoms of the patient were alopecia and gonadal agenesis. Other symptoms such as hearing loss, intellectual disability, and hyperglycemia were remarkable, and these symptoms are often observed in WSS patients. We found a nonsense mutation in the 11th exon of the gene DCAF17 (Refseq: NM_025000) in the patient and her younger brother, which confirmed the diagnosis of WSS. The genetic results also showed that the mutation was inherited from their healthy first-cousin parents.
Pattern Recognition Proteins: First Line of Defense Against Coronaviruses
Authors: Labarrere Carlos A. , Kassab Ghassan S.
Published: September 2021

The rapid outbreak of COVID-19 caused by the novel coronavirus SARS-CoV-2 in Wuhan, China, has become a worldwide pandemic affecting almost 204 million people and causing more than 4.3 million deaths as of August 11 2021. This pandemic has placed a substantial burden on the global healthcare system and the global economy. Availability of novel prophylactic and therapeutic approaches are crucially needed to prevent development of severe disease leading to major complications both acutely and chronically. The success in fighting this virus results from three main achievements: (a) Direct killing of the SARS-CoV-2 virus; (b) Development of a specific vaccine, and (c) Enhancement of the host’s immune system. A fundamental necessity to win the battle against the virus involves a better understanding of the host’s innate and adaptive immune response to the virus. Although the role of the adaptive immune response is directly involved in the generation of a vaccine, the role of innate immunity on RNA viruses in general, and coronaviruses in particular, is mostly unknown. In this review, we will consider the structure of RNA viruses, mainly coronaviruses, and their capacity to affect the lungs and the cardiovascular system. We will also consider the effects of thepattern recognition protein (PRP) tridentcomposed by (a) Surfactant proteins A and D, mannose-binding lectin (MBL) and complement component 1q (C1q), (b) C-reactive protein, and (c) Innate and adaptive IgM antibodies, upon clearance of viral particles and apoptotic cells in lungs and atherosclerotic lesions. We emphasize on the role of pattern recognition protein immune therapies as a combination treatment to prevent development of severe respiratory syndrome and to reduce pulmonary and cardiovascular complications in patients with SARS-CoV-2 and summarize the need of a combined therapeutic approach that takes into account all aspects of immunity against SARS-CoV-2 virus and COVID-19 disease to allow mankind to beat this pandemic killer.
A Bumpy Ride of Mycobacterial Phagosome Maturation: Roleplay of Coronin1 Through Cofilin1 and cAMP
Authors: Saha Saradindu , Hazra Arnab , Ghatak Debika , Singh Ajay Vir , Roy Sadhana , BoseDasgupta Somdeb
Published: September 2021

Phagosome-lysosome fusion in innate immune cells like macrophages and neutrophils marshal an essential role in eliminating intracellular microorganisms. In microbe-challenged macrophages, phagosome-lysosome fusion occurs 4 to 6 h after the phagocytic uptake of the microbe. However, live pathogenic mycobacteria hinder the transfer of phagosomes to lysosomes, up to 20 h post-phagocytic uptake. This period is required to evade pro-inflammatory response and upregulate the acid-stress tolerant proteins. The exact sequence of events through which mycobacteria retards phagolysosome formation remains an enigma. The macrophage coat protein Coronin1(Cor1) is recruited and retained by mycobacteria on the phagosome membrane to retard its maturation by hindering the access of phagosome maturation factors. Mycobacteria-infected macrophages exhibit an increased cAMP level, and based on receptor stimulus, Cor1 expressing cells show a higher level of cAMP than non-Cor1 expressing cells. Here we have shown that infection of bone marrow-derived macrophages with H37Rv causes a Cor1 dependent rise of intracellular cAMP levels at the vicinity of the phagosomes. This increased cAMP fuels cytoskeletal protein Cofilin1 to depolymerize F-actin around the mycobacteria-containing phagosome. Owing to reduced F-actin levels, the movement of the phagosome toward the lysosomes is hindered, thus contributing to the retarded phagosome maturation process. Additionally, Cor1 mediated upregulation of Cofilin1 also contributes to the prevention of phagosomal acidification, which further aids in the retardation of phagosome maturation. Overall, our study provides first-hand information on Cor1 mediated retardation of phagosome maturation, which can be utilized in developing novel peptidomimetics as part of host-directed therapeutics against tuberculosis.
TLR-Agonist Mediated Enhancement of Antibody-Dependent Effector Functions as Strategy For an HIV-1 Cure
Authors: Hvilsom Caroline Thue , Søgaard Ole Schmeltz
Published: September 2021

Background

The current treatment for HIV-1 is based on blocking various stages in the viral replication cycle using combination antiretroviral therapy (ART). Even though ART effectively controls the infection, it is not curative, and patients must therefore continue treatment life-long.

Aim

Here we review recent literature investigating the single or combined effect of toll-like receptor (TLR) agonists and broadly neutralizing antibodies (bNAbs) with the objective to evaluate the evidence for this combination as a means towards an HIV-1 cure.

Results

Multiple preclinical studies found significantly enhanced killing of HIV-1 infected cells by TLR agonist-induced innate immune activation or by Fc-mediated effector functions following bNAb administration. However, monotherapy with either agent did not lead to sustained HIV-1 remission in clinical trials among individuals on long-term ART. Notably, findings in non-human primates suggest that a combination of TLR agonists and bNAbs may be able to induce long-term remission after ART cessation and this approach is currently being further investigated in clinical trials.

Conclusion

Preclinical findings show beneficial effects of either TLR agonist or bNAb administration for enhancing the elimination of HIV-1 infected cells. Further, TLR agonist-mediated stimulation of innate effector functions in combination with bNAbs may enhance antibody-dependent cellular cytotoxicity and non-human primate studies have shown promising results for this combination strategy. Factors such as immune exhaustion, proviral bNAb sensitivity and time of intervention might impact the clinical success.
Case Report: Characterizing the Role of the STXBP2-R190C Monoallelic Mutation Found in a Patient With Hemophagocytic Syndrome and Langerhans Cell Histiocytosis
Authors: Viñas-Giménez Laura , Rincón Rafael , Colobran Roger , de la Cruz Xavier , Celis Verónica Paola , Dapena José Luis , Alsina Laia , Sayós Joan , Martínez-Gallo Mónica
Published: September 2021

Hemophagocytic lymphohistiocytosis (HLH) is a life-threatening hyperinflammatory disorder. HLH can be considered as a threshold disease depending on the trigger and the residual NK-cell cytotoxicity. In this study, we analyzed the molecular and functional impact of a novel monoallelic mutation found in a patient with two episodes of HLH. A 9-month-old child was diagnosed at 2 months of age with cutaneous Langerhans cell histiocytosis (LCH). After successful treatment, the patient developed an HLH episode. At 16 month of age, the patient went through an HSCT losing the engraftment 5 months later concomitant with an HLH relapse. The genetic study revealed a monoallelic mutation in the STXBP2 gene (.pArg190Cys). We transfected COS7 cells to analyze the STXBP2-R190C expression and to test the interaction with STX11. We used the RBL-2H3 cell line expressing STXBP2-WT-EGFP or R190C-EGFP for degranulation assays. Mutation STXBP2-R190C did not affect protein expression or interaction with syntaxin-11. However, we have demonstrated that STXBP2-R190C mutation diminishes degranulation in the RBL-2H3 cell line compared with the RBL-2H3 cell line transfected with STXBP2-WT or nontransfected. These results suggest that STXBP2-R190C mutation acts as a modifier of the degranulation process producing a decrease in degranulation. Therefore, under homeostatic conditions, the presence of one copy of STXBP2-R190 could generate sufficient degranulation capacity. However, it is likely that early in life when adaptive immune system functions are not sufficiently developed, an infection may not be resolved with this genetic background, leading to a hyperinflammation syndrome and eventually develop HLH. This analysis highlights the need for functional testing of new mutations to validate their role in genetic susceptibility and to establish the best possible treatment for these patients.
Chicken DDX1 Acts as an RNA Sensor to Mediate IFN-β Signaling Pathway Activation in Antiviral Innate Immunity
Authors: Lin Zhenyu , Wang Jie , Zhu Wenxian , Yu Xiangyu , Wang Zhaofei , Ma Jingjiao , Wang Hengan , Yan Yaxian , Sun Jianhe , Cheng Yuqiang
Published: September 2021

Chickens are the natural host of Newcastle disease virus (NDV) and avian influenza virus (AIV). The discovery that the RIG-I gene, the primary RNA virus pattern recognition receptor (PRR) in mammals, is naturally absent in chickens has directed attention to studies of chicken RNA PRRs and their functions in antiviral immune responses. Here, we identified Asp-Glu-Ala-Asp (DEAD)-box helicase 1 (DDX1) as an essential RNA virus PRR in chickens and investigated its functions in anti-RNA viral infections. The chDDX1 gene was cloned, and cross-species sequence alignment and phylogenetic tree analyses revealed high conservation of DDX1 among vertebrates. A quantitative RT-PCR showed that chDDX1 mRNA are widely expressed in different tissues in healthy chickens. In addition, chDDX1 was significantly upregulated after infection with AIV, NDV, or GFP-expressing vesicular stomatitis virus (VSV-GFP). Overexpression of chDDX1 in DF-1 cells induced the expression of IFN-β, IFN-stimulated genes (ISGs), and proinflammatory cytokines; it also inhibited NDV and VSV replications. The knockdown of chDDX1 increased the viral yield of NDV and VSV and decreased the production of IFN-β, which was induced by RNA analog polyinosinic-polycytidylic acid (poly[I:C]), by AIV, and by NDV. We used a chicken IRF7 (chIRF7) knockout DF-1 cell line in a series of experiments to demonstrate that chDDX1 activates IFN signaling via the chIRF7 pathway. Finally, an in-vitro pulldown assay showed a strong and direct interaction between poly(I:C) and the chDDX1 protein, indicating that chDDX1 may act as an RNA PRR during IFN activation. In brief, our results suggest that chDDX1 is an important mediator of IFN-β and is involved in RNA- and RNA virus-mediated chDDX1-IRF7-IFN-β signaling pathways.
West Indian Manatees Use Partial Migration to Expand Their Geographic Range Into the Northern Gulf of Mexico
Authors: Cloyed Carl S. , Hieb Elizabeth E. , DaCosta Kayla , Ross Monica , Carmichael Ruth H.
Published: September 2021

Partial migration provides a mechanism for species to shift their geographic ranges into new, environmentally favorable regions but has been poorly studied as a means to alleviate effects of climate change. Populations at the edge of their geographic range are ideal to investigate how migratory behaviors may enable range expansion as adjacent areas become more climatically favorable. We determined the contribution of partial migration to the range expansion of West Indian manatees (Trichechus manatus) using GPS data from tagged individuals that migrated between the northern Gulf of Mexico (nGoM) and primary habitat in peninsular Florida. Most of these manatees migrated to the nGoM annually and exhibited high site fidelity among years. Many individuals spent cumulatively more time in the nGoM than in peninsular Florida, indicating the nGoM is a regular part of their geographic range, and they returned to peninsular Florida to meet temperature-related physiological needs for survival. Autumn migrations most frequently terminated at Crystal River, Florida, and manatees that commenced migration late in the season stopped less frequently and had more directed movements. Spring migrations most frequently terminated at Mobile Bay, Alabama, and several manatees quickly and directly migrated from Florida to nGoM stopover sites. Migrations ranged from 10 to 133 days in length, and variation in duration was primarily driven by use of stopover sites and directedness of travel. These data confirm partial migration as an important component of manatee migratory behavior that has already enabled range shifts for manatees on the U.S.A. Gulf of Mexico coast and has potential to facilitate future responses to climate change. As the most common type of migration across the animal kingdom, partial migration may provide a global mechanism for a diverse variety of species to resist the range limiting effects of climate change.
Oxygen and Nutrient Trapping in the Southern Benguela Upwelling System
Authors: Rixen Tim , Lahajnar Niko , Lamont Tarron , Koppelmann Rolf , Martin Bettina , van Beusekom Justus E. E. , Siddiqui Claire , Pillay Keshnee , Meiritz Luisa
Published: September 2021

The Benguela Upwelling System in the southeast Atlantic Ocean is of crucial socio-economic importance due to its high productivity. However, predicting its response to global change and understanding past changes are still great challenges. Here, we compile data obtained from a research cruise and an oceanographic mooring to demonstrate that a topographically steered nutrient trapping zone develops in a narrow belt along the coast during the main upwelling season in austral spring and summer in the southern Benguela Upwelling System. High nutrient concentrations within this zone increase the impact of upwelling on the productivity of the southern Benguela Upwelling System, but the efficient nutrient trapping operates at the expense of decreasing oxygen concentrations. This enhances the probability of anoxic events emerging toward the end of the upwelling season. However, at the end of the upwelling season, the front that separates the coastally trapped waters from open shelf waters weakens or even collapses due to upwelling cessation and the reversing current regime. This, in addition to a stronger vertical mixing caused by winter cooling, fosters the ventilation of the nutrient trapping zone, which reestablishes during the following upwelling season. The postulated intensification of upwelling and changes in the ecosystem structure in response to global warming seem to reduce the nutrient trapping efficiency by increasing offshore advection of surface waters and plankton blooms. The intensified upwelling and resulting lower biological oxygen consumption appears to mask the expected impacts of global warming on the oxygen minimum zone (OMZ) in the southern Benguela Upwelling System. In contrast to other OMZs, including those in northern Benguela Upwelling Systems, the OMZ in the southern Benguela Upwelling System reveals so far no detectable long-term decrease in oxygen. Thus, the nutrient trapping efficiency seems to be a critical feature mitigating global change impacts on the southern Benguela Upwelling System. Since it is topographically steered, regional impacts on the nutrient trapping efficiency appear also to explain varying responses of upwelling systems to global change as the comparison between southern and northern Benguela Upwelling System shows. This emphasizes the need for further and more comparable studies in order to better understand the response of Eastern Boundary Upwelling Systems and their ecosystem services to global change.
Impacts of Marine Heatwaves on Algal Structure and Carbon Sequestration in Conjunction With Ocean Warming and Acidification
Authors: Gao Guang , Zhao Xin , Jiang Meijia , Gao Lin
Published: September 2021

As the ocean warms, the frequency, duration, intensity, and range of marine heatwaves (MHWs) increase. MHWs are becoming a severe challenge for marine ecosystems. However, our understanding in regard to their impacts on algal structure and carbon sequestration is still deficient or fragmentary, particularly when combined with ocean warming and acidification. In this paper, we reviewed the impacts of MHWs individually and combined with ocean warming and acidification on regime shift in algal community and carbon sequestration of both macroalgae and microalgae. Solid evidence shows that MHWs cause the decline of large canopy macroalgae and increase of turf-forming macroalgae in abundance, leading to the regime shift from kelp forests to seaweed turfs. Furthermore, increased grazing pressure on kelps due to tropicalization facilitates the expansion of turfs that prevent the recovery of kelps through plundering light and space. Meanwhile, MHWs could trigger microalgal blooms and the intensity of algal blooms is regulated by the severity of MHWs and nutrient availability. MHWs could lead to the decrease of carbon burial and sequestration by canopy-forming macroalgae due to depressed growth and increased mortality. The effects of MHWs on the productivity of microalgae are latitude-dependent: negative effects at low and mid-latitudes whilst positive effects at high latitudes. Ocean warming and acidification may accelerate the shift from kelps to turfs and thus decrease the carbon sequestration by canopy-forming macroalgae further. We propose that MHWs combined with ocean warming and acidification would reduce the biodiversity and facilitate the thriving of morphologically simple, ephemeral and opportunistic turfs and diatoms in coastal oceans, and phytoplankton with smaller size in open oceans. This structure shift would not be in favor of long-term carbon sequestration. Future studies could be conducted to test this hypothesis and investigate the impacts of MHWs on carbon sequestration under future ocean conditions.
Silane-Modified Graphene Oxide Composite as a Promising Corrosion-Inhibiting Film for Magnesium Alloy AZ31
Authors: Zhang You , Wang Juping , Zhang Zheng , Wei Kai , Zhang Zhe , Hao Xuelong , Chen Fei
Published: September 2021

In this study, (3-aminopropyl)-triethoxysilane–modified graphene oxide (GO) composite thin films were synthesized on magnesium alloy AZ31 substrate. The structure, composition, and morphology of silane-GO films were analyzed. Electrochemical measurements and immersion tests showed that silane-GO coatings provide effective protection for magnesium alloy substrates, owing to the good barrier property of the layered GO, and decrease the defects on the GO film surface due to the silane modification. In addition, the corrosion product between the outer silane-GO film and Mg alloy substrate also improved the corrosion resistance of the Mg alloy. Thus, silane-GO composite thin films provide an effective approach for protecting the lightweight metal substrate.
Distribution of Ocular Anterior and Posterior Segment Lengths Among a Cataract Surgical Population in Shanghai
Authors: Qi Jiao , He Wenwen , Meng Jiaqi , Wei Ling , Qian Dongjin , Lu Yi , Zhu Xiangjia
Published: September 2021

Purpose: To investigate the distributions of the ocular anterior and posterior segment lengths among a cataract surgical population in Shanghai.

Design: Cross-sectional study.

Methods: Ocular biometric parameters of 23,462 eyes of 23,462 cataract surgery candidates were reviewed. Axial length (AL), anterior chamber depth (ACD), and lens thickness (LT) were obtained using IOL Master. Anterior segment length (ASL = ACD + LT), posterior segment length (PSL = AL – ASL) and the ratio of ASL to PSL (ASL/PSL) were calculated.

Results: The mean ASL was 7.58 ± 0.39 mm, the mean PSL was 17.12 ± 2.64 mm. As the age grew, the ASL increased, and PSL increased firstly then decreased. Male subjects tended to have significantly longer ASL and shorter PSL than female subjects. With the increasing AL, the ASL was firstly decreased to trough at 20–22 mm AL group, then increased gradually, while the PSL increased rapidly. The ASL correlated positively with AL in normal, moderate and highly myopic eyes, negatively in short eyes. The PSL correlated positively with AL across the entire study population. The ASL/PSL was not constant in the eyes with different AL but had a relatively steep downward trend with the increasing AL in the short eyes, then decreased smoothly in normal, moderate and highly myopic eyes.

Conclusions: In Chinese cataractous eyes, longer ASL and shorter PSL were associated with elder age and male gender. The change of ASL over AL was not linear, and the ASL was smallest in the eyes with AL of 20–22 mm. The elongation of the eyeball was mainly due to the extension of the posterior segment.
Deep Learning Assisted Detection of Abdominal Free Fluid in Morison's Pouch During Focused Assessment With Sonography in Trauma
Authors: Cheng Chi-Yung , Chiu I-Min , Hsu Ming-Ya , Pan Hsiu-Yung , Tsai Chih-Min , Lin Chun-Hung Richard
Published: September 2021

Background: The use of focused assessment with sonography in trauma (FAST) enables clinicians to rapidly screen for injury at the bedsides of patients. Pre-hospital FAST improves diagnostic accuracy and streamlines patient care, leading to dispositions to appropriate treatment centers. In this study, we determine the accuracy of artificial intelligence model-assisted free-fluid detection in FAST examinations, and subsequently establish an automated feedback system, which can help inexperienced sonographers improve their interpretation ability and image acquisition skills.

Methods: This is a single-center study of patients admitted to the emergency room from January 2020 to March 2021. We collected 324 patient records for the training model, 36 patient records for validation, and another 36 patient records for testing. We balanced positive and negative Morison's pouch free-fluid detection groups in a 1:1 ratio. The deep learning (DL) model Residual Networks 50-Version 2 (ResNet50-V2) was used for training and validation.

Results: The accuracy, sensitivity, and specificity of the model performance for ascites prediction were 0.961, 0.976, and 0.947, respectively, in the validation set and 0.967, 0.985, and 0.913, respectively, in the test set. Regarding feedback prediction, the model correctly classified qualified and non-qualified images with an accuracy of 0.941 in both the validation and test sets.

Conclusions: The DL algorithm in ResNet50-V2 is able to detect free fluid in Morison's pouch with high accuracy. The automated feedback and instruction system could help inexperienced sonographers improve their interpretation ability and image acquisition skills.
Hypersensitivity Pneumonitis: Diagnostic and Therapeutic Challenges
Authors: Alberti Maria Laura , Rincon-Alvarez Emily , Buendia-Roldan Ivette , Selman Moises
Published: September 2021

Hypersensitivity pneumonitis (HP) is one of the most common interstitial lung diseases (ILD), that presents unique challenges for a confident diagnosis and limited therapeutic options. The disease is triggered by exposure to a wide variety of inciting antigens in susceptible individuals which results in T-cell hyperactivation and bronchioloalveolar inflammation. However, the genetic risk and the pathogenic mechanisms remain incompletely elucidated. Revised diagnostic criteria have recently been proposed, recommending to classify the disease in fibrotic and non-fibrotic HP which has strong therapeutic and outcome consequences. Confident diagnosis depends on the presence of clinical features of ILD, identification of the antigen(s), typical images on high-resolution computed tomography (HRCT), characteristic histopathological features, and lymphocytosis in the bronchoalveolar lavage. However, identifying the source of antigen is usually challenging, and HRCT and histopathology are often heterogeneous and not typical, supporting the notion that diagnosis should include a multidisciplinary assessment. Antigen removal and treating the inflammatory process is crucial in the progression of the disease since chronic persistent inflammation seems to be one of the mechanisms leading to lung fibrotic remodeling. Fibrotic HP has a few therapeutic options but evidence of efficacy is still scanty. Deciphering the molecular pathobiology of HP will contribute to open new therapeutic avenues and will provide vital insights in the search for novel diagnostic and prognostic biomarkers.
A Novel Non-invasive Model Based on GPR for the Prediction of Liver Fibrosis in Patients With Chronic Hepatitis B
Authors: Ding Rongrong , Lu Wei , Zhou Xinlan , Huang Dan , Wang Yanbing , Li Xiufen , Yan Li , Lin Weijia , Song Shu , Zhang Zhanqing , Chen Liang
Published: September 2021

Background:Some controversy remains regarding conventional serum indices for the evaluation of liver fibrosis. Therefore, we aimed to combine the existing index with other serum parameters to discriminate liver fibrosis stages in patients with chronic hepatitis B (CHB).

Methods:A total of 1,622 treatment-naïve CHB patients were divided into training (n= 1,211) and validation (n= 451) cohorts. Liver histology was assessed according to the Scheuer scoring scheme. All common demographic and clinical parameters were analyzed.

Results:By utilizing the results of the logistic regression analysis, we developed a novel index, the product of GPR, international normalized ratio (INR), and type IV collagen (GIVPR), to discriminate liver fibrosis. In the training group, the areas under the ROCs (AUROCs) of GIVPR, APRI, FIB-4, and GPR for significant fibrosis were 0.81, 0.75, 0.72, and 0.77, respectively; the AUROCs of GIVPR, APRI, FIB-4, and GPR for advanced fibrosis were 0.82, 0.74, 0.74, and 0.78, respectively; and the AUROCs of GIVPR, APRI, FIB-4, and GPR for cirrhosis were 0.87, 0.78, 0.78, and 0.83, respectively. Similar results were also obtained in the validation group. Furthermore, the decision curve analysis suggested that GIVPR represented superior clinical benefits in both independent cohorts.

Conclusion:The GIVPR constructed on GPR represents a superior predictive model for discriminating liver fibrosis in CHB patients.
Effectiveness of Facebook Remote Live-Streaming-Guided Exercise for Improving the Functional Fitness of Community-Dwelling Older Adults
Authors: Chang Shao-Hsi , Wang Li-Ting , Chueh Ting-Yu , Hsueh Ming-Chun , Hung Tsung-Min , Wang Yu-Wen
Published: September 2021

Background: The aim of this study was to determine the effect of Facebook remote live-streaming-guided exercise on the functional fitness of community-dwelling older adults.

Method: This study used a non-randomized controlled design with single-blinding (outcome assessors). Older adults (mean age = 70.36 ± 4.51 years) were assigned to either the experimental group (n = 39) or the control group (n = 34). The experimental group participated in a 75-min Facebook remote live-streaming-guided exercise routine twice a week for 8 weeks at home, whereas the control group maintained their original lifestyle without any intervention. Functional fitness was assessed using the Senior Fitness Test, which assessed upper and lower limb flexibility and muscle strength, cardiorespiratory fitness, and balance. The test was administered before and after the intervention.

Results: The results revealed that an 8-week Facebook remote live-streaming-guided exercise intervention increased lower limb flexibility and muscle strength and cardiorespiratory fitness in community-dwelling older adults.

Conclusion: The current findings suggest that a home-based exercise program using the Facebook platform may be a feasible method to broadly improve the functional fitness of community-dwelling older adults.