bluuebunny/crossref_metadata_2025 huggingface dataset:
An Industrial Approach for the Optimization of a New Performing Coated Adsorber for Adsorption Heat Pumps
Authors: Calabrese Luigi , Mittelbach Walter , Bonaccorsi Lucio , Freni Angelo
Published: July 2022

In the present work, the optimization of a new coating formulation was investigated, taking attention to an industrially focused research approach used for the engineering design of the adsorber. The adsorbent was a composite zeolite or silica-gel based coating applied by using new flexible polymer matrices. The FC-80 formulation represents a good compromise between mechanical stability and absorption capacity. Using the developed coating process, a new compact HEX design was developed to reach the AHP target performance with easy and fast manufacturing. The specific cooling power of the coated heat exchanger was estimated to be about 500 W/kg of adsorbent. The new coated HEX was integrated in a new adsorption chiller and has been tested by a laboratory test-rig under realistic operating conditions. Results of preliminary testing demonstrated that the prototype provides a cooling capacity of around 10 kW with a COP of 0.54.
High Variability of Fungal Communities Associated with the Functional Tissues and Rhizosphere Soil of Picea abies in the Southern Baltics
Authors: Marčiulynas Adas , Marčiulynienė Diana , Mishcherikova Valeriia , Franić Iva , Lynikienė Jūratė , Gedminas Artūras , Menkis Audrius
Published: July 2022

Climate change, which leads to higher temperatures, droughts, and storms, is expected to have a strong effect on both health of forest trees and associated biodiversity. The aim of this study was to investigate the diversity and composition of fungal communities associated with the functional tissues and rhizosphere soil of healthy-looking Picea abies to better understand these fungal communities and their potential effect on tree health in the process of climate change. The study sites included 30 P. abies stands, where needles, shoots, roots, and the rhizosphere soil was sampled. DNA was isolated from individual samples, amplified using ITS2 rRNA as a marker and subjected to high-throughput sequencing. The sequence analysis showed the presence of 232,547 high-quality reads, which following clustering were found to represent 2701 non-singleton fungal OTUs. The highest absolute richness of fungal OTUs was in the soil (1895), then in the needles (1049) and shoots (1002), and the lowest was in the roots (641). The overall fungal community was composed of Ascomycota (58.3%), Basidiomycota (37.2%), Zygomycota (2.5%), Chytridiomycota (1.6%), and Glomeromycota (0.4%). The most common fungi based on sequence read abundance were Aspergillus pseudoglaucus (7.9%), Archaeorhizomyces sp. (3.6%), and Rhinocladiella sp. (2.0%). Pathogens were relatively rare, among which the most common were Phacidium lacerum (1.7%), Cyphellophora sessilis (1.4%), and Rhizosphaera kalkhoffii (1.4%). The results showed that the detected diversity of fungal OTUs was generally high, but their relative abundance varied greatly among different study sites, thereby highlighting the complexity of interactions among the host trees, fungi, and local environmental conditions.
N-Trans: Parallel Detection Algorithm for DGA Domain Names
Authors: Yang Cheng , Lu Tianliang , Yan Shangyi , Zhang Jianling , Yu Xingzhan
Published: July 2022

Domain name generation algorithms are widely used in malware, such as botnet binaries, to generate large sequences of domain names of which some are registered by cybercriminals. Accurate detection of malicious domains can effectively defend against cyber attacks. The detection of such malicious domain names by the use of traditional machine learning algorithms has been explored by many researchers, but still is not perfect. To further improve on this, we propose a novel parallel detection model named N-Trans that is based on the N-gram algorithm with the Transformer model. First, we add flag bits to the first and last positions of the domain name for the parallel combination of the N-gram algorithm and Transformer framework to detect a domain name. The model can effectively extract the letter combination features and capture the position features of letters in the domain name. It can capture features such as the first and last letters in the domain name and the position relationship between letters. In addition, it can accurately distinguish between legitimate and malicious domain names. In the experiment, the dataset is the legal domain name of Alexa and the malicious domain name collected by the 360 Security Lab. The experimental results show that the parallel detection model based on N-gram and Transformer achieves 96.97% accuracy for DGA malicious domain name detection. It can effectively and accurately identify malicious domain names and outperforms the mainstream malicious domain name detection algorithms.
Study on the Protection Effect of Sprinklers on Glass by Fire Scale in Building Fires
Authors: Gui Jia , Wang Dong , Jiang Yaqiang , Liu Junjun , Yang Lizhong
Published: July 2022

Window sprinklers are commonly used to protect glass, but there is a lack of research on the effect of fire scale on protection. In this study, full-scale experiments on sprinkler-protected glass in building fires were carried out. The experimental process was simulated using CFD numerical simulation software (FDS), and the effect of the heat release rate on the protection effect was revealed based on the glass surface temperature and heat insulation efficiency. It was found that in a full-size compartment fire, the window sprinkler was able to protect the glass from being damaged by high-temperature smoke. The numerical simulation could effectively simulate the spray distribution pattern of a window sprinkler as well as the gas temperature evolution, and the simulation results matched well with the full-size experiments. The window surface temperatures all decreased rapidly and increased linearly with the HRR after the window sprinkler was activated. The steady-state window center temperatures were 40 °C, 60 °C and 76 °C when the HRR was 2 MW, 4 MW and 6 MW, respectively. The window center temperature was less than the critical temperature of glass breakage, indicating that the window sprinkler could protect the glass from fire damage well, within the fire scale of 6 MW. The thermal insulation efficiency in the edge region was slightly lower than that in the center of the window. In the range of 2 to 6 MW, there was no significant correlation between the thermal insulation efficiency and the HRR, and the thermal insulation efficiency was in the range of 54% to 59%.
Microfluidic Invasion Chemotaxis Platform for 3D Neurovascular Co-Culture
Authors: Sokullu Emel , Cücük Zeynel Levent , Sarabi Misagh Rezapour , Birtek Mehmet Tugrul , Bagheri Hesam Saghaei , Tasoglu Savas
Published: July 2022

Advances in microfabrication and biomaterials have enabled the development of microfluidic chips for studying tissue and organ models. While these platforms have been developed primarily for modeling human diseases, they are also used to uncover cellular and molecular mechanisms through in vitro studies, especially in the neurovascular system, where physiological mechanisms and three-dimensional (3D) architecture are difficult to reconstruct via conventional assays. An extracellular matrix (ECM) model with a stable structure possessing the ability to mimic the natural extracellular environment of the cell efficiently is useful for tissue engineering applications. Conventionally used techniques for this purpose, for example, Matrigels, have drawbacks of owning complex fabrication procedures, in some cases not efficient enough in terms of functionality and expenses. Here, we proposed a fabrication protocol for a GelMA hydrogel, which has shown structural stability and the ability to imitate the natural environment of the cell accurately, inside a microfluidic chip utilizing co-culturing of two human cell lines. The chemical composition of the synthesized GelMA was identified by Fourier transform infrared spectrophotometry (FTIR), its surface morphology was observed by field emission electron microscopy (FESEM), and the structural properties were analyzed by atomic force microscopy (AFM). The swelling behavior of the hydrogel in the microfluidic chip was imaged, and its porosity was examined for 72 h by tracking cell localization using immunofluorescence. GelMA exhibited the desired biomechanical properties, and the viability of cells in both platforms was more than 80% for seven days. Furthermore, GelMA was a viable platform for 3D cell culture studies and was structurally stable over long periods, even when prepared by photopolymerization in a microfluidic platform. This work demonstrated a viable strategy to conduct co-culturing experiments as well as modeling invasion and migration events. This microfluidic assay may have application in drug delivery and dosage optimization studies.
Phytochemical Analysis of the Fruit Pulp Extracts from Annona crassiflora Mart. and Evaluation of Their Antioxidant and Antiproliferative Activities
Authors: Carvalho Natale Cristine C. , Monteiro Odair S. , da Rocha Claudia Q. , Longato Giovanna B. , Smith Robert E. , da Silva Joyce Kelly R. , Maia José Guilherme S.
Published: July 2022

Annona crassiflora Mart., the marolo fruit of the Cerrado biome, is one of the most frequently consumed species from the Brazilian Midwest. This study aimed to evaluate the chemical composition and the antioxidant and cytotoxic properties of the fruit pulp of A. crassiflora collected at Chapada das Mesas, Maranhão, Brazil. The volatile concentrate was identified as mainly ethyl octanoate, ethyl hexanoate, and methyl octanoate. From the ethanol (LFP-E) and ethyl acetate (LFP-A) extracts were identified phenolic acids (p-coumaric, gallic, quinic, and ferulic), flavones and derivatives (apigenin, epicatechin, 2′-5-dimethoxyflavone, 3′,7-dimethoxy-3-hydroxyflavone, kaempferol-3-O-glucoside and 3-O-rutinoside, quercetin-3-O-glucoside, procyanidin B2, and rutin), aporphine alkaloids (xylopine, stephagine, and romucosine), and acetogenin (annonacin). For the LFP-E and LFP-A extracts, the total phenolic compound values were 15.89 and 33.16 mg GAE/g, the flavonoid compound content values were 2.53 and 70.55 mg QE/g, the DPPH radical scavenging activity showed EC50 values of 182.54 and 57.80 µg/mL, and the ABTS radical activity showed TEAC values of 94.66 and 192.61 µM TE/g. The LFP-E extract showed significant cytotoxicity and cell selectivity for the U251-glioma strain, presenting a GI50 value of 21.34 µg/mL, which is close to doxorubicin (11.68 µg/mL), the standard chemotherapeutic drug. The marolo fruit seems to be a promising source for developing innovative and healthy products for the food industry.
Fractional Order Systems and Their Applications
Authors: Lopes António , Chen Liping
Published: July 2022

Fractional calculus (FC) generalizes the concepts of derivative and integral to non-integer orders [...]
TGF-β/VEGF-A Genetic Variants Interplay in Genetic Susceptibility to Non-Melanocytic Skin Cancer
Authors: Scola Letizia , Bongiorno Maria Rita , Forte Giusi Irma , Aiello Anna , Accardi Giulia , Scrimali Chiara , Spina Rossella , Lio Domenico , Candore Giuseppina
Published: July 2022

Differential genetically determined expression of transforming growth factor-β (TGF-β pathway and of vascular endothelial growth factor-A (VEGF-A) might modulate the molecular “milieu” involved in the etio-pathogenesis of non-melanoma skin cancer (NMSC). We have evaluated the frequency of some functionally relevant SNPs of TGF-β and VEGF-A genes in 70 NMSC patients and 161 healthy controls, typed for TGF-β1 rs1800471, TGF-β2 rs900, TGF-βR1 rs334348 and rs334349, TGF-βR2 rs4522809 and VEGF-A rs3025039 SNPs. TGF-βR2 rs1800629G allele and related genotypes were found to be associated with a possible protective role against NMSC, whereas VEGF-A rs3025039T was associated with an increased risk. To evaluate the effect of genotype combinations on NMSC susceptibility, we determined the frequencies of 31 pseudo-haplotypes due to non-random linkage among alleles of loci not lying on the same chromosome. Two pseudo-haplotypes that imply a minor allele of TGF-βR2 or minor allele of VEGF-A SNPs combined with major alleles of the other SNPs were, respectively, associated with a protective effect, and susceptibility to NMSC. In addition, a pseudo-haplotype involving minor alleles of TGF-β2 rs900, TGF-βR1 rs334348 and rs4522809 SNPs might be a susceptibility marker for NMSC. In conclusion, our data suggest that a complex interplay among the genetic polymorphisms of TGF-β, TGF-β receptors and VEGF-A genes might influence the net effect of genetic background of the patients on NMSC development. This might be relevant in the risk evaluation, diagnosis and treatment of NMSC.
Exploration of the Moderating Effects of Physical Activity and Early Life Stress on the Relation between Brain-Derived Neurotrophic Factor (BDNF) rs6265 Variants and Depressive Symptoms among Adolescents
Authors: Soler Catalina Torres , Kanders Sofia H. , Olofsdotter Susanne , Vadlin Sofia , Åslund Cecilia , Nilsson Kent W.
Published: July 2022

Depression affects one in five persons at 18 years of age. Allele A of the brain-derived neurotrophic factor (BDNF) rs6265 is considered to be a risk factor for depression. Previous studies of the interaction between BDNF rs6265, early adversity, and/or physical activity have shown mixed results. In this study, we explored the relation between BDNF rs6265 polymorphism and childhood stress, as well as the moderating effect of physical activity in relation to depressive symptoms using binary logistic regressions and process models 1, 2 and 3 applied to data obtained at three times (waves 1, 2 and 3) from the Survey of Adolescent Life in Västmanland cohort study (SALVe). Results revealed that both childhood stress and physical activity had a moderation effect; physical activity in wave 1 with an R2 change = 0.006, p = 0.013, and the Johnson–Neyman regions of significance (RoS) below 1.259, p = 0.05 for 11.97%; childhood stress in wave 2 with the R2 change = 0.008, p = 0 002, and RoS below 1.561 with 26.71% and >4.515 with 18.20%; and a three-way interaction in wave 1 in genotype AA carriers. These results suggest that allele A is susceptible to physical activity (positive environment) and childhood stress (negative environment).
Patient and Provider Perspectives on Emergency Department Care Experiences among People with Mental Health Concerns
Authors: Navas Carolina , Wells Laura , Bartels Susan A. , Walker Melanie
Published: July 2022

Emergency departments (EDs) are an important source of care for people with mental health (MH) concerns. It can be challenging to treat MH in EDs, and there is little research capturing both patient and provider perspectives of these experiences. We sought to summarize the evidence on ED care experiences for people with MH concerns in North America, from both patient and provider perspectives. Medline and EMBASE were searched using PRISMA guidelines to identify primary studies. Two reviewers conducted a qualitative assessment of included papers and inductive thematic analysis to identify common emerging themes from patient and provider perspectives. Seventeen papers were included. Thematic analysis revealed barriers and facilitators to optimal ED care, which were organized into three themes each with sub-themes: (1) interpersonal factors, including communication, patient–staff interactions, and attitudes and behaviours; (2) environmental factors, including accommodations, wait times, and restraint use; and (3) system-level factors, including discharge planning, resources and policies, and knowledge and expertise. People with MH concerns and ED healthcare providers (HCPs) share converging perspectives on improving ED connections with community resources and diverging perspectives on the interplay between system-level and interpersonal factors. Examining both perspectives simultaneously can inform improvements in ED care for people with MH concerns.
A Portable Vibration System to Induce and Evaluate Susceptibility to Red Drupelet Reversion in Blackberry Cultivars
Authors: Flores-Sosa Angel R. , Fabela-Gallegos Manuel J. , Cruz-Acevedo Mauricio E. , Rivera-Pastrana Dulce M. , Nava Gerardo M. , Mercado-Silva Edmundo M.
Published: July 2022

Red drupelet reversion (RDR) is a physiological disorder in which blackberry drupelets revert from black to red, losing their commercial value. RDR has been associated with mechanical damage caused by vibrations during transport. The goal of the present study was to construct a portable vibration system to quantify RDR progression in different blackberry cultivars. The system was integrated with an electrical signal generator, a monoaural amplifier, a subwoofer type speaker, and an oscilloscope. This system generates vibration intensities reached during fruit commercial transport (10 Hz and 0.5 g’s). To induce RDR, blackberry clamshells cv. ‘Tupi’ were placed in the portable system and subjected to different vibration times. RDR was observed immediately after fruit was subjected to 5 min vibration. To evaluate RDR progression in different cultivars, blackberry clamshells ‘Ak234′, ‘Am151′, and ‘Tupi’ were subjected to vibration during different times; and analyzed after storage (0 to 5 d). ‘Tupi’ blackberries reverted more rapidly than ‘Am151′ and ‘Ak234′ cultivars, suggesting that ‘Tupi’ was more susceptible to RDR. These results highlight that portable vibration system could be a useful and fast tool to evaluate resistance to RDR in blackberries.
Molecular Cloning, Characterization, and Expression Analysis of SIMILAR TO RCD-ONE (SRO) Family Genes Responding to Abiotic and Biotic Stress in Cucumber
Authors: Xiao Lingdi , Zhou Zixian , Zhu Chuxia , Zhao Jindong , Hu Zhaoyang , Liu Shiqiang , Zhou Yong
Published: July 2022

SIMILAR TO RCD-ONE (SRO) is a plant-specific small protein family that controls many biological processes including physiological development and stress responses. The SRO gene family has been studied in several plant species, but no detailed characterization and expression profiles of this important gene family were performed in cucumber. In this study, we characterize the SRO genes in cucumber, and determined their transcript levels in various tissues and under exposure to diverse biotic and abiotic stressors. Four SRO genes (named as CsSRO1–CsSRO4) were identified and isolated, which were distributed on three different chromosomes. Gene duplication analysis showed that only one pair of segmental duplication event was identified, but no tandem duplication events were detected. All CsSROs consist of the PARP domain and a C-terminal RST domain, while the N-terminal WWE domain was only present in CsSRO2 and CsSRO4. SROs from 15 plant species are divided into two groups (I and II), and group I can be further divided into four subgroups (Ia to Id) according to the phylogenetic tree. The conserved motif and gene structure analyses showed that SROs within the same branch of the phylogenetic tree have analogous conserved motifs configuration and gene structures. However, SRO genes possessed variable numbers of introns in different subgroups, which may affect the evolution of new family members. RNA-Seq data and qRT-PCR results showed that the four CsSRO genes have distinct expression pattern in various tissues and under diverse stresses, suggesting their multiple functions in plant growth and stress responses. The findings provide a basis for further research aiming at functional characterization of the regulatory mechanism to reveal the roles of CsSRO genes in developmental and stress-related processes of cucumber.
Comparison of Characteristics of Definition Criteria for Respiratory Sarcopenia—The Otassya Study
Authors: Kera Takeshi , Kawai Hisashi , Ejiri Manami , Ito Kumiko , Hirano Hirohiko , Fujiwara Yoshinori , Ihara Kazushige , Obuchi Shuichi
Published: July 2022

We compared the definitions of respiratory sarcopenia obtained from a model based on forced vital capacity (FVC) and whole-body sarcopenia, as recommended by the Japanese Association of Rehabilitation Nutrition (JARN), and a model based on the peak expiratory flow rate (PEFR), as recommended in our previous study. A total of 554 community-dwelling older people without airway obstruction who participated in our study in 2017 were included in the current study. Respiratory function, sarcopenia, and frailty were assessed. Pearson’s correlation coefficients of the associations of the FVC and PEFR with physical performance and the receiver operating curves of FVC and PEFR’s association with sarcopenia, long-term care insurance (LTCI) certification, and frailty were calculated. The sensitivity and specificity of the two respiratory sarcopenia models were assessed. The FVC and PEFR were associated significantly with physical performance. The areas under the curve for sarcopenia and the LTCI certification in the FVC and PEFR groups were statistically significant in both sexes. While Kera’s model had a lower specificity in determining sarcopenia, it had a sensitivity higher than the JARN model. Both models provide suitable definitions of respiratory sarcopenia. Future studies are required to determine other appropriate variables to define respiratory sarcopenia.
Impact of Immediate and Delayed Breast Reconstruction on Quality of Life of Breast Cancer Patients
Authors: Pačarić Stana , Orkić Želimir , Babić Marko , Farčić Nikolina , Milostić-Srb Andrea , Lovrić Robert , Barać Ivana , Mikšić Štefica , Vujanić Jasenka , Turk Tajana , Gvozdanović Zvjezdana , Pavlović Dragica , Srb Nika , Pačarić Ivana
Published: July 2022

A mastectomy affects the psychological, social, and sexual well-being of patients. Research has confirmed that breast reconstruction is important for improving the quality of life in patients with breast cancer. The aim of this study was to assess the quality of life of patients who underwent a mastectomy followed by immediate or delayed breast reconstruction. This prospective study was conducted from January 2018 to March 2020 at the Clinical Hospital Center Osijek, using the health questionnaire SF-36. The study included 79 patients. The results of the study showed that patients who underwent a mastectomy had the lowest scores in the domain of restriction due to physical difficulties, 18.8 (6.3–31.3), in physical functioning and limitation due to emotional difficulties, 16.7 (8.3–33.3), in mental health. In immediate breast reconstruction, patients rated better physical health (p < 0.001), while patients who underwent delayed breast reconstruction rated their mental health worse (p < 0.001) as measured by the SF-36 questionnaire. Conclusion: The results of this study show that patients without breast reconstruction rated their quality of life worse than patients who underwent immediate and delayed breast reconstruction after mastectomy. There is no difference in the quality of life between patients who underwent immediate and delayed breast reconstruction after mastectomy.
“Ko Au te Whenua, Ko te Whenua Ko Au: I Am the Land, and the Land Is Me”: Healer/Patient Views on the Role of Rongoā Māori (Traditional Māori Healing) in Healing the Land
Authors: Mark Glenis , Boulton Amohia , Allport Tanya , Kerridge Donna , Potaka-Osborne Gill
Published: July 2022

In Rongoā Māori (traditional Māori healing), the connection with the land stems from seeing Papatūānuku/Mother Earth as a part of our identity/whakapapa (genealogy), our culture, and our wellbeing. This qualitative study aimed to explore the holistic nature and meaning of Rongoā Māori. There were 49 practitioner and patient participants who participated in semi-structured interviews and focus groups across Aotearoa/New Zealand. The findings showed four themes: land as an intrinsic part of identity; land as a site and source of healing; reciprocity of the healing relationship; and the importance of kaitiakitanga/conservation to Rongoā Māori. Participants shared narratives of connections between the people and the land that showed that when the land is well, the people are well. Implications of these themes for Indigenous wellbeing and the conservation and protection of our natural environments led to three recommendations to reconnect with the land, support Rongoā Māori healing, and to participate in the conservation and preservation of local land and waterways. It is hoped that in learning more about the connection between the land and Rongoā Māori healing, we begin to place greater value on the need to conserve and preserve both the land and our connections to her through traditional healing practices.
Impacts of Atmospheric and Anthropogenic Factors on Microbiological Pollution of the Recreational Coastal Beaches Neighboring Shipping Ports
Authors: Kraus Romina , Baljak Vanja , Vukić Lušić Darija , Kranjčević Lado , Cenov Arijana , Glad Marin , Kauzlarić Vesna , Lušić Dražen , Grbčić Luka , Alvir Marta , Pećarević Marijana , Jozić Slaven
Published: July 2022

A comparative study of the two northeastern ports of the Adriatic Sea indicated that the port of Rijeka is microbiologically more loaded than the port of Pula and posing a greater threat to other ports through a potential transfer of pathogens by ballast water. Fecal indicator bacteria, Escherichia coli and intestinal enterococci, were investigated seasonally in 2014–2015 in the ports and during the bathing season monitoring in the two bays where ports are located in 2009–2020. In addition, the indicators and pathogens related to human health were determined in the ports’ seawater and sediment. The determined factors contributing to microbiological pollution were higher number of tourists and locals, potential wastewater and ballast water discharge and enclosed port configuration, with high solar radiation and low precipitation reducing the negative effects. Our research points to the necessity of including Clostridium perfringens in monitoring beach sand during the bathing seasons and a wider list of pathogens in port monitoring due to a potential transfer by shipping ballast water.
Effectiveness of Two Stress Reduction Interventions in Patients with Chronic Diabetic Foot Ulcers (PSY-DFU): Protocol for a Longitudinal RCT with a Nested Qualitative Study Involving Family Caregivers
Authors: Pereira M. Graça , Vilaça Margarida , Carvalho Eugenia
Published: July 2022

Diabetic foot ulcer (DFU) is the leading cause of lower-limb amputations, with a significant impact on patients, families, and society. Since DFU medical treatments represent a major socioeconomic burden, cost-effective interventions are needed. This trial aims to assess the effectiveness of a muscle relaxation intervention compared to a hypnosis intervention versus active and passive control groups on DFU healing, physiological indicators of healing prognosis, and quality of life (QoL) in clinically distressed patients with a chronic DFU. A multicenter, randomized controlled trial with three assessment moments (baseline, two months post-intervention, and four months follow-up) will be conducted. Approximately 170 patients will be randomized and allocated to either treatment or control groups. Primary outcomes will be DFU healing, physiological indicators of healing prognosis, and QoL. Secondary outcomes will include perceived stress, psychological morbidity, and DFU representations. The efficacy of sessions on DFU healing will be qualitatively assessed in 12 patients allocated to the treatment and active control groups, as well as their family caregivers. This study will provide evidence regarding the effectiveness of two psychological interventions for the DFU healing process and the QoL of patients, with direct clinical relevance regarding DFU treatment and recurrence.
Reconciling Work and Family Demands and Related Psychosocial Risk and Support Factors among Working Families: A Finnish National Survey Study
Authors: Björk Janina M. , Nordmyr Johanna , Forsman Anna K.
Published: July 2022

Working families commonly struggle with reconciling work and family demands. While the Nordic welfare states have been regarded as forerunners in family-friendly policies, worldwide trends threaten work–family reconciliation also in this context. Therefore, this study aimed to examine the associations between family interference with work (FIW)/work interference with family (WIF) and selected psychosocial risk and support factors in the work and family settings of Finnish working families. Data from the Finnish Quality of Work Life Survey 2018 collected by Statistics Finland were utilized to conduct binary logistic regression analyses (N = 1431). Risk factors in the work setting emerged as key covariates as all of them showed statistically significant associations with WIF or both WIF and FIW. Another key finding was that occasional conflicts within the family were beneficial in the context of both WIF and FIW. To conclude, both distinct and mutual psychosocial risk and support factors of FIW and WIF were identified, at the same time as two socio-demographic factors as well as one workplace factor were identified as covariates specifically of FIW. This study showed that work–family reconciliation is a considerable challenge among Finnish working families, and especially to women.
Dysfunction of Mitochondria in Alzheimer’s Disease: ANT and VDAC Interact with Toxic Proteins and Aid to Determine the Fate of Brain Cells
Authors: Atlante Anna , Valenti Daniela , Latina Valentina , Amadoro Giuseppina
Published: July 2022

Alzheimer’s disease (AD), certainly the most widespread proteinopathy, has as classical neuropathological hallmarks, two groups of protein aggregates: senile plaques and neurofibrillary tangles. However, the research interest is rapidly gaining ground in a better understanding of other pathological features, first, of all the mitochondrial dysfunctions. Several pieces of evidence support the hypothesis that abnormal mitochondrial function may trigger aberrant processing of amyloid progenitor protein or tau and thus neurodegeneration. Here, our aim is to emphasize the role played by two ‘bioenergetic’ proteins inserted in the mitochondrial membranes, inner and outer, respectively, that is, the adenine nucleotide translocator (ANT) and the voltage-dependent anion channel (VDAC), in the progression of AD. To perform this, we will magnify the ANT and VDAC defects, which are measurable hallmarks of mitochondrial dysfunction, and collect all the existing information on their interaction with toxic Alzheimer’s proteins. The pathological convergence of tau and amyloid β-peptide (Aβ) on mitochondria may finally explain why the therapeutic strategies used against the toxic forms of Aβ or tau have not given promising results separately. Furthermore, the crucial role of ANT-1 and VDAC impairment in the onset/progression of AD opens a window for new therapeutic strategies aimed at preserving/improving mitochondrial function, which is suspected to be the driving force leading to plaque and tangle deposition in AD.
Subtype of Neuroblastoma Cells with High KIT Expression Are Dependent on KIT and Its Knockdown Induces Compensatory Activation of Pro-Survival Signaling
Authors: Lebedev Timofey , Buzdin Anton , Khabusheva Elmira , Spirin Pavel , Suntsova Maria , Sorokin Maxim , Popenko Vladimir , Rubtsov Petr , Prassolov Vladimir
Published: July 2022

Neuroblastoma (NB) is a pediatric cancer with high clinical and molecular heterogeneity, and patients with high-risk tumors have limited treatment options. Receptor tyrosine kinase KIT has been identified as a potential marker of high-risk NB and a promising target for NB treatment. We investigated 19,145 tumor RNA expression and molecular pathway activation profiles for 20 cancer types and detected relatively high levels of KIT expression in NB. Increased KIT expression was associated with activation of cell survival pathways, downregulated apoptosis induction, and cell cycle checkpoint control pathways. KIT knockdown with shRNA encoded by lentiviral vectors in SH-SY5Y cells led to reduced cell proliferation and apoptosis induction up to 50%. Our data suggest that apoptosis induction was caused by mitotic catastrophe, and there was a 2-fold decrease in percentage of G2-M cell cycle phase after KIT knockdown. We found that KIT knockdown in NB cells leads to strong upregulation of other pro-survival growth factor signaling cascades such as EPO, NGF, IL-6, and IGF-1 pathways. NGF, IGF-1 and EPO were able to increase cell proliferation in KIT-depleted cells in an ERK1/2-dependent manner. Overall, we show that KIT is a promising therapeutic target in NB, although such therapy efficiency could be impeded by growth factor signaling activation.
Insight and Recent Advances into the Role of Topography on the Cell Differentiation and Proliferation on Biopolymeric Surfaces
Authors: Tudureanu Raluca , Handrea-Dragan Iuliana M. , Boca Sanda , Botiz Ioan
Published: July 2022

It is well known that surface topography plays an important role in cell behavior, including adhesion, migration, orientation, elongation, proliferation and differentiation. Studying these cell functions is essential in order to better understand and control specific characteristics of the cells and thus to enhance their potential in various biomedical applications. This review proposes to investigate the extent to which various surface relief patterns, imprinted in biopolymer films or in polymeric films coated with biopolymers, by utilizing specific lithographic techniques, influence cell behavior and development. We aim to understand how characteristics such as shape, dimension or chemical functionality of surface relief patterns alter the orientation and elongation of cells, and thus, finally make their mark on the cell proliferation and differentiation. We infer that such an insight is a prerequisite for pushing forward the comprehension of the methodologies and technologies used in tissue engineering applications and products, including skin or bone implants and wound or fracture healing.
Transport of Biologically Active Ultrashort Peptides Using POT and LAT Carriers
Authors: Khavinson Vladimir , Linkova Natalia , Kozhevnikova Ekaterina , Dyatlova Anastasiia , Petukhov Mikhael
Published: July 2022

Ultrashort peptides (USPs), consisting of 2–7 amino-acid residues, are a group of signaling molecules that regulate gene expression and protein synthesis under normal conditions in various diseases and ageing. USPs serve as a basis for the development of drugs with a targeted mechanism of action. The purpose of this review is to systematize the available data on USP transport involving POT and LAT transporters in various organs and tissues under normal, pathological and ageing conditions. The carriers of the POT family (PEPT1, PEPT2, PHT1, PHT2) transport predominantly di- and tripeptides into the cell. Methods of molecular modeling and physicochemistry have demonstrated the ability of LAT1 to transfer not only amino acids but also some di- and tripeptides into the cell and out of it. LAT1 and 2 are involved in the regulation of the antioxidant, endocrine, immune and nervous systems’ functions. Analysis of the above data allows us to conclude that, depending on their structure, di- and tripeptides can be transported into the cells of various tissues by POT and LAT transporters. This mechanism is likely to underlie the tissue specificity of peptides, their geroprotective action and effectiveness in the case of neuroimmunoendocrine system disorders.
Cell Autophagy in NASH and NASH-Related Hepatocellular Carcinoma
Authors: Udoh Utibe-Abasi S. , Rajan Pradeep Kumar , Nakafuku Yuto , Finley Robert , Sanabria Juan Ramon
Published: July 2022

Autophagy, a cellular self-digestion process, involves the degradation of targeted cell components such as damaged organelles, unfolded proteins, and intracellular pathogens by lysosomes. It is a major quality control system of the cell and plays an important role in cell differentiation, survival, development, and homeostasis. Alterations in the cell autophagic machinery have been implicated in several disease conditions, including neurodegeneration, autoimmunity, cancer, infection, inflammatory diseases, and aging. In non-alcoholic fatty liver disease, including its inflammatory form, non-alcoholic steatohepatitis (NASH), a decrease in cell autophagic activity, has been implicated in the initial development and progression of steatosis to NASH and hepatocellular carcinoma (HCC). We present an overview of autophagy as it occurs in mammalian cells with an insight into the emerging understanding of the role of autophagy in NASH and NASH-related HCC.
Upregulation of the Long Noncoding RNA CASC10 Promotes Cisplatin Resistance in High-Grade Serous Ovarian Cancer
Authors: Noriega-Rivera Ricardo , Rivera-Serrano Mariela , Rabelo-Fernandez Robert J. , Pérez-Santiago Josué , Valiyeva Fatima , Vivas-Mejía Pablo E.
Published: July 2022

Despite initial responses to first-line treatment with platinum and taxane-based combination chemotherapy, most high-grade serous ovarian carcinoma (HGSOC) patients will relapse and eventually develop a cisplatin-resistant fatal disease. Due to the lethality of this disease, there is an urgent need to develop improved targeted therapies against HGSOC. Herein, we identified CASC10, a long noncoding RNA upregulated in cisplatin-resistant ovarian cancer cells and ovarian cancer patients. We performed RNA sequencing (RNA-seq) in total RNA isolated from the HGSOC cell lines OVCAR3 and OV-90 and their cisplatin-resistant counterparts. Thousands of RNA transcripts were differentially abundant in cisplatin-sensitive vs. cisplatin-resistant HGSOC cells. Further data filtering unveiled CASC10 as one of the top RNA transcripts significantly increased in cisplatin-resistant compared with cisplatin-sensitive cells. Thus, we focused our studies on CASC10, a gene not previously studied in ovarian cancer. SiRNA-mediated CASC10 knockdown significantly reduced cell proliferation and invasion; and sensitized cells to cisplatin treatment. SiRNA-mediated CASC10 knockdown also induced apoptosis, cell cycle arrest, and altered the expression of several CASC10 downstream effectors. Multiple injections of liposomal CASC10-siRNA reduced tumor growth and metastasis in an ovarian cancer mouse model. Our results demonstrated that CASC10 levels mediate the susceptibility of HGSOC cells to cisplatin treatment. Thus, combining siRNA-mediated CASC10 knockdown with cisplatin may represent a plausible therapeutic strategy against HGSOC.
Tropism of the Novel AAVBR1 Capsid Following Subretinal Delivery
Authors: Carroll Lara , Uehara Hironori , Zhang Xiaohui , Ambati Balamurali
Published: July 2022

A serious limitation of current adeno-associated viral (AAV) capsids employed for subretinal delivery is achieving adequate lateral spread beyond the injection site, required for the efficient delivery of gene therapy to the outer retina and/or RPE. AAVBR1 is a unique AAV with exceptional tropism for CNS microvasculature following systemic delivery. Here, we used in vivo and ex vivo analysis to show that subretinal delivery of AAVBR1.GFP in mice achieves superior tropism to RPE and outer retina than either AAV2.GFP or AAV8.GFP, two of the most common capsids used for subretinal delivery. At a low (5 × 108 vg) subretinal dose, the AAVBR1.GFP signal was visible by 48 h and significantly surpassed peak fluorescence of other AAVs in retina and RPE. The co-injection of AAVBR1.GFP with the AAVBR1-specific heptapeptide, NRGTEWD, significantly blocked the AAVBR1.GFP signal, but had no effect on AAV2.GFP fluorescence, confirming that AAVBR1’s enhanced tropism for RPE and outer retina derives from this 7AA modification within the capsid-binding motif. Enhanced dispersal and consequent transduction suggest that AAVBR1 can be employed at a lower dosage than the standard AAV2 capsid to achieve equivalent expression for gene therapy, warranting further evaluation of its utility as a therapeutic vehicle for subretinal delivery.
Hypertension and Cardiovascular Diseases: From Etiopathogenesis to Potential Therapeutic Targets
Authors: Bernatova Iveta , Liskova Silvia , Bartekova Monika
Published: July 2022

Cardiovascular diseases (CVDs) are the top cause of death worldwide, and arterial hypertension per se remains the major preventable cause of CVDs [...]
A Polyclonal Aptamer Library for the Specific Binding of the Gut Bacterium Roseburia intestinalis in Mixtures with Other Gut Microbiome Bacteria and Human Stool Samples
Authors: Xing Hu , Zhang Yiting , Krämer Markus , Kissmann Ann-Kathrin , Amann Valerie , Raber Heinz Fabian , Weil Tanja , Stieger Kai R. , Knippschild Uwe , Henkel Marius , Andersson Jakob , Rosenau Frank
Published: July 2022

Roseburia intestinalis has received attention as a potential probiotic bacterium. Recent studies have demonstrated that changes in its intestinal abundance can cause various diseases, such as obesity, enteritis and atherosclerosis. Probiotic administration or fecal transplantation alter the structure of the intestinal flora, offering possibilities for the prevention and treatment of these diseases. However, current monitoring methods, such as 16S rRNA sequencing, are complex and costly and require specialized personnel to perform the tests, making it difficult to continuously monitor patients during treatment. Hence, the rapid and cost-effective quantification of intestinal bacteria has become an urgent problem to be solved. Aptamers are of emerging interest because their stability, low immunogenicity and ease of modification are attractive properties for a variety of applications. We report a FluCell-SELEX polyclonal aptamer library specific for R. intestinalis isolated after seven evolution rounds, that can bind and label this organism for fluorescence microscopy and binding assays. Moreover, R. intestinalis can be distinguished from other major intestinal bacteria in complex defined mixtures and in human stool samples. We believe that this preliminary evidence opens new avenues towards aptamer-based electronic biosensors as new powerful and inexpensive diagnostic tools for the relative quantitative monitoring of R. intestinalis in gut microbiomes.
A Splice Switch in SIGIRR Causes a Defect of IL-37-Dependent Anti-Inflammatory Activity in Cystic Fibrosis Airway Epithelial Cells
Authors: Ueno-Shuto Keiko , Kamei Shunsuke , Hayashi Megumi , Fukuyama Ayami , Uchida Yuji , Tokutomi Naofumi , Suico Mary Ann , Kai Hirofumi , Shuto Tsuyoshi
Published: July 2022

Cystic fibrosis (CF) is a hereditary disease typically characterized by infection-associated chronic lung inflammation. The persistent activation of toll-like receptor (TLR) signals is considered one of the mechanisms for the CF hyperinflammatory phenotype; however, how negative regulatory signals of TLRs associate with CF inflammation is still elusive. Here, we showed that the cell surface expression of a single immunoglobulin interleukin-1 receptor (IL-1R)-related molecule (SIGIRR), a membrane protein essential for suppressing TLRs- and IL-1R-dependent signals, was remarkably decreased in CF airway epithelial cells compared to non-CF cells. Notably, CF airway epithelial cells specifically and highly expressed a unique, alternative splice isoform of the SIGIRR that lacks exon 8 (Δ8-SIGIRR), which results in the production of a C-terminal truncated form of the SIGIRR. Δ8-SIGIRR was expressed intracellularly, and its over-expression abolished the cell surface expression and function of the full-length SIGIRR (WT-SIGIRR), indicating its dominant-negative effect leading to the deficiency of anti-inflammatory activity in CF cells. Consistently, IL-37, a ligand for the SIGIRR, failed to suppress viral dsRNA analogue poly(I:C)-dependent JNK activation and IL-8 production, confirming the reduction in the functional WT-SIGIRR expression in the CF cells. Together, our studies reveal that SIGIRR-dependent anti-inflammatory activity is defective in CF airway epithelial cells due to the unique splicing switch of the SIGIRR gene and provides the first evidence of IL-37-SIGIRR signaling as a target of CF airway inflammation.
miR449 Protects Airway Regeneration by Controlling AURKA/HDAC6-Mediated Ciliary Disassembly
Authors: Wildung Merit , Herr Christian , Riedel Dietmar , Wiedwald Cornelia , Moiseenko Alena , Ramírez Fidel , Tasena Hataitip , Heimerl Maren , Alevra Mihai , Movsisyan Naira , Schuldt Maike , Volceanov-Hahn Larisa , Provoost Sharen , Nöthe-Menchen Tabea , Urrego Diana , Freytag Bernard , Wallmeier Julia , Beisswenger Christoph , Bals Robert , van den Berge Maarten , Timens Wim , Hiemstra Pieter S. , Brandsma Corry-Anke , Maes Tania , Andreas Stefan , Heijink Irene H. , Pardo Luis A. , Lizé Muriel
Published: July 2022

Airway mucociliary regeneration and function are key players for airway defense and are impaired in chronic obstructive pulmonary disease (COPD). Using transcriptome analysis in COPD-derived bronchial biopsies, we observed a positive correlation between cilia-related genes and microRNA-449 (miR449). In vitro, miR449 was strongly increased during airway epithelial mucociliary differentiation. In vivo, miR449 was upregulated during recovery from chemical or infective insults. miR0449−/− mice (both alleles are deleted) showed impaired ciliated epithelial regeneration after naphthalene and Haemophilus influenzae exposure, accompanied by more intense inflammation and emphysematous manifestations of COPD. The latter occurred spontaneously in aged miR449−/− mice. We identified Aurora kinase A and its effector target HDAC6 as key mediators in miR449-regulated ciliary homeostasis and epithelial regeneration. Aurora kinase A is downregulated upon miR449 overexpression in vitro and upregulated in miR449−/− mouse lungs. Accordingly, imaging studies showed profoundly altered cilia length and morphology accompanied by reduced mucociliary clearance. Pharmacological inhibition of HDAC6 rescued cilia length and coverage in miR449−/− cells, consistent with its tubulin-deacetylating function. Altogether, our study establishes a link between miR449, ciliary dysfunction, and COPD pathogenesis.
Emerging Concepts in Defective Macrophage Phagocytosis in Cystic Fibrosis
Authors: Jaganathan Devi , Bruscia Emanuela M. , Kopp Benjamin T.
Published: July 2022

Cystic fibrosis (CF) is caused by mutations of the cystic fibrosis transmembrane conductance regulator (CFTR) gene. Chronic inflammation and decline in lung function are major reasons for morbidity in CF. Mutant CFTR expressed in phagocytic cells such as macrophages contributes to persistent infection, inflammation, and lung disease in CF. Macrophages play a central role in innate immunity by eliminating pathogenic microbes by a process called phagocytosis. Phagocytosis is required for tissue homeostasis, balancing inflammation, and crosstalk with the adaptive immune system for antigen presentation. This review focused on (1) current understandings of the signaling underlying phagocytic mechanisms; (2) existing evidence for phagocytic dysregulation in CF; and (3) the emerging role of CFTR modulators in influencing CF phagocytic function. Alterations in CF macrophages from receptor initiation to phagosome formation are linked to disease progression in CF. A deeper understanding of macrophages in the context of CFTR and phagocytosis proteins at each step of phagosome formation might contribute to the new therapeutic development of dysregulated innate immunity in CF. Therefore, the review also indicates future areas of research in the context of CFTR and macrophages.