bluuebunny/crossref_metadata_2025 huggingface dataset:
Estimated SARS-CoV-2 Infection and Seroprevalence in Firefighters from a Northeastern Brazilian State: A Cross-Sectional Study
Authors: Borges Lysandro P. , Nascimento Laranda C. , Heimfarth Luana , Souza Daniela R. V. , Martins Aline F. , de Rezende Neto José M. , dos Santos Kezia A. , Matos Igor L. S. , da Invenção Grazielly B. , Oliveira Brenda M. , Santos Aryanne A. , Souza Nicolas A. A. , de Jesus Pamela C. , dos Santos Cliomar A. , Goes Marco A. O. , de Souza Mércia S. F. , Guimarães Adriana G.
Published: August 2021

The new coronavirus has been affecting health worldwide and essential service workers are continually exposed to this infectious agent, increasing the chance of infection and the development of the disease. Thus, this study aimed to estimate the frequency of infection and seroprevalence for SARS-CoV-2 in military firefighters in a city in Northeastern Brazil in January 2021. An observational cross-sectional study was carried out with 123 firefighters who answered a brief questionnaire to collect socio-epidemiological data and underwent RT-PCR and immunofluorescence test (IgM and IgG). The results found reveal a positive seroprevalence, with a high rate of infection in this class of workers, since they are essential service professionals who are exposed to risk due to their working hours, in addition to sharing some spaces and work materials. Besides, there were significant associations between positivity for IgG and IgM, as well as for positive RT-PCR prior to the study and the presence of IgG, with odd ratios of 3.04 and 4.9, respectively. These findings reinforce the need for immunization in this category, whose line of service hinders the adoption of distancing measures, since in many situations physical contact is inevitable.
Promoting Service Leadership Qualities and Well-Being among University Students through an Online Course during COVID-19 Pandemic
Authors: Zhu Xiaoqin , Shek Daniel T. L. , Chan Cathy H. M.
Published: August 2021

The COVID-19 pandemic is a great challenge to leadership education in universities. Although previous findings provide support for the effectiveness of online learning, the impact of online leadership course on students’ learning outcomes and well-being has not been well documented. Using objective outcome and subjective outcome evaluation strategies, the present study examined students’ perceived qualities and effectiveness of an online credit-bearing service leadership course adopting asynchronous mode (primarily online learning) and synchronous mode under COVID-19. Regardless of teaching modes, the subject yielded positive impacts. Specifically, pretest-posttest (N = 228) showed that there were positive changes in students’ service leadership qualities, life satisfaction and psychological well-being. For students’ perception of the course (N = 219), results indicated that most students were positive in their learning experience and satisfied with course design, lecturer quality and the benefits of the course to their development. Students’ changes and subjective perceptions were positively correlated, but with a low effect size. The findings reflected that online service leadership course adopting asynchronous or synchronous mode was effective, and students were positive about their learning experience.
Effect of Train-Induced Wind on the Transmission of COVID-19: A New Insight into Potential Infectious Risks
Authors: Zou Simin , He Xuhui
Published: August 2021

The unprecedented COVID-19 pandemic has caused a traffic tie-up across the world. In addition to home quarantine orders and travel bans, the social distance guideline of about six feet was enacted to reduce the risk of contagion. However, with recent life gradually returning to normal, the crisis is not over. In this research, a moving train test and a Gaussian puff model were employed to investigate the impact of wind raised by a train running on the transmission and dispersion of SARS-CoV-2 from infected individuals. Our findings suggest that the 2 m social distance guideline may not be enough; under train-induced wind action, human respiratory disease-carrier droplets may travel to unexpected places. However, there are deficiencies in passenger safety guidelines and it is necessary to improve the quantitative research in the relationship between train-induced wind and virus transmission. All these findings could provide a fresh insight to contain the spread of COVID-19 and provide a basis for preventing and controlling the pandemic virus, and probe into strategies for control of the disease in the future.
Prevalence of Malnutrition and Associated Factors of Stunting among 6–23-Month-Old Infants in Central Rural China in 2019
Authors: Liu Jing , Sun Jing , Huang Jian , Huo Junsheng
Published: August 2021

This study aimed to evaluate the prevalence of malnutrition and to investigate the associated factors of stunting among 6–23-month-old infants in poor rural areas of central China. The China Nutrition Improvement Project on Children in Poor Areas was conducted in 56 national-level poor counties of seven provinces in 2019. We performed a multivariate binary logistic regression analysis to determine the associated factors of stunting. This cross-sectional study included 17,193 infants. The overall prevalence of stunting was the highest (3.9%), followed by overweight (3.0%), underweight (2.1%), wasting (2.0%), and obesity (0.5%). Girls [OR = 0.55, 95% CI (0.46, 0.65)], infants meeting requirements of minimum diversity diet [OR = 0.81, 95% CI (0.67, 0.98)], and mothers with middle-school or high-school education and above decreased the prevalence of stunting. Infants with diarrhea in two weeks [OR = 1.26,95% CI (0.98, 1.62)] were at higher odds of stunting. The malnutrition status in the study areas was improved, and vulnerable infants were found to need additional and earlier monitoring to detect and fundamentally prevent undernutrition.
Relationship between Competency to Consent to Treatment and Psychological Well-Being: Mediating Effect of Empowerment and Emotion
Authors: Hur Yeun-Joo , Park Joon-Ho , Rhee MinKyu
Published: August 2021

This study was conducted to evaluate the competency to consent to the treatment of psychiatric outpatients and to confirm the role of empowerment and emotional variables in the relationship between competency to consent to treatment and psychological well-being. The study participants consisted of 191 psychiatric outpatients who voluntarily consented to the study among psychiatric outpatients. As a result of competency to consent to treatment evaluation, the score of the psychiatric outpatient’s consent to treatment was higher than the cut-off point for both the overall and sub-factors, confirming that they were overall good. In addition, the effect of the ability of application on psychological well-being among competency to consent to treatment was verified using PROCESS Macro, and the double mediation effect using empowerment and emotional variables was verified to provide an expanded understanding of this. As a result of the analysis, empowerment completely mediated the relation between the ability of application and psychological well-being, and the relation between the ability of application and psychological well-being was sequentially mediated by empowerment and emotion-related variables. Based on these findings, the implications and limitations of this study were discussed.
The Burden of Burnout among Healthcare Professionals of Intensive Care Units and Emergency Departments during the COVID-19 Pandemic: A Systematic Review
Authors: Gualano Maria Rosaria , Sinigaglia Tiziana , Lo Moro Giuseppina , Rousset Stefano , Cremona Agnese , Bert Fabrizio , Siliquini Roberta
Published: August 2021

The primary aim was to evaluate the burnout prevalence among healthcare workers (HCWs) in intensive care units (ICUs) and emergency departments (EDs) during the COVID-19 pandemic. The secondary aim was to identify factors associated with burnout in this population. A systematic review was conducted following PRISMA guidelines by searching PubMed, Embase, PsychINFO, and Scopus from 1 January to 24 November 2020. Studies with information about burnout prevalence/level during the pandemic regarding ICU/ED HCWs were eligible. A total of 927 records were identified. The selection resulted in 11 studies. Most studies were conducted in April/May 2020. Samples ranged from 15 to 12,596 participants. The prevalence of overall burnout ranged from 49.3% to 58%. Nurses seemed to be at higher risk. Both socio-demographic and work-related features were associated with burnout. Many pandemic-related variables were associated with burnout, e.g., shortage in resources, worry regarding COVID-19, and stigma. This review highlighted a substantial burnout prevalence among ICU/ED HCWs. However, this population has presented a high burnout prevalence for a long time, and there is not sufficient evidence to understand if such prevalence is currently increased. It also outlined modifiable factors and the need to improve emergency preparedness both from an individual and structural level.
Overexpression of Flii during Murine Embryonic Development Increases Symmetrical Division of Epidermal Progenitor Cells
Authors: Yang Gink N. , Ahangar Parinaz , Strudwick Xanthe L. , Kopecki Zlatko , Cowin Allison J.
Published: August 2021

Epidermal progenitor cells divide symmetrically and asymmetrically to form stratified epidermis and hair follicles during late embryonic development. Flightless I (Flii), an actin remodelling protein, is implicated in Wnt/β-cat and integrin signalling pathways that govern cell division. This study investigated the effect of altering Flii on the divisional orientation of epidermal progenitor cells (EpSCs) in the basal layer during late murine embryonic development and early adolescence. The effect of altering Flii expression on asymmetric vs. symmetric division was assessed in vitro in adult human primary keratinocytes and in vivo at late embryonic development stages (E16, E17 and E19) as well as adolescence (P21 day-old) in mice with altered Flii expression (Flii knockdown: Flii+/−, wild type: WT, transgenic Flii overexpressing: FliiTg/Tg) using Western blot and immunohistochemistry. Flii+/− embryonic skin showed increased asymmetrical cell division of EpSCs with an increase in epidermal stratification and elevated talin, activated-Itgb1 and Par3 expression. FliiTg/Tg led to increased symmetrical cell division of EpSCs with increased cell proliferation rate, an elevated epidermal SOX9, Flap1 and β-cat expression, a thinner epidermis, but increased hair follicle number and depth. Flii promotes symmetric division of epidermal progenitor cells during murine embryonic development.
Effect of Neferine on DNCB-Induced Atopic Dermatitis in HaCaT Cells and BALB/c Mice
Authors: Yang Chung-Chi , Hung Yen-Ling , Ko Wen-Chin , Tsai Yi-Ju , Chang Jia-Feng , Liang Cher-Wei , Chang Der-Chen , Hung Chi-Feng
Published: August 2021

Atopic dermatitis (AD) is a chronic and persistent inflammatory skin disease characterized by eczematous lesions and itching, and it has become a serious health problem. However, the common clinical treatments provide limited relief and are accompanied by adverse effects. Therefore, there is a need to develop novel and effective therapies to treat AD. Neferine is a small molecule compound isolated from the green embryo of the mature seeds of lotus (Nelumbo nucifera). It has a bisbenzylisoquinoline alkaloid structure. Relevant studies have shown that neferine has many pharmacological and biological activities, including anti-inflammatory, anti-thrombotic, and anti-diabetic activities. However, there are very few studies on neferine in the skin, especially the related effects on inflammatory skin diseases. In this study, we proved that it has the potential to be used in the treatment of atopic dermatitis. Through in vitro studies, we found that neferine inhibited the expression of cytokines and chemokines in TNF-α/IFN-γ-stimulated human keratinocyte (HaCaT) cells, and it reduced the phosphorylation of MAPK and the NF-κB signaling pathway. Through in vivo experiments, we used 2,4-dinitrochlorobenzene (DNCB) to induce atopic dermatitis-like skin inflammation in a mouse model. Our results show that neferine significantly decreased the skin barrier damage, scratching responses, and epidermal hyperplasia induced by DNCB. It significantly decreased transepidermal water loss (TEWL), erythema, blood flow, and ear thickness and increased surface skin hydration. Moreover, it also inhibited the expression of cytokines and the activation of signaling pathways. These results indicate that neferine has good potential as an alternative medicine for the treatment of atopic dermatitis or other skin-related inflammatory diseases.
Mechanisms of Immunotoxicity: Stressors and Evaluators
Authors: Bou Zerdan Maroun , Moussa Sara , Atoui Ali , Assi Hazem I.
Published: August 2021

The immune system defends the body against certain tumor cells and against foreign agents such as fungi, parasites, bacteria, and viruses. One of its main roles is to distinguish endogenous components from non-self-components. An unproperly functioning immune system is prone to primary immune deficiencies caused by either primary immune deficiencies such as genetic defects or secondary immune deficiencies such as physical, chemical, and in some instances, psychological stressors. In the manuscript, we will provide a brief overview of the immune system and immunotoxicology. We will also describe the biochemical mechanisms of immunotoxicants and how to evaluate immunotoxicity.
Differential Angiogenic Potential of 3-Dimension Spheroid of HNSCC Cells in Mouse Xenograft
Authors: Choi So-Young , Kang Soo Hyun , Oh Su Young , Lee Kah Young , Lee Heon-Jin , Gum Sangil , Kwon Tae-Geon , Kim Jin-Wook , Lee Sung-Tak , Hong Yoo Jin , Kim Dae-Geon , Hong Su-Hyung
Published: August 2021

The experimental animal model is still essential in the development of new anticancer drugs. We characterized mouse tumors derived from two-dimensional (2D) monolayer cells or three-dimensional (3D) spheroids to establish an in vivo model with highly standardized conditions. Primary cancer-associated fibroblasts (CAFs) were cultured from head and neck squamous cell carcinoma (HNSCC) tumor tissues and co-injected with monolayer cancer cells or spheroids into the oral mucosa of mice. Mice tumor blood vessels were stained, followed by tissue clearing and 3D Lightsheet fluorescent imaging. We compared the effect of exosomes secreted from 2D or 3D culture conditions on the angiogenesis-related genes in HNSCC cells. Our results showed that both the cells and spheroids co-injected with primary CAFs formed tumors. Interestingly, vasculature was abundantly distributed inside the spheroid-derived but not the monolayer-derived mice tumors. In addition, cisplatin injection more significantly decreased spheroid-derived but not monolayer-derived tumor size in mice. Additionally, exosomes isolated from co-culture media of FaDu spheroid and CAF upregulated angiogenesis-related genes in HNSCC cells as compared to exosomes from FaDu cell and CAF co-culture media under in vitro conditions. The mouse tumor xenograft model derived from 3D spheroids of HNSCC cells with primary CAFs is expected to produce reliable chemotherapy drug screening results given the robust angiogenesis and lack of necrosis inside tumor tissues.
Rare Gain-of-Function KCND3 Variant Associated with Cerebellar Ataxia, Parkinsonism, Cognitive Dysfunction, and Brain Iron Accumulation
Authors: Hsiao Cheng-Tsung , Tropea Thomas F. , Fu Ssu-Ju , Bardakjian Tanya M. , Gonzalez-Alegre Pedro , Soong Bing-Wen , Tang Chih-Yung , Jeng Chung-Jiuan
Published: August 2021

Loss-of-function mutations in the KV4.3 channel-encoding KCND3 gene are linked to neurodegenerative cerebellar ataxia. Patients suffering from neurodegeneration associated with iron deposition may also present with cerebellar ataxia. The mechanism underlying brain iron accumulation remains unclear. Here, we aim to ascertain the potential pathogenic role of KCND3 variant in iron accumulation-related cerebellar ataxia. We presented a patient with slowly progressive cerebellar ataxia, parkinsonism, cognitive impairment, and iron accumulation in the basal ganglia and the cerebellum. Whole exome sequencing analyses identified in the patient a heterozygous KCND3 c.1256G>A (p.R419H) variant predicted to be disease-causing by multiple bioinformatic analyses. In vitro biochemical and immunofluorescence examinations revealed that, compared to the human KV4.3 wild-type channel, the p.R419H variant exhibited normal protein abundance and subcellular localization pattern. Electrophysiological investigation, however, demonstrated that the KV4.3 p.R419H variant was associated with a dominant increase in potassium current amplitudes, as well as notable changes in voltage-dependent gating properties leading to enhanced potassium window current. These observations indicate that, in direct contrast with the loss-of-function KCND3 mutations previously reported in cerebellar ataxia patients, we identified a rare gain-of-function KCND3 variant that may expand the clinical and molecular spectra of neurodegenerative cerebellar disorders associated with brain iron accumulation.
Stochastic Spatial Heterogeneity in Activities of H+-ATP-Ases in Electrically Connected Plant Cells Decreases Threshold for Cooling-Induced Electrical Responses
Authors: Sukhova Ekaterina , Ratnitsyna Daria , Sukhov Vladimir
Published: August 2021

H+-ATP-ases, which support proton efflux through the plasma membrane, are key molecular transporters for electrogenesis in cells of higher plants. Initial activities of the transporters can influence the thresholds of generation of electrical responses induced by stressors and modify other parameters of these responses. Previously, it was theoretically shown that the stochastic heterogeneity of individual cell thresholds for electrical responses in a system of electrically connected neuronal cells can decrease the total threshold of the system (“diversity-induced resonance”, DIR). In the current work, we tested a hypothesis about decreasing the thresholds of generation of cooling-induced electrical responses in a system of electrically connected plant cells with increasing stochastic spatial heterogeny in the initial activities of H+-ATP-ases in these cells. A two-dimensional model of the system of electrically connected excitable cells (simple imitation of plant leaf), which was based on a model previously developed in our works, was used for the present investigation. Simulation showed that increasing dispersion in the distribution of initial activities of H+-ATP-ases between cells decreased the thresholds of generation of cooling-induced electrical responses. In addition, the increasing weakly influenced the amplitudes of electrical responses. Additional analysis showed two different mechanisms of the revealed effect. The increasing spatial heterogeneity in activities of H+-ATP-ases induced a weak positive shift of the membrane potential at rest. The shift decreased the threshold of electrical response generation. However, the decreased threshold induced by increasing the H+-ATP-ase activity heterogeneity was also observed after the elimination of the positive shift. The result showed that the “DIR-like” mechanism also participated in the revealed effect. Finally, we showed that the standard deviation of the membrane potentials before the induction of action potentials could be used for the estimation of thresholds of cooling-induced plant electrical responses. Thus, spatial heterogeneity in the initial activities of H+-ATP-ases can be a new regulatory mechanism influencing the generation of electrical responses in plants under actions of stressors.
Determination of Branched-Chain Amino Acids in Food Supplements and Human Plasma by a CE-MS/MS Method with Enhanced Resolution
Authors: Piestansky Juraj , Matuskova Michaela , Cizmarova Ivana , Olesova Dominika , Mikus Peter
Published: August 2021

In the presented study, a capillary electrophoresis-mass spectrometry method combining high separation efficiency and sensitive detection has been developed and validated, for the first time, to quantify branched chain amino acids (valine, isoleucine, leucine) in commercial food and sport supplement samples and human plasma samples. The separations were performed in a bare fused silica capillary. The background electrolyte was composed of 500 mM formic acid with pH 2.0. The plasma sample pretreatment was realized by simple protein precipitation with acetonitrile. Injection of a short zone of highly basic electrolyte before the sample injection and application of the negative pressure on the separation were accompanied by enhanced resolution of the isobaric amino acids—isoleucine and leucine. The developed method was characterized by favorable validation parameters, such as linearity (r2 > 0.99), accuracy and precision, the limit of detection, lower limit of quantification, or robustness. These parameters were more than sufficient for the quantification of branched chain amino acids in various samples. The determined concentrations of branched chain amino acids in food and sports supplements were in very good agreement with the content declared by the manufacturer. The investigated concentrations of branched chain amino acids were in the range 294.68–359.24 µM for valine, 91.76–95.67 µM for isoleucine, and 196.78–251.24 µM for leucine. These concentrations fall within the physiological limits. The developed CE-MS/MS method represents a suitable alternative to traditional approaches used in branched chain amino acid quality control and bioanalysis.
Physiological and Molecular Responses of Six Apple Rootstocks to Osmotic Stress
Authors: Hezema Yasmine S. , Shukla Mukund R. , Ayyanath Murali M. , Sherif Sherif M. , Saxena Praveen K.
Published: August 2021

The growth and productivity of several apple rootstocks have been evaluated in various previous studies. However, limited information is available on their tolerance to osmotic stress. In the present study, the physiological and molecular responses as well as abscisic acid (ABA) levels were assessed in six apple rootstocks (M26, V3, G41, G935, B9 and B118) osmotically stressed with polyethylene glycol (PEG, 30%) application under greenhouse conditions. Our results showed that V3, G41, G935 and B9 had higher relative water content (RWC), and lower electrolyte leakage (EL) under stress conditions compared to M26 and B118. Additionally, water use efficiency (WUE) was higher in V3, G41 and B9 than M26, which might be partially due to the lower transpiration rate in these tolerant rootstocks. V3, G41 and B9 rootstocks also displayed high endogenous ABA levels which was combined with a reduction in stomatal conductance and decreased water loss. At the transcriptional level, genes involved in ABA-dependent and ABA-independent pathways, e.g., SnRK, DREB, ERD and MYC2, showed higher expression in V3, G41, G935 and B9 rootstocks compared to M26 in response to stress. In contrast, WRKY29 was down-regulated in response to stress in the tolerant rootstocks, and its expression was negatively correlated with ABA content and stomatal closure. Overall, the findings of this study showed that B9, V3 and G41 displayed better osmotic stress tolerance followed by G935 then M26 and B118 rootstocks.
A Critical Assessment of the Association between HLA-G Expression by Carcinomas and Clinical Outcome
Authors: van de Water Ricky B. , Krijgsman Daniëlle , Houvast Ruben D. , Vahrmeijer Alexander L. , Kuppen Peter J. K.
Published: August 2021

Human leukocyte antigen-G (HLA-G) conveys immunological tolerance at the maternal-foetal interface. HLA-G expression by tumour cells may also play such a role, resulting in tumour immune evasion, making HLA-G a potential target for immunotherapies. The aim of this review was to determine to what extent it is justified that HLA-G expression is considered as a target for immune checkpoint inhibiting therapy by critically assessing the association between HLA-G expression by carcinomas and clinical outcome of patients. The used HLA-G-detecting mAb, HLA-G quantification methods and statistically significant HLA-G-associated clinicopathological parameters are discussed. Tumour HLA-G expression correlated with poor clinical outcome in breast, esophageal, gastric and hepatocellular carcinoma patients. Tumour HLA-G expression was not associated with clinical outcome in ovarian and oral carcinoma patients. Cervical, colorectal, lung, and pancreatic carcinoma patients presented discrepant and therefore inconclusive results regarding the association between tumour HLA-G expression and clinical outcome. These disparities might partly be the result of differences in the methodological approach to quantify HLA-G expression between studies. Therefore, implementation of universal methodological procedures is strongly advised. Overall, HLA-G expression did not univocally result in poor clinical outcome of carcinoma patients. This implies that tumour HLA-G expression is not necessarily part of an inhibited tumour-immune response and tumour progression. Consequently, it remains elusive whether HLA-G expression by carcinomas functions as an immune checkpoint molecule affecting a tumour-immune response. It may also reflect derailed control of gene expression in tumours, with no real functional consequences.
Arabidopsis G-Protein β Subunit AGB1 Negatively Regulates DNA Binding of MYB62, a Suppressor in the Gibberellin Pathway
Authors: Qi Xin , Tang Wensi , Li Weiwei , He Zhang , Xu Weiya , Fan Zhijin , Zhou Yongbin , Wang Chunxiao , Xu Zhaoshi , Chen Jun , Gao Shiqin , Ma Youzhi , Chen Ming
Published: August 2021

Plant G proteins are versatile components of transmembrane signaling transduction pathways. The deficient mutant of heterotrimeric G protein leads to defects in plant growth and development, suggesting that it regulates the GA pathway in Arabidopsis. However, the molecular mechanism of G protein regulation of the GA pathway is not understood in plants. In this study, two G protein β subunit (AGB1) mutants, agb1-2 and N692967, were dwarfed after exogenous application of GA3. AGB1 interacts with the DNA-binding domain MYB62, a GA pathway suppressor. Transgenic plants were obtained through overexpression of MYB62 in two backgrounds including the wild-type (MYB62/WT Col-0) and agb1 mutants (MYB62/agb1) in Arabidopsis. Genetic analysis showed that under GA3 treatment, the height of the transgenic plants MYB62/WT and MYB62/agb1 was lower than that of WT. The height of MYB62/agb1 plants was closer to MYB62/WT plants and higher than that of mutants agb1-2 and N692967, suggesting that MYB62 is downstream of AGB1 in the GA pathway. qRT-PCR and competitive DNA binding assays indicated that MYB62 can bind MYB elements in the promoter of GA2ox7, a GA degradation gene, to activate GA2ox7 transcription. AGB1 affected binding of MYB62 on the promoter of GA2ox7, thereby negatively regulating th eactivity of MYB62.
3,6′-Dithiopomalidomide Ameliorates Hippocampal Neurodegeneration, Microgliosis and Astrogliosis and Improves Cognitive Behaviors in Rats with a Moderate Traumatic Brain Injury
Authors: Huang Pen-Sen , Tsai Ping-Yen , Yang Ling-Yu , Lecca Daniela , Luo Weiming , Kim Dong Seok , Hoffer Barry J. , Chiang Yung-Hsiao , Greig Nigel H. , Wang Jia-Yi
Published: August 2021

Traumatic brain injury (TBI) is a leading cause of disability and mortality worldwide. It can instigate immediate cell death, followed by a time-dependent secondary injury that results from disproportionate microglial and astrocyte activation, excessive inflammation and oxidative stress in brain tissue, culminating in both short- and long-term cognitive dysfunction and behavioral deficits. Within the brain, the hippocampus is particularly vulnerable to a TBI. We studied a new pomalidomide (Pom) analog, namely, 3,6′-dithioPom (DP), and Pom as immunomodulatory imide drugs (IMiD) for mitigating TBI-induced hippocampal neurodegeneration, microgliosis, astrogliosis and behavioral impairments in a controlled cortical impact (CCI) model of TBI in rats. Both agents were administered as a single intravenous dose (0.5 mg/kg) at 5 h post injury so that the efficacies could be compared. Pom and DP significantly reduced the contusion volume evaluated at 24 h and 7 days post injury. Both agents ameliorated short-term memory deficits and anxiety behavior at 7 days after a TBI. The number of degenerating neurons in the CA1 and dentate gyrus (DG) regions of the hippocampus after a TBI was reduced by Pom and DP. DP, but not Pom, significantly attenuated the TBI-induced microgliosis and DP was more efficacious than Pom at attenuating the TBI-induced astrogliosis in CA1 and DG at 7D after a TBI. In summary, a single intravenous injection of Pom or DP, given 5 h post TBI, significantly reduced hippocampal neurodegeneration and prevented cognitive deficits with a concomitant attenuation of the neuroinflammation in the hippocampus.
Characterization of Sialic Acid Affinity of the Binding Domain of Mistletoe Lectin Isoform One
Authors: Mohammed Soran , Ferry Natalie
Published: August 2021

Sialic acid (Sia) is considered as one of the most important biomolecules of life since its derivatives and terminal orientations on cell membranes and macromolecules play a major role in many biological and pathological processes. To date, there is only a limited number of active molecules that can selectively bind to Sia and this limitation has made the study of this glycan challenging. The lectin superfamily is a well-known family of glycan binding proteins, which encompasses many strong glycan binding peptides with diverse glycan affinities. Mistletoe lectin (ML) is considered one of the most active members of lectin family which was initially classified in early studies as a galactose binding lectin; more recent studies have suggested that the peptide can also actively bind to Sia. However, the details with respect to Sia binding of ML and the domain responsible for this binding are left unanswered because no comprehensive studies have been instigated. In this study, we sought to identify the binding domain responsible for the sialic acid affinity of mistletoe lectin isoform I (MLI) in comparison to the binding activity of elderberry lectin isoform I (SNA), which has long been identified as a potent Sia binding lectin. In order to execute this, we performed computational carbohydrate-protein docking for MLB and SNA with Neu5Ac and β-Galactose. We further analyzed the coding sequence of both lectins and identified their glycan binding domains, which were later cloned upstream and downstream to green fluorescent protein (GFP) and expressed in Escherichia coli (E. coli). Finally, the glycan affinity of the expressed fusion proteins was assessed by using different biochemical and cell-based assays and the Sia binding domains were identified.
The Role of MicroRNA as Clinical Biomarkers for Breast Cancer Surgery and Treatment
Authors: Davey Matthew G. , Davies Molly , Lowery Aoife J. , Miller Nicola , Kerin Michael J.
Published: August 2021

Breast cancer is the most common cancer diagnosed in women. In recent times, survival outcomes have improved dramatically in accordance with our enhanced understanding of the molecular processes driving breast cancer proliferation and development. Refined surgical approaches, combined with novel and targeted treatment options, have aided the personalisation of breast cancer patient care. Despite this, some patients will unfortunately succumb to the disease. In recent times, translational research efforts have been focused on identifying novel biomarkers capable of informing patient outcome; microRNAs (miRNAs) are small non-coding molecules, which regulate gene expression at a post-transcriptional level. Aberrant miRNA expression profiles have been observed in cancer proliferation and development. The measurement and correlation of miRNA expression levels with oncological outcomes such as response to current conventional therapies, and disease recurrence are being investigated. Herein, we outline the clinical utility of miRNA expression profiles in informing breast cancer prognosis, predicting response to treatment strategies as well as their potential as therapeutic targets to enhance treatment modalities in the era of precision oncology.
The Metabolic Effects of Ketones
Authors: Bikman Benjamin T. , Fisher-Wellman Kelsey H.
Published: August 2021

The phrase “once trash, now a treasure” is an apt description of the evolving view of ketones in biomedical research [...]
Cellular and Exosomal Regulations of Sepsis-Induced Metabolic Alterations
Authors: Appiah Michael G. , Park Eun Jeong , Akama Yuichi , Nakamori Yuki , Kawamoto Eiji , Gaowa Arong , Shimaoka Motomu
Published: August 2021

Sepsis is a sustained systemic inflammatory condition involving multiple organ failures caused by dysregulated immune response to infections. Sepsis induces substantial changes in energy demands at the cellular level leading to metabolic reprogramming in immune cells and stromal cells. Although sepsis-associated organ dysfunction and mortality have been partly attributed to the initial acute hyperinflammation and immunosuppression precipitated by a dysfunction in innate and adaptive immune responses, the late mortality due to metabolic dysfunction and immune paralysis currently represent the major problem in clinics. It is becoming increasingly recognized that intertissue and/or intercellular metabolic crosstalk via endocrine factors modulates maintenance of homeostasis, and pathological events in sepsis and other inflammatory diseases. Exosomes have emerged as a novel means of intercellular communication in the regulation of cellular metabolism, owing to their capacity to transfer bioactive payloads such as proteins, lipids, and nucleic acids to their target cells. Recent evidence demonstrates transfer of intact metabolic intermediates from cancer-associated fibroblasts via exosomes to modify metabolic signaling in recipient cells and promote cancer progression. Here, we review the metabolic regulation of endothelial cells and immune cells in sepsis and highlight the role of exosomes as mediators of cellular metabolic signaling in sepsis.
A Potential Role of Semaphorin 3A during Orthodontic Tooth Movement
Authors: Şen Sinan , Lux Christopher J. , Erber Ralf
Published: August 2021

Background: Induced tooth movement during orthodontic therapy requires mechano-induced bone remodeling. Besides various cytokines and growth-factors, neuronal guidance molecules gained attention for their roles in bone homeostasis and thus, potential roles during tooth movement. Several neuronal guidance molecules have been implicated in the regulation of bone remodeling. Amongst them, Semaphorin 3A is particular interesting as it concurrently induces osteoblast differentiation and disturbs osteoclast differentiation. Methods: Mechano-regulation of Sema3A and its receptors PlexinA1 and Neuropilin (RT-qPCR, WB) was evaluated by applying compressive and tension forces to primary human periodontal fibroblasts (hPDLF) and alveolar bone osteoblasts (hOB). The association of the transcription factor Osterix (SP7) and SEMA3A was studied by RT-qPCR. Mechanisms involved in SEMA3A-mediated osteoblast differentiation were assessed by Rac1GTPase pull-downs, β-catenin expression analyses (RT-qPCR) and nuclear translocation assays (IF). Osteogenic markers were analyzed by RT-qPCR. Results: SEMA3A, PLXNA1 and NRP1 were differentially regulated by tension or compressive forces in hPDLF. Osterix (SP7) displayed the same pattern of regulation. Recombinant Sema3A induced the activation of Rac1GTPase, the nuclear translocation of β-catenin and the expression of osteogenic marker genes. Conclusion: Sema3A, its receptors and Osterix are regulated by mechanical forces in hPDLF. SEMA3A upregulation was associated with Osterix (SP7) modulation. Sema3A-enhanced osteogenic marker gene expression in hOB might be dependent on a pathway involving Rac1GTPase and β-catenin. Thus, Semaphorin 3A might contribute to bone remodeling during induced tooth movement.
MiR-7-5p Is Involved in Ferroptosis Signaling and Radioresistance Thru the Generation of ROS in Radioresistant HeLa and SAS Cell Lines
Authors: Tomita Kazuo , Nagasawa Taisuke , Kuwahara Yoshikazu , Torii Seiji , Igarashi Kento , Roudkenar Mehryar Habibi , Roushandeh Amaneh Mohammadi , Kurimasa Akihiro , Sato Tomoaki
Published: August 2021

In cancer therapy, radioresistance or chemoresistance cells are major problems. We established clinically relevant radioresistant (CRR) cells that can survive over 30 days after 2 Gy/day X-ray exposures. These cells also show resistance to anticancer agents and hydrogen peroxide (H2O2). We have previously demonstrated that all the CRR cells examined had up-regulated miR-7-5p and after miR-7-5p knockdown, they lost radioresistance. However, the mechanism of losing radioresistance remains to be elucidated. Therefore, we investigated the role of miR-7-5p in radioresistance by knockdown of miR-7-5p using CRR cells. As a result, knockdown of miR-7-5p increased reactive oxygen species (ROS), mitochondrial membrane potential, and intracellular Fe2+ amount. Furthermore, miR-7-5p knockdown results in the down-regulation of the iron storage gene expression such as ferritin, up-regulation of the ferroptosis marker ALOX12 gene expression, and increases of Liperfluo amount. H2O2 treatment after ALOX12 overexpression led to the enhancement of intracellular H2O2 amount and lipid peroxidation. By contrast, miR-7-5p knockdown seemed not to be involved in COX-2 and glycolysis signaling but affected the morphology of CRR cells. These results indicate that miR-7-5p control radioresistance via ROS generation that leads to ferroptosis.
Arbitrary-Order Bernstein–Bézier Functions for DGFEM Transport on 3D Polygonal Grids
Authors: Hackemack Michael
Published: August 2021

In this paper, we present an arbitrary-order discontinuous Galerkin finite element discretization of the SN transport equation on 3D extruded polygonal prisms. Basis functions are formed by the tensor product of 2D polygonal Bernstein–Bézier functions and 1D Lagrange polynomials. For a polynomial degree p, these functions span {xayb}(a+b)≤p⊗{zc}c∈(0,p) with a dimension of np(p+1)+(p+1)(p−1)(p−2)/2 on an extruded n-gon. Numerical tests confirm that the functions capture exactly monomial solutions, achieve expected convergence rates, and provide full resolution in the thick diffusion limit.
Wheat Resistance to Stripe and Leaf Rusts Conferred by Introgression of Slow Rusting Resistance Genes
Authors: Omara Reda Ibrahim , Shahin Atef Abdelfattah , Ahmed Shaimaa Mahmoud , Mostafa Yasser Sabry , Alamri Saad Abdulrahman , Hashem Mohamed , Elsharkawy Mohsen Mohamed
Published: August 2021

Twenty-three wheat genotypes were evaluated for stripe and leaf rusts, caused by Puccinia striiformis f. sp. tritici and Puccinia triticina f. sp. tritici, respectively, at seedling and adult stages under greenhouses and field conditions during the 2019/2020 and 2020/2021 growing seasons. The race analysis revealed that 250E254 and TTTST races for stripe and leaf rusts, respectively were the most aggressive. Eight wheat genotypes (Misr-3, Misr-4, Giza-171, Gemmeiza-12, Lr34/Yr18, Lr37/Yr17, Lr46/Yr29, and Lr67/Yr46) were resistant to stripe and leaf rusts at seedling and adult stages. This result was confirmed by identifying the resistance genes: Lr34/Yr18, Lr37/Yr17, Lr46/Yr29, and Lr67/Yr46 in these genotypes showing their role in the resistance. Sids-14 and Shandweel-1 genotypes were susceptible to stripe and leaf rusts. Twelve crosses between the two new susceptible wheat genotypes and the three slow rusting genes (Lr34/Yr18, Lr37/Yr17, and Lr67/Yr46) were conducted. The frequency distribution of disease severity (%) in F2 plants of the twelve crosses was ranged from 0 to 80%. Resistant F2 plants were selected and the resistance genes were detected. This study is important for introducing new active resistance genes into the breeding programs and preserving diversity among recently released wheat genotypes.
Banana Cultivar Field Screening for Resistance to Fusarium oxysporum f.sp. cubense Tropical Race 4 in the Northern Territory
Authors: Mintoff Sharl J. L. , Nguyen Tuan V. , Kelly Chris , Cullen Samantha , Hearnden Mark , Williams Robert , Daniells Jeffrey W. , Tran-Nguyen Lucy T. T.
Published: August 2021

Fusarium oxysporum f.sp. cubense, causal agent of Panama disease, is one of the biggest threats to global banana production, particularly the Cavendish competent tropical race 4 (Foc TR4). It continues to spread globally with detections occurring in regions of the Middle East and new continents such as Africa and South America in the last decade. As the search was on for new management strategies and resistant cultivars to combat the disease, a banana cultivar-screening trial took place in the Northern Territory of Australia, which examined the responses of 24 banana cultivars to the soil borne fungus. These cultivars included material from TBRI, FHIA and selections from Thailand, Indonesia and Australia and evaluated for their resistance to tropical race 4 for two cropping cycles. Several cultivars displayed considerable resistance to Foc TR4, including several FHIA parental lines and hybrids, the Cavendish (AAA) selections GCTCV 215 and GCTCV 247 from TBRI and an Indonesian selection CJ19 showed either very little to no plant death due to the disease.
Insight into the Systematics of Novel Entomopathogenic Fungi Associated with Armored Scale Insect, Kuwanaspis howardi (Hemiptera: Diaspididae) in China
Authors: Xu Xiu-Lan , Zeng Qian , Lv Yi-Cong , Jeewon Rajesh , Maharachchikumbura Sajeewa S. N. , Wanasinghe Dhanushka N. , Hyde Kevin D. , Xiao Qian-Gang , Liu Ying-Gao , Yang Chun-Lin
Published: August 2021

This study led to the discovery of three entomopathogenic fungi associated with Kuwanaspis howardi, a scale insect on Phyllostachys heteroclada (fishscale bamboo) and Pleioblastus amarus (bitter bamboo) in China. Two of these species belong to Podonectria: P. kuwanaspidis X.L. Xu & C.L. Yang sp. nov. and P. novae-zelandiae Dingley. The new species P. kuwanaspidis has wider and thicker setae, longer and wider asci, longer ascospores, and more septa as compared with similar Podonectria species. The morphs of extant species P. novae-zelandiae is confirmed based on sexual and asexual morphologies. Maximum likelihood and Bayesian inference analyses of ITS, LSU, SSU, tef1-α, and rpb2 sequence data provide further evidence for the validity of the two species and their placement in Podonectriaceae (Pleosporales). The second new species, Microcera kuwanaspidis X.L. Xu & C.L. Yang sp. nov., is established based on DNA sequence data from ITS, LSU, SSU, tef1-α, rpb1, rpb2, acl1, act, cmdA, and his3 gene regions, and it is characterized by morphological differences in septum numbers and single conidial mass.
Age-Dependent Enclosure Use in Juvenile Chinese Crocodile Lizards, Shinisaurus crocodilurus crocodilurus
Authors: Carter Kimberley C. , Hicks James J. , Kane Daniel , Tapley Benjamin , Michaels Christopher J.
Published: August 2021

This study compared the resource use of juvenile zoo-living Chinese crocodile lizards, Shinisaurus crocodilurus crocodilurus across three observation windows, spanning nine months, accounting for time of day and lizard age, and under consistent environmental conditions. Lizards showed a significant difference in proportionate resource use, quantified using a modified spread of participation indices between the second and final sampling period, such that with increasing age, resources were more equally utilised. The time of day did not have a significant effect on resource use. Lizards in this study significantly increased their use of water bodies and branches outside the bask zone and decreased their use of the land areas within the bask zones over time. Resource use data suggests the importance of providing enclosures which cater to ontogenetic shifts in captive individuals or within mixed age groupings.
The Elucidation of the Molecular Mechanism of the Extrusion Process
Authors: Doskocz Joanna , Dałek Paulina , Przybyło Magdalena , Trzebicka Barbara , Foryś Aleksander , Kobyliukh Anastasiia , Iglič Aleš , Langner Marek
Published: August 2021

Extrusion is a popular method for producing homogenous population of unilamellar liposomes. The technique relies on forcing a lipid suspension through cylindrical pores in a polycarbonate membrane. The quantification of the extrusion and/or recalibration processes make possible the acquisition of experimental data, which can be correlated with the mechanical properties of the lipid bilayer. In this work, the force needed for the extrusion process was correlated with the mechanical properties of a lipid bilayer derived from other experiments. Measurements were performed using a home-made dedicated device capable of maintaining a stable volumetric flux of a liposome suspension through well-defined pores and to continuously measure the extrusion force. Based on the obtained results, the correlation between the lipid bilayer bending rigidity and extrusion force was derived. Specifically, it was found that the bending rigidity of liposomes formed from well-defined lipid mixtures agrees with data obtained by others using flicker-noise spectroscopy or micromanipulation. The other issue addressed in the presented studies was the identification of molecular mechanisms leading to the formation of unilamellar vesicles in the extrusion process. Finally, it was demonstrated that during the extrusion, lipids are not exchanged between vesicles, i.e., vesicles can divide but no membrane fusion or lipid exchange between bilayers was detected.
Clinical Evaluation of Flowable Composite Materials in Permanent Molars Small Class I Restorations: 3-Year Double Blind Clinical Study
Authors: Dukić Walter , Majić Mia , Prica Natalija , Oreški Ivan
Published: August 2021

This study evaluated the 3-year clinical performance of four different flowable composite materials used in Small Class I restorations in permanent molars. This double-blinded, clinical study analyzed 229 Small Class I restorations/103 children at baseline, 12, 24, and 36 months with modified United States Public Health Services (USPHS) criteria. The tested flowable materials were Voco Grandio Flow + Voco Solobond M, Vivadent Tetric EvoFlow + Vivadent Excite, Dentsply X-Flow + Dentsply Prime&Bond NT, and 3M ESPE Filtek Supreme XT Flow + 3M ESPE Scotchbond Universal. The retention and marginal adaptation rates were highest for Grandio Flow and X Flow materials after 36 months, resulting in the highest score of clinical acceptability at 95.3% and 97.6%, respectively. The Tetric EvoFlow and Filtek Supreme XT Flow had the same retention rate after 36 months at 88.1%. Statistical significance was found in Grandio flow material in postoperative sensitivity criteria (p = 0.021). Tetric EvoFlow showed statistical differences in retention (p = 0.01), color match (p = 0.004), and marginal adaptation (p = 0.042). Filtek Supreme showed statistical differences in retention (p = 0.01) and marginal adaptation (p < 0.001). The flowable composite materials showed excellent clinical efficacy after 36 months of their clinical usage. There was no difference among the tested flowable composite materials quality in Small Class I restorations over time.
The Effect of Functionally Graded Materials on Temperature during Frictional Heating: Under Uniform Sliding
Authors: Yevtushenko Aleksander , Topczewska Katarzyna , Zamojski Przemysław
Published: August 2021

The mathematical model of heating process for a friction system made of functionally graded materials (FGMs) was proposed. For this purpose, the boundary-value problem of heat conduction was formulated for two semi-spaces under uniform sliding taking into consideration heating due to friction. Assuming an exponential change in thermal conductivities of the materials, the exact, as well as asymptotic (for small values of time), solutions to this problem were obtained. A numerical analysis was performed for two elements made of ZrO2–Ti-6Al-4V and Al3O2–TiC composites. The influence of the gradient parameters of both materials on the evolution and spatial distributions of the temperature were investigated. The temperatures of the elements made of FGMs were compared with the temperatures found for the homogeneous ceramic materials.