bluuebunny/crossref_metadata_2025 huggingface dataset:
Genistein Ameliorates Renal Fibrosis Through Regulation Snail via m6A RNA Demethylase ALKBH5
Authors: Ning Yichun , Chen Jing , Shi Yiqin , Song Nana , Yu Xiaofang , Fang Yi , Ding Xiaoqiang
Published: November 2020

Renal tubule-interstitial fibrosis is related to chronic kidney disease progression and a typical feature of the aging kidney. Epigenetic modifications of fibrosis-prone genes regulate the development of renal fibrosis. As a kind of “epigenetic diet”, soy isoflavone genistein was reported to have renal protective action and epigenetic-modulating effects. However, its renal protection role and underlying mechanisms are yet to be fully clarified. Herein, we showed that genistein exhibits a demonstrable anti-fibrotic effect on kidney in vivo UUO (unilateral ureteral occlusion) model and renal epithelial cells in vitro model. The mechanism is strongly associated with epithelial-to-mesenchymal transition and m6A RNA demethylase ALKBH5. Mouse fibrotic kidneys induced by UUO exhibited adverse expression of renal fibrosis-related proteins and significant increases in the total m6A level. As an eraser, ALKBH5 showed severer suppression in the renal fibrosis process. However, genistein pretreatment restored ALKBH5 loss remarkably and reduced renal fibrosis, abnormal protein, and inflammatory markers. The examination of possible mechanisms revealed that genistein promoted ALKBH5 and maybe induced the level of mRNA m6A methylation in some epithelial-to-mesenchymal transition-related transcription factors. We found snail was the critical regulator and critical for the protective role of genistein. To verify the relationship between ALKBH5 and snail, we generated knockdown and overexpression of ALKBH5 cells in vitro. ALKBH5 knockdown enhanced the mesenchymal phenotype marker α-smooth muscle actin and snail expression. In agreement, overexpression ALKBH5 increased epithelial adhesion molecule E-cadherin and reduced snail expression. In conclusion, genistein increased renal ALKBH5 expression in UUO-induced renal fibrosis and reduced RNA m6A levels and ameliorates renal damages.
Micellized Protein Transduction Domain-Bone Morphogenetic Protein-7 Efficiently Blocks Renal Fibrosis Via Inhibition of Transforming Growth Factor-Beta–Mediated Epithelial–Mesenchymal Transition
Authors: Kim Seonghun , Jeong Cheol-Hee , Song Sang Hyun , Um Jo Eun , Kim Hyun Sil , Yun Jun Seop , Han Dawool , Cho Eunae Sandra , Nam Bo Young , Yook Jong In , Ku Minhee , Yang Jaemoon , Kim Man-Deuk , Kim Nam Hee , Yoo Tae-Hyun
Published: November 2020

Tubulointerstitial renal fibrosis is a chronic disease process affecting chronic kidney disease (CKD). While the etiological role of transforming growth factor-beta (TGF-β) is well known for epithelial–mesenchymal transition (EMT) in chronic kidney disease, effective therapeutics for renal fibrosis are largely limited. As a member of the TGF-β superfamily, bone morphogenetic protein-7 (BMP-7) plays an important role as an endogenous antagonist of TGF-β, inhibiting fibrotic progression in many organs. However, soluble rhBMP-7 is hardly available for therapeutics due to its limited pharmacodynamic profile and rapid clearance in clinical settings. In this study, we have developed a novel therapeutic approach with protein transduction domain (PTD) fused BMP-7 in micelle (mPTD-BMP-7) for long-range signalingin vivo. Contrary to rhBMP-7 targeting its cognate receptors, the nano-sized mPTD-BMP-7 is transduced into cells through an endosomal pathway and secreted to the exosome having active BMP-7. Further, transduced mPTD-BMP-7 successfully activates SMAD1/5/8 and inhibits the TGF-β–mediated epithelial–mesenchymal transition processin vitroand in anin vivounilateral ureter obstruction model. To determine the clinical relevance of our strategy, we also developed an intra-arterial administration of mPTD-BMP-7 through renal artery in pigs. Interestingly, mPTD-BMP-7 through renal artery intervention effectively delivered into Bowman’s space and inhibits unilateral ureter obstruction–induced renal fibrosis in pigs. Our results provide a novel therapeutic targeting TGF-β–mediated renal fibrosis and other organs as well as a clinically available approach for kidney.
Metabolic Profile and Performance Responses of Ranunculus asiaticus L. Hybrids as Affected by Light Quality of Photoperiodic Lighting
Authors: Carillo Petronia , Dell’Aversana Emilia , Modarelli Giuseppe Carlo , Fusco Giovanna Marta , De Pascale Stefania , Paradiso Roberta
Published: November 2020

Ranunculus asiaticus is a quantitative long day plant grown for cut flowers and flowering potted plants production. We evaluated the influence of light spectrum of three light sources for end-of-day photoperiodic treatments, with different phytochrome photoequilibria (PPE) induced at plant level, on the metabolic profiling of two hybrids of R. asiaticus L., MBO and MDR, in plants from vernalized tuberous roots. The following treatments were compared with natural day length (NL): white fluorescence lamp (FL, PPE 0.84), light emitting diodes (LEDs) Red:Far Red light at 3:1 ratio (R:FR 3:1, PPE 0.84), and LEDs Red:Far Red light at 1:3 ratio (R:FR 1:3, PPE 0.63). Measurements were carried out to evaluate the time course of carbohydrate, amino acid, and protein levels throughout the growing cycle in tuberous roots and leaves, in relation to the different plant stages (pre-planting, vegetative phase, and flowering). The study of metabolic profiling suggested that the differences between the tuberous root reserves of the two R. asiaticus hybrids could be responsible for the capacity of MBO to exert an early flowering. In particular, the proton-consuming synthesis during the pre-planting of two amino acids, alanine and γ-aminobutyric acid (GABA), is able to buffer the cytoplasmic acidosis and pH altered by the vernalization process, and GABA itself can efficiently scavenge reactive oxygen species. This fast response to the stress caused by vernalization allows MBO plants to accelerate the process of vegetative development and flowering. Some other changes in metabolites profile were certainly related to the different responses to day length and photoperiodic light quality in the two hybrids, such as dose exerted by low R:FR lighting in both MBO and MDR. However, most of the responses are under a strict genetic control.
Influence of Organized vs Non Organized Physical Activity on School Adaptation Behavior
Authors: Mosoi Adrian A. , Beckmann Jürgen , Mirifar Arash , Martinent Guillaume , Balint Lorand
Published: November 2020

It is now well-established that physical activity has positive effects on both physical and mental health. However, the influence of organized physical activity (i.e., programs controlled and supervised by a trainer) on school adaptive behavior of adolescents with disabilities and/or behavioral disorders remains unclear. School behavior adaptation involves the ability to learn, conform to school norms and manage school activities without major behavior conflicts. A cross-sectional study was conducted to test the differences between organized physical activity and non-organized physical activity in an after school program. Eighty Romanian adolescents were recruited and allocated to three groups: (a) with disabilities [Ds;N= 17,Mage= 14.55 years (SD= 1.16), 12 males and 5 females], (b) with conduct disorders [CDs,N= 21,Mage= 14.52 years (SD= 1.11) 16 males and 5 females], and (c) participants who had not shown signs of conduct disorders or disabilities [as a control group;N= 42,Mage= 14.2 years (SD= 0.46) 20 males and 22 females]. Personality traits, school behavior, and sensorimotor coordination were assessed by using the Eysenck personality questionnaire—junior scale, school in-adaptability questionnaire scale, and Vienna Test System Sport (SMK—sensorimotor coordination test) respectively. Multivariate analysis of variance MANOVA (3 × 3) and discriminant analysis were used to examine differences between the psychological and sensorimotor coordination outcomes across three groups and three types of physical activity context: (a) organized physical activity, (b) non-organized physical activity, and (c) no physical activity. The findings indicate that not participating in an organized physical activity program results in a reduced level of physical mobility and consequently is associated with maladaptive social and psychological outcomes. Thus, we argued that attending in an organized physical activity program is more beneficial for participants with disabilities and/or behavior disorders, due to an increase in the probability of school integration and development of their motor skills. Clearly more research is needed in order to investigate these effects in neurophysiological levels.
Supporting Patients With Untreated Prostate Cancer on Active Surveillance: What Causes an Increase in Anxiety During the First 10 Months?
Authors: Alvisi Maria Francesca , Dordoni Paola , Rancati Tiziana , Avuzzi Barbara , Nicolai Nicola , Badenchini Fabio , De Luca Letizia , Magnani Tiziana , Marenghi Cristina , Menichetti Julia , Silvia Villa , Fabiana Zollo , Roberto Salvioni , Riccardo Valdagni , Lara Bellardita ,   the Prostate Cancer Multidisciplinary Clinic Working Group
Published: November 2020

Background

The psychological burden possibly deriving from not immediately undergoing radical treatment for prostate cancer (PCa) could be a potential disadvantage of active surveillance (AS), especially in the eve of some relevant clinical exams [i.e., re-biopsy, prostate-specific antigen (PSA) test, and medical examination]. Even if it is known from the literature that the majority of PCa men in AS do not report heightened anxiety, there is a minority of patients who show clinically significant levels of anxiety after diagnosis. The present study aimed to investigate if demographic, clinical, and psychological variables at the entrance in AS (T0) were associated with the risk of developing clinically significant PCa-related anxiety 2 months before the first re-biopsy (T1) and to offer psychological support to improve quality of life (QoL).

Materials and Methods

A total of 236 patients participated in the PCa Research International: AS (PRIAS) protocol and in PRIAS-QoL study. Demographic/clinical features, health-related QoL domains, coping with cancer, PCa-related anxiety [Memorial Anxiety Scale for PCa (MAX-PC)], personality traits, and decision-making-related factors were assessed at T0. MAX-PC was also administered at T1. PCa-related anxiety at T1 was considered to be of clinical significance if the MAX-PC score was ≥1.5. Multivariable logistic regression coupled to bootstrap was used to detect factors associated with high levels of anxiety.

Results

The median age was 64.4 years. Fifty-six patients (24%) reported MAX-PC total score above the cutoff. Three factors were associated with a high level of PCa anxiety at T1: anxious preoccupation [odds ratio (OR) = 4.36], extraversion (OR = 1.9), and prostate-related symptoms (median OR = 0.46). Physical well-being was associated with a low PCa anxiety subscale (median OR = 0.15); neuroticism and functional well-being were associated with PSA anxiety (median OR = 7.05 and 0.73, respectively). Neuroticism and helplessness/hopelessness were associated with fear of progression (median OR = 18.1 and 5.8, respectively).

Conclusion

Only a partial portion of the sample experienced significant levels of anxiety after 10 months. Psychological assessment should be routinely conducted to detect risk factors (i.e., anxious preoccupation, extraversion) for increased anxiety, offering tailored psychological interventions aimed at promoting interpersonal awareness and emotional well-being.
The Power of Empowerment: Predictors and Benefits of Shared Leadership in Organizations
Authors: Edelmann Charlotte M. , Boen Filip , Fransen Katrien
Published: November 2020

Leadership plays an essential part in creating competitive advantage and well-being among employees. One way in which formal leaders can deal with the variety of responsibilities that comes with their role is to share their responsibilities with team members (i.e., shared leadership). Although there is abundant literature on how high-quality peer leadership benefits team effectiveness (TE) and well-being, there is only limited evidence about the underpinning mechanisms of these relationships and how the formal leader can support this process. To address this lacuna, we conducted an online survey study with 146 employees from various organizations. The results suggest that an empowering leadership style of the formal leader is associated with higher perceived peer leadership quality (PLQ) on four different leadership roles (i.e., task, motivational, social, and external leader). In addition, formal leaders who empower their team members are also perceived as better leaders themselves. Moreover, the improved PLQ was in turn positively related to TE and work satisfaction, while being negatively related to burnout. In line with the social identity approach, we found that team identification mediated these relationships. Thus, high-quality peer leaders succeeded in creating a shared sense of “us” in the team, and this team identification in turn generated all the positive outcomes. To conclude, by sharing their lead and empowering the peer leaders in their team, formal leaders are key drivers of the team’s effectiveness, while also enhancing team members’ health and well-being.
Preverbal Production and Early Lexical Development in Children With Cochlear Implants: A Longitudinal Study Following Pre-implanted Children Until 12 Months After Cochlear Implant Activation
Authors: Majorano Marinella , Brondino Margherita , Morelli Marika , Ferrari Rachele , Lavelli Manuela , Guerzoni Letizia , Cuda Domenico , Persici Valentina
Published: November 2020

Studies have shown that children vary in the trajectories of their language development after cochlear implant (CI) activation. The aim of the present study is to assess the preverbal and lexical development of a group of 20 Italian-speaking children observed longitudinally before CI activation and at three, 6 and 12 months after CI surgery (mean age at the first session: 17.5 months; SD: 8.3; and range: 10–35). The group of children with CIs (G-CI) was compared with two groups of normally-hearing (NH) children, one age-matched (G-NHA; mean age at the first session: 17.4 months; SD: 8.0; and range: 10–34) and one language-matched (G-NHL;n= 20; mean age at the first session: 11.2 months; SD: 0.4; and range: 11–12). The spontaneous interactions between children and their mothers during free-play were transcribed. Preverbal babbling production and first words were considered for each child. Data analysis showed significant differences in babbling and word production between groups, with a lower production of words in children with CIs compared to the G-NHA group and a higher production of babbling compared to the G-NHL children. Word production 1 year after activation was significantly lower for the children with CIs than for language-matched children only when maternal education was controlled for. Furthermore, latent class growth analysis showed that children with CIs belonged mainly to classes that exhibited a low level of initial production but also progressive increases over time. Babbling production had a statistically significant effect on lexical growth but not on class membership, and only for groups showing slower and constant increases. Results highlight the importance of preverbal vocal patterns for later lexical development and may support families and speech therapists in the early identification of risk and protective factors for language delay in children with CIs.
Two's Company, Three's a Crowd? Maternal and Paternal Talk About Their Infant Differs in Associations With Wellbeing, Couple Relationship Quality, and Caregiving Sensitivity
Authors: Foley Sarah , Álvarez Carolina , McCarthy Jade , Hughes Claire
Published: November 2020

Problems of depression and anxiety are common in early parenthood and adversely affect parenting quality (1). Rumination is closely linked to poor wellbeing (2), suggesting that self-focus may be one mediator of the association between wellbeing and caregiving [e.g., (3)]. Framed within an international study of first-time mothers and fathers (4), the current study included 396 British mothers and fathers (in 198 heterosexual cohabiting couple relationships) of first-born 4-month-old infants. Parents reported on their symptoms of depression, anxiety and satisfaction in their couple relationship. Five-minute speech samples were transcribed and coded for parents' pronoun use (i.e., “I” and either infant- or partner-inclusive use of “We”), whilst observations in the Still-Face paradigm were coded for parental sensitivity to infants' cues. Our first goal was to test whether new parents' self-focus was associated with wellbeing and couple relationship quality. We also examined whether (i) self-focus mediated the expected association between wellbeing and caregiving sensitivity and (ii) couple relationship quality moderated the expected association between self-focus and caregiver sensitivity. Finally, we compared results for mothers and fathers. Our results illustrate gender-specific associations. First, although mean levels of self-focus and partner-inclusive talk were similar for mothers and fathers, infant-inclusive use of the “we” pronoun was higher in mothers than fathers. Second, self-focus was unrelated to either mothers' or fathers' wellbeing, but was associated with fathers' report of reduced couple relationship quality. In addition, poor perinatal wellbeing was associated with reduced partner-inclusive talk for fathers, but with reduced use of infant-inclusive talk for mothers. Third, mediation models suggest that reduced infant-inclusive talk underpins the association between poor wellbeing and reduced sensitivity in mothers, but not fathers. Fourth, in the context of good couple relationship quality, mothers' elevated partner-inclusive talk was associated with reduced caregiving sensitivity. These findings are discussed in terms of their implications for interventions to support new mothers and fathers, who may benefit from distinct strategies to foster attention to their developing infant.
No Two Workforces Are the Same: A Systematic Review of Enumerations and Definitions of Public Health Workforces
Authors: Watts Rory D. , Bowles Devin C. , Ryan Eli , Fisher Colleen , Li Ian W.
Published: November 2020

The delivery and coordination of public health functions is essential to national and global health, however, there are considerable problems in defining the people who work in public health, as well as estimating their number. Therefore, the aim of this systematic review was to identify and explore research which has defined and enumerated public health workforces. In particular, how were such workforces defined? Who was included in these workforces? And how did researchers make judgments about the size of a workforce? In this systematic review, we identified 82 publications which enumerated a public health workforce between 2000 and November 2018. Most workforce definitions were unique and study-specific and included workers based on their occupation or their place of work. Common occupations included public health nurses and physicians, epidemiologists, and community health workers. National workforces varied by size, with the United States and Switzerland having the largest public health workforces per-capita, although definitions used varied substantially. Normative assessments (e.g., assessments of ideal workforce size) were informed through opinion, benchmarks or “service-target” models. There are very few regular, consistent enumerations within countries, and fewer still which capture a substantial proportion of the public heath workforce. Assessing the size of the public health workforce is often overlooked and would be aided by fit-for-purpose data, alignment of occupations and functions to international standards, and transparency in normative methods.
Ultrasonic Cutting of Frozen Semen Straws to Optimize the Use of Spermatozoa for In Vitro Fertilization
Authors: Kim Sung Woo , Lee Jae-Yeong , Kim Bongki , Kim Chan-Lan , Hwang In-Sul , Ko Yeoung-Gyu , Lee Sung-Soo
Published: November 2020

The objective of the present study was to establish conditions for using technology that can potentially enhance the efficiency of bovine embryos derived from in vitro fertilization (IVF) with frozen semen. Frozen semen from selected bulls can be stored indefinitely in liquid nitrogen as genetic resources; however, these resources are considered consumable because they cannot be regenerated. Therefore, to optimize the utilization of frozen semen, as many oocytes as possible should be fertilized with one straw. However, a sufficient number of prepared oocytes might not be available for one experiment, which can limit the use of the total spermatozoa population. Thus, an economical method for producing embryos needs to be established by optimizing technology for transplantable embryos. In this study, the utilization of frozen semen was increased by dividing the straw with an ultrasonic cutter. The post-thaw survival rate of uncut straws from Korean Proven Bulls did not differ from that of half cuttings. When ultrasonic cutting was applied to frozen semen, spermatozoa could be prepared for IVF trials at least four times, and blastocysts were produced. Therefore, cutting frozen semen with an ultrasonic cutter represents a potentially useful tool to expand genetic resources from excellent breeding stocks. This approach could also be valuable in the field of IVF of endangered species or rare breeds for their preservation, as well as in ovum pick-up (OPU) techniques.
Ancylostoma ceylanicum: The Neglected Zoonotic Parasite of Community Dogs in Thailand and Its Genetic Diversity among Asian Countries
Authors: Kladkempetch Doolyawat , Tangtrongsup Sahatchai , Tiwananthagorn Saruda
Published: November 2020

Ancylostoma ceylanicum is a zoonotic helminth that is commonly found in domestic dogs and cats throughout Asia but is largely neglected in many countries. This study aimed to confirm the species of hookworm in dogs and soil environments and investigate the evolutionary analyses of A. ceylanicum among Thai and Asian populations. In a total of 299 dog fecal samples and 212 soil samples from 53 temples, the prevalence rates of hookworm infection by microscopic examination were 26.4% (79/299) and 10.4% (22/212) in dog and soil samples, respectively. A PCR-RFLP targeting the ITS region was then utilized to identify the hookworm species. In dogs, A. ceylanicum was the main hookworm species, and the rates of A. ceylanicum and A. caninum infections were 96.6% and 3.5%, respectively. The genetic characterization and diversity indices of the A. ceylanicumcox1 gene among Thai and Asian populations were evaluated. Nine haplotypes were identified from Thai A. ceylanicum, in which the haplotype diversity and the nucleotide diversity were 0.4436 and 0.0036, respectively. The highest nucleotide diversity of Chinese A. ceylanicum populations suggested that it could be the ancestor of the populations. Pairwise fixation indices indicated that Thai A. ceylanicum was closely related to the Malaysian population, suggesting a gene flow between these populations. The temples with hookworm-positive dogs were associated with the presence of hookworm-contaminated soil, as these levels showed an approximately four-fold increase compared with those in temples with hookworm-negative dogs (OR = 4.38, 95% CI: 1.55–12.37). Interestingly, the genotypes of A. ceylanicum in the contaminating soil and infecting dogs were identical. Therefore, increased awareness and concern from the wider public communities with regard to the responsibility of temples and municipal offices to provide proper deworming programs to community dogs should be strongly endorsed to reduce the risk of the transmission of this zoonotic disease. In addition, parasitic examination and treatment should be strongly implemented before dogs are imported and exported worldwide.
Potential Inhibitory Effect of Apis mellifera’s Venom and of Its Two Main Components—Melittin and PLA2—on Escherichia coli F1F0-ATPase
Authors: Nehme Hala , Ayde Helena , El Obeid Dany , Sabatier Jean Marc , Fajloun Ziad
Published: November 2020

Bacterial resistance has become a worrying problem for human health, especially since certain bacterial strains of Escherichia coli (E. coli) can cause very serious infections. Thus, the search for novel natural inhibitors with new bacterial targets would be crucial to overcome resistance to antibiotics. Here, we evaluate the inhibitory effects of Apis mellifera bee venom (BV-Am) and of its two main components -melittin and phospholipase A2 (PLA2)- on E. coli F1F0-ATPase enzyme, a crucial molecular target for the survival of these bacteria. Thus, we optimized a spectrophotometric method to evaluate the enzymatic activity by quantifying the released phosphate from ATP hydrolysis catalyzed by E. coli F1F0-ATPase. The protocol developed for inhibition assays of this enzyme was validated by two reference inhibitors, thymoquinone (IC50 = 57.5 μM) and quercetin (IC50 = 30 μM). Results showed that BV-Am has a dose-dependent inhibitory effect on E. coli F1F0-ATPase with 50% inhibition at 18.43 ± 0.92 μg/mL. Melittin inhibits this enzyme with IC50 = 9.03 ± 0.27 µM, emphasizing a more inhibitory effect than the two previous reference inhibitors adopted. Likewise, PLA2 inhibits E. coli F1F0-ATPase with a dose-dependent effect (50% inhibition at 2.11 ± 0.11 μg/mL) and its combination with melittin enhanced the inhibition extent of this enzyme. Crude venom and mainly melittin and PLA2, inhibit E. coli F1F0-ATPase and could be considered as important candidates for combating resistant bacteria.
Alpha-Glucosidase and Alpha-Amylase Inhibitory Activities, Molecular Docking, and Antioxidant Capacities of Salvia aurita Constituents
Authors: Etsassala Ninon G. E. R. , Badmus Jelili A. , Marnewick Jeanine L. , Iwuoha Emmanuel I. , Nchu Felix , Hussein Ahmed A.
Published: November 2020

Diabetes mellitus (DM) is one of the most dangerous metabolic diseases with a high rate of mortality worldwide. It is well known that insulin resistance and deficiency in insulin production from pancreatic β-cells are the main characteristics of DM. Due to the detrimental side effects of the current treatment, there is a considerable need to develop new effective antidiabetic drugs, especially alpha-glucosidase and alpha-amylase inhibitors with lesser adverse effects. These inhibitors are known to be directly involved in the delay of carbohydrate digestion, resulting in a reduction of glucose absorption rate and, consequently, reducing the postprandial rise of plasma glucose, which can reduce the risk of long-term diabetes complications. Furthermore, natural products are well-known sources for the discovery of new bioactive compounds that can serve as scaffolds for drug discovery, including that of new antidiabetic drugs. The phytochemical investigation of Salvia aurita collected from Hogobach Pass, Eastern Cape Province, South Africa (SA), yielded four known abietane diterpenes namely carnosol (1), rosmanol (2), 7-methoxyrosmanol (3), 12-methoxycarnosic acid (4), and one flavonoid named 4,7-dimethylapigenin (5). Structural characterization of these isolated compounds was conducted using 1 and 2D NMR, in comparison with reported spectroscopic data. These compounds are reported for the first time from S. aurita. The biological evaluation of the isolated compound against alpha-glucosidase exhibited strong inhibitory activities for 3 and 2 with the half maximal inhibitory concentration (IC50) values of 4.2 ± 0.7 and 16.4 ± 1.1 µg/mL respectively, while 4 and 1 demonstrated strong alpha-amylase inhibitory activity amongst the isolated compounds with IC50 values of 16.2 ± 0.3 and 19.8 ± 1.4 µg/mL. Molecular docking analysis confirms the strong inhibitory activity of 3 against alpha-glucosidase. Additionally, excellent antioxidant capacities were displayed by 2, 1, and 3, respectively, with oxygen radical absorbance capacity (ORAC) (25.79 ± 0.01; 23.96 ± 0.01; 23.94 ± 0.02) mM Trolox equivalent (TE)/g; 1 and 2 as ferric-ion reducing antioxidant power (FRAP) (3.92 ± 0.002; 1.52 ± 0.002) mM ascorbic acid equivalent (AAE)/g; 5 and 2 as Trolox equivalent absorbance capacity (TEAC) (3.19 ± 0.003; 2.06 ± 0.003) mM TE/g. The methanolic extract of S. aurita is a rich source of abietane diterpenes with excellent antioxidant and antidiabetic activities that can be useful to modulate oxidative stress and might possibly be excellent candidates for the management of diabetes. This is the first scientific report on the phytochemical isolation and biological evaluation of the alpha-glucosidase and alpha-amylase inhibitory activities of Salvia aurita.
Antioxidants N-Acetylcysteine and Vitamin C Improve T Cell Commitment to Memory and Long-Term Maintenance of Immunological Memory in Old Mice
Authors: Meryk Andreas , Grasse Marco , Balasco Luigi , Kapferer Werner , Grubeck-Loebenstein Beatrix , Pangrazzi Luca
Published: November 2020

Aging is characterized by reduced immune responses, a process known as immunosenescence. Shortly after their generation, antigen-experienced adaptive immune cells, such as CD8+ and CD4+ T cells, migrate into the bone marrow (BM), in which they can be maintained for long periods of time within survival niches. Interestingly, we recently observed how oxidative stress may negatively support the maintenance of immunological memory in the BM in old age. To assess whether the generation and maintenance of immunological memory could be improved by scavenging oxygen radicals, we vaccinated 18-months (old) and 3-weeks (young) mice with alum-OVA, in the presence/absence of antioxidants vitamin C (Vc) and/or N-acetylcysteine (NAC). To monitor the phenotype of the immune cell population, blood was withdrawn at several time-points, and BM and spleen were harvested 91 days after the first alum-OVA dose. Only in old mice, memory T cell commitment was boosted with some antioxidant treatments. In addition, oxidative stress and the expression of pro-inflammatory molecules decreased in old mice. Finally, changes in the phenotype of dendritic cells, important regulators of T cell activation, were additionally observed. Taken together, our data show that the generation and maintenance of memory T cells in old age may be improved by targeting oxidative stress.
Two-Lane Highways Crest Curve Design. The Case Study of Italian Guidelines
Authors: Guerrieri Marco
Published: November 2020

The main purpose of the research is to evaluate the crest vertical curves radii Rv, not considering a conventional value of the opposing vehicle height h2, but the average vehicle heights h2(m) and the value of the 15th percentile of the height distribution h2(15) of the passenger car population. The study only considered car models with more than 20,000 registered vehicles in Italy. One hundred and fifteen car models belonging to different brands were taken into consideration, for a total of over 9 million vehicles. For the statistical sample analyzed, the following vehicle heights were estimated: h2(m) = 1.48 m and h2(15) = 1.39 m. The deviations between the crest radii calculated with the Italian standard (h2 = 1.10 m), and those obtained for h2(m) = 1.48 m and h2(15) = 1.39 m are up to 12%. The differences ΔHv between the values of the visible vehicle body height Hv = Hv(t) calculated using, respectively, h2(15) = 1.39 m and h2(m) = 1.48 m are modest. The value h2(m) = 1.48 m could be adopted in order to reduce the highways construction costs. In fact, the research shows that the value h2 = 1.10 m is too conservative and leads to oversizing of the crest vertical curves. Therefore, it would be necessary to make an appropriate choice of h2 value in order to take into account the current heights of passenger cars.
A Sensitivity Analysis of the Damage Behavior of a Leading-Edge Subject to Bird Strike
Authors: Di Caprio Francesco , Sellitto Andrea , Saputo Salvatore , Guida Michele , Riccio Aniello
Published: November 2020

This paper aims to investigate the crashworthiness capability of a commercial aircraft metallic sandwich leading edge, subjected to bird strike events. A sensitivity analysis is presented, aimed to assess the influence of the skin parameters (inner and outer faces and core thicknesses) on the leading-edge crashworthiness and to determine, among the configurations able to withstand a bird strike event, the best compromise in terms of weight and structural performances. In order to easily manage the design parameters and the output data, the ModeFrontier code was used in conjunction with the FE code Abaqus/Explicit. A dedicated python routine was developed to define a fully parametric simplified leading-edge model. To fulfill the aerodynamic requirements, the external surfaces were considered fixed during the sensitivity analysis, and, thus, only the internal leading edge’s components were modified to study their influence on the structural response. The total mass of the model, the maximum deformation and the energy dissipated due to material failure and the plastic deformations were monitored and used to compare and assess the behavior of each configuration.
Receiver Integration with Arrayed Waveguide Gratings toward Multi-Wavelength Data-Centric Communications and Computing
Authors: Doi Yoshiyuki , Yoshimatsu Toshihide , Nakanishi Yasuhiko , Tsunashima Satoshi , Nada Masahiro , Kamei Shin , Sano Kimikazu , Ishii Yuzo
Published: November 2020

This paper reviews receivers that feature low-loss multimode-output arrayed waveguide gratings (MM-AWGs) for wavelength division multiplexing (WDM) as well as hybrid integration techniques with high-speed throughput of up to 100 Gb/s and beyond. A design of optical coupling between higher-order multimode beams and a photodiode for a flat-top spectral shape is described in detail. The WDM photoreceivers were fabricated with different approaches. A 10-Gb/s photoreceiver was developed for a 1.25-Gb/s baud rate and assembled for eight-channel WDM by mechanical alignment. A receiver with 40-Gb/s throughput was built by using visual alignment for a 10-Gb/s baud rate and four-channel WDM. A 100-Gb/s receiver assembled by active alignment with a four-channel by 25-Gb/s baud rate is the basis for beyond-100 Gb/s and future multi-wavelength integrated devices toward data-centric communications and computing.
A Study on the External Stone Cladding System in Production and Installation Stages: The Case of Hong Kong
Authors: Yiu Chun Fai , Kim Yoo-Jun , Jeong WoonSeong , Chi Hung-Lin , Kim Min-Koo
Published: November 2020

The successful quality management of the external stone cladding system in production and installation stages is of vital importance to ensure the high quality of the completed system. Nevertheless, little research has been conducted in this area. This research aimed to report the current status of the external stone cladding system in the production and installation stages in Hong Kong. To do so, this paper examines its current practices and major issues occurred through case studies, questionnaire surveys, and interviews. The results revealed the insufficiency in control mechanism and quality control in the system in Hong Kong. Furthermore, the factors to ensure the quality of the two stages were determined. Lastly, this research suggested recommendations on the possible measures to improve the system quality: pre-testing of stone materials and anchorage system, quality assurance of suppliers and manufacturers, regular inspections and audits on production, and continuous site quality supervision and checklist. The findings and outcomes of the research could lead to actions to guarantee steady quality for the stone cladding façade.
Aerodynamic Study of the NASA’s X-43A Hypersonic Aircraft
Authors: Navó Àlex , Bergada Josep M.
Published: November 2020

A 2D aerodynamic study of the NASA’s X-43A hypersonic aircraft is developed using two different approaches. The first one is analytical and based on the resolution of the oblique shock wave and Prandtl–Meyer expansion wave theories supported by an in-house program and considering a simplified aircraft’s design. The second approach involves the use of a Computational Fluid Dynamics (CFD) package, OpenFOAM and the real shape of the aircraft. The aerodynamic characteristics defined as the lift and drag coefficients, the aerodynamic efficiency and the pitching moment coefficient are calculated for different angles of attack. Evaluations are made for an incident Mach number of 7 and an altitude of 30 km. For both methodologies, the required angles of attack to achieve a Vertical Force Balance (VFB) and a completely zero pitching moment conditions are considered. In addition, an analysis to optimise the nose configuration of the aircraft is performed. The mass flow rate throughout the scramjet as a function of the angle of attack is also presented in the CFD model in addition to the pressure, density, temperature and Mach fields. Before presenting the corresponding results, a comparison between the aerodynamic coefficients in terms of the angle of attack of both models is carried out in order to properly validate the CFD model. The paper clarifies the requirements needed to make sure that both oblique shock waves originating from the leading edge meet just at the scramjet inlet clarifying the advantages of fulfilling such condition.
Five-Year Climatology of Local Convections in the Dabie Mountains
Authors: Zheng Linlin , Sun Jianhua , Qiu Xuexing , Yang Zuxiang
Published: November 2020

Local Convection in Dabie Mountains (LCDM) occurs more frequently over the Dabie Mountains and brings severe weather to adjacent areas. In order to understand the characteristics of LCDM, their spatial distribution, the monthly and diurnal variations, and possible mechanisms are investigated. Based on radar composite reflectivity data over the 5-y period of 2014–2018 during warm seasons (April–September), a total of 195 cases of LCDM are identified. The LCDM exhibits maximum frequency on the windward slopes of the Dabie Mountains with a secondary maximum on lee slopes. It is demonstrated that LCDM peaks in July and August, while their diurnal variation exhibits a major peak in the afternoon during 12:00–16:00 local solar time (LST). Most LCDM does not leave the Dabie Mountains (NoOut-Type), accounting for 89.7% overall, and has an average 3.5 h lifespan. In contrast, the lifespans of Out-Types (i.e., LCDMs that move away from the Dabie Mountains) are longer (5.8 h on average), while most Out-Type LCDMs develop on southern slopes (‘South-Type’) and a few are also reinforced on northern slopes (‘North-Type’). The South-Type mainly produces short-duration heavy precipitation, while the ‘North-Type’ predominately generates thunderstorms high winds. It is suggested that LCDM is thermally induced, and that both the ‘South-Type’ and ‘North-Type’ are controlled by southerly wind perturbation. Lifting by upslope wind and heat sources over windward slopes has led to ‘South-Type’ development, while ascent induced by wave-like perturbations on lee slopes has led to ‘North-Type’. These mechanisms should be further investigated in future work by using field experiments and numerical simulations.
SGLT2 Inhibition by Intraperitoneal Dapagliflozin Mitigates Peritoneal Fibrosis and Ultrafiltration Failure in a Mouse Model of Chronic Peritoneal Exposure to High-Glucose Dialysate
Authors: Balzer Michael S. , Rong Song , Nordlohne Johannes , Zemtsovski Jan D. , Schmidt Sonja , Stapel Britta , Bartosova Maria , von Vietinghoff Sibylle , Haller Hermann , Schmitt Claus P. , Shushakova Nelli
Published: November 2020

Peritoneal dialysis (PD) is limited by glucose-mediated peritoneal membrane (PM) fibrosis, angiogenesis, and ultrafiltration failure. Influencing PM integrity by pharmacologically targeting sodium-dependent glucose transporter (SGLT)-mediated glucose uptake has not been studied. In this study, wildtype C57Bl/6N mice were treated with high-glucose dialysate via an intraperitoneal catheter, with or without addition of selective SGLT2 inhibitor dapagliflozin. PM structural changes, ultrafiltration capacity, and peritoneal equilibration testing (PET) status for glucose, urea, and creatinine were analyzed. Expression of SGLT and facilitative glucose transporters (GLUT) was analyzed by real-time PCR, immunofluorescence, and immunohistochemistry. Peritoneal effluents were analyzed for cellular and cytokine composition. We found that peritoneal SGLT2 was expressed in mesothelial cells and in skeletal muscle. Dapagliflozin significantly reduced effluent transforming growth factor (TGF-β) concentrations, peritoneal thickening, and fibrosis, as well as microvessel density, resulting in improved ultrafiltration, despite the fact that it did not affect development of high-glucose transporter status. In vitro, dapagliflozin reduced monocyte chemoattractant protein-1 release under high-glucose conditions in human and murine peritoneal mesothelial cells. Proinflammatory cytokine release in macrophages was reduced only when cultured in high-glucose conditions with an additional inflammatory stimulus. In summary, dapagliflozin improved structural and functional peritoneal health in the context of high-glucose PD.
Visual-Attentional Load Unveils Slowed Processing Speed in Multiple Sclerosis Patients: A Pilot Study with a Tablet-Based Videogame
Authors: Pitteri Marco , Dapor Caterina , Ziccardi Stefano , Guandalini Maddalena , Meggiato Riccardo , Calabrese Massimiliano
Published: November 2020

Slowing in information processing speed (IPS) is the key cognitive deficit in multiple sclerosis (MS). Testing IPS in different cognitive load conditions by using computerized tools might reveal initial IPS slowness underestimated by classic paper-and-pencil tests. To investigate the extent to which IPS can be affected by increased task demands, we developed three tasks based on the manipulation of the visual-attentional load, delivered with a home-made, tablet-based videogame. Fifty-one patients with MS (pwMS), classified as having no cognitive impairment in classic paper-and-pencil tests, and 20 healthy controls (HC) underwent the videogame tasks; reaction times (RTs) and accuracy were recorded. A significant reduced performance of pwMS as compared with HC was found on the videogame tasks, with pwMS being on average slower and less accurate than HC. Furthermore, pwMS showed a significantly more pronounced decrement in accuracy as a function of the visual-attentional load, suggesting a higher susceptibility to increased task demands. Significant correlations among the Symbol Digit Modalities Test (SDMT) and the videogame mean RTs and accuracy were found, providing evidence for the concurrent validity of the videogame as a valid tool to test IPS in pwMS. The high potential that might derive from the adoption of computerized assessment tools in clinical practice should be taken into consideration and investigated further.
Postural Control Dysfunction and Balance Rehabilitation in Older Adults with Mild Cognitive Impairment
Authors: Liu Xuan , Chen Michelle H. , Yue Guang H.
Published: November 2020

Older adults with mild cognitive impairment (MCI) are at an increased risk for falls and fall-related injuries. It is unclear whether current balance rehabilitation techniques largely developed in cognitively intact populations would be successful in older adults with MCI. This mapping review examined the available balance rehabilitation research conducted in older adults with MCI. Databases Medline, Cinahl, Cochrane, PubMed, Scopus, and PsycINFO were systematically searched from inception to August 2020. Twenty-one studies with 16 original randomized controlled trials (RCTs) involving 1201 older adults with MCI (>age 60) met the inclusion criteria, of which 17 studies showed significant treatment effects on balance functions. However, only six studies demonstrated adequate quality (at least single-blind, no significant dropouts, and intervention and control groups are equivalent at baseline) and evidence (medium or large effect size on at least one balance outcome) in improving balance in this population, and none of them are double- or triple-blind. Therefore, more high-quality RCTs are needed to inform future balance rehabilitation program development for older adults with MCI. Moreover, few studies examined the incidence of falls after the intervention, which limits clinical utility. Future RCTs should prospectively monitor falls or changes in risk of falls after the intervention.
The Role of the T2–FLAIR Mismatch Sign as an Imaging Marker of IDH Status in a Mixed Population of Low- and High-Grade Gliomas
Authors: Kapsalaki Eftychia Z. , Brotis Alexandros G. , Tsikrika Alexandra , Tzerefos Christos , Paschalis Thanos , Dardiotis Efthymios , Fountas Konstantinos N.
Published: November 2020

Our study evaluated the role of the T2–fluid-attenuated inversion recovery (FLAIR) mismatch sign in detecting isocitrate dehydrogenase (IDH) mutations based on a mixed sample of 24 patients with low- and high- grade gliomas. The association between the two was realized using univariate and multivariate logistic regression analysis. There was a substantial agreement between the two raters for the detection of the T2–FLAIR mismatch sign (Cohen’s kappa coefficient was 0.647). The T2–FLAIR mismatch sign when co-registered with the degree of tumor homogeneity were significant predictors of the IDH status (OR 29.642; 95% CI 1.73–509.15, p = 0.019). The probability of being IDH mutant in the presence of T2–FLAIR mismatch sign was as high as 92.9% (95% CI 63–99%). The sensitivity and specificity of T2–FLAIR mismatch sign in the detection of the IDH mutation was 88.9% and 86.7%, respectively. The T2–FLAIR mismatch sign may be an easy to use and helpful tool in recognizing IDH mutant patients, particularly if formal IDH testing is not available. We suggest that the adoption of a protocol based on imaging and histological data for optimal glioma characterization could be very helpful.
CPT1A Over-Expression Increases Reactive Oxygen Species in the Mitochondria and Promotes Antioxidant Defenses in Prostate Cancer
Authors: Joshi Molishree , Kim Jihye , D’Alessandro Angelo , Monk Emily , Bruce Kimberley , Elajaili Hanan , Nozik-Grayck Eva , Goodspeed Andrew , Costello James C. , Schlaepfer Isabel R.
Published: November 2020

Cancers reprogram their metabolism to adapt to environmental changes. In this study, we examined the consequences of altered expression of the mitochondrial enzyme carnitine palmitoyl transferase I (CPT1A) in prostate cancer (PCa) cell models. Using transcriptomic and metabolomic analyses, we compared LNCaP-C4-2 cell lines with depleted (knockdown (KD)) or increased (overexpression (OE)) CPT1A expression. Mitochondrial reactive oxygen species (ROS) were also measured. Transcriptomic analysis identified ER stress, serine biosynthesis and lipid catabolism as significantly upregulated pathways in the OE versus KD cells. On the other hand, androgen response was significantly downregulated in OE cells. These changes associated with increased acyl-carnitines, serine synthesis and glutathione precursors in OE cells. Unexpectedly, OE cells showed increased mitochondrial ROS but when challenged with fatty acids and no androgens, the Superoxide dismutase 2 (SOD2) enzyme increased in the OE cells, suggesting better antioxidant defenses with excess CPT1A expression. Public databases also showed decreased androgen response correlation with increased serine-related metabolism in advanced PCa. Lastly, worse progression free survival was observed with increased lipid catabolism and decreased androgen response. Excess CPT1A is associated with a ROS-mediated stress phenotype that can support PCa disease progression. This study provides a rationale for targeting lipid catabolic pathways for therapy in hormonal cancers.