bluuebunny/crossref_metadata_2025 huggingface dataset:
Gaining Insights To Understand The Anti-Inflammatory Functions of Mesenchymal Stem Cell-Derived Conditioned Medium In Combination With Stigmasterol In IL-1β-Stimulated Rat Articular Chondrocytes – An In-Vitro Approach
Authors: Sampath Samuel Joshua Pragasam , Rath Subha Narayan , Kotikalapudi Nagasuryaprasad , Venkatesan Vijayalakshmi
Published: June 2021

Osteoarthritis (OA) is the most prevalent joint disease predominantly characterized by inflammation which drives cartilage destruction. Mesenchymal stem cells-condition medium (MSC-CM) or the secretome is enriched with bioactive factors and possesses anti-inflammatory and regenerative effects. The present study aimed at evaluating the effects of combining MSC-conditioned medium with stigmasterol compared with per se treatments in alleviating interleukin-1beta (IL-1β)-induced inflammation in rat chondrocytes. Stigmasterol is a phytosterol exhibiting anti-inflammatory effects. IL-1β (10ng/ml) was used to induce inflammation and mimic OA in-vitro in primary rat articular chondrocytes. The IL-1β-stimulated chondrocytes were treated with MSC-CM, stigmasterol, and a combination of MSC-CM and stigmasterol for 24 hours. Cell viability was measured using MTT assay. Protein expression of inducible nitric oxide synthase (iNOS), interleukin-6 (IL-6), collagen II (COL2A1) and matrix metalloproteinase (MMP)‑13 were evaluated by immunofluorescence. Gene expression levels of MMP-3, MMP-13 and A Disintegrin-like and Metalloproteinases with Thrombospondin Motifs (ADAMTS)-5 were measured using qRT-PCR. NF-κB signaling pathway was studied using western blotting. A significant reduction in the expression of iNOS, IL-6, MMP-3, MMP-13 and ADAMTS-5 and a significant increase in COL2A1 expression was observed in the rat chondrocytes across all the treatment groups. However, the combination treatment of MSC-CM and stigmasterol remarkably reversed the IL-1β-induced pro-inflammatory/pro-catabolic responses to near normal levels comparable to the control group. The combination treatment (MSC-CM+stigmasterol) elicited a superior anti-inflammatory/anti-catabolic effect by inhibiting the IL-1β-induced NF-κB activation evidenced by the negligible phosphorylation of p65 and IκBα subunits, thereby emphasizing the benefit of the combination therapy over the per se treatments.
Gut Microbial Shifts By Synbiotic Combination of Pediococcus Acidilactici and Lactulose In Weaned Piglets Challenged With Shiga Toxin-Producing Escherichia coli
Authors: Guevarra Robin B. , Cho Jae Hyoung , Cho Jin Ho , Song Minho , Lee Jun Hyung , Kim Hyeri , Kim Sheena , Kim Eun Sol , Keum Gi Beom , Kang Jung Sun , Cho Won Tak , Lee Chan Ho , Watthanaphansak Suphot , Kim In Ho , Kim Hyeun Bum
Published: June 2021

Background: Development of alternatives to in-feed antibiotics in the swine industry have been the focused of many pig gut microbiota studies to improve animal health. In this study, we evaluated the effects of probiotic Pediococcus acidilactici (PRO), prebiotic lactulose (PRE), and their synbiotic combination (SYN) on weaned pig gut microbiota using 16S rRNA gene sequencing in weaned piglets challenged with Shiga-toxin producing Escherichia coli (STEC). Results: Our data showed that prebiotics, probiotics and synbiotics improved the intestinal health in weaned piglets. No significant differences were observed in species richness and species diversity in weaned piglets fed prebiotics, probiotics and their synbiotic combination. However, beta diversity analysis revealed distinct clustering of the microbiota of according to dietary treatment and by oral challenge of STEC. At the phylum level, Firmicutes to Bacteroidetes ratio was lower in the dietary treatment groups than the control group. Oral supplementation of prebiotics, probiotics and synbiotics enriched the abundance of Prevotella and Roseburia. Succinivibrio was elevated in PRO group; however, Phascolarctobacterium was depleted with STEC challenge regardless of dietary treatment. Overall, our data showed that administration of synbiotics in piglets improved intestinal health through gut microbiota modulation. Conclusions: Our data indicated that prebiotics, probiotics and their synbiotic combination could promote intestinal health through gut microbiota modulation in weaned piglets.
M2-Polarized Macrophages Mediate Wound Healing by Regulating Connective Tissue Growth Factor via AKT, ERK 1/2, and STAT 3 Signaling Pathways
Authors: Zhang Si-Min , Wei Chuan-Yuan , Wang Qiang , Wang Lu , Lu Lu , Qi Fa-Zhi
Published: June 2021

Background: Timely and sufficient recruitment of M1 macrophages and M2 polarization are necessary for fibrous repair during cutaneous wound healing. The inherent mechanism of how M2 polarization mediate wound healing is worth exploring and illustrating. Abnormally up-regulated connective tissue growth factor (CTGF) is closely related with multiple organ fibrosis, including cardiac, pulmonary, hepatic, renal, and cutaneous fibrosis. Previous studies have reported that M2-polarized macrophages contribute to hepatic and renal fibrosis by secreting CTGF. It is worth discussing if M2 macrophages regulate fibrosis through secreting CTGF in cutaneous wound healing.Methods: We established the murine full-thickness excisional wound model and inhibited macrophages during proliferation phase (mainly M2 and M1-M2 polarization) with clodronate liposomes to analyze how M2 macrophages mediate wound healing rates, collagen deposition, collagen 1/3 expression, and Ki67 expression in vivo. Furthermore, M2 polarization was induced by IL-4 and in vitro. F4/80+CD206+ M2 macrophages were measured by flow cytometry. The morphological characteristics were observed. Secretion of IL-6, TNF-α, IL-10, TGF-β1, and CTGF was tested by ELISA. CTGF gene of M2 was blocked using siCTGF. Effects of M2 on proliferation and migration of fibroblasts were detected by CCK8 and cellular wound healing assay. Protein level of AKT, ERK1/2, and STAT3 pathway were assessed by western blotting.Results: Depletion of macrophages at proliferation phase (mainly M2 and M1-M2 polarization) resulted in delayed cutaneous wound closure and down-regulation of wound healing rates, collagen deposition, collagen 1/3 expression, and Ki67 expression. M2 polarization was induced, which producing more CTGF, TGF-β1, and IL-6, as well as less TNF-α and IL-10. Blockade of CTGF in M2 macrophages deactivated fibroblast proliferation and migration. Addition of recombinant CTGF restored the promotional effects of M2 macrophages on fibroblast proliferation and migration. Blockade of CTGF in M2 mediate fibroblasts via down-regulating AKT, ERK1/2, and STAT3 signaling pathway.Conclusion: Our research, for the first time, indicated that M2-polarized macrophages promoted cutaneous wound healing by secreting CTGF, which further mediating proliferation and migration of fibroblasts via AKT, ERK1/2, and STAT3 signaling pathway.
Visual analytics of combustion on time-varying turbulent-flow
Authors: An Yifei , Shan Guihua , Liu Jun , Yang Bo
Published: June 2021

Visualization is crucial for analyzing the turbulent combustion simulation. Time-varying data allows us to investigate the evolution process of the turbulent flow field. To study the combustion effects, we calculated the enstrophy of the flow field since high enstrophy region can display valuable features, and extract components based on these features. We isolated large components to track their behaviors and characterized them using volume and spatial locations, which helps scientists to explore the dynamics and temporal changes of intense events individually. We analyzed the components' structures and visualized them in contouring and statistical charts.
Identification of Natural Selection in Genomic Data with Deep Convolutional Neural Network
Authors: Fadja Arnaud Nguembang , Riguzzi Fabrizio , Bertorelle Giorgio , Trucchi Emiliano
Published: June 2021

Background: With the increase in the size of genomic datasets describing variability in populations, extracting relevant information becomes increasingly useful as well as complex. Recently, computational methodologies such as Supervised Machine Learning and specifically Convolutional Neural Networks have been proposed to order to make inferences on demographic and adaptive processes using genomic data, Even though it was already shown to be powerful and efficient in different fields of investigation, Supervised Machine Learning has still to be explored as to unfold its enormous potential in evolutionary genomics. Results: The paper proposes a method based on Supervised Machine Learning for classifying genomic data, represented as windows of genomic sequences from a sample of individuals belonging to the same population. A Convolutional Neural Network is used to test whether a genomic window shows the signature of natural selection. Experiments performed on simulated data show that the proposed model can accurately predict neutral and selection processes on genomic data with more than 99% accuracy.
“Making It Okay”: Professionals in High-stress Environments Construct Their Understanding of the Impact of a Yoga-based Retreat Designed to Build Resilience
Authors: Reeves Tegan Jemma , Dyer Natalie L. , Borden Sara , Dusek Jeffery A. , Khalsa Sat Bir Singh
Published: June 2021

Background: While there is growing evidence for resilience building programs, to date research has not explored how professionals construct their understanding of program impact. Methods: Using a qualitative exploration of reflections on a yoga-based retreat at Kripalu Center for Yoga & Health, nested in a larger study, the current inquiry aims to explore long-term perceptions of an occupation-oriented program designed to improve resilience. Called RISE (resilience, integration, self-awareness, engagement), the immersion program was a 5-day professional development for professionals in high-stress jobs. Through a grounded constructivist lens, inductive coding and iterative thematic analysis was employedResults: Semi-structured interviews of 17 adult professionals who attended RISE, conducted 3 months after completion of the program, illustrated two integrated perceptions woven through five themes. Persistent threads of experiential learning and sense of permission provided structure for themes found. Five interrelated themes related to psychological health and workplace dynamics were: (1) use of acquired behavioral skills and practices; (2) lived mindfulness; (3) resilience to stress and emotion regulation (4) self-care and self-compassion, and (5) sharing with others. Conclusion: Findings provide meaningful interpretation of previously reported program efficacy by contextualizing perceived benefits within participants constructed understanding of change. Specifically, environmental, social, and experiential considerations have suggested implications for resilience building programs.
Predation Risk is a Function of Seasonality Rather than Habitat Complexity in a Tropical Semi-arid Forest
Authors: Ferreira Anthony , Faria Renato
Published: June 2021

Predator-prey dynamic is one of the most important species’ interactions in the natural structuring of communities, and is among the more complex ecological processes studied by ecologists. We measure predation risk using artificial lizard replicas to test two competing hypotheses regarding predation pressure in semi-arid environments: (1) predation risk is dependent on the habitat structural complexity; and (2) predation risk is dependent on seasonality. We placed 960 replicas along three sites with different physical structures and in both seasons for seven consecutive days in a caatinga area in northeastern Brazil. Birds were responsible for the majority of attacks and more frequently on artificial lizards placed in trees. Attacks focused on the most vulnerable areas of the body (head and torso), proving that were perceived by predators as true prey items. We found that predation risk is not dependent on the habitat structural complexity, but rather dependent on the caatinga seasonality, with the overall attack being 19% higher in the dry season. Our study suggests that potential predation risk is highly context-dependent and that seasonality consistently drives of trophic interactions strength in the caatinga, an important ecological finding that could contribute to better understanding the complex evolution of predator-prey interactions within communities of animals living in different habitats.
Risk Evaluation of Early-stage Hormone Receptor-positive and Human Epidermal Growth Factor Receptor 2-negative Breast Cancer Patients: a Population-based Study From Taiwan
Authors: Lei Lei , Chan Han-Ching , Lu Tzu-Pin , Cheng Hung-Chun Skye
Published: June 2021

PURPOSE: To assess the prognostic value of the Dutch criteria for patients with early-stage hormone receptor-positive and human epidermal growth factor receptor 2-negative breast cancer from the Taiwan Cancer Database. PATIENTS AND METHODS:We included 8,295 patients with early-stage node-negative breast cancer who underwent surgery during January 2008–December 2012. Patients were stratified into low- and high-risk groups based on the Dutch criteria. The Kaplan–Meier method and log-rank test were used to estimate the difference in breast cancer-specific survival (BCSS) and overall survival (OS) between groups. Multivariable analysis was used to evaluate the prognostic value of the Dutch criteria.RESULTS: Overall, the low-risk and high-risk groups comprised 5,375 and 2,920 patients, respectively. In the low- and high-risk groups, the 5-year BCSS rate was 99.6% and 98.2% (P<0.0001) and the 5-year OS rate was 98.3% and 96.8% (P<0.0001), respectively. The hazard ratio for BCSS was 4.18 (95% confidence interval [CI], 2.63–6.63, P<0.0001), and the hazard ratio for OS was 1.94 (95% CI, 1.48–2.55); both were significantly poorer in the high-risk group than in the low-risk group. In the low-risk group, the 5-year BCSS and OS of patients who did and did not receive adjuvant chemotherapy were similar (99.5% versus 99.6% [P=0.927] and 98.8% and 98.1% [P=0.0683], respectively). CONCLUSIONS: The prognosis of low-risk patients as classified using the Dutch criteria is excellent with or without adjuvant chemotherapy. The benefit of multi-gene testing for chemotherapy decision-making might be minimal in these patients.
Acromegaly Disease Activity According to ACRODAT®, in Spain: ACROVAL Study
Authors: Marazuela Monica , Blanco Concepción , Bernabeu Ignacio , Menendez Edelmiro , Villar Rocío , Paja Miguel , Sampedro-Nuñez Miguel , Samaniego Maria Luz , Díaz-Muñoz Marcos , Sánchez-Cenizo Laura
Published: June 2021

Objectives: To evaluate disease activity status using the Acromegaly Disease Activity Tool (ACRODAT®) in a cohort of Spanish acromegaly patients, to assess the relationship between the level of disease activity according to both ACRODAT® and the physicians’ clinical evaluation, and to study the potential discrepancies in the perception of symptoms between physicians and patients.Design: Multicenter, observational, descriptive and cross-sectional study. Methods: Disease activity was assessed in adult patients with acromegaly under pharmacological treatment during at least 6 months using ACRODAT®.Results: According to ACRODAT®, 48.2%, 31.8% and 20.0% of a total of 111 patients were classified as having a stable disease (S), mild disease activity (M-DA) and significant disease activity (S-DA) respectively. ACRODAT® classification of disease activity significantly correlated with physicians’ opinion, with a moderate inter-rater agreement and a specificity of 92.45% (PPV=86.21%). No correlation was found between IGF-1 levels and severity of symptoms or quality of life (QoL). A decision to take clinical action was significantly more frequent in S-DA and M-DA patients than S patients but no action was taken on 5 (22.7%) and 27 (77.1%) S-DA and M-DA patients, respectivelyConclusions: ACRODAT® detected disease activity in 51.8% of patients. Interestingly, although M-DA and S-DA patients were likely to be in the process of being controlled, action was not always taken on these patients. ACRODAT® is a validated and highly specific tool that may be useful to routinely monitor acromegaly and to identify patients with non-obvious disease activity by incorporating “patient-centered” parameters like symptoms and QoL to the clinical evaluation of acromegaly.
Genetic Diversity of Meat Quality Related Genes in Argentinean Pigs
Authors: Rodriguez Viviana Rita , Maffioly Joaquin Ignacio , Zdanovicz Lara Azul , Fabre Romina , Barrandeguy Maria Eugenia , García Maria Victoria , Lagadari Mariana
Published: June 2021

Background: The genetic influence on pork quality exists between breeds and within a breed. The variation is caused by a large set of genes and pork quality traits have a multi factorial background. Research into the genetics of meat quality found causative mutations associated with marked effects on pig meat value. The main objective of this study was to investigate the diversity of single nucleotide polymorphisms (SNPs) of meat quality-related genes in pigs from commercial and family farms in the North-West of Argentina. A screen for SNPs in RYR1, RN, CAST, and SOX6 candidate genes and the differentiation of their genotypes by PCR–RFLP was conducted. Results: All genes were characterized by a high level of polymorphism and heterozygosity. Additionally, both populations, commercial and Creole pigs, showed genetic closeness for the analyzed SNPs and a moderate selection for RYR1 and RN loci consistent with their allele´s adverse effects. Conclusions: The results obtained here highlighted the role of pig genotypes as a source of basic variability potentially affecting processed meat products as well as fresh meat.
In-Silico Design of Peptides for Inhibition of HLA-A*03-KLIETYFSK Complex as a New Drug Design for Treatment of Multiples Sclerosis Disease
Authors: Ghobadi Zahra , mahnam karim , Shakhsi-Niaei Mostafa
Published: June 2021

Multiple sclerosis is recognized as a chronic inflammatory disease. Human leukocyte antigen (HLA) plays an important role in initiating adaptive immune responses. HLA class I is present in almost all nucleated cells and presents the cleaved endogenous peptide antigens to cytotoxic T cells. HLA-A*03 is one of the HLA class I alleles, which is reported as substantially related HLA to MS disease. In 2011, structure of the HLA-A*03 in complex was identified with an immunodominant proteolipid protein (PLP) epitope (KLIETYFSK). This complex has been reported as an important autoantigen-presenting complex in MS pathogenesis. In this study, new peptides were designed to bind to this complex that may prevent specific pathogenic cytotoxic T cell binding to this autoantigen-presenting complex and CNS demyelination. Herein, 14 new helical peptides containing 19 amino acids were designed and their structures were predicted using the PEP-FOLD server. Binding of each designed peptide to the mentioned complex was then performed. A mutation approach was used by the BeAtMuSiC server to improve binding affinity of the designed peptide. In each position, amino acid substitutions leading to an increase in binding affinity of the peptide to the mentioned complex were determined. Finally, the resulting complexes were simulated for 40 ns using AMBER18 software. The results revealed that out of 14 designed peptides, “WRYWWKDWAKQFRQFYRWF” peptide exhibited the highest affinity for binding to the mentioned complex. This peptide can be considered as a potential drug to control multiple sclerosis disease in patients carrying the HLA-A*03 allele.
Tree diversity and natural regeneration in Tropical Dry Deciduous Forest of Panna Tiger Reserve, India
Authors: Parveen Talat , Ilyas Orus
Published: June 2021

The disturbance is a major factor driving the decline of tropical forests and their associated fauna. Henceforth, basic information on species diversity would be useful for assessing the success of management in the fragmented and human-disturbed landscape. We accounted for tree species diversity and their regeneration pattern from the tropical dry deciduous forest of Panna Tiger Reserve (PTR), India. Considering this, random vegetation sampling along with transects was carried out in different ranges of PTR. It is spread over in an area of 2998.98 km2 that situated in the northern part of Madhya Pradesh and distributed in Panna and Chhatarpur district. The tropical dry deciduous forest inventory in the 10.6132-ha area yielded a total of 46 woody species of > 10 cm GBH, belonged to 23 Families and 40 genera. The regeneration represented 27 species of < 30 cm height (seedling) under 16 families and 24 genera while sapling, which ranges from > 30cm to 1.3m, showed 24 species of 13 families and 32 genera. The Shannon diversity of Trees, seedlings, and saplings was 2.684, 2.525, and 2.401 respectively. A total stand density and basal area of 2391 stems of trees were estimated as 225.285 stand ha− 1 and 90.016 m2ha− 1 respectively. Tectona grandis scored the highest IVI value of 59.44 (19.81% of total IVI for all species) among the dominated tree species, followed by Acacia catechu (24.94), Abrus precatorius (23.25), Zizyphus xylopyra (22.94), Anogeissus latifolia (22.16) and Lagerstroemia parviflora (22.18). Nearly 23.913% of the total number of species was recorded as rare species. The highest seedling density was obtained for Diospyros melanoxylon followed by Zizyphus xylopyra, Aegle marmelos, Wrightia tintoria, and Tectona grandis, which declined in the subsequent sapling stage and showed a reverse pattern. Hence, the highest sapling density was recorded for Tectona grandis then Aegle marmelos, Wrightia tintoria, Diospyros melanoxylon, and Zizyphus xylopyra. A total of 36.956% of tree species were found to fail to establish in the community because species were represented by only adult or tree stage that listed as Not-regenerating. In terms of the most diverse family among the plant categories; viz. Tree, Seedling, Sapling, Fabaceae had the highest species richness. The highest tree stand density (127.576 stand ha− 1) was recorded in the girth class of 31-60cm (48.687% of the total tree stand density) followed by 10-30cm and 61-90cm. Likewise, a total basal area of 20.824 m2ha− 1 was occupied by 31-60cm that contributed 23.051% of the total basal area, so our data on the population structure of forest shows a similar trend wherein the distribution curve exponentially decreases with increasing girth classes that indicates not only a mid-successional forest but also a human-disturbed.
The Anti-Inflammatory Activity of Palmitoylethanolamide Ameliorates Osteoarthritis Induced by Monosodium Iodoacetate in Sprague Dawley Rats
Authors: Jung Jae In , Lee Hyun Sook , Jeon Young Eun , Kim So Mi , Hong Su Hee , Moon Joo Myung , Lim Cho Young , Kim Yoon Hee , Kim Eun Ji
Published: June 2021

Novel treatment strategies are urgently required for osteoarthritis (OA), a degenerative joint disease. Palmitoylethanolamide (PEA) is a naturally occurring fatty acid amide with analgesic and anti-inflammatory effects. We aimed to examine its effect on OA and molecular mechanism of actions in monosodium iodoacetate (MIA)-induced OA Sprague Dawley rats. The experimental animals were divided into five groups: normal control group (injected with saline + treated with phosphate-buffered saline (PBS), NOR), control group (injected with MIA + treated with PBS, CON), 50 or 100 mg/kg body weight (BW)/day PEA-treated group (injected with MIA + treated with 50 or 100 mg of PEA/kg BW/day, PEA50 or PEA 100), and positive control group (injected with MIA + treated with 6 mg of diclofenac/kg BW/day, DiC). Changes in blood and body parameters, gene expression of inflammatory mediators and cytokines, knee thickness, and joint tissue were observed. We found no adverse effects of oral administration of PEA on BW, liver, or kidneys. PEA reduced knee joint swelling and cartilage degradation in MIA-induced OA rats. The serum levels of leukotriene B4, nitric oxide, tumor necrosis factor (TNF)-α, interleukin (IL)-1β, and prostaglandin E2 considerably reduced in the PEA100 group compared to those in the CON group. In the synovia of knee joints, mRNA expression of iNOS, 5-Lox, Cox-2, Il-1β, Tnf-α, Mmp-2, -3, -9, and − 13 noticeably reduced with MIA administration. Meanwhile, Timp-1 mRNA expression noticeably decreased in the CON group but increased to the normal level with PEA treatment. Thus, we demonstrated that PEA can be used as an effective therapeutic agent for OA.
A Novel Nomogram for Predicting Cancer-specific Survival in Women With Uterine Sarcoma: a Large Population-based Study
Authors: Li Yuan-jie , Lyu Jun , Li Chen , He Hai-rong , Wang Jin-feng , Wang Yue-ling , Fang Jing , Ji Jing
Published: June 2021

Background: To perform a comprehensive nomogram to predict the cancer-specific survival (CSS) for uterine sarcoma (US) based on the Surveillance, Epidemiology, and End Results (SEER) database.Methods: A total of 3861 patients with US between 2010 and 2015 were identified in this study. They were randomly divided into a training cohort (n = 2702) and a validation cohort (n = 1159) in a 7-to-3 ratio by R software. We performed multivariate Cox analysis to select predictive variables and identify independent prognostic factors. Then, the discrimination and calibration of the nomogram were evaluated by concordance index (C-index) and the area under the curve (AUC). Finally, the net reclassification improvement (NRI), the integrated discrimination improvement (IDI), calibration plotting, and decision-curve analysis (DCA) were used to evaluate the benefits of the new prediction model.Results: We have established a nomogram to predict 1-, 3-, and 5-year CSS for US patients. In this nomogram, pathology grade has the highest risk on CSS in US, followed by age at diagnosis, then surgery status. Comparing to the AJCC staging system, the nomogram showed better predictive discrimination with higher C-index in both training and validation cohort (0.796 and 0.767 vs0.706 and 0.713, respectively) . Furthermore, AUC value, calibration plotting, NRI, IDI, and DCA also demonstrated better performance than the traditional system.Conclusion: Our study validated the first comprehensive nomogram for US which could provide more accurately and individualized survival predictions for US patients in clinical practice.
The Preventive Effect of Lactobacillus Fermentum SCHY34 Isolated from Traditional Fermented Yak Yogurt on Lead Acetate-Induced Neurological Damage in SD Rats
Authors: Long Xingyao , Wu Haibo , Zhou Yujing , Wan Yunxiao , Kan Xunmei , Gong Jianjun , Zhao Xin
Published: June 2021

Background: Lead is a heavy metal that is widespread in nature and has extremely strong chemical toxicity in the human body especially harmful to the human nervous system. Lactic acid bacteria (LAB) can be used to maintain the balance of the intestinal microbiota, and recent reports have shown that LAB can remove metal ions through adsorption. In this experiment, Sprague-Dawley (SD) rats were treated with 200 mg/L of lead acetate solution daily to induce chronic lead poisoning, and oral LF-SCHY34 to study its mitigation effects and mechanisms on rat neurotoxicity.Results: Through electron microscopy and energy spectrum analysis, it was found that the surface of the lactic acid bacteria adsorbed a large amount of lead ions, and the O and N elements in the bacteria were significantly reduced. Animal experiments showed that LF-SCHY34 maintained the morphology of rat liver, kidney, and hippocampi, reduced the accumulation of lead in the blood, liver, kidney, and brain tissue, reduced the activity of alanine aminotransferase (ALT), aspartate aminotransferase (AST), creatinine (CRE), and blood urea nitrogen (BUN) in rat serum, and increased δ-aminolevulinic acid dehydratase (δ-ALAD) activity in serum. Further, LF-SCHY34 alleviated the lead-induced decline in spatial memory and response capacity of SD rats, and also regulated the secretion of neurotransmitters and related enzyme activities in the brain tissue of rats. LF-SCHY34 inhibited the secretion of glutamate and the activity of monoamine oxidase in brain tissue, promoted the synthesis of glutamine (Glu), norepinephrine (NE), and cyclic adenosine monophosphate (cAMP), and increased the activities of glutamine synthetase (GS), acetylcholinesterase (AchE), and adenylate cyclase (AC). In addition, the expression of genes related to cognitive capacity in rat brain tissues such as calmodulin (CaM), protein kinase A (PKA), brain-derived neurotrophic factor (BDNF), c-fos, c-jun was increased by LF-SCHY as was the expression of the antioxidation genes and the anti-apoptotic gene. Conclusions: Compared with the lead poisoning treatment drug EDTA, LF-SCHY34 not only had greater lead discharge capacity than EDTA, but also had a greater alleviating effect on organ damage and oxidative damage caused by lead. As a food-grade LAB, LF-SCHY34 has great potential and research value for removing heavy metals from food and alleviating the toxicity of heavy metals.
Involvement of SIRT1-eNOS Axis in Vascular Senescence Responses to Ursolic Acid and Exercise Training in Aged Type 2 Diabetes Model of Rats
Authors: Pordanjani Masume Kazemi , Banitalebi Ebrahim , Roghani Mehrdad , Hemmati Roohullah
Published: June 2021

Background

Ursolic acid (UA) mediates the vasorelaxant activity via nitric oxide (NO) release, and up-regulation of eNOS in endothelial cells in disease conditions with increased oxidative stress. The present study aimed to reflect on the impact of eight weeks of a combination of ursolic acid (UA) supplementation and resistance/endurance training in old male Wistar rats having high-fat diet and/or low-dose streptozotocin-induced type 2 diabetes (HFD/STZ-induced T2D), with an emphasis on sirtuin 1 (SIRT1)-endothelial nitric oxide synthase (eNOS) axis and oxidative stress (OS) indices in their aortic tissues.
Methods

A total number of 56 21-month-old male Wistar rats with HFD/STZ-induced T2Dwere randomized into seven groups (n = eight animals per group): (1) sedentary old non-diabetic (C); (2) sedentary HFD/STZ-induced T2D (D); (3) sedentary HFD/STZ-induced T2D plus UA (UA) (DU); (4) endurance-trained HFD/STZ-induced T2D (DE); (5) resistance-trained HFD/STZ-induced T2D (DR); (6) endurance-trained HFD/STZ-induced T2D plus UA (DEU); and (7) resistance-trained STZ-diabetic plus UA (DRU) rats.
Results

The study results established no significant interaction between the UA supplementation and the resistance/endurance training with regard to the levels of glucose (p = 0.534), insulin (p = 0.327), high-density lipoprotein cholesterol (HDL-c) (p = 0.960), cholesterol (p = 0.107), SIRT1 (p = 0.640), and eNOS (p = 0.151). However, the resistance/endurance training plus the UA consumption could partially reverse the levels of malondialdehyde (MDA) (p = 0.001), nitric oxide (NO) (p = 0.009), as well as total antioxidant capacity (TAC) (p = 0.016).
Conclusions

In general, the UA supplementation combined with the resistance/endurance training did not affect vascular aging biomarkers. To develop novel practical nutritional strategies involving UA intake, further studies are thus needed to clarify how chronic consumption of UA with/without resistance/endurance training reverses vascular aging process in old male Wistar rats with HFD/STZ-induced T2D.
Mir-455-3p Inhibits Hepatocellular Carcinoma Tumorigenesis, Lymphangiogenesis and Angiogenesis via Regulating Vascular Endothelial Growth Factor C as well as Vascular Endothelial Growth Factor Receptor-2
Authors: Bin Xiaoyun , Wang Jianchu , Lu Libai , Ye Guanbin , Zhou Sufang
Published: June 2021

Background: MicroRNAs (miRNAs), functioning as tumor suppressors or oncogenes, exert a considerable regulative influence in biological processes. Previous studies showed that miR-455-3p was significantly down-regulated in hepatocellular carcinoma (HCC), while the specific role of miR-455-3p in HCC is unclear. Methods: QRT-PCR was used to detect miR-455-3p expression levels in HCC cells and tissues. We adopted colony formation, EdU, CCK-8, transwell assays and wound-healing to identify the influences of miR-455-3p on proliferation, invasion and migration in HHCC and HuH-7 cells. Western blot analysis, angiogenesis assays, dual-luciferase reporter gene assay and bioinformatics analysis were also adopted to investigate the underlying molecular mechanisms. Results: MiR-455-3p was down-regulated in HCC tissues and cells. In vitro experiments identified miR-455-3p overexpression inhibited HCC cell proliferation, migration and invasion. Interestingly, it was identified that vascular endothelial growth factor C (VEGFC) was the downstream target gene of miR-455-3p. Additionally, overexpression of miR-455-3p in HCC cells and human umbilical vein endothelial cells (HUVECs) cells led to decreased expression of VEGFC, vascular endothelial growth factor receptor (VEGFR)-2, and subsequently decreased phosphatidylinositol 3-kinase (AKT) signaling pathway. Furthermore, in vivo restoration of miR-455-3p significantly suppressed tumorigenicity of HuH-7 cells in nude mice and inhibited both angiogenesis and lymphangiogenesis of tumor xenografts. Conclusions: Our findings suggest that miR-455-3p could play a role in HCC tumorigenesis at least in part by modulation of angiogenesis and lymphangiogenesis through targeting VEGFC, and could simultaneously block AKT signaling pathways.
Trend Assessment of Global, UVB, UVA Irradiation and Dry Bulb Temperature at the Lowest Terrestrial Site on Earth: Dead Sea, Israel
Authors: Kudish Avraham I , Evseev Efim G
Published: June 2021

The Dead Sea basin is lowest terrestrial site on the globe. A meteorological station monitoring the global, UVB and UVA irradiation and the dry bulb temperature was established in 1995 in conjunction with a study of bio-climatological properties of the region with regard to photoclimatherapy treatment of dermatological diseases. The availability of such irradiation and dry bulb temperature databases has been utilized to perform a study to determine if any trends regarding either irradiation or dry bulb temperature exist at this unique site. There was no indication of any trends, based upon a p-value analysis, regarding the global, UVB and UVA irradiation. The global irradiation database included the time interval 1995-2020; whereas the corresponding time interval for the UVB and UVA irradiation databases was 1995-2018. The dry bulb temperature database consisted of the time interval 1995-2020 and, once again, no trends were observed throughout the year with the exception of the nocturnal time interval, between 18:00 to 06:00, during the month of October which exhibited a warming trend of 0.78°C/decade
Genome Mining of Antimicrobial Gene Clusters from Phyllospheric Bacteria Isolated from Solanum Lycopersicum and Lactuca Sativa to Identify Biocontrol Properties
Authors: Muñoz Claudia Y. , Zhou Lu , Yi Yunhai , Kuipers Oscar P.
Published: June 2021

BackgroundBiocontrol agents are sustainable eco-friendly alternatives for chemical pesticides that cause adverse effects in the environment and toxicity in animals including humans. An improved understanding of the phyllosphere microbiology is of vital importance for biocontrol development. Most studies have been directed towards beneficial plant-microbe interactions and ignore the pathogens that might affect humans when consuming vegetables. In this study we extended this perspective and investigated potential biocontrol strains isolated from the tomato and lettuce phyllosphere that can promote plant growth and antagonize mammalian pathogens as well as plant pathogens. Subsequently, we mined into their genomes for discovery of antimicrobial biosynthetic gene clusters (BGCs), several of which are good candidates to produce protectants against microbial plant and mammalian pathogens.Results The antimicrobial activity of 69 newly isolated strains from a healthy tomato and lettuce phyllosphere against several plant and mammalian pathogens was determined with plates assays. Three strains with the highest antimicrobial activity against the relevant pathogens were selected and characterized (Bacillus subtilis STRP31, Bacillus velezensis SPL51, and Paenibacillus sp. PL91). All three strains showed a plant growth promotion effect by the production of volatile compounds (VOCs) on tomato and lettuce. In addition, genome mining of these isolates showed the presence of a large variety of biosynthetic gene clusters. A total of 39 BGCs were identified, of which several are already known, such as bacilysin, bacillibactin, surfactin, subtilomycin, etc., but also several novel ones. Further analysis revealed that among the novel BGCs, one NRPS and two bacteriocins are encoded which were analyzed in more depth.Conclusions Several antimicrobial BGCs were found in the selected strains, including the rediscovery of known ones, but also the discovery of novel ones. Our study serves as support for subsequent examination and characterization of novel antimicrobial metabolites, and the possibility of developing biocontrol agents.
A Probabilistic Model For Co-Occurrence Analysis in Bibliometrics
Authors: Zhou Xiaobei , Zhou Miao , Huang Desheng , Cui Lei
Published: June 2021

The co-occurrence analysis of Medical Subject Heading (MeSH) terms in the bibliographic database is popularly used in bibliometrics. Practically for making the result interpretable, it is necessary to apply a certain filter procedure of co-occurrence matrix for removing the low-frequency items that should not appear in the final result due to their low representativeness for co-occurrence analysis. Unfortunately, there is rare research referring to determine a critical threshold to remove noise of data for co-occurrence analysis. Here, we propose a probabilistic model for co-occurrence analysis that can calculate statistical significance (p-values) of co-occurred items. With help of this model, the dimensionality of co-occurrence network could be conveniently reduced according to selection of different levels of p-value thresholds. The conceptual model framework, simulation and practical applications are illustrated in the manuscript. Further details (including all reproducible codes) can be downloaded from the project website: https://github.com/Miao-zhou/Co-occurrence-analysis.git.
Ajuga Bracteosa Transgenic Regenerants Display Better Pharmacological Potential
Authors: Rubnawaz Samina , Kayani Waqas Khan , Akhtar Nosheen , Mahmood Rashid , Mehmood Furrukh , Khan Asif , Mirza Bushra
Published: June 2021

Ajuga bracteosa Wall. ex Benth is an endangered medicinal herb used against different ailments in folklore medicines. Here, we aimed to create a new insight to the fundamental mechanisms of genetic transformation in the ethnomedicinal usage of this plant. We transformed the plant with rol genes of Agrobacterium rhizogenes and raised the regenerants from the hairy roots. The transgenic regenerants were screened for in vitro antioxidant activities, a range of in vivo assays, and linked the activities with elemental analysis, polyphenol content and different phytochemicals found through HPLC. Among 18 polyphenolic standards, kaempferol was found most abundant in all transgenic lines (up to 101.26 ± 6 µg/mg). Furthermore, among all tested plant extracts, transgenic line 3 (ABRL3) showed maximum phenolics (13.39 ± 2µg GAE/mg) and flavonoids content (4.75 ± 0.16 µg QE/mg). ABRL3 also demonstrated potent total antioxidant capacity (8.16 ± 1 µg AAE/mg), total reducing power, (6.60 ± 1.17 µg AAE/mg), DPPH activity (IC50 = 59.5 ± 0.8µg/mL), hydroxyl ion scavenging (IC50 = 122.5 ± 0.90 µg/mL), and iron chelating power (IC50 = 154.8 ± 2 µg/mL) among all plants. Transformed plant extracts also produced significant analgesic, anti-inflammatory, anticoagulant, and antidepressant properties in in vivo mice model as compared to control untransformed plant material. Additionally, no abnormal behavior or lethality was observed in any animal tested. In conclusion, transgenic regenerants of A. bracteosa pose better pharmacological properties under the effect of rol genes as compared to wild type plants.
Neuroretinal Dysfunction in Patients Affected by Neurofibromatosis Type 1
Authors: Moramarco Antonietta , Lucchino Luca , Mallone Fabiana , Marcelli Michela , Alisi Ludovico , Roberti Vincenzo , Giustini Sandra , LAMBIASE ALESSANDRO , Nebbioso Marcella
Published: June 2021

The aim of the study was to examine neuroretinal function by using the mfERG test in patients with neurofibromatosis type 1 (NF1) without optic pathway gliomas (OPGs). This study was conducted on 35 patients (35 eyes) with NF1 and 30 healthy subjects (30 eyes) for the control group. Each subject underwent a complete ophthalmological examination including multifocal electroretinography (mfERG). 1.5-Tesla magnetic resonance imaging (MRI) scan of the brain was performed in NF1 patients to assess the presence of OPGs. All participants were recruited having a best corrected visual acuity (BCVA) of no less than 20/20 in each eye. The amplitude and implicit time of the P1 wave (first-order Kernel component) were evaluated on mfERG. Data analysis was carried out in the two central degrees and in the four quadrants from two to 25 degrees of visual field. Statistically significant results were obtained for the P1 wave amplitudes in the 4 quadrants in NF1 patients compared to healthy subjects, while the reduction was not significant in the 2 central degrees. A statistically significant difference was observed among the P1 wave amplitudes as recorded in the 4 quadrants within the NF1 group, with lower amplitudes in the nasal quadrants. No differences in the implicit times were recorded in the 4 quadrants and in the 2 central degrees as compared between NF1 patients and controls. The present study demonstrates impaired neuroretinal function in NF1 patients. Altered intracellular signal transduction due to abnormal neurofibromin-mediated cyclic adenosine monophosphate (cAMP) generation, could be involved. Our results suggest a possible use of mfERG as subclinical retinal damage indicator with a potential utility in clinical practice for the follow-up of NF1 patients.
Engineer Design Process Assisted by Explainable Deep Learning Network
Authors: Hsu Chia-Wei , Yang An-Cheng , Kung Pei-Ching , Tsou Nien-Ti , Chen Nan-Yow
Published: June 2021

Engineering simulation accelerates the development of reliable and repeatable design processes in various domains. However, the computing resource consumption is dramatically raised in the whole development processes. Making the most of these simulation data becomes more and more important in modern industrial product design. In the present study, we proposed a workflow comprised of a series of machine learning algorithms (mainly deep neuron networks) to be an alternative to the numerical simulation. We have applied the workflow to the field of dental implant design process. The process is based on a complex, time-dependent, multi-physical biomechanical theory, known as mechano-regulatory method. It has been used to evaluate the performance of dental implants and to assess the tissue recovery after the oral surgery procedures. We provided a deep learning network (DLN) with calibrated simulation data that came from different simulation conditions with experimental verification. The DLN achieves nearly exact result of simulated bone healing history around implants. The correlation of the predicted essential physical properties of surrounding bones (e.g. strain and fluid velocity) and performance indexes of implants (e.g. bone area and bone-implant contact) were greater than 0.980 and 0.947, respectively. The testing AUC values for the classification of each tissue phenotype were ranging from 0.90 to 0.99. The DLN reduced hours of simulation time to seconds. Moreover, our DLN is explainable via Deep Taylor decomposition, suggesting that the transverse fluid velocity, upper and lower parts of dental implants are the keys that influence bone healing and the distribution of tissue phenotypes the most. Many examples of commercial dental implants with designs which follow these design strategies can be found. This work demonstrates that DLN with proper network design is capable to replace complex, time-dependent, multi-physical models/theories, as well as to reveal the underlying features without prior professional knowledge.
Effects of the Covid-19 pandemic on maternity staff in 2020 – a scoping review
Authors: Schmitt Nadine , Mattern Elke , Cignacco Eva , Seliger Gregor , König-Bachmann Martina , Striebich Sabine , Ayerle Gertrud M.
Published: June 2021

In the spring of 2020, the SARS-CoV-2 virus caused the Covid-19 pandemic, bringing with it drastic changes and challenges for health systems and medical staff. Among the affected were obstetricians and midwives, whose close physical contact with pregnant women, women who recently gave birth, and their children was indispensable. In the obstetric setting, births cannot be postponed, and maternity staff had to adapt to assure obstetric safety while balancing evidence-based standards with the new challenges posed by the pandemic. This scoping review gives a comprehensive overview of the effecs the Covid-19 pandemic had on maternity staff. We followed the evidence-based approach described by Arksey & O’Malley: we searched several databases for English and German articles published between January 2020 and January 2021 that discussed or touched upon the effects the pandemic had on maternity staff in OECD countries and China. We found that structural challenges caused by the crisis and its subjective effects on maternity staff fell into two main topic areas. Structural challenges (the first main topic) were divided into five subtopics: staff shortages and restructuring; personal protective equipment and tests; switching to virtual communication; handling women with a positive SARS-CoV-2 infection; and excluding accompanying persons. The pandemic also strongly affected the staff’s mental health (the second main topic.) Attempting to meet challenges posed by the pandemic while afraid of contamination, suffering overwork and exhaustion, and struggling to resolve ethical-moral dilemmas had severe negative subjective effects. Several studies indicated increased depression, anxiety, stress levels, and risk of post-traumatic stress symptoms, although the crisis also generated strong occupational solidarity. Care for pregnant, birthing, and breast-feeding women cannot be interrupted, even during a pandemic crisis that requires social distancing. Maternity staff sometimes had to abandon normal standards of obstetric care and were confronted with enormous challenges and structural adjustments that did not leave them unscathed: their mental health suffered considerably. Researchers should study maternity staff’s experiences during the pandemic to prepare recommendations that will protect staff during future epidemics.
Subclinical Acromegaly: to Treat or Not to Treat?
Authors: Shimon Ilan , Adnan Zaina , Hirsch Dania , Duskin-Bitan Hadar , Akirov Amit
Published: June 2021

Objective
Patients with acromegaly usually present with the classical signs of acromegaly, whereas patients without the specific signs or symptoms are rarely diagnosed. This unique entity can be named "subclinical acromegaly".
Methods
This was a retrospective study. Our study group consisted of 8 patients (6 females) with incidentally diagnosed acromegaly, most following head MRI for unrelated reasons and without the specific signs of acromegaly.
Results
Mean age at diagnosis was 50.1 ± 16.3 years. Baseline IGF-1 ranged between 1.27–2.08 x upper limit of normal (ULN). MRI depicted a pituitary microadenoma in 6 patients, one patient presented with an intrasellar macroadenoma and one had no visible pituitary mass. Mean calculated SAGIT clinical score was 4.6. Three patients underwent trans-sphenoidal resection; two achieved hormonal remission and one improved but did not normalize IGF-1 following surgery. Five patients (including one following surgery) were given somatostatin analogs, and three normalized IGF-1. Several patients improved clinically following treatment, reporting improvement in snoring, hypertension, or weight loss, and pituitary adenoma decreased in size in 2 patients that responded to medical treatment.
Conclusions
we report a series of 8 patients with very mild and subclinical acromegaly. It is uncertain whether all such patients will gain clinical benefit from treatment, but some experienced clinical improvement due to treatment.