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Blind football players use head movements to accurately identify sound location when trapping a ball. Accurate sound localization is likely important for motor learning of ball trapping in blind football. However, whether head movements affect the acquisition of ball-trapping skills remains unclear. Therefore, this study examined the effect of head movements on skill acquisition during ball trapping. Overall, 20 sighted male college students were recruited and assigned to one of the following two groups: the conventional training group, where they were instructed to move leftward and rightward to align their body with the ball's trajectory, and the head-movement-focused group, where they were instructed to follow the ball with their faces until the ball touched their feet, in addition to the conventional training instructions. Both groups underwent a 2-day training for ball trapping according to the specific instructions. The head-movement-focused group showed a decrease in errors in ball trapping at near distances and with larger downward head rotations in the sagittal plane compared to the conventional training group, indicating that during the skill acquisition training for ball trapping, the sound source can be localized more accurately using larger head rotations toward the ball. These results may help beginner-level players acquire better precision in their movements while playing blind football.

Blind football players use head movements to accurately identify sound location when trapping a ball. Accurate sound localization is likely important for motor learning of ball trapping in blind football. However, whether head movements affect the acquisition of ball-trapping skills remains unclear. Therefore, this study examined the effect of head movements on skill acquisition during ball trapping. Overall, 20 sighted male college students were recruited and assigned to one of the following two groups: the conventional training group, where they were instructed to move leftward and rightward to align their body with the ball's trajectory, and the head-movement-focused group, where they were instructed to follow the ball with their faces until the ball touched their feet, in addition to the conventional training instructions. Both groups underwent a 2-day training for ball trapping according to the specific instructions. The head-movement-focused group showed a decrease in errors in ball trapping at near distances and with larger downward head rotations in the sagittal plane compared to the conventional training group, indicating that during the skill acquisition training for ball trapping, the sound source can be localized more accurately using larger head rotations toward the ball. These results may help beginner-level players acquire better precision in their movements while playing blind football. [ABSTRACT FROM AUTHOR]

BACKGROUND:Fatigue is a common adverse event during lenvatinib treatment in patients with hepatocellular carcinoma. One mechanism contributing to development of fatigue might involve abnormal adenosine triphosphate synthesis that is caused by carnitine deficiency. To address this possibility, we examined the relationship between carnitine levels and fatigue during lenvatinib treatment. METHODS:This prospective study evaluated 20 patients with hepatocellular carcinoma who underwent lenvatinib treatment. Both blood and urine samples were collected from the patients before starting lenvatinib therapy (day 0), and on days 3, 7, 14, and 28 thereafter. Plasma and urine concentrations of free and acyl carnitine (AC) were assessed at each time point. The changes in daily fatigue were evaluated using the Brief Fatigue Inventory (BFI). RESULTS:Plasma levels of free carnitine (FC) at days 3 and 7 were significantly higher compared with baseline (p = 0.005, p = 0.005, respectively). The urine FC level at day 3 was significantly higher compared with baseline (p = 0.030) and that of day 7 tended to be higher compared with baseline (p = 0.057). The plasma AC concentration at days 14 and 28 was significantly higher compared with that of baseline (p = 0.002, p = 0.005, respectively). The plasma AC-to-FC (AC/FC) ratio on days 14 and 28 was significantly higher compared with baseline (p = 0.001, p = 0.003, respectively). There were significant correlations between the plasma AC/FC ratio and the change in the BFI score at days 14 and 28 (r = 0.461, p = 0.041; r = 0.770, p = 0.002, respectively). CONCLUSIONS:Longitudinal assessments of carnitine and fatigue in patients with hepatocellular carcinoma suggest that lenvatinib affects the carnitine system in patients undergoing lenvatinib therapy and that carnitine insufficiency increases fatigue. The occurrence of carnitine insufficiency may be a common cause of fatigue during the treatment.

Chromosome abnormalities induces profound alterations in gene expression, leading to various disease phenotypes. Recent studies on yeast and mammalian cells have demonstrated that aneuploidy exerts detrimental effects on organismal growth and development, regardless of the karyotype, suggesting that aneuploidy-associated stress plays an important role in disease pathogenesis. However, whether and how this effect alters cellular homeostasis and long-term features of human disease are not fully understood. Here, we aimed to investigate cellular stress responses in human trisomy syndromes, using fibroblasts and induced pluripotent stem cells (iPSCs). Dermal fibroblasts derived from patients with trisomy 21, 18 and 13 showed a severe impairment of cell proliferation and enhanced premature senescence. These phenomena were accompanied by perturbation of protein homeostasis, leading to the accumulation of protein aggregates. We found that treatment with sodium 4-phenylbutyrate (4-PBA), a chemical chaperone, decreased the protein aggregates in trisomy fibroblasts. Notably, 4-PBA treatment successfully prevented the progression of premature senescence in secondary fibroblasts derived from trisomy 21 iPSCs. Our study reveals aneuploidy-associated stress as a potential therapeutic target for human trisomies, including Down syndrome.

The incidence of heatstroke has been increasing. Heatstroke has been shown to affect physiological barrier functions. However, there are few studies of the effect of heat stress on the blood-brain barrier (BBB) function. In this study, we investigated the influence of heat stress on brain microvascular endothelial cells in vivo and in vitro. Heatstroke model mice administered Texas Red-dextran showed leakage outside the brain vessel walls. In addition, trans-endothelial electrical resistance (TEER) value was significantly reduced in induced pluripotent stem (iPS) cell-derived brain microvascular endothelial cells under heat stress by reducing claudin-5 expression. In addition, our results showed that the expression level of P-glycoprotein (P-gp) was increased in iPS cell-derived brain microvascular endothelial cells under heat stress. Furthermore, serum from heatstroke model mice could impair the BBB integrity of iPS cell-derived brain microvascular endothelial cells. These results suggest that BBB integrity was affected by heat stress in vivo and in vitro and provide important insights into the development of new therapeutic strategies for heatstroke patients.

For about 70 years, L-glucose had been considered non-metabolizable by either mammalian or bacterial cells. Recently, however, an L-glucose catabolic pathway has been discovered in Paracoccus laeviglucosivorans, and the genes responsible cloned. Scyllo-inositol dehydrogenase is involved in the first step in the pathway that oxidizes L-glucose to produce L-glucono-1,5-lactone with concomitant reduction of NAD+ dependent manner. Here, we report the crystal structure of the ternary complex of scyllo-inositol dehydrogenase with NAD+ and L-glucono-1,5-lactone at 1.8 Å resolution. The enzyme adopts a homo-tetrameric structure, similar to those of the inositol dehydrogenase family, and the electron densities of the bound sugar was clearly observed, allowing identification of the residues responsible for interaction with the substrate in the catalytic site. In addition to the conserved catalytic residues (Lys106, Asp191, and His195), another residue, His318, located in the loop region of the adjacent subunit, is involved in substrate recognition. Site-directed mutagenesis confirmed the role of these residues in catalytic activity. We also report the complex structures of the enzyme with myo-inositol and scyllo-inosose. The Arg178 residue located in the flexible loop at the entrance of the catalytic site is also involved in substrate recognition, and plays an important role in accepting both L-glucose and inositols as substrates. On the basis of these structural features, which have not been identified in the known inositol dehydrogenases, and a phylogenetic analysis of IDH family enzymes, we suggest a novel subfamily of the GFO/IDH/MocA family. Since many enzymes in this family have not biochemically characterized, our results could promote to find their activities with various substrates.

Porphyromonas gingivalis is a bacterium frequently isolated from chronic periodontal lesions and is involved in the development of chronic periodontitis. To colonize the gingival crevice, P. gingivalis has to adapt to environmental stresses. Microbial gene expression is regulated by transcription factors such as those in two-component systems and extracytoplasmic function (ECF) sigma factors. ECF sigma factors are involved in the regulation of environmental stress response genes; however, the roles of individual ECF sigma factors are largely unknown. The purpose of this study was to investigate the functions, including autoaggregation, hemagglutination, gingipain activity, susceptibility to antimicrobial agents, and surface structure formation, of P. gingivalis ECF sigma factors encoded by SigP (PGN_0274), SigCH (PGN_0319), PGN_0450, PGN_0970, and SigH (PGN_1740). Various physiological aspects of the sigP mutant were affected; autoaggregation was significantly decreased at 60 min (p < 0.001), hemagglutination activity was markedly reduced, and enzymatic activities of Kgp and Rgps were significantly decreased (p < 0.001). The other mutants also showed approximately 50% reduction in Rgps activity. Kgp activity was significantly reduced in the sigH mutant (p < 0.001). No significant differences in susceptibilities to tetracycline and ofloxacin were observed in the mutants compared to those of the wild-type strain. However, the sigP mutant displayed an increased susceptibility to ampicillin, whereas the PGN_0450 and sigH mutants showed reduced susceptibility. Transmission electron microscopy images revealed increased levels of outer membrane vesicles formed at the cell surfaces of the sigP mutant. These results indicate that SigP is important for bacterial surface-associated activities, including gingipain activity, autoaggregation, hemagglutination, vesicle formation, and antimicrobial susceptibility.

Capnocytophaga ochracea is present in the dental plaque biofilm of patients with periodontitis. Biofilm cells change their phenotype through quorum sensing in response to fluctuations in cell-population density. Quorum sensing is mediated by auto-inducers (AIs). AI-2 is involved in intercellular signaling, and production of its distant precursor is catalyzed by LuxS, an enzyme involved in the activated methyl cycle. Our aim was to clarify the role of LuxS in biofilm formation by C. ochracea. Two luxS-deficient mutants, TmAI2 and LKT7, were constructed from C. ochracea ATCC 27872 by homologous recombination. The mutants produced significantly less AI-2 than the wild type. The growth rates of these mutants were similar to that of the wild-type in both undiluted Tryptic soy broth and 0.5 × Tryptic soy broth. However, according to crystal violet staining, they produced significantly less biofilm than the wild type. Confocal laser scanning microscopy and scanning electron microscopy showed that the biofilm of the TmAI2 strain had a rougher structure than that of the wild type. Complementation of TmAI-2 with extrinsic AI-2 from the culture supernatant of wild-type strain did not restore biofilm formation by the TmAI2 strain, but complementation of LKT7 strain with luxS partially restored biofilm formation. These results indicate that LuxS is involved in biofilm formation by C. ochracea, and that the attenuation of biofilm formation by the mutants is likely caused by a defect in the activated methyl cycle rather than by a loss of AI-2.

BackgroundThe pluripotent state of embryonic stem (ES) cells is controlled by a network of specific transcription factors. Recent studies also suggested the significant contribution of mitochondria on the regulation of pluripotent stem cells. However, the molecules involved in these regulations are still unknown.Methodology/principal findingsIn this study, we found that prohibitin 2 (PHB2), a pleiotrophic factor mainly localized in mitochondria, is a crucial regulatory factor for the homeostasis and differentiation of ES cells. PHB2 was highly expressed in undifferentiated mouse ES cells, and the expression was decreased during the differentiation of ES cells. Knockdown of PHB2 induced significant apoptosis in pluripotent ES cells, whereas enhanced expression of PHB2 contributed to the proliferation of ES cells. However, enhanced expression of PHB2 strongly inhibited ES cell differentiation into neuronal and endodermal cells. Interestingly, only PHB2 with intact mitochondrial targeting signal showed these specific effects on ES cells. Moreover, overexpression of PHB2 enhanced the processing of a dynamin-like GTPase (OPA1) that regulates mitochondrial fusion and cristae remodeling, which could induce partial dysfunction of mitochondria.Conclusions/significanceOur results suggest that PHB2 is a crucial mitochondrial regulator for homeostasis and lineage-specific differentiation of ES cells.

Vinculin, a 116-kDa membrane cytoskeletal protein, is an important molecule for cell adhesion; however, little is known about its other cellular functions. Here, we demonstrated that vinculin binds to Rab5 and is required for Staphylococcus aureus (S. aureus) uptake in cells. Viunculin directly bound to Rab5 and enhanced the activation of S. aureus uptake. Over-expression of active vinculin mutants enhanced S. aureus uptake, whereas over-expression of an inactive vinculin mutant decreased S. aureus uptake. Vinculin bound to Rab5 at the N-terminal region (1-258) of vinculin. Vinculin and Rab5 were involved in the S. aureus-induced phosphorylation of MAP kinases (p38, Erk, and JNK) and IL-6 expression. Finally, vinculin and Rab5 knockdown reduced infection of S. aureus, phosphorylation of MAPKs and IL-6 expression in murine lungs. Our results suggest that vinculin binds to Rab5 and that these two molecules cooperatively enhance bacterial infection and the inflammatory response.

Fission yeast, Schizoaccharomyces pombe, is a model for studying cellular quiescence. Shifting to a medium that lacks a nitrogen-source induces proliferative cells to enter long-term G0 quiescence. Klf1 is a Krüppel-like transcription factor with a 7-amino acid Cys2His2-type zinc finger motif. The deletion mutant, ∆klf1, normally divides in vegetative medium, but proliferation is not restored after long-term G0 quiescence. Cell biologic, transcriptomic, and metabolomic analyses revealed a unique phenotype of the ∆klf1 mutant in quiescence. Mutant cells had diminished transcripts related to signaling molecules for switching to differentiation; however, proliferative metabolites for cell-wall assembly and antioxidants had significantly increased. Further, the size of ∆klf1 cells increased markedly during quiescence due to the aberrant accumulation of Calcofluor-positive, chitin-like materials beneath the cell wall. After 4 weeks of quiescence, reversible proliferation ability was lost, but metabolism was maintained. Klf1 thus plays a role in G0 phase longevity by enhancing the differentiation signal and suppressing metabolism for growth. If Klf1 is lost, S. pombe fails to maintain a constant cell size and normal cell morphology during quiescence.

Porphyromonas gingivalis is a bacterium frequently isolated from chronic periodontal lesions and is involved in the development of chronic periodontitis. To colonize the gingival crevice, P. gingivalis has to adapt to environmental stresses. Microbial gene expression is regulated by transcription factors such as those in two-component systems and extracytoplasmic function (ECF) sigma factors. ECF sigma factors are involved in the regulation of environmental stress response genes; however, the roles of individual ECF sigma factors are largely unknown. The purpose of this study was to investigate the functions, including autoaggregation, hemagglutination, gingipain activity, susceptibility to antimicrobial agents, and surface structure formation, of P. gingivalis ECF sigma factors encoded by SigP (PGN_0274), SigCH (PGN_0319), PGN_0450, PGN_0970, and SigH (PGN_1740). Various physiological aspects of the sigP mutant were affected; autoaggregation was significantly decreased at 60 min (p < 0.001), hemagglutination activity was markedly reduced, and enzymatic activities of Kgp and Rgps were significantly decreased (p < 0.001). The other mutants also showed approximately 50% reduction in Rgps activity. Kgp activity was significantly reduced in the sigH mutant (p < 0.001). No significant differences in susceptibilities to tetracycline and ofloxacin were observed in the mutants compared to those of the wild-type strain. However, the sigP mutant displayed an increased susceptibility to ampicillin, whereas the PGN_0450 and sigH mutants showed reduced susceptibility. Transmission electron microscopy images revealed increased levels of outer membrane vesicles formed at the cell surfaces of the sigP mutant. These results indicate that SigP is important for bacterial surface-associated activities, including gingipain activity, autoaggregation, hemagglutination, vesicle formation, and antimicrobial susceptibility. [ABSTRACT FROM AUTHOR]

Capnocytophaga ochracea is present in the dental plaque biofilm of patients with periodontitis. Biofilm cells change their phenotype through quorum sensing in response to fluctuations in cell-population density. Quorum sensing is mediated by auto-inducers (AIs). AI-2 is involved in intercellular signaling, and production of its distant precursor is catalyzed by LuxS, an enzyme involved in the activated methyl cycle. Our aim was to clarify the role of LuxS in biofilm formation by C. ochracea. Two luxS-deficient mutants, TmAI2 and LKT7, were constructed from C. ochracea ATCC 27872 by homologous recombination. The mutants produced significantly less AI-2 than the wild type. The growth rates of these mutants were similar to that of the wild-type in both undiluted Tryptic soy broth and 0.5 × Tryptic soy broth. However, according to crystal violet staining, they produced significantly less biofilm than the wild type. Confocal laser scanning microscopy and scanning electron microscopy showed that the biofilm of the TmAI2 strain had a rougher structure than that of the wild type. Complementation of TmAI-2 with extrinsic AI-2 from the culture supernatant of wild-type strain did not restore biofilm formation by the TmAI2 strain, but complementation of LKT7 strain with luxS partially restored biofilm formation. These results indicate that LuxS is involved in biofilm formation by C. ochracea, and that the attenuation of biofilm formation by the mutants is likely caused by a defect in the activated methyl cycle rather than by a loss of AI-2. [ABSTRACT FROM AUTHOR]

Background: The pluripotent state of embryonic stem (ES) cells is controlled by a network of specific transcription factors. Recent studies also suggested the significant contribution of mitochondria on the regulation of pluripotent stem cells. However, the molecules involved in these regulations are still unknown. Methodology/Principal Findings: In this study, we found that prohibitin 2 (PHB2), a pleiotrophic factor mainly localized in mitochondria, is a crucial regulatory factor for the homeostasis and differentiation of ES cells. PHB2 was highly expressed in undifferentiated mouse ES cells, and the expression was decreased during the differentiation of ES cells. Knockdown of PHB2 induced significant apoptosis in pluripotent ES cells, whereas enhanced expression of PHB2 contributed to the proliferation of ES cells. However, enhanced expression of PHB2 strongly inhibited ES cell differentiation into neuronal and endodermal cells. Interestingly, only PHB2 with intact mitochondrial targeting signal showed these specific effects on ES cells. Moreover, overexpression of PHB2 enhanced the processing of a dynamin-like GTPase (OPA1) that regulates mitochondrial fusion and cristae remodeling, which could induce partial dysfunction of mitochondria. Conclusions/Significance: Our results suggest that PHB2 is a crucial mitochondrial regulator for homeostasis and lineage-specific differentiation of ES cells. [ABSTRACT FROM AUTHOR]

Vinculin, a 116-kDa membrane cytoskeletal protein, is an important molecule for cell adhesion; however, little is known about its other cellular functions. Here, we demonstrated that vinculin binds to Rab5 and is required for Staphylococcus aureus (S. aureus) uptake in cells. Viunculin directly bound to Rab5 and enhanced the activation of S. aureus uptake. Over-expression of active vinculin mutants enhanced S. aureus uptake, whereas over-expression of an inactive vinculin mutant decreased S. aureus uptake. Vinculin bound to Rab5 at the N-terminal region (1-258) of vinculin. Vinculin and Rab5 were involved in the S. aureus-induced phosphorylation of MAP kinases (p38, Erk, and JNK) and IL-6 expression. Finally, vinculin and Rab5 knockdown reduced infection of S. aureus, phosphorylation of MAPKs and IL-6 expression in murine lungs. Our results suggest that vinculin binds to Rab5 and that these two molecules cooperatively enhance bacterial infection and the inflammatory response. [ABSTRACT FROM AUTHOR]

Porphyromonas gingivalis is a keystone pathogen for periodontal disease. The bacteria are black-pigmented and require heme for growth. P. gingivalis exhibit resistance to many antimicrobial peptides, which contributes to their success in the oral cavity. P. gingivalis W50 was resistant to the antimicrobial peptide LGL13K but susceptible to the all-D-amino acid stereoisomer, DGL13K. Upon prolonged exposure to DGL13K, a novel non-pigmented mutant was isolated. Exposure to the L-isomer, LGL13K, did not produce a non-pigmented mutant. The goal of this study was to characterize the genomic and cellular changes that led to the non-pigmented phenotype upon treatment with DGL13K. The non-pigmented mutant showed a low minimum inhibitory concentration and two-fold extended minimum duration for killing by DGL13K, consistent with tolerance to this peptide. The DGL13K-tolerant bacteria exhibited synonymous mutations in the hagA gene. The mutations did not prevent mRNA expression but were predicted to alter mRNA structure. The non-pigmented bacteria were deficient in hemagglutination and hemoglobin binding, suggesting that the HagA protein was not expressed. This was supported by whole cell enzyme-linked immunosorbent assay and gingipain activity assays, which suggested the absence of HagA but not of two closely related gingipains. In vivo virulence was similar for wild type and non-pigmented bacteria in the Galleria mellonella model. The results suggest that, unlike LGL13K, DGL13K can defeat multiple bacterial resistance mechanisms but bacteria can gain tolerance to DGL13K through mutations in the hagA gene. [ABSTRACT FROM AUTHOR]

Objective: To explore whether miR-199a-5p regulated BBB integrity through PI3K/Akt pathway after ischemia stroke. Methods: Adult male Sprague-Dawley rats with permanent middle cerebral artery occlusion(MCAO) were used in experiment. The Ludmila Belayev 12-point scoring was used to measure the neurological function of MCAO rats. The Evans Blue Stain, immunofluorescence staining, western-blotting and RT-PCR were performed to evaluate the effects of miR-199a-5p mimic on BBB integrity in rats following MCAO. Results: The result suggested that miR-199a-5p mimic treatment possessed the potential to boost proprioception and motor activity of MCAO rats. MiR-199a-5p decreased the expression of PIK3R2 after MCAO, activated Akt signaling pathway, and increased the expression of Claudin-5 and VEGF in the ischemic penumbra. Furthermore, miR-199a-5p alleviated inflammation after cerebral ischemia. BBB leakage and neurocyte apoptosis were cut down in MCAO rats treated with miR-199a-5p mimic. Conclusions: MiR-199a-5p mimic decreased the expression of PIK3R2 and activated Akt signaling pathway after ischemia stroke, reduced the expression of inflammatory cytokines, and attenuated BBB disruption after ischemic stroke. [ABSTRACT FROM AUTHOR]

Left atrial strain (LAS) measured by two-dimensional speckle tracking echocardiography (2DSTE) is considered to be a marker of LA structural remodeling, but it remains unsettled. We investigated the potential usefulness and clinical relevance of LAS to detect atrial remodeling including fibrosis by analyzing gene expression in cardiovascular surgery patients. Preoperative 2DSTE was performed in 131 patients (92 patients with sinus rhythm [SR] patients including paroxysmal AF [PAF], 39 atrial fibrillation [AF]) undergoing cardiovascular surgery. Atrial samples were obtained from the left atrial appendages, and mRNA expression level was analyzed by real-time reverse transcription polymerase chain reaction (RT-PCR) in 59 cases (24 PAF, 35 AF). Mean value of left atrial reservoir strain (mLASr) correlated with left atrial volume index (LAVI), and left atrial conduit strain (mLAScd). mLASr also correlated with left atrial contractile strain (mLASct) in SR patients including PAF. mLASr was significantly lower, and LAVI was higher, in the AF group, compared with SR patients including PAF. The expression of COL1A1 mRNA encoding collagen type I α1 significantly increased in AF patients (p = 0.031). mLASr negatively correlated with COL1A1 expression level, and multivariate regression analysis showed that mLASr was an independent predictor of atrial COL1A1 expression level, even after adjusting for age, sex, and BMI. But, neither mLAScd / mLASct nor LAVI (bp) correlated with COL1A1 gene expression. The expression level of COL1A1 mRNA strongly correlated with ECM-related genes (COL3A1, FN1). It also correlated ECM degradation-related genes (MMP2, TIMP1, and TIMP2), pro-fibrogenic cytokines (TGFB1 encoding TGFβ1, END1, PDGFD, CTGF), oxidant stress-related genes (NOX2, NOX4), ACE, inflammation-related genes (NLRP, IL1B, MCP-1), and apoptosis (BAX). Among the fibrosis-related genes examined, univariable regression analysis showed that log (COL1A1) was associated with log (TGFB1) (adjusted R2 = 0.685, p<0.001), log (NOX4) (adjusted R2 = 0.622, p<0.001), log (NOX2) (adjusted R2 = 0.611, p<0.001), suggesting that TGFB1 and NOX4 was the potent independent determinants of COL1A1 expression level. mLASr negatively correlated with the ECM-related genes, and fibrosis-related gene expression level including TGFB1, NOX2, and NLRP3 in PAF patients. PAF patients with low mLASr had higher expression of the fibrosis-related gene expression, compared with those with high mLASr. These results suggest that LASr correlates with atrial COL1A1 gene expression associated with fibrosis-related gene expression. Patients with low LASr exhibit increased atrial fibrosis-related gene expression, even those with PAF, highlighting the utility of LAS as a marker for LA fibrosis in cardiovascular surgery patients. [ABSTRACT FROM AUTHOR]

Nowadays, environmental issues and cleaner products are interest to many customers, considering whether to buy or continue using a product. This will affect the perception, attitude of upper managers in the process of strategic choices and operational management behavior. This study is based on the Upper Echelon Theory, research under the influence of customer pressure to attitude toward the environmental, decision choices for cleaner production strategies, implementation of environmental management accounting towards achieving green competitive advantage of Vietnamese manufacturing enterprises. In addition, the role of two moderator variables: (1) perceived benefit of cleaner production strategies and (2) perceived benefit of environmental management accounting in the research model is also considered. This study surveyed 234 CEOs of Vietnamese manufacturing enterprises. This study employed PLS-SEM, version 3 for data analysis. Results have shown that all relationships are statistically significant. Moderator variables have a statistically significant and positive impact in relationships in which they play a moderator role. This study helps CEOs realize the importance of producing products that are customer-oriented, environmentally friendly, and the implementation of environmental management accounting will have a strong impact on achieving a sustainable competitive advantage. [ABSTRACT FROM AUTHOR]

The National Sustainable Development Agenda Innovation Demonstration Zones (NSDAIDZs) aim to spearhead green development through scientific and technological innovation, showcasing sustainable development to other regions in China and offering valuable insights for countries worldwide. Taking Chengde City, which is one of the cities in the second batch of NSDAIDZs, as a case study, we examine the quantitative impact of technological innovation on green development. Additionally, it investigates the threshold effect of Research and development investments (R&D investments) on the relationship between technological innovation and green development. The results indicate that: (1) technological innovation has a positive promoting effect on green development, with a 1.01% increase in green development for every one unit increase in technological innovation; (2) The positive effect of technological innovation on green development becomes fully realized only when R&D investments and the upgrading of industrial structure surpass a specific threshold value. We contribute to the existing research on the connection between technological innovation and green development in innovation demonstration zones. It also provides empirical insights to foster a mutually beneficial relationship between R&D investments, industrial structure upgrading, and technological innovation, ultimately maximizing the promoting role of technological innovation in green development. [ABSTRACT FROM AUTHOR]

Non-thermal atmospheric-pressure plasma (NTAPP) is attracting widespread interest for use in medical applications. The tissue repair capacity of NTAPP has been reported in various fields; however, little is known about its effect on fracture healing. Non-union or delayed union after a fracture is a clinical challenge. In this study, we aimed to investigate how NTAPP irradiation promotes fracture healing in a non-union fracture model and its underlying mechanism, in vitro and in vivo. For the in vivo study, we created normal and non-union fracture models in LEW/SsNSlc rats to investigate the effects of NTAPP. To create a fracture, a transverse osteotomy was performed in the middle of the femoral shaft. To induce the non-union fracture model, the periosteum surrounding the fracture site was cauterized after a normal fracture model was created. The normal fracture model showed no significant difference in bone healing between the control and NTAPP-treated groups. The non-union fracture model demonstrated that the NTAPP-treated group showed consistent improvement in fracture healing. Histological and biomechanical assessments confirmed the fracture healing. The in vitro study using pre-osteoblastic MC3T3-E1 cells demonstrated that NTAPP irradiation under specific conditions did not reduce cell proliferation but did enhance osteoblastic differentiation. Overall, these results suggest that NTAPP is a novel approach to the treatment of bone fractures. [ABSTRACT FROM AUTHOR]

Bumblebees are crucial for both natural ecosystems and agriculture, but their decline in distribution and abundance over the past decade is alarming. The global importance of bumblebees in natural ecosystems and agricultural food production cannot be overstated. However, the reported decline over the past decade has led to a surge of interest in understanding and addressing bumblebee population decline. Hence, we aimed to detect disruptions in the gut microbiome of male and worker bumblebees reared indoor and outdoor to assess potential resilience to environmental stress. Using the Illumina MiSeq platform for 16s rRNA amplicon sequencing, we analyzed the gut microbiome of male and worker bees that were raised indoors (designated as the IM and IW group) and those that were raised outdoors (also designated as the OM and OW group). Our results show presence of core bacteria Neisseriaceae, Orbaceae, Lactobacillaceae and Bifidobacteriaceae from indoor reared worker bees. However, a higher abundance of Bifidobacterium and absence of Fructobacillus from indoor reared worker bees was also observed. Indoor-reared male bees had lower diversity and fewer observed OTUs compared to outdoor-reared male bees. Additionally, the relative abundance of Actinobacteriota, Bacteroidota, and Firmicutes was significantly lower in indoor-reared males, while Proteobacteria was significantly increased. Despite this, we did not observe any dysbiosis in the gut microbiota of indoor-reared bumblebees when comparing the role of the gut symbionts among the groups. These results suggest that indoor-reared Bombus terrestris may be resilient to environmental stress when used as outdoor pollinators. [ABSTRACT FROM AUTHOR]

Prior research has questioned the appropriateness of internal focus instructions or the juxtaposition to external and control conditions. Moreover, there has been a lack of research conducted to test a variety of internal conditions on motor performance. The purpose of the present study was to address those critiques and add to the attentional focus literature by varying the location of an internal focus while performing a standing long jump. Participants performed a standing long jump during five separate conditions (internal focus: toes, knees, hips, arms; and control). The analysis revealed that all internal focus conditions performed worse than the control condition. Furthermore, the only difference between internal conditions was found between arms and knees, where the knee condition resulted in a significantly shorter jump distance relative to the arms. Regardless of the location specified, all internal focus conditions led to detriments in jump performance when compared to the control condition. These findings add to a large body of work demonstrating the importance of instructional content on motor performance. [ABSTRACT FROM AUTHOR]

Interleukin-17F (IL-17F), considered a pro-inflammatory cytokine, has been shown to contribute to skeletal tissue degradation and hence chronic inflammation in rheumatoid arthritis (RA). In this study we utilized bioinformatics tools to analyze the effect of three exonic SNPs (rs2397084, rs11465553, and rs763780) on the structure and function of the IL-17F gene, and evaluated their association with RA in Pakistani patients. The predicted deleterious and damaging effects of identified genetic variants were assessed through the utilization of multiple bioinformatics tools including PROVEAN, SNP&GO, SIFT, and PolyPhen2. Structural and functional effects of these variants on protein structures were evaluated through the use of additional tools such as I-Mutant, MutPred, and ConSurf. Three-dimensional (3D) models of both the wild-type and mutant proteins were constructed through the utilization of I-TASSER software, with subsequent structural comparisons between the models conducted through the use of the TM-align score. A total of 500 individuals, 250 cases and 250 controls, were genotyped through Tri-ARMS-PCR method and the resultant data was statistically analyzed using various inheritance models. Our bioinformatics analysis showed significant structural differences for wild type and mutant protein (TM-scores and RMSD values were 0.85934 and 2.34 for rs2397084 (E126G), 0.87388 and 2.49 for rs11465553 (V155I), and 0.86572 and 0.86572 for rs763780 (H161R) with decrease stability for the later. Overall, these tools enabled us to predict that these variants are crucial in causing disease phenotypes. We further tested each of these single nucleotide variants for their association with RA. Our analysis revealed a strong positive association between the genetic variant rs763780 and the risk of developing rheumatoid arthritis (RA) at both the genotypic and allelic levels. The genotypic association was statistically significant[χ2 = 111.8; P value <0.0001], as was the allelic level [OR 3.444 (2.539–4.672); P value 0.0008]. These findings suggest that the presence of this genetic variant may increase the susceptibility to RA. Similarly, we observed a significant distribution of the genetic variant rs11465553 at the genotypic level [χ2 = 25.24; P value = 0.0001]. However, this variant did not show a significant association with RA at the allelic level [OR = 1.194 (0.930–1.531); P value = 0.183]. However, the distribution of variant rs2397084 was more or less random across our sample with no significant association either at genotypic and or allelic level. Put together, our association study and in silico prediction of decreasing of IL17-F protein stabilty confirmed that two SNPs, rs11465553 and rs763780 are crucial to the suscetibility of and showed that these RA in Pakistani patients. [ABSTRACT FROM AUTHOR]

The purpose of this study was to evaluate, in vivo, the biocompatibility, biomineralization, collagen maturation and the in vitro antibacterial and cytotoxicity of resinous endodontic sealers containing calcium hydroxide. Forty rats were implanted with polyethylene tubes containing Sealer 26, Sealer Plus, Dia-ProSeal and an empty tube, examined after 7, 15, 30 and 60 days. Antimicrobial activity was evaluated against Enterococcus faecalis by Agar Diffusion Test (ADT) through inhibition zones. For cytotoxicity, undifferentiated pulp cells (OD-21) were cultured and assessed using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay, exposed to dilution of serial extracts at 6, 24, 48h. Cytotoxicity was analyzed by two-way ANOVA and Bonferroni correction. Kruskal-Wallis test followed by Dunn test was performed for nonparametric data (p<0.05). MTT assay revealed cell proliferation affected by sealers extract in all periods (p<0.0001), except for Dia-Proseal and Sealer Plus ⅛ dilution. Subcutaneous analysis showed at day 7th moderate inflammatory infiltration. After 30 days, Sealer 26 still showed moderate inflammatory infiltrate compared to mild inflammation from control and Dia-ProSeal (p = 0.006). At day 60th, all groups showed similar mild inflammatory infiltrate (p>0.05). Sealer 26 induced more biomineralization than other sealers in all periods. At 7 and 15 days, all sealers had significant percentage of immature collagen fibers. After 60 days Sealer 26 showed more mature fibers compared to other sealers (p<0.001). All sealers had a smaller zone of inhibition than chlorhexidine, but with no significant difference among any group (p>0.05). All sealers showed satisfactory biological responses with in vitro/in vivo biocompatibility and antimicrobial activity against planktonic bacteria. Sealer 26 induced more biomineralization than Sealer Plus and Dia-ProSeal. [ABSTRACT FROM AUTHOR]

Since dual channel supply chain has become one of the main modes of supply chain, its research has acquired great significance. This paper constructs a low-carbon dual channel supply chain composed of one manufacturer and one retailer. The manufacturer produces low-carbon product and high carbon product with substitution relationship. The retailer sells high carbon product in traditional channel. The manufacturer also sells low-carbon product in direct channel. The government, manufacturer and retailer conduct a three-level Stackelberg game. This paper studies the optimal decisions of the government, manufacturer and retailer under the three modes of carbon tax + subsidy, carbon tax only and subsidy only. It has been found that for social welfare, the carbon tax + subsidy model is higher than the subsidy model and carbon tax model. For manufacturer profit, the subsidy mode is the highest, followed by the carbon tax + subsidy mode. For retailer profit, the carbon tax + subsidy model is equal to the carbon tax model. The increase in the proportion of consumers who prefer high carbon product in the total market or product cost of low-carbon product, will increase the profit of traditional channel and reduce the profit of direct channel. [ABSTRACT FROM AUTHOR]

Objectives: Infections are the most common non-cardiovascular cause of death among dialysis patients. Earlier studies have shown similar or higher risk of infectious complications in peritoneal dialysis (PD) compared to hemodialysis (HD) patients, but comparisons to home HD patients have been rare. We investigated the risk of severe infections after start of continuous ambulatory PD (CAPD) and automated PD (APD) as compared to home HD. Methods: All adult patients (n = 536), who were on home dialysis at day 90 from starting kidney replacement therapy (KRT) between 2004 and 2017 in Helsinki healthcare district, were included. We defined severe infection as an infection with C-reactive protein of 100 mg/l or higher. Cumulative incidence of first severe infection was assessed considering death as a competing risk. Hazard ratios were estimated using Cox regression with propensity score adjustment. Results: The risk of getting a severe infection during the first year of dialysis was 35% for CAPD, 25% for APD and 11% for home HD patients. During five years of follow-up, the hazard ratio of severe infection was 2.8 [95% CI 1.6–4.8] for CAPD and 2.2 [95% CI 1.4–3.5] for APD in comparison to home HD. Incidence rate of severe infections per 1000 patient-years was 537 for CAPD, 371 for APD, and 197 for home HD patients. When excluding peritonitis, the incidence rate was not higher among PD than home HD patients. Conclusions: CAPD and APD patients had higher risk of severe infections than home HD patients. This was explained by PD-associated peritonitis. [ABSTRACT FROM AUTHOR]

This partially randomised controlled, crossover study sought to investigate the effects of normobaric hypoxia (NH) and hypobaric hypoxia (HH) on cognitive performance, the physiological response at rest and after a 3-min step-test. Twenty healthy participants (10 females and 10 males, 27.6±6.2yrs, 73.6±13.7kg, 175.3±8.9cm) completed a cognitive performance test, followed by the modified Harvard-step protocol, in four environments: normobaric normoxia (NN; PiO2: 146.0±1.5mmHg), NH (PiO2: 100.9±1.3mmHg), HH at the first day of ascent (HH1: PiO2 = 105.6±0.4mmHg) and HH after an overnight stay (HH2: PiO2 = 106.0±0.5mmHg). At rest and/or exercise, SpO2, NIRS, and cardiovascular and perceptual data were collected. The cerebral tissue oxygenation index and the cognitive performance (throughput, accuracy, and reaction time) were not different between the hypoxic conditions (all p>0.05). In NH, SpO2 was higher compared to HH1 (ΔSpO2 NH vs HH1: 1.7±0.5%, p = 0.003) whilst heart rate (ΔHR NH vs HH2: 5.8±2.6 bpm, p = 0.03) and sympathetic activation (ΔSNSi NH vs HH2: 0.8±0.4, p = 0.03) were lower in NH compared to HH2. Heart rate (ΔHR HH1 vs HH2: 6.9±2.6 bpm, p = 0.01) and sympathetic action (ΔSNSi HH1 vs HH2: 0.9±0.4, p = 0.02) were both lower in HH1 compared to HH2. In conclusion, cognitive performance and cerebral oxygenation didn't differ between the hypoxic conditions. SpO2 was only higher in NH compared to HH1. In HH2, heart rate and sympathetic activation were higher compared to both NH and HH1. These conclusions account for a PiO2 between 100–106 mmHg. [ABSTRACT FROM AUTHOR]

Objectives: T-helper 17 cell-mediated response and their effector IL-17 cytokine induced by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection is a major cause of COVID-19 disease severity and death. Therefore, the study aimed to determine if IL-17 level in saliva mirrors its circulatory level and hence can be used as a non-invasive biomarker for disease severity. Methods: Interleukin-17 (IL-17) level was evaluated by ELISA in saliva and blood of 201 adult COVID-19 patients with different levels of severity. The IL-17 saliva level was also associated with COVID-19 disease severity, and need for mechanical ventilation and/or death within 29 days after admission of severe COVID-19 patients. Results: We found that IL-17 level in saliva of COVID-19 patients reflected its circulatory level. High IL-17 level in saliva was associated with COVID-19 severity (P<0.001), need for mechanical ventilation (P = 0.002), and/or death by 29 days (P = 0.002), after adjusting for patients' demographics, comorbidity, and COVID-19 serum severity markers such as D-Dimer, C-reactive protein, and ferritin. Conclusion: We propose that saliva IL-17 level could be used as a biomarker to identify patients at risk of developing severe COVID-19. [ABSTRACT FROM AUTHOR]

This study evaluated the effects of maternal fish oil supplementation rich in n-3 PUFA on the performance and bone health of offspring broilers at embryonic development stage and at market age. Ross 708 broiler breeder hens were fed standard diets containing either 2.3% soybean oil (SO) or fish oil (FO) for 28 days. Their fertilized eggs were collected and hatched. For a pre-hatch study, left tibia samples were collected at 18 days of incubation. For a post-hatch study, a total of 240 male chicks from each maternal treatment were randomly selected and assigned to 12 floor pens and provided with the same broiler diets. At 42 days of age, growth performance, body composition, bone microstructure, and expression of key bone marrow osteogenic and adipogenic genes were evaluated. One-way ANOVA was performed, and means were compared by student's t-test. Maternal use of FO in breeder hen diet increased bone mineral content (p < 0.01), bone tissue volume (p < 0.05), and bone surface area (p < 0.05), but decreased total porosity volume (p < 0.01) during the embryonic development period. The FO group showed higher body weight gain and feed intake at the finisher stage than the SO group. Body composition analyses by dual-energy X-ray absorptiometry showed that the FO group had higher fat percentage and higher fat mass at day 1, but higher lean mass and total body mass at market age. The decreased expression of key adipogenic genes in the FO group suggested that prenatal FO supplementation in breeder hen diet suppressed adipogenesis in offspring bone marrow. Furthermore, no major differences were observed in expression of osteogenesis marker genes, microstructure change in trabecular bone, or bone mineral density. However, a significant higher close pores/open pores ratio suggested an improvement on bone health of the FO group. Thus, this study indicates that maternal fish oil diet rich in n-3 PUFA could have a favorable impact on fat mass and skeletal integrity in broiler offspring. [ABSTRACT FROM AUTHOR]

The nasal route of immunization has become a real alternative to injections. It is indeed described as more efficient at inducing immune protection, since it initiates both mucosal and systemic immunity, thus protecting against both the infection itself and the transmission of pathogens by the host. However, the use of immunomodulators should be limited since they induce inflammation. Here we investigated in vitro the mechanisms underlying the enhancement of antigen immunogenicity by starch nanoparticles (NPL) delivery systems in H292 epithelial cells, as well as the NPL's immunomodulatory effect. We observed that NPL had no intrinsic immunomodulatory effect but enhanced the immunogenicity of an E. coli lysate (Ag) merely by increasing its intracellular delivery. Moreover, we demonstrated the importance of the NPL density on their efficiency by comparing reticulated (NPL) and non-reticulated particles (NPL·NR). These results show that an efficient delivery system is sufficient to induce a mucosal immune response without the use of immunomodulators. [ABSTRACT FROM AUTHOR]

Many lichens are well known to accumulate radiocaesium and, thus acting as biomonitors of contamination levels. However, the actual localisation and chemical forms of radiocaesium in contaminated lichens have not yet been elucidated because, despite their high radioactivity, these forms are present in trace amounts as chemical entities. Here, we use autoradiography and demonstrate for the first time in situ microscale localisation of radiocaesium within thallus tissues to investigate the radiocaesium forms and their accumulation mechanism. Radiocaesium distributions showed similar trends in lichen tissues collected two and six years after the Fukushima nuclear accident. The radiocaesium was localised in the brown pigmented parts i.e., melanin-like substances, in the lower cortex of lichen thallus. Quantum chemical calculations showed that functional group of melanin-like substances can chelate Cs+ ion, which indicates that the Cs+ ions form complexes with the substances. Based on these findings, we suggest that radiocaesium ions may be retained stably in melanin-like substances for long periods (two to six years) due to steric factors, such as those seen in porphyrin-like structures and via multimer formation in the lower cortex. In addition, electron microscopy and autoradiography were used to observe radiocaesium-bearing microparticles (CsMPs) on/in the upper cortex and around the medullary layer. Micron-sized particles appeared to adhere to the surface tissue of the thallus, as shown by electron microscopy, suggesting that the particles were trapped by development of an adhesive layer; that is, CsMPs were trapped both physically and physiologically. These findings provide information on in situ localisation of two chemical forms of radiocaesium, cations and particles, in lichen thallus tissues and their accumulation mechanisms. [ABSTRACT FROM AUTHOR]

Positive and counter-selectable markers have been successfully integrated as a part of numerous genetic assays in many model organisms. In this study, we investigate the mechanism of resistance to arginine analog canavanine and its applicability for genetic selection in Schizosaccharomyces pombe. Deletion of both the arginine permease gene cat1 and SPBC18H10.16/vhc1 (formerly mistakenly called can1) provides strong drug resistance, while the single SPBC18H10.16/vhc1 deletion does not have an impact on canavanine resistance. Surprisingly, the widely used can1-1 allele does not encode for a defective arginine permease but rather corresponds to the any1-523C>T allele. The strong canavanine-resistance conferred by this allele arises from an inability to deposit basic amino acid transporters on the cellular membrane. any1-523C>T leads to reduced post-translational modifications of Any1 regulated by the Tor2 kinase. We also demonstrate that any1-523C>T is a dominate allele. Our results uncover the mechanisms of canavanine-resistance in fission yeast and open the opportunity of using cat1, vhc1 and any1 mutant alleles in genetic assays. [ABSTRACT FROM AUTHOR]

Introduction: Drug errors pose a major health hazard to a number of patient populations. However, patients with type 2 diabetes mellitus seem especially vulnerable to this risk as diabetes mellitus is usually concomitant with various comorbidities and polypharmacy, which present significant risk factors for the occurrence of drug errors. Despite this fact, there is little data on drug errors from patients' perspective. The present survey aimed to examine the viewpoints of patients with type 2 diabetes mellitus regarding their experiences with medication errors, the overall treatment satisfaction, and their perceptions on how a medication error was handled in daily hospital routine. Materials and methods: Inpatients at the Department of Endocrinology and Diabetology of the University Hospital of Graz were included in the survey. Out of 100 patients, one-half had insulin therapy before hospitalization while the other half had no insulin therapy prior to admission. After giving informed consent, patients filled out a questionnaire with 22 items. Results: Independent of their preexisting therapy, 25% of patients already suffered at least one drug error, whereby prescribing a wrong dose seemed to be the most common type of error. Furthermore, 26% of patients in the non-insulin versus 50% in the insulin group (p = 0.084) were convinced that drug errors were addressed honestly by the medical staff, while 54% in the non-insulin versus 80% in the insulin-group (p = 0.061) assumed that adequate measures were taken to prevent drug errors. Finally, 9 out of 10 patients seemed satisfied with their treatment regardless of their diabetes therapy. Discussion/conclusion: The results of the survey clearly showed that patients experienced at least one medication error during hospitalization. However, these errors only rarely led to patient harm. The survey also revealed the value of an honest and respectful doctor-patient relationship regarding patient perception of medication errors and general complaints. Increasing patient awareness on the existing in-hospital error management systems could eliminate treatment-related concerns and create a climate of trust that is essential for effective treatment. [ABSTRACT FROM AUTHOR]

Late Pleistocene hunter-gatherers in East Asia adopted pottery, yet the ability to reconstruct circulation, mobility, and exchange has been hampered, in part, due to problematic regional geochronology. The driving forces behind pottery adoption is unclear. The purpose of this study is to test our results of the first systematic petrographic pottery sourcing from the pre-Younger Dryas by utilizing neutron activation analysis. We examine samples from the Sankauyama I site on Tanegashima Island, southern Japan, dating to the Incipient Jomon, ca. 14,000/13,500–12,800 cal BP, with a well-defined geochronology. Our NAA results corroborate with the petrographic study suggesting that pottery was mainly produced in-situ, but some vessels were transported long distances from another island. Changing from high mobility, sedentary Incipient Jomon foragers made pottery, occasionally investing in long-distance ceramic vessel transportation and exchange likely involving ocean crossing. This may be associated with a risk-buffering strategy in the context of rising sea levels and isolation of Tanegashima. [ABSTRACT FROM AUTHOR]