Activation of heme oxygenase-1 by laminar shear stress ameliorates high glucose-induced endothelial cell and smooth muscle cell dysfunction.

High glucose (HG)-induced endothelial cell (EC) and smooth muscle cell (SMC) dysfunction is critical in diabetes-associated atherosclerosis. However, the roles of heme oxygenase-1 (HO-1), a stress-response protein, in hemodynamic force-generated shear stress and HG-induced metabolic stress remain unclear. This investigation examined the cellular effects and mechanisms of HO-1 under physiologically high shear stress (HSS) in HG-treated ECs and adjacent SMCs. We found that exposure of human aortic ECs to HSS significantly increased HO-1 expression; however, this upregulation appeared to be independent of adenosine monophosphate-activated protein kinase, a regulator of HO-1. Furthermore, HSS inhibited the expression of HG-induced intercellular adhesion molecule-1, vascular cell adhesion molecule-1, and reactive oxygen species (ROS) production in ECs. In an EC/SMC co-culture, compared with static conditions, subjecting ECs close to SMCs to HSS and HG significantly suppressed SMC proliferation while increasing the expression of physiological contractile phenotype markers, such as α-smooth muscle actin and serum response factor. Moreover, HSS and HG decreased the expression of vimentin, an atherogenic synthetic phenotypic marker, in SMCs. Transfecting ECs with HO-1-specific small interfering (si)RNA reversed HSS inhibition on HG-induced inflammation and ROS production in ECs. Similarly, reversed HSS inhibition on HG-induced proliferation and synthetic phenotype formation were observed in co-cultured SMCs. Our findings provide insights into the mechanisms underlying EC-SMC interplay during HG-induced metabolic stress. Strategies to promote HSS in the vessel wall, such as continuous exercise, or the development of HO-1 analogs and mimics of the HSS effect, could provide an effective approach for preventing and treating diabetes-related atherosclerotic vascular complications.

Simulated microgravity attenuates skin wound healing by inhibiting dermal fibroblast migration via F-actin/YAP signaling pathway.

Skin and its cell components continuously subject to extrinsic and intrinsic mechanical forces and are mechanical sensitive. Disturbed mechanical homeostasis may lead to changes in skin functions. Gravity is the integral mechanical force on the earth, however, how gravity contributes to the maintenance of skin function and how microgravity in space affects the wound healing are poorly understood. Here, using microgravity analogs, we show that simulated microgravity (SMG) inhibits the healing of cutaneous wound and the accumulation of dermal fibroblasts in the wound bed. In vitro, SMG inhibits the migration of human foreskin fibroblast cells (HFF-1), and decreases the F-actin polymerization and YAP (yes-associated protein) activity. The SMG-inhibited migration can be recovered by activating YAP or F-actin polymerization using lysophosphatidic acid (LPA) or jasplakinolide (Jasp), suggesting the involvement of F-actin/YAP signaling pathway in this process. In SMG rats, LPA treatment improves the cutaneous healing with increased dermal fibroblasts in the wound bed. Together, our results demonstrate that SMG attenuates the cutaneous wound healing by inhibiting dermal fibroblast migration, and propose the crucial role of F-actin/YAP mechano-transduction in the maintenance of skin homeostasis under normal gravity, and YAP as a possible therapeutic target for the skin care of astronauts in space.

Time-dependent impact of type 2 diabetes mellitus on incident prodromal Alzheimer disease: A longitudinal study in 1395 participants.

BACKGROUND AND PURPOSE: This study was undertaken to investigate the longitudinal impact of type 2 diabetes mellitus (T2DM) on the prodromal and dementia stages of Alzheimer disease (AD), focusing on diabetes duration and other comorbidities. METHODS: A total of 1395 dementia-free individuals aged 55-90 years with maximum 15-year follow-up data were enrolled from the Alzheimer's Disease Neuroimaging Initiative database. Cox proportional hazards regression models were used to estimate hazard ratios (HRs) of the incidence of prodromal or dementia stages of AD. RESULTS: Longer T2DM duration (≥5 years; multiadjusted HR = 2.19, 95% confidence interval [CI] = 1.05-4.58), but not shorter T2DM duration (<5 years), was associated with a significantly increased risk of incident prodromal AD over a mean follow-up of 4.8 years. APOE ε4 allele (HR = 3.32, 95% CI = 1.41-7.79) and comorbid coronary artery disease (CAD; HR = 3.20, 95% CI = 1.29-7.95) further increased the risk of incident prodromal AD in patients with T2DM. No significant association was observed between T2DM and the risk of progression from prodromal AD to AD dementia. CONCLUSIONS: T2DM, which is characterized by a longer duration, increases the incidence risk of prodromal AD but not AD dementia. APOE ε4 allele and comorbid CAD strengthen the relationship between T2DM and prodromal AD. These findings highlight T2DM characteristics and its comorbidities as predictors for accurate prediction of AD and screening of at-risk populations.

mDIXON-Quant technique diagnostic accuracy for assessing bone mineral density in male adult population.

BACKGROUND: To investigate the diagnostic efficacy of mDIXON-Quant technique for prediction of bone loss in male adults. METHODS: One hundred thirty-eight male adults were divided into normal, osteopenia, and osteoporosis groups based on DXA and QCT for the lumbar spine. Differences in mDIXON-Quant parameters [fat fraction (FF) and T2* value] among three groups, as well as the correlation of mDIXON-Quant parameters and bone mineral density (BMD) were analyzed. The areas under the curves (AUCs) for mDIXON-Quant parameters for prediction of low bone mass were calculated. RESULTS: According to DXA standard, FF and T2* value were significantly increased in osteoporosis group compared with normal group (P = 0.012 and P < 0.001). According to QCT standard, FF was significantly increased in osteopenia and osteoporosis groups compared with normal group (both P < 0.001). T2* values were significantly different among three groups (all P < 0.05). After correction for age and body mass index, FF was negatively correlated with areal BMD and volumetric BMD (r = -0.205 and -0.604, respectively; both P < 0.05), and so was T2* value (r = -0.324 and -0.444, respectively; both P < 0.05). The AUCs for predicting low bone mass according to DXA and QCT standards were 0.642 and 0.898 for FF, 0.648 and 0.740 for T2* value, and 0.677 and 0.920 for both combined, respectively. CONCLUSIONS: FF combined with T2* value has a better diagnostic efficacy than FF or T2* value alone in prediction of low bone mass in male adults, which is expected to be a promising MRI method for the screening of bone quality. TRIAL REGISTRATION: ChiCTR1900024511 (Registered 13-07-2019).

A preliminary study on degenerate characteristics of lumbar and abdominal muscles in middle-aged and elderly people with varying bone mass.

BACKGROUND: With the wide application of QCT in the clinical assessment of osteoporosis and sarcopenia, the characteristics of musculoskeletal degeneration in middle-aged and elderly people need to be further revealed. We aimed to investigate the degenerate characteristics of lumbar and abdominal muscles in middle-aged and elderly people with varying bone mass. METHODS: A total of 430 patients aged 40-88 years were divided into normal, osteopenia, and osteoporosis groups according to quantitative computed tomography (QCT) criteria. The skeletal muscular mass indexes (SMIs) of five muscles [abdominal wall muscles (AWM), rectus abdominis (RA), psoas major muscle (PMM), posterior vertebral muscles (PVM), and paravertebral muscles (PM)] included in lumbar and abdominal muscles were measured by QCT. Differences in SMIs among three groups, as well as the correlation between SMIs and volumetric bone mineral density (vBMD) were analyzed. The areas under the curves (AUCs) for SMIs for prediction of low bone mass and osteoporosis were calculated. RESULTS: In male group, SMIs of RA and PM in osteopenia group were significantly lower than those in the normal group (P = 0.001 and 0.023, respectively). In female group, only SMI of RA in osteopenia group was significantly lower than that in the normal group (P = 0.007). SMI of RA was positively correlated with vBMD with the highest coefficients in male and female groups (r = 0.309 and 0.444, respectively). SMIs of AWM and RA had higher AUCs varying from 0.613 to 0.737 for prediction of low bone mass and osteoporosis in both genders. CONCLUSIONS: The changes of SMIs of the lumbar and abdominal muscles in patients with varying bone mass are asynchronous. SMI of RA is expected to be a promising imaging marker for predicting abnormal bone mass. TRIAL REGISTRATION: ChiCTR1900024511 (Registered 13-07-2019).

Evaluation of MYBL1 as the master regulator for pachytene spermatocyte genes dysregulated in interspecific hybrid dzo.

Misregulation of spermatogenesis transcription factors (TF) in hybrids can lead to misexpression, which is a mechanism for hybrid male sterility (HMS). We used dzo (male offspring of Bos taurus ♂ × Bos grunniens ♀) in bovines to investigate the relationship of the key TF with HMS via RNA sequencing and assay for transposase-accessible chromatin with high-throughput sequencing analyses. RNA sequencing showed that the widespread misexpression in dzo was associated with spermatogenesis-related genes and somatic or progenitor genes. The transition from leptotene or zygotene spermatocytes to pachytene spermatocytes may be the key stage for meiosis arrest in dzo. The analysis of TF-binding motif enrichment revealed that the male meiosis-specific master TF MYB proto-oncogene like 1 (MYBL1, known as A-MYB) motif was enriched on the promoters of downregulated pachytene spermatocyte genes in dzo. Assay for transposase-accessible chromatin with high-throughput sequencing revealed that TF-binding sites for MYBL1, nuclear transcription factor Y, and regulatory factor X were enriched in the low-chromatin accessibility region of dzo. The target genes of the MYBL1-binding motif were associated with meiosis-specific genes and significantly downregulated in dzo testis. The transcription factor MYBL1 may be the candidate master regulator for pachytene spermatocyte genes dysregulated in interspecific HMS dzo. This study reported that a few upstream TF regulation changes might exert a cascading effect downstream in a regulatory network as a mechanism for HMS.

Estimating the occurrence of labial bone perforation and implantation into the maxillary sinus maxillary premolars based on the morphology of maxillary premolars: A clinical study.

STATEMENT OF PROBLEM: Previous studies have classified the sagittal root position of the maxillary anterior teeth and measured buccal plate thickness to aid treatment planning. A thin labial wall and buccal concavity may cause buccal perforation, dehiscence, or both in maxillary premolars. However, data on the restoration-driven principle to classify the maxillary premolar region are lacking. PURPOSE: The purpose of this clinical study was to investigate the occurrence of labial bone perforation and implantation into the maxillary sinus between various tooth-alveolar classifications with respect to the crown axis in maxillary premolars. MATERIAL AND METHODS: Cone beam computed tomography images of 399 participants (1596 teeth) were analyzed to determine the probability of labial bone perforation and implantation into the maxillary sinus when associated with variables that included tooth position and tooth-alveolar classification. RESULTS: The morphology in the maxillary premolars was classified as straight, oblique, or boot-shaped. The first premolars were 62.3% straight, 37.0% oblique, and 0.8% boot-shaped, and labial bone perforation occurred in 4.2% (21 of 497) of the straight, 54.2% (160 of 295) of the oblique, and 83.3% (5 of 6) of the boot-shaped first premolars when the virtual implant was 3.5×10 mm. When the virtual tapered implant was 4.3×10 mm, labial bone perforation occurred in 8.5% (42 of 497) of the straight, 68.5% (202 of 295) of the oblique, and 83.3% (5 of 6) of the boot-shaped first premolars. The second premolars were 92.4% straight, 7.5% oblique, and 0.1% boot-shaped, and labial bone perforation occurred in 0.5% (4 of 737) of the straight, 33.3% (20 of 60) of the oblique, and 0% (0 of 1) of the boot-shaped, respectively, when the virtual tapered implant was 3.5×10 mm; and labial bone perforation occurred in 1.3% (10/737) of the straight, 53.3% (32/60) of the oblique, and 100% (1/1) of the boot-shaped second premolars when the virtual tapered implant was 4.3×10 mm. CONCLUSIONS: When an implant is placed in the long axis of a maxillary premolar, the tooth position and tooth-alveolar classification should be considered when assessing the risk of labial bone perforation. Attention should be paid to the implant direction, diameter, and length in the oblique and boot-shaped maxillary premolars.

An Update in Imaging Evaluation of Histopathological Grade of Soft Tissue Sarcomas Using Structural and Quantitative Imaging and Radiomics.

Over the past two decades, considerable efforts have been made to develop non-invasive methods for determining tumor grade or surrogates for predicting the biological behavior, aiding early treatment decisions, and providing prognostic information. The development of new imaging tools, such as diffusion-weighted imaging, diffusion kurtosis imaging, perfusion imaging, and magnetic resonance spectroscopy have provided leverage in the diagnosis of soft tissue sarcomas. Artificial intelligence is a new technology used to study and simulate human thinking and abilities, which can extract and analyze advanced and quantitative image features from medical images with high throughput for an in-depth characterization of the spatial heterogeneity of tumor tissues. This article reviews the current imaging modalities used to predict the histopathological grade of soft tissue sarcomas and highlights the advantages and limitations of each modality. LEVEL OF EVIDENCE: 5 TECHNICAL EFFICACY: Stage 2.

Correlation between musculoskeletal mass and perfusion in patients with gastrointestinal malignancy: a preliminary study based on quantitative CT and CT perfusion.

BACKGROUND: To investigate the correlation between musculoskeletal mass and perfusion using quantitative computer tomography (QCT) and CT perfusion (CTP) in patients with gastrointestinal malignancy. METHODS: In this prospective study, 96 patients (mean age 66 years, range 25-90; 63.5% male) with gastrointestinal malignancy underwent QCT and CTP between May 2019 and February 2021. Bone mineral density (BMD) and body composition [perivertebral muscular mass index (PMI), skeletal muscular mass index (SMI) and muscular fat fraction] were evaluated through QCT. Musculoskeletal perfusion parameters were measured by CTP. Differences in these parameters between (or among) two (or three) groups (grouped by BMD, SMI, and TNM staging) were analyzed. RESULTS: There were significant differences in PMI and muscular fat fraction among normal (n = 30), osteopenia (n = 43), and osteoporosis (n = 23) groups (both P < 0.001). Blood flow (r = 0.336, P = 0.001; adjusted for age and gender, r = 0.383, P < 0.001), blood volume (r = 0.238, P = 0.011; adjusted for age and gender, r = 0.329, P = 0.001), and flow extraction product (r = 0.217, P = 0.034; adjusted for age and gender, r = 0.320, P = 0.002) vaules of vertebral perfusion showed positive correlation with BMD. However, the relationships between PMI and perfusion parameters of perivertebral muscle were not significant. No significant differences were found in musculoskeletal mass and perfusion parameters between different TNM staging. CONCLUSIONS: The changes of bone mass and perivertebral muscular mass in patients with gastrointestinal malignancy are synchronous. Decreased vertebral bone mass is accompanied with reduced perivertebral muscular mass, increased muscular fat, and decreased bone perfusion. However, the changes of perfusion in vertebra and perivertebral muscles are asynchronous. Musculoskeletal mass and perfusion have no correlation with TNM staging of the patients with gastrointestinal malignancy. TRIAL REGISTRATION: SHSY-IEC-4.1/20-242/01 (Registered 09-12-2020, Retrospectively registered).

Research Trends in Artificial Intelligence-Associated Nursing Activities Based on a Review of Academic Studies Published From 2001 to 2020.

The present study referred to the technology-based learning model to conduct a systematic review of the dimensions of nursing activities, research samples, research methods, roles of artificial intelligence, applied artificial intelligence algorithms, evaluation measure of algorithms, and research foci. Based on the Preferred Reporting Items for Systematic Reviews and Meta-Analyses procedure, this study obtained and analyzed a total of 102 high-quality artificial intelligence-associated nursing activities studies published from 2001 to 2020 in the Web of Science database. The results showed: (1) In terms of nursing activities, nursing management was explored the most, followed by nursing assessment; (2) quantitative methods were most frequently adopted in artificial intelligence-associated nursing activities studies to investigate issues related to patients, followed by nursing staff; (3) the most adopted roles of artificial intelligence in artificial intelligence-associated nursing activities studies were profiling and prediction, followed by assessment and evaluation; (4) artificial intelligence-associated nursing activities studies frequently mixed applied artificial intelligence algorithms and evaluation measure of algorithms; (5) in the dimension of research foci, most studies mainly paid attention to the design or evaluation of the artificial intelligence systems/instruments, followed by investigating the correlation and affect issues. Based on the findings, several recommendations are raised as a reference for future researchers, educators, and policy makers.

Marine Antimicrobial Peptide TP4 Exerts Anticancer Effects on Human Synovial Sarcoma Cells via Calcium Overload, Reactive Oxygen Species Production and Mitochondrial Hyperpolarization.

Synovial sarcoma is a rare but aggressive soft-tissue sarcoma associated with translocation t(X;18). Metastasis occurs in approximately 50% of all patients, and curative outcomes are difficult to achieve in this group. Since the efficacies of current therapeutic approaches for metastatic synovial sarcoma remain limited, new therapeutic agents are urgently needed. Tilapia piscidin 4 (TP4), a marine antimicrobial peptide, is known to exhibit multiple biological functions, including anti-bacterial, wound-healing, immunomodulatory, and anticancer activities. In the present study, we assessed the anticancer activity of TP4 in human synovial sarcoma cells and determined the underlying mechanisms. We first demonstrated that TP4 can induce necrotic cell death in human synovial sarcoma AsKa-SS and SW982 cells lines. In addition, we saw that TP4 initiates reactive oxygen species (ROS) production and downregulates antioxidant proteins, such as uncoupling protein-2, superoxide dismutase (SOD)-1, and SOD-2. Moreover, TP4-induced mitochondrial hyperpolarization is followed by elevation of mitochondrial ROS. Calcium overload is also triggered by TP4, and cell death can be attenuated by a necrosis inhibitor, ROS scavenger or calcium chelator. In our experiments, TP4 displayed strong anticancer activity in human synovial sarcoma cells by disrupting oxidative status, promoting mitochondrial hyperpolarization and causing calcium overload.

A gene co-expression network analysis of the candidate genes and molecular pathways associated with feather follicle traits of chicken skin.

Back and thigh skin of chickens showed significant differences in the thickness and the feather follicle density and size, which are important traits for slaughtered chickens' appearance. In the present study, global gene expression profiling was conducted in the back and thigh skin of chickens using Microarray technology. The results showed that 676 genes were differentially expressed between back and thigh skin. The expression of the differentially expressed genes (DEGs), including PPP1R3C, IGF1, PTCHD1, HOXB6, FGF9, CAMK4, SHH, BMP8B, FOXN1 and PTGER2, was validated by real-time quantitative polymerase chain reaction (RT-qPCR), and the results were consistent with microarray results. Functional analysis revealed that the DEGs were significantly involved in cell proliferation, differentiation, apoptosis, adhesion and transport process, and the pathways were significantly mapped into the ECM-receptor interaction, peroxisome, focal adhesion, Hedgehog and PPAR signalling pathways. Protein-protein interaction network analysis suggested that signalling pathways related to feathers morphogenesis and development, such as Wnt, FGF, MAPK, SHH and BMP signalling pathways, occupied important positions in the network. Genes involved in these signalling pathways and adhesion molecules might play a vital role in skin and feather follicle development. Further single nucleotide polymorphism (SNP) association analysis of Wnt3A showed that the AC genotype of SNP g.255361 C>A significantly increased the feather follicle density of thigh skin. Our findings may provide new insights on candidate genes and pathways related to skin and feather follicle formation of chickens.

Factors influencing university teachers' use of a mobile technology-enhanced teaching (MTT) platform.

The main purpose of this study was to examine the critical factors influencing university teachers' use of a mobile technology-enhanced teaching (MTT) platform during the new coronavirus (COVID-19) epidemic. An integrated model with multiple factors drawing from the theoretical models and learning theories was proposed in this study to examine university teachers' intentions to use an MTT platform. The multiple factors included the individual factor (e.g., growth mindset, help seeking, and self-efficacy), the social factor (e.g., social norms), and the technological acceptance factor (e.g., perceived usefulness and perceived ease of use). The survey method was used to collect data on university teachers' perceptions of the MTT platform use, and a two-step structural equation modeling approach was used for the data analysis. Based on the path analysis of a total of 214 valid responses, the results identified that growth mindset, help seeking, and self-efficacy from the individual factor, as well as perceived usefulness from the technology acceptance factor were the significant determinants of university teachers' intentions to adopt the MTT. The contributions of this study are twofold. First, the proposed model was derived from multiple literature sources, providing a sound theoretical foundation to understand MTT platform use from an academic angle. Second, university teachers' viewpoints are a unique observation of their actual platform use, providing practical insights into the improvement and maintenance of MTT-related platforms for all educators. The findings are especially valuable during the post-COVID-19 era.

SlCAND1, encoding cullin-associated Nedd8-dissociated protein 1, regulates plant height, flowering time, seed germination, and root architecture in tomato.

KEY MESSAGE: Silencing of SlCAND1 expression resulted in dwarfish, loss of apical dominance, early flowering, suppression of seed germination, and abnormal root architecture in tomato Cullin-RING E3 ligases (CRLs)-dependent ubiquitin proteasome system mediates degradation of numerous proteins that controls a wide range of developmental and physiological processes in eukaryotes. Cullin-associated Nedd8-dissociated protein 1 (CAND1) acts as an exchange factor allowing substrate recognition part exchange and plays a vital role in reactivating CRLs. The present study reports on the identification of SlCAND1, the only one CAND gene in tomato. SlCAND1 expression is ubiquitous and positively regulated by multiple plant hormones. Silencing of SlCAND1 expression using RNAi strategy resulted in a pleiotropic and gibberellin/auxin-associated phenotypes, including dwarf plant with reduced internode length, loss of apical dominance, early flowering, low seed germination percentage, delayed seed germination speed, short primary root, and increased lateral root proliferation and elongation. Moreover, application of exogenous GA3 or IAA could partly rescue some SlCAND1-silenced phenotypes, and the expression levels of gibberellin/auxin-related genes were altered in SlCAND1-RNAi lines. These facts revealed that SlCAND1 is required for gibberellin/auxin-associated regulatory network in tomato. Although SlCAND1 is crucial for multiple developmental processes during vegetative growth stage, SlCAND1-RNAi lines didn't exhibit visible effect on fruit development and ripening. Meanwhile, we discussed that multiple physiological functions of SlCAND1 in tomato are different to previous report of its ortholog in Arabidopsis. Our study adds a new perspective on the functional roles of CAND1 in plants, and strongly supports the hypothesis that CAND1 and its regulated ubiquitin proteasome system are pivotal for plant vegetative growth but possibly have different roles in diverse plant species.

A serological framework to investigate acute primary and post-primary dengue cases reporting across the Philippines.

BACKGROUND: In dengue-endemic countries, targeting limited control interventions to populations at risk of severe disease could enable increased efficiency. Individuals who have had their first (primary) dengue infection are at risk of developing more severe secondary disease, thus could be targeted for disease prevention. Currently, there is no reliable algorithm for determining primary and post-primary (infection with more than one flavivirus) status from a single serum sample. In this study, we developed and validated an immune status algorithm using single acute serum samples from reporting patients and investigated dengue immuno-epidemiological patterns across the Philippines. METHODS: During 2015/2016, a cross-sectional sample of 10,137 dengue case reports provided serum for molecular (anti-DENV PCR) and serological (anti-DENV IgM/G capture ELISA) assay. Using mixture modelling, we re-assessed IgM/G seroprevalence and estimated functional, disease day-specific, IgG:IgM ratios that categorised the reporting population as negative, historical, primary and post-primary for dengue. We validated our algorithm against WHO gold standard criteria and investigated cross-reactivity with Zika by assaying a random subset for anti-ZIKV IgM and IgG. Lastly, using our algorithm, we explored immuno-epidemiological patterns of dengue across the Philippines. RESULTS: Our modelled IgM and IgG seroprevalence thresholds were lower than kit-provided thresholds. Individuals anti-DENV PCR+ or IgM+ were classified as active dengue infections (83.1%, 6998/8425). IgG- and IgG+ active dengue infections on disease days 1 and 2 were categorised as primary and post-primary, respectively, while those on disease days 3 to 5 with IgG:IgM ratios below and above 0.45 were classified as primary and post-primary, respectively. A significant proportion of post-primary dengue infections had elevated anti-ZIKV IgG inferring previous Zika exposure. Our algorithm achieved 90.5% serological agreement with WHO standard practice. Post-primary dengue infections were more likely to be older and present with severe symptoms. Finally, we identified a spatio-temporal cluster of primary dengue case reporting in northern Luzon during 2016. CONCLUSIONS: Our dengue immune status algorithm can equip surveillance operations with the means to target dengue control efforts. The algorithm accurately identified primary dengue infections who are at risk of future severe disease.

A novel microRNA, SlymiR208, promotes leaf senescence via regulating cytokinin biosynthesis in tomato.

Leaf senescence is a highly-programmed developmental process during the plant life cycle. Cytokinin (CK) has been widely acknowledged as a negative regulator to delay leaf senescence. MiRNAs play key roles in a variety of developmental and physiological processes through negatively regulating their target gene expression. However, to date, the roles of microRNAs (miRNAs) in CK biosynthesis remain unclear, and the knowledge on miRNA regulation of leaf senescence is still very limited. Isopentenyltransferases (IPTs) catalyze the initial and rate-limiting step of CK biosynthesis in higher plants. Our previous work uncovered that silencing of SlIPT4 expression in tomato resulted in premature leaf senescence. Here, we identified a novel tomato miRNA, SlymiR208, which regulates the expression of SlIPT2 and SlIPT4 at the post-transcriptional level. SlymiR208 expression is ubiquitous in tomato and exhibits an opposite transition to its target transcripts in aged leaf. SlymiR208 overexpression in tomato sharply reduced the transcript levels of SlIPT2 and SlIPT4, and the concentrations of endogenous CKs in leaves. The early leaf senescence caused by SlymiR208 overexpression was consistent with the phenotype of SlIPT4-silenced lines. The data demonstrated that SlymiR208 is a positive regulator in leaf senescence through negatively regulating CK biosynthesis via targeting SlIPT2 and SlIPT4 in tomato. This study indicated that post-transcriptional regulation via miRNA is a control point of CK biosynthesis and added a new layer to the understanding of the regulation of CK biosynthesis in tomato and a new factual proof to support that miRNAs are involved in leaf senescence.

Age-Related Differences in the Uncanny Valley Effect.

BACKGROUND: Due to declining birthrates and an increasing aging population, shortage of the caregiving labor force has become a global issue. Among various efforts toward the solution, introducing robotic products for assistance could provide an effective way to help older adults in their daily lives. As previous studies have indicated that older adults' acceptance of robots is lower than that of younger adults, enhancing older adults' acceptance of robots is imperative. Because older adults' first impressions based on a robot's appearance might affect their acceptance of the robot, we investigated the uncanny valley effect (UVE) here. The UVE refers to the phenomenon that people rate robots more positively as robots become more humanlike, but only up to a certain point; as robots approach a near-perfect similarity to human appearance, likeability drops and forms the uncanny valley. Nevertheless, evidence for the UVE came mainly from younger adults. OBJECTIVE: The present study aimed to examine whether the UVE varies across different age groups and whether a robot's appearance would affect participants' acceptance of the robot's service or companionship. METHODS: An online questionnaire study was conducted with 255 participants, including younger (n = 77, age 18-39 years), middle-aged (n = 87, age 40-59 years), and older (n = 91, age 60-87 years) adults. Participants were asked to view each picture in a set selected from a total of 83 robot pictures and evaluate their impressions of each robot and the intention of use regarding robot function as a service provider or a companion. RESULTS: The UVE was found in younger and middle-aged adults; however, older adults did not show the UVE. Older adults preferred humanlike over non-humanlike robots, regardless of robot function. CONCLUSION: The design of assistive robots should take the UVE into consideration by customizing robot appearance based on the age group of the intended user.

Identifying Features that Enhance Older Adults' Acceptance of Robots: A Mixed Methods Study.

BACKGROUND: With global aging, robots are considered a promising solution for handling the shortage of aged care and companionships. However, these technologies would serve little purpose if their intended users do not accept them. While the socioemotional selectivity theory predicts that older adults would accept robots that offer emotionally meaningful relationships, selective optimization with compensation model predicts that older adults would accept robots that compensate for their functional losses. OBJECTIVE: The present study aims to understand older adults' expectations for robots and to compare older adults' acceptance ratings for 2 existing robots: one of them is a more human-like and more service-oriented robot and the other one is a more animal-like and more companion-oriented robot. METHODS: A mixed methods study was conducted with 33 healthy, community-dwelling Taiwanese older adults (age range: 59-82 years). Participants first completed a semi-structured interview regarding their ideal robot. After receiving information about the 2 existing robots, they then completed the Unified Theory of Acceptance and Use of Technology questionnaires to report their pre-implementation acceptance of the 2 robots. RESULTS: Interviews were transcribed for conventional content analysis with satisfactory inter-rater reliability. From the interview data, a collection of older adults' ideal robot characteristics emerged with highlights of humanlike qualities. From the questionnaire data, respondents showed a higher level of acceptance toward the more service-oriented robot than the more companion-oriented robot in terms of attitude, perceived adaptiveness, and perceived usefulness. From the mixed methods analyses, the finding that older adults had a higher level of positive attitude towards the more service-oriented robot than the more companion-oriented robot was predicted by higher expectation or preference for robots with more service-related functions. CONCLUSION: This study identified older adults' preference toward more functional and humanlike robots. Our findings provide practical suggestions for future robot designs that target the older population.

Critical Excitation of the Fundamental Quasi-Shear Mode Wave in Waveguide Bars for Elevated Temperature Applications.

The safety of critical pressure equipment in elevated temperature is increasingly important. Moreover, the on-line monitoring method is potentially useful to improve their safety. A waveguide bar system can enable monitoring of critical equipment working in elevated temperature using reliable ultrasonic technology. Among the waveguide bar system, the matching mechanism of the transducer and the waveguide bar is crucial to propagate the pure fundamental quasi-shear mode (shorten for SH0*) wave. In the present research, the loading line sources that can excite pure SH0* wave are investigated and the anti-plane shear loading source is selected. The critical values about the geometric dimensions of the junctions between the piezoelectric transducer and the waveguide bar are explored by simulation and experiments. On the condition that the excitation sources satisfy the critical values, the loading can be approximated to an anti-plane shear one to excite the pure SH0* wave. Some waveguide bar systems are designed based on the simulated critical values and some experiments at high temperature are carried out. The experimental results verify that the designed waveguide bar systems can excite the pure SH0* wave at elevated temperatures, which verify the reliability of the simulated critical results.

The CCL5/CCR5 Axis Promotes Vascular Smooth Muscle Cell Proliferation and Atherogenic Phenotype Switching.

BACKGROUND/AIMS: Hyperlipidemia induces dysfunction in the smooth muscle cells (SMCs) of the blood vessels, and the vascular remodeling that ensues is a key proatherogenic factor contributing to cardiovascular events. Chemokines and chemokine receptors play crucial roles in vascular remodeling. Here, we examined whether the hyperlipidemia-derived chemokine CCL5 and its receptor CCR5 influence vascular SMC proliferation, phenotypic switching, and explored the underlying mechanisms. METHODS: Thoracoabdominal aorta were isolated from wild-type, CCL5 and CCR5 double-knockout mice (CCL5-/-CCR5-/-) fed a high-fat diet (HFD) for 12 weeks. Expression of the contractile, synthetic, and proliferation markers were assayed using immunohistochemical and western blotting. The effects of CCL5 and palmitic acid on cultured SMC proliferation and phenotypic modulation were evaluated using flow cytometry, bromodeoxyuridine (BrdU), and western blotting. RESULTS: Wild-type mice fed an HFD showed markedly increased total cholesterol, triglyceride, and CCL5 serum levels, as well as significantly increased CCL5 and CCR5 expression in the thoracoabdominal aorta vs. normal-diet-fed controls. HFD-fed CCL5-/-CCR5-/- mice showed significantly decreased expression of the synthetic phenotype marker osteopontin and the proliferation marker proliferating cell nuclear antigen, and increased expression of the contractile phenotype marker smooth muscle α-actin in the thoracoabdominal aorta vs. wild-type HFD-fed mice. Human aorta-derived SMCs stimulated with palmitic acid showed significantly increased expression of CCL5, CCR5, and synthetic phenotype markers, as well as increased proliferation. CCL5-treated SMCs showed increased cell cycle regulatory protein expression, paralleling increased synthetic and decreased contractile phenotype marker expression. Inhibition of CCR5 activity by the specific antagonist maraviroc or its expression using small interfering RNA significantly inhibited human aortic SMC proliferation and synthetic phenotype formation. Therefore, CCL5 induces SMC proliferation and phenotypic switching from a contractile to synthetic phenotype via CCR5. CCL5-mediated SMC stimulation activated ERK1/2, Akt/p70S6K, p38 MAPK, and NF-κB signaling. NF-κB inhibition significantly reduced CCR5 expression along with CCR5-induced SMC proliferation and synthetic phenotype formation. CONCLUSIONS: Hyperlipidemia-induced CCL5/CCR5 axis activation serves as a pivotal mediator of vascular remodeling, indicating that CCL5 and CCR5 are key chemokine-related factors in atherogenesis. SMC proliferation and synthetic phenotype transformation attenuation by CCR5 pharmacological inhibition may offer a new approach to treatment or prevention of atherosclerotic diseases associated with hyperlipidemia.