Spraying humic acid regulator on cultivated Codonopsis pilosula (Franch.) Nannf. to improve yield of active constituents.

Plant growth regulators have been used in the cultivation of medicinal plants to increase yield, but the existing regulators decreased the content of active constituents which benefit human health. Therefore, it is necessary to find a new growth regulator to achieve the win-win goal of increasing yield and improving active constituents' accumulation. The potential of replacing chlorocholine chloride with a new humic acid-based growth regulator was evaluated by measuring the yield and active constituents' accumulation of Codonopsis pilosula. Three treatments including water (CK), chlorocholine chloride (T1) and humic acid regulator (T2) were applied by foliar spraying. Among them, both chlorocholine chloride and humic acid regulator belong to biostimulant. The result showed that the root yield in T1 and T2 were significantly increased by 59.1% and 54.9% compared with CK, respectively, and there was no significant difference between T1 and T2. Compared with CK, the yields of lobetyolin, syringin and atractylenolide III of Codonopsis pilosula were significantly decreased by 6.3%, 7.3% and 13.0% in T1, but were significantly increased by 22.8%, 14.8% and 32.0% in T2, respectively. Redundancy analyses showed that photosynthetic rate, sucrose phosphoric acid synthetase and phosphomannomutase had higher degree of explanation for yield and quality. Linear regression results indicated that photosynthetic rate and phosphomannomutase were the main factors to affect yield and active constituents yields, respectively. In addition, the output-input ratios based on the yields of polysaccharides, lobetyolin, syringin and atractylenolide III of Codonopsis pilosula in T2 was significantly increased by 6.5%, 15.2%, 8.7% and 31.2% respectively as compared with T1. Overall, compared with water treatment, both chlorocholine chloride and humic acid regulator treatments can increase the root yield of Codonopsis pilosula. Compared with chlorocholine chloride, humic acid regulator can improve the yield of active constituents and economic benefits of Codonopsis pilosula. This study indicated that reasonable selection of plant growth regulators is of great significance for achieving a win-win goal of increasing the root yield and active constituents of medicinal plants.

Drinking and driving: A systematic review of the impacts of alcohol consumption on manual and automated driving performance.

INTRODUCTION: Almost a third of car accidents involve driving after alcohol consumption. Autonomous vehicles (AVs) may offer accident-prevention benefits, but at current automation levels, drivers must still perform manual driving tasks when automated systems fail. Therefore, understanding how alcohol affects driving in both manual and automated contexts offers insight into the role of future vehicle design in mediating crash risks for alcohol-impaired driving. METHOD: This study conducted a systematic review on alcohol effects on manual and automated (takeover) driving performance. Fifty-three articles from eight databases were analyzed, with findings structured based on the information processing model, which can be extended to the AV takeover model. RESULTS: The literature indicates that different Blood Alcohol Concentration (BAC) levels affect driving skills essential for traffic safety at various information processing stages, such as delayed reacting time, impaired cognitive abilities, and hindered execution of driving tasks. Additionally, the driver's driving experience, drinking habits, and external driving environment play important roles in influencing driving performance. CONCLUSIONS: Future work is needed to examine the effects of alcohol on driving performance, particularly in AVs and takeover situations, and to develop driver monitoring systems. PRACTICAL APPLICATIONS: Findings from this review can inform future experiments, AV technology design, and the development of driver state monitoring systems.

SMARTSeiz: Deep Learning with Attention Mechanism for Accurate Seizure Recognition in IoT Healthcare Devices.

The Internet of Things (IoT) is capable of controlling the healthcare monitoring system for remote-based patients. Epilepsy, a chronic brain syndrome characterized by recurrent, unpredictable attacks, affects individuals of all ages. IoT-based seizure monitoring can greatly enhance seizure patients' quality of life. IoT device acquires patient data and transmits it to a computer program so that doctors can examine it. Currently, doctors invest significant manual effort in inspecting Electroencephalograph (EEG) signals to identify seizure activity. However, EEG-based seizure detection algorithms face challenges in real-world scenarios due to non-stationary EEG data and variable seizure patterns among patients and recording sessions. Therefore, a sophisticated computer-based approach is necessary to analyze complex EEG records. In this work, the authors proposed a hybrid approach by combining traditional convolution neural (CN) and recurrent neural networks (RNN) along with an attention mechanism for the automatic recognition of epileptic seizures through EEG signal analysis. This attention mechanism focuses on significant subsets of EEG data for class recognition, resulting in improved model performance. The proposed methods are evaluated using a publicly available UCI epileptic seizure recognition dataset, which consists of five classes: four normal conditions and one abnormal seizure condition. Experimental results demonstrate that the suggested approach achieves an overall accuracy of 97.05% for the five-class EEG recognition data, with an accuracy of 99.52% for binary classification distinguishing seizure cases from normal instances. Furthermore, the proposed intelligent seizure recognition model is compatible with an IoMT (Internet of Medical Things) cloud-based smart healthcare framework.

Driving Aggressively or Conservatively? Investigating the Effects of Automated Vehicle Interaction Type and Road Event on Drivers' Trust and Preferred Driving Style.

OBJECTIVE: This study aimed to investigate the impact of automated vehicle (AV) interaction mode on drivers' trust and preferred driving styles in response to pedestrian- and traffic-related road events. BACKGROUND: The rising popularity of AVs highlights the need for a deeper understanding of the factors that influence trust in AV. Trust is a crucial element, particularly because current AVs are only partially automated and may require manual takeover; miscalibrated trust could have an adverse effect on safe driver-vehicle interaction. However, before attempting to calibrate trust, it is vital to comprehend the factors that contribute to trust in automation. METHODS: Thirty-six individuals participated in the experiment. Driving scenarios incorporated adaptive SAE Level 2 AV algorithms, driven by participants' event-based trust in AVs and preferences for AV driving styles. The study measured participants' trust, preferences, and the number of takeover behaviors. RESULTS: Higher levels of trust and preference for more aggressive AV driving styles were found in response to pedestrian-related events compared to traffic-related events. Furthermore, drivers preferred the trust-based adaptive mode and had fewer takeover behaviors than the preference-based adaptive and fixed modes. Lastly, participants with higher trust in AVs favored more aggressive driving styles and made fewer takeover attempts. CONCLUSION: Adaptive AV interaction modes that depend on real-time event-based trust and event types may represent a promising approach to human-automation interaction in vehicles. APPLICATION: Findings from this study can support future driver- and situation-aware AVs that can adapt their behavior for improved driver-vehicle interaction.

Age is more than just a number: The relationship among age, non-chronological age factors, self-perceived driving abilities, and autonomous vehicle acceptance.

Globally, adults aged 65 and older are a rapidly-growing population. Aging is associated with declines in perceptual, cognitive, and physical abilities, which often creates challenges in completing daily activities, such as driving. Autonomous vehicles (AVs) promise to provide older adults one way to maintain their mobility and independence. However, recent surveys of AV acceptance suggest that older adults have a lower AV acceptance compared to younger generations. One challenge is that most of these assessments have not accounted for the various non-chronological age factors that contribute to how older adults perceive their own driving skills and the utility of AVs. To fill this research gap, this study investigated the effects of non-chronological age factors and rated self-perceived driving abilities on AV acceptance across three age groups. An online survey was conducted using Amazon Mechanical Turk (MTurk), for which 438 valid responses were received. Respondents were categorized into a younger (18-40 years), middle-aged (41-64 years), and older (65-79 years) adult age group. Results showed that drivers of a younger age, with higher educational attainment, who rated themselves to have higher social support, and who have lower rated self-perceived driving abilities, report being more willing to accept AVs. Findings from this work can help to inform models of AV technology acceptance and guide in the development of marketing strategies to promote knowledge of AVs.

The effects of age and physical exercise on multimodal signal responses: Implications for semi-autonomous vehicle takeover requests.

The present study examined whether the non-chronological age factor, engagement in physical exercise, affected responses to multimodal (combinations of visual, auditory, and/or tactile) signals differently between younger and older adults in complex environments. Forty-eight younger and older adults were divided into exercise and non-exercise groups, and rode in a simulated Level 3 autonomous vehicle under four different task conditions (baseline, video watching, headway estimation, and video-headway combination), while being asked to respond to various multimodal warning signals. Overall, bi- and trimodal warnings had faster response times for both age groups across driving conditions, but was more pronounced for older adults. Engagement in physical exercise was associated with smaller maximum braking force for younger participants only, and also corresponded to longer average fixation durations, compared to the non-exercise group. Findings from this research can help to guide decisions about the design of warning and information systems for semi-autonomous vehicles.

Takeover requests for automated driving: The effects of signal direction, lead time, and modality on takeover performance.

Vehicle-to-driver takeover will still be needed in semi-autonomous vehicles. Due to the complexity of the takeover process, it is important to develop interfaces to support good takeover performance. Multimodal displays have been proposed as a candidate for the design of takeover requests (TORs), but many questions remain unanswered regarding the effectiveness of this approach. This study investigated the effects of takeover signal direction (ipsilateral vs. contralateral), lead time (4 vs. 7 s), and modality (uni-, bi-, and trimodal combinations of visual, auditory, and tactile signals) on automated vehicle takeover performance. Twenty-four participants rode in a simulated SAE Level 3 vehicle and performed a series of takeover tasks when presented with a TOR. Overall, single and multimodal signals with a tactile component were correlated with the faster takeover and information processing times, and were perceived as most useful. Ipsilateral signals showed a marginally significant benefit to takeover times compared to contralateral signals. Finally, a shorter lead time was associated with faster takeover times, but also poorer takeover quality. Findings from this study can inform the design of in-vehicle information and warning systems for next-generation transportation.

Correction: Highly porous and elastic aerogel based on ultralong hydroxyapatite nanowires for high-performance bone regeneration and neovascularization.

Correction for 'Highly porous and elastic aerogel based on ultralong hydroxyapatite nanowires for high-performance bone regeneration and neovascularization' by Gao-Jian Huang et al., J. Mater. Chem. B, 2021, 9, 1277-1287, DOI: 10.1039/D0TB02288H.

Highly porous and elastic aerogel based on ultralong hydroxyapatite nanowires for high-performance bone regeneration and neovascularization.

Hydroxyapatite (HAP) is promising for the clinical treatment of bone defects because of its excellent biocompatibility and osteo-conductivity. However, highly porous HAP scaffolds usually exhibit high brittleness and poor mechanical properties, thus organic constituents are usually added to form composite materials. In this work, a highly porous and elastic aerogel made from ultralong HAP nanowires with ultrahigh porosity (∼98.5%), excellent elasticity and suitable porous structure is prepared as the high-performance scaffold for bone defect repair. The highly porous structure of the as-prepared aerogel is beneficial to bone ingrowth and matter/fluid transfer, and the high elasticity can ensure the structural integrity of the scaffold during bone regeneration. Therefore, the HAP nanowire aerogel scaffold can promote the adhesion, proliferation and migration of rat bone marrow derived mesenchymal stem cells (rBMSCs), and elevate the protein expression of osteogenesis and angiogenesis related genes. The in vivo experimental results demonstrate that the HAP nanowire aerogel scaffold is favorable for the ingrowth of new bone and blood vessels, and thus can greatly accelerate bone regeneration and neovascularization. The as-prepared HAP nanowire aerogel scaffold shows promising potential for biomedical applications such as bone defect repair.

Arrb2 promotes endothelial progenitor cell-mediated postischemic neovascularization.

Background and aim: Modulating biological functions of endothelial progenitor cells (EPCs) is essential for therapeutic angiogenesis in ischemic vascular diseases. This study aimed to explore the role and molecular mechanisms of ß-arrestin 2 (Arrb2) in EPCs biology and angiogenic therapy. Methods: The influence of Arrb2 on postischemic neovascularization was evaluated in Arrb2-deficient mice. The proliferation, apoptosis, and various functions of EPCs were analyzed in vitro by manipulating the expression of Arrb2. Finally, the in vivo effect of Arrb2 on EPC-mediated neovascularization was investigated in a mouse model of hind-limb ischemia (HLI). Results: Arrb2-deficient mice exhibited impaired blood flow recovery based on laser Doppler measurements and reduced capillary density in the adductor muscle after unilateral HLI. Arrb2-deficient mice also showed restricted intraplug angiogenesis in subcutaneously implanted Matrigel plugs. In vitro, lentivirus-mediated Arrb2 overexpression promoted EPC proliferation, migration, adhesion, and tube formation, whereas Arrb2 knockdown had opposite effects. In addition, the overexpression of Arrb2 in EPCs protected them from hypoxia-induced apoptosis and improved intraplug angiogenesis ex vivo. Mechanistically, Arrb2 interacted with and activated extracellular signal-regulated kinase (ERK)1/2 and protein kinase B (Akt) signaling pathways. Finally, the transplantation of EPCs overexpressing Arrb2 resulted in a significantly higher blood flow restoration in ischemic hind limb and higher capillary density during histological analysis compared with control or Arrb2-knockdown EPC-treated nude mice. Conclusions: The data indicated that Arrb2 augmented EPC-mediated neovascularization through the activation of ERK and Akt signaling pathways. This novel biological function of Arrb2 might provide a potential therapeutic option to promote EPCs in the treatment of ischemic vascular diseases.

Targeting HSP90 attenuates angiotensin II-induced adventitial remodelling via suppression of mitochondrial fission.

AIMS: Adventitial remodelling presenting with the phenotypic switch of adventitial fibroblasts (AFs) to myofibroblasts is reportedly involved in the evolution of several vascular diseases, including hypertension. In our previous study, we reported that heat shock protein 90 (HSP90) inhibition by 17-dime-thylaminoethylamino-17-demethoxygeldanamycin (17-DMAG) markedly attenuates angiotensin II (AngII)-induced abdominal aortic aneurysm formation by simultaneously inhibiting several key signalling and transcriptional pathways in vascular smooth muscle cells; however, little is known about its role on AFs. Given that the AF phenotypic switch is likely to be associated with mitochondrial function and calcineurin (CN), a client protein of HSP90 that mediates mitochondrial fission and function, the aim of this study was to investigate whether mitochondrial fission contributes to phenotypic switch of AF, and if it does, we further aimed to determine whether HSP90 inhibition attenuates mitochondrial fission and subsequently suppresses AF transformation and adventitial remodelling in AngII-induced hypertensive mice. METHODS AND RESULTS: In primary mouse AFs, we found that CN-dependent dephosphorylation of Drp1 induced mitochondrial fission and regulated mitochondrial reactive oxygen species production, which stimulated AF proliferation, migration, and phenotypic switching in AngII-treated AFs. Moreover, AngII was found to increase the binding of HSP90 and CN in AFs, while HSP90 inhibition significantly reversed AngII-induced mitochondrial fission and AF phenotypic switching by modulating the CN-dependent dephosphorylation of Drp1. Consistent with the effects in AFs, in an animal model of AngII-induced adventitial remodelling, 17-DMAG markedly reduced mitochondrial fission, AF differentiation, vessel wall thickening, and fibrosis in the aortic adventitia, which were mediated by CN/Drp1 signalling pathways. CONCLUSIONS: Our study suggests that CN/Drp1-dependent mitochondrial fission may be essential for understanding adventitial remodelling in hypertension and that HSP90 inhibition may serve as a novel approach for the treatment of adventitial remodelling-related diseases.

Sirtuin 3-mediated pyruvate dehydrogenase activity determines brown adipocytes phenotype under high-salt conditions.

Previous study indicated that Sirtuin 3 (SIRT3) is a central regulator of adaptive thermogenesis in brown adipose tissue (BAT). Here we investigate the role of SIRT3 in the modulation of cellular phenotype in BAT under high salt intake (HS). HS downregulated SIRT3 level in BAT, accompanied by decreased oxygen consumption rate, and caused a severe loss of BAT characteristics. Mechanically, SIRT3 interacted with pyruvate dehydrogenase E1α (PDHA1) and deacetylated Lys-83 both in vitro and in vivo under HS. In parallel, HS suppressed salt-induced kinase (Sik) 2 phosphorylation. Silencing Sik2 further diminished SIRT3 activity and enhanced acetylation of PDHA1 K83 level. Reconstruction of SIRT3 restored PDH activity and thermogenic markers expression in differentiated brown adipocytes from SIRT3 knockout (KO) mice. In addition, loss of SIRT3 induced selective remodelling of phospholipids and glycerolipids in BAT exposure to HS. These data indicate that SIRT3 is an essential enzymatic switch that controls brown adipose cell phenotype.

Atorvastatin plus therapeutic ultrasound improve postnatal neovascularization in response to hindlimb ischemia via the PI3K-Akt pathway.

Statins and therapeutic ultrasound (TUS) have been shown to ameliorate angiogenesis on ischemic hindlimb animals and promote human umbilical vein endothelial cells (HUVECs) tube formation and proliferation. Here, we evaluate the therapeutic effect of TUS in combination with atorvastatin (Ator) therapy on angiogenesis in hindlimb ischemia and HUVECs. After subjecting excision of the left femoral artery, all mice were randomly distributed to one of four groups: Control; Ator treated mice (Ator); TUS treated mice (TUS); and Ator plus TUS treated mice (Ator+TUS). At day 14 post-surgery, the Ator plus TUS treatment cohort had the greatest blood perfusion, accompanied by elevated capillary density. In vitro, Ator plus TUS augmented tube formation, migration and proliferative capacities of HUVECs. Additionally, the united administration upregulated expression of angiogenic factors phosphorylated Akt (p-Akt), phosphorylated endothelial nitric oxide synthase (p-eNOS), as well as vascular endothelial growth factor (VEGF), both in vivo and in vitro. These benefits could be blocked by either phosphoinositide 3-kinase (PI3K) or eNOS inhibitor. Our data indicated that the united administration could significantly enhance ischemia-mediated angiogenesis and exert a protective effect against ischemic/hypoxia induced damage among HUVECs through up-regulating VEGF expression and activating the PI3K-Akt-eNOS pathway.

Impact of work pressure, work stress and work-family conflict on firefighter burnout.

Little research has explored burnout and its causes in the American fire service. Data were collected from career firefighters in the southeastern United States (n = 208) to explore these relationships. A hierarchical regression model was tested to examine predictors of burnout including sociodemographic characteristics (model 1), work pressure (model 2), work stress and work-family conflict (model 3) and interaction terms (model 4). The main findings suggest that perceived work stress and work-family conflict emerged as the significant predictors of burnout (both p < .001). Interventions and programs aimed at these predictors could potentially curtail burnout among firefighters.

Sirtuin 3-induced macrophage autophagy in regulating NLRP3 inflammasome activation.

Defective autophagy of monocytes or macrophages might result in NLRP3 inflammasome activation and cause vascular metabolic inflammation. However, the mechanism underlying the initiation of the autophagy response to hyperlipidaemia remains unclear. Sirtuin 3 (SIRT3), an NAD-dependent deacetylase, is sensitive to the metabolic status and mediates adaptation responses. In this study, we investigated the role of SIRT3-mediated autophagy in regulating NLRP3 inflammasome activation. We determined that the inhibition of autophagy and the activation of the NLRP3 inflammasome were concomitant with reduced SIRT3 levels both in peripheral blood monocytes from obese humans and in palmitate-treated THP-1 cells. Furthermore, we demonstrated that SIRT3 could form a molecular complex with ATG5, while SIRT3 overexpression altered the acetylation of endogenous ATG5. ATG5 acetylation inhibited autophagosome maturation and induced NLRP3 inflammasome activation. In parallel, SIRT3 overexpression in THP-1 cells decreased the palmitate-induced generation of mitochondrial reactive oxygen species, restored autophagy, and attenuated NLRP3 inflammasome activation. The incubation of human aortic endothelial cells (HAECs) with macrophage-conditioned medium (MCM) induced HAEC expression of vascular cell adhesion molecule-1, intercellular adhesion molecule 1, α-smooth muscle actin, and collagen-1. The effect of MCM could be reversed by the addition of neutralizing anti-IL-1ß antibody or the overexpression of SIRT3. Consistent with this, en face analyses displayed a marked increase in α-SMC-positive endothelial cells in SIRT3-/- mice with acute hyperlipidaemia. Taken together, these findings revealed that SIRT3-deficient macrophages displayed impaired autophagy and accelerated NLRP3 inflammasome activation and endothelial dysfunction.

Sirtuin 3 Deficiency Accelerates Hypertensive Cardiac Remodeling by Impairing Angiogenesis.

BACKGROUND: Emerging evidence indicates that impaired angiogenesis may contribute to hypertension-induced cardiac remodeling. The nicotinamide adenine dinucleotide-dependent deacetylase Sirtuin 3 (SIRT3) has the potential to modulate angiogenesis, but this has not been confirmed. As such, the aim of this study was to examine the relationship between SIRT3-mediated angiogenesis and cardiac remodeling. METHODS AND RESULTS: Our experiments were performed on SIRT3 knockout and age-matched wild-type mice infused with angiotensin II (1400 ng/kg per minute) or saline for 14 days. After angiotensin II infusion, SIRT3 knockout mice developed more severe microvascular rarefaction and functional hypoxia in cardiac tissues compared with wild-type mice. These events were concomitant with mitochondrial dysfunction and enhanced collagen I and collagen III expression, leading to cardiac fibrosis. Silencing SIRT3 facilitated angiotensin II-induced aberrant Pink/Parkin acetylation and impaired mitophagy, while excessive mitochondrial reactive oxygen species generation limited angiogenic capacity in primary mouse cardiac microvascular endothelial cells. Moreover, SIRT3 overexpression in cardiac microvascular endothelial cells enhanced Pink/Parkin-mediated mitophagy, attenuated mitochondrial reactive oxygen species generation, and restored vessel sprouting and tube formation. In parallel, endothelial cell-specific SIRT3 transgenic mice showed decreased fibrosis, as well as improved cardiac function and microvascular network, compared with wild-type mice with similar stimuli. CONCLUSIONS: Collectively, these findings suggest that SIRT3 could promote angiogenesis through attenuating mitochondrial dysfunction caused by defective mitophagy.

Haematopoietic TLR4 deletion attenuates perivascular brown adipose tissue inflammation in atherosclerotic mice.

AIMS: To investigate whether haematopoietic TLR4 deletion attenuates perivascular brown adipose tissue inflammation in atherosclerotic mice. METHODS AND RESULTS: Experiments were performed using irradiated LDL receptor-deficient (LDLR-/-) mice with marrow from either TLR4-deficient (TLR4-/-) or age-matched wild-type (WT) mice. After 12 weeks of being fed a high-cholesterol diet, TLR4-/-→LDLR-/- mice developed fewer atherosclerotic lesions in the aorta compared to WT→LDLR-/- mice. This effect was associated with an increase in multilocular lipid droplets and mitochondria in perivascular adipose tissue (PVAT). Immunofluorescence analysis confirmed that there was an increase in capillary density and M2 macrophage infiltration, accompanied by a decrease in tumour necrosis factor (TNF)-α expression in the localized PVAT of TLR4-/-→LDLR-/- mice. In vitro studies indicated that bone marrow-derived macrophages (BMDMs) from WT mice demonstrated an M1-like phenotype and expression of inflammatory cytokines induced by palmitate. These effects were attenuated in BMDMs isolated from TLR4-/- mice. Furthermore, brown adipocytes incubated with conditioned medium (CM) derived from palmitate-treated BMDMs, exhibited larger and more unilocular lipid droplets, and reduced expression of brown adipocyte-specific markers and perilipin-1 compared to those observed in brown adipocytes exposed to CM from palmitate-treated BMDMs of TLR4-/- mice. This decreased potency was primarily due to TNF-α, as demonstrated by the capacity of the TNF-α neutralizing antibody to reverse these effects. CONCLUSIONS: These results suggest that haematopoietic-specific deletion of TLR4 promotes PVAT homeostasis, which is involved in reducing macrophage-induced TNF-α secretion and increasing mitochondrial biogenesis in brown adipocytes.