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Chronic cerebral hypoperfusion is an important pathological factor in many neurodegenerative diseases, such as cerebral small vessel disease (CSVD). One of the most used animal models for chronic cerebral hypoperfusion is the bilateral common carotid artery stenosis (BCAS) mouse. For the therapy of CSVD and other diseases, it will be beneficial to understand the pathological alterations of the BCAS mouse, particularly vascular pathological changes. A mouse model of BCAS was used, and 8 weeks later, cognitive function of the mice was examined by using novel object recognition test and eight-arm radial maze test. 11.7 T magnetic resonance imaging (MRI) and luxol fast blue staining were used to evaluate the injury of the corpus callosum (CC), anterior commissure (AC), internal capsule (IC), and optic tract (Opt) in the cerebral white matter of mice. Three-dimensional vascular images of the whole brain of mice were acquired using fluorescence micro-optical sectioning tomography (fMOST) with a high resolution of 0.32 × 0.32 × 1.00 μm3. Then, the damaged white matter regions were further extracted to analyze the vessel length density, volume fraction, tortuosity, and the number of vessels of different internal diameters. The mouse cerebral caudal rhinal vein was also extracted and analyzed for its branch number and divergent angle in this study. BCAS modeling for 8 weeks resulted in impaired spatial working memory, reduced brain white matter integrity, and myelin degradation in mice, and CC showed the most severe white matter damage. 3D revascularization of the whole mouse brain showed that the number of large vessels was reduced and the number of small vessels was increased in BCAS mice. Further analysis revealed that the vessel length density and volume fraction in the damaged white matter region of BCAS mice were significantly reduced, and the vascular lesions were most noticeable in the CC. At the same time, the number of small vessels in the above white matter regions was significantly reduced, while the number of microvessels was significantly increased in BCAS mice, and the vascular tortuosity was also significantly increased. In addition, the analysis of caudal rhinal vein extraction revealed that the number of branches and the average divergent angle in BCAS mice were significantly reduced. The BCAS modeling for 8 weeks will lead to vascular lesions in whole brain of mice, and the caudal nasal vein was also damaged, while BCAS mice mainly mitigated the damages by increasing microvessels. What is more, the vascular lesions in white matter of mouse brain can cause white matter damage and spatial working memory deficit. These results provide evidence for the vascular pathological alterations caused by chronic hypoperfusion. [ABSTRACT FROM AUTHOR]

Transparent conductive films that are based on nanowire networks are essential to construct flexible, wearable, and even stretchable electronics. However, large-scale precise micropatterning, especially with regard to the controllability of the organizing orientation of nanowires, is a critical challenge. Herein, we proposed a liquid film rupture self-assembly approach for manufacturing transparent conductive films with microstructure arrays based on a highly ordered nanowire network. The large-scale microstructure conductive films were fabricated through air–liquid interface self-assembly and liquid film rupture self-assembly. Six typical micropattern morphologies, including square, hexagon, circle, serpentine, etc., were prepared to reveal the universal applicability of the proposed approach. The homogeneity and controllability of this approach were verified for multiple assemblies. With the assembly cycles increasing, the optical transmittance decreases slightly. In addition, theoretical model analysis is carried out, and the analytical formula of the speed of the film moving with the surface tension and the density of the liquid film is presented. Finally, the feasibility of this approach for piezoresistive strain sensors is verified. This fabrication approach demonstrated a cost-effective and efficient method for precisely arranging nanowires, which is useful in transparent and wearable applications. [ABSTRACT FROM AUTHOR]

Neuroma, a pathological response to peripheral nerve injury, refers to the abnormal growth of nerve tissue characterized by disorganized axonal proliferation. Commonly occurring after nerve injuries, surgeries, or amputations, this condition leads to the formation of painful nodular structures. Traditional treatment options include surgical excision and pharmacological management, aiming to alleviate symptoms. However, these approaches often offer temporary relief without addressing the underlying regenerative challenges, necessitating the exploration of advanced strategies such as tissue-engineered materials for more comprehensive and effective solutions. In this study, we discussed the etiology, molecular mechanisms, and histological morphology of traumatic neuromas after peripheral nerve injury. Subsequently, we summarized and analyzed current nonsurgical and surgical treatment options, along with their advantages and disadvantages. Additionally, we emphasized recent advancements in treating traumatic neuromas with tissue-engineered material strategies. By integrating biomaterials, growth factors, cell-based approaches, and electrical stimulation, tissue engineering offers a comprehensive solution surpassing mere symptomatic relief, striving for the structural and functional restoration of damaged nerves. In conclusion, the utilization of tissue-engineered materials has the potential to significantly reduce the risk of neuroma recurrence after surgical treatment. [ABSTRACT FROM AUTHOR]

Copyright of Journal of Central South University is the property of Springer Nature and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Aim: To explore the neuroprotective effects of ARA290 and the role of β‐common receptor (βCR) in a mouse model of middle cerebral artery occlusion (MCAO). Methods: This study included male C57BL/6J mice that underwent MCAO and reperfusion. The neuroprotective effect of ARA290 on MCAO‐induced brain injury was investigated using neurological function tests (Longa and modified neurological severity score). Cerebral infarction was examined by 2, 3, 5‐triphenyl tetrazolium chloride staining, neuronal apoptosis was assessed by immunofluorescence staining, blood parameters were measured using a flow cytometry‐based automated hematology analyzer, liquid chromatography with tandem mass spectrometry was used to identify the serum metabolomics signature, inflammatory cytokines and liver index were detected by commercially available kits, and the protein levels of the erythropoietin (EPO) receptor and βCR were measured by western blot. Results: ARA290 exerted a qualitatively similar neuroprotective effect after MCAO as EPO. ARA290 significantly reduced neuronal apoptosis and the level of inflammatory cytokines in the brain tissue. However, ARA290's neuroprotective effect was significantly suppressed following the injection of siRNA against βCR. Conclusion: ARA290 provided a neuroprotective effect via βCR in cerebral ischemic mice without causing erythropoiesis. This study provides novel insights into the role of ARA290 in ischemic stroke intervention. [ABSTRACT FROM AUTHOR]

This study aims to investigate the factors that influence the willingness of highway construction enterprises in China to adopt intelligent construction technology. Based on the existing literature, a TOSE framework was proposed, and four dimensions and 15 hypothesized influencing factors were identified through expert interviews. By using a combination of PLS-SEM and ANN, 513 survey data were analyzed to determine the linear and non-linear relationships of the influencing factors on the willingness to adopt. The results showed that all 14 hypothesized factors had varying degrees of positive or negative effects on the willingness to adopt, except for organizational culture, which was found to have no significant impact. Specifically, technology cost was found to be the most influential negative factor, while market demand and organizational structure were the most influential positive factors. The findings of this study have important reference value for decision makers and participants in highway construction enterprises, as well as other construction companies when considering the adoption of smart construction technologies. The originality of this research lies in the novel application of the TOSE framework to investigate smart construction technology adoption, and the combined use of PLS-SEM and ANN to examine both linear and nonlinear relationships between variables for the first time. [ABSTRACT FROM AUTHOR]

Apart from cancer, metabolic reprogramming is also prevalent in other diseases, such as bacterial infections. Bacterial infections can affect a variety of cells, tissues, organs, and bodies, leading to a series of clinical diseases. Common Pathogenic bacteria include Helicobacter pylori, Salmonella enterica, Mycobacterium tuberculosis, Staphylococcus aureus, and so on. Amino acids are important and essential nutrients in bacterial physiology and support not only their proliferation but also their evasion of host immune defenses. Many pathogenic bacteria or opportunistic pathogens infect the host and lead to significant changes in metabolites, especially the proteinogenic amino acids, to inhibit the host's immune mechanism to achieve its immune evasion and pathogenicity. Here, we review the regulation of host metabolism, while host cells are infected by some common pathogenic bacteria, and discuss how amino acids of metabolic reprogramming affect bacterial infections, revealing the potential adjunctive application of amino acids alongside antibiotics. [ABSTRACT FROM AUTHOR]

A new two-step, one-pot synthesis of benzo[f][1,2]thiazepine 1,1-dioxides was developed, which contains a visible-light mediated aza Paternò–Büchi reaction of benzo[d]isothiazole 1,1-dioxides with alkenes and a Lewis acid catalyzed ring-expansion of azetidine. In this work, the mechanism of the aza Paternò–Büchi reaction was also investigated. [ABSTRACT FROM AUTHOR]

A Sc(OTf)3 catalyzed intramolecular cyclization reaction of 2-alkyl-1,4-benzoquinone derived from D–A cyclopropane was discovered. This reaction involves single-electron transfer, proton-transfer, an aromatization driven spin center shift, and radical coupling processes, and offers an efficient method for the synthesis of 6-chromanols from D–A cyclopropanes. [ABSTRACT FROM AUTHOR]

Porous structure is an important three-dimensional morphological feature of the peripheral nerve guidance conduit (NGC), which permits the infiltration of cells, nutrients, and molecular signals and the discharge of metabolic waste. Porous structures with precisely customized pore sizes, porosities, and connectivities are being used to construct fully permeable, semi-permeable, and asymmetric peripheral NGCs for the replacement of traditional nerve autografts in the treatment of long-segment peripheral nerve injury. In this review, the features of porous structures and the classification of NGCs based on these characteristics are discussed. Common methods for constructing 3D porous NGCs in current research are described, as well as the pore characteristics and the parameters used to tune the pores. The effects of the porous structure on the physical properties of NGCs, including biodegradation, mechanical performance, and permeability, were analyzed. Pore structure affects the biological behavior of Schwann cells, macrophages, fibroblasts, and vascular endothelial cells during peripheral nerve regeneration. The construction of ideal porous structures is a significant advancement in the regeneration of peripheral nerve tissue engineering materials. The purpose of this review is to generalize, summarize, and analyze methods for the preparation of porous NGCs and their biological functions in promoting peripheral nerve regeneration to guide the development of medical nerve repair materials. [ABSTRACT FROM AUTHOR]

Wireless sensor network nodes are widely used in wearable devices, consumer electronics, and industrial electronics and are a crucial component of the Internet of Things (IoT). Recently, advanced power technology with sustainable energy supply and pollution-free characteristics has become a popular research focus. Herein, to realize an unattended and reliable power supply unit suitable for distributed IoT systems, we develop a high-performance triboelectric-electromagnetic hybrid nanogenerator (TEHNG) to harvest mechanical energy. The TEHNG achieves a high load power of 21.8 mW by implementing improvements of material optimization, configuration optimization and pyramid microstructure design. To realize a self-powered integrated microsystem, a power management module, energy storage module, sensing signal processing module, and microcontroller unit are integrated into the TEHNG. Furthermore, an all-in-one wireless multisensing microsystem comprising the TEHNG, the abovementioned integrated functional circuit and three sensors (temperature, pressure, and ultraviolet) is built. The milliwatt microsystem operates continuously with the TEHNG as the only power supply, achieving self-powered operations of sensing environmental variables and transmitting wireless data to a terminal in real time. This shows tremendous application potential in the IoT field. [ABSTRACT FROM AUTHOR]

An alcohol dehydrogenase LkADH was successfully engineered to exhibit improved activity and substrate tolerance for the production of (S)‐2‐chloro‐1‐(3,4‐difluorophenyl)ethanol, an important precursor of ticagrelor. Five potential hotspots were identified for enzyme mutagenesis by using natural residue abundance as an indicator to evaluate their potential plasticity. A semi‐rational strategy named "aromatic residue scanning" was applied to randomly mutate these five sites simultaneously by using tyrosine, tryptophan, and phenylalanine as "exploratory residues" to introduce steric hindrance or potential π‐π interactions. The best variant Lk‐S96Y/L199W identified with 17.2‐fold improvement in catalytic efficiency could completely reduce up to 600 g/L (3.1 M) 2‐chloro‐1‐(3,4‐difluorophenyl)ethenone in 12 h with >99.5 % ee, giving the highest space‐time yield ever reported. This study, therefore, offers a strategy for mutating alcohol dehydrogenase to reduce aromatic substrates and provides an efficient variant for the efficient synthesis of (S)‐2‐chloro‐1‐(3,4‐difluorophenyl)ethanol. [ABSTRACT FROM AUTHOR]

Nanomaterials with bone-mimicking characteristics and easily internalized by the cell could create suitable microenvironments in which to regulate the therapeutic effects of bone regeneration. This review provides an overview of the current state-of-the-art research in developing and using nanomaterials for better bone injury repair. First, an overview of the hierarchical architecture from the macroscale to the nanoscale of natural bone is presented, as these bone tissue microstructures and compositions are the basis for constructing bone substitutes. Next, urgent clinical issues associated with bone injury that require resolution and the potential of nanomaterials to overcome them are discussed. Finally, nanomaterials are classified as inorganic or organic based on their chemical properties. Their basic characteristics and the results of related bone engineering studies are described. This review describes theoretical and technical bases for the development of innovative methods for repairing damaged bone and should inspire therapeutic strategies with potential for clinical applications. [ABSTRACT FROM AUTHOR]

As one of the promising human—machine interfaces, wearable sensors play an important role in modern society, which advances the development of wearable fields, especially in the promising applications of electronic skin (e-skin), robotics, prosthetics, and healthcare. In the last decades, wearable sensors tend to be capable of attractive capabilities such as miniaturization, multifunction, and smart integration, and wearable properties such as lightweight, flexibility, stretchability, and conformability for wider applications. In this work, we developed a stretchable multifunctional sensor based on porous silver nanowire/silicone rubber conductive film (P-AgNW/SR). Its unique structural configuration, i.e., an assembly of the P-AgNW/SR with good conductivity, stability, and resistance response, and the insulated silicone rubber layer, provided the feasibility for realizing multiple sensing capabilities. Specifically, porous microstructures of the P-AgNW/SR made the device to be used for pressure sensing, exhibiting outstanding dynamic and static resistive responsive behaviors and having a maximum sensitivity of 9.062 %·N−1 in a continuous compressive force range of ∼ 16 N. With the merit of the good piezoresistive property of AgNW/SR networks embedded into the surface of micropores of the P-AgNW/SR, the device was verified to be a temperature sensor for detecting temperature changes in the human body and environment. The temperature sensor had good sensitivity of 0.844 %·°C−1, high linearity of 0.999 in the range of 25–125 °C, and remarkable dynamic stability. Besides, the developed sensor was demonstrated to be a single electrode-triboelectric sensor for active sensing, owing to the unique assembly of the conductive P-AgNW/SR electrode and the silicone rubber friction layer. Based on the coupling effect of the triboelectrification and electrostatic induction, the generated electrical signals could be used to sense the human motions, according to the quantitative correlation between the human motions and the features in amplitude and waveform of the output signals. Thus, the developed stretchable sensor successfully achieved the integration of two types of passive sensing capabilities, i.e., pressure and temperature sensing, and one type of active sensing capability, i.e., triboelectric sensing, demonstrating the feasibility of monitoring multiple variables of the human body and environment. [ABSTRACT FROM AUTHOR]

We report the results of long-term reverberation mapping campaigns of the nearby active galactic nuclei (AGNs) NGC 4151, spanning from 1994 to 2022, based on archived observations of the FAST Spectrograph Publicly Archived Programs and our new observations with the 2.3 m telescope at the Wyoming Infrared Observatory. We reduce and calibrate all the spectra in a consistent way, and derive light curves of the broad H β line and 5100 Å continuum. Continuum light curves are also constructed using public archival photometric data to increase sampling cadences. We subtract the host galaxy contamination using Hubble Space Telescope imaging to correct fluxes of the calibrated light curves. Utilizing the long-term archival photometric data, we complete the absolute flux-calibration of the AGN continuum. We find that the H β time delays are correlated with the 5100 Å luminosities as |$\tau _{\rm H\beta }\propto L_{5100}^{0.46\pm 0.16}$|⁠. This is remarkably consistent with Bentz et al. (2013)'s global size–luminosity relationship of AGNs. Moreover, the data sets for five of the seasons allow us to obtain the velocity-resolved delays of the H β line, showing diverse structures (outflows, inflows, and discs). Combining our results with previous independent measurements, we find the measured dynamics of the H β broad-line region (BLR) are possibly related to the long-term trend of the luminosity. There is also a possible additional ∼1.86 yr time lag between the variation in BLR radius and luminosity. These results suggest that dynamical changes in the BLR may be driven by the effects of radiation pressure. [ABSTRACT FROM AUTHOR]

Developing luminescent radicals with tunable emission is a challenging task due to the limitation of alternative skeletons. Herein, a series of carbene‐triphenylamine hybrids were prepared by the direct C2‐arylation of N‐heterocyclic carbenes with 4‐bromo‐N,N‐bis(4‐methoxyphenyl)aniline. These hybrids showed multiple redox‐active properties and could be converted to carbon‐centered luminescent radicals with blue‐to‐cyan emissions (λmax: 436–486 nm) or nitrogen‐centered luminescent radicals with orange emissions (λmax: 590–623 nm) through chemical reduction or oxidation, respectively. The radical species were characterized by electron paramagnetic resonance spectroscopy, ultraviolet‐visible spectroscopy, and single‐crystal X‐ray diffractometry analysis. Notably, the corresponding nitrogen‐centered radicals exhibited good stability in atmospheric air, and their thermal decomposition temperatures were determined to be above 200 °C. In addition, spectral and theoretical calculations indicate that all radicals exhibit anti‐Kasha emissions. [ABSTRACT FROM AUTHOR]

High tumor mutation load (TMB-H, or TMB ≥ 10) has been approved by the U.S. FDA as a biomarker for pembrolizumab treatment of solid tumors, including non‑small cell lung cancer (NSCLC). Patients with cancer who have immunotherapy-resistant gene mutations cannot achieve clinical benefits even in TMB-H. In this study, we aimed to identify gene mutations associated with immunotherapy resistance and further informed mechanisms in NSCLC. A combined cohort of 350 immune checkpoint blockade-treated patients from Memorial Sloan Kettering Cancer Center (MSKCC) was used to identify genes whose mutations could negatively influence immunotherapy efficacy. An external NSCLC cohort for which profession-free survival (PFS) data were available was used for independent validation. CIBERSORT algorithms were used to characterize tumor immune infiltrating patterns. Immunogenomic features were analysed in the TCGA NSCLC cohort. We observed that PBRM1 mutations independently and negatively influence immunotherapy efficacy. Survival analysis showed that the overall survival (OS) and PFS of patients with PBRM1 mutations (MT) were significantly shorter than the wild type (WT). Moreover, compared with PBRM1-WT/TMB-H group, OS was worse in the PBRM1-MT/TMB-H group. Notably, in patients with TMB-H/PBRM1-MT, it was equal to that in the low-TMB group. The CIBERSORT algorithm further confirmed that the immune infiltration abundance of CD8+ T cells and activated CD4+ memory T was significantly lower in the MT group. Immunogenomic differences were observed in terms of immune signatures, T-cell receptor repertoire, and immune-related genes between WT and MT groups. Nevertheless, we noticed an inverse relationship, given that MT tumors had a higher TMB than the WT group in MSKCC and TCGA cohort. In conclusion, our study revealed that NSCLC with PBRM1 mutation might be an immunologically cold phenotype and exhibited immunotherapy resistance. NSCLC with PBRM1 mutation might be misclassified as immunoresponsive based on TMB. [ABSTRACT FROM AUTHOR]

Wearable electronics, as essential components of the Internet of Things (IoT), have attracted widespread attention, and the trend is to configure attractive wearable smart microsystems by integrating sensing, powering, and other functions. Herein, we developed an elastic hybrid triboelectric–electromagnetic microenergy harvester (named EHTE) to realize hybrid sensing and microenergy simultaneously. This EHTE is a highly integrated triboelectric nanogenerator (TENG) and electromagnetic nanogenerator (EMG). Based on the triboelectric–electromagnetic hybrid mechanism, an enhanced electrical output of the EHTE was achieved successfully, which demonstrates the feasibility of the EHTE for microelectronics powering. Moreover, with the merits of the EMG, the developed hybrid microenergy harvester integrated both active frequency sensing and passive inductive sensing capabilities. Specifically, the almost linear correlation of the electromagnetic outputs to the frequencies of the external stimulus endowed the proposed EHTE with an outstanding active frequency sensing ability. In addition, due to the unique structural configuration of the EMG (i.e., a conductive permanent magnet (PM), hybrid deformation layer, and flexible printed circuit board (FPCB) coil), an opportunity was provided for the developed EHTE to serve as a passive inductive sensor based on the eddy current effect (i.e., a form of electromagnetic induction). Therefore, the developed EHTE successfully achieved the integration of hybrid sensing (i.e., active frequency sensing and passive inductive sensing) and microenergy (i.e., the combination of electromagnetic effect and triboelectric effect) within a single device, which demonstrates the potential of this newly developed EHTE for wearable electronic applications, especially in applications of compact active microsystems. [ABSTRACT FROM AUTHOR]

Two undescribed phenylpropenoid glycosides (1 − 2) and one known analogues (3) have been isolated and identified from the roots of Illicium dunnianum. The structures of these new compounds were elucidated by extensive spectroscopic analyses (1 D-, 2 D-NMR, HRESIMS, IR, UV) and chemical methods. The anti-inflammatory activities of all isolates were evaluated by measuring their inhibitory effects on PGE2 production in LPS stimulated RAW 264.7 macrophages. [ABSTRACT FROM AUTHOR]

Futibatinib, a highly selective, irreversible potent fibroblast growth factor receptor (FGFR) inhibitor, has been proved to be effective in clinical trials of intrahepatic cholangiocarcinoma (ICCA) patients. An ultra-high performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) method to determine the concentration of futibatinib in beagle dog plasma was developed and validated for the study of pharmacokinetics. After the plasma protein was removed by acetonitrile precipitation, futibatinib was detected and derazantinib was used as the internal standard (IS). Futibatinib and IS were separated in an UPLC BEH C18 column (2.1 mm × 50 mm, 1.7 μm) with acetonitrile and 0.1% formic acid as the mobile phase, and the flow rate was 0.3 mL/min. Under the positive ion condition of an electrospray spray ion (ESI+) source, multireaction detection was used, and the ion pairs for futibatinib and IS were m/z 418.99 ⟶ 295.97 and 468.96 ⟶ 382.00, respectively. Futibatinib had a good linear relationship in the linear range of 0.5∼100 ng/mL; the lower limit of quantification (LLOQ) was 0.5 ng/mL. The RSDs of the intraday and interday precision were all less than 10.70%, and the RE value of accuracy was between −3.87% and 3.28%. The extraction recovery of futibatinib was more than 80%, and the matrix effect was around 100%, and futibatinib was found to be stable under four experimental conditions. The new optimized and validated UPLC-MS/MS method was an effective tool to determine the concentration of futibatinib in plasma and has been successfully applied to the pharmacokinetics of futibatinib in beagle dogs. This method would also be used to study drug-drug interaction (DDI). [ABSTRACT FROM AUTHOR]

Objective: Fear of recurrence is a common psychosocial sequela among patients with heart disease. Analyses of coronary heart disease, particularly in elderly patients, are relatively rare. This study aimed to investigate the current situation in this context, as well as the influencing fear factors concerning recurrence in elderly patients with coronary heart disease.Methods: A total of 200 elderly outpatients with coronary heart disease were recruited to participate in this survey from a tertiary hospital in Baoding (China). The questionnaires included items from the Disease Progression Simplified Scale, the Simplified Coping Style Questionnaire, and the Social Support Rating Scale (SSRS). Univariate and multivariate regression analyses were adopted to investigate the influencing factors on the fear of recurrence.Results: The fear of recurrence score in elderly patients with coronary heart disease was (38.46 ± 8.13), among which 119 cases (59.5%) scored higher than 34 points. The SSRS total average score was (34.89 ± 9.83) points. Positive coping style and social support were negatively correlated with the total score of recurrence fear (r =  - 0.621, - 0.413, both P < 0.001). There was a positive correlation between negative coping style and the total score of recurrence fear (r = 0.232, P < 0.001). Multiple linear regression analysis showed that the course of the disease, the number of disease recurrence cases, active coping, and social support were relevant factors in fear of recurrence (all P < 0.05).Conclusion: The detection rate of fear of recurrence in elderly patients with coronary heart disease was relatively high but could be reduced by active interventions and enhancing social support. [ABSTRACT FROM AUTHOR]

Organic radicals, which have unique doublet spin-configuration, provide an alternative method to overcome the efficiency limitation of organic light-emitting diodes (OLEDs) based on conventional fluorescent organic molecules. Further, they have made great breakthroughs in deep-red and near-infrared OLEDs. However, it is difficult to extend their fluorescence into a short-wavelength region because of the natural narrow bandgap of the organic radicals. Herein, we significantly expand the scope of luminescent radicals by showing a new platform of carbon-centered radicals derived from N-heterocyclic carbenes that produce blue to green emissions (444–529 nm). Time-dependent density functional theory calculations and experimental investigations disclose that the fluorescence originates from the high-energy excited states to the ground state, demonstrating an anti-Kasha behavior. The present work provides an efficient and modular approach toward a library of carbon-centered radicals that feature anti-Kasha's rule emission, rendering them as potential new emitters in the short-wavelength region. Organic radicals, which have unique doublet spin-configuration, provide an alternative method to overcome the efficiency limitation of organic light-emitting diodes (OLEDs) but extending their fluorescence into a short-wavelength region remains challenging. Here, the authors significantly expand the scope of luminescent radicals by showing a new platform of carbon-centered radicals that produce blue to green emission. [ABSTRACT FROM AUTHOR]

With the gradual improvement of people’s health awareness, wearable devices occupy an important position in daily health care and human physiological activity monitoring. As traditional silicon-based electronic products face problems such as interface mismatch, silk fibroin has gradually become an alternative choice for next-generation wearable electronic devices due to its excellent performance. Herein, an ultra-thin transparent and flexible multi-functional sensor based on silk hydrogel with self-patterned microstructure is proposed. The silk hydrogel exhibits superior transparency (>82%) and thin thickness (∼100 ÎĽ m). Furthermore, the self-patterned microstructure on the silk hydrogel surface is beneficial for the high sensitivity of pressure sensing response (1.6 kPaâˆ'1). This device exhibits advantageous performance on temperature (top sensitivity of 6.25% °Câˆ'1) and humidity (top sensitivity of 0.16% RHâˆ'1) sensing response. It also shows fast response (0.16 s) and durable stability (over 2000 dynamic cycles). Moreover, this device can be applied to monitor human facial expression, joint movements, temperature change, breathing and other health indicators. It is worth mentioning that this multi-functional sensor can monitor the signal of breathing and throat, so it can be applied to the clinical physiological activity monitoring of patients with upper respiratory tract infection. In addition, we also demonstrate a grasping and relaxing experiment of intelligent manipulator to verify the pressure and temperature sensing performance, providing a possibility for its application in the field of prosthetics. According to these advantages, the reported ultra-thin transparent multi-functional sensor based on silk hydrogel has broad prospects in the fields of health monitoring, intelligent prosthetics, and electronic skin, etc. [ABSTRACT FROM AUTHOR]

The rapid development of advanced manufacturing technologies in micro-electro-mechanical system (MEMS) fields has promoted the advance in wearable electronics. Among them, wearable biomechanical micro-energy harvesters have attracted much attention in recent years to meet the unique power supply demands of wearable electronics serving as sustainable power sources. In the meanwhile, they also have been successfully demonstrated to be either self-powered sensors or other functional devices for wearable electronic applications. Herein, we overview the state-of-the-art of biomechanical micro-energy harvesters for wearable electronic applications, including the summary of working principles and structural configurations of biomechanical micro-energy harvesters. In detail, three promising technologies for biomechanical micro-energy harvesting are studied, i.e. electromagnetic effect, piezoelectric effect, and electrostatic effect. As for the structural configurations, two essential factors to affect the properties of biomechanical micro-energy harvesters are emphasized, i.e. new materials, and advanced manufacturing technologies. For wearable application scenarios, fiber/fabric-based materials and biodegradable/ecofriendly materials are investigated. For advanced manufacturing technologies, micro/nano fabrication technologies for precise fabrication and large-scale fabrication technologies for mass fabrication are summarized. Moreover, we review the wearable electronic applications of biomechanical micro-energy harvesters for powering, sensing, and actuating, respectively, which reveals the feasibility of constructing the smart wearable microsystems based on the abundant function of biomechanical micro-energy harvesters. Finally, we conclude the review and discussed the future development trends of biomechanical micro-energy harvesters for wearable electronic applications. [ABSTRACT FROM AUTHOR]

Wearable electronics, as essential components of the Internet of Things (IoT), have attracted widespread attention, and the trend is to configure attractive wearable smart microsystems by integrating sensing, powering, and other functions. Herein, we developed an elastic hybrid triboelectric–electromagnetic microenergy harvester (named EHTE) to realize hybrid sensing and microenergy simultaneously. This EHTE is a highly integrated triboelectric nanogenerator (TENG) and electromagnetic nanogenerator (EMG). Based on the triboelectric–electromagnetic hybrid mechanism, an enhanced electrical output of the EHTE was achieved successfully, which demonstrates the feasibility of the EHTE for microelectronics powering. Moreover, with the merits of the EMG, the developed hybrid microenergy harvester integrated both active frequency sensing and passive inductive sensing capabilities. Specifically, the almost linear correlation of the electromagnetic outputs to the frequencies of the external stimulus endowed the proposed EHTE with an outstanding active frequency sensing ability. In addition, due to the unique structural configuration of the EMG (i.e., a conductive permanent magnet (PM), hybrid deformation layer, and flexible printed circuit board (FPCB) coil), an opportunity was provided for the developed EHTE to serve as a passive inductive sensor based on the eddy current effect (i.e., a form of electromagnetic induction). Therefore, the developed EHTE successfully achieved the integration of hybrid sensing (i.e., active frequency sensing and passive inductive sensing) and microenergy (i.e., the combination of electromagnetic effect and triboelectric effect) within a single device, which demonstrates the potential of this newly developed EHTE for wearable electronic applications, especially in applications of compact active microsystems. [ABSTRACT FROM AUTHOR]

Copyright of Journal of Central South University is the property of Springer Nature and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Copyright of Journal of Central South University is the property of Springer Nature and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

The "Spring-red-leaf" crabapple cultivar has young red leaves and mature green leaves. However, the mechanism of anthocyanin biosynthesis in crabapple leaves in spring remains unknown. In this study, Illumina RNA sequencing (RNA-Seq) was performed on Malus 'Radiant' leaf tissues in different stages of development. Twenty-two genes in the anthocyanin biosynthesis pathway and 44 MYB transcription factors (TFs) were significantly enriched among differentially expressed genes (DEGs). Three R2R3-MYB TFs in subgroup 22 of the MYB TF family, MrMYB44-like1 , MrMYB44-like2 , and MrMYB44-like3 , were highly expressed in green leaves according to RNA-Seq and quantitative real-time quantitative PCR results. Their expression levels were negatively correlated with anthocyanin content. In transient assays, overexpression of MrMYB44-like1 , MrMYB44-like2 , or MrMYB44-like3 inhibited anthocyanin accumulation and reduced pigment in leaf disks of M. 'Radiant' and fruit peels of M. domestica 'Fuji.' When the conserved region of the three MrMYB44-like s was silenced, the anthocyanin biosynthesis pathway was activated and pigments increased in both tissues. Moreover, bimolecular fluorescence complementation assays showed MrMYB44-like s interacted with MrWRKY6 to form protein complexes that regulated anthocyanin biosynthesis. [ABSTRACT FROM AUTHOR]

Background: Malnutrition is highly prevalent in critically ill patients. The modified Nutrition Risk in the Critically ill (mNUTRIC) score has been introduced to evaluate the nutritional risk of patients in an intensive care unit (ICU). The mNUTRIC score is a predictive factor of mortality for patients in a medical or mixed ICU, whereas the relationship between mNUTRIC and prognosis of patients in a cardiothoracic surgery recovery unit (CSRU) is unclear and related researches are limited. Methods: We conducted this retrospective cohort study to explore the value of mNUTRIC score in CSRU patients. We identified totally 4059 patients from the Multiparameter Intelligent Monitoring in Intensive Care III (MIMIC III) database. Results: The optimal cut‐off value of mNUTRIC score was 4 and a total of 1498 (36.9%) patients were considered to be at high nutritional risk (mNUTRIC ≥ 4). A multivariate logistic regression model indicated that patients at high nutritional risk have higher hospital mortality compared to those at low nutritional risk (odds ratio = 2.49, 95% confidence interval (CI) = 1.32‐4.70, p = 0.005]. Furthermore, a Cox regression model was established adjusted for age, white blood cell and body mass index. The Kaplan–Meier curve indicated that patients at high nutritional risk have poorer 365‐days [hazard ratio (HR) = 1.76, 95% CI = 1.30‐2.37, p < 0.001] and 1000‐days (HR = 2.30, 95% CI = 1.87–2.83, p < 0.001) overall survival. Conclusions: The mNUTRIC score could not only predict hospital mortality, but also be an independent prognostic factor for long‐term survival in CSRU patients. More well‐designed clinical trials are needed to verify and update our findings. [ABSTRACT FROM AUTHOR]

Copyright of Journal of Zhejiang University: Science A is the property of Springer Nature and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

As lightweight materials, granulated rubber–weathered rock material (WRM) mixtures could be utilized as backfills in geosynthetics reinforcement structures to reduce deformations. However, the deformation behaviour of geosynthetics in granulated rubber–WRM mixtures is not clear. In this paper, pullout tests considering different normal pressures (30 kPa, 50 kPa and 100 kPa) and different granulated rubber contents (10%, 15% and 30%) are performed. Sensor-enable geobelts (SEGB) are employed, which can realize distributed measurements on the strains of SEGB inside soil. Two constitutive models—bilinear model and hyperbolic model are established based on tensile tests and direct shear tests to capture the full stress–strain curves and the interfacial shear responses, respectively, and are employed in the derivation of load transfer equation for pullout process. Numerical results of load transfer equation give distributions of tensile forces, strains, displacements and shear stresses. Test results validate the established constitutive models. Rubber content has an optimal value for the best geobelt–soil interaction. The deformations of geobelts in pullout process start from the front end, but decrease rapidly in soil. Under high normal pressures, the front part of geobelts exhibit quasi-plasticity. The shear stress distributes more uniformly under low normal pressure. [ABSTRACT FROM AUTHOR]

Copyright of Journal of Zhejiang University: Science A is the property of Springer Nature and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

In this study, two new mixed-ligand coordination polymers (CPs) {[Cd6(nbta)3(bimb)4(H2O)](H2O)3}n (1, bimb = 4,4′-bis((1H-imidazol-1-yl)methyl)−1,1′-biphenyl) and [Co3(bib)2(nbta)2]n (2, bib = 1,4-bis(benzimidazol-1-yl)−2-butene) have been successfully prepared by reaction of 5-nitro-1,2,3-benzenetricarboxylic acid (H3nbta) with different N-donor ligands under the solvothermal conditions. The as-prepared two CPs have been studied via the elemental analysis along with the single crystal X-ray diffraction. The inhibitory effect of synthesized new mixed-ligand coordination polymers on K562 leukemia cells was evaluated by CCK-8 assay. And the percentage of apoptotic cells after CPs 1 and 2 treatment was assessed by Annexin V-FITC/PI assay. Finally the in vivo effect of CPs on tumor was conducted by tumor volume and mice weight measurement. [ABSTRACT FROM AUTHOR]

Copyright of Canadian Geotechnical Journal is the property of Canadian Science Publishing and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

With the development of intelligent transportation, driverless is another important means that will utterly change traditional travels in the future. In order to adapt to the large-scale and complex traffic environment of driverless, we propose a dynamic bidirectional A* algorithm for driverless navigation planning. On the basis of this, theoretical simulations under different traffic flow conditions are realized, and the feasibility of the algorithm is verified. The vehicular self-organizing network is an important development direction of driverless in the future. In order to verify the performance of the algorithm in the vehicular self-organizing network environment, we adopt the OMNeT++ and SUMO bidirectional coupling, and perform joint simulation experiments on the open source framework Veins. In the traffic states with different traffic densities, the path planned by the dynamic bidirectional A* algorithm in the Vanet environment can reduce travel time and improve travel efficiency more effectively than that of the traditional bidirectional A* algorithm. [ABSTRACT FROM AUTHOR]

We investigate the atomic structure and electronic properties of monolayers of copper phthalocyanines (CuPc) deposited on epitaxial graphene substrate. We focus in particular on hexadecafluorophthalocyanine (F16CuPc), using both theoretical and experimental (scanning tunneling microscopy - STM) studies. For the individual CuPc and F16CuPc molecules, we calculated the electronic and optical properties using density functional theory (DFT) and time-dependent DFT and found a red-shift in the absorption peaks of F16CuPc relative to those of CuPc. In F16CuPc, the electronic wavefunctions are more polarized toward the electronegative fluorine atoms and away from the Cu atom at the center of the molecule. When adsorbed on graphene, the molecules lie flat and form closely packed patterns: F16CuPc forms a hexagonal pattern with two well-ordered alternating α and β stripes while CuPc arranges into a square lattice. The competition between molecule-substrate and intermolecular van der Waals interactions plays a crucial role in establishing the molecular patterns leading to tunable electron transfer from graphene to the molecules. This transfer is controlled by the layer thickness of, or the applied voltage on, epitaxial graphene resulting in selective F16CuPc adsorption, as observed in STM experiments. In addition, phthalocyanine adsorption modifies the electronic structure of the underlying graphene substrate introducing intensity smoothing in the range of 2-3 eV below the Dirac point (ED) and a small peak in the density of states at ∼0.4 eV above ED. [ABSTRACT FROM AUTHOR]

Background: Bridging studies are mandatory in the EU and USA if the reference biological product used in the biosimilar comparability exercise is foreign sourced. However, it has been argued that the duplication of bridging studies may limit biosimilar development. Objective: The aim of the study was to explore whether it is necessary to conduct pharmacokinetic (PK)/pharmacodynamic (PD) bridging studies for biosimilars. This study examines similarities and differences between EU- and US-licensed reference biological products, based on literature-reported PK and/or PD data. Methods: We searched PubMed, Drugs@FDA, and European Medicines Agency (EMA) databases to identify biosimilar bridging studies designed to evaluate similarities between EU- and US-licensed reference biological products. PK and/or PD parameters were retrieved; the ratio of the parameter value of the EU-licensed product to that of the US-licensed product and its corresponding 90% confidence intervals (CIs) were calculated. Similarity was declared if the 90% CIs for the ratios of the PK or PD parameters were within the range of 80–125%. Results: Thirty-one bridging studies were identified for 11 biosimilars, including adalimumab (n = 10), bevacizumab (n = 4), epoetin alfa (n = 1), etanercept (n = 2), filgrastim (n = 1), infliximab (n = 3), insulin glargine (n = 1), insulin lispro (n = 1), PEGfilgrastim (n = 2), rituximab (n = 2), and trastuzumab (n = 4). Most studies showed PK and/or PD similarities between the EU- and US-licensed reference biological products. However, among the 31 studies, only three studies (accounting for two biologics, PEGfilgrastim and adalimumab) showed dissimilarity between the EU and US reference products. Although one bridging study on PEGfilgrastim (Sandoz) indicated dissimilar PKs (maximum observed plasma concentration [Cmax] and area under the concentration–time curve [AUC]) between the reference products, the other study (Mylan) demonstrated similar PK. Moreover, two of ten studies involving adalimumab failed to demonstrate similarities between the reference products. However, for both cases, PK similarities were later confirmed in the follow-up bridging studies with larger sample sizes. Conclusion: Our analysis reveals that, in most cases, the reference biological products originated from the EU and those from the USA are almost indistinguishable in terms of PK/PD properties. Additional in vivo bridging studies between reference products from different global regions may not be required if similar physicochemical and structural properties are evident in vitro. [ABSTRACT FROM AUTHOR]

Extracellular vesicles (EVs) are phospholipid membrane-enclosed entities containing specific proteins, RNA, miRNA, and lncRNA. EVs are released by various cells and play a vital role in cell communication by transferring their contents from the host cells to the recipient cells. The role of EVs has been characterized in a wide range of physiological and pathophysiological processes. In this context, we highlight recent advances in our understanding of the regulatory effects of EVs, with a focus on bone metabolism and the bone microenvironment. The roles of EVs in cell communication among bone-related cells, stem cells, tumor cells, and other cells under physiological or pathological conditions are also discussed. In addition, promising applications for EVs in treating bone-related diseases are proposed. [ABSTRACT FROM AUTHOR]

Background and Objectives: The adoption of a domestic reference product in bioequivalence (BE) studies for generic drug applications is required by some countries. The objective of this study is to assess the feasibility of this by investigating whether innovative products from different countries are bioequivalent. Methods: Data were collected from all generic drug applications received by the Taiwan regulatory authority 2012-2016. If a submission package contained BE studies, that generic product was compared separately with different reference products, and the resulting data included in this analysis. A method of adjusted indirect comparison was used to evaluate the BE of reference products from different sources. The relationship between in vitro dissolution and in vivo BE was also explored. Results: The present study included 10 drugs and a total of 11 comparisons. Seven comparisons for maximum concentration ( C ) (63.6%) and all comparisons (100.0%) for area under the curve up to last measurable time point (AUC) complied with the BE criterion. Similar in vitro dissolution profiles were observed in all comparisons. Among the comparisons that failed to demonstrate BE, only one was considered to be possibly related to product difference, with point estimates of indirect comparison for C significantly greater than unity (22%). Discordance between in vitro and in vivo observations was probably due to either drugs with highly variable properties or a lack of discriminatory dissolution testing method. Conclusions: Although this retrospective analysis only included a few drugs and product formulation types, i.e., immediate release, delayed release, and orally disintegrating tablet, these preliminary results suggest that using a foreign reference product in BE studies for generic drug applications could be a feasible approach, but with some restrictions: comparable dissolution profiles, same innovator company, same size, weight, and type of coating as the domestic reference product, etc. Further investigations for other complex formulations are required. [ABSTRACT FROM AUTHOR]

CRISPR/Cas9-mediated genome editing is a next-generation strategy for genetic modifications. Typically, sgRNA is constitutively expressed relying on RNA polymerase III promoters. Polymerase II promoters initiate transcription in a flexible manner, but sgRNAs generated by RNA polymerase II promoter lost their nuclease activity. To express sgRNAs in a tissue-specific fashion and endow CRISPR with more versatile function, a novel system was established in a polycistron, where miRNAs (or shRNAs) and sgRNAs alternately emerged and co-expressed under the control of a single polymerase II promoter. Effective expression and further processing of functional miRNAs and sgRNAs were achieved. The redundant nucleotides adjacent to sgRNA were degraded, and 5′- cap structure was responsible for the compromised nuclease capacity of sgRNA: Cas9 complex. Furthermore, this strategy fulfilled conducting multiplex genome editing, as well as executing neural- specific genome editing and enhancing the proportion of homologous recombination via inhibiting NHEJ pathway by shRNA. In summary, we designed a new construction for efficient expression of sgRNAs with miRNAs (shRNAs) by virtue of RNA polymerase II promoters, which will spur the development of safer, more controllable/regulable and powerful CRISPR/Cas9 system-mediated genome editing in a wide variety of further biomedical applications. [ABSTRACT FROM AUTHOR]

The online version of the original article can be found at https://doi.org/10.1186/s12872-022-02853-w B Correction to: BMC Cardiovascular Disorders b https://doi.org/10.1186/s12872-022-02853-w Following publication of the original article [1], the affiliations of the authors Jing Zhen, Jin Jiao and Jing Li has been updated has shown below: SP 1 sp Office of Infection and Control,Affiliated Hospital of Hebei University, Baoding, China. SP 6 sp School of Nursing, Hebei University, Baoding, China. [Extracted from the article]

Three ternary copper(II) complexes [Cu(L)(phen)] ( 1), [Cu(L)(phen)] ( 2), and [Cu(L)(phen)] ·2HO ( 3) (L = 4-fluoro-2-(picolinamido)benzoic acid, L = 4,5-difluoro-2-(picolinamido)benzoic acid, L = 4,5-difluoro-2-((2-hydroxybenzylidene)amino)benzoic acid, phen = 1,10-phenanthroline) have been synthesized and characterized by physicochemical and spectroscopic methods. In addition, X-ray crystallography showed that the Cu atoms in each of the complexes are five-coordinate, adopting distorted square pyramidal or trigonal bipyramidal geometries. The interactions of the complexes with calf-thymus DNA were investigated by UV absorption, fluorescence spectroscopy and viscosity measurements. In addition, the complexes were screened for in vitro cytotoxicity against A549 (human pulmonary carcinoma cells), Jurkat (human T lymphocyte cell line) and HepG-2 (human liver hepatocellular carcinoma cells); these experiments showed that complex 3 exhibited the most effective cytotoxicities (IC = 1.224-7.099 µM). Antibacterial studies revealed that complex 3 also exhibited highest activity, consistent with the DNA binding affinities. [ABSTRACT FROM AUTHOR]

In this paper, we present experimental results on the formation of air bubbles in a non-Newtonian liquid. Flow-focusing technology with pressure-driven fluid pumping is used to demonstrate and study the bubble production process. The liquid phase consists of aqueous polyacrylamide at concentrations ranging from 0.01 to 0.10 wt%. Additionally, the solution contains sodium lauryl sulfate, an anionic surfactant, at concentrations ranging from 0.01 to 0.10 wt%. We report on bubble production with pressure ratios (dispersed/continuous phases) ranging from 0.6 to 0.9; the range spans from the minimum ratio required to produce bubbles to the pressure ratio required to produce an air jet. Within this range of pressure ratios, the bubbles lengths are polydisperse, a clear deviation from previous studies involving Newtonian continuous phase fluids. Although the continuous phase contains two additives, we deduce that the polymer is mainly responsible for this change in behavior from Newtonian fluids. The addition of surfactant though provides a means of manipulating this behavior for a certain range of polymer concentrations. We characterize the efficiency of the surfactant by performing a mass transport analysis using Schmidt ( Sc), Sherwood ( Sh), and Reynolds ( Re) numbers. Despite this observation, the average bubble lengths follow trends established for Newtonian fluids. [ABSTRACT FROM AUTHOR]