Search

Summary: A partial model‐free, data‐driven adaptive optimal output feedback (OPFB) control scheme with low computational cost continuous‐time is proposed in this paper. The design objective is to obtain the optimal control law by using measurable input and output data, without some knowledge of system model information. Firstly, the system states are decoupled into measurable and unmeasurable parts, and a new state‐space equation is built to estimate the unmeasurable states by using a reduced‐order observer. Based on this, a parametrization method is utilized to reconstruct the system states. Subsequently, by using the reconstructed states, the adaptive dynamic programming (ADP) Bellman equations based on policy‐iteration (PI) and value‐iteration (VI) are presented to solve the control problems with initially stable and unstable conditions, respectively. Then, the convergence of the system is proved. Compared with the early proposed OPFB algorithms, only the unknown internal state needs to be reconstructed. Therefore, the computation cost and design complexity are reduced for the proposed scheme. The effectiveness of the proposed scheme is verified through two numerical simulations. In addition, a practical inverted pendulum experiment is carried out to demonstrate the performance of the proposed scheme. [ABSTRACT FROM AUTHOR]

Background: To date, an effective means to preoperatively predict the malignant transformation of sinonasal inverted papilloma (SIP) remains lacking due to similarities in clinical appearance. This study aimed to retrospectively evaluate dynamic contrast‐enhanced magnetic resonance imaging (DCE‐MRI) parameters and microvessel structure in tumors with histologically confirmed SIP and inverted papilloma‐associated squamous cell carcinoma (IP‐SCC), as well as correlate DCE‐MRI findings with angiogenesis biomarkers. Methods: Absolute quantitative DCE‐MRI parameters (Ktrans, Kep, Ve) based on the Tofts model and model‐free semi‐quantitative indices (Tpeak, WR, MaxSlope) of SIP (n = 22) and IP‐SCC (n = 20) were investigated. Regions of interest (ROIs) were oriented according to the tumor subsites in the surgical records. Micro‐vessel density (MVD) counts and tight junction protein (claudin‐5) expression were evaluated in tumor specimens obtained during surgery. Differences in the above data were compared between the two groups. Correlations between DCE‐MRI parameters and angiogenic biomarkers were analyzed. Results: Compared with SIP specimens, IP‐SCC specimens were characterized by a significantly higher MVD and a leakier microvessel barrier. The values of Tpeak and Ve were significantly higher for SIP than those for IP‐SCC, whereas WR, MaxSlope, and Kep were significantly lower, indicating early enhancement and a faster dispersion model in IP‐SCC. MVD was positively correlated with WR and Kep and negatively correlated with Tpeak. Tpeak was slightly positively correlated to claudin‐5 expression. Conclusion: DCE‐MRI can serve as a noninvasive biomarker of angiogenesis in the malignant transformation from SIP to IP‐SCC. DCE‐MRI may assist in the differentiation of malignancies and treatment selection. [ABSTRACT FROM AUTHOR]

Background: Patients with ischemic heart disease (IHD) experience a high incidence of progression to heart failure (HF) despite current therapies. We speculated that steroid hormone metabolic disorders distinct adverse phenotypes and contribute to HF. Methods: We measured 18 steroids using liquid chromatography with tandem mass spectrometry in 2023 patients from the Registry Study of Biomarkers in Ischemic Heart Disease (BIOMS‐IHD), including 1091 patients with IHD in a retrospective discovery set and 932 patients with IHD in a multicentre validation set. Our outcomes included incident HF after a median follow‐up of 4 years. Results: We demonstrated steroid‐based signatures of inflammation, coronary microvascular dysfunction and left ventricular hypertrophy that were associated with subsequent HF events in patients with IHD. In both cohorts, patients with a high steroid–heart failure score (SHFS) (>1) exhibited a greater risk of incident HF than patients with a low SHFS (≤1). The SHFS further improved the prognostic accuracy beyond clinical variables (net reclassification improvement of 0.628 in the discovery set and 0.299 in the validation set) and demonstrated the maximal effect of steroid signatures in patients with IHD who had lower B‐type natriuretic peptide levels (pinteraction = 0.038). Conclusions: A steroid‐based strategy can simply and effectively identify individuals at higher HF risk who may derive benefit from more intensive follow‐ups. [ABSTRACT FROM AUTHOR]

The absorptivity of solar thermal absorber materials affects the heliothermal conversion efficiency of concentrated solar power systems. The solar absorbing ceramics were prepared by the fixed mixture of bauxit, Fe2O3, and TiO2 with adding CuO in different percentages. The absorptivity and thermal shock resistance with the effect of adding CuO in different percentages were studied. Fe2O3 and TiO2 have excellent optical properties, and CuO decreases the material's band gap to boost the electronic transition and increase the material absorptivity. The results showed that the material is sintered at 1380°C with an excellent absorptivity of 94.00% in the spectrum range of 0.3–2.5 μm, and the bending strength is 132.94 MPa. The bending strength was increased by 21.07% after 30 thermal shock cycles (1000°C‐room temperature, air cooling). The liquid phase facilitates the synthesis of hercynite with excellent high temperature properties. The hercynite improves the thermal shock resistance of the material. [ABSTRACT FROM AUTHOR]

Zirconia‐corundum‐mullite composites were prepared from andalusite, ZrO2, and α‐Al2O3 and evaluated for application as solar thermal storage materials in this study. The effects of ZrO2 concentration (0–25 wt%) and sintering temperature(1500–1650°C) on the bending strength, phase composition, microstructure, dimensional stability, and thermal shock resistance of the samples were investigated. The results showed that sample C2 (containing 10 wt% ZrO2) sintered at 1600°C exhibited the best properties. A portion of Y2O3 existed in ZrO2, which excited a small amount of t‐ZrO2 in the sample after sintering, while the other portion of Y2O3 was separated from ZrO2 and participated in the formation of a high‐temperature liquid phase. The liquid phase reduced the dimensional stability of the sample. However, the liquid phase could also promote sintering, reducing the optimal sintering temperature, with lower sintering temperatures increasing the dimensional stability of the sample. Once again, the C2 sample exhibited the highest thermal shock resistance, with a strength loss of 2.76 MPa after 30 thermal shock tests. The thermal storage density(25–1100°C) of C2 was 1121 kJ/kg. In summary, sample C2 exhibits a high degree of dimensional stability and thermal shock resistance and can thus be used as a reliable solar thermal storage material. [ABSTRACT FROM AUTHOR]

Mental rotation is the ability to mentally rotate two‐dimensional and three‐dimensional objects in one's mind. Previous studies have examined the relationship between mental rotation abilities and embodied cognition. However, conflicting findings underscore the necessity for further investigation. This study aims to investigate how different levels of embodiment in mental rotation training affect mental rotation training. Three versions of mental rotation training with different levels of embodiment (keyboard, touchpad and augmented reality) were developed for this study. A quasi‐experimental study was conducted with a total of 125 university students to explore how different training versions affect participants' training performances, perception of the usability of the training and mental rotation ability. The results suggest those who used the versions with higher levels of bodily engagement performed better than those who used the versions with lower levels of bodily engagement (p < 0.001). Participants' mental rotation ability also improved significantly after training with the augmented reality (AR1) version compared to those in the keyboard group (p = 0.01). The learning analytics results provide additional clarity by indicating that the participants' mental rotation ability can be predicted by their training performance in the AR condition (p < 0.001). This study has significant implications for the potential of using embodied AR training to improve mental rotation ability. Practitioner notesWhat is already known about this topicMental rotation ability is a malleable trait that can be improved through repeated and long‐term game‐based training.Short‐term training using digital games has limited impacts on mental rotation ability.Mental rotation abilities are linked to our bodily interactions with the physical world.What this paper addsInvestigates how different levels of bodily engagement in a digital game affect short‐term mental rotation training.Investigates how different levels of bodily engagement in a mental rotation training game affect players' game performance and perception of the usability of the game.Investigates if players' performance in a mental rotation training game can predict their mental rotation ability and self‐diagnosed sense of direction.Leverages learning analytics to explain findings generated by traditional research methods.Implications for practice and/or policyLeveraging augmented reality technology in more embodied mental rotation training games can facilitate short‐term gains in mental rotation.Game‐based learning researchers should consider leveraging learning analytics techniques to provide richer and more nuanced explanations for findings generated by traditional research methods.Game performance in effective mental rotation training games can predict mental rotation abilities, thus potentially assessing such abilities. [ABSTRACT FROM AUTHOR]

The cyclability of aqueous zinc‐ion batteries is greatly influenced by Zn dendrites and parasitic reactions. Although separator modifications have proven to be effective in addressing these issues, most of the developed separators are too thick to meet practical requirements. Herein, an amino (−NH2)‐functionalized Zr‐based metal–organic framework (MOF), i.e., UiO‐66‐NH2, is incorporated into lignocellulose separator. The amino functional groups not only possess good zincophilicity but also strongly interact with H2O molecules through hydrogen bonding. Therefore, the abundant intersecting subnano‐sized channels within UiO‐66‐NH2 act as desolvation sieves and facilitate the migration and uniform distribution of Zn2+ ions. Even at a rather low thickness of 20 µm, the modified separator can significantly improve the reversibility of Zn electrochemistry and suppress water‐induced hydrogen evolution. With the use of this separator, the Zn electrodes demonstrate a working life exceeding 2000 h at a current density of 2 mA cm−2 with remarkable dendrite‐free characteristic and remain operationally viable under ultrahigh areal capacity of 25 mAh cm−2. Additionally, the resultant Zn//MnO2 battery provides superior rate capability and excellent cyclability. This study provides novel insights into the utilization of amino functional groups to inhibit unfavorable phenomena in aqueous batteries. [ABSTRACT FROM AUTHOR]

A strong polarization electric field (PEF) in III‐nitride semiconductors has adverse effects on the performance of III‐N light‐emitting diodes (LEDs). However, to reduce the PEF of III‐N LEDs based on the polar plane (c‐plane) remains a big challenge. Here, a weak PEF blue LED on c‐plane GaN with an InGaN/AlGaN superlattices (SLs) quantum barrier and InGaN quantum well grown by metal‐organic chemical vapor deposition is proposed. The InGaN/SLs multiple quantum wells (MQWs) show a significant reduction of PEF compared with traditional InGaN/GaN MQWs. A low electric field of 0.5 MV cm−1 is obtained, which is confirmed by power‐dependent photoluminescence (PL) and time‐resolved PL measurements. The proposed LEDs with InGaN/AlGaN SLs barriers present a low efficiency droop, a great wavelength stability, and a high −3 dB E‐O modulation bandwidth up to 1.01 GHz. This work demonstrates the role of InGaN/AlGaN SLs barriers in reducing the PEF of III‐N LEDs and provides a feasible technical route to achieve the weak PEF LEDs on c‐plane, which can be expanded and applied to the preparation of high‐performance, long wavelength, and deep UV III‐N LEDs. [ABSTRACT FROM AUTHOR]

The out‐of‐band energy loss caused by in‐built color filters significantly degrades the signal‐to‐noise ratio and the dynamic range of conventional image sensors, which has restricted the attempt to develop ultrahigh‐density imaging devices by merely shrinking the pixel size. This issue will be more serious for security cameras, which need to collect both visible (VIS) and near‐infrared (NIR) light. The existing solutions mostly explore complex photonic nanostructures, which are often too complicated for production. In this work, a pixelated spectral router is demonstrated utilizing a 2D Si3N4 Mie‐type metagrating that can spatially divide NIR (850 nm) and VIS (400–700 nm) light to different pixels at high efficiencies. It has a minimum feature size larger than 360 nm, highly promising for massive production. Compared with the traditional filter design, this router can gain ≈42% and ≈30% signal enhancement for NIR and VIS bands, respectively. It is shown that it also has good polarization insensitivity and incident angle tolerance. The NIR–VIS simultaneous imaging is inspected without any complex reconstruction algorithm. Mode analysis indicates that the periodic interference of multipolar scattered fields caused by this metagrating provides the necessary degrees of freedom to spatially optimize the routing functions for broadband photons. [ABSTRACT FROM AUTHOR]

Establishing a valid in vitro model to represent tumor heterogeneity and biology is critical but challenging. Tumor organoids are self‐assembled three‐dimensional cell clusters which are of great significance for recapitulating the histopathological, genetic, and phenotypic characteristics of primary tissues. The organoid has emerged as an attractive in vitro platform for tumor biology research and high‐throughput drug screening in cancer medicine. Organoids offer unique advantages over cell lines and patient‐derived xenograft models, but there are no standardized methods to guide the culture of organoids, leading to confusion in organoid studies that may affect accurate judgments of tumor biology. This review summarizes the shortcomings of current organoid culture methods, presents the latest research findings on organoid standardization, and proposes an outlook for organoid modeling. [ABSTRACT FROM AUTHOR]

Zn ion energy storage devices have received widespread attention because of their high safety, environmental friendliness, low cost, and high energy density. However, Zn metal anodes usually suffer from disadvantages such as dendrite growth, low coulombic efficiency, and volume expansion during plating/stripping, which severely hampers the practical applications. Here, we construct 3D Zn frameworks by exploring different conductive hosts and modify 3D hosts by plating Sn to suppress Zn dendrites and side reactions. The electrode which optimized by electroplating Zn after chemically plating Sn on Cu foam (Sn−Cu foam@Zn) exhibits stable polarization voltage distribution and almost 100% coulombic efficiency over 200 cycles of Zn plating/stripping. Furthermore, when pairing with V2O5 cathode, the full cell showed fast reaction kinetics and a capacity of 113 mAh g−1 after 1000 cycles at a current density of 1 A g−1, which is 90.4% of the initial capacity. This work provides a new strategy for the development of high‐performance Zn anodes. [ABSTRACT FROM AUTHOR]

In traditional power systems, the positive sequence fault component (PSFC) based criteria is often used to identify the fault directions. If the PSFC impedance angle of the inverter‐interfaced distributed generator (IIDG) is between 0 and 90°, the traditional PSFC‐based criteria will remain applicable in active distribution networks (ADNs). However, due to the diversity of the IIDG fault control mode and the uncertainty of the positive sequence voltage variation caused by faults, the PSFC impedance angle of IIDG is difficult to determine. To solve this problem, this paper proposes a two‐stage fault control scheme for IIDG. At different stages, IIDGs select different power references to meet different requirements. In the first stage, the PSFC impedance angle of IIDG is fixed to a given value, thereby maintaining the applicability of the PSFC‐based criteria in ADN. The detailed power reference calculation method of IIDG is given for this stage. In the second stage, IIDGs can select different fault control modes to support the fault voltage flexibly. By using the proposed two‐stage IIDG fault control scheme, the protection devices can accurately identify the fault direction in ADNs, which is verified by the MATLAB simulation results. © 2022 Institute of Electrical Engineers of Japan. Published by Wiley Periodicals LLC. [ABSTRACT FROM AUTHOR]

Background: Triterpene acid is one of the typical active constituents of Eucalyptus bark, which is the main by‐product of the Eucalyptus wood industry. Our studies have demonstrated that triterpene acid stress could inhibit climbing and increase mortality in Pomacea canaliculata (Lamarck). However, limited attention has been paid to the proteomic responses of this snail under triterpene acid stress. Result: Using iTRAQ‐based quantitative proteomics, we elucidated the regulatory mechanism in the livers of P. canaliculata held in chlorine‐free water and exposed to 100 mg L−1 oleanolic acid (OA) for 24 h. A total of 4308 proteins were identified, of which 274 were differentially expressed proteins (DEPs) including 168 (61.31%) differentially upregulated proteins and 106 (38.69%) differentially downregulated proteins. Bioinformatics analysis revealed that P. canaliculata responses to OA stress are mainly involved in glucose metabolism, energy synthesis, immune response, stress response, protein synthesis, and apoptosis. According to KEGG analysis, the 274 DEPs were mapped to 168 KEGG pathways and 10 KEGG pathways were significantly enriched (P < 0.05). Furthermore, qRT‐PCR was performed for histone H4, catalase, isocitrate dehydrogenase, superoxide dismutase, ferritin, lipase, and tropomyosin to validate the iTRAQ results. Conclusion: Proteomic analysis suggested that OA stress led to the disruption of glucose metabolism, energy synthesis, and protein synthesis, and triggered a series of molecular pathways containing many key proteins involved in the immune process, thereby helping P. canaliculata resist OA stress. © 2022 Society of Chemical Industry. [ABSTRACT FROM AUTHOR]

Hydrogels with injectability and robustness have great promise in clinical practice. However, current injectable hydrogels are usually mechanically weak. Here, an idea, "preformed hydrogel reversion", is proposed to develop robust injectable hydrogels through an intermediate unit‐mediated, continuous structural inheritance strategy. In this strategy, robust preformed hydrogels are physically disassembled into intermediate injectable structure‐inherited microgels (SIMs), and upon encountering water in physiological environment, the SIMs can construct a macroscopical robust structure with the driving force of hydrogen bonds (H‐bonds). The physical disassembly and construction process enables the inheritance of robust structures through SIMs, thereby realizing both excellent injectability and robustness. Beyond that, the SIMs also exhibit long‐term storage stability and convenient usability. Using protein drug loading and hemostasis as examples, it is demonstrated that the SIM system shows superiorities in biomedical applications. The proposed idea of "preformed hydrogel reversion" can open new horizons for developing robust injectable hydrogels for diverse applications. [ABSTRACT FROM AUTHOR]

The significance of exploring optimal electrode materials cannot be overstated, particularly in mitigating the critical issues posed by sluggish redox kinetics, significant volume variations, and severe structural collapse resulting from the insertion and extraction of sodium ions. These efforts are crucial for enhancing the longevity and rapid charging capabilities of sodium‐ion batteries (SIBs). Herein, a defect engineering strategy for the in situ encapsulation of single‐phase ternary iron phosphoselenide into porous carbon by robust chemical bonds with the formation of rod‐like multicavity nanohybrids (FePSe3@C) is presented. The incorporation of Se atom not only modulates the electronic structure of the central metal Fe atom and enhances the intrinsic electrical conductivity, but also generates numerous additional reaction sites and accelerates the reaction kinetics of FePSe3@C, as corroborated by theoretical calculations and kinetic analysis. Notably, the FePSe3@C demonstrates an outstanding rate capability of 321.7 mAh g−1 even at 20 A g−1 and long cycling stability over 1000 cycles. The sodium‐ion full cell, pairing the FePSe3@C anode with the Na3V2(PO4)3@C cathode, exhibits a remarkable energy density of 202 Wh kg−1, demonstrating its practical applicability. This work provides a controllable defect and morphology engineering strategy to construct advanced materials with fast charge transfer for high‐power/energy SIBs. [ABSTRACT FROM AUTHOR]

Tandem catalysis, which allows multiple steps of a reaction to take place without the need for separation and purification, is highly desired for the design of efficient and environmentally‐friendly chemical processes. Herein, the pyrolysis of UiO‐66‐NH2, an amino‐functionalized metal‐organic framework, produces nitrogen‐rich carbon‐ZrO2 composite (CN‐ZrO2). This composite is rich in basic sites and effectively catalyzes the Knoevenagel condensation reaction. After loading Pt nanoparticles onto this composite support, a tandem catalyst (Pt/CN‐ZrO2) is produced to be capable of the one‐step Knoevenagel condensation‐hydrogenation reaction to produce an alpha‐alkylated nitrile. The tandem catalyst exhibits >99 % aldehyde conversion and >99 % selectivity toward alpha‐alkylated nitrile under 1 MPa H2 at 80 °C. This catalyst could be reused for five times in the presence of malononitrile without significant deactivation and is versatile for one‐step condensation‐hydrogenation of various aldehydes. The good performance of Pt/CN‐ZrO2 could be ascribed to the synergistic interaction between Pt and CN‐ZrO2 composite supports that lead to the appropriate hydrogenation activity of supported Pt nanoparticles. [ABSTRACT FROM AUTHOR]

Desktop virtualization, which is to make the desktop virtual so that users can access any application through the network with any devices at any time and any place, is being widely used now as an emerging trend. However, it is important to further improve this approach while maintaining good user experience. Though the simple protocol for independent computing environments as a virtual desktop solution can achieve a user experience similar to an interaction with a local machine, there are still many deficiencies in it. For instance, it cannot apply to environment of high controllability of user, and the quality of graphic interactive experience is to be improved. In this paper, to meet QoE requirements of user, we build a feasible file transfer and sharing mechanism and propose a graphics subsystem optimization strategy based on simple protocol for independent computing environments (SPICE), namely Transparent Desktop. We also verify that the Transparent Desktop can provide users with ubiquitous desktop services of higher efficiency, stronger user-controllability and better QoE through the experimental. Copyright © 2016 John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]

Multifunctionality, integration, and miniaturization are the mainstream trends in modern device development. However, optical display and depth perception, essential for innovative applications like intelligent driving and mixed reality, are typically achieved separately in complex and bulky optical systems. Metasurfaces, ultrathin artificial optical surfaces with strong light–matter interaction capabilities at the nanoscale, offer a versatile platform for creating multifunctional, highly integrated, and miniaturized devices by fully exploring spatial multiplexing and utilizing variables like location, polarization, and frequency. In this study, a multifunctional metasurface that integrates meta‐holography with Dammann gratings is presented. By engineering the phase profile, the device can display specific holographic images in the Fresnel region while simultaneously producing a high‐density spot cloud with over 37 000 spots covering the entire half space. As a proof‐of‐concept, a projection and reconstruction experiment is performed to elaborate its potential for retrieving three‐dimensional (3D) spatial information of real scenarios. The simultaneous generation of display and point cloud holds significant promise for applications in cutting‐edge imaging technologies such as intelligent driving and robot vision. [ABSTRACT FROM AUTHOR]

It is crucial to develop advanced optoelectronic devices that incorporate multiple functions, including sensing, storage, and computing, which is considered at the forefront of semiconductor optoelectronics to meet emerging functional diversification. In this study, by stacking the n‐type Ga2O3 with the n‐type MoS2 flakes, a Ga2O3/MoS2 heterostructure optoelectronic device with high rectification ratio of ≈105 and on/off ratio of ≈108 is fabricated, which achieves high detectivity of 1.34 × 109 Jones and high responsivity of 28.92 mA/W. More importantly, the Ga2O3/MoS2 heterostructure device shows potential ability to integrate sensing and memorizing, simultaneously, which can be used as artificial neuromorphic synaptic. The device exhibits excellent photo‐induced synaptic functions including short‐term plasticity, long‐term plasticity, and paired‐pulse facilitation, realizing the ability to couple light and electrical signals by Pavlovian associative learning. At last, the device also demonstrates the information processing ability to act as optoelectronic logic gate AND by synergistically regulating the light on/off states and gate voltage. The research introduces an innovative strategy for the development of next‐generation optoelectronic devices which are highly integrated with sensing, memory, and logic processing functions, demonstrating great application prospects in constructing an efficient artificial neuromorphic visual and logic systems. [ABSTRACT FROM AUTHOR]

Aim Methods Results Conclusions Reversible cognitive frailty (RCF) is an ideal target to prevent asymptomatic cognitive impairment and dependency. This study aimed to develop and validate prediction models for incident RCF.A total of 1230 older adults aged ≥60 years from China Health and Retirement Longitudinal Study 2011–2013 survey were included as the training set. The modified Poisson regression and three machine learning algorithms including eXtreme Gradient Boosting, support vector machine and random forest were used to develop prediction models. All models were evaluated internally with fivefold cross‐validation, and evaluated externally using a temporal validation method through the China Health and Retirement Longitudinal Study 2013–2015 survey.The incidence of RCF was 27.4% in the training set and 27.5% in the external validation set. A total of 13 important predictors were selected to develop the model, including age, education, contact with their children, medical insurance, vision impairment, heart diseases, medication types, self‐rated health, pain locations, loneliness, self‐medication, night‐time sleep and having running water. All models showed acceptable or approximately acceptable discrimination (AUC 0.683–0.809) for the training set, but fair discrimination (AUC 0.568–0.666) for the internal and external validation. For calibration, only modified Poisson regression and eXtreme Gradient Boosting were acceptable in the training set. All models had acceptable overall prediction performance and clinical usefulness. Older adults were divided into three groups by the risk scoring tool constructed based on modified Poisson regression: low risk (≤24), median risk (24–29) and high risk (>29).This risk tool could assist healthcare providers to predict incident RCF among older adults in the next 2 years, facilitating early identification of a high‐risk population of RCF. Geriatr Gerontol Int 2024; ••: ••–••. [ABSTRACT FROM AUTHOR]

Butylene fipronil (BFPN) is a phenylpyrazole insecticide, acting at the γ‐aminobutyric acid (GABA) receptor. Here, we show that BFPN inducedcytotoxicity in PC12 murinenervous cells, which lacks GABA receptor. Treatment with BFPN for 48 hours significantly enhanced G0/G1 arrest and induced apoptosis. BFPN decreased the expression of cyclin‐dependent kinase (CDK4 and CDK6) and increased P16 and cyclin D1. Simultaneously, Bcl‐2 protein was declined while Bax and cytochrome c were significantly enhanced in BFPN‐treated groups. The apoptotic enzymes caspase‐8, ‐9, and ‐3 were also activated by BFPN. Furthermore, treatment with BFPN significantly stimulated reactive oxygen species (ROS) generation, and pretreatment with antioxidant diphenyleneiodonium, substantially reduced cell death. Overall, these results suggest that BFPN is effective to induce G0/G1‐phase arrest and apoptosis in PC12 murine nervous cell. Stimulating ROS generation and activation of P16‐CDK4/6‐cyclin D1 and mitochondrial apoptotic pathway may participate in the cytotoxicity of BFPN. [ABSTRACT FROM AUTHOR]

Topical timolol and lasers are widely used for the treatment of infantile hemangioma (IH), and they can replace propranolol as the first-line treatment of IH. We aimed to investigate the efficacy and safety of topical timolol alone or lasers plus topical timolol versus lasers alone for the treatment of IH using a meta-analysis. We searched the PubMed, Embase, Cochrane Library, China National Knowledge Infrastructure, and Wanfang databases. A more conservative random effect model meta-analysis technique was used to analyze the efficacy and adverse reactions of timolol and lasers. Ten RCTs with a total of 979 patients with IH were included in this meta-analysis. Treatment with topical timolol alone was as effective as lasers in treating IH (risk ratio [RR] = 0.99, p = 0.94), with similar adverse events. The difference was not statistically significant (RR = 1.67, p = 0.14). Combined treatment with topical timolol and lasers showed a favorable response rate compared with treatment with either lasers (RR = 1.23, p = 0.01) or topical timolol (RR = 1.35, p = 0.001) alone. Furthermore, compared to topical timolol alone, the combined treatment indicated similar risks of adverse events (RR = 0.70, p = 0.38) but fewer risks of adverse events (RR = 0.39, p = 0.004) compared to lasers alone. This meta-analysis provided evidences that a combined treatment with topical timolol and lasers might be more effective than a single treatment strategy in infants with IH, and with no significant increase in adverse reactions. The combination of topical timolol and laser therapy might be the preferred choice for the treatment of IHs., (© 2022 Wiley Periodicals LLC.)