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Background: Exosomes and other secretory membrane vesicles, collectively referred to as extracellular vesicles (EVs), have garnered increasing attention in research due to their biological characteristics. Notably, studies have shown promising results regarding the role of stem cell‐derived extracellular vesicles (SC‐EVs) in skin and plastic surgery applications. This study aims to elucidate current trends in SC‐EVs within the context of skin and plastic surgery and offer insights for future research directions in advancing this critical field. Methods: A comprehensive search was conducted for relevant studies on SC‐EVs in skin and plastic surgery spanning from 2003 to 2023, utilizing the Web of Science database. Subsequently, data analysis was performed using VOSviewer and CiteSpace. Results: A total of 1089 studies were identified, with a noticeable annual increase in publications on SC‐EVs' application in skin and plastic surgery. China emerged as the leading contributor to this field, with Shanghai Jiao Tong University being a notable institution. Stem Cell Research & Therapy and the International Journal of Molecular Sciences were the top journals publishing relevant articles. Author Fu Xiaobing from the Chinese People's Liberation Army General Hospital had the highest publication count in this area. Keyword co‐occurrence analysis revealed six distinct clusters, with "exosomes" being the most prevalent keyword in recent years. Wound healing and skin rejuvenation emerged as primary research focuses and hotspots in this field. Conclusion: This comprehensive review offers insights into global trends surrounding SC‐EVs in skin and plastic surgery. Analysis of journals, institutions, references, and keywords provides valuable guidance for researchers in determining future research directions. [ABSTRACT FROM AUTHOR]

As the integration of renewable energy expands, effective energy system management becomes increasingly crucial. Distributed renewable generation microgrids offer green energy and resilience. Combining them with energy storage and a suitable energy management system (EMS) is essential due to the variability in renewable energy generation. Reinforcement learning (RL)-based EMSs have shown promising results in handling these complexities. However, concerns about policy robustness arise with the growing number of grid intermittent disruptions or disconnections from the main utility. This study investigates the resilience of RL-based EMSs to unforeseen grid disconnections when trained in grid-connected scenarios. Specifically, we evaluate the resilience of policies derived from advantage actor–critic (A2C) and proximal policy optimization (PPO) networks trained in both grid-connected and uncertain grid-connectivity scenarios. Stochastic models, incorporating solar energy and load uncertainties and utilizing real-world data, are employed in the simulation. Our findings indicate that grid-trained PPO and A2C excel in cost coverage, with PPO performing better. However, in isolated or uncertain connectivity scenarios, the demand coverage performance hierarchy shifts. The disruption-trained A2C model achieves the best demand coverage when islanded, whereas the grid-connected A2C network performs best in an uncertain grid connectivity scenario. This study enhances the understanding of the resilience of RL-based solutions using varied training methods and provides an analysis of the EMS policies generated. [ABSTRACT FROM AUTHOR]

"Exercise is the best medicine" is well known, but the optimal dose of physical activity (PA) for males and females across different age groups is still unknown. This study, using data from the four waves of CHARLS, aimed to determine the optimal PA dose that reduces frailty risks among older adults across various age groups and both sexes. We created a frailty index score using 63 health-related variables and used 0.21 as the frailty cut point. Binary logistic regression was used to compare the effect of vigorous, moderate, and light intensity PA under IPAQ criteria on frailty risk. The study found that regardless of whether males or females, the optimal effect of vigorous-intensity PA in reducing the risk of frailty is consistently observed throughout the entire old age career. Moreover, the age groups at which moderate-intensity PA reduces the risk of frailty were from age 70 for males and from age 80 for females. And light-intensity PA had no effect on reducing the risk of frailty. Moderate and vigorous intensity of PA in older adults should be promoted, but guidelines and recommendations must account for optimal associations with PA dose across genders and age groups. [ABSTRACT FROM AUTHOR]

Dual gate device with mobility of 20cm2/Vs has been applied to improve power consumption of oxide products, the devices show high on‐state current of more than 45uA, good uniformity of ΔVth 1.03V, PBTS of 2.18V. The optimized pixel design of 14inch WQXGA achieves high aperture ratio of 74% and transmittance of over 9.5%. This 120Hz demo with brightness of 150nit can significantly reduce power consumption by 65%, from 2.1W to 1.27W. [ABSTRACT FROM AUTHOR]

In recent years, the continuous progress of wireless communication and sensor technology has enabled sensors to be better integrated into mobile devices. Therefore, sensor-based Human Activity Recognition (HAR) has attracted widespread attention among researchers, especially in the fields of wearable technology and ubiquitous computing. In these applications, mobile devices' built-in accelerometers and gyroscopes have been typically used for human activity recognition. However, devices such as smartphones were placed in users' pockets and not fixed to their bodies, and the resulting changes in the orientation of the sensors due to users' habits or external forces can lead to a decrease in the accuracy of activity recognition. Unfortunately, there is currently a lack of publicly available datasets specifically designed to address the issue of device angle change. The contributions of this study are as follows. First, we constructed a dataset with eight different sensor placement angles using accelerometers and gyroscopes as a prerequisite for the subsequent research. Second, we introduced the Madgwick algorithm to extract quaternion mode features and alleviate the impact of angle changes on recognition performance by fusing raw accelerometer data and quaternion mode features. The resulting study provides a comprehensive analysis. On the one hand, we fine-tuned ResNet and tested its stability on our dataset, achieving a recognition accuracy of 97.13%. We included two independent experiments, one for user-related scenarios and the other for user-independent scenarios. In addition, we validated our research results on two publicly available datasets, demonstrating that our method has good generalization performance. [ABSTRACT FROM AUTHOR]

Adipose tissue macrophages can promote beige adipose thermogenesis by altering local sympathetic activity. Here, we perform sympathectomy in mice and further eradicate subcutaneous adipose macrophages and discover that these macrophages have a direct beige-promoting function that is independent of sympathetic system. We further identify adipocyte Ets1 as a vital mediator in this process. The anti-inflammatory M2 macrophages suppress Ets1 expression in adipocytes, transcriptionally activate mitochondrial biogenesis, as well as suppress mitochondrial clearance, thereby increasing the mitochondrial numbers and promoting the beiging process. Male adipocyte Ets1 knock-in mice are completely cold intolerant, whereas male mice lacking Ets1 in adipocytes show enhanced energy expenditure and are resistant to metabolic disorders caused by high-fat-diet. Our findings elucidate a direct communication between M2 macrophages and adipocytes, and uncover a function for Ets1 in responding to macrophages and negatively governing mitochondrial content and beige adipocyte formation. Adipose beiging is a positive biological change, which is often thought to be primarily sympathetically induced. Here, the authors show that M2 macrophages can independently promote beige adipogenesis, further revealing the adipocyte transcription factor Ets1 as a negative regulator of this process. [ABSTRACT FROM AUTHOR]

Adipose tissue macrophages can promote beige adipose thermogenesis by altering local sympathetic activity. Here, we perform sympathectomy in mice and further eradicate subcutaneous adipose macrophages and discover that these macrophages have a direct beige-promoting function that is independent of sympathetic system. We further identify adipocyte Ets1 as a vital mediator in this process. The anti-inflammatory M2 macrophages suppress Ets1 expression in adipocytes, transcriptionally activate mitochondrial biogenesis, as well as suppress mitochondrial clearance, thereby increasing the mitochondrial numbers and promoting the beiging process. Male adipocyte Ets1 knock-in mice are completely cold intolerant, whereas male mice lacking Ets1 in adipocytes show enhanced energy expenditure and are resistant to metabolic disorders caused by high-fat-diet. Our findings elucidate a direct communication between M2 macrophages and adipocytes, and uncover a function for Ets1 in responding to macrophages and negatively governing mitochondrial content and beige adipocyte formation.Adipose beiging is a positive biological change, which is often thought to be primarily sympathetically induced. Here, the authors show that M2 macrophages can independently promote beige adipogenesis, further revealing the adipocyte transcription factor Ets1 as a negative regulator of this process. [ABSTRACT FROM AUTHOR]

This was a prospective, randomized, double‐blind, single‐center placebo‐controlled trial to assess the efficacy and safety of melatonin as an add‐on treatment for infantile epileptic spasms syndrome (IESS). Participants aged 3 months to 2 years with a primary diagnosis of IESS were recruited and assigned to two groups in a 1:1 ratio. Both treatment groups received a combination of adrenocorticotrophic hormone (ACTH) and magnesium sulfate (MgSO4) for 2 weeks, and the treatment group also received melatonin (3 mg) between 20:00 and 21:00 daily, 0.5–1 h before bedtime. The study's primary endpoint was the average reduction rate in spasm frequency assessed by seizure diaries. Secondary endpoints included assessment of the response rate, EEG hypsarrhythmia (Kramer score), and psychomotor development (Denver Developmental Screening Test, DDST). Sleep quality was assessed by using the Brief Infant Sleep Questionnaire (BISQ), the Infant Sleep Assessment Scale (ISAS), and actigraphy. Safety parameters were also evaluated. Statistical analyses were conducted on intention‐to‐treat and per‐protocol populations. The trial is registered at Clinicaltrials.gov (ChiCTR2000036208). Out of 119 screened patients, 70 were randomized and 66 completed treatments. In the intention‐to‐treat population, there were no significant differences in the average percentage reduction of spasm frequency (median [interquartile range, IQR: Q3–Q1], 100% [46.7%] vs. 66.7% [55.3%], p =.288), the 3‐day response rate (51.4% vs. 37.1%, p =.229), the 28‐day response rate (42.9% vs. 28.6%, p =.212), EEG Kramer scores (2 [3.5] vs. 2 [3], p =.853), or DDST comprehensive months (5 [2.5] vs. 6 [6], p =.239) between the melatonin (n = 35) and placebo (n = 35) groups. However, caregivers reported improved sleep quality after melatonin treatment, with 85.7% reporting regular sleep compared to 42.9% with placebo (42.9%, p <.001). The melatonin group had lower ISAS scores in 4–11‐month‐old patients compared to the placebo (mean ± SD, 29.3 ± 4.4 vs. 35.2 ± 5.9, p <.001). Moreover, the median (IQR) value of sleep‐onset latency was shortened by 6.0 (24.5) min after melatonin treatment, while that in the placebo group was extended by 3.0 (22.0) min (p =.030). The serum melatonin (6:00 h) level (pg/mL) of the children in the melatonin group after treatment was significantly higher than in the placebo group (median [IQR], 84.8 [142] vs. 17.5 [37.6], p <.001). No adverse effects related to melatonin were observed in the study, and there were no significant differences in adverse effects between the melatonin and placebo groups. Although not statistically significant, the results of this randomized clinical trial proved that melatonin supplementation, as an add‐on treatment, can improve spasm control rate in the treatment of IESS. For IESS children treated with ACTH, the addition of melatonin was found to improve sleep quality, shorten sleep onset latency, and increase blood melatonin levels. Moreover, it was observed to be a safe treatment option. [ABSTRACT FROM AUTHOR]

Catalytic ozonation, with enhanced efficiency and reduced byproduct formation at lower temperatures, proved to be efficient in ethyl acetate (EA) degradation. In this work, MMn2O4 (M = Cu, Co, Ni, Mg) catalysts were prepared via a redox-precipitation method to explore the catalytic ozonation mechanism of EA. Among all the catalysts, CuMn exhibited superior catalytic activity at 120 °C, achieving nearly 100% EA conversion and above 90% CO2 selectivity with an O3/EA molar ratio of 10. Many characterizations were conducted, such as SEM, BET and XPS, for revealing the properties of the catalysts. Plentiful active sites, abundant oxygen vacancies, more acid sites and higher reduction ability contributed to the excellent performance of CuMn. Moreover, the addition of NO induced a degree of inhibition to EA conversion due to its competition for ozone. H2O had little effect on the catalytic ozonation of CuMn, as the conversion of EA could reach a stable platform at ~89% even with 5.0 vol.% of H2O. The presence of SO2 usually caused catalyst deactivation. However, the conversion could gradually recover once SO2 was discontinued due to the reactivation of ozone. A detailed reaction mechanism for catalytic ozonation was proposed via in situ DRIFTS measurements and DFT calculations. [ABSTRACT FROM AUTHOR]

The surface coatings of cereal plants are dominated by waxy β-diketones crucial for drought resistance and, therefore, grain yield. Here, barley (Hordeum vulgare) wax analyses reveal β-diketone and associated 2-alkanol ester profiles suggesting a common C16 3-ketoacid precursor. Isotope analysis further shows that the major (C31) diketone is synthesized from two plastidial C16 acyl units. Previous studies identified a gene cluster encoding enzymes responsible for β-diketone formation in barley, but left their biochemical functions unknown. Various assays now characterize one of these enzymes as a thioesterase producing long-chain (mainly C16) 3-ketoacids, and another one as a polyketide synthase (PKS) condensing the 3-ketoacids with long-chain (mainly C16) acyl-CoAs into β-diketones. The two enzymes are localized to the plastids and Endoplasmic Reticulum (ER), respectively, implying substrate transfer between these two sub-cellular compartments. Overall, our findings define a two-step pathway involving an unprecedented PKS reaction leading directly to the β-diketone products. Barley plants coat their organs with waxy diketones to protect against late-summer droughts. These diketones are formed by two enzymes, one diverting common fatty acids from normal metabolism and the other one linking two fatty acid units together. [ABSTRACT FROM AUTHOR]

Emotion recognition is one of the most important research directions in the field of brain–computer interface (BCI). However, to conduct electroencephalogram (EEG)-based emotion recognition, there exist difficulties regarding EEG signal processing; moreover, the performance of classification models in this regard is restricted. To counter these issues, the 2022 World Robot Contest successfully held an affective BCI competition, thus promoting the innovation of EEG-based emotion recognition. In this paper, we propose the Transformer-based ensemble (TBEM) deep learning model. TBEM comprises two models: a pure convolutional neural network (CNN) model and a cascaded CNN-Transformer hybrid model. The proposed model won the abovementioned affective BCI competition's final championship in the 2022 World Robot Contest, demonstrating the effectiveness of the proposed TBEM deep learning model for EEG-based emotion recognition. [ABSTRACT FROM AUTHOR]

A hierarchical controller is proposed for achieving high‐accuracy control and the dynamic balance with the presence of multiple faults of actuator, the external disturbance, and the model uncertainties in multicylinder hydraulic press machine (MCHPM). The method divides the controller design into three steps: Virtual fault‐tolerant control law, control allocation algorithm, and actuator control law, which are progressive. First, to precisely compensate the lumped disturbances including the multiple faults of actuator, the external disturbance, and the model uncertainties, a disturbance observer (DO) is developed. By combining the observer with the sliding mode control (SMC), a virtual fault‐tolerant control law is designed. Second, a highly integrated control allocation algorithm for the virtual fault‐tolerant control law is proposed to get the desired driving force, taking into account dynamic control allocation (DCA), multiobjective optimization (MOO) and Analytic Hierarchy Process (AHP) simultaneously. Third, taking the driving force obtained from above control allocation algorithm as the desired target, the control law of each cylinder is calculated. The global stability for the whole system is proved by the Lyapunov theory. Lastly, results of simulation and experiment show that the proposed controller can effectively handle different faults and have more superior control performance. [ABSTRACT FROM AUTHOR]

The bird cherry‐oat aphid Rhopalosiphum padi (L.) (Hemiptera: Aphididae) is a key pest of wheat in China. Chitosan oligosaccharide (COS) has been widely used due to its biocompatibility, antibacterial activity, environmental friendliness and convenient extraction. This study was aimed at determining the acute toxicity of COS on R. padi and transgenerational effects of sublethal concentrations of COS on the biological characteristics of R. padi. The results indicated that COS possessed acute toxicity against R. padi after 48 h of exposure (LC50: 1227.35 mg/L). The sublethal concentration of COS (LC15: 260 mg/L) induced a decrease in adult longevity, adult prereproductive period and fecundity in the first filial generation (F1). Moreover, in F1 progeny, nymphal (1st–3rd), preadult and total prereproductive period significantly enhanced due to sublethal dose. Moreover, finite rate of increase (λ), the intrinsic rate of increase (r) and net reproductive rate (R0) of F1 progeny were significantly decreased, whereas a sublethal COS concentration exposure significantly increased the mean generation time (T) of F1 progeny. Overall, the study shows that sublethal concentration of COS can significantly suppress population growth of R. padi F1 generation, showing the potential of COS as a biorational option to manage aphids. [ABSTRACT FROM AUTHOR]

The divergent synthesis of dihydropyrimidouracil and pyrimidouracil derivatives from N‐uracil amidines and tertiaryamines by an oxidative C(sp3)−N cleavage cascade cyclization reaction is first described. This transformation enables the formation of new C(sp3)−N and C(sp2)−N bonds via the selection of different oxidation conditions. The features of this method include tunable product selectivity, excellent chemoselectivity, readily available starting materials, broad substrate scope, good tolerance of functional groups, and moderate to high yields. [ABSTRACT FROM AUTHOR]

Background: Circulating tumor cells (CTCs), an indispensable liquid biopsy classifier, can provide extra information for the diagnosis and prognosis of hepatocellular carcinoma (HCC). Methods: We systematically analyzed the peripheral blood of preoperative HCC patients (n = 270) for CTC number, Ki67 index reflecting the proliferative CTC percentage (PCP), and CTC clusters correlated with the characteristics of malignant HCC tumors. Results: Driver gene mutations were found with high levels of consistency between CTCs and primary tumors (n = 73). CTC number and PCP were associated with tumor size, microvascular invasion (MVI), presence or absence of multiple tumors, and thrombosis significantly. CTC number and PCP robustly separated patients with and without relapse, with a sensitivity of 88.89%/81.48% and a specificity of 72.73%/94.81% in the training set (n = 104) and corresponding values of 80.00%/86.67% and 78.38%/89.19% in the validation set (n = 52), showing a better performance than that associated with the alpha‐fetoprotein (AFP) level. CTC number, PCP, CTC clusters, and MVI were independent significant risk factors for HCC recurrence (P = 0.0375, P < 0.0001, P = 0.0017, and P = 0.0157). A nomogram model based on these risk factors showed a considerable prediction ability for HCC recurrence (area under the curve = 0.947). PCP (training: log‐rank P < 0.0001; hazard ratio [HR] 30.13, 95% confidence interval [CI] = 11.12–81.62; validation: log‐rank P < 0.0001; HR 25.73, 95% CI = 5.28–106.60) and CTC clusters (training: log‐rank P < 0.0001; HR 17.34, 95% CI = 7.46–40.30; validation: log‐rank P < 0.0001; HR 9.92, 95% CI = 2.55–38.58) were more significantly correlated with worse recurrence‐free survival than CTC number (training: log‐rank P < 0.0001; HR 14.93, 95% CI = 4.48–49.78; validation: log‐rank P = 0.0007; HR 9.03, 95% CI = 2.53–32.24). Conclusion: PCP and CTC clusters may predict HCC recurrence and improve the performance of the serum biomarker AFP. [ABSTRACT FROM AUTHOR]

Most research about compartmental models of infection disease often consider the transmission rate as a constant, which is not ideal for the dynamic surveillance of infectious diseases. This study fully utilized continuously updated real-time epidemiological data and proposed a SEAIUHR model incorporating asymptomatic and symptomatic infectiousness, reported and unreported cases, inpatient and non-inpatient cases, and vaccine inoculation. This study proposed a novel approach based on our model to calculate the time-varying transmission rate with an under-report rate, vaccination efficiency, and relaxation of social distancing behavior. The proposed method was evaluated based on epidemiological data from the United States. The results suggest that using this approach to combine epidemiological data can provide a clearer understanding of the spread rule of epidemic, offering data support for subsequent related research. [ABSTRACT FROM AUTHOR]

Using benzylamines as the C4 source of 1,4‐dihydropyridines (1,4‐DHPs), a Cu‐catalyzed oxidative [1+2+1+2] cascade cyclization for the synthesis of 1,4‐DHPs was firstly developed. A broad range of easily available N,N‐dimethyl enaminones and benzylamines are employed smoothly to provide a diverse range of 1,4‐DHPs with high efficiency. This method is performed by a one‐pot cascade C(sp3)−H bond functionalization/C(sp3)−N cleavage/cyclization strategy to form simultaneously two C(sp3)−C(sp2) bonds, two C(sp2)−N bonds, and a 1,4‐DHP ring. [ABSTRACT FROM AUTHOR]

An oxidative [3+2+1] cyclization of enaminones and N‐alkenyl‐2‐pyrrolidinone is described for the synthesis of 4‐alkylated 1,4‐dihydropyridines (1,4‐DHPs). By using terminal olefin as the C4 source of the 1,4‐DHP skeleton, this synthetic strategy provides a series of 1,4‐DHPs through a 1,1‐difunctionalization/cyclization process. In this protocol, two C(sp3)−C(sp2) bonds and a C(sp2)−N bond are simultaneously formed, the hydrogen source on the newly formed methyl group of the 1,4‐DHP skeleton is confirmed and a possible mechanism is proposed. [ABSTRACT FROM AUTHOR]

Chronic kidney disease (CKD) is a disease with decreased, irreversible renal function. Pruritus is the most common skin symptom in patients with CKD, especially in end‐stage renal disease. The underlying molecular and neural mechanism of CKD‐associated pruritus (CKD‐aP) remains obscure. Our data show that the level of allantoin increases in the serum of CKD‐aP and CKD model mice. Allantoin could induce scratching behavior in mice and active DRG neurons. The calcium influx and action potential reduced significantly in DRG neurons of MrgprD KO or TRPV1 KO mice. U73122, an antagonist of phospholipase C, could also block calcium influx in DRG neurons induced by allantoin. Thus, our results concluded that allantoin plays an important role in CKD‐aP, mediated by MrgprD and TrpV1, in CKD patients. [ABSTRACT FROM AUTHOR]

Background: Symbiotic bacteria affect physiology and ecology of insect hosts. The Sitobion miscanthi L type symbiont (SMLS) is a recently discovered and widely distributed secondary symbiont in the grain aphid Sitobion miscanthi Takahashi in China. Results: In this study, SMLS‐infected (SI) and SMLS‐uninfected (SU) aphid strains were obtained from field population. The artificially SMLS‐re‐infected (SRI) strain was established by injecting SU aphids with the SI strain hemolymph containing SMLS. The SRI and SU strains had identical genetic backgrounds and similar microbial community structures. Compared with the SU strain, adult longevity, survival rate, and fecundity were significantly greater in the SRI strain (biological fitness of 1.48). Moreover, the SRI strain spent more time ingesting phloem than the SU strain. A comparative transcriptome analysis indicated that reproduction‐ and longevity‐related genes were more highly expressed in the SRI strain than in the SU strain. Conclusion: The findings indicated that the infection with SMLS enhanced the Sitobion miscanthi fitness and feeding behavior. The beneficial effect of the SMLS on hosts could explain why it frequently infects the field populations in the grain aphid Sitobion miscanthi Takahashi in China. © 2022 Society of Chemical Industry. [ABSTRACT FROM AUTHOR]

Introduction: To observe the characteristics of suction loss in small-incision lenticule extraction (SMILE) and analyze the factors affecting the stability of the suction ring, classify and grade suction loss, and determine the principles for its prevention and control. Methods: This study enrolled patients who underwent SMILE between June 2014 and June 2017. The relationship between the stability of the suction ring and suction loss was ascertained using surgical records and video recordings. The suction loss was classified and graded according to its characteristics and relationship with eye or head movement. The effect of target intervention on suction loss was observed. Results: Suction loss can be divided into sudden and progressive types. According to the severity, the latter was divided into three grades (grade 1A or 1B, 2 and 3). Of the 1200 eyes (608 patients), two (0.17%) had sudden suction loss, and 132 (11%) had progressive suction loss. The superior part, inferior part, and other parts accounted for 63.4%, 19.3%, and 17.3% of progressive suction loss, respectively. The proportion of grades 1A, 1B, 2, and 3 suction loss was 53%, 34%, 12%, and 1%, respectively. The location of the threatened suction loss was opposite to the direction of the patient's head movement. After the intraoperative intervention, grades 1 and 2 did not develop into "actual" suction loss. Conclusions: Progressive suction loss was the most frequently observed suction loss during SMILE procedure. Grading suction loss can elucidate its underlying mechanism, which can guide targeted intervention measures to effectively control and reduce suction loss-induced damage, and further improve the safety and efficacy of SMILE. [ABSTRACT FROM AUTHOR]

Background: Emerging evidence indicates that myristoylated alanine‐rich C kinase substrate like 1 (MARCKSL1) is involved in the progression of esophageal squamous cell carcinoma (ESCC). However, the underpinning mechanism is unclear. Here, we investigated the mechanisms involving MARCKSL1 in ESCC progression. Methods: CCK8, Transwell and wound‐healing assays were employed to test the effect of MARCKSL1 on proliferation, invasion and migration in vitro. Next, transcriptome profiling was conducted through RNA sequencing to reveal the underlying mechanism of MARCKSL1 in ESCC progression, which was subsequently verified by western blot and qPCR analysis. Moreover, immunofluorescence and gelatin degradation assays were performed to reveal the ability of MARCKSL1 to mediate invadopodia formation and extracellular matrix (ECM) degradation. Finally, the correlation between MARCKSL1 and the clinicopathological features of ESCC patients was assessed based on TCGA database analysis and immunohistochemistry staining of tissue microarrays. Results: Knockdown of MARCKSL1 markedly attenuated the cell motility capacity of ESCC cells in vitro, while MARCKSL1 overexpression had the opposite effect. Transcriptomic analysis showed that MARCKSL1 mediated the mobility and migration of ESCC cells. In addition, overexpression of MARCKSL1 increased the colocalization of F‐actin and cortactin at the frontier edge of migrating cells and ECM degradation. Furthermore, in ESCC patients, the mRNA level of MARCKSL1 in esophageal carcinomas (n = 182) was found to be notably higher than that in adjacent esophageal epithelia (n = 286) and the expression levels of MARCKSL1 in the tumor tissues (n = 811) were significantly increased compared to those in noncancerous esophageal tissues (n = 442) with a large sample size. Higher expression of MARCKSL1 was positively correlated with lymph node metastasis and associated with worse survival rates of patients with ESCC. Conclusion: MARCKSL1 promotes cell migration and invasion by interacting with F‐actin and cortactin to regulate invadopodia formation and ECM degeneration. High MARCKSL1 expression is positively correlated with poor prognosis in ESCC patients with lymph node metastasis. [ABSTRACT FROM AUTHOR]

Beta-cypermethrin is one of the most widely used pyrethroid insecticides. However, its continuous and extensive use developed pests' resistance to beta-cypermethrin. To identify candidate genes for potential resistance phenotypes and facilitate more targeted studies, we screened out a wide range of resistance-related genes by comparing multiple transcripts before and after the induction of multiple agents. In this study, transcriptomes were compared to elucidate the mechanisms and genetic basis of potential resistance between Rhopalosiphum padi (R. padi) sensitive (SS) and resistant (Beta-R) strains to beta-cypermethrin (resistance ratio: 4588.48). These two strains of aphids were treated with a spray solution of lethal beta-cypermethrin concentration (i.e., LC50). To obtain diverse transcripts, we obtained 17,985,440–25,478,353 clean data from different transcript groups, of which 17,183 genes were annotated. Subsequently, these transcripts were divided into multiple groups for comparison purposes to obtain more comprehensive genes related to resistance. There were 178 to 2856 differentially expressed genes (DEGs) in these transcript groups. The DEGs, including the enriched ones, were classified according to the GO and KEGG Pathway databases. Besides, some drug-resistant DEGs were related to cuticle proteins and detoxification metabolic processes. Among them, 17 genes related to cuticle protein were upregulated and 20 were downregulated, 11 genes related to P450 were upregulated and 25 were downregulated, 7 genes related to UGT were upregulated and 15 were downregulated, 2 genes related to ABC transporter were upregulated and 4 were downregulated, 2 genes related to trypsin were upregulated and 1 were downregulated. Finally, qRT-PCR by DEGs confirmed the observed trend in the RNA sequencing expression profile, and most of the results were consistent between qRT-PCR and RNA sequencing (RNA-seq). The results of this study are highly significant in understanding the resistance phenomenon in R. padi and other similar wheat aphids, establishing the valuable basis for further research in the complex mechanism of R. padi resistance to beta-cypermethrin. [ABSTRACT FROM AUTHOR]

In order to give epoxy resin good flame retardance, a novel bio‐based flame retardant based on 2‐aminopyrimidine (referred to as VAD) was synthesized from renewable vanillin as one of the starting materials. Its structure was confirmed by NMR and mass spectra. The epoxy resins containing VAD were prepared by utilizing 4,4‐diaminodiphenylmethane (DDM) as a co‐curing agent, and their flame‐retardant, mechanical and thermal properties and corresponding mechanisms were studied. VAD accelerated the cross‐linking reaction of DDM and E51 (diglycidyl ether of bisphenol A). 12.5 wt% VAD made the epoxy resin achieve UL‐94 V‐0 rating and its limited oxygen index (LOI) value increase from 22.4% to 32.3%. The cone calorimetric testing results revealed the decline in the values of total heat release (THR) and peak of heat release rate (pk‐HRR) and the obvious enhancement of residue yield. A certain amount of VAD enhanced the flame inhibition, charring and barrier effects, resulting in good flame retardance of the epoxy resin. Furthermore, the tensile strength, flexural strength and flexural modulus of the epoxy resin with 12.5 wt% loading of VAD were 6.5%, 14.9%, 15.2% higher than those of EP, indicating the strengthening effect of VAD. This work guarantees VAD to be a promising flame retardant for enhancing the fire retardancy of epoxy resin without compromising its mechanical properties. [ABSTRACT FROM AUTHOR]

Simple Summary: Pest control mainly relies on the use of chemical insecticides, whereas insecticide resistance is problematic for the effective management of insect pests. Sulfoxaflor is a new sulfoximine insecticide. The wheat aphid Sitobion miscanthi is one of the most important pests adversely affecting wheat cultivation. We obtained an S. miscanthi field population highly resistant to sulfoxaflor, despite this insecticide not having been widely and continuously used for control of wheat aphids in China. The understanding of the cross-resistance or multi-resistance spectrum and fitness cost caused by insecticide resistance is important for selecting suitable insecticides to integratively manage insecticide resistance. Our findings suggest that the S. miscanthi population that is highly resistant to sulfoxaflor had moderate resistance to two pyrethroid insecticides, which was accompanied by severely adverse biological fitness. The study provides valuable information regarding the rational use of pesticides and may be relevant for exploring new mechanisms of insecticide resistance. Sulfoxaflor belongs to a new class of insecticides that is effective against many sap-feeding pests. In this study on Sitobion miscanthi (Takahashi) (i.e., the predominant wheat pest), a highly sulfoxaflor-resistant (SulR) population was obtained from a field. Its resistance to the other seven insecticides and its biological fitness were analyzed using a leaf-dip method and a two-sex life table approach, respectively. Compared with the relatively susceptible (SS) population, the SulR population was highly resistant to sulfoxaflor, with a relative insecticide resistance ratio (RR) of 199.8 and was moderately resistant to beta-cypermethrin (RR = 14.5) and bifenthrin (RR = 42.1) but exhibited low resistance to chlorpyrifos (RR = 5.7). Additionally, the SulR population had a relative fitness of 0.73, with a significantly prolonged developmental period as well as a lower survival rate and poorer reproductive performance than the SS population. In conclusion, our results suggest that S. miscanthi populations that are highly resistant to sulfoxaflor exist in the field. The possibility that insects may develop multi-resistance between sulfoxaflor and pyrethroids is a concern. Furthermore, the high sulfoxaflor resistance of S. miscanthi was accompanied by a considerable fitness cost. The study data may be useful for improving the rational use of insecticides and for exploring novel insecticide resistance mechanisms. [ABSTRACT FROM AUTHOR]

Interests in using nonlinear acoustic methods for incipient damage detection continue to grow tremendously as the understanding of nonlinearities in micro-cracked and cracked solids. It is widely known that nonlinear effects caused by cracks are stronger than crack-induced linear phenomena. However, understanding physical mechanisms related to various nonlinearities still needs to be clarified, which is vital to implementing nonlinear ultrasonics for engineering applications. To this end, an element-based homogenized method is proposed, which can consider the randomness of distributed microcracks in the framework of continuum mechanics. A quadrilateral element with one horizontal crack is constructed as a reference model. The reference model is homogenized to be orthotropic but with different moduli in tension and compression to account for stiffness asymmetric due to crack opening and closing. Unlike the existing homogenized method, which usually simplifies the representative volume element as a homogeneous part and requires only one constitutive model for the equivalent material of the whole structure, we assign the constitutive relationship of the same reference model to all the finite elements but with random principal material directions to take randomly oriented microcracks into consideration. The proposed method is compared with the finite element contact model that defines contact properties on crack surfaces. It is validated that the proposed method agrees well with the contact model for simulating the nonlinearities in wave interaction with the microcracks but at a much lower computational cost. [ABSTRACT FROM AUTHOR]

A silver‐catalyzed protocol for the synthesis of 3‐(1H‐isochromen)‐chromones is described. The method involves an initial 6‐endo‐dig cyclization of o‐alkynylbenzaldehydes and domino C−H alkylation and chromone annulation of the o‐hydroxyarylenaminones, which enables the installation of 1H‐isochromen and chromone in a single structure. This synthetic strategy is advantageous for the excellent regioselectivity, step economy, concise one‐pot methodology, gram‐scale synthesis, as well as high bond‐forming efficiency. [ABSTRACT FROM AUTHOR]

Automatic seizure detection algorithms are necessary for patients with refractory epilepsy. Many excellent algorithms have achieved good results in seizure detection. Still, most of them are based on discontinuous intracranial electroencephalogram (iEEG) and ignore the impact of different channels on detection. This study aimed to evaluate the proposed algorithm using continuous, long-term iEEG to show its applicability in clinical routine. In this study, we introduced the ability of the transformer network to calculate the attention between the channels of input signals into seizure detection. We proposed an end-to-end model that included convolution and transformer layers. The model did not need feature engineering or format transformation of the original multi-channel time series. Through evaluation on two datasets, we demonstrated experimentally that the transformer layer could improve the performance of the seizure detection algorithm. For the SWEC-ETHZ iEEG dataset, we achieved 97.5% event-based sensitivity, 0.06/h FDR, and 13.7 s latency. For the TJU-HH iEEG dataset, we achieved 98.1% event-based sensitivity, 0.22/h FDR, and 9.9 s latency. In addition, statistics showed that the model allocated more attention to the channels close to the seizure onset zone within 20 s after the seizure onset, which improved the explainability of the model. This paper provides a new method to improve the performance and explainability of automatic seizure detection. [ABSTRACT FROM AUTHOR]

Forest ecosystem detection and assessment usually requires accurate spatial distribution information of forest tree species. Remote sensing technology has been confirmed as the most important method for tree species acquisition, and space-borne hyperspectral imagery, with the advantages of high spectral resolution, provides a better possibility for tree species classification. However, the present in-orbit hyperspectral imager has proved to be too low in spatial resolution to meet the accuracy needs of tree species classification. In this study, we firstly explored and evaluated the effectiveness of the Gram-Schmidt (GS) Harmonic analysis fusion (HAF) method for image fusion of GaoFen-5 (GF-5) and Sentinel-2A. Then, the Integrated Forest Z-Score (IFZ) was used to extract forest information from the fused image. Next, the spectral and textural features of the fused image, and topographic features extracted from DEM were selected according to random forest importance ranking (Mean Decreasing Gini (MDG) and Mean Decreasing Accuracy (MDA)), and imported into the random forest classifier to complete tree species classification. The results showed that: comparing some evaluation factors such as information entropy, average gradient and standard deviation of the fused images, the GS fusion image was proven to have a higher degree of spatial integration and spectral fidelity. The random forest importance ranking showed that WBI, Aspect, NDNI, ARI2, FRI were more important for tree species classification. Both the classification accuracy and kappa coefficients of the fused images were significantly greatly improved when compared to those of original GF-5 images. The overall classification accuracy ranged from 61.17% to 86.93% for different feature combination scenarios, and accuracy of the selected method based on MDA achieved higher results (OA = 86.93%, Kappa = 0.85). This study demonstrated the feasibility of fusion of GF-5 and Sentinel-2A images for tree species classification, which further provides good reference for application of in-orbit hyperspectral images. [ABSTRACT FROM AUTHOR]

Multi-modal biomedical imaging has played an essential role in tumor diagnosis. However, constructing a multi-modal imaging contrast agent with high affinity to a tumor is challenging. Herein, we studied the design and application of a PET/MRI dual-modal imaging agent based on superparamagnetic iron oxide nanoparticles (SPION). αvβ3-targeting RGD peptide and 64Cu were conjugated onto SPION. Small animal PET and MR imaging in glioblastoma tumor-bearing mice revealed that this dual-modal imaging contrast agent could potentially be utilized for PET/MRI dual-modal imaging for the tumor diagnosis. [ABSTRACT FROM AUTHOR]

Both tobacco-specific carcinogen 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK) and nicotine can be metabolized by cytochrome P450 2A13 (CYP2A13). Previous studies have shown that nicotine has a potential inhibitory effect on the toxicity of NNK. However, due to the lack of CYP2A13 activity in conventional lung cell lines, there had been no systematic in vitro investigation for the key target organ, the lung. Here, BEAS-2B cells stably expressing CYP2A13 (B-2A13 cells) were constructed to investigate the effects of nicotine on the cytotoxicity and genotoxicity of NNK. The results showed more sensitivity for NNK-induced cytotoxicity in B-2A13 cells than in BEAS-2B and B-vector cells. NNK significantly induced DNA damage, cell cycle arrest, and chromosomal damage in B-2A13 cells, but had no significant effect on BEAS-2B cells and the vector control cells. The combination of different concentration gradient of nicotine without cytotoxic effects and a single concentration of NNK reduced or even counteracted the cytotoxicity and multi-dimensional genotoxicity in a dose-dependent manner. In conclusion, CYP2A13 caused the cytotoxicity and genotoxicity of NNK in BEAS-2B cells, and the addition of nicotine could inhibit the toxicity of NNK. [ABSTRACT FROM AUTHOR]

Background: Detection of mild cognitive impairment (MCI) is essential to screen high risk of Alzheimer's disease (AD). However, subtle changes during MCI make it challenging to classify in machine learning. The previous pathological analysis pointed out that the hippocampus is the critical hub for the white matter (WM) network of MCI. Damage to the white matter pathways around the hippocampus is the main cause of memory decline in MCI. Therefore, it is vital to biologically extract features from the WM network driven by hippocampus-related regions to improve classification performance. Methods: Our study proposes a method for feature extraction of the whole-brain WM network. First, 42 MCI and 54 normal control (NC) subjects were recruited using diffusion tensor imaging (DTI), resting-state functional magnetic resonance imaging (rs-fMRI), and T1-weighted (T1w) imaging. Second, mean diffusivity (MD) and fractional anisotropy (FA) were calculated from DTI, and the whole-brain WM networks were obtained. Third, regions of interest (ROIs) with significant functional connectivity to the hippocampus were selected for feature extraction, and the hippocampus (HIP)-related WM networks were obtained. Furthermore, the rank sum test with Bonferroni correction was used to retain significantly different connectivity between MCI and NC, and significant HIP-related WM networks were obtained. Finally, the classification performances of these three WM networks were compared to select the optimal feature and classifier. Results: (1) For the features, the whole-brain WM network, HIP-related WM network, and significant HIP-related WM network are significantly improved in turn. Also, the accuracy of MD networks as features is better than FA. (2) For the classification algorithm, the support vector machine (SVM) classifier with radial basis function, taking the significant HIP-related WM network in MD as a feature, has the optimal classification performance (accuracy = 89.4%, AUC = 0.954). (3) For the pathologic mechanism, the hippocampus and thalamus are crucial hubs of the WM network for MCI. Conclusion: Feature extraction from the WM network driven by hippocampus-related regions provides an effective method for the early diagnosis of AD. [ABSTRACT FROM AUTHOR]

Currently, imaging, fecal immunochemical tests (FITs) and serum carcinoembryonic antigen (CEA) tests are not adequate for the early detection and evaluation of metastasis and recurrence in colorectal cancer (CRC). To comprehensively identify and validate more accurate noninvasive biomarkers in urine, we implement a staged discovery-verification-validation pipeline in 657 urine and 993 tissue samples from healthy controls and CRC patients with a distinct metastatic risk. The generated diagnostic signature combined with the FIT test reveals a significantly increased sensitivity (+21.2% in the training set, +43.7% in the validation set) compared to FIT alone. Moreover, the generated metastatic signature for risk stratification correctly predicts over 50% of CEA-negative metastatic patients. The tissue validation shows that elevated urinary protein biomarkers reflect their alterations in tissue. Here, we show promising urinary protein signatures and provide potential interventional targets to reliably detect CRC, although further multi-center external validation is needed to generalize the findings. More sensitive and specific non-invasive biomarkers are desired for early detection of cancer. Here, the authors show a protein signature in the urine that increases sensitivity for colorectal cancer detection when combined with fecal immunochemical tests and corrects diagnosis in some fecal immunochemical tests-negative patients. [ABSTRACT FROM AUTHOR]

The C(sp2)−H phosphorothiolation involving cyclization process through a transition‐metal‐free strategy is reported. It provides an attractive approach for the construction valuable S‐3‐chromon phosphorothioates from o‐hydroxyarylenaminones and P(O)SH compounds in the presence of 1.0 equiv. of iodine at 60 °C. This novel protocol shows readily available chemicals, broad substrate scope, and mild reaction conditions. [ABSTRACT FROM AUTHOR]

Spinal cord injury (SCI) results from various pathogenic factors that destroy the normal structure and function of the spinal cord, subsequently causing sensory, motor, and autonomic nerve dysfunction. SCI is one of the most common causes of disability and death globally. It leads to severe physical and mental injury to patients and causes a substantial economic burden on families and the society. The pathological changes and underlying mechanisms within SCI involve oxidative stress, apoptosis, inflammation, etc. As a traditional therapy, acupuncture has a positive effect promoting the recovery of SCI. Acupuncture-induced neuroprotection includes several mechanisms such as reducing oxidative stress, inhibiting the inflammatory response and neuronal apoptosis, alleviating glial scar formation, promoting neural stem cell differentiation, and improving microcirculation within the injured area. Therefore, the recent studies exploring the mechanism of acupuncture therapy in SCI will help provide a theoretical basis for applying acupuncture and seeking a better treatment target and acupuncture approach for SCI patients. [ABSTRACT FROM AUTHOR]

Exercise preconditioning has attracted extensive attention to induce endogenous neuroprotection and has become the hotspot in neurotherapy. The training exercise is given multiple times before cerebral ischemia, effectively inducing ischemic tolerance and alleviating secondary brain damage post-stroke. Compared with other preconditioning methods, the main advantages of exercise include easy clinical operation and being readily accepted by patients. However, the specific mechanism behind exercise preconditioning to ameliorate brain injury is complex. It involves multi-pathway and multi-target regulation, including regulation of inflammatory response, oxidative stress, apoptosis inhibition, and neurogenesis promotion. The current review summarizes the recent studies on the mechanism of neuroprotection induced by exercise, providing the theoretical basis of applying exercise therapy to prevent and treat ischemic stroke. In addition, we highlight the various limitations and future challenges of translational medicine from fundamental study to clinical application. [ABSTRACT FROM AUTHOR]

The phenotype of nitrogen permease regulator-like 2 (NPRL2) gene-related epilepsy clinically manifests as a range of epilepsy syndromes, including familial focal epilepsy with variable foci (FFEVF), sleep-related hypermotor epilepsy (SHE), temporal lobe epilepsy (TLE), frontal lobe epilepsy (FLE), and infantile spasms (IS). The association between phenotype and genotype of NPRL2 variants has not been widely explored. This study aimed to explore the phenotype and genotype spectrum of NPRL2 -related epilepsy. Here, we presented two clinical cases with NPRL2 -related epilepsy, and discussed the characteristics, diagnosis, and treatment processes in the context of existing literature. Two novel NPRL2 likely pathogenic variants were identified by next-generation sequencing, including one splicing mutation (c.933-1G>A), and one frameshift mutation (c.257delG). The results of literature review showed that there were a total of 20 patients with NPRL2 -related epilepsy whose mutations were mostly missense and hereditary. These findings indicate that the possibility of NPRL2 gene mutations in focal epilepsy should be considered for patients with family history, and that patients carrying different NPRL2 variants have different clinical manifestations. Our study expanded the genotype spectrum of NPRL2 and suggested that the type of NPRL2 variants might provide important information for the prognosis evaluation. [ABSTRACT FROM AUTHOR]

The electroencephalography (EEG) microstate has recently emerged as a new whole-brain mapping tool for studying the temporal dynamics of the human brain. Meanwhile, the neuromodulation effect of external stimulation on the human brain is of increasing interest to neuroscientists. Acupuncture, which originated in ancient China, is recognized as an external neuromodulation method with therapeutic effects. Effective acupuncture could elicit the deqi effect, which is a combination of multiple sensations. However, whether the EEG microstate could be used to reveal the neuromodulation effect of acupuncture with deqi remains largely unclear. In this study, multichannel EEG data were recorded from 16 healthy subjects during acupuncture manipulation, as well as during pre- and post-manipulation tactile controls and pre- and post-acupuncture rest controls. As the basic acupuncture unit for regulating the central nervous system, the Hegu acupoint was used in this study, and each subject's acupuncture deqi behavior scores were collected. To reveal the neuroimaging evidence of acupuncture with deqi , EEG microstate analysis was conducted to obtain the microstate maps and microstate parameters for different conditions. Furthermore, Pearson's correlation was analyzed to investigate the correlation relationship between microstate parameters and deqi behavioral scores. Results showed that: (1) compared with tactile controls, acupuncture manipulation caused significantly increased deqi behavioral scores. (2) Acupuncture manipulation significantly increased the duration, occurrence, and contribution parameters of microstate C, whereas it decreased those parameters of microstate D. (3) Microstate C's duration parameter showed a significantly positive correlation with acupuncture deqi behavior scores. (4) Acupuncture manipulation significantly increased the transition probabilities with microstate C as node, whereas it reduced the transition probabilities with microstate D as node. (5) Microstate B→C's transition probability also showed a significantly positive correlation with acupuncture deqi behavior scores. Taken together, the temporal dynamic feature of EEG microstate could be used as objective neuroimaging evidence to reveal the neuromodulation effect of acupuncture with deqi. [ABSTRACT FROM AUTHOR]

Aimed at monitoring the aerodynamic heating on the spacecraft leading edge structure, a temperature field reconstruction method for curved surface using a distributed sensor array is proposed in this paper. Limited by the sensor number and system weight, a sparse sensor array is usually used to measure the temperatures at the discrete positions. Considering the majority of heat energy transfers on the leading edge surface rather than the hollow inside or thermal insulation material, the temperature field on the curved surface of leading edge structure can be reconstructed through inverse distance weighting (IDW) method with improved accuracy by introducing arc-length distances rather than straight-line distances. Furthermore, the non-dominated sorting genetic algorithm II (NSGA-II) is employed to optimize the distribution of the sensor array. Taking a three-dimensional spacecraft leading edge structure as an example, a finite element model is used to validate the proposed method. The influences of search radius and random initial population inputs on the optimized results are investigated. The results show that the use of search radius plays an important role in optimizing the arrangement of sensor array. [ABSTRACT FROM AUTHOR]

Copper(II)‐mediated unprecedented intermolecular radical [3+2] annulation of N,N‐dimethyl enaminones has been developed. The protocol is promoted simply by copper(II) chloride to access 5‐acyl‐3‐furancarboxaldehydes with acceptable to good yields and broad substrate scope. This reaction allows the formation of multiple new bonds, including C(sp2)−O bond between two nucleophilic sites, C(sp2)−C(sp2) bond and C=O bond, through a radical cyclization process. Moreover, gram‐synthesis and application research show the potential application value of this transformation in industry. [ABSTRACT FROM AUTHOR]

Background: Vagus nerve stimulation (VNS) has been demonstrated to be safe and effective for patients with refractory epilepsy, but there are few reports on the use of VNS for postencephalitic epilepsy (PEE). This retrospective study aimed to evaluate the efficacy of VNS for refractory PEE. Methods: We retrospectively studied 20 patients with refractory PEE who underwent VNS between August 2017 and October 2019 in Chinese PLA General Hospital and Beijing Children's Hospital. VNS efficacy was evaluated based on seizure reduction, effective rate (percentage of cases with seizure reduction ≥ 50%), McHugh classification, modified Early Childhood Epilepsy Severity Scale (E-Chess) score, and Grand Total EEG (GTE) score. The follow-up time points were 3, 6, and 12 months after VNS. Pre- and postoperative data were compared and analyzed. Results: The median [interquartile range (IQR)] seizure reduction rates at 3, 6, and 12 months after VNS were 23.72% (0, 55%), 46.61% (0, 79.04%), and 67.99% (0, 93.78%), respectively. The effective rates were 30% at 3 months, 45% at 6 months, and 70% at 12 months. E-chess scores before the operation and at 3, 6, and 12 months after the operation were 10 (10, 10.75), 9 (9, 10), 9 (9, 9.75), and 9 (8.25, 9) (P < 0.05), respectively. GTE scores before surgery and at 12 months after the operation were 11 (9, 13) and 9 (7, 11) (P < 0.05), respectively. The mean intensity of VNS current was 1.76 ± 0.39 (range: 1.0–2.5) mA. No intraoperative complications or severe post-operative adverse effects were reported. Conclusions: Our study shows that VNS can reduce the frequency and severity of seizure in patients with refractory PEE. VNS has a good application prospect in patients with refractory PEE. [ABSTRACT FROM AUTHOR]

SUMMARY: Suberin is a complex hydrophobic polymer of aliphatic and phenolic compounds which controls the movement of gases, water, and solutes and protects plants from environmental stresses and pathogenic infection. The synthesis and regulatory pathways of suberin remain unknown in Brachypodium distachyon. Here we describe the identification of a B. distachyon gene, BdFAR4, encoding a fatty acyl‐coenzyme A reductase (FAR) by a reverse genetic approach, and investigate the molecular relevance of BdFAR4 in the root suberin synthesis of B. distachyon. BdFAR4 is specifically expressed throughout root development. Heterologous expression of BdFAR4 in yeast (Saccharomyces cerevisiae) afforded the production of C20:0 and C22:0 fatty alcohols. The loss‐of‐function knockout of BdFAR4 by CRISPR/Cas9‐mediated gene editing significantly reduced the content of C20:0 and C22:0 fatty alcohols associated with root suberin. In contrast, overexpression of BdFAR4 in B. distachyon and tomato (Solanum lycopersicum) resulted in the accumulation of root suberin‐associated C20:0 and C22:0 fatty alcohols, suggesting that BdFAR4 preferentially accepts C20:0 and C22:0 fatty acyl‐CoAs as substrates. The BdFAR4 protein was localized to the endoplasmic reticulum in Arabidopsis thaliana protoplasts and Nicotiana benthamiana leaf epidermal cells. BdFAR4 transcript levels can be increased by abiotic stresses and abscisic acid treatment. Furthermore, yeast one‐hybrid, dual‐luciferase activity, and electrophoretic mobility shift assays indicated that the R2R3‐MYB transcription factor BdMYB41 directly binds to the promoter of BdFAR4. Taken together, these results imply that BdFAR4 is essential for the production of root suberin‐associated fatty alcohols, especially under stress conditions, and that its activity is transcriptionally regulated by the BdMYB41 transcription factor. [ABSTRACT FROM AUTHOR]