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Abstract Mica is a promising substrate for flexible photonic applications because it can be fabricated using wafer‐scale multiple exfoliations. However, the large lattice mismatch between mica and III‐nitrides hinders their application in III‐nitride semiconductor devices. In this study, two types of light‐emitting diode (LED) epilayers, blue and green, are epitaxially fabricated on 2‐inch exfoliated mica substrates using sputtered AlN as a buffer layer to address the lattice mismatch. The LED epilayers on mica substrate exhibit excellent single‐crystalline quality with a low threading dislocation density of 2.07 × 109 cm−2 in the GaN region and smooth surface morphology with a root mean square (RMS) roughness of 0.58 nm in a 5 × 5 µm2 scanned area, demonstrating that mica is an excellent platform for III‐nitride semiconductors. Moreover, the structures are reproduced stably on multiple exfoliated mica at the wafer scale, which verified the reusability and reproducibility of III‐nitride/mica in terms of crystallinity, surface morphology, and transparency. Strong electroluminescence of the LED epilayers confirmed the potential of mica in electrically driven flexible opto‐electronics. Therefore, this results demonstrated the potential of mica substrates in III‐nitride semiconductors and provide a novel pathway for revolutionizing the fabrication of III‐nitride‐based flexible devices.

Abstract This paper proposes a virtual inertia control strategy for wind farms based on auto disturbance rejection controller with artificial bee colony (ABC) algorithm. First, based on the system frequency dynamic response equation, an active disturbance rejection controller is designed according to the non‐linear feedback control law and the extended state observer to improve the anti‐interference capability of the virtual inertia control system. Second, in order to solve the problem of difficulty in tuning the parameters of the active disturbance rejection control (ADRC), an ABC algorithm based on nectar collection behaviour was proposed to iteratively optimize the parameters of ADRC. Finally, the proposed control method is effectively verified based on Matlab/Simulink. The simulation results show that compared with traditional algorithms, the proposed ABC‐ADRC can effectively control the rotor speed to adjust the frequency of the power grid system, achieve power sharing and adaptive noise elimination, reduce the complexity of parameter settings, not only improve anti‐interference ability, but also enhance the robustness of the system.

Abstract Recurrent heat stress and pathogen invasion seriously threaten crop production, and abiotic stress often antagonizes biotic stress response against pathogens. However, the molecular mechanisms of trade-offs between thermotolerance and defense remain obscure. Here, we identify a rice thermo-sensitive mutant that displays a defect in floret development under high temperature with a mutation in SUPPRESSOR OF GENE SILENCING 3a (OsSGS3a). OsSGS3a interacts with its homolog OsSGS3b and modulates the biogenesis of trans-acting small interfering RNA (tasiRNA) targeting AUXIN RESPONSE FACTORS (ARFs). We find that OsSGS3a/b positively, while OsARF3a/b and OsARF3la/lb negatively modulate thermotolerance. Moreover, OsSGS3a negatively, while OsARF3a/b and OsARF3la/lb positively regulate disease resistance to the bacterial pathogen Xanthomonas oryzae pv. oryzae (Xoo) and the fungal pathogen Magnaporthe oryzae (M. oryzae). Taken together, our study uncovers a previously unknown trade-off mechanism that regulates distinct immunity and thermotolerance through the OsSGS3-tasiRNA-OsARF3 module, highlighting the regulation of abiotic-biotic stress response trade-off in plants.

Abstract Since the discovery, lipid droplets (LDs) have been recognized to be sites of cellular energy reserves, providing energy when necessary to sustain cellular life activities. Many studies have reported large numbers of LDs in eggs and early embryos from insects to mammals. The questions of how LDs are formed, what role they play, and what their significance is for embryonic development have been attracting the attention of researchers. Studies in recent years have revealed that in addition to providing energy for embryonic development, LDs in eggs and embryos also function to resist lipotoxicity, resist oxidative stress, inhibit bacterial infection, and provide lipid and membrane components for embryonic development. Removal of LDs from fertilized eggs or early embryos artificially leads to embryonic developmental arrest and defects. This paper reviews recent studies to explain the role and effect mechanisms of LDs in the embryonic development of several species and the genes involved in the regulation. The review contributes to understanding the embryonic development mechanism and provides new insight for the diagnosis and treatment of diseases related to embryonic developmental abnormalities.

Based on the observed biological activity of 1,2,4-triazin-5-one derivatives and their cyclic analogues, a novel series of 7H-thiazolo[3,2-b]-1,2,4-triazin-7-one derivatives that contain ester moiety compounds 3a-3g, carboxylic acid moiety compounds 4a-4g and piperazine amide moiety compounds 5a-5k at position-3 of the thiazolotriazinone scaffold were synthesized. The intermolecular cyclization occurred regioselectively at N2-position of 1,2,4-triazine ring was characterized by X-ray single-crystal diffraction analysis. The in vitro biological activities of the target compounds were assayed against some bacterial strains. Compared with ciprofloxacin, compounds 3g and 4g exhibited more excellent antibacterial activity, especially the activity against Staphylococcus aureus and Escherichia coli, showing that the fluorine at the para position of the benzyl group would be the best choice. In addition, compounds 4e-4g with carboxylic acid moiety can enhance the antibacterial activity. Compounds 5g-5k containing bulky 1-(substituted phenyl)piperazine moiety were found with slightly less biological activity. Similar to ciprofloxacin, the docking result of target compounds with DNA topoisomerase II indicates the carboxyl group of the target compounds with carboxylic acid moiety has a crucial salt bridge interaction with Mg2+ in the protein.

The consumption of edible vegetable oil is an important source of essential fatty acids and vitamin E for the human body. Guiding residents to consume scientifically and reasonably control the intake of edible oils is an important part of promoting the construction of a healthy China. Currently, Chinese residents have an insufficient understanding of the scientific consumption of edible oils, leading to an intake exceeding the dietary recommendations, resulting in excessive fat intake and increasing the risk of chronic diseases such as obesity and cardiovascular diseases. Based on the Theory of Planned Behavior (TPB) and using Structural Equation Modeling (SEM), this study analyzed the cognitive preferences and willingness to pay a premium for edible vegetable oils among urban consumers in China. The survey included 1098 Chinese urban consumers of vegetable oils. The research found that attitudes, health value, monetary value, and environmental endowment of urban residents are the main predicting factors of the intention to purchase high-quality vegetable oils. This study confirms the applicability of the Theory of Planned Behavior in the consumption of high-quality vegetable oils and provides theoretical contributions and insights for Chinese enterprises and policymakers in formulating marketing strategies for vegetable oils.

Highlights Biochar-supported nZVI for persulfate activation was applied in an in-situ pilot-scale remediation, which effectively removed pollutants by 99% with limited ecological risks.

Abstract In patients with acute ST-elevation myocardial infarction (STEMI), it is essential to restore myocardial perfusion as soon as possible. However, a considerable proportion of patients have no-reflow. No-reflow increases the risk of major adverse cardiac events and even death. The role of blood eosinophil count in predicting no-reflow in STEMI patients has not been determined, particularly after primary percutaneous coronary intervention (pPCI). The present study aimed to evaluate the predictive value of eosinophil counts for no-reflow in patients with STEMI who underwent pPCI. A total of 674 STEMI patients who underwent pPCI were enrolled. The subjects were divided into two groups according to eosinophil counts for primary analysis and with or without T2DM for secondary analysis. Logistic regression analysis was used to determine whether eosinophil count was an independent predictor of no-reflow in the entire cohort, and subgroup and receiver operating characteristic (ROC) curves were explored to evaluate its predictive value. DeLong’s test was used to compare the area under curves of the three ROC curves. The low eosinophil count was an independent predictor for no-reflow in whole cohort (adjusted OR: 2.012, 95% CI 1.242–3.259, p = 0.004) and in patients with T2DM (adjusted OR: 4.312, 95% CI 1.878–9.900, p = 0.001). In patients without T2DM, hemoglobin, but not low eosinophil count, was an independent predictor of no-reflow. The results of the ROC curve analysis revealed that a low eosinophil count had moderate predictive efficiency for predicting no-reflow in patients with T2DM, and the power was superior to all populations and patients without T2DM. Our data suggest that decreased eosinophil count was an independent risk factor for no-reflow in patients with STEMI who underwent pPCI, especially in T2DM patients, which provides guidance for clinicians to identify patients at a higher risk of developing no-reflow and lowering their risk.

Waterlogging has been shown to have a significant inhibitory effect on plant growth. However, the response mechanisms of the soil environment of sugar beet seedlings under waterlogging conditions still need to be fully understood. This study aimed to investigate the effects of waterlogging treatments on the content of effective nutrients and the microbial communities in the rhizosphere and non-rhizosphere using high-throughput sequencing. We set up waterlogging and non-waterlogging treatments, sampled sugar beet seedlings after 10 days of waterlogging, determined the effective soil nutrients in the rhizosphere and non-rhizosphere of the plants, and analyzed the differences in microbial diversity at ten days of waterlogging. The results showed that waterlogging significantly affected available potassium (AK) content. The Ak content of waterlogged soil was significantly higher than that of non-waterlogged soil. Waterlogging caused no significant difference in available nitrogen (AN) content and pH. Moreover, the plant growth-promoting bacteria Pseudomonas was significantly enriched in sugar beet waterlogged rhizospheres compared with the non-waterlogged ones. Similarly, the harmful fungi Gibellulopsis and Alternaria were enriched in sugar beet non-waterlogged rhizosphere. The network analysis revealed that waterlogging built a less complex root-microbial network than non-waterlogging. These findings implied that sugar beets subjected to waterlogging stress were enriched with beneficial microorganisms in the rhizosphere, potentially alleviating the stress.

To improve the performance of GaN‐based green micro‐light emitting diodes (μ‐LEDs) array, a modular‐architected p‐type region, which consists of polarization‐induced graded AlGaN and Al0.2Ga0.8N/GaN superlattices (SLs), is proposed to enhance p‐type conductivity. The designed p‐type structure shows a hole concentration of 1.7 × 1018 cm−3 which leads to an excellent conductivity of 2.48 Ω−1 cm−1. As a result, the fabricated μ‐LEDs array with 16 × 16 pixels exhibits a differential resistance of 7 Ω and a light output power of 7.9 mW, which is about 4 times in magnitude lower and 2 times in magnitude higher than those of μ‐LEDs array equipped with the p‐type layer using graded AlGaN and p‐GaN, respectively. Furthermore, in a visible light communication test, it exhibits a data rate improvement of 35%, with a value of 1.03 Gbps. A new approach is provided to enhance the p‐type conductivity of III‐nitride devices, which is definitely promising to improve their performance and expand their applications.

In this study, wireless sensor networks and time base generators are used to solve the fixed-time containment control problem in multi-agent systems with fixed topologies. A new event-triggered control protocol is proposed, which combines a fully distributed method and a time base generator (TBG). The goal is to converge the states of all followers to the convex hull formed by the leader. The controller reduces communication and improves control efficiency by integrating a fully distributed control mechanism using wireless sensor networks. In addition, a time base generator (TBG) is added to ensure that the dwell time continues to be pre-specified and independent of initial conditions. Using matrix theory, the original system is transformed into an error system, and its stability is analyzed by the Lyapunov method. The necessary and sufficient conditions for solving the time consensus containment control problem in multi-agent systems are determined and Zeno behavior is avoided. The effectiveness of the proposed control algorithm is illustrated by numerical examples.

BackgroundWhile insulin-like growth factor 1 (IGF-1) exerts a cardioprotective effect in the setting of atherosclerosis, insulin-like growth factor binding protein 2 (IGFBP-2) is involved in metabolic syndrome. Although IGF-1 and IGFBP-2 are known to be predictors for mortality in patients with heart failure, their use in clinic as prognostic biomarkers for acute coronary syndrome (ACS) requires investigation. We evaluated the relationship between IGF-1 and IGFBP-2 levels at admission and the risk of major adverse cardiovascular events (MACEs) in patients with ACS.MethodsA total of 277 ACS patients and 42 healthy controls were included in this prospective cohort study. Plasma samples were obtained and analyzed at admission. Patients were followed for MACEs after hospitalization.ResultsAmong patients who suffered acute myocardial infarction, plasma levels of IGF-1 and IGFBP-2 were lower and higher, respectively, as compared to healthy controls (both p

Abstract Background The leaf is a determinate organ essential for photosynthesis, whose size and shape determine plant architecture and strongly affect agronomic traits. In soybean, the molecular mechanism of leaf development is not well understood. The flowering repressor gene E1, which encodes a legume-specific B3-like protein, is known to be the gene with the largest influence on soybean flowering and maturity. However, knowledge of its potential other functions remains poor. Results Here, we identified a novel function of E1 protein in leaf development. Unifoliolate leaves of E1-overexpression (E1-OE) lines were smaller and curlier than those of wild type DongNong 50 (DN50) and Williams 82 (W82). Transverse histological sections showed disorganized cells and significantly elevated palisade tissue number, spongy tissue number, and bulliform cell number in E1-OE lines. Our results indicate that E1 binds to the promoters of the leaf- development-related CINCINNATA (CIN)-like TEOSINTE BRANCHED1/CYCLOIDEA/PROLIFERATING CELL FACTOR (TCP) transcription factor genes to negatively regulate their expression. Conclusions Our findings identify E1 as an important new factor in soybean leaf development.

Continuous cropping can lead to increased soil-borne diseases of sugar beet (Beta vulgaris L.), resulting in a reduction in its yield quality. However, our understanding of the influence of continuous cropping on sugar beet-associated microbial community is limited and their interactions remain unclear. Here, we described and analyzed microbial diversity (N = 30) from three sugar beet belowground compartments (bulk soil, rhizosphere soil, and beetroot) using 16S rRNA and ITS sequencing. The continuous cropping showed lower bacterial alpha diversity in three belowground compartments and higher fungal alpha diversity in roots compared to the non-continuous cropping. There were significant differences in fungal community composition between the two groups. Compared with non-continuous cropping, continuous cropping increased the relative abundance of potentially pathogenic fungi such as Tausonia, Gilbellulopsis, and Fusarium, but decreased the relative abundance of Olpidium. The fungal flora in the three compartments displayed different keystone taxa. Fungi were more closely related to environmental factors than bacteria. Overall, changes in microbial diversity and composition under continuous cropping were more pronounced in the fungal communities, and the results of the study could guide development strategies to mitigate continuous crop adversity.

The COVID-19 pandemic has drawn the attention of educators to the blended learning model. This study developed a remote blended game-based learning activity that integrates digital game--based learning (DGBL) and blended learning (including online synchronous and asynchronous learning). This method emphasizes that in the online synchronous learning activity, students firstly use mini-educational digital games for group collaborative autonomous pre-learning and then take part in a problem-solving discussion activity guided by the teacher. Afterwards, students complete personal inquiry learning tasks in the asynchronous online activity and conduct asynchronous discussions. This study employed a quasi-experimental design. Participants were 73 senior high school students. The first group used the remote blended game-based learning that integrated DGBL into online synchronous learning. The second group used the face-to-face blended game-based learning approach that integrated DGBL into physical classroom learning. The third group used the remote blended video-based learning that integrated online synchronous video-based learning. The three groups conducted the same online asynchronous inquiry learning tasks. The results found that the remote blended game-based learning activity not only significantly promoted the students' learning performance in online synchronous learning but also supported their learning performance in online asynchronous learning. Besides, most students' discussion messages were mostly related to the learning tasks and topic.

This paper presents an advanced virtual inertia control strategy for wind farms to provide transient power support in the presence of frequency events, where a fuzzy active disturbance rejection controller is developed to enable the operation of an energy storage system (ESS) so as to provide support for frequency regulation of the power grid. To effectively estimate the system frequency under uncertain noises, fuzzy rules are presented to adaptively tune the parameters of the extended state observer and to realize the power-sharing, to improve the anti-interference ability of the wind power system. Finally, simulation analysis in MATLAB/Simulink is provided to validate the effectiveness of the proposed control strategy. Simulation results show that the developed virtual inertia control strategy based on fuzzy active disturbance rejection control has a good inertia support capability. In addition, the proposed method is able to improve the anti-noise capability of the wind power system.

Salt stress is a major factor limiting the growth and yield of soybean (Glycine max). Wild soybeans (Glycine soja) contain high allelic diversity and beneficial alleles that can be re-introduced into domesticated soybeans to improve adaption to the environment. However, very few beneficial alleles have been identified from wild soybean. Here, we demonstrate that wild soybean is more salt tolerant than cultivated soybean and examine dehydration responsive element-binding (DREB) family transcription factor genes to look for advantageous alleles that might improve drought tolerance in cultivated soybean. Our genome-wide analysis identified 103 DREB genes from the Glycine max genome. By combined RNA-sequencing and population genetics of wild, landrace, and cultivated soybean accessions, we show that the natural variation in DREB3a and DREB3b is related to differences in salt tolerance in soybean accessions. Interestingly, DREB3b, but not DREB3a, appears to have undergone artificial selection. Soybean plants carrying the wild soybean DREB3b allele (DREB3b39Del) are more salt tolerant than those containing the reference genome allele (DREB3bRef). Together, our results suggest that the loss of the DREB3b39Del allele through domestication of cultivated soybean may be associated with a reduction in salt tolerance. Our findings provide crucial information for improving salt tolerance in soybean through molecular breeding.

In the present work, a single-crystalline epitaxial nonpolar a-plane AlN film with in-plane two-folder symmetries was successfully achieved on an r-plane sapphire substrate, by combining physical vapor deposition and a high-temperature annealing technique. Moreover, by varying the AlN thickness, the evolution of crystalline quality and structure were systematically investigated using X-ray diffraction, Raman spectroscopy, and atomic force microscopy. The crystalline quality was much improved by the annealing treatment. Most importantly, when the thickness of AlN was increased up to 1000 nm, the AlN lattice was found to endure strong distortion along the out-of-plane direction, and the lattice showed an obvious expansion. The change of the surface morphology induced by high-temperature annealing was also tracked, and the morphology displayed structural anisotropy along the [11¯00] direction. Our results act as a crucial platform to better understand and employ the nonpolar AlN template; in particular, it is of importance for subsequent device fabrication.

This paper presents a data-driven virtual inertia control method for doubly fed induction generator (DFIG)-based wind turbine to provide inertia support in the presence of frequency events. The Markov parameters of the system are first obtained by monitoring the grid frequency and system operation state. Then, a data-driven state observer is developed to evaluate the state vector of the optimal controller. Furthermore, the optimal controller of the inertia emulation system is developed through the closed solution of the differential Riccati equation. Moreover, a differential Riccati equation with self-correction capability is developed to enhance the anti-noise ability to reject noise interference in frequency measurement process. Finally, the simulation verification was performed in Matlab/Simulink to validate the effectiveness of the proposed control strategy. Simulation results showed that the proposed virtual inertia controller can adaptively tune control parameters online to provide transient inertia supports for the power grid by releasing the kinetic energy, so as to improve the robustness and anti-interference ability of the control system of the wind power system.

Background: Educational board games have been receiving attention from educators in recent years. Designing the rules of board games based on cognitive theory, and further analysing educational board games from more dimensions are important issues that warrant further study. Purpose: The research designed a board game called Chemistry Story to promote students' learning of the concept of element combination in chemical substances. The design of the cognitive mechanism of the board game was based on three cognitive design principles, namely schema connection theory, attention, and cognitive scaffolding. Sample: The participants were 48 eighth-grade students in Taiwan. Their average age was 13.8. Design and methods: A one-group pretest-posttest design was adopted. The research explored students' learning achievement, flow, and acceptance after using this board game for learning. Moreover, this research analysed the differences in students' flow while playing with game components made of different materials (paper, wood, and plastic), and explored the relationship with learning achievement, perceived usefulness, and perceived ease of use. Results: The results showed that students' concept of element combination in chemical substances improved through playing this board game. In addition, students had considerable engagement and acceptance of the board game's learning activities with the game components made of different materials. The results of the correlation analysis showed that students with low academic achievement were more likely to feel that Chemistry Story was helpful to their studies. It was also found that the wooden material components brought a better sense of engagement and game acceptance. Conclusion: When designing educational board game products, we should not only consider the target knowledge of the board game and the design of the game mechanism, but also consider the students' feelings about the materials used to make the components, and choose materials that can bring students a better learning experience, so as to enhance the positive influence on their learning.

A series of novel 7-oxo-7H-thiazolo[3,2-b]-1,2,4-triazine-2-carboxylic acid derivatives was synthesized in good yields by a multi-step procedure that included the generation of the S-alkylated derivatives from 6-substituted arylmethyl-3-mercapto-1,2,4-triazin-5-ones with ethyl 2-chloroacetoacetate, intramolecular cyclization with microwave irradiation, hydrolysis and amidation. All of the target compounds were fully characterized through 1H-NMR, 13C-NMR and HRMS spectra. The intramolecular cyclization occurred regioselectively at the N2-position of 1,2,4-triazine ring, which was confirmed by compound 3e using single-crystal X-ray diffraction analysis. The antibacterial and antitubercular activities of the target compounds were evaluated. Compared with Ciprofloxacin and Rifampicin, compounds 5d, 5f and 5g containing the terminal amide fragment exhibited broad spectrum antibacterial activity, and carboxylic acid derivatives or its corresponding ethyl esters had less effect on antibacterial properties. The most potent compound 5f also displayed excellent in vitro antitubercular activity against Mycobacterium smegmatis (minimum inhibitory concentration (MIC) = 50 μg/mL) and better growth inhibition activity of leucyl-tRNA synthetase (78.24 ± 4.05% at 15 μg/mL).

The construction of a physical collection of open reading frames (ORFeomes) for genes of any model organism is a useful tool for the exploration of gene function, gene regulation, and protein-protein interaction. Here we describe in detail a protocol that has been used to develop the first collection of transcription factor (TF) and co-regulator (CR) open reading frames (TFome) in maize (Burdo et al., 2014). This TFome is being used to establish the architecture of gene regulatory networks (GRNs) responsible for the control of transcription of all genes in an organism. The protocol outlined here describes how to proceed when only an incomplete genome with partial annotation is available. TFome clones are made in a recombination-ready vector of the Gateway? system, allowing for the facile transfer of the ORFs to other Gateway?-compatible vectors, such as those suitable for expression in other host species. Although this protocol was developed for the maize TFome it can readily be applied to the generation of complete ORFeome collections in other eukaryotic species.[Protocol overview] An important aspect of successful TFome generation is the initial effort spent to establish a reliable set of gene models so that they can be subsequently amplified or synthesized. An actual TFome construction protocol for a particular species will depend on available resources such as a full-length cDNA (flcDNA) collection and a reliable reference genome (Figure 1). In the case of maize, a flcDNA collection and a draft genome was available, but the former provided only 30% of the needed clones, and the latter contained gaps and some erroneous gene models. In order to develop a near-complete set of target gene models for maize TFs, a bioinformatics pipeline was developed as described by Yilmaz et al. (2009). In brief, a two-pronged search process was developed. The first involved making a collection of protein sequences of TFs in other species and available from databases such as PlantTFDB, PlnTFDB and DBDTF. These sequences were then used to search gene models from the draft maize genome using BLASTP. The second process involved developing a collection of domains that define TF families and that are mostly annotated in the PFAM database (Finn et al., 2014). These domains were then used to search the draft maize genome using BLASTX. The number of TF families that exist and their naming is subject to change as new members are discovered and studied. Table 1 provides a list of known TF families with alternative names along with the respective PFAM domains whose presence or absence defines each TF family. HMM models for each domain can be obtained from the PFAM database (pfam.xfam.org). Following the BLAST search, redundant models are eliminated and then based on the TF motifs present in each gene model, gene models are assigned to a TF or Co-Regulator (CR) family according to the criteria specified in Table 1. Lastly, it is recommended to set up a database to store information on each TF family. The GRASSIUS (www.grassius.org) website was established to access the stored information on TF gene models for maize, sorghum, rice, Brachypodium, sugarcane and other grasses (Burdo et al., 2014). In the following section, an assumption is made that at least a draft genome or draft transcriptome is available and that a set of gene models is available that have been determined ab initio or with additional manual annotation. Familiarity with the use of PERL scripts is advantageous for the gene model assembly phase.Figure 1. Flowchart for the generation of a TFome project. Flowchart outlining the general strategy for template identification, PCR amplification and cloning of transcription factor (TF) full length (FL) open reading frames (ORFs). (modified from Burdo et al., 2014)

How do early bilingual experiences influence children's neural architecture for word processing? Dual language acquisition can yield common influences that may be shared across different bilingual groups, as well as language-specific influences stemming from a given language pairing. To investigate these effects, we examined bilingual English speakers of Chinese or Spanish, and English monolinguals, all raised in the US (N = 152, ages 5-10). Children completed an English morphological word processing task during fNIRS neuroimaging. The findings revealed both language-specific and shared bilingual effects. The language-specific effects were that Chinese and Spanish bilinguals showed principled differences in their neural organization for English lexical morphology. The common bilingual effects shared by the two groups were that in both bilingual groups, increased home language proficiency was associated with stronger left superior temporal gyrus (STG) activation when processing the English word structures that are most dissimilar from the home language. The findings inform theories of language and brain development during the key periods of neural reorganization for learning to read by illuminating experience-based plasticity in linguistically diverse learners.

IntroductionAKCEA-TTR-LRx is a ligand-conjugated antisense (LICA) drug in development for the treatment of hereditary transthyretin amyloidosis (hATTR), a fatal disease caused by mutations in the transthyretin (TTR) gene. AKCEA-TTR-LRx shares the same nucleotide sequence as inotersen, an antisense medicine approved for use in hATTR polyneuropathy (hATTR-PN). Unlike inotersen, AKCEA-TTR-LRx is conjugated to a triantennary N-acetylgalactosamine moiety that supports receptor-mediated uptake by hepatocytes, the primary source of circulating TTR. This advanced design increases drug potency to allow for lower and less frequent dosing. The NEURO-TTRansform study will investigate whether AKCEA-TTR-LRx is safe and efficacious, with the aim of improving neurologic function and quality of life in hATTR-PN patients.Methods/designApproximately 140 adults with stage 1 (independent ambulation) or 2 (requires ambulatory support) hATTR-PN are anticipated to enroll in this multicenter, open-label, randomized, phase 3 study. Patients will be assigned 6:1 to AKCEA-TTR-LRx 45 mg subcutaneously every 4 weeks or inotersen 300 mg once weekly until the prespecified week 35 interim efficacy analysis, after which patients receiving inotersen will receive AKCEA-TTR-LRx 45 mg subcutaneously every 4 weeks. All patients will then receive AKCEA-TTR-LRx through the remainder of the study treatment period. The final efficacy analysis at week 66 will compare the AKCEA-TTR-LRx arm with the historical placebo arm from the phase 3 trial of inotersen (NEURO-TTR). The primary outcome measures are between-group differences in the change from baseline in serum TTR, modified Neuropathy Impairment Score + 7, and Norfolk Quality of Life-Diabetic Neuropathy questionnaire.ConclusionNEURO-TTRansform is designed to determine whether targeted delivery of AKCEA-TTR-LRx to hepatocytes with lower and less frequent doses will translate into clinical and quality-of-life benefits for patients with hATTR-PN.Trial registrationThe study is registered at ClinicalTrials.gov (NCT04136184) and EudraCT (2019-001698-10).

Pathological social withdrawal (PSW), an extreme form of socially avoidant behaviour, is emerging as a global public health issue. Prior PSW theories implicate personal values that deviate from sociocultural norms resulting in inner conflict and mental health problems. Speculatively, this conflict could manifest or be embedded within a person's cognitive and affective self-concepts (self-construal and self-esteem respectively). In this study, we tested the hypotheses that compared to those without PSW, individuals with PSW would have lower personal and collective self-esteem, and endorse independent and/or interdependent self-construals to differing degrees. 343 Taiwanese adults completed a two-step online survey, which consisted measuring their social withdrawal condition, sociocultural deviance, personal/collective self-esteem, independent/interdependent self-construal and mental health problems. As expected, data showed that the affected group had lower self-esteem than the unaffected group, but no group difference emerged in either self-construal dimension. We also found that personal self-esteem in the PSW group was (concurrently) associated with sociocultural deviance and symptoms of poor mental health. Our results tentatively supported theories of PSW, suggesting that the influences individuals' personal self-esteem and sociocultural deviance should be considered in future studies or treatments/preventions., Author(s): Alison Fang-Wei Wu [sup.1] , Tai-Li Chou [sup.2] , Caroline Catmur [sup.1] , Jennifer Y. F. Lau [sup.1] Author Affiliations: (1) grid.13097.3c, 0000 0001 2322 6764, Department of Psychology, [...]

AimsAmyloidogenic transthyretin (ATTR) amyloidosis is a fatal disease characterized by progressive cardiomyopathy and/or polyneuropathy. AKCEA-TTR-LRx (ION-682884) is a ligand-conjugated antisense drug designed for receptor-mediated uptake by hepatocytes, the primary source of circulating transthyretin (TTR). Enhanced delivery of the antisense pharmacophore is expected to increase drug potency and support lower, less frequent dosing in treatment.Methods and resultsAKCEA-TTR-LRx demonstrated an approximate 50-fold and 30-fold increase in potency compared with the unconjugated antisense drug, inotersen, in human hepatocyte cell culture and mice expressing a mutated human genomic TTR sequence, respectively. This increase in potency was supported by a preferential distribution of AKCEA-TTR-LRx to liver hepatocytes in the transgenic hTTR mouse model. A randomized, placebo-controlled, phase 1 study was conducted to evaluate AKCEA-TTR-LRx in healthy volunteers (ClinicalTrials.gov: NCT03728634). Eligible participants were assigned to one of three multiple-dose cohorts (45, 60, and 90 mg) or a single-dose cohort (120 mg), and then randomized 10:2 (active : placebo) to receive a total of 4 SC doses (Day 1, 29, 57, and 85) in the multiple-dose cohorts or 1 SC dose in the single-dose cohort. The primary endpoint was safety and tolerability; pharmacokinetics and pharmacodynamics were secondary endpoints. All randomized participants completed treatment. No serious adverse events were reported. In the multiple-dose cohorts, AKCEA-TTR-LRx reduced TTR levels from baseline to 2 weeks after the last dose of 45, 60, or 90 mg by a mean (SD) of -85.7% (8.0), -90.5% (7.4), and -93.8% (3.4), compared with -5.9% (14.0) for pooled placebo (P

This study investigates the cross-linguistic transfer of literacy skills in Spanish-English, Chinese-English bilingual, and English monolingual children (N = 283, 5-10 years). Research question 1 examines English literacy and asks how phonological and morpho-semantic skills contribute to word reading as a function of children's language background. Structural equation modeling revealed contrasting bilingual effects: compared to English monolinguals, Spanish-English bilinguals relied more on phonological awareness in word reading, whereas Chinese-English bilinguals relied more on lexical knowledge. Research question 2 examines relations between bilinguals' heritage language proficiency and English literacy. Results revealed direct and indirect effects of heritage language meta-linguistic skills on English word reading. The study yields implications for reading theories and instructional practices in optimizing literacy in linguistically diverse children.

Sweat sensors targeting exercise or chemically induced sweat have shown promise for noninvasive health monitoring. Natural thermoregulatory sweat is an attractive alternative as it can be accessed during routine and sedentary activity without impeding user lifestyles and potentially preserves correlations between sweat and blood biomarkers. We present simple glove-based sensors to accumulate natural sweat with minimal evaporation, capitalizing on high sweat gland densities to collect hundreds of microliters in just 30 min without active sweat stimulation. Sensing electrodes are patterned on nitrile gloves and finger cots for in situ detection of diverse biomarkers, including electrolytes and xenobiotics, and multiple gloves or cots are worn in sequence to track overarching analyte dynamics. Direct integration of sensors into gloves represents a simple and low-overhead scheme for natural sweat analysis, enabling sweat-based physiological monitoring to become practical and routine without requiring highly complex or miniaturized components for analyte collection and signal transduction.

The tobacco epidemic is a public health threat that has taken a heavy toll of lives around the globe each year. Smoking affects both the smokers and those who are exposed to secondhand smoke, and careful tracking of exposure can be key to mitigating the potential hazards. For smokers, the variation of chemical compositions between commercial cigarettes has led to ambiguity in estimating the health risks, both for active smokers and others involuntarily exposed to tobacco smoke and byproducts. In this regard, sweat possesses an attractive opportunity to monitor smoke exposure due to sweat's abundance in biomolecules and its great accessibility. Here, we present a wearable sweat band to monitor nicotine, a prominent ingredient in cigarettes, as a viable way to quantitatively assess a wearer's exposure to smoking. Both smokers and normal subjects are tested to demonstrate the use of this device for smoke-related health monitoring. Our results exhibit confirmable and elevated nicotine levels in sweat for subjects inhaling cigarette smoke. This continuous and personalized sweat sensing device is leverage to monitor smoke pollution for a potentially broad population.