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As technology-enhanced children’s learning has gained wide attention, programmable robots have been gradually introduced in early childhood education. Hence, it would be valuable to understand how young children perceive robot programming learning. Draw-a-picture technique is an ideal method to elicit ideas, thoughts, and feelings for children with limited literacy, and epistemic network analysis (ENA) is a novel analytical method to analyze children’s conceptions through the visualized network model. Therefore, this study employed a draw-a-picture technique and ENA to explore 189 5-6-year-old young children’s conceptions of robot programming learning and probe whether their conceptions differ by gender and learning achievements. Results revealed that most children believed that with robot programming kits, they could engage in programming activities with peers in any location and held positive emotions and attitudes. In addition, young children’s conceptions of robot programming learning differ notably by gender and learning achievements. Based on the current findings, several suggestions were proposed, which could set a reference for future robot programming teaching in early childhood education.

This study aimed to determine the perceptions and attitudes of preservice teachers of Chinese as a foreign language (CFL) toward applying information and computer technology (ICT) and image-generative artificial intelligence (image-GAI) tools in CFL teaching from the perspective of drawings. This 2-week study involved 20 preservice CFL teachers from a university in northern Taiwan. Various data were collected, including questionnaire responses and drawings (both hand-drawn and artificial-intelligence-assisted) by preservice teachers. The collected data were analyzed to determine how the experience of using image-GAI tools influenced how preservice CFL teachers perceive ICT-assisted CFL teaching, and how they perceive the potential of image-GAI tools in enhancing their creativity. The results indicated that most conceptions held by the preservice CFL teachers of ICT-assisted Chinese language teaching involved teachers and learners as the primary people involved, and that they tended to adopt a teacher-centered teaching mode. The preservice CFL teachers had positive attitudes toward using image-GAI tools in CFL teaching. However, they were more reserved regarding whether generative AI tools can promote diversity in CFL teaching and enhance the creativity of preservice teachers. The most common elements in the drawings by the preservice teachers were the activities and the people involved in CFL teaching. Two other noteworthy findings were (1) most preservice CFL teachers believed that this new technology (image-GAI tools) better reflected their understanding of ICT and CFL teaching, and (2) that their drawings indicated that having experience of using image-GAI tools influenced their perception of ICT and CFL teaching.

With the rapid development of generative artificial intelligence (GAI), the performance and usability of related tools, such as ChatGPT, have significantly improved. The advancement has fostered researchers to increasingly focus on students' perceptions and application of the roles, functionalities, and interaction patterns of these tools in higher education. The present study adopted the draw-a-picture technique to explore the viewpoints and conceptions of undergraduates with different growth mindsets regarding the roles and functionalities of ChatGPT in learning. It also analyzed their interaction process with ChatGPT, especially their interaction skills and question types. The results showed that there were significant differences in the conceptions of "locations," "learning content," and "learning activities" of students with different growth mindsets. In the interaction process between undergraduates and ChatGPT, significant differences existed in the interaction skills and question types of students with different growth mindsets. Besides, students with different growth mindsets also had different learning achievements and critical thinking tendencies. The findings revealed the conceptions of students with different growth mindsets regarding the roles and functionalities of ChatGPT in learning, and also provided valuable insights for teachers. These findings are beneficial for educators to more accurately adjust and optimize the application of these tools in teaching activities based on students' different growth mindsets.

Abstract Tetrahydro-β-carboline skeletons are prominent and ubiquitous in an extraordinary range of indole alkaloid natural products and pharmaceutical compounds. Powerful synthetic approaches for stereoselective synthesis of tetrahydro-β-carboline skeletons have immense impacts and have attracted enormous attention. Here, we outline a general chiral phosphoric acid catalyzed asymmetric 1,3-dipolar cycloaddition of 3,4-dihydro-β-carboline-2-oxide type nitrone that enables access to three types of chiral tetrahydro-β-carbolines bearing continuous multi-chiral centers and quaternary chiral centers. The method displays different endo/exo selectivity from traditional nitrone chemistry. The distinct power of this strategy has been illustrated by application to collective and enantiodivergent total syntheses of 40 tetrahydro-β-carboline-type indole alkaloid natural products with divergent stereochemistry and varied architectures.

Abstract Machine learning is becoming a preferred method for the virtual screening of organic materials due to its cost-effectiveness over traditional computationally demanding techniques. However, the scarcity of labeled data for organic materials poses a significant challenge for training advanced machine learning models. This study showcases the potential of utilizing databases of drug-like small molecules and chemical reactions to pretrain the BERT model, enhancing its performance in the virtual screening of organic materials. By fine-tuning the BERT models with data from five virtual screening tasks, the version pretrained with the USPTO–SMILES dataset achieved R2 scores exceeding 0.94 for three tasks and over 0.81 for two others. This performance surpasses that of models pretrained on the small molecule or organic materials databases and outperforms three traditional machine learning models trained directly on virtual screening data. The success of the USPTO–SMILES pretrained BERT model can be attributed to the diverse array of organic building blocks in the USPTO database, offering a broader exploration of the chemical space. The study further suggests that accessing a reaction database with a wider range of reactions than the USPTO could further enhance model performance. Overall, this research validates the feasibility of applying transfer learning across different chemical domains for the efficient virtual screening of organic materials. Scientific contribution This study verifies the feasibility of applying transfer learning to large language models in different chemical fields to help organic materials perform virtual screening. Through the comparison of transfer learning from different chemical fields to a variety of organic material molecules, the high precision virtual screening of organic materials is realized.

Abstract In order to accurately predict the content and variation trend of dissolved gas in transformer oil and guide the condition maintenance of power transformers, a combined prediction model based on multi‐information fusion is proposed and its effectiveness is analysed. First of all, based on the possibility of pathological and missing historical sample data, a detection and filling method based on variable weight combination samples is established. Second, the authors propose two models. Aiming at the non‐linear and non‐stationary characteristics of gas content, a univariate decomposition prediction mode HBA‐VMD‐TCN which based on the Honey Badger algorithm, variational mode decomposition and time convolutional network (TCN) is established. Then the multivariate Informer prediction model is established for gas content affected by multiple variables. Third, the cross‐entropy theory is used to determine the weight coefficients of the two models, and the multi‐information fusion combined prediction model is formed. Finally, on the basis of the above, a method to determine the time step and the position information of the transition point adaptively in the process of prediction is proposed to further improve the prediction accuracy. The results show that, through a series of simulation experiments of model comparison and transformer anomaly prediction, the accuracy and effectiveness of the combined prediction model are verified.

This study reviews the journal publications of artificial intelligence-supported online learning (AIoL) in the Web of Science (WOS) database from 1997 to 2019 taking into account the contributing countries/areas, leading journals, highly cited papers, authors, research areas, research topics, roles of AIoL, and adopted artificial intelligence (AI) algorithms. Results indicate that, from 1997 to 2009, AIoL research focused on the combination of intelligent tutoring systems and distance learning. In 2010-2014, AIoL research emphasized learner-oriented learning. In 2015-2019, learner-system interactions to facilitate personalized, adaptive, and collaborative learning became the main focus. "Intelligent tutoring systems" have played the most important role in AIoL, followed by "profiling and prediction," and "adaptive systems with personalization." Accordingly, the roles and research trends as well as several suggestions for future research in the field of AIoL are provided as a reference for researchers and policy makers.

Abstract Suppressor of Mek1 (Smek1) is a regulatory subunit of protein phosphatase 4. Genome‐wide association studies have shown the protective effect of SMEK1 in Alzheimer's disease (AD). However, the physiological and pathological roles of Smek1 in AD and other tauopathies are largely unclear. Here, the role of Smek1 in preventing neurodegeneration is investigated in tauopathy. Smek1 is downregulated in the aged human brain. Through single‐cell sequencing, a novel neuronal cluster is identified that possesses neurodegenerative characteristics in Smek1−/− mice. Smek1 deficiency caused markedly more severe motor and cognitive impairments in mice, as well as neuronal loss, gliosis, and tau hyperphosphorylation at major glycogen synthase kinase 3β (Gsk3β) sites. Protein‐protein interaction analysis revealed that the Ran‐binding domain (RanBD) in the N‐terminus of Smek1 facilitated binding with kinesin family member 2A (Kif2a). Depletion of Smek1 resulted in cytoplasmic aggregation of Kif2a, axon outgrowth defects, and impaired mitochondrial axonal trafficking. Downregulation of Kif2a markedly attenuated tau hyperphosphorylation and axon outgrowth defects in shSmek1 cells. For the first time, this study demonstrates that Smek1 deficiency progressively induces neurodegeneration by exacerbating tau pathology and mitochondrial dysfunction in an age‐dependent manner.

ObjectiveThe aim of this study was to enhance the precision of categorization of endometrial lesions in ultrasound images via a data enhancement framework based on deep learning (DL), through addressing diagnostic accuracy challenges, contributing to future research.Materials and methodsUltrasound image datasets from 734 patients across six hospitals were collected. A data enhancement framework, including image features cleaning and soften label, was devised and validated across multiple DL models, including ResNet50, DenseNet169, DenseNet201, and ViT-B. A hybrid model, integrating convolutional neural network and transformer architectures for optimal performance, to predict lesion types was developed.ResultsImplementation of our novel strategies resulted in a substantial enhancement in model accuracy. The ensemble model achieved accuracy and macro-area under the receiver operating characteristic curve values of 0.809 of 0.911, respectively, underscoring the potential for use of DL in endometrial lesion ultrasound image classification.ConclusionWe successfully developed a data enhancement framework to accurately classify endometrial lesions in ultrasound images. Integration of anomaly detection, data cleaning, and soften label strategies enhanced the comprehension of lesion image features by the model, thereby boosting its classification capacity. Our research offers valuable insights for future studies and lays the foundation for creation of more precise diagnostic tools.

BackgroundThe effectiveness of Tuina therapy has been confirmed in treating pain of patients with cervical spondylosis (CS), however, its therapeutic mechanism is still unclear. This study aimed to observe the changes of regional brain activity following Tuina therapy in patients with painful CS based on resting-state functional magnetic resonance imaging (rs-fMRI) data.MethodsA total of 27 patients with CS and 27 healthy subjects (HCs) were enrolled in this study. All patients received Tuina therapy every 2 days for 2 weeks. The clinical manifestations of patients were evaluated by the Visual Analog Scale (VAS) and Neck Disability Index (NDI) before and after treatment. In addition, rs-fMRI data were collected and preprocessed in all patients before and after treatment, as well as HCs. HCs underwent a 1-time rs-fMRI scan, whereas CS patients underwent 2-times of rs-fMRI scan. The measure of regional homogeneity (ReHo) was calculated and compared between groups. Finally, relationships between altered brain regions and clinical characteristics were evaluated by Pearson’s correlation analysis.ResultsAfter Tuina therapy, VAS and NDI scores of patients decreased. Before treatment, CS patients showed higher ReHo values in the left middle temporal gyrus, left thalamus, right anterior and posterior cingulate gyrus, left inferior parietal gyrus and lower ReHo values in the right gyrus rectus when compared with HCs. After treatment, CS patients exhibited higher ReHo values in the left inferior temporal gyrus, right anterior and posterior cingulate gyrus, left inferior parietal gyrus and lower ReHo values in the right rectus gyrus when compared with HCs. CS patients after treatment demonstrated higher ReHo values in the left inferior occipital gyrus when compared with those before treatment. Positive correlations were found between ReHo values of the right rectus gyrus and VAS, NDI scores in CS patients before treatment. Differences of VAS scores between before and after treatment were negatively correlated with ReHo values of the left inferior temporal gyrus in CS patients after treatment.ConclusionThis study demonstrated the presence of asynchronous activity in certain brain regions in CS patients, which might be associated with pain and cervical spine dysfunction. Tuina therapy might modulate asynchronous activity of abnormal brain regions, which might contribute to the effectiveness of Tuina therapy in alleviating pain and cervical spine dysfunction in CS patients.

Abstract Background Circulating miRNAs (c-miR) have been shown to be potential biomarkers in sarcopenia, but the miRNAs response to aerobic exercise in older people remains inconclusive. We sought to examine the exercise benefits on physical fitness and miRNAs, and to explore the mediating effect of miRNAs on training-induced fitness changes. Methods This controlled trial recruited 58 community-dwelling older adults and randomized them into exercise group (EX) and control group (CON). EX received 8-week supervised moderate intensity cycling training 3x/week. C-miR expression (c-miR-21, c-miR-126, c-miR-146a, c-miR-222), physical fitness (body composition, cardiorespiratory fitness, muscular fitness) and physical activity level (PAL, measured as in daily step counts) were evaluated at baseline, post-training, and post-16-week follow-up. The mediating effect of miRNA expression onto exercise-induced physical fitness change was determined by causal mediation analysis (CMA). Results Exercise significantly improved body fat and cardiorespiratory fitness in older people while maintaining muscle mass and strength, and augmented expression of c-miR-126, c-miR-146a, and c-miR-222 for up to 16 weeks post-training. Notably, older people in EX had substantially higher daily step counts than CON throughout the study even after the active training period. However, CMA revealed no significant indirect effect but a potential mediating effect of c-miR-21, but not the rest, onto the body composition, cardiorespiratory fitness, and lower limb strength. Conclusion An eight-week supervised MICT program promoted a higher level of physical activity up to 16 weeks post-training, which induces better cardiorespiratory fitness and resists decline in muscular measures. C-miRNA, especially c-miR-21, potentially mediates the training effect upon fitness.

Abstract The torrent frogs of the genus Amolops represent a great anuran diversification in southern China and Southeast Asia. Previous studies have shown that, the diversity of this genus still remains underestimated. During herpetological surveys from 2021 to 2022, several Amolops specimens were collected from the international border regions of southwestern Yunnan Province, China. Herein, we utilized molecular phylogenetic and morphological data to identify these specimens. Our findings indicate the presence of a separate and previously unknown lineage in the A. viridimaculatus group, which we formally describe as a new species. Furthermore, the specimen from Xishuangbanna National Nature Reserve clustered with A. vitreus from the paratype, supporting the morphological diagnosis. Therefore, we describe a new species and a new species record for China. Our study contributes to the species richness of the genus Amolops as well as the diversity of amphibians in China. Notably, our discovery brings the total number of Amolops species to 85 and the total number of torrent frog species known to occur in China to 53. In addition, our study further confirmed that Yunnan and Indochina Peninsula have similar faunal composition, implying that more studies are needed to achieve a complete understanding of the species diversity and distribution pattern.

Abstract Tibetan Buddhist monasteries are widely distributed throughout the Qinghai–Tibet Plateau and are significant locations for human–wildlife coexistence. Given the significance of their historical and contemporary social influence, it is crucial to ascertain whether there exists a non‐negligible correlation between these monasteries and their surrounding wildlife. In contrast to sacred mountains and lakes, there have been few studies that have examined the relationship between Tibetan Buddhist monasteries and wildlife communities. Using birds as a model ecological community, generalized mixed effect models (GLMM) were employed to examine relationships between the presence of Tibetan Buddhist monasteries and the number of individuals (relative abundance), avian species richness and diversity, using data from bird‐watching checklists (n = 262) obtained from the China Bird Report. Our models also included landscape‐wide environmental factors, including the ratio of woodland habitat, grassland habitat and open habitats, human footprint index, distance to nearest human occupation (villages), distance to water, altitude, time, presence of monastery and their interactions. Observation time was included as a model covariate. The presence of Tibetan Buddhist monasteries and the interactions between the presence of monasteries and environmental variables exhibit a significant correlation with the number of individual birds recorded (relative abundance), but not with observed species richness or diversity. Moreover, the relative abundance of birds was found to be significantly higher in areas around monasteries compared to those without monasteries. The abundance of species from eight families, namely Accipitridae, Corvidae, Columbidae, Passeridae, Leiothrichidae, Friningillidae, Musciapidae and Turidae, was significantly positively correlated with the presence of monasteries. Notably, the positive correlation of Accipitridae with the presence of celestial burial grounds around monasteries suggests a relationship between celestial burial practices and Accipitridae abundance at these sites. Our study reveals a significant positive correlation between Tibetan Buddhist monasteries and aspects of avian community composition in the eastern Qinghai–Tibetan Plateau, thus highlights their potential role in the preservation of avian populations in fragmented landscape habitats. We encourage the government and relevant national parks stakeholders to implement targeted management strategies that take into account the unique patterns of human–wildlife coexistence in these areas, and to leverage the cultural advantages of the region to promote ecological conservation. Read the free Plain Language Summary for this article on the Journal blog.

Abstract Background Chronic cough is a common symptom in patients post the coronavirus disease 2019 (COVID-19). In this study, we aimed to investigate the efficacy of inhaled corticosteroids (ICS) and the clinical characteristics of patients with post-COVID-19 chronic cough during the Omicron era. Methods An ambispective, longitudinal cohort study was conducted that included patients with post-COVID-19 who attended the respiratory clinic at our hospital between January 1, 2023, and March 31, 2023 with a complaint of persistent cough lasting more than 8 weeks. At 30 and 60 days after the first clinic visit for post-COVID-19 chronic cough, enrolled patients were prospectively followed up. We compared the changes in symptoms and pulmonary function between patients receiving ICS treatment (ICS group) and those not receiving ICS treatment (NICS group) at the two visits. Results A total of 104 patients with post-COVID-19 chronic cough were enrolled in this study (ICS group, n = 51; NICS group, n = 53). The most common symptoms accompanying post-COVID-19 chronic cough were sputum (58.7%, 61/104) and dyspnea (48.1%, 50/104). Seventy-one (82.6%, 71/86) patients had airway hyperresponsiveness, and 49 patients (47.1%, 49/104) were newly diagnosed with asthma. Most patients (95.2%, 99/104) exhibited improvement at 60 days after the first visit. The pulmonary function parameters of the patients in the ICS group were significantly improved compared to the baseline values (P

The surge in global energy demand mandates a significant expansion of electric power substations. Nevertheless, the ecological consequences of electric power substation operation, particularly concerning the electromagnetic field, on soil microbial communities and nitrogen enrichment remain unexplored. In this study, we collected soil samples from six distinct sites at varying distances from an electric power substation in Xintang village, southeastern China, and investigated the impacts of electromagnetic field on the microbial diversity and community structures employing metagenomic sequencing technique. Our results showed discernible dissimilarities in the fungal community across the six distinct sites, each characterized by unique magnetic and electric intensities, whereas comparable variations were not evident within bacterial communities. Correlation analysis revealed a diminished nitrogen fixation capacity at the site nearest to the substation, characterized by low moisture content, elevated pH, and robust magnetic induction intensity and electric field intensity. Conversely, heightened nitrification processes were observed at this location compared to others. These findings were substantiated by the relative abundance of key genes associated with ammonium nitrogen and nitrate nitrogen production. This study provides insights into the relationships between soil microbial communities and the enduring operation of electric power substations, thereby contributing fundamental information essential for the rigorous environmental impact assessments of these facilities.

BackgroundEarly ventricular tachycardia/fibrillation (VT/VF) in patients with ST-elevation myocardial infarction (STEMI) has higher morbidity and mortality. This study examines gender-differentiated risk factors and underlying mechanisms for early onset VT/VF in STEMI.MethodsWe analyzed data from 2,964 consecutive STEMI patients between January 1, 2008 and December 31, 2021. Early VT/VF was defined as occurrence of spontaneous VT/VF of ≥30 s or requirement of immediate cardioversion/defibrillation within the first 48 h after symptoms. An ex vivo ischemic-reperfusion experiments were conducted in 8-week-old ApoE−/− mice fed a high-fat diet to explore the underlying mechanisms of early VT/VF.ResultsIn 255 of out 2,964 STEMI patients who experienced early VT/VF, the age was younger (58.6 ± 13.8 vs. 61.0 ± 13.0 years old, P = 0.008) with a male predominance. The plasma levels of L5, the most electronegative subclass of low-density lipoprotein, was higher in early VT/VF patients compared to those without early VT/VF (n = 21, L5: 14.1 ± 22.6% vs. n = 46, L5: 4.3 ± 9.9%, P = 0.016). In the experimental setup, all male mice (n = 4) developed VT/VF post sham operation, whereas no such incidence was observed in the female mice (n = 3). Significantly, male mice exhibited considerably slower cardiac conduction velocity as compared to their female counterparts in whole heart preparations (25.01 ± 0.93 cm/s vs.42.32 ± 5.70 cm/s, P

Ticks are primary vectors for many tick-borne pathogens (TBPs) and pose a serious threat to veterinary and public health. Information on the presence of TBPs in Chinese Milu deer (Elaphurus davidianus) is limited. In this study, a total of 102 Chinese Milu deer blood samples were examined for Anaplasma spp., Theileria spp., Babesia spp., Rickettsia spp., and Borrelia spp., and three TBPs were identified: Anaplasma phagocytophilum (48; 47.1 %), Candidatus Anaplasma boleense (47; 46.1%), and Theileria capreoli (8; 7.8 %). Genetic and phylogenetic analysis of the 16S rRNA and 18S rRNA confirmed their identity with corresponding TBPs. To our knowledge, this is the first report on Candidatus A. boleense and T. capreoli detection in Chinese Milu deer. A high prevalence of A. phagocytophilum with veterinary and medical significance was identified in endangered Chinese Milu deer, which could act as potential zoonotic reservoirs. The identification of the TBPs in Chinese Milu deer provides useful information for the prevention and control of tick-borne diseases.

Abstract An efficient one-pot strategy for the facile synthesis of double boron–oxygen-fused polycyclic aromatic hydrocarbons (dBO-PAHs) with high regioselectivity and efficient skeletal editing is developed. The boron–oxygen-fused rings exhibit low aromaticity, endowing the polycyclic aromatic hydrocarbons with high chemical and thermal stabilities. The incorporation of the boron–oxygen units enables the polycyclic aromatic hydrocarbons to show single-component, low-temperature ultralong afterglow of up to 20 s. Moreover, the boron–oxygen-fused polycyclic aromatic hydrocarbons can also serve as ideal n-type host materials for high-brightness and high-efficiency deep-blue OLEDs; compared to single host, devices using boron–oxygen-fused polycyclic aromatic hydrocarbons-based co-hosts exhibit dramatically brightness and efficiency enhancements with significantly reduced efficiency roll-offs; device 9 demonstrates a high color-purity (Commission International de l’Eclairage CIEy = 0.104), and also achieves a record-high external quantum efficiency (28.0%) among Pt(II)-based deep-blue OLEDs with Commission International de l’Eclairage CIEy

Abstract Background Androgenetic alopecia (AGA), one of the most common types of hair loss, is associated with oxidative stress, inflammation and aging. Derinat, a transient receptor potential canonical channels (TRPCs) inhibitor, restrains TRPCs-mediated increase intracellular Ca2+ signaling, which initiates the skin aging process with intracellular reactive oxygen species (ROS) accumulation. This study investigated whether Derinat protected skin from oxidative stress-induced damage and aging, thus inhibiting AGA pathogenesis. Methods The lifespan of Caenorhabditis elegans was measured to examine the capacity of Derinat to oppose the oxidative stress induced-aging process, which drives the hair cycle from anagen to catagen phase. The experiments that used BALB/c-nu and C57BL/6 mice determined the effects of Derinat on hair cycle and oxidative stress in skin. To further apply Derinat to clinical study, the resulting relationship between AGA pathogenesis and TRPCs-regulated oxidative stress was confirmed using the bioinformatics approach. We consequently used the parameters of hair density, hair diameter, hair recovery and quality of life index to evaluate the effect of Derinat treatment on AGA subjects. Results Derinat restrained the oxidative stress induced-aging process sufficiently to extend the lifespan of worms. Derinat also changed the hair growth patterns of mice by maintenance of the hair cycle at the anagen phase. This efficacy was due to reduction of TRPCs-mediated ROS accumulation. Because the bioinformatics analysis found that AGA pathogenesis is associated with TRPCs-regulated oxidative stress and inflammation, treatment with Derinat in AGA subjects increased positive outcomes of oral medication while mitigating the impairment of AGA subjects’ quality of life. Conclusions Derinat restrains AGA pathogenesis and may provide a new therapeutic approach for treating AGA. ClinicalTrials.gov Identifier NCT05450861, https://register.clinicaltrials.gov , date of registration 07/11/2022. Trial registration ClinicalTrials.gov Identifier NCT05450861, https://register.clinicaltrials.gov , date of registration 07/11/2022

Abstract The current study explores the potential function and the underlying mechanisms of endothelial cell-derived R-spondin 3 (RSPO3) neuroprotection against ischemia/reperfusion-induced neuronal cell injury. In both neuronal cells (Neuro-2a) and primary murine cortical neurons, pretreatment with RSPO3 ameliorated oxygen and glucose deprivation (OGD)/re-oxygenation (OGD/R)-induced neuronal cell death and oxidative injury. In neurons RSPO3 activated the Akt, Erk and β-Catenin signaling cascade, but only Erk inhibitors reversed RSPO3-induced neuroprotection against OGD/R. In mouse embryonic fibroblasts (MEFs) and neuronal cells, RSPO3-induced LGR4-Gab1-Gαi1/3 association was required for Erk activation, and either silencing or knockout of Gαi1 and Gαi3 abolished RSPO3-induced neuroprotection. In mice, middle cerebral artery occlusion (MCAO) increased RSPO3 expression and Erk activation in ischemic penumbra brain tissues. Endothelial knockdown or knockout of RSPO3 inhibited Erk activation in the ischemic penumbra brain tissues and increased MCAO-induced cerebral ischemic injury in mice. Conversely, endothelial overexpression of RSPO3 ameliorated MCAO-induced cerebral ischemic injury. We conclude that RSPO3 activates Gαi1/3-Erk signaling to protect neuronal cells from ischemia/reperfusion injury.

Diabetic retinopathy (DR) is one of the most common retinal vascular diseases and one of the main causes of blindness worldwide. Early detection and treatment can effectively delay vision decline and even blindness in patients with DR. In recent years, artificial intelligence (AI) models constructed by machine learning and deep learning (DL) algorithms have been widely used in ophthalmology research, especially in diagnosing and treating ophthalmic diseases, particularly DR. Regarding DR, AI has mainly been used in its diagnosis, grading, and lesion recognition and segmentation, and good research and application results have been achieved. This study summarizes the research progress in AI models based on machine learning and DL algorithms for DR diagnosis and discusses some limitations and challenges in AI research.

For semiconducting two-dimensional transition metal dichalcogenides (TMDs), the carrier transport properties of the material are affected by strain engineering. In this study, we investigate the carrier mobility of monolayer hafnium disulphide (HfS2) under different biaxial strains by first-principles calculations combined with the Kubo–Greenwood mobility approach and the compact band model. The decrease/increase in the effective mass of the conduction band (CB) of monolayer HfS2 caused by biaxial tensile/compressive strain is the major reason for the enhancement/degradation of its electron mobility. The lower hole effective mass of the valence bands (VB) in monolayer HfS2 under biaxial compressive strain improves its hole transport performance compared to that under biaxial tensile strain. In summary, biaxial compressive strain causes a decrease in both the effective mass and phonon scattering rate of monolayer HfS2, resulting in an increase in its carrier mobility. Under the biaxial compressive strain reaches 4%, the electron mobility enhancement ratio of the CB of monolayer HfS2 is ~90%. For the VB of monolayer HfS2, the maximum hole mobility enhancement ratio appears to be ~13% at a biaxial compressive strain of 4%. Our results indicate that the carrier transport performance of monolayer HfS2 can be greatly improved by strain engineering.

This study was designed to compare the antioxidant, antitumor and anti-inflammatory effects of essential oils from the bark and flower of Magnolia officinalis Rehd. et Wils. Distillation extraction and steam distillation were used to extract EOs from the bark and flower. The results showed that the contents of EOs of SDE-F and SDE-B were much higher than that of SD-F and SD-B. EOs from the bark were rich in eudesmol (especially α-eudesmol) and exhibited a stronger antioxidant effect than the flower. The anti-tumor effects of SD-B and SD-F on HepG2 and MDA-MB-231 cells were better than that of SDE-B and SDE-F. The inhibitory rates of SD-B and SD-F on MDA-MB-231 cells were 59.21% and 48.27%, exceeding that of positive control 5-fluorouracil (47.04%) at 50 μg/mL. All four EOs exhibited excellent anti-inflammatory activities through the regulation of nitric oxide production and pro-inflammation cytokines in LPS-induced RAW 264.7 cells and they also remarkably suppressed the mRNA expressions of nitric oxide synthase, IL-6 and TNF-α at the concentration higher than that of positive control dexamethasone. These results indicated significant differences in the composition, and anti-inflammatory and anti-tumor activities of EOs extracted by different methods and provided a theoretical basis for their development and utilization.

Olaquindox (OLA) and quinocetone (QCT) have been prohibited in aquatic products due to their significant toxicity and side effects. In this study, rapid and visual europium nanoparticle (EuNP)-based lateral flow strip biosensors (LFSBs) were developed for the simultaneous quantitative detection of OLA, QCT, and 3-methyl-quinoxaline-2-carboxylic acid (MQCA) in fish feed and tissue. The EuNP-LFSBs enabled sensitive detection for OLA, QCT, and MQCA with a limit of detection of 0.067, 0.017, and 0.099 ng/mL (R2 ≥ 0.9776) within 10 min. The average recovery of the EuNP-LFSBs was 95.13%, and relative standard deviations were below 9.38%. The method was verified by high-performance liquid chromatography (HPLC), and the test results were consistent. Therefore, the proposed LFSBs serve as a powerful tool to monitor quinoxalines in fish feeds and their residues in fish tissues.

Abstract Chronic heavy alcohol use is associated with lethal arrhythmias. Whether common East Asian-specific aldehyde dehydrogenase deficiency (ALDH2*2) contributes to arrhythmogenesis caused by low level alcohol use remains unclear. Here we show 59 habitual alcohol users carrying ALDH2 rs671 have longer QT interval (corrected) and higher ventricular tachyarrhythmia events compared with 137 ALDH2 wild-type (Wt) habitual alcohol users and 57 alcohol non-users. Notably, we observe QT prolongation and a higher risk of premature ventricular contractions among human ALDH2 variants showing habitual light-to-moderate alcohol consumption. We recapitulate a human electrophysiological QT prolongation phenotype using a mouse ALDH2*2 knock-in (KI) model treated with 4% ethanol, which shows markedly reduced total amount of connexin43 albeit increased lateralization accompanied by markedly downregulated sarcolemmal Nav1.5, Kv1.4 and Kv4.2 expressions compared to EtOH-treated Wt mice. Whole-cell patch-clamps reveal a more pronounced action potential prolongation in EtOH-treated ALDH2*2 KI mice. By programmed electrical stimulation, rotors are only provokable in EtOH-treated ALDH2*2 KI mice along with higher number and duration of ventricular arrhythmia episodes. The present research helps formulate safe alcohol drinking guideline for ALDH2 deficient population and develop novel protective agents for these subjects.

Wolfberry, also known as goji berry or Lycium barbarum, is a highly valued fruit with significant health benefits and nutritional value. For more efficient and comprehensive usage of published L. barbarum genomic data, we established the Wolfberry database. The utility of the Wolfberry Genome Database (WGDB) is highlighted through the Genome browser, which enables the user to explore the L. barbarum genome, browse specific chromosomes, and access gene sequences. Gene annotation features provide comprehensive information about gene functions, locations, expression profiles, pathway involvement, protein domains, and regulatory transcription factors. The transcriptome feature allows the user to explore gene expression patterns using transcripts per kilobase million (TPM) and fragments per kilobase per million mapped reads (FPKM) metrics. The Metabolism pathway page provides insights into metabolic pathways and the involvement of the selected genes. In addition to the database content, we also introduce six analysis tools developed for the WGDB. These tools offer functionalities for gene function prediction, nucleotide and amino acid BLAST analysis, protein domain analysis, GO annotation, and gene expression pattern analysis. The WGDB is freely accessible at https://cosbi7.ee.ncku.edu.tw/Wolfberry/. Overall, WGDB serves as a valuable resource for researchers interested in the genomics and transcriptomics of L. barbarum. Its user-friendly web interface and comprehensive data facilitate the exploration of gene functions, regulatory mechanisms, and metabolic pathways, ultimately contributing to a deeper understanding of wolfberry and its potential applications in agronomy and nutrition.

Summary: LMNA gene mutation can cause muscular dystrophy, and post-translational modification plays a critical role in regulating its function. Here, we identify that lamin A is palmitoylated at cysteine 522, 588, and 591 residues, which are reversely catalyzed by palmitoyltransferase zinc finger DHHC-type palmitoyltransferase 5 (ZDHHC5) and depalmitoylase α/β hydrolase domain 7 (ABHD7). Furthermore, the metabolite lactate promotes palmitoylation of lamin A by inhibiting the interaction between it and ABHD7. Interestingly, low-level palmitoylation of lamin A promotes, whereas high-level palmitoylation of lamin A inhibits, murine myoblast differentiation. Together, these observations suggest that ABHD7-mediated depalmitoylation of lamin A controls myoblast differentiation.

Genetic load and inbreeding are recognized as important factors to be considered in conservation programs. Elevated levels of both can increase the risk of population extinction by negatively impacting fitness-related characters in many species of plants and animals, including humans (inbreeding depression). Genomic techniques are increasingly used in measuring and understanding genetic load and inbreeding and their importance in evolution and conservation. We used whole genome resequencing data from two sibling grouse species in subarctic Eurasia to quantify both. We found a large range of inbreeding measured as FROH (fraction of runs of homozygosity) in individuals from different populations of Chinese Grouse (Tetrastes sewerzowi) and Hazel Grouse (T. bonasia). FROH estimated from genome-wide runs of homozygosity (ROH) ranged from 0.02 to 0.24 among Chinese Grouse populations and from 0.01 to 0.44 in Hazel Grouse. Individuals from a population of Chinese Grouse residing in the Qilian mountains and from the European populations of Hazel Grouse (including samples from Sweden, Germany and Northeast Poland) were the most inbred (FROH ranged from 0.10 to 0.23 and 0.11 to 0.44, respectively). These levels are comparable to other highly inbred populations of birds. Hazel Grouse from northern China and Chinese Grouse residing in the Qinghai-Tibetan Plateau showed relatively lower inbreeding levels. Comparisons of the ratio between deleterious missense mutations and synonymous mutations revealed higher levels in Chinese Grouse as compared to Hazel Grouse. These results are possibly explained by higher fixation rates, mutational melt down, in the range-restricted Chinese Grouse compared to the wide-ranging Hazel Grouse. However, when we compared the relatively more severe class of loss-of-function mutations, Hazel Grouse had slightly higher levels than Chinese Grouse, a result which may indicate that purifying selection (purging) has been more efficient in Chinese Grouse on this class of mutations.

Abstract Endothelial dysfunction (ED) is critical in the development and progression of cardiovascular (CV) disorders, yet effective therapeutic targets for ED remain elusive due to limited understanding of its underlying molecular mechanisms. To address this gap, we employed a systems biology approach to identify potential targets for ED. Our study combined multi omics data integration, with siRNA screening, high content imaging and network analysis to prioritise key ED genes and identify a pro‐ and anti‐ED network. We found 26 genes that, upon silencing, exacerbated the ED phenotypes tested, and network propagation identified a pro‐ED network enriched in functions associated with inflammatory responses. Conversely, 31 genes ameliorated ED phenotypes, pointing to potential ED targets, and the respective anti‐ED network was enriched in hypoxia, angiogenesis and cancer‐related processes. An independent screen with 17 drugs found general agreement with the trends from our siRNA screen and further highlighted DUSP1, IL6 and CCL2 as potential candidates for targeting ED. Overall, our results demonstrate the potential of integrated system biology approaches in discovering disease‐specific candidate drug targets for endothelial dysfunction.

Abstract The mitochondrial integrity and function in endothelial cells are essential for angiogenesis. TIMM44 (translocase of inner mitochondrial membrane 44) is essential for integrity and function of mitochondria. Here we explored the potential function and the possible mechanisms of TIMM44 in angiogenesis. In HUVECs, human retinal microvascular endothelial cells and hCMEC/D3 brain endothelial cells, silence of TIMM44 by targeted shRNA largely inhibited cell proliferation, migration and in vitro capillary tube formation. TIMM44 silencing disrupted mitochondrial functions in endothelial cells, causing mitochondrial protein input arrest, ATP reduction, ROS production, and mitochondrial depolarization, and leading to apoptosis activation. TIMM44 knockout, by Cas9-sgRNA strategy, also disrupted mitochondrial functions and inhibited endothelial cell proliferation, migration and in vitro capillary tube formation. Moreover, treatment with MB-10 (“MitoBloCK-10”), a TIMM44 blocker, similarly induced mitochondrial dysfunction and suppressed angiogenic activity in endothelial cells. Contrarily, ectopic overexpression of TIMM44 increased ATP contents and augmented endothelial cell proliferation, migration and in vitro capillary tube formation. In adult mouse retinas, endothelial knockdown of TIMM44, by intravitreous injection of endothelial specific TIMM44 shRNA adenovirus, inhibited retinal angiogenesis, causing vascular leakage, acellular capillary growth, and retinal ganglion cells degeneration. Significant oxidative stress was detected in TIMM44-silenced retinal tissues. Moreover, intravitreous injection of MB-10 similarly induced oxidative injury and inhibited retinal angiogenesis in vivo. Together, the mitochondrial protein TIMM44 is important for angiogenesis in vitro and in vivo, representing as a novel and promising therapeutic target of diseases with abnormal angiogenesis.