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Microbiota-directed complementary food (MDCF) formulations have been designed to repair the gut communities of malnourished children. A randomized controlled trial demonstrated that one formulation, MDCF-2, improved weight gain in malnourished Bangladeshi children compared to a more calorically dense standard nutritional intervention. Metagenome-assembled genomes from study participants revealed a correlation between ponderal growth and expression of MDCF-2 glycan utilization pathways by Prevotella copri strains. To test this correlation, here we use gnotobiotic mice colonized with defined consortia of age- and ponderal growth-associated gut bacterial strains, with or without P. copri isolates closely matching the metagenome-assembled genomes. Combining gut metagenomics and metatranscriptomics with host single-nucleus RNA sequencing and gut metabolomic analyses, we identify a key role of P. copri in metabolizing MDCF-2 glycans and uncover its interactions with other microbes including Bifidobacterium infantis. P. copri-containing consortia mediated weight gain and modulated energy metabolism within intestinal epithelial cells. Our results reveal structure-function relationships between MDCF-2 and members of the gut microbiota of malnourished children with potential implications for future therapies.

To date, very limited research interest has been given to the strategies English medium instruction (EMI) teachers or lecturers deploy to provide corrective feedback (CF) on the language use to their students during class interaction. In other words, when EMI teachers incidentally focus on students' problematic language use, how do they correct it -- providing explicit correction or using recast or elicitation? This article reports on a study that examined CF types EMI teachers and lecturers used during classroom discourse, drawing on data collected from classroom observations and recordings of six different EMI classes in high school and university settings in Korea. The frequency and types of CF used in reactive language-related episodes (LREs) were identified in the EMI classes and compared between the two settings and across disciplines (social science, mathematics, and computer science). Findings showed that all the EMI teachers and lecturers offered CF to their students but with different frequency; the schoolteachers offered CF more frequently than the university lecturers. Also, the schoolteachers used more various types of CF than the lecturers. In both settings, CF occurred most frequently in mathematics compared to the other two disciplines. This article ends with suggestions for ways the findings of this study can be used to raise EMI teachers' awareness of various options for providing CF on students' linguistic errors during their incidental teaching practices.

Kindergarten is emphasized as a critical first entry into the education system, as politicians and pundits believe kindergartners' success can lead to later academic achievement. Therefore, a comprehensive understanding of kindergarten school readiness data should consider how it is measured and how that affects learning. Using the Early Childhood Longitudinal Studies--Kindergarten (ECLS-K) cohort 2010-2011 data, the author examined the relationship between teacher reports about children's academic readiness at kindergarten entrance and their later outcomes in reading, math, and science through fifth grade. This study used a latent basis growth model with time-invariant predictors to analyze the relationship's trajectory. Overall, findings determined that teachers' perceptions of children's Approaches to Learning, mathematical thinking, and science significantly impacted later achievements in math and science direct assessments throughout elementary education. This research discussed the practice and policy implications on teachers' perceptions of school readiness and its impact on later academic outcomes.

Abstract In recent years, the prevalence and fatality rates of atherosclerotic cardiovascular disease have not only shown a consistent rise that cannot be ignored, but have also become a pressing social health problem that requires urgent attention. While interventional surgery and drug therapy offer significant therapeutic results, they often come with common side effects. Geniposide, an active component extracted from the Chinese medicine Gardenia jasminoides Ellis, shows promise in the management of cardiac conditions. This review comprehensively outlines the underlying pharmacological mechanisms by which geniposide exerts its effects on atherosclerosis. Geniposide exhibits a range of beneficial effects including alleviating inflammation, inhibiting the development of macrophage foam cells, improving lipid metabolism, and preventing platelet aggregation and thrombosis. It also demonstrates mitochondrial preservation, anti-apoptotic effects, and modulation of autophagy. Moreover, geniposide shows potential in improving oxidative stress and endoplasmic reticulum stress by maintaining the body’s antioxidant and oxidative balance. Additionally, this review comprehensively details the biological properties of geniposide, including methods of extraction and purification, as well as its pharmacokinetics and toxicological characteristics. It further discusses the clinical applications of related biopharmaceuticals, emphasizing the potential of geniposide in the prevention and treatment of atherosclerotic cardiovascular diseases. Furthermore, it highlights the limitations of current research, aiming to provide insights for future studies. Graphical Abstract

Abstract Zika virus (ZIKV) infection may lead to severe neurological consequences, including seizures, and early infancy death. However, the involved mechanisms are still largely unknown. TRPC channels play an important role in regulating nervous system excitability and are implicated in seizure development. We investigated whether TRPCs might be involved in the pathogenesis of ZIKV infection. We found that ZIKV infection increases TRPC4 expression in host cells via the interaction between the ZIKV-NS3 protein and CaMKII, enhancing TRPC4-mediated calcium influx. Pharmacological inhibition of CaMKII decreased both pCREB and TRPC4 protein levels, whereas the suppression of either TRPC4 or CaMKII improved the survival rate of ZIKV-infected cells and reduced viral protein production, likely by impeding the replication phase of the viral life cycle. TRPC4 or CaMKII inhibitors also reduced seizures and increased the survival of ZIKV-infected neonatal mice and blocked the spread of ZIKV in brain organoids derived from human-induced pluripotent stem cells. These findings suggest that targeting CaMKII or TRPC4 may offer a promising approach for developing novel anti-ZIKV therapies, capable of preventing ZIKV-associated seizures and death.

Abstract Loop diuretics are prevailing drugs to manage fluid overload in heart failure. However, adjusting to loop diuretic doses is strenuous due to the lack of a diuretic guideline. Accordingly, we developed a novel clinician decision support system for adjusting loop diuretics dosage with a Long Short-Term Memory (LSTM) algorithm using time-series EMRs. Weight measurements were used as the target to estimate fluid loss during diuretic therapy. We designed the TSFD-LSTM, a bi-directional LSTM model with an attention mechanism, to forecast weight change 48 h after heart failure patients were injected with loop diuretics. The model utilized 65 variables, including disease conditions, concurrent medications, laboratory results, vital signs, and physical measurements from EMRs. The framework processed four sequences simultaneously as inputs. An ablation study on attention mechanisms and a comparison with the transformer model as a baseline were conducted. The TSFD-LSTM outperformed the other models, achieving 85% predictive accuracy with MAE and MSE values of 0.56 and 1.45, respectively. Thus, the TSFD-LSTM model can aid in personalized loop diuretic treatment and prevent adverse drug events, contributing to improved healthcare efficacy for heart failure patients.

Abstract Kindergarten is emphasized as a critical first entry into the education system, as politicians and pundits believe kindergartners’ success can lead to later academic achievement. Therefore, a comprehensive understanding of kindergarten school readiness data should consider how it is measured and how that affects learning. Using the Early Childhood Longitudinal Studies—Kindergarten (ECLS-K) cohort 2010–2011 data, the author examined the relationship between teacher reports about children’s academic readiness at kindergarten entrance and their later outcomes in reading, math, and science through fifth grade. This study used a latent basis growth model with time-invariant predictors to analyze the relationship's trajectory. Overall, findings determined that teachers’ perceptions of children’s Approaches to Learning, mathematical thinking, and science significantly impacted later achievements in math and science direct assessments throughout elementary education. This research discussed the practice and policy implications on teachers’ perceptions of school readiness and its impact on later academic outcomes.

In order to investigate the formation mechanism of the quality of baked green tea, we used metabolomics based on ultra-high performance liquid chromatography-quadrupole-Exactive mass spectrometry (UPLC-Q-Exactive/MS) to analyze the differences in the chemical compositions of green tea samples at different stages of thermal processing such as fixation, drying and roasting. A total of 125 compounds were identified, including 10 flavanols, 14 dimeric catechins, 19 flavanol-O-glycosides, 5 flavone-C-glycosides, 8 N-ethyl-2-pyrrolidinone-substituted flavan-3-ols (EPSF), 16 amino acids, 13 phenolic acids, 4 organic acids, 11 alkaloids, 13 lipids, 4 aroma glycosides and 8 other compounds. The results of partial least squares-discriminant analysis (PLS-DA) and heat map analysis showed that the chemical components obviously changed during the thermal processing of green tea, and 114 significantly differential compounds were selected (P < 0.05). In the three stages of thermal processing, the contents of most catechins and dimeric catechins decreased, and the contents of EPSFs, flavone- C-glycosides, and lipid compounds significantly increased. The contents of aroma glycosides (phenylethyl primeveroside, linalool primeveroside, and linalool oxide primeveroside) increased by 439% to 2 497% during the fixation process. The content of N-(1-deoxy-D-fructosyl)theanine increased by 820% to 1 290% during the drying process. The contents of flavanol-O-glycosides (myricetin 3-galactoside, kaempferol-3-galactoside, kaempferol 3-arabinoside, myricetin 3-glucoside and kaempferol-3-glucoside) decreased significantly during roasting. This study can provide a theoretical reference for future improvement of green tea quality.

Abstract Morinda citrifolia L. (Noni) has been widely used in traditional medicine in tropical zones and has become increasingly popular globally owing to its health benefits. Most noni fruits are consumed as juice, which is traditionally produced by the natural fermentation of noni fruits. In this study, the metabolic profiles of noni fruit juice (NJ1) and fermented noni fruit juices (NJ2 and NJ3) was compared. A total of 74, 83, and 91 compounds including anthraquinones, coumarins, flavonoids, phenolic acids, phenolics, terpenoids, and miscellaneous (acids, carbohydrates, vitamins, fatty acids, etc.) were tentatively identified from NJ1, NJ2, and NJ3 in both positive and negative electrospray ionization modes. The phenolic compound composition differed significantly between noni juice and fermented noni juice. The results of the unsupervised principal component analysis and hierarchical clustering analysis showed that the non-fermented juice group clustered with the fermented juice groups. Asperulosidic acid, isoasperulosidic acid, and rutin levels were higher in the NJ1 group than those in the NJ2 group. Deacetylasperulosidic acid and monotropein contents in NJ2 were higher than those in NJ1. Similarly, NJ1 had higher asperulosidic acid and isoasperulosidic acid than those in NJ3. The findings from this study have the potential to enhance the quality of fermented noni juice.

Abstract Although adamantinomatous craniopharyngioma (ACP) is a tumour with low histological malignancy, there are very few therapeutic options other than surgery. ACP has high histological complexity, and the unique features of the immunological microenvironment within ACP remain elusive. Further elucidation of the tumour microenvironment is particularly important to expand our knowledge of potential therapeutic targets. Here, we performed integrative analysis of 58,081 nuclei through single-nucleus RNA sequencing and spatial transcriptomics on ACP specimens to characterize the features and intercellular network within the microenvironment. The ACP environment is highly immunosuppressive with low levels of T-cell infiltration/cytotoxicity. Moreover, tumour-associated macrophages (TAMs), which originate from distinct sources, highly infiltrate the microenvironment. Using spatial transcriptomic data, we observed one kind of non-microglial derived TAM that highly expressed GPNMB close to the terminally differentiated epithelial cell characterized by RHCG, and this colocalization was verified by asmFISH. We also found the positive correlation of infiltration between these two cell types in datasets with larger cohort. According to intercellular communication analysis, we report a regulatory network that could facilitate the keratinization of RHCG+ epithelial cells, eventually causing tumour progression. Our findings provide a comprehensive analysis of the ACP immune microenvironment and reveal a potential therapeutic strategy base on interfering with these two types of cells.

Abstract Percutaneous coronary intervention (PCI) addresses myocardial ischaemia, but a significant subset of patients encounter major adverse cardiovascular events (MACE) post‐treatment. This meta‐analysis investigated the relationship between the post‐PCI triglyceride‐glucose (TyG) index and MACE. Comprehensive searches of the Embase, PubMed, Cochrane Library, and Web of Science databases were conducted up to 3 March 2023, using relevant keywords. The effect size was determined based on I2 statistic using random‐effects models. Cluster‐robust standard errors crafted the dose–response curve, and the GRADE Evaluation Scale was employed to rate the quality of evidence. The group with the highest TyG index had significantly higher post‐PCI MACE rates than the lowest index group, with hazard ratios (HRs) of 2.04 (95% CI 1.65–2.52; I2 = 77%). Each unit increase in TyG index corresponded to HRs of 1.82 for MACE (95% CI 1.34–2.46; I2 = 92%), 2.57 for non‐fatal MI (95% CI 1.49–4.41; I2 = 63%), and 2.06 for revascularization (95% CI 1.23–3.50; I2 = 90%). A linear relationship between TyG index and MACE risk was established (R2 = 0.6114). For all‐cause mortality, the HR was 1.93 (95% CI 1.35–2.75; I2 = 50%), indicating a higher mortality risk with elevated TyG index. The GRADE assessment yielded high certainty for non‐fatal MI but low certainty for all‐cause mortality, revascularization, and MACE. The TyG index may predict risks of post‐PCI MACE, all‐cause mortality, non‐fatal MI, and revascularization, with varied levels of certainty. A potential linear association between the TyG index and MACE post‐PCI was identified. Future research should validate these findings.

Abstract This study explores the progression of intracerebral hemorrhage (ICH) in patients with mild to moderate traumatic brain injury (TBI). It aims to predict the risk of ICH progression using initial CT scans and identify clinical factors associated with this progression. A retrospective analysis of TBI patients between January 2010 and December 2021 was performed, focusing on initial CT evaluations and demographic, comorbid, and medical history data. ICH was categorized into intraparenchymal hemorrhage (IPH), petechial hemorrhage (PH), and subarachnoid hemorrhage (SAH). Within our study cohort, we identified a 22.2% progression rate of ICH among 650 TBI patients. The Random Forest algorithm identified variables such as petechial hemorrhage (PH) and countercoup injury as significant predictors of ICH progression. The XGBoost algorithm, incorporating key variables identified through SHAP values, demonstrated robust performance, achieving an AUC of 0.9. Additionally, an individual risk assessment diagram, utilizing significant SHAP values, visually represented the impact of each variable on the risk of ICH progression, providing personalized risk profiles. This approach, highlighted by an AUC of 0.913, underscores the model’s precision in predicting ICH progression, marking a significant step towards enhancing TBI patient management through early identification of ICH progression risks.

Abstract 6-Gingerol, the main bioactive compound of ginger, has antioxidant, anti-inflammatory, anti-cancer and neuroprotective effects. However, it is unclear whether 6-Gingerol has protective effects against hepatic ischemia/reperfusion (I/R) injury. In this study, the mouse liver I/R injury model and the mouse AML12 cell hypoxia/reoxygenation (H/R) model were established by pretreatment with 6-Gingerol at different concentrations to explore the potential effects of 6-Gingerol. Serum transaminase levels, liver necrotic area, cell viability, inflammatory response, and cell apoptosis were used to assess the effect of 6-Gingerol on hepatic I/R or cell H/R injury. Quantitative polymerase chain reaction (qPCR) and Western blotting were used to detect the mRNA and protein expression. The results show that 6-Gingerol decreased serum alanine aminotransferase (ALT), aspartate aminotransferase (AST) levels, liver necrosis, inflammatory cytokines IL-1β, IL-6, MCP-1, TNF-α expression, Ly6g+ inflammatory cell infiltration, protein phosphorylation of NF-κB signaling pathway, Terminal deoxynucleotidyl transferase dUTP nick-end labeling (TUNEL) positive cells, cell apoptosis rate, the protein expression of pro-apoptotic protein BAX and C-Caspase3, increased cell viability, and expression of anti-apoptotic protein BCL-2. Moreover, 6-Gingerol could increase the mRNA and protein expression of mitogen activated protein kinase phosphatase 5 (MKP5) and inhibit the activation of P38/JNK signaling pathway. In MKP5 knockout (KO) mice, the protective effect of 6-gingerol and the inhibition of P38/JNK pathway were significantly weakened. Therefore, our results suggest that 6-Gingerol exerts anti-inflammatory and anti-apoptotic effects to attenuate hepatic I/R injury by regulating the MKP5-mediated P38/JNK signaling pathway.

Summary: Empathy, crucial for social interaction, is impaired across various neuropsychiatric conditions. However, the genetic and neural underpinnings of empathy variability remain elusive. By combining forward genetic mapping with transcriptome analysis, we discover that aryl hydrocarbon receptor nuclear translocator 2 (ARNT2) is a key driver modulating observational fear, a basic form of affective empathy. Disrupted ARNT2 expression in the anterior cingulate cortex (ACC) reduces affect sharing in mice. Specifically, selective ARNT2 ablation in somatostatin (SST)-expressing interneurons leads to decreased pyramidal cell excitability, increased spontaneous firing, aberrant Ca2+ dynamics, and disrupted theta oscillations in the ACC, resulting in reduced vicarious freezing. We further demonstrate that ARNT2-expressing SST interneurons govern affective state discrimination, uncovering a potential mechanism by which ARNT2 polymorphisms associate with emotion recognition in humans. Our findings advance our understanding of the molecular mechanism controlling empathic capacity and highlight the neural substrates underlying social affective dysfunctions in psychiatric disorders.

The TRICHOME BIREFRINGENCE-LIKE (TBL) gene encodes a class of proteins related to xylan acetylation, which has been shown to play an important role in plant response to environmental stresses. This gene family has been meticulously investigated in Arabidopsis thaliana, whereas there have been no related reports in Eucalyptus grandis. In this study, we identified 49 TBL genes in E. grandis. A conserved amino acid motif was identified, which plays an important role in the execution of the function of TBL gene family members. The expression of TBL genes was generally upregulated in jasmonic acid-treated experiments, whereas it has been found that jasmonic acid activates the expression of genes involved in the defense functions of the plant body, suggesting that TBL genes play an important function in the response of the plant to stress. The principle of the action of TBL genes is supported by the finding that the xylan acetylation process increases the rigidity of the cell wall of the plant body and thus improves the plant’s resistance to stress. The results of this study provide new information about the TBL gene family in E. grandis and will help in the study of the evolution, inheritance, and function of TBL genes in E. grandis, while confirming their functions.

Abstract The successful utilization of an eco‐friendly and biocompatible parylene‐C substrate for high‐performance solution‐processed double‐walled carbon nanotube (CNT) electrode‐based perovskite solar cells (PSCs) was demonstrated. Through the use of a novel inversion transfer technique, vertical separation of the binders from the CNTs was induced, rendering a stronger p‐doping effect and thereby a higher conductivity of the CNTs. The resulting foldable devices exhibited a power conversion efficiency of 18.11%, which is the highest reported among CNT transparent electrode‐based PSCs to date, and withstood more than 10,000 folding cycles at a radius of 0.5 mm, demonstrating unprecedented mechanical stability. Furthermore, solar modules were fabricated using entirely laser scribing processes to assess the potential of the solution‐processable nanocarbon electrode. Notably, this is the only one to be processed entirely by the laser scribing process and to be biocompatible as well as eco‐friendly among the previously reported nonindium tin oxide‐based perovskite solar modules.

Abstract Graphitic carbon nitride (CN), as a nonmetallic photocatalyst, has gained considerable attention for its cost‐effectiveness and environmentally friendly nature in catalyzing solar‐driven CO2 conversion into valuable products. However, the photocatalytic efficiency of CO2 reduction with CN remains low, accompanied by challenges in achieving desirable product selectivity. To address these limitations, a two‐step hydrothermal‐calcination tandem synthesis strategy is presented, introducing carbon quantum dots (CQDs) into CN and forming ultra‐thin CQD/CN nanosheets. The integration of CQDs induces a distinct work function with CN, creating a robust interface electric field after the combination. This electric field facilitates the accumulation of photoelectrons in the CQDs region, providing an abundant source of reduced electrons for the photocatalytic process. Remarkably, the CQD/CN nanosheets exhibit an average CO yield of 120 µmol g−1, showcasing an outstanding CO selectivity of 92.8%. The discovery in the work not only presents an innovative pathway for the development of high‐performance photocatalysts grounded in non‐metallic CN materials employing CQDs but also opens new avenues for versatile application prospects in environmental protection and sustainable cleaning energy.

Multiple myeloma (MM) is the most prevalent malignant monoclonal disease of plasma cells. There is mounting evidence that interactions with the bone marrow (BM) niche are essential for the differentiation, proliferation, survival, migration, and treatment resistance of myeloma cells. For this reason, gaining a deeper comprehension of how BM microenvironment compartments interact with myeloma cells may inspire new therapeutic ideas that enhance patient outcomes. This review will concentrate on the most recent findings regarding the mechanisms of interaction between microenvironment and MM and highlight research on treatment targeting the BM niche.

IntroductionPrevious research has highlighted the duality of self-consciousness, which simultaneously plays adaptive and maladaptive roles. This study aims to develop a measure that categorically distinguishes between different types of self-consciousness styles based on the Regulatory Focus Theory (RFT) and examines their relationship with mental health-related indicators.MethodsData were gathered through an online mental health survey conducted at a University Student Counseling Center in Seoul. The study involved exploratory factor analysis, confirmatory factor analysis, and reliability and validity analysis, which resulted in the development of a 14-question Self-Consciousness Type Scale (SCTS).ResultsBoth exploratory and confirmatory factor analyses validated the two-factor structure of the SCTS. The fit indices of the final model indicated a good fit, with high internal consistency for both sub-factors. Convergent and discriminant validity were confirmed through correlations between the sub-scales. Cluster analysis identified four distinct subtypes of self-consciousness styles: Growth-oriented, Defensive, Ambivalent, and Low-focus self-consciousness. Group difference analysis revealed significant differences in mental health-related variables among the subtypes, supporting the 2 × 2 model of prevention-focused and promotion-focused self-consciousness.DiscussionThe findings support the SCTS as a valid measurement tool capable of distinguishing four distinct types of self-consciousness, aligning with the multidimensional model of self-consciousness. The study’s limitations and implications were discussed based on the results, emphasizing the potential applications of the SCTS in mental health research and practice.